4,507 results on '"M, Berger"'
Search Results
2. Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration
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Marlene Saßmannshausen, Charlotte Behning, Jonas Weinz, Lukas Goerdt, Jan H. Terheyden, Petrus Chang, Matthias Schmid, Stephen H. Poor, Nadia Zakaria, Robert P. Finger, Frank G. Holz, Maximilian Pfau, Steffen Schmitz-Valckenberg, Sarah Thiele, H. Agostini, L. Altay, R. Atia, F. Bandello, P.G. Basile, C. Behning, M. Belmouhand, M. Berger, A. Binns, C.J.F. Boon, M. Böttger, C. Bouchet, J.E. Brazier, T. Butt, C. Carapezzi, J. Carlton, A. Carneiro, A. Charil, R. Coimbra, M. Cozzi, D.P. Crabb, J. Cunha-Vaz, C. Dahlke, L. de Sisternes, H. Dunbar, R.P. Finger, E. Fletcher, H. Floyd, C. Francisco, M. Gutfleisch, R. Hogg, F.G. Holz, C.B. Hoyng, A. Kilani, J. Krätzschmar, L. Kühlewein, M. Larsen, S. Leal, Y.T.E. Lechanteur, U.F.O. Luhmann, A. Lüning, I. Marques, C. Martinho, G. Montesano, Z. Mulyukov, M. Paques, B. Parodi, M. Parravano, S. Penas, T. Peters, T. Peto, M. Pfau, S. Poor, S. Priglinger, D. Rowen, G.S. Rubin, J. Sahel, C. Sánchez, O. Sander, M. Saßmannshausen, M. Schmid, S. Schmitz-Valckenberg, H. Schrinner-Fenske, J. Siedlecki, R. Silva, A. Skelly, E. Souied, G. Staurenghi, L. Stöhr, D.J. Taylor, J.H. Terheyden, S. Thiele, A. Tufail, M. Varano, L. Vieweg, L. Wintergerst, A. Wolf, and N. Zakaria
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Ophthalmology - Published
- 2023
3. Cases in Precision Medicine: Is There an Obligation to Return Reinterpreted Genetic Results to Former Patients?
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Paul S. Appelbaum, Wylie Burke, Erik Parens, Jessica Roberts, Sara M. Berger, and Wendy K. Chung
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Internal Medicine ,General Medicine - Published
- 2023
4. Exploring Limited English Proficiency in the Clinical Outcomes of Pediatric Burn Patients
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Juan Pablo Santana, Philip Kyung Woo Hong, Lauren A. Indelicato, Amy M. Berger, Shawn D. Larson, Janice A. Taylor, Moiz M. Mustafa, Saleem Islam, Dan Neal, and Robin T. Petroze
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Surgery - Abstract
Limited English proficiency (LEP) is linked to lower health care access and worse clinical outcomes. This study aims to explore the potential role of LEP on clinical outcomes of pediatric burn patients.We conducted a single-institution retrospective study of burn patients presenting at a tertiary pediatric burn referral program between January 2016 and December 2020. Patient demographics, burn mechanism, severity, interventions, and primary patient language were abstracted from the electronic health record. Clinical outcomes (length of stay [LOS], clinic follow-up, and 30-day readmission) of patients with LEP were compared to patients with English as primary language (EPL).Thirty-five (4.2%) patients with LEP were identified of 840 total patients. On univariate analysis, there was no difference in mean total body surface area (6.5% versus 6.1%), report of physical abuse (2.9% versus 8.9%), or need for grafting (14.3% versus 15.0%) comparing patients with LEP to those with EPL. Patients with LEP were more likely to have a scald burn (68.6% versus 48.9%, P = 0.025) and less likely to have a flame/fire burn (20.0% versus 37.6%, P = 0.047). On multivariate analysis, there was no difference between patients with LEP compared to patients with EPL for LOS (2.9 versus 3.5 d), 30-day readmissions (5.6% versus 5.7%), or clinic follow-up (80.6% versus 75.0%). In patients with10% total body surface area, patients with LEP had a longer emergency department LOS (277 min versus 145 min, P = 0.06) but no difference in outcome measures.Pediatric patients with LEP were not found to have worse burn outcomes compared to EPL patients in our patient sample. However, a true association is difficult to determine given the small sample size of LEP patients and the potential underestimation of language discordancy as recorded in the electronic medical record. Further research is needed to better explore the role of primary language and health communication as a social determinant of health in pediatric burn patients.
