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1. Creating academic-community partnerships to jointly enhance advocacy and research on violence and disability: Two case examples

Author

Emily M. Lund, Leanne Beers, Katherine E. McDonald, Christina Nicolaidis, Sandra M. Leotti, Marsha Katz, and Rosemary B. Hughes

Subjects
Community-Based Participatory Research, Social Psychology, business.industry, Psychological intervention, Participatory action research, PsycINFO, Violence, Public relations, Research process, Community-Institutional Relations, Interpersonal violence, Clinical Psychology, Intervention (law), Humans, Academic community, Disabled Persons, Sociology, business, Neurodiversity
Abstract

OBJECTIVE This article describes the use of community-based participatory research (CBPR) to foster bidirectional and equitable academic-community partnerships in two studies related to interpersonal violence and disability. METHOD We analyzed our methods and experiences in conducting these studies to focus on the ways in which CBPR methodology was used to jointly promote and enhance research and advocacy surrounding violence and disability in the research processes themselves and the resulting assessment and intervention products. RESULTS Our use of CBPR methodology allowed us to identify and address critical issues related to violence in the disability community, such as disability-related forms and experiences of violence, concerns and barriers linked to mandated reporting laws, and inaccessible measures and interventions, and to address them in research products. Additionally, our bidirectional academic-community partnerships led us to address overall accessibility of the research process itself as a means by which to amplify advocate voices in science. CONCLUSIONS Full, meaningful, and equitable participation of people with disabilities at every stage of the research process allows for the creation of partnerships that jointly advance research and advocacy around violence and disability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Published
2022

2. COVID-19 Vaccine Responses in Patients With Plasma Cell Dyscrasias After Complete Vaccination

Author

Mansi Shah, Gratian Salaru, Stephanie Beers, Dennis L. Cooper, Yong Lin, and Alissa Gabel

Subjects
Cancer Research, COVID-19 Vaccines, Plasma cell, Article, Viral vector, Hypogammaglobulinemia, Pharmacotherapy, medicine, Humans, Monoclonal antibody therapy, Multiple myeloma, biology, business.industry, Vaccination, serologic response, Antibodies, Monoclonal, COVID-19, Immunoglobulins, Intravenous, Hematology, medicine.disease, immunocompromised, medicine.anatomical_structure, Oncology, Immunology, biology.protein, Antibody, Multiple Myeloma, business, vaccine boosters
Abstract

Introduction: Due to functional hypogammaglobulinemia, multiple myeloma patients are at increased risk for infection and generally have poorer responses to vaccines. In this study, we examined antibody responses after complete COVID-19 vaccination in patients with plasma cell dyscrasias, most of whom were receiving treatment. Patients and Methods: Real world study of consecutive patients with multiple myeloma and other plasma cell dyscrasias (PCD) were evaluated after complete vaccination with either the 2-shot mRNA vaccines from BioNTech and Moderna or the 1-shot adenoviral vector vaccine from Johnson & Johnson (J&J). Patients received vaccines 1-4 months before antibody testing without controlling for the type of vaccine or the timing of drug therapy. Patients with a clinical history or antibody evidence of prior infection were excluded. Anti-nucleocapsid and quantitative anti-spike antibody levels were measured with the Roche Elecys assay. Results: 95% of patients had detectable antibody responses. Multivariate analysis showed that higher age, ongoing anti-CD38 monoclonal antibody therapy and the J&J vaccine negatively affected quantitative response. A small number of ineffectively vaccinated patients receiving IVIG subsequently had detectable nucleocapsid and spike antibodies confirming the presence of the latter in currently administered IVIG. Conclusions: Nearly all PCD had detectable anti-spike antibodies after vaccination but age, anti-CD38 monoclonal antibody therapy, and the single-shot J&J vaccine negatively affected responses. In patients who received the J&J vaccine, second doses or heterologous mRNA vaccines should be tested. Quantitative antibody testing might make future management more rational, particularly in patients with poor responses.

Published
2022

3. Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency

Author

Kevin H.M. Kuo, Sujit Sheth, Stefan W. Eber, Vicky R. Breakey, Heng Wang, Satheesh Chonat, Hanny Al-Samkari, D. Holmes Morton, Rachael F. Grace, Eduard J. van Beers, PeterW. Forbes, Robert J. Klaassen, Nina Kollmar, and Mukta Sharma

Subjects
Adult, Hemolytic anemia, Pediatrics, medicine.medical_specialty, Anemia, Pyruvate Kinase, Disease, Pyruvate Metabolism, Inborn Errors, Quality of life, medicine, Humans, Prospective Studies, Child, Fatigue, business.industry, Anemia, Hemolytic, Congenital Nonspherocytic, Hematology, Jaundice, medicine.disease, humanities, Clinical trial, Cohort, Quality of Life, medicine.symptom, business, Pyruvate kinase deficiency
Abstract

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.0, and Functional Assessment of Cancer Therapy-Anemia) and fatigue (Patient Reported Outcomes Measurement Information System Fatigue and Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue). Significant variability in HRQoL and fatigue was reported for adults and children, although individual scores were stable over a 2-year interval. Although adults who were regularly transfused reported worse HRQoL and fatigue compared with those who were not (EuroQol-visual analog scale, 58 vs 80; P = .01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. HRQoL and fatigue significantly differed in children by genotype, with the worst scores in those with 2 severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. Additionally, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. Although current treatments for PKD are limited to supportive care, new therapies are in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments. This trial was registered at www.clinicaltrials.gov as #NCT02053480.

Published
2022

4. Advancing Antiracism in Community-Based Research Practices in Early Childhood and Family Mental Health

Author

Noel Bravo, Claudine Sherwood, Jessica X. Ouyang, Ambrose Lane, Simone N. Banks-Mackey, Sarah Barclay Hoffman, Satyani K.L. McPherson, Destiny N. Sharp, Sabrina F. Zuskov, Hillary A. Robertson, Chioma M. Oruh, Ruthie Arbit, Randall S. Baylor, Karyn A. Hartz, Dominique Charlot-Swilley, Lee Beers, Matthew G. Biel, Ar'Reon Watson, J. Corey Williams, Janaire T. Hawkins, Sharra E. Greer, Claire Boogaard, Nia Imani Bodrick, Erica E. Coates, Celene E. Domitrovich, Travis Spencer, Christina Morris, Stephanie G. Thomas, Jenise Patterson, Arrealia Gavins, Erin T. Mathis, Huynh-Nhu Le, Susan Caleb, Torrian Brent, Linwood Cole, Gail Avent, and Sharon Singh

Subjects
medicine.medical_specialty, Adolescent, Psychological intervention, Indigenous, Racism, White supremacy, Developmental and Educational Psychology, Child and adolescent psychiatry, medicine, Humans, Sociology, Justice (ethics), Early childhood, Child, Systemic Racism, Family Health, business.industry, Research, Public relations, Mental health, United States, Psychiatry and Mental health, Mental Health, Child, Preschool, business, Construct (philosophy)
Abstract

Structural racism-the ways that institutional policies, practices, and other norms operate to create and sustain race-based inequities1-has historically been foundational to the operations of academic medical centers and research institutions. Since its inception, academic medicine has depended on the exploitation of vulnerable communities to achieve medical, educational, and research goals.2 Research practices have long ignored or taken advantage of the individuals purportedly benefiting from the research, a dynamic most manifestly true for Black, Indigenous, and People of Color (BIPOC) communities in the United States. Reflecting current practices in racial justice work, we intentionally use the term "BIPOC" to highlight shared experiences within racially and ethnically minoritized communities, given the history of white supremacy in the United States. We acknowledge limitations of this term, which collapses myriad unique communities and histories into 1 construct. Specifically, child and adolescent psychiatry has historically been driven by Eurocentric approaches, paradigms, and methodology. These nonparticipatory dominant research practices have contributed to a lack of culturally responsive interventions for BIPOC communities, a paucity of evidence-based practices with demonstrated effectiveness within BIPOC communities, and disparities in access and quality of care.3 Mental health research involving BIPOC communities has been replete with exploitation and inequality.2.

Published
2022

5. Motivational regulations and lifestyle in muscle-wasted COPD patients undergoing pulmonary rehabilitation

Author

Annemie M. W. J. Schols, Martijn van Beers, Coby van de Bool, Stef P. J. Kremers, and Jessie J.M. Meis

Subjects
COPD, medicine.medical_specialty, Motivation, Nutrition and Dietetics, business.industry, Copd patients, Physical activity, Nutrition. Foods and food supply, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Chronic obstructive pulmonary disease, Behavior change, Pulmonary disease, medicine.disease, Diet, Self-determination theory, Pulmonary rehabilitation, Low muscle mass, Physical therapy, Medicine, TX341-641, business
Abstract

Summary: Background & Aims: Low physical activity (PA) levels and a poor-quality diet are common in chronic obstructive pulmonary disease (COPD) patients eligible for pulmonary rehabilitation (PR). PR may improve short-term nutritional status and exercise capacity but generally not long-term lifestyle outcomes. We hypothesized that healthy lifestyle motivation is related to PA levels and dietary quality before PR and the responsiveness thereof after PR. Methods: Before and after standardized outpatient PR, 81 COPD patients with low muscle mass completed validated motivational regulation self-reports. Physical (in)activity was assessed before and after PR through 7-day accelerometry (GT3X Actigraph). Dietary quality was assessed using a validated cross-check dietary history before and after PR and quantified as the Mean Adequacy Ratio (MAR). Results: Patients' baseline motivational profile was unrelated to dietary quality or PA. Baseline integrated motivation and its change during PR significantly predicted MAR change during PR and its levels after PR. Baseline introjected motivation and its change during PR significantly predicted PA change during PR and its levels after PR. Conclusions: Specific motivational regulations predict dietary quality and PA improvements of patients with COPD admitted to PR. Therefore, targeting integrated and introjected motivation may be key to achieving lasting behavior change after PR. Registry site: Maastricht University Medical Centre+. Clinical trial identifier number: NCT01344135.

Published
2021

6. Amyotrophic lateral sclerosis is a systemic disease: peripheral contributions to inflammation-mediated neurodegeneration

Author

Weihua Zhao, David R. Beers, and Stanley H. Appel

Subjects
Inflammation, Motor Neurons, Programmed cell death, Microglia, business.industry, Amyotrophic Lateral Sclerosis, Autophagy, Neurodegeneration, medicine.disease, medicine.anatomical_structure, Immune system, Neurology, Neuroinflammatory Diseases, medicine, Cytokines, Humans, Neurology (clinical), medicine.symptom, Amyotrophic lateral sclerosis, business, Neuroscience, Neuroinflammation
Abstract

Purpose of review Neuroinflammation is an important mediator of the pathogenesis of disease in amyotrophic lateral sclerosis (ALS). Genetic mutations such as C9orf72 have begun to define the numerous cell autonomous pathways that initiate motor neuron injury. Yet, it is the signalling to surrounding glia and peripherally derived immune cells that initiates the noncell autonomous inflammatory process and promotes self-propagating motor neuron cell death. The purpose of this review is to explore the systemic immune/inflammatory contributions to the pathogenesis of ALS: what are the peripheral pro-inflammatory signatures, what initiates their presence and do they represent potential therapeutic targets. Recent findings In ALS, motor neuron cell death is initiated by multiple cell autonomous pathways leading to misfolded proteins, oxidative stress, altered mitochondria, impaired autophagy and altered RNA metabolism, which collectively promote noncell autonomous inflammatory reactivity. The resulting disease is characterized by activated microglia and astrocytes as well as peripherally derived pro-inflammatory innate and adaptive immune cells. In this unrelenting disorder, circulating blood monocytes and natural killer cells are pro-inflammatory. Furthermore, regulatory T lymphocytes are dysfunctional, and pro-inflammatory cytokines and acute phase proteins are elevated. Summary The collective dysregulation of cells and cytokines in patients with ALS accurately reflect increased disease burdens, more rapid progression rates and reduced survival times, reinforcing the concept of ALS as a disorder with extensive systemic pro-inflammatory responses. These increased systemic pro-inflammatory immune constituents provide potentially meaningful therapeutic targets.

Published
2021

7. Prognostic significance of FCGR2B expression for the response of DLBCL patients to rituximab or obinutuzumab treatment

Author

Christopher Rushton, Wolfram Klapper, Jonathan C. Strefford, Cathy Burton, Mark S. Cragg, Ryan D. Morin, Stephen A. Beers, Andrea Knapp, Malgorzata Nowicka, Christopher R. Bolen, Chern Lee, Chantal E. Hargreaves, Laura K. Hilton, Pedro Farinha, Matthew J. Carter, Margaret Ashton-Key, Matthew J. J. Rose-Zerilli, Kathleen N. Potter, Graham W. Slack, Maurizio Martelli, Christian Klein, Mikkel Z. Oestergaard, Umberto Vitolo, Laurie H. Sehn, Farheen Mir, Marek Trneny, Russell Foxall, and David W. Scott

Subjects
0301 basic medicine, Oncology, Vincristine, medicine.medical_specialty, Cyclophosphamide, FCGR2B, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, Obinutuzumab, Chemoimmunotherapy, Prednisone, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Lymphoid Neoplasia, business.industry, Receptors, IgG, Hematology, Prognosis, medicine.disease, Lymphoma, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, medicine.drug
Abstract

Fc γ receptor IIB (FcγRIIB) is an inhibitory molecule capable of reducing antibody immunotherapy efficacy. We hypothesized its expression could confer resistance in patients with diffuse large B-cell lymphoma (DLBCL) treated with anti-CD20 monoclonal antibody (mAb) chemoimmunotherapy, with outcomes varying depending on mAb (rituximab [R]/obinutuzumab [G]) because of different mechanisms of action. We evaluated correlates between FCGR2B messenger RNA and/or FcγRIIB protein expression and outcomes in 3 de novo DLBCL discovery cohorts treated with R plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) reported by Arthur, Schmitz, and Reddy, and R-CHOP/G-CHOP-treated patients in the GOYA trial (NCT01287741). In the discovery cohorts, higher FCGR2B expression was associated with significantly shorter progression-free survival (PFS; Arthur: hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.19; P = .0360; Schmitz: HR, 1.13; 95% CI, 1.02-1.26; P = .0243). Similar results were observed in GOYA with R-CHOP (HR, 1.26; 95% CI, 1.00-1.58; P = .0455), but not G-CHOP (HR, 0.91; 95% CI, 0.69-1.20; P = .50). A nonsignificant trend that high FCGR2B expression favored G-CHOP over R-CHOP was observed (HR, 0.67; 95% CI, 0.44-1.02; P = .0622); however, low FCGR2B expression favored R-CHOP (HR, 1.58; 95% CI, 1.00-2.50; P = .0503). In Arthur and GOYA, FCGR2B expression was associated with tumor FcγRIIB expression; correlating with shorter PFS for R-CHOP (HR, 2.17; 95% CI, 1.04-4.50; P = .0378), but not G-CHOP (HR, 1.37; 95% CI, 0.66-2.87; P = .3997). This effect was independent of established prognostic biomarkers. High FcγRIIB/FCGR2B expression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP.

Published
2021

8. Acute Brain-Derived Neurotrophic Factor DNA Methylation Trajectories in Cerebrospinal Fluid and Associations With Outcomes Following Severe Traumatic Brain Injury in Adults

Author

Sue R. Beers, Amery Treble-Barna, John R. Shaffer, Lacey W. Heinsberg, David O. Okonkwo, Yvette P. Conley, Daniel E. Weeks, and Ava M. Puccio

Subjects
Brain-derived neurotrophic factor, Epigenetic biomarkers, 0303 health sciences, Traumatic brain injury, business.industry, General Medicine, medicine.disease, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, DNA methylation, medicine, Epigenetics, business, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Background. Epigenetic biomarkers have the potential to explain outcome heterogeneity following traumatic brain injury (TBI) but are largely unexplored. Objective. This exploratory pilot study characterized brain-derived neurotrophic factor ( BDNF) DNA methylation trajectories following severe TBI. Methods. Brain-derived neurotrophic factor DNA methylation trajectories in cerebrospinal fluid (CSF) over the first 5 days following severe TBI in 112 adults were examined in association with 3- and 12-month outcomes. Results. Group-based trajectory analysis revealed low and high DNA methylation groups at two BDNF cytosine-phosphate-guanine (CpG) targets that showed suggestive associations ( P < .05) with outcomes. Membership in the high DNA methylation groups was associated with better outcomes after controlling for age, sex, and injury severity. Associations of age × trajectory group interactions with outcomes at a third CpG site revealed a pattern of the same or better outcomes with higher ages in the high DNA methylation group and worse outcomes with higher ages in the low DNA methylation group. Conclusions. Although no observed associations met the empirical significance threshold after correcting for multiple comparisons, suggestive associations of the main effect models were consistent in their direction of effect and were observed across two CpG sites and two outcome time points. Results suggest that higher acute CSF BDNF DNA methylation may promote recovery following severe TBI in adults, and this effect may be more robust with higher age. While the results require replication in larger and racially diverse independent samples, BDNF DNA methylation may serve as an early postinjury biomarker helping to explain outcome heterogeneity following TBI.

Published
2021

9. Lactate dehydrogenase to carboxyhemoglobin ratio as a biomarker of heme release to heme processing is associated with higher tricuspid regurgitant jet velocity and early death in sickle cell disease

Author

Caterina P. Minniti, Annelies J. Van Vuren, Eduard J. van Beers, Gregory J. Kato, John H. Baird, and Laurel Mendelsohn

Subjects
Adult, Cell, Early death, Disease, Anemia, Sickle Cell, Heme, Correspondences, Hemolysis, chemistry.chemical_compound, Jet velocity, Lactate dehydrogenase, Correspondence, medicine, Humans, Carbon Monoxide, L-Lactate Dehydrogenase, business.industry, Hematology, Tricuspid Valve Insufficiency, medicine.anatomical_structure, chemistry, Carboxyhemoglobin, Cancer research, Biomarker (medicine), business, Biomarkers
Published
2021

10. Effect of Intensive Blood Pressure on the Progression of Non-Diabetic Chronic Kidney Disease at Varying Degrees of Proteinuria

Author

Annalisa Perna, Paul Der Mesropian, Elvira O. Gosmanova, Swati Mehta, Roy O. Mathew, Kelly Beers, Gulvahid Shaikh, Krishnakumar Hongalgi, Loay Salman, Mauricio R Monrroy Prado, and Paul J. Feustel

Subjects
medicine.medical_specialty, Renal function, Blood Pressure, 030204 cardiovascular system & hematology, urologic and male genital diseases, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Albuminuria, Humans, In patient, 030212 general & internal medicine, Renal Insufficiency, Chronic, Randomized Controlled Trials as Topic, Proteinuria, business.industry, General Medicine, medicine.disease, female genital diseases and pregnancy complications, Pooled analysis, Blood pressure, Hypertension, Disease Progression, Cardiology, medicine.symptom, business, Non diabetic, Kidney disease
Abstract

The ideal blood pressure (BP) target for renoprotection is uncertain in patients with non-diabetic chronic kidney disease (CKD), especially considering the influence exerted by pre-existing proteinuria. In this pooled analysis of landmark trials, we coalesced individual data from 5001 such subjects randomized to intensive versus standard BP targets. We employed multivariable regression to evaluate the relationship between follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CKD progression (defined as glomerular filtration rate decline by 50% or end-stage renal disease), focusing on the potential for effect modification by baseline proteinuria or albuminuria. The median follow-up was 3.2 years. We found that SBP rather than DBP was the primary predictor of renal outcomes. The optimal SBP target was 110-129 mm Hg. We observed a strong interaction between SBP and proteinuria such that lower SBP ranges were significantly linked with progressively lower CKD risk in grade A3 albuminuria or ≥0.5-1 g/day proteinuria (relative to SBP 110-119 mm Hg, the adjusted HR for SBP 120-129 mm Hg, 130-139 mm Hg, and 140-149 mm Hg was 1.5, 2.3, and 3.3, respectively; all p0.05), while in grade A1 albuminuria or proteinuria 0.1). We conclude that in non-diabetic CKD, stricter BP targets

Published
2021

11. Determination of the sleep–wake pattern and feasibility of NREM/REM discrimination using the non-invasive piezoelectric system in rats

Author

Charles Verdonk, Théo Vanneau, Pascal Van Beers, Mounir Chennaoui, D. Gomez-Merino, Aurélie Trignol, Michael Quiquempoix, Fabien Sauvet, Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), and Institut de Recherche Biomédicale des Armées (IRBA)-Université de Paris (UP)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cognitive Neuroscience, Sleep wake, Polysomnography, Rapid eye movement sleep, Sleep, REM, Audiology, Non-rapid eye movement sleep, 03 medical and health sciences, Behavioral Neuroscience, Mice, 0302 clinical medicine, Respiration, Medicine, Animals, Spectral analysis, Wakefulness, ComputingMilieux_MISCELLANEOUS, business.industry, Non invasive, Eye movement, Electroencephalography, General Medicine, Sleep in non-human animals, Rats, 030228 respiratory system, Feasibility Studies, business, Sleep, 030217 neurology & neurosurgery
Abstract

The piezoelectric cage-floor sensors have been used to successfully dissect sleep patterns in mice based on signal features related to respiration and body movements. We studied performance of the piezoelectric system to quantify the sleep-wake pattern in the rat over 7 days of recording compared with a visual electroencephalogram/electromyogram scoring, and under two light/dark (LD12:12 and LD16:8) photoperiods leading to change in the 24-hr sleep characteristics (N = 7 per group). The total sleep time (%/24 hr) over the 7 days recording and hourly sleep time over the last 24-hr recording were not statistically different between methods under the two photoperiods. Both methods detected higher total sleep time with the LD16:8 photoperiod compared with LD12:12 (p < .05), and correlated significantly (p < .001) at light and dark periods during each photoperiod. The accuracies for discrimination of sleep-wake patterns between methods were 81.9% and 84.9% for LD12:12 and LD16:8, respectively. In addition, spectral analysis of the respiratory signal given by piezo during all 10-s periods of the corresponding non-rapid eye movement and rapid eye movement sleep periods recorded by electroencephalogram/electromyogram resulted in selection of 36 features that could be inserted in an automated non-rapid eye movement sleep and rapid eye movement sleep classification, with 90% accuracy with the electroencephalogram/electromyogram visual scoring. The piezo system proved to be a reliable non-invasive alternative to electroencephalogram recording to study total sleep time in rat, with feasibility to discriminate between non-rapid eye movement and rapid eye movement sleep stages. This will be interesting in pharmacological or bio-behavioural studies evaluating sleep patterns or the restorative functions of sleep in the body and the brain.

Published
2022

12. Serum Biomarkers of Regeneration and Plasticity are Associated with Functional Outcome in Pediatric Neurocritical Illness: An Exploratory Study

Author

Keri Janesko-Feldman, Ericka L. Fink, Amy K. Wagner, Patrick M. Kochanek, Sue R. Beers, Lesley Doughty, Pamela Rubin, Craig M. Smith, Amy J. Houtrow, Chunyan Wang, Amery Treble-Barna, Dorothy Pollon, Catherine Madurski, Jessica M. Jarvis, and Anthony Fabio

Subjects
Vascular Endothelial Growth Factor A, medicine.medical_specialty, Neurology, Adolescent, S100 Calcium Binding Protein beta Subunit, Critical Care and Intensive Care Medicine, Article, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Regeneration, Child, Acquired brain injury, Pediatric intensive care unit, business.industry, Neurointensive care, Repeated measures design, 030208 emergency & critical care medicine, medicine.disease, Phosphopyruvate Hydratase, Biomarker (medicine), Female, Neurology (clinical), Sample collection, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Pediatric neurocritical care survivorship is frequently accompanied by functional impairments. Lack of prognostic biomarkers is a barrier to early identification and management of impairment. We explored the association between blood biomarkers and functional impairment in children with acute acquired brain injury. This study is a secondary analysis of a randomized control trial evaluating early versus usual care rehabilitation in the pediatric intensive care unit (PICU). Forty-four children (17 [39%] female, median age 11 [interquartile range 6–13] years) with acute acquired brain injury admitted to the PICU were studied. A single center obtained serum samples on admission days 0, 1, 3, 5, and the day closest to hospital discharge. Biomarkers relevant to brain injury (neuron specific enolase [NSE], S100b), inflammation (interleukin [IL-6], C-reactive protein), and regeneration (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF]) were collected. Biomarkers were analyzed using a Luminex® bioassay. Functional status scale (FSS) scores were abstracted from the medical record. New functional impairment was defined as a (worse) FSS score at hospital discharge compared to pre-PICU (baseline). Individual biomarker fluorescence index (FI) values for each sample collection day were correlated with new functional impairment using Spearman rank correlation coefficient (ρ). Trends in repeated measures of biomarker FI over time were explored graphically, and the association between repeated measures of biomarker FI and new functional impairment was analyzed using covariate adjusted linear mixed-effect models. Functional impairment was inversely correlated with markers of regeneration and plasticity including BDNF at day 3 (ρ = − 0.404, p = .015), day 5 (ρ = − 0.549, p = 0.005) and hospital discharge (ρ = − 0.420, p = 0.026) and VEGF at day 1 (ρ = − 0.282, p = 0.008) and hospital discharge (ρ = − 0.378, p = 0.047), such that lower levels of both markers at each time point were associated with greater impairment. Similarly, repeated measures of BDNF and VEGF were inversely correlated with new functional impairment (B = − 0.001, p = 0.001 and B = − 0.001, p = 0.003, respectively). NSE, a biomarker of acute brain injury, showed a positive correlation between day 0 levels and new functional impairment (ρ = 0.320, p = 0.044). Blood-based biomarkers of regeneration and plasticity may hold prognostic utility for functional impairment among pediatric patients with neurocritical illness and warrant further investigation.

Published
2021

13. Swear words for sale

Author

Gerardine M. Pereira and Kristy Beers Fägersten

Subjects
050101 languages & linguistics, Linguistics and Language, Demographics, Commodification, business.industry, media_common.quotation_subject, 05 social sciences, Taboo, Devaluation, 050801 communication & media studies, Clothing, Language and Linguistics, Linguistics, 0508 media and communications, Word usage, 0501 psychology and cognitive sciences, Optimal distinctiveness theory, business, Psychology, media_common, Spoken language
Abstract

Swearing has traditionally been associated with spoken language; however, swear words are appearing more often in print and, notably, explicitly featured in commercial products. In this paper, we consider this development an example of the commodification of swear words, or ‘swear words for sale’. Our analyses of English-language swear word products show that the taboo nature of swear words is exploited and capitalized upon for commercial gain. We argue that swear word commodities trade on sociolinguistically incongruous aspects of swear word usage, increasing salability of the swear word products by targeting specific demographics. Specifically, we analyze (1) women’s apparel and accessories, (2) domestic items and home décor, and (3) children’s products for adults or articles targeting parents of young children. The study concludes with a discussion of whether the popularization of swearing via such commodification may ultimately result in a loss of distinctiveness and devaluation.

Published
2021

14. Posterolateral or direct lateral approach for hemiarthroplasty after femoral neck fractures: a systematic review

Author

Mohit Bhandari, Loes W A H van Beers, Nienke W. Willigenburg, Hanna C. Willems, Maria C. J. M. Tol, Rudolf W. Poolman, Taco Gosens, and Martin J. Heetveld

Subjects
medicine.medical_specialty, Surgical approach, surgical approach, business.industry, Femoral Neck Fractures, Surgery, Treatment Outcome, trauma, hip fractures, Activities of Daily Living, Quality of Life, Medicine, Humans, Orthopedics and Sports Medicine, Prospective Studies, Hemiarthroplasty, business, Posterolateral approach, Lateral approach, Retrospective Studies
Abstract

Background: The posterolateral approach (PLA) and direct lateral approach (DLA) are the most commonly used approaches for inserting a hemiarthroplasty in the treatment of femoral neck fractures. A recent review concluded that the routine use of PLA should be questioned, but this conclusion itself can be questioned. The aim of this study is to provide an updated overview and critical appraisal of the available evidence, focussing on outcomes most relevant for patients. Methods: We conducted a comprehensive search of literature in the MEDLINE and EMBASE databases and Cochrane Library. Studies (till June 2018) to identify hip fracture clinical trials/comparative studies comparing alternative surgical approaches (PLA and DLA). We explored sources of heterogeneity and conducted pooled analyses when appropriate. Results: 264 potentially eligible studies were identified of which 1 RCT, 3 prospective, 3 registry data and 5 retrospective studies were included. The RCT consisted performance and attrition bias. The mean MINORS score of the prospective/register studies was 17.3 (SD 3.5) and 13.8 (SD 1.9) of the 5 retrospective studies. The GRADE score for all the outcomes was very low. Due to the high and various types of biases across the included studies, we did not pool the data. None of studies assessed the activities of daily living functionality. 6 studies reported significantly more dislocations or reoperations due to dislocation in the PLA group, 6 other studies found no differences. DLA patients were more likely to develop abductor insufficiency leading to limping and more need for walking aids. The PLA patients tended to have better quality of life, less pain and more satisfaction compared to the DLA patients. Conclusion: Based on low-quality studies, PLA may be associated with more dislocations, but patients had less walking problems and a lower tendency to abductor insufficiency compared with DLA. Further clinical trials with methodology rigor are needed to determine which approach is more effective in terms of outcomes relevant to patients.

Published
2021

15. A remarkable case of HbH disease illustrates the relative contributions of the α-globin enhancers to gene expression

Author

Anna M. Rose, Andreas Glenthøj, Chris Fisher, Cornelis L. Harteveld, Douglas R. Higgs, Damien J. Downes, Mohsin Badat, E.J. van Beers, and James O.J. Davies

Subjects
Adult, Male, Erythroblasts, Genotype, Immunology, beta-Globins, Disease, Biology, Biochemistry, α globin, Text mining, alpha-Globins, alpha-Thalassemia, Gene expression, Humans, Erythropoiesis, RNA, Messenger, Enhancer, Alleles, Sequence Deletion, Genetics, Hemoglobin H, Suriname, business.industry, Hemoglobin E, Cell Biology, Hematology, Chromatin, Pedigree, Enhancer Elements, Genetic, Gene Expression Regulation, Female, business, Chromosomes, Human, Pair 16, Gene Deletion
Published
2021

16. Analytical Validation of SKY92 for the Identification of High-Risk Multiple Myeloma

Author

Pieter Sonneveld, Mark van Duin, Daphne Huigh, Rowan Kuiper, Martin H. van Vliet, Lizanne Bosman, Belinda Dumee, Leonie de Best, Marieke Spaan, Erik H. van Beers, and Hematology

Subjects
0301 basic medicine, Restricted maximum likelihood, Concordance, Blood Donors, Risk Assessment, Sensitivity and Specificity, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Recurrence, Cell Line, Tumor, Biomarkers, Tumor, Medicine, Humans, Relapse risk, Short survival, Multiple myeloma, Reproducibility, business.industry, Gene Expression Profiling, Reproducibility of Results, Reference cell, Gene expression classifier, medicine.disease, Prognosis, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, Case-Control Studies, Molecular Medicine, business, Nuclear medicine, Multiple Myeloma, Transcriptome
Abstract

Multiple myeloma (MM) is an incurable plasma cell cancer with a large variability in survival. Patients with MM classified as high risk by the SKY92 gene expression classifier are at high risk of relapse and short survival. Analytical validation of the SKY92 assay was performed with primary bone marrow specimens from 12 patients with MM and 7 reference cell line specimens. The SKY92 results were 100% concordant with the reference and/or their expected result for sensitivity, specificity, microarray stability, and RLT buffer stability. The SKY92 results were 90% concordant for primary specimen stability, 96.4% concordant for intermediate precision, and 80% to 100% concordant for RNA stability. For the cell-line reproducibility, the concordance was at least 92.9%, except for one near-cut point specimen. For the clinical specimen reproducibility, the concordance was 100%, except for two near-cut point specimens. Three independent laboratories were concordant in ≥77.8% and ≥92.9% of experiments for patient specimens and cell lines, respectively. Statistical acceptance thresholds were developed as Δ ≤1.48 (change in SKY92 score) and SD ≤0.45 (SD across SKY92 scores). Using the Clinical and Laboratory Standards Institute method of choice (EP05-A2/A3), restricted maximum likelihood, the observed Δ values (0 to 1.14) and SDs (0.22 to 0.31) passed acceptance criteria. Thus, we successfully present analytical validation for the SKY92 assay as a prognostic molecular test for individual patients with MM.

Published
2021

17. Multi-Institutional Assessment and Crowdsourcing Evaluation of Deep Learning for Automated Classification of Breast Density

Author

Etta D. Pisano, Sheela Agarwal, Katharina Hoebel, Jay B. Patel, Praveer Singh, Keith J. Dreyer, Ken Chang, Bibb Allen, Nathan Gaw, Andrew Beers, Laura Brink, Laura Coombs, Nishanth Thumbavanam Arun, Jayashree Kalpathy-Cramer, Meesam Shah, and Mike Tilkin

Subjects
Digital mammography, Computer science, Breast Neoplasms, BI-RADS, Machine learning, computer.software_genre, Crowdsourcing, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Deep Learning, 0302 clinical medicine, Artificial Intelligence, Humans, Radiology, Nuclear Medicine and imaging, Generalizability theory, Breast Density, Artificial neural network, business.industry, Deep learning, Sampling (statistics), Data set, 030220 oncology & carcinogenesis, Female, Artificial intelligence, business, computer, Mammography
Abstract

Objective We developed deep learning algorithms to automatically assess BI-RADS breast density. Methods Using a large multi-institution patient cohort of 108,230 digital screening mammograms from the Digital Mammographic Imaging Screening Trial, we investigated the effect of data, model, and training parameters on overall model performance and provided crowdsourcing evaluation from the attendees of the ACR 2019 Annual Meeting. Results Our best-performing algorithm achieved good agreement with radiologists who were qualified interpreters of mammograms, with a four-class κ of 0.667. When training was performed with randomly sampled images from the data set versus sampling equal number of images from each density category, the model predictions were biased away from the low-prevalence categories such as extremely dense breasts. The net result was an increase in sensitivity and a decrease in specificity for predicting dense breasts for equal class compared with random sampling. We also found that the performance of the model degrades when we evaluate on digital mammography data formats that differ from the one that we trained on, emphasizing the importance of multi-institutional training sets. Lastly, we showed that crowdsourced annotations, including those from attendees who routinely read mammograms, had higher agreement with our algorithm than with the original interpreting radiologists. Conclusion We demonstrated the possible parameters that can influence the performance of the model and how crowdsourcing can be used for evaluation. This study was performed in tandem with the development of the ACR AI-LAB, a platform for democratizing artificial intelligence.

Published
2020

18. The neurophysiology and seizure outcomes of late onset unexplained epilepsy

Author

Louis Beers, Reisa A. Sperling, Page B. Pennell, Keith A. Johnson, Michael J. Properzi, Yuxiang Zhang, Jasmeer P. Chhatwal, Mohammad Al-Akaidi, Gad A. Marshall, Joseph J. Locascio, Rani A. Sarkis, Aaron P. Schultz, and Emile Farah

Subjects
Male, medicine.medical_specialty, Late onset, Electroencephalography, Article, 050105 experimental psychology, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Framingham Heart Study, Atrophy, Neuroimaging, Seizures, Physiology (medical), Internal medicine, Humans, Medicine, 0501 psychology and cognitive sciences, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, 05 social sciences, Brain, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, White Matter, Sensory Systems, Hyperintensity, Neurology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective To investigate neurophysiologic and neuroimaging characteristics of patients with late onset unexplained epilepsy (LOUE). Methods We performed a retrospective chart review of elderly patients with ICD9 diagnosis codes consistent with epilepsy/seizures. Inclusion criteria included unprovoked seizures, and absence of cortical lesions on magnetic resonance imaging (MRI). Electroencephalograms (EEGs) findings were also analyzed. MRI images were scored for degree of white matter hyperintensities (Fazekas Scale) and mesial temporal atrophy (MTA). Vascular risk factors, and Framingham Heart Study general cardiovascular disease (FHS-CVD) risk scores were compared to controls from the Harvard Aging Brain study (HABS). Results We identified 224 LOUE patients and 8% were drug resistant. Epileptiform abnormalities were captured on EEG in 35%. The location was temporal with left sided predominance in 49%. Fazekas scale consisted of 25% beginning of confluent lesions, and 10% large confluent lesions. MTA scores consisted of 21% moderate-severe hippocampal atrophy. LOUE patients had on average a 2.3% (adjusted), 7.4% (unadjusted) increased FHS-CVD score. Conclusions Our findings highlight LOUE as pharmacosensitive and left temporal predominant. Given the higher prevalence of vascular risk factors, investigations are needed to study their role in pathophysiology. Significance Physicians caring for patients with LOUE should evaluate for vascular risk factors and investigate the presence of hippocampal atrophy.

Published
2020

19. Study protocol: Effectiveness of dual-mobility cups compared with uni-polar cups for preventing dislocation after primary total hip arthroplasty in elderly patients — design of a randomized controlled trial nested in the Dutch Arthroplasty Registry

Author

Rudolf W. Poolman, Dirk Jan F Moojen, Loes W A H van Beers, Tess Glastra van Loon, Marieke F. van Wier, Bart C. H. van der Wal, Amanda D. Klaassen, Nienke W. Willigenburg, and APH - Quality of Care

Subjects
medicine.medical_specialty, Arthroplasty, Replacement, Hip, medicine.medical_treatment, MEDLINE, Prosthesis Design, law.invention, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, Hip Dislocation, Humans, Medicine, Single-Blind Method, Orthopedics and Sports Medicine, Prospective Studies, Registries, 030212 general & internal medicine, Aged, Netherlands, Randomized Controlled Trials as Topic, Protocol (science), Orthopedic surgery, 030222 orthopedics, Hip Fractures, business.industry, Articles, General Medicine, Dual mobility, Arthroplasty, Quality-adjusted life year, Physical therapy, Surgery, Hip Prosthesis, business, RD701-811, Research Article, Total hip arthroplasty
Abstract

Background and purpose — Dislocation is the leading reason for early revision surgery after total hip arthroplasty (THA). The dual-mobility (DM) cup was developed to provide more stability and mechanically reduce the risk of dislocation. Despite the increased use of DM cups, high-quality evidence of their (cost-)effectiveness is lacking. The primary objective of this randomized controlled trial (RCT) is to investigate whether there is a difference in the number of hip dislocations following primary THA, using the posterolateral approach, with a DM cup compared with a unipolar (UP) cup in elderly patients 1 year after surgery. Secondary outcomes include the number of revision surgeries, patient-reported outcome measures (PROMs), and cost-effectiveness. Methods and analysis — This is a prospective multicenter nationwide, single-blinded RCT nested in the Dutch Arthroplasty Registry. Patients ≥ 70 years old, undergoing elective primary THA using the posterolateral approach, will be eligible. After written informed consent, 1,100 participants will be randomly allocated to the intervention or control group. The intervention group receives a THA with a DM cup and the control group a THA with a UP cup. PROMs are collected preoperatively, and 3 months, 1 and 2 years postoperatively. Primary outcome is the difference in number of dislocations between the UP and DM cup within 1 year, reported in the registry (revisions), or by the patients (closed or open reduction). Data will be analyzed using multilevel models as appropriate for each outcome (linear/logistic/survival). An economic evaluation will be performed from the healthcare and societal perspective, for dislocation and quality adjusted life years (QALYs). Trial registration — This RCT is registered at www.clinicaltrials.gov with identification number NCT04031820.

Published
2020

20. Elevated acute phase proteins reflect peripheral inflammation and disease severity in patients with amyotrophic lateral sclerosis

Author

Alireza Faridar, Shixiang Wen, Jason R. Thonhoff, Aaron D. Thome, David R. Beers, Weihua Zhao, Jinghong Wang, Daniel Neal, and Stanley H. Appel

Subjects
Male, 0301 basic medicine, Immunology, Lipopolysaccharide Receptors, lcsh:Medicine, Inflammation, Disease, Monocytes, Article, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Amyotrophic lateral sclerosis, lcsh:Science, Cells, Cultured, Disease burden, Neuroinflammation, Aged, Multidisciplinary, biology, business.industry, Amyotrophic Lateral Sclerosis, lcsh:R, Acute-phase protein, Parkinson Disease, Middle Aged, medicine.disease, 030104 developmental biology, ROC Curve, Neurology, Disease Progression, biology.protein, Female, lcsh:Q, medicine.symptom, business, Lipopolysaccharide binding protein, Biomarkers, 030217 neurology & neurosurgery, Acute-Phase Proteins, Frontotemporal dementia
Abstract

Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem pro-inflammatory neuromuscular disorder compromising muscle function resulting in death. Neuroinflammation is known to accelerate disease progression and accentuate disease severity, but peripheral inflammatory processes are not well documented. Acute phase proteins (APPs), plasma proteins synthesized in the liver, are increased in response to inflammation. The objective of this study was to provide evidence for peripheral inflammation by examining levels of APPs, and their contribution to disease burden and progression rates. Levels of APPs, including soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP), and C-reactive protein (CRP), were elevated in sera, and correlated positively with increased disease burden and faster progression. sCD14 was also elevated in patients’ CSF and urine. After a 3 year follow-up, 72% of the patients with sCD14 levels above the receiver operating characteristics cutoff were deceased whereas only 28% below the cutoff were deceased. Furthermore, disease onset sites were associated with disease progression rates and APP levels. These APPs were not elevated in sera of patients with Alzheimer’s Disease, frontotemporal dementia, or Parkinson’s Disease. These collective APPs accurately reflect disease burden, progression rates, and survival times, reinforcing the concept of ALS as a disorder with extensive systemic pro-inflammatory responses.