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- 2023
5. The experiences of pediatric nurses deployed to adult COVID-19 wards
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F. Darchen, H. Audouin, M. Berger, and V. Juin-Leonard
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Pediatrics, Perinatology and Child Health - Published
- 2023
6. Methods for think-aloud interviews in health-related resource-use research: the PECUNIA RUM instrument
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L.M.M. Janssen, I. Pokhilenko, R.M.W.A. Drost, A.T.G. Paulus, J. Thorn, W. Hollingworth, S. Noble, M. Berger, J. Simon, and S.M.A.A. Evers
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PEOPLE THINK ,PROTOCOLS ,patient involvement ,think-aloud ,CHALLENGES ,IMPACT ,Health Policy ,COST ,QUESTIONNAIRE ,General Medicine ,Resource-use measurement ,ANSWER ,Instrument development ,SELF-REPORTS ,CARE UTILIZATION ,qualitative research methods ,Pharmacology (medical) - Abstract
BackgroundThe think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent's perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap.MethodsMethods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A 'before the interview' (including translation, recruitment, training), Part B 'during the interview' (including setting, opening, completing the instrument, open-ended questions, closing), and part C 'after the interview' (including transcription and data analysis, trustworthiness).ConclusionsThis manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.
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- 2023
7. Dimensional Reduction for Single-Molecule Imaging of DNA and Nucleosome Condensation by Polyamines, HP1α and Ki-67
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Nils A. Benning, Jacob Kæstel-Hansen, Fahad Rashid, Sangwoo Park, Raquel Merino Urteaga, Ting-Wei Liao, Jingzhou Hao, James M. Berger, Nikos S. Hatzakis, and Taekjip Ha
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Materials Chemistry ,Physical and Theoretical Chemistry ,Surfaces, Coatings and Films - Abstract
Macromolecules organize themselves into discrete membrane-less compartments. Mounting evidence has suggested that nucleosomes as well as DNA itself can undergo clustering or condensation to regulate genomic activity. Current in vitro condensation studies provide insight into the physical properties of condensates, such as surface tension and diffusion. However, methods that provide the resolution needed for complex kinetic studies of multicomponent condensation are desired. Here, we use a supported lipid bilayer platform in tandem with total internal reflection microscopy to observe the two-dimensional movement of DNA and nucleosomes at the single-molecule resolution. This dimensional reduction from three-dimensional studies allows us to observe the initial condensation events and dissolution of these early condensates in the presence of physiological condensing agents. Using polyamines, we observed that the initial condensation happens on a time scale of minutes while dissolution occurs within seconds upon charge inversion. Polyamine valency, DNA length, and GC content affect the threshold polyamine concentration for condensation. Protein-based nucleosome condensing agents, HP1α and Ki-67, have much lower threshold concentrations for condensation than charge-based condensing agents, with Ki-67 being the most effective, requiring as low as 100 pM for nucleosome condensation. In addition, we did not observe condensate dissolution even at the highest concentrations of HP1α and Ki-67 tested. We also introduce a two-color imaging scheme where nucleosomes of high density labeled in one color are used to demarcate condensate boundaries and identical nucleosomes of another color at low density can be tracked relative to the boundaries after Ki-67-mediated condensation. Our platform should enable the ultimate resolution of single molecules in condensation dynamics studies of chromatin components under defined physicochemical conditions.
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- 2023
8. Impact of ß-hydroxy-ß-methylbutyrate (HMB) in critically ill patients on the endocrine axis – A post-hoc cohort study of the HMB-ICU trial
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Olivier Pantet, Marina V. Viana, Mariëlle P.K.J. Engelen, Nicolaas E.P. Deutz, Stéphanie Gran, and Mette M. Berger
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism - Published
- 2023
9. Post Intensive Care Syndrome (PICS) physical, cognitive, and mental health outcomes 6-months to 7 years after a major burn injury: A cross-sectional study
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Dan, Carel, Olivier, Pantet, Anne-Sylvie, Ramelet, and Mette M, Berger
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Intensive Care Units ,Cross-Sectional Studies ,Cognition ,Critical Care ,Outcome Assessment, Health Care ,Humans ,Burns/complications ,Burns/epidemiology ,Critically ill ,Major burns ,Risk factors ,Survivor ,Emergency Medicine ,Surgery ,General Medicine ,Burns ,Critical Care and Intensive Care Medicine - Abstract
The Post Intensive Care Syndrome (PICS) has been described in intensive care (ICU) survivors, being present in 50% of patients surviving 12 months, with well-defined risk factors. Severely burned patients combine many of these risk factors, but the prevalence of PICS has not yet been documented in burns. The study aimed to answer this question and identify associations of PICS with clinical characteristics. Cross-sectional descriptive study of major burn survivors admitted to the burn ICU between 2013 and 2019. Main inclusion criteria: major burns>20 %BSA and ICU admission. The PICS components were assessed using three questionnaires: 1) Physical with Burn Specific Health Scale-Brief (BSHS-B); 2) Cognitive health with MacNair Cognitive Difficulties Self-Rating Scale (CDS); 3) Mental health with the Hospital Anxiety and Depression Scale (HADS) questionnaire. PICS was considered present if at least one component out of three was abnormal. Data as mean±SD. Among the 288 patients admitted during the period, 132 met the inclusion criteria: 53 patients were finally enrolled. They were aged 44 ± 18 years at the time of injury and burned 24 ± 20 BSA % and stayed 25 ± 44 days in the ICU. PICS was identified in 35 patients (66 %): more than one component was altered in 21 patients (60 %). Principal risk factors were more than 3 general anesthetics, prolonged mechanical ventilation (>4 days), ICU stay (>8 days), and hospital stay (>25 days) CONCLUSION: PICS occurred in 66 % of major burns with two or three components affected simultaneously in 60 %, i.e. more frequently than in general ICU patients.