Published
2020

21. Chemical Mechanical Surface Nano-Structuring (CMNS) Implementation on Titanium Based Implants to Enhance Corrosion Resistance and Control Biocompatibility

Author

G. Bahar Basim, Debashish Sur, and Kimberly Beers

Subjects
Materials science, Passivation, Biocompatibility, business.industry, Mechanical Engineering, technology, industry, and agriculture, chemistry.chemical_element, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, 0104 chemical sciences, Corrosion, chemistry, Machining, Mechanics of Materials, Chemical-mechanical planarization, Microelectronics, General Materials Science, Wafer, 0210 nano-technology, business, Titanium
Abstract

Titanium is the metal of choice for many implantable devices including dental prostheses, orthopaedic devices and cardiac pacemakers. Titanium and its alloys are favoured for hard tissue replacement because of their high strength to density ratio providing excellent mechanical properties and biocompatible surface characteristics promoting in-vivo passivation due to spontaneous formation of a native protective oxide layer in the presence of an oxidizer. This study focuses on the development of a three-dimensional chemical, mechanical, surface nano-structuring (CMNS) process to induce smoothness or controlled nano-roughness on the bio-implant surfaces, particularly for applications in dental implants. CMNS is an extension of the chemical mechanical polishing (CMP) process. CMP is utilized in microelectronics manufacturing for planarizing the wafer surfaces to enable photolithography and multilayer metallization. In biomaterials applications, the same approach can be utilized to induce controlled surface nanostructure on three-dimensional implantable objects to promote or demote cell attachment. As a synergistic method of nano-structuring on the implant surfaces, CMNS also makes the titanium surface more adaptable for the bio-compatible coatings as well as the cell and tissue growth as demonstrated by the electrochemical and surface wettability evaluations on implants prepared by DI-water machining versus oil based machining.

Published
2020

22. A novel signature based on microvascular invasion predicts the recurrence of HCC

Author

Zhihui Wang, Binbin Du, Yanzhou Zhang, Fang Wang, and Beers Jarad

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, Multivariate analysis, Mrna expression, mRNA, lcsh:Medicine, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Internal medicine, Cancer genome, medicine, Humans, Retrospective Studies, Signature hepatocellular carcinoma, Framingham Risk Score, Receiver operating characteristic analysis, business.industry, Research, Liver Neoplasms, lcsh:R, General Medicine, Prognosis, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Neoplasm Recurrence, Local, business, Microvascular invasion
Abstract

Background and objectives In hepatocellular carcinoma (HCC) patients, microvascular invasion (MVI) is associated with worse outcomes regardless of treatment. No single reliable preoperative factor exists to predict MVI. The aim of the work described here was to develop a new MVI− based mRNA biomarker to differentiate between high and low risk patients. Methods Using The Cancer Genome Atlas (TCGA) database, we collected data from 315 HCC patients, including mRNA expression and complete clinical data. We generated a seven-mRNA signature to predict patient outcomes. The mRNA signature was validated using the GSE36376 cohort. Finally, we tested the formula in our own 53 HCC patients using qPCR for the seven mRNAs and analyzing the computed tomography (CT) features. Results This seven‐mRNA signature significantly correlated with length of recurrence-free survival (RFS) and overall survival (OS) for both the training and validation groups. RFS and OS were briefer in high risk versus low risk patients. A Kaplan–Meier analysis also indicated that survival time was significantly shortened in the high risk group versus the low risk group. Time-dependent receiver operating characteristic analysis demonstrated good predictive performance for the seven-mRNA signature. The mRNA signature also acts as an independent factor according to a Multivariate analysis. Our results are consistent with the seven-mRNA formula risk score. Conclusion Our research showed a novel seven-mRNA biomarker based on MVI predicting RFS and OS in HCC patients. This mRNA signature can stratify patients into subgroups based on their risk of recurrence to help guide individualized treatment and precision management in HCC.

Published
2020

23. Thin Film Characterization on Cu/SnAg Solder Interface for 3D Packaging Technologies

Author

Kimberly Beers, Andrew E. Hollowell, and G. Bahar Basim

Subjects
Materials science, business.industry, Mechanical Engineering, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, 0104 chemical sciences, Mechanics of Materials, Plating, Soldering, Optoelectronics, Microelectronics, General Materials Science, Wafer, Thin film, 0210 nano-technology, Electroplating, business, Current density, Flip chip
Abstract

Copper is a commonly used interconnect metal in microelectronic interconnects due to its exceptional electrical and thermal properties. Particularly in applications of the 2.5 and 3D integration, Cu is utilized in through-silicon-vias (TSVs) and flip chip interconnects between microelectronic chips for providing miniaturization, lower power and higher performance than current 2D packaging approaches. SnAg capped Cu pillars are a common high-density interconnect technology for flip chip bonding. For these interconnects, specific properties of the Cu surface, such as roughness and cleanliness, are an important factor in the process to ensure quality solder bumps. During electroplating, tight processing parameters must be met so that defects are avoided, and high bump uniformity is achieved. An understanding of the interactions at the solder and Cu pillar interface is needed, based on the electroplating parameters, to determine the best method for populating solder on the wafer surface. In this study, surface treatment techniques such as oxygen plasma cleaning were performed on the Cu surfaces and the SnAg plating chemistry for depositing the solder were evaluated through hull cell testing to qualitatively determine the range of current densities to investigate. It was observed that current density while plating played a large role in solder bump deposition morphology. At the higher current densities greater than 60 mA/cm2, bump height non-uniformity and dendritic growth are observed and at lower current densities, less than or equal to 60 mA/cm2, uniform, continuous bump height occurred.

Published
2020

24. Inclusion in responsible innovation: revisiting the desirability of opening up

Author

Barbara van Mierlo, Pieter J. Beers, and A.C. Hoes

Subjects
Information Systems and Management, Strategy and Management, media_common.quotation_subject, WASS, 050905 science studies, 0603 philosophy, ethics and religion, Panacea (medicine), Order (exchange), Management of Technology and Innovation, Political science, greenhouse sector, Responsible innovation, opening up, media_common, business.industry, 05 social sciences, Closing (real estate), Perspective (graphical), 06 humanities and the arts, Public relations, Innovation- and Risk Management and Information Governance, inclusion, Framing (social sciences), Balance (accounting), issue framing, Technologie and Innovatie, Knowledge Technology and Innovation, dairy, Kennis, 060301 applied ethics, 0509 other social sciences, business, Kennis, Technologie and Innovatie, Inclusion (education), Meaning (linguistics)
Abstract

We investigate opening up, a crucial aim of responsible innovation, in the situation of companies initiating sector-wide change in order to take societal responsibility. Two case studies in agriculture were conducted, using a framing perspective that enlightens how issues are (re-)defined and acquire meaning in conversations. For both industry-led innovation initiatives, this showed when and how the initiatives’ issue frames opened up and closed down. The results suggest that the inclusion of actors is not the panacea for opening up the innovation processes, given that responsiveness seemed more relevant. Furthermore, we confirm that closing down may occur simultaneously with opening up and as such is an inherent part of responsible innovation processes. Hence, in addition to the advocated opening up, the question of how to balance it with closing down in order to arrive at collaborative action deserves full attention.

Published
2020

25. DeepNeuro: an open-source deep learning toolbox for neuroimaging

Author

Katharina Hoebel, Jayashree Kalpathy-Cramer, James M. Brown, Andrew Beers, Bruce R. Rosen, K. Ina Ly, Priscilla K. Brastianos, Elizabeth R. Gerstner, Ken Chang, Sara M. Tolaney, and Jay B. Patel

Subjects
Computer science, Evaluation data, Neuroimaging, Article, 050105 experimental psychology, 03 medical and health sciences, Deep Learning, 0302 clinical medicine, Human–computer interaction, Image Processing, Computer-Assisted, Humans, Preprocessor, 0501 psychology and cognitive sciences, computer.programming_language, Artificial neural network, business.industry, General Neuroscience, Deep learning, 05 social sciences, Python (programming language), Toolbox, Open source, Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Software, Information Systems
Abstract

Translating deep learning research from theory into clinical practice has unique challenges, specifically in the field of neuroimaging. In this paper, we present DeepNeuro, a Python-based deep learning framework that puts deep neural networks for neuroimaging into practical usage with a minimum of friction during implementation. We show how this framework can be used to design deep learning pipelines that can load and preprocess data, design and train various neural network architectures, and evaluate and visualize the results of trained networks on evaluation data. We present a way of reproducibly packaging data pre- and postprocessing functions common in the neuroimaging community, which facilitates consistent performance of networks across variable users, institutions, and scanners. We show how deep learning pipelines created with DeepNeuro can be concisely packaged into shareable Docker and Singularity containers with user-friendly command-line interfaces.

Published
2020

26. Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia

Author

Stephanie van Straaten, Stephan J. L. Bakker, Michele F Eisenga, Richard van Wijk, Martin H. de Borst, Andreas Glenthøj, Annelies J. Van Vuren, Carlo A. J. M. Gaillard, Eduard J. van Beers, Groningen Kidney Center (GKC), and Groningen Institute for Organ Transplantation (GIOT)

Subjects
0301 basic medicine, Ineffective erythropoiesis, Fibroblast growth factor 23, medicine.medical_specialty, SICKLE-CELL-DISEASE, Iron, Peptide Hormones, Inflammation, 030204 cardiovascular system & hematology, Hereditary Hemolytic Anemia, medicine.disease_cause, Anemia, Hemolytic, Congenital, MURINE, 03 medical and health sciences, 0302 clinical medicine, Red Cells, Iron, and Erythropoiesis, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Erythropoietin, business.industry, Hematology, Erythroferrone, Fibroblast Growth Factors, Fibroblast Growth Factor-23, stomatognathic diseases, 030104 developmental biology, Endocrinology, Fibroblast growth factor receptor, Erythropoiesis, medicine.symptom, business, REGULATOR, BONE, medicine.drug
Abstract

Recently, erythropoietin (EPO) was identified as regulator of fibroblast growth factor 23 (FGF23). Proteolytic cleavage of biologically active intact FGF23 (iFGF23) results in the formation of C-terminal fragments (cFGF23). An increase in cFGF23 relative to iFGF23 suppresses FGF receptor signaling by competitive inhibition. EPO lowers the i:cFGF23 ratio, thereby overcoming iFGF23-mediated suppression of erythropoiesis. We investigated EPO-FGF23 signaling and levels of erythroferrone (ERFE) in 90 patients with hereditary hemolytic anemia (www.trialregister.nl [NL5189]). We show, for the first time, the importance of EPO-FGF23 signaling in hereditary hemolytic anemia: there was a clear correlation between total FGF23 and EPO levels (r = +0.64; 95% confidence interval [CI], 0.09-0.89), which persisted after adjustment for iron load, inflammation, and kidney function. There was no correlation between iFGF23 and EPO. Data are consistent with a low i:cFGF23 ratio. Therefore, as expected, we report a correlation between EPO and ERFE in a diverse set of hereditary hemolytic anemias (r = +0.47; 95% CI, 0.14-0.69). There was no association between ERFE and total FGF23 or iFGF23, which suggests that ERFE does not contribute to the connection between FGF23 and EPO. These findings open a new area of research and might provide potentially new druggable targets with the opportunity to ameliorate ineffective erythropoiesis and the development of disease complications in hereditary hemolytic anemias.

Published
2020

27. Conditional deletion of Nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice

Author

Dmytro Dvornikov, Jan Hegermann, Simon G. Fraumann, Daniela Rotin, Surafel Mulugeta, Felix Herth, Michael Kreuter, Julia Duerr, Hiroshi Kawabe, Magdalena Szczygiel, Ayça Seyhan Agircan, Ursula Klingmüller, Clemens Kreutz, Mark O. Wielpütz, Dominik Leitz, Matthias Ochs, Marcus A. Mall, Theresa A. Engelmann, Philip Konietzke, Piotr K. Zadora, Thomas Muley, Michael F. Beers, and Lars Knudsen

Subjects
Proteomics, 0301 basic medicine, Pathology, Ubiquitylation, Biopsy, Nedd4 Ubiquitin Protein Ligases, General Physics and Astronomy, Pathogenesis, Mice, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, Pulmonary fibrosis, lcsh:Science, Lung, Mice, Knockout, Multidisciplinary, Interstitial lung disease, Pirfenidone, Middle Aged, respiratory system, Mucin-5B, humanities, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine.drug, Adult, medicine.medical_specialty, Pyridones, Science, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Animals, Humans, Epithelial Sodium Channels, Aged, NEDD4L, Respiratory tract diseases, business.industry, Ubiquitination, Epithelial Cells, General Chemistry, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Disease Models, Animal, 030104 developmental biology, lcsh:Q, business
Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by patchy scarring of the distal lung with limited therapeutic options and poor prognosis. Here, we show that conditional deletion of the ubiquitin ligase Nedd4-2 (Nedd4l) in lung epithelial cells in adult mice produces chronic lung disease sharing key features with IPF including progressive fibrosis and bronchiolization with increased expression of Muc5b in peripheral airways, honeycombing and characteristic alterations in the lung proteome. NEDD4-2 is implicated in the regulation of the epithelial Na+ channel critical for proper airway surface hydration and mucus clearance and the regulation of TGFβ signaling, which promotes fibrotic remodeling. Our data support a role of mucociliary dysfunction and aberrant epithelial pro-fibrotic response in the multifactorial disease pathogenesis. Further, treatment with the anti-fibrotic drug pirfenidone reduced pulmonary fibrosis in this model. This model may therefore aid studies of the pathogenesis and therapy of IPF., Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Here, the authors show that deficiency of the E3 ubiqutin-protein ligase Nedd4-2 in airway epithelial cells causes IPF-like disease in adult mice. This model may aid studies of the pathogenesis and therapy of IPF.

Published
2020

28. When Is Moving a Cursor With a Computer Mouse Intuitive?

Author

Robert J. van Beers, Margreet Schonwetter, Eli Brenner, Marielle J. Stam, Jeroen B. J. Smeets, Myriam L. de Graaf, AMS - Sports, IBBA, and Sensorimotor Control

Subjects
Computer science, Experimental and Cognitive Psychology, Frame of reference, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Artificial Intelligence, Humans, 0501 psychology and cognitive sciences, Computer vision, Computer Peripherals, business.industry, Action, intention, and motor control, perception/action, 05 social sciences, frames of reference, Cursor (user interface), Sensory Systems, body regions, Short and Sweet, Ophthalmology, tool use, sensorimotor transformations, Artificial intelligence, Computer mouse, business, 030217 neurology & neurosurgery, computer mouse, Intuition, Psychomotor Performance
Abstract

Contains fulltext : 226706.pdf (Publisher’s version ) (Open Access) People have a good intuition of how to move a computer mouse to place a cursor at a desired position on a screen. This is surprising because the hand and the mouse are at different locations and they generally move in different directions and over different distances. But using a computer mouse is not always intuitive: try positioning a cursor after turning the mouse by 90° in your hand. To examine when using a computer mouse is intuitive, we asked participants to move a cursor to targets on a screen by moving a mouse along a surface. We varied the orientation of this surface in space and that of the mouse in the hand. Participants performed best when the mapping between hand and cursor motion was close to what we are accustomed to, either in space or relative to the forearm. 4 p.

Published
2020

29. Prediction of regaining consciousness despite an early epileptiform EEG after cardiac arrest

Author

Jong Woo Lee, Andrea O. Rossetti, Louis Beers, Jan Novy, Mauro Oddo, Vincent Alvarez, and Giuseppina Barbella

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Receiver operating characteristic, business.industry, media_common.quotation_subject, 030208 emergency & critical care medicine, Retrospective cohort study, Electroencephalography, Clinical neurophysiology, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Internal medicine, Cohort, medicine, Cardiology, Neurology (clinical), Consciousness, business, 030217 neurology & neurosurgery, Cohort study, media_common
Abstract

ObjectiveAfter cardiac arrest (CA), epileptiform EEG, occurring in about 1/3 of patients, often but not invariably heralds poor prognosis. We tested the hypothesis that a combination of specific EEG features identifies patients who may regain consciousness despite early epileptiform patterns.MethodsWe retrospectively analyzed a registry of comatose patients post-CA (2 Swiss centers), including those with epileptiform EEG. Background and epileptiform features in EEGs 12–36 hours or 36–72 hours from CA were scored according to the American Clinical Neurophysiology Society nomenclature. Best Cerebral Performance Category (CPC) score within 3 months (CPC 1–3 vs 4–5) was the primary outcome. Significant EEG variables were combined in a score assessed with receiver operating characteristic curves, and independently validated in a US cohort; its correlation with serum neuron-specific enolase (NSE) was also tested.ResultsOf 488 patients, 107 (21.9%) had epileptiform EEG p < 0.00001 each), 12–36 and 36–72 hours reactivity (p < 0.0001 each), 36–72 hours normal background amplitude (p = 0.0004), and stimulus-induced discharges (p = 0.0001) correlated with favorable outcome. The combined 6-point score cutoff ≥2 was 100% sensitive (95% confidence interval [CI], 78%–100%) and 70% specific (95% CI, 59%–80%) for CPC 1–3 (area under the curve [AUC], 0.98; 95% CI, 0.94–1.00). Increasing score correlated with NSE (ρ = −0.46, p = 0.0001). In the validation cohort (41 patients), the score was 100% sensitive (95% CI, 60%–100%) and 88% specific (95% CI, 73%–97%) for CPC 1–3 (AUC, 0.96; 95% CI, 0.91–1.00).ConclusionPrognostic value of early epileptiform EEG after CA can be estimated combining timing, continuity, reactivity, and amplitude features in a score that correlates with neuronal damage.

Published
2020

30. Racial and Ethnic Disparities in Pregnancy-Related Acute Kidney Injury

Author

Kinsuk Chauhan, Mihir Dave, Huei Hsun Wen, Lili Chan, Aparna Saha, Steven G. Coca, Girish N. Nadkarni, and Kelly Beers

Subjects
medicine.medical_specialty, Original Investigations, urologic and male genital diseases, Logistic regression, White People, Miscarriage, Pregnancy, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Eclampsia, business.industry, Incidence (epidemiology), Infant, Newborn, Retrospective cohort study, Hispanic or Latino, General Medicine, Odds ratio, Acute Kidney Injury, medicine.disease, United States, female genital diseases and pregnancy complications, Black or African American, Female, Diagnosis code, business
Abstract

BACKGROUND: Pregnancy-related AKI (PR-AKI) is increasing in the United States. PR-AKI is associated with adverse maternal outcomes. Disparities in racial/ethnic differences in PR-AKI by race have not been studied. METHODS: This was a retrospective cohort study using the National Inpatient Sample (NIS) from 2005 to 2015. We identified patients who were admitted for a pregnancy-related diagnosis using the Neomat variable provided by the NIS database that indicates the presence of a maternal or neonatal diagnosis code or procedure code. PR-AKI was identified using ICD codes. Survey logistic regression was used for multivariable analysis adjusting for age, medical comorbidities, socioeconomic factors, and hospital/admission factors. RESULTS: From 48,316,430 maternal hospitalizations, 34,001 (0.07%) were complicated by PR-AKI. Hospitalizations for PR-AKI increased from 3.5/10,000 hospitalizations in 2005 to 11.8/10,000 hospitalizations in 2015 with the largest increase seen in patients aged ≥35 and black patients. PR-AKI was associated with higher odds of miscarriage (adjusted odds ratio [aOR], 1.64; 95% CI, 1.34 to 2.07) and mortality (aOR, 1.53; 95% CI, 1.25 to 1.88). After adjustment for age, medical comorbidities, and socioeconomic factors, blacks were more likely than whites to develop PR-AKI (aOR, 1.17; 95% CI, 1.04 to 1.33). On subgroup analyses in hospitalizations of patients with PR-AKI, blacks and Hispanics were more likely to have preeclampsia/eclampsia compared with whites (aOR, 1.29; 95% CI, 1.01 to 1.65; and aOR, 1.69; 95% CI, 1.23 to 2.31, respectively). Increased odds of mortality in PR-AKI compared with whites were only seen in black patients (aOR, 1.61; 95% CI, 1.02 to 2.55). CONCLUSIONS: The incidence of PR-AKI has increased and the largest increase was seen in older patients and black patients. PR-AKI is associated with miscarriages, adverse discharge from hospital, and mortality. Black and Hispanic patients with PR-AKI were more likely to have adverse outcomes than white patients. Further research is needed to identify factors contributing to these discrepancies.

Published
2020

31. Natural language processing of electronic health records is superior to billing codes to identify symptom burden in hemodialysis patients

Author

Kumardeep Chaudhary, Alex D. Federman, Lili Chan, Steven G. Coca, Kinsuk Chauhan, Girish N. Nadkarni, Neha Debnath, Kelly Beers, Pattharawin Pattharanitima, Aparna Saha, Amy A. Yau, Aine Duffy, Peter Kotanko, Judy H. Cho, and Tielman Van Vleck

Subjects
0301 basic medicine, Databases, Factual, Nausea, 030232 urology & nephrology, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Electronic Health Records, Humans, Medicine, Depression (differential diagnoses), Natural Language Processing, business.industry, Patient-centered outcomes, Geriatric nephrology, Biobank, 030104 developmental biology, Nephrology, Informatics, Cohort, Vomiting, Artificial intelligence, medicine.symptom, business, computer, Algorithms, Natural language processing
Abstract

Symptoms are common in patients on maintenance hemodialysis but identification is challenging. New informatics approaches including natural language processing (NLP) can be utilized to identify symptoms from narrative clinical documentation. Here we utilized NLP to identify seven patient symptoms from notes of maintenance hemodialysis patients of the BioMe Biobank and validated our findings using a separate cohort and the MIMIC-III database. NLP performance was compared for symptom detection with International Classification of Diseases (ICD)-9/10 codes and the performance of both methods were validated against manual chart review. From 1034 and 519 hemodialysis patients within BioMe and MIMIC-III databases, respectively, the most frequently identified symptoms by NLP were fatigue, pain, and nausea/vomiting. In BioMe, sensitivity for NLP (0.85 - 0.99) was higher than for ICD codes (0.09 - 0.59) for all symptoms with similar results in the BioMe validation cohort and MIMIC-III. ICD codes were significantly more specific for nausea/vomiting in BioMe and more specific for fatigue, depression, and pain in the MIMIC-III database. A majority of patients in both cohorts had four or more symptoms. Patients with more symptoms identified by NLP, ICD, and chart review had more clinical encounters. NLP had higher specificity in inpatient notes but higher sensitivity in outpatient notes and performed similarly across pain severity subgroups. Thus, NLP had higher sensitivity compared to ICD codes for identification of seven common hemodialysis-related symptoms, with comparable specificity between the two methods. Hence, NLP may be useful for the high-throughput identification of patient-centered outcomes when using electronic health records.

Published
2020

32. Beneficial effects of exercise training on cognitive performances during total sleep deprivation in healthy subjects

Author

Mathias Guillard, Cyprien Bourrilhon, D. Gomez-Merino, Pierre-Emmanuel Tardo-Dino, Arnaud Rabat, Pierrick J. Arnal, Fabien Sauvet, Mounir Chennaoui, Mégane Erblang, Pascal Van Beers, Alexandra Malgoyre, C. Drogou, and Damien Leger

Subjects
Adult, Male, Multiple Sleep Latency Test, endocrine system, medicine.medical_specialty, Time Factors, Microsleep, Polysomnography, media_common.quotation_subject, education, Audiology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Reaction Time, medicine, Humans, Attention, Effects of sleep deprivation on cognitive performance, Wakefulness, Exercise, media_common, medicine.diagnostic_test, business.industry, Psychomotor vigilance task, VO2 max, General Medicine, Training effect, Healthy Volunteers, Sleep deprivation, Memory, Short-Term, 030228 respiratory system, Sleep Deprivation, France, medicine.symptom, business, Psychomotor Performance, 030217 neurology & neurosurgery, Vigilance (psychology)
Abstract

Objective Exercise training has been shown to improve learning and memory, and to protect against the negative impact of sleep deprivation. The aim of this study was to investigate the effects of seven weeks of moderate- and high-intensity interval exercise training on vigilance/sustained attention, inhibition processes and working memory during 40-h total sleep deprivation (TSD) in 16 healthy young men. Methods The subjects were evaluated before (Baseline, BAS) and during TSD, and the day after a night of recovery sleep (Recovery, REC). Results Exercise training significantly decreased errors and increased speed assessed by the psychomotor vigilance task (PVT) during TSD and REC while no difference was found in executive inhibition (Go–noGo task) and working memory (2-Back task) performances. The multiple sleep latency test results were higher during BAS and REC at Post-exercise training, and no difference occurred in subjective sleepiness and daytime microsleeps over the 40-h TSD. The PVT speed was positively correlated with maximal oxygen consumption and maximal aerobic power measured before entry in the in-laboratory TSD protocol, and stage 3 sleep duration measured during the first night in the in-laboratory TSD protocol (N-1). Exercise training effects on sleep were found during the night recovery with lower stage-3 sleep and higher rapid eye movement (REM) sleep durations. An exercise training effect was also found on free insulin-like growth factor I levels with lower levels during TSD at Post-exercise training. Conclusions In healthy young men, exercise training reduced sleep pressure at baseline and protected against sustained attention deficits induced by TSD with persistent effect after one night of recovery sleep. Nevertheless, exercise training was not effective in reducing deficits in executive inhibition and working memory induced by TSD.

Published
2020

33. Prognostic gene expression analysis in a retrospective, multinational cohort of 155 multiple myeloma patients treated outside clinical trials

Author

Rowan Kuiper, Yan-Ting Chen, Stefania Oliva, Erik T. Valent, Torsten Haferlach, Alessandra Larocca, Wee Joo Chng, Pieter Sonneveld, Martin H. van Vliet, Erik H. van Beers, and Hematology

Subjects
Oncology, medicine.medical_specialty, Pharmacogenomic Variants, Clinical Biochemistry, Bone Marrow Cells, Context (language use), Internal medicine, Biomarkers, Tumor, Humans, Medicine, Multiple myeloma, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, business.industry, Gene Expression Profiling, Biochemistry (medical), Hazard ratio, Disease Management, gene expression profiling, multiple myeloma, prognostication, Hematology, General Medicine, Prognosis, medicine.disease, Confidence interval, Clinical trial, Gene expression profiling, medicine.anatomical_structure, Cohort, Bone marrow, Multiple Myeloma, Transcriptome, business
Abstract

Objectives: Typically, prognostic capability of gene expression profiling (GEP) is studied in the context of clinical trials, for which 50%-80% of patients are not eligible, possibly limiting the generalizability of findings to routine practice. Here, we evaluate GEP analysis outside clinical trials, aiming to improve clinical risk assessment of multiple myeloma (MM) patients. Methods: A total of 155 bone marrow samples from MM patients were collected from which RNA was analyzed by microarray. Sixteen previously developed GEP-based markers were evaluated, combined with survival data, and studied using Cox proportional hazard regression. Results: Gene expression profiling-based markers SKY92 and the PR-cluster were shown to be independent prognostic factors for survival, with hazard ratios and 95% confidence interval of 3.6 [2.0-6.8] (P

Published
2022

34. Treatment of Autoimmune Diseases with Therapeutic Antibodies

Author

van Beers, Joyce J B C, Damoiseaux, Jan G M C, Houen, Gunnar, RS: Carim - B01 Blood proteins & engineering, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Central Diagnostic Lab

Subjects
Programmed cell death, Biological Products, biology, business.industry, Autoimmune Diseases/therapy, Cell, medicine.disease, Infections, Mice, Immune system, medicine.anatomical_structure, Immunologic Deficiency Syndromes/therapy, Immunology, Knockout mouse, medicine, Primary immunodeficiency, biology.protein, Animals, Humans, Disease Susceptibility, Antibody, business, Immunodeficiency, Function (biology)
Abstract

Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the autoimmunology clinic and many more are on the edge to follow. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas the former target results in neutralization of the soluble factor, the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency. Knowing the exact function of the respective components enables the risk stratification for possible infectious complications in patients treated with biologics. Much of the understanding of the function of immune cells and their associated molecules, in relation to redundancy in the immune system, is derived from studies in knockout mice. However, as mice are not men in terms of their life-expectancy, their infection exposure, or the composition of their immune system, the most useful knowledge for estimating the consequence of therapeutic intervention on immune competence comes from monitoring patients. In the current chapter, we focus on patients with a primary immunodeficiency (PID) because they provide us with a unique perspective to estimate the redundancy of a certain genetic defect for overall immune competence. These patients have inborn errors of the immune system that, in general, are due to single gene defects. Depending on the immunological pathway that is defective, patients can present with different types of (opportunistic) infectious diseases, as well as other clinical manifestations. Based on selected examples, we focus in this chapter on finding parallels in the infectious risk of autoimmune patients treated with biologics and PID patients with a defect in the immunological pathway that is affected by the respective biologic. The goal is to learn from the (dis)similarities between both patient populations in terms of safety profiles of biologic treatments.

Published
2022

35. Quantification of hepatic steatosis with ultrasound: promising role of attenuation imaging coefficient in a biopsy-proven cohort

Author

Marco Dioguardi Burgio, Philippe Garteiser, Valérie Paradis, Valérie Vilgrain, Edouard Reizine, Maxime Ronot, Pierre-Emmanuel Rautou, Bernard E. Van Beers, and Laurent Castera

Subjects
Adult, Male, medicine.medical_specialty, Biopsy, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Aged, Ultrasonography, Neuroradiology, Aged, 80 and over, medicine.diagnostic_test, business.industry, Attenuation, Ultrasound, General Medicine, Middle Aged, medicine.disease, Fatty Liver, Liver, ROC Curve, 030220 oncology & carcinogenesis, Attenuation coefficient, Liver biopsy, Mann–Whitney U test, Female, Radiology, Steatosis, Nuclear medicine, business
Abstract

To prospectively assess the role of the US attenuation imaging coefficient (AC) for the diagnosis and quantification of hepatic steatosis.One hundred and one patients underwent liver biopsy and US-AC measurement on the same day. Liver steatosis was graded according to biopsy as absent (S05%), mild (S1 5-33%), moderate (S2 33-66%), or severe (S366%); liver fibrosis was graded from F0 to F4. The correlation between AC and steatosis on pathology (%) was calculated using the Pearson correlation coefficient. The Student t or Mann-Whitney U test was used to compare continuous variables and ROC curve analysis was used to assess diagnostic performance of AC in diagnosing steatosis.Overall, 43 (42%), 35 (35%), 12 (12%), and 11 (11%) patients were classified as S0, S1, S2, and S3, respectively. The AC was positively correlated with steatosis as a continuous variable (%) on pathology (r = 0.58, p0.01). Patients with steatosis of any grade had a higher AC than those without steatosis (mean 0.77 ± 0.13 vs. 0.63 ± 0.09 dB/cm/MHz, respectively; p0.01, AUROC = 0.805). Patients with S2-S3 had a higher AC than patients with S0-1 (0.85 ± 0.11 vs. 0.67 ± 0.11 dB/cm/MHz, respectively; p0.01, AUROC = 0.892). AC0.69 dB/cm/MHz had a sensitivity and specificity of 76% and 86%, respectively, for diagnosing any grade of steatosis (S1-S3), and AC0.72 dB/cm/MHz had a sensitivity and specificity of 96% and 74%, respectively, for diagnosing S2-S3. The presence of advanced fibrosis (F3-F4) did not affect the calculated AC.The attenuation imaging coefficient is a promising quantitative technique for the non-invasive diagnosis and quantification of hepatic steatosis.• Measurement of the attenuation coefficient is achieved with a very high rate of technical success. • We found a significant positive correlation between the attenuation coefficient and the grade of steatosis on pathology. • The attenuation imaging coefficient is a promising quantitative technique for the noninvasive diagnosis and quantification of hepatic steatosis.

Published
2019

36. Perinatal Mental Health Task Force: Integrating Care Across a Pediatric Hospital Setting

Author

Melissa Long, Penelope Theodorou, Lee Beers, Sarah Barclay Hoffman, Lamia Soghier, and Lenore Jarvis

Subjects
Best practice, Advisory Committees, Interpersonal communication, Nursing, Multidisciplinary approach, Early Medical Intervention, Intensive Care Units, Neonatal, Intervention (counseling), Health care, Humans, Childbirth, Medicine, Program Development, Mood Disorders, business.industry, Puerperal Disorders, Hospitals, Pediatric, Anxiety Disorders, Mental health, Psychological evaluation, Mental Health, District of Columbia, Pediatrics, Perinatology and Child Health, Female, Emergency Service, Hospital, business
Abstract

Perinatal mood and anxiety disorders (PMADs) are the most common complication of childbirth, with suicide a leading cause of postpartum deaths. PMADs are associated with poor maternal, infant, and family outcomes. Identification and early intervention are imperative for successful treatment. This case study describes the implementation and outcomes of a multidisciplinary Perinatal Mental Health Task Force (“Task Force”) at one urban academic children’s hospital that was created to promote systems change and health care policy solutions for improved identification and treatment of PMADs. Using the social ecological model as a framework, the Task Force addressed care at the individual, interpersonal, organizational, community, and policy levels. The Task Force applied lessons learned from division-specific screening initiatives to create best practices and make hospital-wide recommendations. This foundational work enabled us to build community bridges and break down internal barriers to shift our pediatric hospital toward prioritizing perinatal mental health. As a result, screening expanded to multiple hospital locations and became a hospital corporate goal, the Perinatal Mental Health Screening Tool Kit was created and disseminated within the community, Task Force members testified in governmental hearings and joined national organizations to inform policy, and Task Force and community collaborations resulted in significant grant funding. Lessons learned have been disseminated nationally. Moving forward, we aim to expand our program and partnerships to ensure that caregivers of infants receive appropriate mental health support to strengthen family well-being. The Task Force can serve as a model for advocates looking to expand and integrate PMAD care.

Published
2021

37. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author

Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan, Backues, Steven, Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric, Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima, Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio, Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter, Barmada, Sami, Barreiro, Esther, Barreto, George, Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav, Basagoudanavar, Suresh, Bassham, Diane, Bast, Robert, Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne, Baumgarner, Bradley, Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz, Beck, George, Beers, Michael, Begun, Jakob, Behrends, Christian, Behrens, Georg, Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno, Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin, Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri, Besteiro, Sebastien, Betin, Virginie, Beyaert, Rudi, Bezbradica, Jelena, Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor, Bijian, Krikor, Billes, Viktor, Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa, Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, Blasiak, Janusz, Blomgran, Robert, Blomgren, Klas, Blum, Janice, Boada-Romero, Emilio, Boban, Mirta, Boesze-Battaglia, Kathleen, Boeuf, Philippe, Boland, Barry, Bomont, Pascale, Bonaldo, Paolo, Bonam, Srinivasa Reddy, Bonfili, Laura, Bonifacino, Juan, Boone, Brian, Bootman, Martin, Bordi, Matteo, Borner, Christoph, Bornhauser, Beat, Borthakur, Gautam, Bosch, Jürgen, Bose, Santanu, botana, luis, Botas, Juan, Boulanger, Chantal, Boulton, Michael, Bourdenx, Mathieu, Bourgeois, Benjamin, Bourke, Nollaig, Bousquet, Guilhem, Boya, Patricia, Bozhkov, Peter, Bozi, Luiz, Bozkurt, Tolga, Brackney, Doug, Brandts, Christian, Braun, Ralf, Braus, Gerhard, Bravo-Sagua, Roberto, Bravo-San Pedro, José, Brest, Patrick, Bringer, Marie-Agnès, Briones-Herrera, Alfredo, Broaddus, V Courtney, Brodersen, Peter, Brodsky, Jeffrey, Brody, Steven, Bronson, Paola, Bronstein, Jeff, Brown, Carolyn, Brown, Rhoderick, Brum, Patricia, Brumell, John, Brunetti-Pierri, Nicola, Bruno, Daniele, Bryson-Richardson, Robert, Bucci, Cecilia, Buchrieser, Carmen, Bueno, Marta, Buitrago-Molina, Laura Elisa, Buraschi, Simone, Buch, Shilpa, Buchan, J Ross, Buckingham, Erin, Budak, Hikmet, Budini, Mauricio, Bultynck, Geert, Burada, Florin, Burgoyne, Joseph, Burón, M Isabel, Bustos, Victor, Büttner, Sabrina, Butturini, Elena, Byrd, Aaron, Cabas, Isabel, Cabrera-Benitez, Sandra, Cadwell, Ken, Cai, Jingjing, Cai, Lu, Cai, Qian, Cairó, Montserrat, Calbet, Jose, Caldwell, Guy, Caldwell, Kim, Call, Jarrod, Calvani, Riccardo, Calvo, Ana, Calvo-Rubio Barrera, Miguel, Camara, Niels OS, Camonis, Jacques, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Edward, Campbell-Valois, François-Xavier, Campello, Silvia, Campesi, Ilaria, Campos, Juliane, Camuzard, Olivier, Cancino, Jorge, Candido de Almeida, Danilo, Canesi, Laura, Caniggia, Isabella, Canonico, Barbara, Cantí, Carles, Cao, Bin, Caraglia, Michele, Caramés, Beatriz, Carchman, Evie, Cardenal-Muñoz, Elena, Cardenas, Cesar, Cardenas, Luis, Cardoso, Sandra, Carew, Jennifer, Carle, Georges, Carleton, Gillian, Carloni, Silvia, Carmona-Gutierrez, Didac, Carneiro, Leticia, Carnevali, Oliana, Carosi, Julian, Carra, Serena, Carrier, Alice, Carrier, Lucie, Carroll, Bernadette, Carter, A Brent, Carvalho, Andreia Neves, Casanova, Magali, Casas, Caty, Casas, Josefina, Cassioli, Chiara, Castillo, Eliseo, Castillo, Karen, Castillo-Lluva, Sonia, Castoldi, Francesca, Castori, Marco, Castro, Ariel, Castro-Caldas, Margarida, Castro-Hernandez, Javier, Castro-Obregon, Susana, Catz, Sergio, Cavadas, Claudia, Cavaliere, Federica, Cavallini, Gabriella, Cavinato, Maria, Cayuela, Maria, Cebollada Rica, Paula, Cecarini, Valentina, Cecconi, Francesco, Cechowska-Pasko, Marzanna, Cenci, Simone, Ceperuelo-Mallafré, Victòria, Cerqueira, João, Cerutti, Janete, Cervia, Davide, Cetintas, Vildan Bozok, Cetrullo, Silvia, Chae, Han-Jung, Chagin, Andrei, Chai, Chee-Yin, Chakrabarti, Gopal, Chakrabarti, Oishee, Chakraborty, Tapas, Chakraborty, Trinad, Chami, mounia, Chamilos, Georgios, Chan, David, Chan, Edmond, Chan, Edward, Chan, H.Y. Edwin, Chan, Helen, Chan, Hung, Chan, Matthew, Chan, Yau Sang, Chandra, Partha, Chang, Chih-Peng, Chang, Chunmei, Chang, Hao-Chun, Chang, Kai, Chao, Jie, Chapman, Tracey, Charlet-Berguerand, Nicolas, Chatterjee, Samrat, Chaube, Shail, Chaudhary, Anu, Chauhan, Santosh, Chaum, Edward, Checler, Frédéric, Cheetham, Michael, Chen, Chang-Shi, Chen, Guang-Chao, Chen, Jian-Fu, Chen, Liam, Chen, Leilei, Chen, Lin, Chen, Mingliang, Chen, Mu-Kuan, Chen, Ning, Chen, Quan, Chen, Ruey-Hwa, Chen, Shi, Chen, Wei, Chen, Weiqiang, Chen, Xin-Ming, Chen, Xiong-Wen, Chen, Xu, Chen, Yan, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Zhefan Stephen, Chen, Zhi, Chen, Zhi-Hua, Chen, Zhijian, Chen, Zhixiang, Cheng, Hanhua, Cheng, Jun, Cheng, Shi-Yuan, Cheng, Wei, Cheng, Xiaodong, Cheng, Xiu-Tang, Cheng, Yiyun, Cheng, Zhiyong, Chen, Zhong, Cheong, Heesun, Cheong, Jit Kong, Chernyak, Boris, Cherry, Sara, Cheung, Chi Fai Randy, Cheung, Chun Hei Antonio, Cheung, King-Ho, Chevet, Eric, Chi, Richard, Chiang, Alan Kwok Shing, Chiaradonna, Ferdinando, Chiarelli, Roberto, Chiariello, Mario, Chica, Nathalia, Chiocca, Susanna, Chiong, Mario, Chiou, Shih-Hwa, Chiramel, Abhilash, Chiurchiù, Valerio, Cho, Dong-Hyung, Choe, Seong-Kyu, Choi, Augustine, Choi, Mary, Choudhury, Kamalika Roy, Chow, Norman, Chu, Charleen, Chua, Jason, Chua, John Jia En, Chung, Hyewon, Chung, Kin Pan, Chung, Seockhoon, Chung, So-Hyang, Chung, Yuen-Li, Cianfanelli, Valentina, Ciechomska, Iwona, Cifuentes, Mariana, Cinque, Laura, Cirak, Sebahattin, Cirone, Mara, Clague, Michael, Clarke, Robert, Clementi, Emilio, Coccia, Eliana, Codogno, Patrice, Cohen, Ehud, Cohen, Mickael, Colasanti, Tania, Colasuonno, Fiorella, Colbert, Robert, Colell, Anna, Čolić, Miodrag, Coll, Nuria, Collins, Mark, Colombo, María, Colón-Ramos, Daniel, Combaret, Lydie, Comincini, Sergio, Cominetti, Márcia, Consiglio, Antonella, Conte, Andrea, Conti, Fabrizio, Contu, Viorica Raluca, Cookson, Mark, Coombs, Kevin, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corkery, Dale, Cordes, Nils, Cortese, Katia, Costa, Maria do Carmo, Costantino, Sarah, Costelli, Paola, Coto-Montes, Ana, Crack, Peter, Crespo, Jose, Criollo, Alfredo, Crippa, Valeria, Cristofani, Riccardo, Csizmadia, Tamas, Cuadrado, Antonio, Cui, Bing, Cui, Jun, Cui, Yixian, Cui, Yong, Culetto, Emmanuel, Cumino, Andrea, Cybulsky, Andrey, Czaja, Mark, Czuczwar, Stanislaw, D'Adamo, Stefania, D'Amelio, Marcello, D'Arcangelo, Daniela, D'Lugos, Andrew, D'Orazi, Gabriella, da Silva, James, Dafsari, Hormos Salimi, Dagda, Ruben, Dagdas, Yasin, Daglia, Maria, Dai, Xiaoxia, Dai, Yun, Dai, Yuyuan, Dal Col, Jessica, Dalhaimer, Paul, Dalla Valle, Luisa, Dallenga, Tobias, Dalmasso, Guillaume, Damme, Markus, Dando, Ilaria, Dantuma, Nico, Darling, April, Das, Hiranmoy, Dasarathy, Srinivasan, Dasari, Santosh, Dash, Srikanta, Daumke, Oliver, Dauphinee, Adrian, Davies, Jeffrey, Dávila, Valeria, Davis, Roger, Davis, Tanja, Dayalan Naidu, Sharadha, De Amicis, Francesca, De Bosscher, Karolien, De Felice, Francesca, De Franceschi, Lucia, De Leonibus, Chiara, de Mattos Barbosa, Mayara, De Meyer, Guido, De Milito, Angelo, De Nunzio, Cosimo, De Palma, Clara, De Santi, Mauro, De Virgilio, Claudio, De Zio, Daniela, Debnath, Jayanta, DeBosch, Brian, Decuypere, Jean-Paul, Deehan, Mark, Deflorian, Gianluca, DeGregori, James, Dehay, Benjamin, Del Rio, Gabriel, Delaney, Joe, Delbridge, Lea, Delorme-Axford, Elizabeth, Delpino, M Victoria, Demarchi, Francesca, Dembitz, Vilma, Demers, Nicholas, Deng, Hongbin, Deng, Zhiqiang, Dengjel, Joern, Dent, Paul, Denton, Donna, DePamphilis, Melvin, Der, Channing, Deretic, Vojo, Descoteaux, Albert, Devis, Laura, Devkota, Sushil, Devuyst, Olivier, Dewson, Grant, Dharmasivam, Mahendiran, Dhiman, Rohan, di Bernardo, Diego, Di Cristina, Manlio, Di Domenico, Fabio, Di Fazio, Pietro, Di Fonzo, Alessio, Di Guardo, Giovanni, Di Guglielmo, Gianni, Di Leo, Luca, Di Malta, Chiara, Di Nardo, Alessia, Di Rienzo, Martina, Di Sano, Federica, Diallinas, George, Diao, Jiajie, Diaz-Araya, Guillermo, Díaz-Laviada, Inés, Dickinson, Jared, Diederich, Marc, Dieudé, Mélanie, Dikic, Ivan, Ding, Shiping, Ding, Wen-Xing, Dini, Luciana, Dinić, Jelena, Dinic, Miroslav, Dinkova-Kostova, Albena, Dionne, Marc, Distler, Jörg, Diwan, Abhinav, Dixon, Ian, Djavaheri-Mergny, Mojgan, Dobrinski, Ina, Dobrovinskaya, Oxana, Dobrowolski, Radek, Dobson, Renwick, Đokić, Jelena, Dokmeci Emre, Serap, Donadelli, Massimo, Dong, Bo, Dong, Xiaonan, Dong, Zhiwu, Dorn Ii, Gerald, Dotsch, Volker, Dou, Huan, Dou, Juan, Dowaidar, Moataz, Dridi, Sami, Drucker, Liat, Du, Ailian, Du, Caigan, Du, Guangwei, Du, Hai-Ning, Du, Li-Lin, du Toit, André, Duan, Shao-Bin, Duan, Xiaoqiong, Duarte, Sónia, Dubrovska, Anna, Dunlop, Elaine, Dupont, Nicolas, Durán, Raúl, Dwarakanath, Bilikere, Dyshlovoy, Sergey, Ebrahimi-Fakhari, Darius, Eckhart, Leopold, Edelstein, Charles, Efferth, Thomas, Eftekharpour, Eftekhar, Eichinger, Ludwig, Eid, Nabil, Eisenberg, Tobias, Eissa, N Tony, Eissa, Sanaa, Ejarque, Miriam, El Andaloussi, Abdeljabar, El-Hage, Nazira, El-Naggar, Shahenda, Eleuteri, Anna Maria, El-Shafey, Eman, Elgendy, Mohamed, Eliopoulos, Aristides, Elizalde, María, Elks, Philip, Elsasser, Hans-Peter, Elsherbiny, Eslam, Emerling, Brooke, Emre, N., Eng, Christina, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelsen, Agnete, Enserink, Jorrit, Escalante, Ricardo, Esclatine, Audrey, Escobar-Henriques, Mafalda, Eskelinen, Eeva-Liisa, Espert, Lucile, Eusebio, Makandjou-Ola, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Facchiano, Francesco, Fadeel, Bengt, Fader, Claudio, Faesen, Alex, Fairlie, W Douglas, Falcó, Alberto, Falkenburger, Bjorn, Fan, Daping, Fan, Jie, Fan, Yanbo, Fang, Evandro, Fang, Yanshan, Fang, Yognqi, Fanto, Manolis, Farfel-Becker, Tamar, Faure, Mathias, Fazeli, Gholamreza, Fedele, Anthony, Feldman, Arthur, Feng, Du, Feng, Jiachun, Feng, Lifeng, Feng, Yibin, Feng, Yuchen, Feng, Wei, Fenz Araujo, Thais, Ferguson, Thomas, Fernández, Álvaro, Fernandez-Checa, Jose, Fernández-Veledo, Sonia, Fernie, Alisdair, Ferrante, Anthony, Ferraresi, Alessandra, Ferrari, Merari, Ferreira, Julio, Ferro-Novick, Susan, Figueras, Antonio, Filadi, Riccardo, Filigheddu, Nicoletta, Filippi-Chiela, Eduardo, Filomeni, Giuseppe, Fimia, Gian Maria, Fineschi, Vittorio, Finetti, Francesca, Finkbeiner, Steven, Fisher, Edward, Fisher, Paul, Flamigni, Flavio, Fliesler, Steven, Flo, Trude, Florance, Ida, Florey, Oliver, Florio, Tullio, Fodor, Erika, Follo, Carlo, Fon, Edward, Forlino, Antonella, Fornai, Francesco, Fortini, Paola, Fracassi, Anna, Fraldi, Alessandro, Franco, Brunella, Franco, Rodrigo, Franconi, Flavia, Frankel, Lisa, Friedman, Scott, Fröhlich, Leopold, Frühbeck, Gema, Fuentes, Jose, Fujiki, Yukio, Fujita, Naonobu, Fujiwara, Yuuki, Fukuda, Mitsunori, Fulda, Simone, Furic, Luc, Furuya, Norihiko, Fusco, Carmela, Gack, Michaela, Gaffke, Lidia, Galadari, Sehamuddin, Galasso, Alessia, Galindo, Maria, Gallolu Kankanamalage, Sachith, Galluzzi, Lorenzo, Galy, Vincent, Gammoh, Noor, Gan, Boyi, Ganley, Ian, Gao, Feng, Gao, Hui, Gao, Minghui, Gao, Ping, Gao, Shou-Jiang, Gao, Wentao, Gao, Xiaobo, Garcera, Ana, Garcia, Maria Noé, Garcia, Verónica, García-del Portillo, Francisco, Garcia-Escudero, Vega, Garcia-Garcia, Aracely, Garcia-Macia, Marina, García-Moreno, Diana, Garcia-Ruiz, Carmen, García-Sanz, Patricia, Garg, Abhishek, Gargini, Ricardo, Garofalo, Tina, Garry, Robert, Gassen, Nils, Gatica, Damian, Ge, Liang, Ge, Wanzhong, Geiss-Friedlander, Ruth, Gelfi, Cecilia, Genschik, Pascal, Gentle, Ian, Gerbino, Valeria, Gerhardt, Christoph, Germain, Kyla, Germain, Marc, Gewirtz, David, Ghasemipour Afshar, Elham, Ghavami, Saeid, Ghigo, Alessandra, Ghosh, Manosij, Giamas, Georgios, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibson, Gary, Gibson, Spencer, Ginet, Vanessa, Giniger, Edward, Giorgi, Carlotta, Girao, Henrique, Girardin, Stephen, Giridharan, Mridhula, Giuliano, Sandy, Giulivi, Cecilia, Giuriato, Sylvie, Giustiniani, Julien, Gluschko, Alexander, Goder, Veit, Goginashvili, Alexander, Golab, Jakub, Goldstone, David, Golebiewska, Anna, Gomes, Luciana, Gomez, Rodrigo, Gómez-Sánchez, Rubén, Gomez-Puerto, Maria Catalina, Gomez-Sintes, Raquel, Gong, Qingqiu, Goni, Felix, González-Gallego, Javier, Gonzalez-Hernandez, Tomas, Gonzalez-Polo, Rosa, Gonzalez-Reyes, Jose, González-Rodríguez, Patricia, Goping, Ing Swie, Gorbatyuk, Marina, Gorbunov, Nikolai, Görgülü, Kıvanç, Gorojod, Roxana, Gorski, Sharon, Goruppi, Sandro, Gotor, Cecilia, Gottlieb, Roberta, Gozes, Illana, Gozuacik, Devrim, Graef, Martin, Gräler, Markus, Granatiero, Veronica, Grasso, Daniel, Gray, Joshua, Green, Douglas, Greenhough, Alexander, Gregory, Stephen, Griffin, Edward, Grinstaff, Mark, Gros, Frederic, Grose, Charles, Gross, Angelina, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Gu, Xueyan, Guan, Jun-Lin, Guardia, Carlos, Guda, Kishore, Guerra, Flora, Guerri, Consuelo, Guha, Prasun, Guillén, Carlos, Gujar, Shashi, 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Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier, Hesselson, Daniel, Hetz, Claudio, Heussler, Volker, Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph, Hlavacek, William, Ho, Emmanuel, Ho, Idy, Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G Aaron, Hochstrasser, Mark, Hoet, Peter, Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina, Hombrebueno, Jose, Yi-Ren Hong, Chang-Won Hong, Hooper, Lora, Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael, Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias, Hubert, Virginie, Hubner, Christian, Hughes, Stephanie, Hughes, William, Humbert, Magali, Hummer, Gerhard, Hurley, James, Hussain, Sabah, Hussain, Salik, Hussey, Patrick, Hutabarat, Martina, Hwang, Hui-Yun, Hwang, Seungmin, Ieni, Antonio, Ikeda, Fumiyo, Imagawa, Yusuke, Imai, Yuzuru, Imbriano, Carol, Imoto, Masaya, Inman, Denise, Inoki, Ken, Iovanna, Juan, Iozzo, Renato, Ippolito, Giuseppe, Irazoqui, Javier, Iribarren, Pablo, Ishaq, Mohd, ISHIKAWA, Makoto, Ishimwe, Nestor, Isidoro, Ciro, Ismail, Nahed, Issazadeh-Navikas, Shohreh, Itakura, Eisuke, Ito, Daisuke, Ivankovic, Davor, Ivanova, Saška, Iyer, Anand Krishnan V, Izquierdo, José, Izumi, Masanori, Jäättelä, Marja, Jabir, Majid Sakhi, Jackson, William, Jacobo-Herrera, Nadia, Jacomin, Anne-Claire, Jacquin, Elise, Jadiya, Pooja, Jaeschke, Hartmut, Jagannath, Chinnaswamy, Jakobi, Arjen, Jakobsson, Johan, Janji, Bassam, Jansen-Dürr, Pidder, Jansson, Patric, Jantsch, Jonathan, Januszewski, Sławomir, Jassey, Alagie, Jean, Steve, Jeltsch-David, Hélène, Jendelova, Pavla, Jenny, Andreas, Jensen, Thomas, Jessen, Niels, Jewell, Jenna, Ji, Jing, Jia, Lijun, Jia, Rui, Jiang, Liwen, Jiang, Qing, Jiang, Richeng, Jiang, Teng, Jiang, Xuejun, Jiang, Yu, Jimenez-Sanchez, Maria, Jin, Eun-Jung, Jin, Fengyan, Jin, Hongchuan, Jin, Li, Jin, Luqi, Jin, Meiyan, Jin, Si, Jo, Eun-Kyeong, Joffre, Carine, Johansen, Terje, Johnson, Gail, Johnston, Simon, Jokitalo, Eija, Jolly, Mohit Kumar, Joosten, Leo, Jordan, Joaquin, Joseph, Bertrand, Ju, Dianwen, Ju, Jeong-Sun, Ju, Jingfang, Juárez, Esmeralda, Judith, Delphine, Juhász, Gábor, Jun, Youngsoo, Jung, Chang Hwa, Jung, Sung-Chul, Jung, Yong Keun, Jungbluth, Heinz, Jungverdorben, Johannes, Just, Steffen, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kaganovich, Daniel, Kahana, Alon, Kain, Renate, Kajimura, Shinjo, Kalamvoki, Maria, Kalia, Manjula, Kalinowski, Danuta, Kaludercic, Nina, Kalvari, Ioanna, Kaminska, Joanna, Kaminskyy, Vitaliy, Kanamori, Hiromitsu, Kanasaki, Keizo, Kang, Chanhee, Kang, Rui, Kang, Sang Sun, Kaniyappan, Senthilvelrajan, 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Adi, Kimmelman, Alec, Kimura, Tomonori, King, Matthew, Kinghorn, Kerri, Kinsey, Conan, Kirkin, Vladimir, Kirshenbaum, Lorrie, Kiselev, Sergey, Kishi, Shuji, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kitsis, Richard, Kittler, Josef, Kjaerulff, Ole, Klein, Peter, Klopstock, Thomas, Klucken, Jochen, Knævelsrud, Helene, Knorr, Roland, Ko, Ben, Ko, Fred, Ko, Jiunn-Liang, Kobayashi, Hotaka, Kobayashi, Satoru, Koch, Ina, Koch, Jan, Koenig, Ulrich, Kögel, Donat, Koh, Young Ho, Koike, Masato, Kohlwein, Sepp, Kocaturk, Nur, Komatsu, Masaaki, König, Jeannette, Kono, Toru, Kopp, Benjamin, Korcsmaros, Tamas, Korkmaz, Gözde, Korolchuk, Viktor, Korsnes, Mónica Suárez, Koskela, Ali, Kota, Janaiah, Kotake, Yaichiro, Kotler, Monica, Kou, Yanjun, Koukourakis, Michael, Koustas, Evangelos, Kovacs, Attila, Kovács, Tibor, Koya, Daisuke, Kozako, Tomohiro, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna, Kretz-Remy, Carole, Kroemer, Guido, Ktistakis, Nicholas, Kuchitsu, Kazuyuki, Kuenen, Sabine, Kuerschner, Lars, Kukar, Thomas, Kumar, Ajay, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad, Kume, Shinji, Kumsta, Caroline, Kundu, Chanakya, Kundu, Mondira, Kunnumakkara, Ajaikumar, Kurgan, Lukasz, Kutateladze, Tatiana, Kutlu, Ozlem, Kwak, SeongAe, Kwon, Ho Jeong, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert, Labonté, Patrick, Ladoire, Sylvain, Laface, Ilaria, Lafont, Frank, Lagace, Diane, Lahiri, Vikramjit, Lai, Zhibing, Laird, Angela, Lakkaraju, Aparna, Lamark, Trond, Lan, Sheng-Hui, Landajuela, Ane, Lane, Darius, Lane, Jon, Lang, Charles, Lange, Carsten, Langel, Ülo, Langer, Rupert, Lapaquette, Pierre, Laporte, Jocelyn, LaRusso, Nicholas, Lastres-Becker, Isabel, Lau, Wilson Chun Yu, Laurie, Gordon, Lavandero, Sergio, Law, Betty Yuen Kwan, Law, Helen Ka-wai, Layfield, Rob, Le, Weidong, Le Stunff, Herve, Leary, Alexandre, Lebrun, Jean-Jacques, Leck, Lionel, Leduc-Gaudet, Jean-Philippe, Lee, Changwook, Lee, Chung-Pei, Lee, Da-Hye, Lee, Edward, Lee, Erinna, Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason, Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella, Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu, Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia, Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy, Levine, Beth, Lewis, Patrick, Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, 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Alexandre, Victor, Victor, Vidal, Michel, Vidoni, Chiara, Vieira, Otilia, Vierstra, Richard, Viganó, Sonia, Vihinen, Helena, Vijayan, Vinoy, Vila, Miquel, Vilar, Marçal, Villalba, José, Villalobo, Antonio, Villarejo-Zori, Beatriz, Villarroya, Francesc, Villarroya, Joan, Vincent, Olivier, Vindis, Cecile, Viret, Christophe, Viscomi, Maria Teresa, Visnjic, Dora, Vitale, Ilio, Vocadlo, David, Voitsekhovskaja, Olga, Volonté, Cinzia, Volta, Mattia, Vomero, Marta, Von Haefen, Clarissa, Vooijs, Marc, Voos, Wolfgang, Vucicevic, Ljubica, Wade-Martins, Richard, Waguri, Satoshi, Waite, Kenrick, Wakatsuki, Shuji, Walker, David, Walker, Mark, Walker, Simon, Walter, Jochen, Wandosell, Francisco, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, PengWei, Wang, PeiPei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, wang, yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy, Wegrzyn, Grzegorz, Wehman, Ann, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver, Weihl, Conrad, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally, Whitton, J Lindsay, Whitworth, Alexander, Wiktorska, Katarzyna, Wildenberg, Manon, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin, Williams, Roger, Williamson, Peter, Wilson, Richard, Winner, Beate, Winsor, Nathaniel, Witkin, Steven, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, Jinrong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin, Yiu, Stephanie Pei Tung, Yoo, Young, Yoshida, Kiyotsugu, Yoshii, Saori, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond, Zacks, David, Zaffagnini, Gabriele, Zambelli, Vanessa, Zanella, Isabella, Zang, Qun, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott, Zeng, Jialiu, Zeng, Ju-deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin, Zhang, Leshuai, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, ZHOU, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith, Stallings, Christina, Tong, Chun-Kit, Ahmad, S. Tariq, Alim Al-Bari, M. Abdul, Bechara, Luiz R.G., Behrens, Georg M.N., Bhuiyan, Md. Shenuarin, Broaddus, V. Courtney, Buchan, J. Ross, Burón, M. Isabel, Carter, A. Brent, Chan, Matthew T.V., Choi, Augustine M.K., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew, D’Orazi, Gabriella, De Meyer, Guido R.Y., Delpino, M. Victoria, Distler, Jörg H.W., Dixon, Ian M.C., Dobson, Renwick C.J., 2nd Dorn, Gerald, Eissa, N. Tony, Engelsen, Agnete S.T., Fairlie, W. Douglas, Ferreira, Julio C.B., H.B., Ranjitha, Hanson, Phyllis I., Hejtmancik, J. Fielding, Ho, Idy H.T., Hobbs, G. Aaron, Hoet, Peter H.M., Huang, Michael L.H., Iyer, Anand Krishnan V., Johnson, Gail V.W., Joosten, Leo A.B., Karim, Md. Razaul, Kaufmann, Stefan H.E., Ko, Ben C.B., Leck, Lionel Y.W., Lima, Thania R.R., Livingston, J. Andrew, Martin, Alexandre P.J., Montes, L. Ruth, Murphy, J. Patrick, Ng, Charlene C.W., Nicolao, M. Celeste, O’Donovan, Tracey, O’Leary, Seónadh, O’Rourke, Eyleen, O’Sullivan, Mary, O’Sullivan, Timothy, Omary, M. Bishr, Pereira, Gustavo J.S., Ratnayaka, J. Arjuna, Riazuddin, S. Amer, Rouschop, Kasper M.A., Sanderson, J. Thomas, Scaglione, K. Matthew, Schapira, Anthony H.V., Scovassi, A. Ivana, St. Clair, Daret, Sunahara, Karen K.S., Symons, J. David, Triola, Gemma, van Wijk, Sjoerd J.L., Vanrell, M. Cristina, Vasconcelos, M. Helena, Whitton, J. Lindsay, Williams, Robin S.B., Wong, W. Wei-Lynn, Wu, William K.K., Yakhine-Diop, Sokhna M.S., Yu, W. Haung, Zhang, Kalin Y.B., Dong, X. Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. Y., Antas, P., Antebi, A., Anton, Z., Anwar, T., Apetoh, L., Apostolova, N., Araki, T., Araki, Y., Arasaki, K., Araujo, W. L., Araya, J., Arden, C., Arevalo, M. -A., Arguelles, S., Arias, E., Arikkath, J., Arimoto, H., Ariosa, A. R., Armstrong-James, D., Arnaune-Pelloquin, L., Aroca, A., Arroyo, D. S., Arsov, I., Artero, R., Asaro, D. M. L., Aschner, M., Ashrafizadeh, M., Ashur-Fabian, O., Atanasov, A. G., Au, A. K., Auberger, P., Auner, H. W., Aurelian, L., Autelli, R., Avagliano, L., Avalos, Y., Aveic, S., Aveleira, C. A., Avin-Wittenberg, T., Aydin, Y., Ayton, S., Ayyadevara, S., Azzopardi, M., Baba, M., Backer, J. M., Backues, S. K., Bae, D. -H., Bae, O. -N., Bae, S. H., Baehrecke, E. H., Baek, A., Baek, S. -H., Baek, S. H., Bagetta, G., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bai, Y., Bairagi, N., Baksi, S., Balbi, T., Baldari, C. T., Balduini, W., Ballabio, A., Ballester, M., Balazadeh, S., Balzan, R., Bandopadhyay, R., Banerjee, S., Banreti, A., Bao, Y., Baptista, M. S., Baracca, A., Barbati, C., Bargiela, A., Barila, D., Barlow, P. G., Barmada, S. J., Barreiro, E., Barreto, G. E., Bartek, J., Bartel, B., Bartolome, A., Barve, G. R., Basagoudanavar, S. H., Bassham, D. C., Bast, R. C., Basu, A., Batoko, H., Batten, I., Baulieu, E. E., Baumgarner, B. L., Bayry, J., Beale, R., Beau, I., Beaumatin, F., Bechara, L. R. G., Beck, G. R., Beers, M. F., Begun, J., Behrends, C., Behrens, G. M. N., Bei, R., Bejarano, E., Bel, S., Behl, C., Belaid, A., Belgareh-Touze, N., Bellarosa, C., Belleudi, F., Bello Perez, M., Bello-Morales, R., Beltran, J. S. D. O., Beltran, S., Benbrook, D. M., Bendorius, M., Benitez, B. A., Benito-Cuesta, I., Bensalem, J., Berchtold, M. W., Berezowska, S., Bergamaschi, D., Bergami, M., Bergmann, A., Berliocchi, L., Berlioz-Torrent, C., Bernard, A., Berthoux, L., Besirli, C. G., Besteiro, S., Betin, V. M., Beyaert, R., Bezbradica, J. S., Bhaskar, K., Bhatia-Kissova, I., Bhattacharya, R., Bhattacharya, S., Bhattacharyya, S., Bhuiyan, M. S., Bhutia, S. K., Bi, L., Bi, X., Biden, T. J., Bijian, K., Billes, V. A., Binart, N., Bincoletto, C., Birgisdottir, A. B., Bjorkoy, G., Blanco, G., Blas-Garcia, A., Blasiak, J., Blomgran, R., Blomgren, K., Blum, J. S., Boada-Romero, E., Boban, M., Boesze-Battaglia, K., Boeuf, P., Boland, B., Bomont, P., Bonaldo, P., Bonam, S. R., Bonfili, L., Bonifacino, J. S., Boone, B. A., Bootman, M. D., Bordi, M., Borner, C., Bornhauser, B. C., Borthakur, G., Bosch, J., Bose, S., Botana, L. M., Botas, J., Boulanger, C. M., Boulton, M. E., Bourdenx, M., Bourgeois, B., Bourke, N. M., Bousquet, G., Boya, P., Bozhkov, P. V., Bozi, L. H. M., Bozkurt, T. O., Brackney, D. E., Brandts, C. H., Braun, R. J., Braus, G. H., Bravo-Sagua, R., Bravo-San Pedro, J. M., Brest, P., Bringer, M. -A., Briones-Herrera, A., Broaddus, V. C., Brodersen, P., Brodsky, J. L., Brody, S. L., Bronson, P. G., Bronstein, J. M., Brown, C. N., Brown, R. E., Brum, P. C., Brumell, J. H., Brunetti-Pierri, N., Bruno, D., Bryson-Richardson, R. J., Bucci, C., Buchrieser, C., Bueno, M., Buitrago-Molina, L. E., Buraschi, S., Buch, S., Buchan, J. R., Buckingham, E. M., Budak, H., Budini, M., Bultynck, G., Burada, F., Burgoyne, J. R., Buron, M. I., Bustos, V., Buttner, S., Butturini, E., Byrd, A., Cabas, I., Cabrera-Benitez, S., Cadwell, K., Cai, J., Cai, L., Cai, Q., Cairo, M., Calbet, J. A., Caldwell, G. A., Caldwell, K. A., Call, J. A., Calvani, R., Calvo, A. C., Calvo-Rubio Barrera, M., Camara, N. O. S., Camonis, J. H., Camougrand, N., Campanella, M., Campbell, E. M., Campbell-Valois, F. -X., Campello, S., Campesi, I., Campos, J. C., Camuzard, O., Cancino, J., Candido de Almeida, D., Canesi, L., Caniggia, I., Canonico, B., Canti, C., Cao, B., Caraglia, M., Carames, B., Carchman, E. H., Cardenal-Munoz, E., Cardenas, C., Cardenas, L., Cardoso, S. M., Carew, J. S., Carle, G. F., Carleton, G., Carloni, S., Carmona-Gutierrez, D., Carneiro, L. A., Carnevali, O., Carosi, J. M., Carra, S., Carrier, A., Carrier, L., Carroll, B., Carter, A. B., Carvalho, A. N., Casanova, M., Casas, C., Casas, J., Cassioli, C., Castillo, E. F., Castillo, K., Castillo-Lluva, S., Castoldi, F., Castori, M., Castro, A. F., Castro-Caldas, M., Castro-Hernandez, J., Castro-Obregon, S., Catz, S. D., Cavadas, C., Cavaliere, F., Cavallini, G., Cavinato, M., Cayuela, M. L., Cebollada Rica, P., Cecarini, V., Cecconi, F., Cechowska-Pasko, M., Cenci, S., Ceperuelo-Mallafre, V., Cerqueira, J. J., Cerutti, J. M., Cervia, D., Cetintas, V. B., Cetrullo, S., Chae, H. -J., Chagin, A. S., Chai, C. -Y., Chakrabarti, G., Chakrabarti, O., Chakraborty, T., Chami, M., Chamilos, G., Chan, D. W., Chan, E. Y. W., Chan, E. D., Chan, H. Y. E., Chan, H. H., Chan, H., Chan, M. T. V., Chan, Y. S., Chandra, P. K., Chang, C. -P., Chang, C., Chang, H. -C., Chang, K., Chao, J., Chapman, T., Charlet-Berguerand, N., Chatterjee, S., Chaube, S. K., Chaudhary, A., Chauhan, S., Chaum, E., Checler, F., Cheetham, M. E., Chen, C. -S., Chen, G. -C., Chen, J. -F., Chen, L. L., Chen, L., Chen, M., Chen, M. -K., Chen, N., Chen, Q., Chen, R. -H., Chen, S., Chen, W., Chen, X. -M., Chen, X. -W., Chen, X., Chen, Y., Chen, Y. -G., Chen, Y. -J., Chen, Y. -Q., Chen, Z. S., Chen, Z., Chen, Z. -H., Chen, Z. J., Cheng, H., Cheng, J., Cheng, S. -Y., Cheng, W., Cheng, X., Cheng, X. -T., Cheng, Y., Cheng, Z., Cheong, H., Cheong, J. K., Chernyak, B. V., Cherry, S., Cheung, C. F. R., Cheung, C. H. A., Cheung, K. -H., Chevet, E., Chi, R. J., Chiang, A. K. S., Chiaradonna, F., Chiarelli, R., Chiariello, M., Chica, N., Chiocca, S., Chiong, M., Chiou, S. -H., Chiramel, A. I., Chiurchiu, V., Cho, D. -H., Choe, S. -K., Choi, A. M. K., Choi, M. E., Choudhury, K. R., Chow, N. S., Chu, C. T., Chua, J. P., Chua, J. J. E., Chung, H., Chung, K. P., Chung, S., Chung, S. -H., Chung, Y. -L., Cianfanelli, V., Ciechomska, I. A., Cifuentes, M., Cinque, L., Cirak, S., Cirone, M., Clague, M. J., Clarke, R., Clementi, E., Coccia, E. M., Codogno, P., Cohen, E., Cohen, M. M., Colasanti, T., Colasuonno, F., Colbert, R. A., Colell, A., Colic, M., Coll, N. S., Collins, M. O., Colombo, M. I., Colon-Ramos, D. A., Combaret, L., Comincini, S., Cominetti, M. R., Consiglio, A., Conte, A., Conti, F., Contu, V. R., Cookson, M. R., Coombs, K. M., Coppens, I., Corasaniti, M. T., Corkery, D. P., Cordes, N., Cortese, K., Costa, M. D. C., Costantino, S., Costelli, P., Coto-Montes, A., Crack, P. J., Crespo, J. L., Criollo, A., Crippa, V., Cristofani, R., Csizmadia, T., Cuadrado, A., Cui, B., Cui, J., Cui, Y., Culetto, E., Cumino, A. C., Cybulsky, A. V., Czaja, M. J., Czuczwar, S. J., D'Adamo, S., D'Amelio, M., D'Arcangelo, D., D'Lugos, A. C., D'Orazi, G., da Silva, J. A., Dafsari, H. S., Dagda, R. K., Dagdas, Y., Daglia, M., Dai, X., Dai, Y., Dal Col, J., Dalhaimer, P., Dalla Valle, L., Dallenga, T., Dalmasso, G., Damme, M., Dando, I., Dantuma, N. P., Darling, A. L., Das, H., Dasarathy, S., Dasari, S. K., Dash, S., Daumke, O., Dauphinee, A. N., Davies, J. S., Davila, V. A., Davis, R. J., Davis, T., Dayalan Naidu, S., De Amicis, F., De Bosscher, K., De Felice, F., De Franceschi, L., De Leonibus, C., de Mattos Barbosa, M. G., De Meyer, G. R. Y., De Milito, A., De Nunzio, C., De Palma, C., De Santi, M., De Virgilio, C., De Zio, D., Debnath, J., Debosch, B. J., Decuypere, J. -P., Deehan, M. A., Deflorian, G., Degregori, J., Dehay, B., Del Rio, G., Delaney, J. R., Delbridge, L. M. D., Delorme-Axford, E., Delpino, M. V., Demarchi, F., Dembitz, V., Demers, N. D., Deng, H., Deng, Z., Dengjel, J., Dent, P., Denton, D., Depamphilis, M. L., Der, C. J., Deretic, V., Descoteaux, A., Devis, L., Devkota, S., Devuyst, O., Dewson, G., Dharmasivam, M., Dhiman, R., di Bernardo, D., Di Cristina, M., Di Domenico, F., Di Fazio, P., Di Fonzo, A., Di Guardo, G., Di Guglielmo, G. M., Di Leo, L., Di Malta, C., Di Nardo, A., Di Rienzo, M., Di Sano, F., Diallinas, G., Diao, J., Diaz-Araya, G., Diaz-Laviada, I., Dickinson, J. M., Diederich, M., Dieude, M., Dikic, I., Ding, S., Ding, W. -X., Dini, L., Dinic, J., Dinic, M., Dinkova-Kostova, A. T., Dionne, M. S., Distler, J. H. W., Diwan, A., Dixon, I. M. C., Djavaheri-Mergny, M., Dobrinski, I., Dobrovinskaya, O., Dobrowolski, R., Dobson, R. C. J., Dokic, J., Dokmeci Emre, S., Donadelli, M., Dong, B., Dong, X., Dong, Z., Dorn II, G. W., Dotsch, V., Dou, H., Dou, J., Dowaidar, M., Dridi, S., Drucker, L., Du, A., Du, C., Du, G., Du, H. -N., Du, L. -L., du Toit, A., Duan, S. -B., Duan, X., Duarte, S. P., Dubrovska, A., Dunlop, E. A., Dupont, N., Duran, R. V., Dwarakanath, B. S., Dyshlovoy, S. A., Ebrahimi-Fakhari, D., Eckhart, L., Edelstein, C. L., Efferth, T., Eftekharpour, E., Eichinger, L., Eid, N., Eisenberg, T., Eissa, N. T., Eissa, S., Ejarque, M., El Andaloussi, A., El-Hage, N., El-Naggar, S., Eleuteri, A. M., El-Shafey, E. S., Elgendy, M., Eliopoulos, A. G., Elizalde, M. M., Elks, P. M., Elsasser, H. -P., Elsherbiny, E. S., Emerling, B. M., Emre, N. C. T., Eng, C. H., Engedal, N., Engelbrecht, A. -M., Engelsen, A. S. T., Enserink, J. M., Escalante, R., Esclatine, A., Escobar-Henriques, M., Eskelinen, E. -L., Espert, L., Eusebio, M. -O., Fabrias, G., Fabrizi, C., Facchiano, A., Facchiano, F., Fadeel, B., Fader, C., Faesen, A. C., Fairlie, W. D., Falco, A., Falkenburger, B. H., Fan, D., Fan, J., Fan, Y., Fang, E. F., Fang, Y., Fanto, M., Farfel-Becker, T., Faure, M., Fazeli, G., Fedele, A. O., Feldman, A. M., Feng, D., Feng, J., Feng, L., Feng, Y., Feng, W., Fenz Araujo, T., Ferguson, T. A., Fernandez, A. F., Fernandez-Checa, J. C., Fernandez-Veledo, S., Fernie, A. R., Ferrante, A. W., Ferraresi, A., Ferrari, M. F., Ferreira, J. C. B., Ferro-Novick, S., Figueras, A., Filadi, R., Filigheddu, N., Filippi-Chiela, E., Filomeni, G., Fimia, G. M., Fineschi, V., Finetti, F., Finkbeiner, S., Fisher, E. A., Fisher, P. B., Flamigni, F., Fliesler, S. J., Flo, T. H., Florance, I., Florey, O., Florio, T., Fodor, E., Follo, C., Fon, E. A., Forlino, A., Fornai, F., Fortini, P., Fracassi, A., Fraldi, A., Franco, B., Franco, R., Franconi, F., Frankel, L. B., Friedman, S. L., Frohlich, L. F., Fruhbeck, G., Fuentes, J. M., Fujiki, Y., Fujita, N., Fujiwara, Y., Fukuda, M., Fulda, S., Furic, L., Furuya, N., Fusco, C., Gack, M. U., Gaffke, L., Galadari, S., Galasso, A., Galindo, M. F., Gallolu Kankanamalage, S., Galluzzi, L., Galy, V., Gammoh, N., Gan, B., Ganley, I. G., Gao, F., Gao, H., Gao, M., Gao, P., Gao, S. -J., Gao, W., Gao, X., Garcera, A., Garcia, M. N., Garcia, V. E., Garcia-Del Portillo, F., Garcia-Escudero, V., Garcia-Garcia, A., Garcia-Macia, M., Garcia-Moreno, D., Garcia-Ruiz, C., Garcia-Sanz, P., Garg, A. D., Gargini, R., Garofalo, T., Garry, R. F., Gassen, N. C., Gatica, D., Ge, L., Ge, W., Geiss-Friedlander, R., Gelfi, C., Genschik, P., Gentle, I. E., Gerbino, V., Gerhardt, C., Germain, K., Germain, M., Gewirtz, D. A., Ghasemipour Afshar, E., Ghavami, S., Ghigo, A., Ghosh, M., Giamas, G., Giampietri, C., Giatromanolaki, A., Gibson, G. E., Gibson, S. B., Ginet, V., Giniger, E., Giorgi, C., Girao, H., Girardin, S. E., Giridharan, M., Giuliano, S., Giulivi, C., Giuriato, S., Giustiniani, J., Gluschko, A., Goder, V., Goginashvili, A., Golab, J., Goldstone, D. C., Golebiewska, A., Gomes, L. R., Gomez, R., Gomez-Sanchez, R., Gomez-Puerto, M. C., Gomez-Sintes, R., Gong, Q., Goni, F. M., Gonzalez-Gallego, J., Gonzalez-Hernandez, T., Gonzalez-Polo, R. A., Gonzalez-Reyes, J. A., Gonzalez-Rodriguez, P., Goping, I. S., Gorbatyuk, M. S., Gorbunov, N. V., Gorgulu, K., Gorojod, R. M., Gorski, S. M., Goruppi, S., Gotor, C., Gottlieb, R. A., Gozes, I., Gozuacik, D., Graef, M., Graler, M. H., Granatiero, V., Grasso, D., Gray, J. P., Green, D. R., Greenhough, A., Gregory, S. L., Griffin, E. F., Grinstaff, M. W., Gros, F., Grose, C., Gross, A. S., Gruber, F., Grumati, P., Grune, T., Gu, X., Guan, J. -L., Guardia, C. M., Guda, K., Guerra, F., Guerri, C., Guha, P., Guillen, C., Gujar, S., Gukovskaya, A., Gukovsky, I., Gunst, J., Gunther, A., Guntur, A. R., Guo, C., Guo, H., Guo, L. -W., Guo, M., Gupta, P., Gupta, S. K., Gupta, S., Gupta, V. B., Gupta, V., Gustafsson, A. B., Gutterman, D. D., H. B, R., Haapasalo, A., Haber, J. E., Hac, A., Hadano, S., Hafren, A. J., Haidar, M., Hall, B. S., Hallden, G., Hamacher-Brady, A., Hamann, A., Hamasaki, M., Han, W., Hansen, M., Hanson, P. I., Hao, Z., Harada, M., Harhaji-Trajkovic, L., Hariharan, N., Haroon, N., Harris, J., Hasegawa, T., Hasima Nagoor, N., Haspel, J. A., Haucke, V., Hawkins, W. 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E., Periyasamy, P., Perl, A., Perrotta, C., Perrotta, I., Pestell, R. G., Petersen, M., Petrache, I., Petrovski, G., Pfirrmann, T., Pfister, A. S., Philips, J. A., Pi, H., Picca, A., Pickrell, A. M., Picot, S., Pierantoni, G. M., Pierdominici, M., Pierre, P., Pierrefite-Carle, V., Pierzynowska, K., Pietrocola, F., Pietruczuk, M., Pignata, C., Pimentel-Muinos, F. X., Pinar, M., Pinheiro, R. O., Pinkas-Kramarski, R., Pinton, P., Pircs, K., Piya, S., Pizzo, P., Plantinga, T. S., Platta, H. W., Plaza-Zabala, A., Plomann, M., Plotnikov, E. Y., Plun-Favreau, H., Pluta, R., Pocock, R., Poggeler, S., Pohl, C., Poirot, M., Poletti, A., Ponpuak, M., Popelka, H., Popova, B., Porta, H., Porte Alcon, S., Portilla-Fernandez, E., Post, M., Potts, M. B., Poulton, J., Powers, T., Prahlad, V., Prajsnar, T. K., Pratico, D., Prencipe, R., Priault, M., Proikas-Cezanne, T., Promponas, V. J., Proud, C. G., Puertollano, R., Puglielli, L., Pulinilkunnil, T., Puri, D., Puri, R., Puyal, J., Qi, X., Qi, Y., Qian, W., Qiang, L., Qiu, Y., Quadrilatero, J., Quarleri, J., Raben, N., Rabinowich, H., Ragona, D., Ragusa, M. J., Rahimi, N., Rahmati, M., Raia, V., Raimundo, N., Rajasekaran, N. -S., Ramachandra Rao, S., Rami, A., Ramirez-Pardo, I., Ramsden, D. B., Randow, F., Rangarajan, P. N., Ranieri, D., Rao, H., Rao, L., Rao, R., Rathore, S., Ratnayaka, J. A., Ratovitski, E. A., Ravanan, P., Ravegnini, G., Ray, S. K., Razani, B., Rebecca, V., Reggiori, F., Regnier-Vigouroux, A., Reichert, A. S., Reigada, D., Reiling, J. H., Rein, T., Reipert, S., Rekha, R. S., Ren, H., Ren, J., Ren, W., Renault, T., Renga, G., Reue, K., Rewitz, K., Ribeiro de Andrade Ramos, B., Riazuddin, S. A., Ribeiro-Rodrigues, T. M., Ricci, J. -E., Ricci, R., Riccio, V., Richardson, D. R., Rikihisa, Y., Risbud, M. V., Risueno, R. M., Ritis, K., Rizza, S., Rizzuto, R., Roberts, H. C., Roberts, L. D., Robinson, K. J., Roccheri, M. C., Rocchi, S., Rodney, G. G., Rodrigues, T., Rodrigues Silva, V. R., Rodriguez, A., Rodriguez-Barrueco, R., Rodriguez-Henche, N., Rodriguez-Rocha, H., Roelofs, J., Rogers, R. S., Rogov, V. V., Rojo, A. I., Rolka, K., Romanello, V., Romani, L., Romano, A., Romano, P. S., Romeo-Guitart, D., Romero, L. C., Romero, M., Roney, J. C., Rongo, C., Roperto, S., Rosenfeldt, M. T., Rosenstiel, P., Rosenwald, A. G., Roth, K. A., Roth, L., Roth, S., Rouschop, K. M. A., Roussel, B. D., Roux, S., Rovere-Querini, P., Roy, A., Rozieres, A., Ruano, D., Rubinsztein, D. C., Rubtsova, M. P., Ruckdeschel, K., Ruckenstuhl, C., Rudolf, E., Rudolf, R., Ruggieri, A., Ruparelia, A. A., Rusmini, P., Russell, R. R., Russo, G. L., Russo, M., Russo, R., Ryabaya, O. O., Ryan, K. M., Ryu, K. -Y., Sabater-Arcis, M., Sachdev, U., Sacher, M., Sachse, C., Sadhu, A., Sadoshima, J., Safren, N., Saftig, P., Sagona, A. P., Sahay, G., Sahebkar, A., Sahin, M., Sahin, O., Sahni, S., Saito, N., Saito, S., Saito, T., Sakai, R., Sakai, Y., Sakamaki, J. -I., Saksela, K., Salazar, G., Salazar-Degracia, A., Salekdeh, G. H., Saluja, A. K., Sampaio-Marques, B., Sanchez, M. C., Sanchez-Alcazar, J. A., Sanchez-Vera, V., Sancho-Shimizu, V., Sanderson, J. T., Sandri, M., Santaguida, S., Santambrogio, L., Santana, M. M., Santoni, G., Sanz, A., Sanz, P., Saran, S., Sardiello, M., Sargeant, T. J., Sarin, A., Sarkar, C., Sarkar, S., Sarrias, M. -R., Sarmah, D. T., Sarparanta, J., Sathyanarayan, A., Sathyanarayanan, R., Scaglione, K. M., Scatozza, F., Schaefer, L., Schafer, Z. T., Schaible, U. E., Schapira, A. H. V., Scharl, M., Schatzl, H. M., Schein, C. H., Scheper, W., Scheuring, D., Schiaffino, M. V., Schiappacassi, M., Schindl, R., Schlattner, U., Schmidt, O., Schmitt, R., Schmidt, S. D., Schmitz, I., Schmukler, E., Schneider, A., Schneider, B. E., Schober, R., Schoijet, A. C., Schott, M. B., Schramm, M., Schroder, B., Schuh, K., Schuller, C., Schulze, R. J., Schurmanns, L., Schwamborn, J. C., Schwarten, M., Scialo, F., Sciarretta, S., Scott, M. J., Scotto, K. W., Scovassi, A. I., Scrima, A., Scrivo, A., Sebastian, D., Sebti, S., Sedej, S., Segatori, L., Segev, N., Seglen, P. O., Seiliez, I., Seki, E., Selleck, S. B., Sellke, F. W., Selsby, J. T., Sendtner, M., Senturk, S., Seranova, E., Sergi, C., Serra-Moreno, R., Sesaki, H., Settembre, C., Setty, S. R. G., Sgarbi, G., Sha, O., Shacka, J. J., Shah, J. A., Shang, D., Shao, C., Shao, F., Sharbati, S., Sharkey, L. M., Sharma, D., Sharma, G., Sharma, K., Sharma, P., Sharma, S., Shen, H. -M., Shen, H., Shen, J., Shen, M., Shen, W., Shen, Z., Sheng, R., Sheng, Z., Sheng, Z. -H., Shi, J., Shi, X., Shi, Y. -H., Shiba-Fukushima, K., Shieh, J. -J., Shimada, Y., Shimizu, S., Shimozawa, M., Shintani, T., Shoemaker, C. J., Shojaei, S., Shoji, I., Shravage, B. V., Shridhar, V., Shu, C. -W., Shu, H. -B., Shui, K., Shukla, A. 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S., Steinkasserer, A., Stenmark, H., Sterneckert, J., Stevens, C., Stoka, V., Storch, S., Stork, B., Strappazzon, F., Strohecker, A. M., Stupack, D. G., Su, H., Su, L. -Y., Su, L., Suarez-Fontes, A. M., Subauste, C. S., Subbian, S., Subirada, P. V., Sudhandiran, G., Sue, C. M., Sui, X., Summers, C., Sun, G., Sun, J., Sun, K., Sun, M. -X., Sun, Q., Sun, Y., Sun, Z., Sunahara, K. K. S., Sundberg, E., Susztak, K., Sutovsky, P., Suzuki, H., Sweeney, G., Symons, J. D., Sze, S. C. W., Szewczyk, N. J., Tabecka-Lonczynska, A., Tabolacci, C., Tacke, F., Taegtmeyer, H., Tafani, M., Tagaya, M., Tai, H., Tait, S. W. G., Takahashi, Y., Takats, S., Talwar, P., Tam, C., Tam, S. Y., Tampellini, D., Tamura, A., Tan, C. T., Tan, E. -K., Tan, Y. -Q., Tanaka, M., Tang, D., Tang, J., Tang, T. -S., Tanida, I., Tao, Z., Taouis, M., Tatenhorst, L., Tavernarakis, N., Taylor, A., Taylor, G. A., Taylor, J. M., Tchetina, E., Tee, A. R., Tegeder, I., Teis, D., Teixeira, N., Teixeira-Clerc, F., Tekirdag, K. A., Tencomnao, T., Tenreiro, S., Tepikin, A. V., Testillano, P. S., Tettamanti, G., Tharaux, P. -L., Thedieck, K., Thekkinghat, A. A., Thellung, S., Thinwa, J. W., Thirumalaikumar, V. P., Thomas, S. M., Thomes, P. G., Thorburn, A., Thukral, L., Thum, T., Thumm, M., Tian, L., Tichy, A., Till, A., Timmerman, V., Titorenko, V. I., Todi, S. V., Todorova, K., Toivonen, J. M., Tomaipitinca, L., Tomar, D., Tomas-Zapico, C., Tomic, S., Tong, B. C. -K., Tong, C., Tong, X., Tooze, S. A., Torgersen, M. L., Torii, S., Torres-Lopez, L., Torriglia, A., Towers, C. G., Towns, R., Toyokuni, S., Trajkovic, V., Tramontano, D., Tran, Q. -G., Travassos, L. H., Trelford, C. B., Tremel, S., Trougakos, I. P., Tsao, B. P., Tschan, M. P., Tse, H. -F., Tse, T. F., Tsugawa, H., Tsvetkov, A. S., Tumbarello, D. A., Tumtas, Y., Tunon, M. J., Turcotte, S., Turk, B., Turk, V., Turner, B. J., Tuxworth, R. I., Tyler, J. K., Tyutereva, E. V., Uchiyama, Y., Ugun-Klusek, A., Uhlig, H. H., Ulamek-Koziol, M., Ulasov, I. V., Umekawa, M., Ungermann, C., Unno, R., Urbe, S., Uribe-Carretero, E., Ustun, S., Uversky, V. N., Vaccari, T., Vaccaro, M. I., Vahsen, B. F., Vakifahmetoglu-Norberg, H., Valdor, R., Valente, M. J., Valko, A., Vallee, R. B., Valverde, A. M., Van den Berghe, G., van der Veen, S., Van Kaer, L., van Loosdregt, J., van Wijk, S. J. L., Vandenberghe, W., Vanhorebeek, I., Vannier-Santos, M. A., Vannini, N., Vanrell, M. C., Vantaggiato, C., Varano, G., Varela-Nieto, I., Varga, M., Vasconcelos, M. H., Vats, S., Vavvas, D. G., Vega-Naredo, I., Vega-Rubin-de-Celis, S., Velasco, G., Velazquez, A. P., Vellai, T., Vellenga, E., Velotti, F., Verdier, M., Verginis, P., Vergne, I., Verkade, P., Verma, M., Verstreken, P., Vervliet, T., Vervoorts, J., Vessoni, A. T., Victor, V. M., Vidal, M., Vidoni, C., Vieira, O. V., Vierstra, R. D., Vigano, S., Vihinen, H., Vijayan, V., Vila, M., Vilar, M., Villalba, J. M., Villalobo, A., Villarejo-Zori, B., Villarroya, F., Villarroya, J., Vincent, O., Vindis, C., Viret, C., Viscomi, M. T., Visnjic, D., Vitale, I., Vocadlo, D. J., Voitsekhovskaja, O. V., Volonte, C., Volta, M., Vomero, M., Von Haefen, C., Vooijs, M. A., Voos, W., Vucicevic, L., Wade-Martins, R., Waguri, S., Waite, K. A., Wakatsuki, S., Walker, D. W., Walker, M. J., Walker, S. A., Walter, J., Wandosell, F. G., Wang, B., Wang, C. -Y., Wang, C., Wang, D., Wang, F., Wang, G., Wang, H., Wang, H. -G., Wang, J., Wang, K., Wang, L., Wang, M. H., Wang, M., Wang, N., Wang, P., Wang, Q. J., Wang, Q., Wang, Q. K., Wang, Q. A., Wang, W. -T., Wang, W., Wang, X., Wang, Y., Wang, Y. -Y., Wang, Z., Warnes, G., Warnsmann, V., Watada, H., Watanabe, E., Watchon, M., Wawrzynska, A., Weaver, T. E., Wegrzyn, G., Wehman, A. M., Wei, H., Wei, L., Wei, T., Wei, Y., Weiergraber, O. H., Weihl, C. C., Weindl, G., Weiskirchen, R., Wells, A., Wen, R. H., Wen, X., Werner, A., Weykopf, B., Wheatley, S. P., Whitton, J. L., Whitworth, A. J., Wiktorska, K., Wildenberg, M. E., Wileman, T., Wilkinson, S., Willbold, D., Williams, B., Williams, R. S. B., Williams, R. L., Williamson, P. R., Wilson, R. A., Winner, B., Winsor, N. J., Witkin, S. S., Wodrich, H., Woehlbier, U., Wollert, T., Wong, E., Wong, J. H., Wong, R. W., Wong, V. K. W., Wong, W. W. -L., Wu, A. -G., Wu, C., Wu, J., Wu, K. K., Wu, M., Wu, S. -Y., Wu, S., Wu, W. K. K., Wu, X., Wu, Y. -W., Wu, Y., Xavier, R. J., Xia, H., Xia, L., Xia, Z., Xiang, G., Xiang, J., Xiang, M., Xiang, W., Xiao, B., Xiao, G., Xiao, H., Xiao, H. -T., Xiao, J., Xiao, L., Xiao, S., Xiao, Y., Xie, B., Xie, C. -M., Xie, M., Xie, Y., Xie, Z., Xilouri, M., Xu, C., Xu, E., Xu, H., Xu, J., Xu, L., Xu, W. W., Xu, X., Xue, Y., Yakhine-Diop, S. M. S., Yamaguchi, M., Yamaguchi, O., Yamamoto, A., Yamashina, S., Yan, S., Yan, S. -J., Yan, Z., Yanagi, Y., Yang, C., Yang, D. -S., Yang, H., Yang, H. -T., Yang, J. -M., Yang, J., Yang, L., Yang, M., Yang, P. -M., Yang, Q., Yang, S., Yang, S. -F., Yang, W., Yang, W. Y., Yang, X., Yang, Y., Yao, H., Yao, S., Yao, X., Yao, Y. -G., Yao, Y. -M., Yasui, T., Yazdankhah, M., Yen, P. M., Yi, C., Yin, X. -M., Yin, Y., Yin, Z., Ying, M., Ying, Z., Yip, C. K., Yiu, S. P. T., Yoo, Y. H., Yoshida, K., Yoshii, S. R., Yoshimori, T., Yousefi, B., Yu, B., Yu, H., Yu, J., Yu, L., Yu, M. -L., Yu, S. -W., Yu, V. C., Yu, W. H., Yu, Z., Yuan, J., Yuan, L. -Q., Yuan, S., Yuan, S. -S. F., Yuan, Y., Yuan, Z., Yue, J., Yue, Z., Yun, J., Yung, R. L., Zacks, D. N., Zaffagnini, G., Zambelli, V. O., Zanella, I., Zang, Q. S., Zanivan, S., Zappavigna, S., Zaragoza, P., Zarbalis, K. S., Zarebkohan, A., Zarrouk, A., Zeitlin, S. O., Zeng, J., Zeng, J. -D., Zerovnik, E., Zhan, L., Zhang, B., Zhang, D. D., Zhang, H., Zhang, H. -L., Zhang, J., Zhang, J. -P., Zhang, K. Y. B., Zhang, L. W., Zhang, L., Zhang, M., Zhang, P., Zhang, S., Zhang, W., Zhang, X., Zhang, X. -W., Zhang, X. D., Zhang, Y., Zhang, Y. -D., Zhang, Y. -Y., Zhang, Z., Zhao, H., Zhao, L., Zhao, S., Zhao, T., Zhao, X. -F., Zhao, Y., Zheng, G., Zheng, K., Zheng, L., Zheng, S., Zheng, X. -L., Zheng, Y., Zheng, Z. -G., Zhivotovsky, B., Zhong, Q., Zhou, A., Zhou, B., Zhou, C., Zhou, G., Zhou, H., Zhou, J., Zhou, K., Zhou, R., Zhou, X. -J., Zhou, Y., Zhou, Z. -Y., Zhou, Z., Zhu, B., Zhu, C., Zhu, G. -Q., Zhu, H., Zhu, W. -G., Zhu, Y., Zhuang, H., Zhuang, X., Zientara-Rytter, K., Zimmermann, C. M., Ziviani, E., Zoladek, T., Zong, W. -X., Zorov, D. B., Zorzano, A., Zou, W., Zou, Z., Zuryn, S., Zwerschke, W., Brand-Saberi, B., Dong, X. C., Kenchappa, C. S., Lin, Y., Oshima, S., Rong, Y., Sluimer, J. C., Stallings, C. L., Tong, C. -K., and Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Published
2021

38. Lung Nodule Malignancy Prediction in Sequential CT Scans: Summary of ISBI 2018 Challenge

Author

Amir A. Amini, Michael F. McNitt-Gray, Keyvan Farahani, Yoganand Balagurunathan, Paul F. Pinsky, Gustavo Perez, Laura Alexandra Daza, Sandy Napel, Jayashree Kalpathy-Cramer, M. Mehdi Farhangi, Lubomir M. Hadjiiski, Alireza Mehrtash, Wiem Safta, Ali Gholipour, Joseph Enguehard, Ehwa Yang, Ricard Delgado-Gonzalo, Aditya Bagari, Renkun Ni, Benjamin Veasey, Kiran Vaidhya, Tina Kapur, Jung Won Moon, Hichem Frigui, Laura Silvana Castillo, Gabriel Bernardino, Pablo Arbeláez, Dmitry B. Goldgof, Xue Feng, and Andrew Beers

Subjects
nodules challenge, Lung Neoplasms, Engineering, Biomedical imaging, Pathology, Medical diagnosis, Tomography, Computed tomography, Lung, NLST, Cancer, Radiological and Ultrasound Technology, Lung Cancer, X-Ray Computed, Computer Science Applications, Nuclear Medicine & Medical Imaging, medicine.anatomical_structure, Cohort, Radiology, indeterminate pulmonary nodules, Algorithms, medicine.medical_specialty, Bioengineering, ISBI 2018, Malignancy, Article, Clinical Research, Information and Computing Sciences, medicine, Training, Humans, computed comography, Electrical and Electronic Engineering, Lung cancer, Receiver operating characteristic, business.industry, Solitary Pulmonary Nodule, Deep learning, medicine.disease, deep learning methods in lung CT, Good Health and Well Being, ROC Curve, cancer detection in longitudinal CT, National Lung Screening Trial, business, Tomography, X-Ray Computed, Software
Abstract

Lung cancer is by far the leading cause of cancer death in the US. Recent studies have demonstrated the effectiveness of screening using low dose CT (LDCT) in reducing lung cancer related mortality. While lung nodules are detected with a high rate of sensitivity, this exam has a low specificity rate and it is still difficult to separate benign and malignant lesions. The ISBI 2018 Lung Nodule Malignancy Prediction Challenge, developed by a team from the Quantitative Imaging Network of the National Cancer Institute, was focused on the prediction of lung nodule malignancy from two sequential LDCT screening exams using automated (non-manual) algorithms. We curated a cohort of 100 subjects who participated in the National Lung Screening Trial and had established pathological diagnoses. Data from 30 subjects were randomly selected for training and the remaining was used for testing. Participants were evaluated based on the area under the receiver operating characteristic curve (AUC) of nodule-wise malignancy scores generated by their algorithms on the test set. The challenge had 17 participants, with 11 teams submitting reports with method description, mandated by the challenge rules. Participants used quantitative methods, resulting in a reporting test AUC ranging from 0.698 to 0.913. The top five contestants used deep learning approaches, reporting an AUC between 0.87 - 0.91. The team's predictor did not achieve significant differences from each other nor from a volume change estimate (p =.05 with Bonferroni-Holm's correction).

Published
2021

39. Cerebellar and Prefrontal Structures Associated with Executive Functioning in Pediatric Patients with Congenital Heart Defects

Author

Julia Wallace, Vincent Lee, Rafael Ceschin, Daryaneh Badaly, Ashok Panigrahy, Aurélia Berdaa-Sahel, Shahida Sulaiman, Cheryl Burns, Cecilia W. Lo, Alexandria Zahner, and Sue R. Beers

Subjects
Cerebellum, medicine.medical_specialty, Working memory, business.industry, Cognitive flexibility, Neuropsychology, Cognition, Audiology, Executive functions, medicine.anatomical_structure, Medicine, Young adult, business, Executive dysfunction
Abstract

ObjectiveChildren, adolescents, and young adults with congenital heart defects (CHD) often display cognitive and behavioral manifestations of executive dysfunction. We consider the prefrontal and cerebellar brain structures as mechanisms for executive dysfunction among those with CHD.Method55 participants with CHD (M age = 13.93) and 95 healthy controls (M age = 13.13) completed magnetic resonance imaging (MRI) of the brain, from which we extracted volumetric data on prefrontal and cerebellar regions. Participants also completed neuropsychological tests of executive functioning; their parents completed behavioral ratings of their executive functions.ResultsCompared to healthy controls, those with CHD had smaller cerebellums and lateral, medial, and orbital prefrontal regions, they performed more poorly on tests of working memory, inhibitory control, and mental flexibility, and their parents rated them as having poorer executive functions across several indices. Across both groups, there were significant correlations for cerebellar and/or prefrontal volumes with cognitive assessments of working memory, mental flexibility, and inhibitory control and with behavioral ratings of working memory, task initiation, and emotional control. Greater prefrontal volumes were associated with better working memory, among those with larger cerebellums (with group differences based on the measure and the prefrontal region). Greater prefrontal volumes were related to better emotional regulation only among participants with CHD with smaller cerebellar volumes, and with poorer inhibition and emotional regulation only among healthy controls with larger cerebellar volumes.ConclusionThe cerebellum modulates the relationships between prefrontal regions and executive functioning differently for pediatric patients with CHD versus health controls.

Published
2021

40. Working memory training efficacy in COPD: the randomised, double-blind, placebo-controlled Cogtrain trial

Author

Lisanne Schuurman, Katrijn Houben, Annemie M. W. J. Schols, Sarah Mount, Harry R. Gosker, Martijn van Beers, Daisy J.A. Janssen, Frits M.E. Franssen, Pulmonologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Section Eating Disorders and Obesity, RS: FPN CPS II, RS: CAPHRI - R1 - Ageing and Long-Term Care, Health Services Research, and Fac. Health, Medicine and Life Sciences

Subjects
Pulmonary and Respiratory Medicine, Working memory training, medicine.medical_specialty, MILD COGNITIVE IMPAIRMENT, STRESS, Placebo, OBSTRUCTIVE PULMONARY-DISEASE, ADHERENCE, Intervention (counseling), Original Research Articles, DIETARY-INTAKE, Medicine, COPD, Effects of sleep deprivation on cognitive performance, BATTERY, Sedentary lifestyle, Recall, business.industry, EXECUTIVE FUNCTIONS, Cognition, ASSOCIATION, PERFORMANCE, medicine.disease, Physical therapy, business, BEHAVIOR
Abstract

Background Cognitive impairment is highly prevalent in COPD and is associated with a sedentary lifestyle, unhealthy diet and increased cognitive stress susceptibility. Enhancement of cognitive performance by working memory training (WMT) may reverse these effects. Therefore, this study aimed to investigate the efficacy of WMT in COPD on cognitive performance, healthy lifestyle behaviours and cognitive stress susceptibility. Methods The double-blind randomised, placebo-controlled Cogtrain trial consisted of a 12-week training phase comprising 30 active or sham WMT sessions, followed by a second 12-week maintenance phase with 12 sessions. Measurements took place at baseline and after the first and second phases. The primary outcome was cognitive performance. Secondary outcomes were the recall of prespecified healthy lifestyle goals, physical capacity and activity, dietary quality and cognitive stress susceptibility. Motivation towards exercising and healthy eating and psychological wellbeing were exploratory outcomes. Results Sixty-four patients with moderate COPD (45% male, aged 66.2±7.2 years, median forced expiratory volume in 1 s 60.6% predicted) were randomised. WMT significantly increased patients’ performance on the trained tasks in the first phase, which remained stable in the second phase. Of the 17 cognitive outcome measures, only one measure of memory improved after the first phase and one measure of reaction time after the second phase. This intervention did not influence physical capacity and activity, recall of prespecified healthy lifestyle goals, psychological wellbeing or cognitive stress susceptibility. Conclusion WMT improved performance on the trained tasks but not overall cognitive performance, healthy lifestyle behaviours or cognitive stress susceptibility in patients with COPD., Working memory training improves performance on the trained tasks but not overall cognitive performance, healthy lifestyle behaviours or cognitive stress susceptibility in patients with COPD https://bit.ly/3ErjIx2

Published
2021

41. Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis

Author

Yi Luo, Denis Streltsov, Mary K. Porteous, Carly McCoubrey, Pitchumani Sivakumar, Edward Cantu, Jason D. Christie, Gabor Jarai, John Ryan Thompson, Michael F. Beers, and Ron Ammar

Subjects
Proteomics, Oncology, medicine.medical_specialty, Proteome, Idiopathic pulmonary fibrosis, Lung injury, Diseases of the respiratory system, FEV1/FVC ratio, Internal medicine, medicine, Humans, CCL17, Lung, RC705-779, business.industry, Research, Gene Expression Profiling, Blood Proteins, Extracellular matrix, respiratory system, medicine.disease, Fold change, respiratory tract diseases, medicine.anatomical_structure, Case-Control Studies, Mast cells, CCL28, Chemokines, Transcriptome, business, Biomarkers, CCL22
Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a significant unmet medical need. Development of transformational therapies for IPF is challenging in part to due to lack of robust predictive biomarkers of prognosis and treatment response. Importantly, circulating biomarkers of IPF are limited and none are in clinical use. Methods We previously reported dysregulated pathways and new disease biomarkers in advanced IPF through RNA sequencing of lung tissues from a cohort of transplant-stage IPF patients (n = 36) in comparison to normal healthy donors (n = 19) and patients with acute lung injury (n = 11). Here we performed proteomic profiling of matching plasma samples from these cohorts through the Somascan-1300 SomaLogics platform. Results Comparative analyses of lung transcriptomic and plasma proteomic signatures identified a set of 34 differentially expressed analytes (fold change (FC) ≥ ± 1.5, false discovery ratio (FDR) ≤ 0.1) in IPF samples compared to healthy controls. IPF samples showed strong enrichment of chemotaxis, tumor infiltration and mast cell migration pathways and downregulated extracellular matrix (ECM) degradation. Mucosal (CCL25 and CCL28) and Th2 (CCL17 and CCL22) chemokines were markedly upregulated in IPF and highly correlated within the subjects. The mast cell maturation chemokine, CXCL12, was also upregulated in IPF plasma (fold change 1.92, FDR 0.006) and significantly correlated (Pearson r = − 0.38, p = 0.022) to lung function (%predicted FVC), with a concomitant increase in the mast cell Tryptase, TPSB2. Markers of collagen III and VI degradation (C3M and C6M) were significantly downregulated (C3M p Conclusions Our study identifies a panel of tissue and circulating biomarkers with clinical utility in IPF that can be validated in future studies across larger cohorts.

Published
2021

42. Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms

Author

C. Drogou, Anne Boland, Robert Olaso, Mounir Chennaoui, Céline Derbois, Fabien Sauvet, Claire Thomas, Jean-François Deleuze, Maxime Prost, D. Gomez-Merino, Pascal Van Beers, Damien Leger, Mathias Guillard, Mégane Erblang, Rodolphe Dorey, Michael Quiquempoix, and Arnaud Rabat

Subjects
medicine.medical_specialty, sleep deprivation, cognitive responses, genetic polymorphisms, A2A receptor, TNF-α, IL1-β, IL-6, COMT, Science, media_common.quotation_subject, Single-nucleotide polymorphism, behavioral disciplines and activities, Article, General Biochemistry, Genetics and Molecular Biology, Internal medicine, mental disorders, medicine, Allele, Ecology, Evolution, Behavior and Systematics, media_common, Psychomotor learning, Cognitive vulnerability, business.industry, Paleontology, Sleep deprivation, Endocrinology, Space and Planetary Science, Wakefulness, medicine.symptom, business, Vigilance (psychology), rs4680
Abstract

Several genetic polymorphisms differentiate between healthy individuals who are more cognitively vulnerable or resistant during total sleep deprivation (TSD). Common metrics of cognitive functioning for classifying vulnerable and resilient individuals include the Psychomotor Vigilance Test (PVT), Go/noGo executive inhibition task, and subjective daytime sleepiness. We evaluated the influence of 14 single-nucleotide polymorphisms (SNPs) on cognitive responses during total sleep deprivation (continuous wakefulness for 38 h) in 47 healthy subjects (age 37.0 ± 1.1 years). SNPs selected after a literature review included SNPs of the adenosine-A2A receptor gene (including the most studied rs5751876), pro-inflammatory cytokines (TNF-α, IL1-β, IL-6), catechol-O-methyl-transferase (COMT), and PER3. Subjects performed a psychomotor vigilance test (PVT) and a Go/noGo-inhibition task, and completed the Karolinska Sleepiness Scale (KSS) every 6 h during TSD. For PVT lapses (reaction time >500 ms), an interaction between SNP and SDT (p < 0.05) was observed for ADORA2A (rs5751862 and rs2236624) and TNF-α (rs1800629). During TSD, carriers of the A allele for ADORA2A (rs5751862) and TNF-α were significantly more impaired for cognitive responses than their respective ancestral G/G genotypes. Carriers of the ancestral G/G genotype of ADORA2A rs5751862 were found to be very similar to the most resilient subjects for PVT lapses and Go/noGo commission errors. Carriers of the ancestral G/G genotype of COMT were close to the most vulnerable subjects. ADORA2A (rs5751862) was significantly associated with COMT (rs4680) (p = 0.001). In conclusion, we show that genetic polymorphisms in ADORA2A (rs5751862), TNF-α (rs1800629), and COMT (rs4680) are involved in creating profiles of high vulnerability or high resilience to sleep deprivation. (NCT03859882).

Published
2021
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43. Relationships Between Regional Cerebral Blood Flow and Neurocognitive Outcomes in Children and Adolescents With Congenital Heart Disease

Author

Jacqueline Weinberg, Vincent J. Schmithorst, Daryaneh Badaly, Sue R. Beers, Ashok Panigrahy, Vincent Lee, and Cecilia W. Lo

Subjects
Pulmonary and Respiratory Medicine, Heart Defects, Congenital, medicine.medical_specialty, Adolescent, Precuneus, NIH Toolbox, Article, Internal medicine, Medicine, Humans, Child, Default mode network, business.industry, Brain, General Medicine, Magnetic Resonance Imaging, Dorsolateral prefrontal cortex, medicine.anatomical_structure, Treatment Outcome, Cerebral blood flow, Regional Blood Flow, Posterior cingulate, Cerebrovascular Circulation, Cardiology, Surgery, Spin Labels, Cardiology and Cardiovascular Medicine, business, Insula, Neurocognitive
Abstract

OBJECTIVE: To identify regional cerebral blood flow (rCBF) alterations in children and adolescents with congenital heart disease (CHD) in relation to neurocognitive outcomes using a non-biased data-driven approach. METHODS: This is a prospective, observational study of children and adolescents with CHD without brain injury and healthy controls using pseudo-continuous arterial spin labeling (pCASL) MRI. Quantitative rCBF was compared between participants with CHD and healthy controls using a voxel-wise data-driven method. Mediation analysis was then performed on a voxelwise basis, with the grouping variable as the independent variable, neurocognitive outcomes (from the NIH Toolbox Cognitive Battery) as the dependent variables, and rCBF as the mediator. RESULTS: After motion correction, a total of 80 studies were analyzable (27 for patients with CHD, 53 for controls). We found steeper age-related decline in rCBF among those with CHD compared to normal controls in the insula/ventromedial prefrontal regions (salience network) and the dorsal anterior cingulate and precuneus/posterior cingulate (default mode network), and posterior parietal/dorsolateral prefrontal (central executive network) (FWE-corrected p < 0.05). The reduced rCBF in the default mode/salience network was found to mediate poorer performance on an index of crystallized cognition from the NIH Toolbox Cognitive Battery in those with CHD compared to controls. In contrast, reduced rCBF in the central executive network/salience network mediated reduced deficits in fluid cognition among patients with CHD compared to controls. CONCLUSION: Regional cerebral blood flow alterations mediate domain-specific differences in cognitive performance in children and adolescents with CHD compared to healthy controls, independent of injury, and are likely related to brain and cognitive reserve mechanisms. Further research is needed to evaluate the potential of interventions in CHD targeting regional cerebral blood flow across lifespan.

Published
2021

44. School-Based Health Centers and Pediatric Practice

Author

Chris Kjolhede, April C. Lee, Cheryl Duncan De Pinto, Sonja C. O’Leary, Marti Baum, Nathaniel Savio Beers, Sara Moran Bode, Erica J. Gibson, Peter Gorski, Viju Jacob, Marian Larkin, Ryan Christopher, and Heidi Schumacher

Subjects
Mental Health Services, Medical home, medicine.medical_specialty, Pediatric practice, Adolescent, business.industry, Child Health Services, education, MEDLINE, Primary care, Pediatrics, Mental health, Health Services Accessibility, United States, Health equity, Adolescent Health Services, Family medicine, Pediatrics, Perinatology and Child Health, Health care, medicine, Humans, Child, business, School-based health centers, School Health Services
Abstract

School-based health centers (SBHCs) are unique health care settings for our nation’s school-aged children and adolescents. SBHCs represent the collaboration between the health and school communities to support the health and mental health needs and the academic achievements of children and adolescents, particularly students with health disparities or poor access to health care. SBHCs improve access to health care services for students by decreasing financial, geographic, age, and cultural barriers. This policy statement provides an overview of SBHCs, including the scope of services as well as some of the documented benefits and challenges. This policy statement also reviews the role of SBHCs in working with the pediatric medical home and provides recommendations that support the coordination of SBHCs with pediatric primary care providers and the pediatric medical home.

Published
2021

45. Population genomics of Drosophila suzukii reveal longitudinal population structure and signals of migrations in and out of the continental United States

Author

Ashfaq A. Sial, Hannah J. Burrack, Stephen P. Hesler, Lauren M Diepenbrock, Elizabeth H. Beers, Steven Van Timmeren, Betsey Miller, Brian A. Little, Joanna C. Chiu, Dori Edson Nava, Rufus Isaacs, Bo Zhao, Philip D. Fanning, Gregory M. Loeb, Cherre Sade Bezerra Da Silva, Vaughn M. Walton, Claudio Ioriatti, Frank G. Zalom, Xin-Geng Wang, Derek A. Wilson, Kyle M Lewald, William R. Conner, Francis A. Drummond, Kent M. Daane, Michael Gaffney, Dara G. Stockton, Yoosook Lee, Anna K. Wallingford, Dalila Rendon, Antoine Abrieux, Felipe Andreazza, and Macdonald, S

Subjects
AcademicSubjects/SCI01140, Genetic Markers, AcademicSubjects/SCI00010, Range (biology), Biology, QH426-470, AcademicSubjects/SCI01180, Population genomics, Drosophila suzukii, Genetics, Animals, East Asia, invasion genomics, Molecular Biology, Drosophila, Genetics (clinical), Investigation, Genetic diversity, Ecology, business.industry, population structure, genetic diversity, Genomics, biology.organism_classification, United States, spotted-wing drosophila, Settore AGR/11 - ENTOMOLOGIA GENERALE E APPLICATA, Agriculture, Fruit, AcademicSubjects/SCI00960, Zero Hunger, Metagenomics, PEST analysis, business
Abstract

Drosophila suzukii, or spotted-wing drosophila, is now an established pest in many parts of the world, causing significant damage to numerous fruit crop industries. Native to East Asia, D. suzukii infestations started in the United States a decade ago, occupying a wide range of climates. To better understand invasion ecology of this pest, knowledge of past migration events, population structure, and genetic diversity is needed. In this study, we sequenced whole genomes of 237 individual flies collected across the continental United States, as well as several sites in Europe, Brazil, and Asia, to identify and analyze hundreds of thousands of genetic markers. We observed strong population structure between Western and Eastern US populations, but no evidence of any population structure between different latitudes within the continental United States, suggesting that there are no broad-scale adaptations occurring in response to differences in winter climates. We detect admixture from Hawaii to the Western United States and from the Eastern United States to Europe, in agreement with previously identified introduction routes inferred from microsatellite analysis. We also detect potential signals of admixture from the Western United States back to Asia, which could have important implications for shipping and quarantine policies for exported agriculture. We anticipate this large genomic dataset will spur future research into the genomic adaptations underlying D. suzukii pest activity and development of novel control methods for this agricultural pest.

Published
2021

46. The Stark Splitting of Millimeter Wave Transitions of Water

Author

Gerald P. Klein and Yardley Beers

Subjects
Field (physics), business.industry, Chemistry, Computational physics, Physics and Chemistry, symbols.namesake, Dipole, Wavelength, Optics, Stark effect, Extremely high frequency, Modulation (music), Moment (physics), symbols, Millimeter, Physics::Chemical Physics, business, Astrophysics::Galaxy Astrophysics
Abstract

This paper first discusses the technique of making Stark measurements at millimeter wavelengths. The details of correcting for residual overlap between the lines, the effects of modulation, and of the field inhomogeneity are discussed. Finally the measured frequencies and the empirical Stark coefficients for one H(2)O, and one D(2)O, and five HDO lines between 85 and 250 GHz are given. The final analysis of the data to give values of the dipole moment will be given in another paper.

Published
2021

47. Skeletal muscle mass at C3 is a strong predictor for skeletal muscle mass at L3 in sarcopenic and non-sarcopenic patients with head and neck cancer

Author

M.A. van Beers, Ernst J. Smid, Najiba Chargi, N. Carrillo Minulina, Jan Willem Dankbaar, Sandra I. Bril, and R. de Bree

Subjects
Cancer Research, Sarcopenia, business.industry, Head and neck cancer, Anatomy, medicine.disease, Skeletal muscle mass, Oncology, Head and Neck Neoplasms, Medicine, Humans, Oral Surgery, business, Muscle, Skeletal
Published
2021

48. B-Cell Analysis for Monitoring Patients Undergoing B-Cell Depletion for the Treatment of Autoimmune Diseases

Author

Jan Damoiseaux, Joyce J. B. C. van Beers, Matthias Busch, Pieter van Paassen, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Central Diagnostic Lab, RS: Carim - B01 Blood proteins & engineering, Interne Geneeskunde, RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, MUMC+: MA Nefrologie (9), and MUMC+: MA Klinische Immunologie (9)

Subjects
CD38, Immunoglobulin D, Maintenance therapy, Antigens, CD, immune system diseases, Remission Induction Therapy, medicine, Humans, CD20, Antigens, B cell, Autoimmune disease, B-Lymphocytes, biology, business.industry, Autoimmune Diseases/therapy, Antigens, CD20, medicine.disease, CD, medicine.anatomical_structure, Immunology, biology.protein, Bone marrow, business
Abstract

B-cell depleting therapy is increasingly used in the treatment of many distinct autoimmune diseases. This not only involves remission induction therapy, but also maintenance therapy. In this respect, it is of importance to monitor composition of the B-cell compartment in the peripheral blood. This can be performed at the time of initiation of the therapy, especially in those cases in which the expected clinical effect is not achieved. If B-cells are absent, B-cell depletion may not be the best treatment option; if B-cells are present, the efficacy may be hampered by neutralizing antibodies. For monitoring B-cell recovery it is important not to just enumerate B-cells, but to also phenotype the B-cells. A phenotype of IgD-CD27++CD38++ indicates the presence of circulating plasmablasts that lack CD20 and which are therefore not sensitive for B-cell depletion with anti-CD20 biologicals. A phenotype of IgD+CD27-CD38++ on the other hand, indicates recovery from the bone marrow with transitional B-cells. This chapter will focus on B-cell analyses by flow cytometry.

Published
2021

49. Necro-inflammatory activity grading in chronic viral hepatitis with three-dimensional multifrequency MR elastography

Author

Ralph Sinkus, Gwenaël Pagé, Valérie Vilgrain, Gaspard d’Assignies, Philippe Garteiser, Helena S. Leitão, Bernard E. Van Beers, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Ralph, Sinkus, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord

Subjects
Adult, Male, medicine.medical_specialty, Cirrhosis, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Science, Imaging techniques, Article, 030218 nuclear medicine & medical imaging, Shear modulus, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, Hepatitis B, Chronic, Imaging, Three-Dimensional, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], medicine, Humans, Aged, Hepatitis, Multidisciplinary, medicine.diagnostic_test, Hepatology, business.industry, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diagnostic markers, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Elastography, business, Viral hepatitis, Nuclear medicine
Abstract

The purpose of this study was to assess the diagnostic value of multifrequency MR elastography for grading necro-inflammation in the liver. Fifty participants with chronic hepatitis B or C were recruited for this institutional review board-approved study. Their liver was examined with multifrequency MR elastography. The storage, shear and loss moduli, and the damping ratio were measured at 56 Hz. The multifrequency wave dispersion coefficient of the shear modulus was calculated. The measurements were compared to reference markers of necro-inflammation and fibrosis with Spearman correlations and multiple regression analysis. Diagnostic accuracy was assessed. At multiple regression analysis, necro-inflammation was the only determinant of the multifrequency dispersion coefficient, whereas fibrosis was the only determinant of the storage, loss and shear moduli. The multifrequency dispersion coefficient had the largest AUC for necro-inflammatory activity A ≥ 2 [0.84 (0.71–0.93) vs. storage modulus AUC: 0.65 (0.50–0.79), p = 0.03], whereas the storage modulus had the largest AUC for fibrosis F ≥ 2 [AUC (95% confidence intervals) 0.91 (0.79–0.98)] and cirrhosis F4 [0.97 (0.88–1.00)]. The measurement of the multifrequency dispersion coefficient at three-dimensional MR elastography has the potential to grade liver necro-inflammation in patients with chronic vial hepatitis.

Published
2021

50. Prospective comparison of transient elastography, MRI and serum scores for grading steatosis and detecting non-alcoholic steatohepatitis in bariatric surgery candidates

Author

Philippe Garteiser, Pauline Jouet, Marco Dioguardi Burgio, Bernard E. Van Beers, Pierre Bedossa, Daniela Calabrese, Séverine Ledoux, Laurent Castera, Muriel Coupaye, Marina Esposito-Farèse, Sabrina Doblas, and Simon Msika

Subjects
medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, bariatric surgery, NASH, non-alcoholic steatohepatitis, LSM, liver stiffness measurement, RC799-869, NAFLD, Nonalcoholic fatty liver disease, Non-invasive diagnosis, Internal Medicine, steatosis, AUROC, area under the receiver operating characteristic curve, Immunology and Allergy, Medicine, ST, SteatoTest, Grading (tumors), NAS, NAFLD activity score, Se, sensitivity, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, Gastroenterology, NASH, Diseases of the digestive system. Gastroenterology, medicine.disease, MRI-PDFF, MRI-proton density fat fraction, transient elastography, CAP, PPV, positive predictive value, Surgery, TE, transient elastography, FLIP, fatty liver inhibition of progression, HSI, hepatic steatosis index, NPV, negative predictive value, Liver biopsy, Sp, specificity, Steatosis, Steatohepatitis, CAP, controlled attenuation parameter, business, Transient elastography, Body mass index, MRI-PDFF, FLI, fatty liver index, Research Article
Abstract

Background & Aims Tools for the non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) in morbidly obese patients with suspected non-alcoholic fatty liver disease (NAFLD) are an unmet clinical need. We prospectively compared the performance of transient elastography, MRI, and 3 serum scores for the diagnosis of NAFLD, grading of steatosis and detection of NASH in bariatric surgery candidates. Methods Of 186 patients screened, 152 underwent liver biopsy, which was used as a reference for NAFLD (steatosis [S]>5%), steatosis grading and NASH diagnosis. Biopsies were read by a single expert pathologist. MRI-based proton density fat fraction (MRI-PDFF) was measured in an open-bore, vertical field 1.0T scanner and controlled attenuation parameter (CAP) was measured by transient elastography, using the XL probe. Serum scores (SteatoTest, hepatic steatosis index and fatty liver index) were also calculated. Results The applicability of MRI was better than that of FibroScan (98% vs. 79%; p 5%, S>33%, S>66% and NASH, respectively. Transient elastography had an AUROC of 0.80 for significant fibrosis (F0-F1 vs. F2-F3). MRI-PDFF had AUROCs of 0.97, 0.95, 0.92 and 0.84 for S>5%, S>33%, S>66% and NASH, respectively. When compared head-to-head in the 97 patients with all valid tests available, MRI-PDFF outperformed CAP for grading steatosis (S>33%, AUROC 0.97 vs. 0.78; p 66%, AUROC 0.93 vs. 0.75; p = 0.0015) and diagnosing NASH (AUROC 0.82 vs. 0.68; p = 0.0056). When compared in “intention to diagnose” analysis, MRI-PDFF outperformed CAP, hepatic steatosis index and fatty liver index for grading steatosis (S>5%, S>33% and S>66%). Conclusion MRI-PDFF outperforms CAP for diagnosing NAFLD, grading steatosis and excluding NASH in morbidly obese patients undergoing bariatric surgery. Lay summary Non-invasive tests for detecting fatty liver and steatohepatitis, the active form of the disease, have not been well studied in obese patients who are candidates for bariatric surgery. The most popular tests for this purpose are Fibroscan, which can be used to measure the controlled attenuation parameter (CAP), and magnetic resonance imaging, which can be used to measure the proton density fat fraction (MRI-PDFF). We found that, when taking liver biopsy as a reference, MRI-PDFF performed better than CAP for detecting and grading fatty liver as well as excluding steatohepatitis in morbidly obese patients undergoing bariatric surgery., Graphical abstract, Highlights • NAFLD/NASH is common in morbidly obese patients undergoing bariatric surgery. • Non-invasive diagnosis of NAFLD/NASH is an unmet need in this population. • We compared MRI-PDFF, CAP and serum scores for grading steatosis and diagnosing NASH, using liver biopsy as a reference. • Applicability of magnetic resonance imaging was better than that of Fibroscan. • MRI-PDFF outperformed CAP for diagnosing and grading steatosis, as well as excluding NASH.

Published
2021

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