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- 2023
10. Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II
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Tung T. Le, Meiling Wu, Joyce H. Lee, Neti Bhatt, James T. Inman, James M. Berger, and Michelle D. Wang
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Cell Biology ,Molecular Biology - Abstract
Etoposide is a broadly employed chemotherapeutic and eukaryotic topoisomerase II poison that stabilizes cleaved DNA intermediates to promote DNA breakage and cytotoxicity. How etoposide perturbs topoisomerase dynamics is not known. Here we investigated the action of etoposide on yeast topoisomerase II, human topoisomerase IIα and human topoisomerase IIβ using several sensitive single-molecule detection methods. Unexpectedly, we found that etoposide induces topoisomerase to trap DNA loops, compacting DNA and restructuring DNA topology. Loop trapping occurs after ATP hydrolysis but before strand ejection from the enzyme. Although etoposide decreases the innate stability of topoisomerase dimers, it increases the ability of the enzyme to act as a stable roadblock. Interestingly, the three topoisomerases show similar etoposide-mediated resistance to dimer separation and sliding along DNA but different abilities to compact DNA and chirally relax DNA supercoils. These data provide unique mechanistic insights into the functional consequences of etoposide on topoisomerase II dynamics.
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- 2023
11. How to deal with micronutrient product shortage - Editorial
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Francisca Joly, Manpreet Mundi, Rocco Barazzoni, Mette M. Berger, Frederico Bozzetti, Cristina Cuerda, Palle B. Jeppesen, Simon Lal, Georg Lamprecht, Kinga Szczepanek, André Van Gossum, Stéphane Schneider, Alan Shenkin, Geert Wanten, and Loris Pironi
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Nutrition and Dietetics ,All institutes and research themes of the Radboud University Medical Center ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Critical Care and Intensive Care Medicine - Abstract
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- 2023
12. Pitfalls in the interpretation of blood tests used to assess and monitor micronutrient nutrition status
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Mette M. Berger, Dinesh Talwar, and Alan Shenkin
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Nutrition and Dietetics ,Medicine (miscellaneous) - Abstract
Assessment of micronutrient (MN) status is of particular importance in patients who require medical nutrition therapy, especially those requiring parenteral nutrition. Blood testing is generally the only tool available in clinical settings to assess MN status. However, using plasma or serum concentration faces pitfalls mainly because of the impact of inflammation that diverts the MNs from the circulating compartment. This review aims to review the blood tests that are useful and provide information about how to integrate functional markers of status to reach a clinically relevant diagnosis. Most impacted, with a significant and proportional decrease in plasma concentrations, are iron, selenium, zinc, thiamin, folic acid, cobalamin, and vitamins A, C, and D; copper is the only MN for which the plasma concentration increases. Therefore, a surrogate marker of inflammation, C-reactive protein, must always be determined simultaneously. Validated intracellular and functional tests are proposed to improve status assessment. A protocol is suggested for tests required both on commencing and during nutrition support. A timely turnaround of analysis is essential for results to be clinically useful. In some cases, the appropriate provision of MNs should be commenced before results have been obtained to confirm the clinical assessment. Laboratory tests of MN status are an area prone to misuse and misinterpretation. The appropriate use and interpretation of such tests are essential to ensure the correct management of nutrition problems.
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- 2022
13. Social determinants of health in pediatric scald burns: Is food access an issue?
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Philip Kyung Woo Hong, Juan Pablo Santana, Shawn D. Larson, Amy M. Berger, Lauren A. Indelicato, Janice A. Taylor, Moiz M. Mustafa, Saleem Islam, Dan Neal, and Robin T. Petroze
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Male ,Social Determinants of Health ,Humans ,Infant ,Female ,Surgery ,Burns ,Child ,Poverty ,Retrospective Studies - Abstract
Burn injury risk, severity, and outcomes have been associated with socioeconomic status. Limited data exist to evaluate health access-related influences at a structural population level. This study evaluated factors at the Census-tract level, specifically evaluating food access and social vulnerability in pediatric scald burns.A single-institution retrospective review using the trauma registry and electronic medical record was conducted of pediatric burns between 2016 and 2020. Home address was coded to the Census-tract level and bulk analyzed. Socioeconomic metrics of the home environment were evaluated from publicly available databases, the United States Food and Drug Administration Food Access Research Atlas, and the Centers for Disease Control's Social Vulnerability Index.There were 840 patients that met inclusion criteria (49.8% scald, N = 418). The mean total body surface area for scalds was 6.6% with an age of 10.2 years; 76% (n = 317) of scalds had Medicaid, and 15% (n = 63) were due to hot noodles. Scalds occurred more in females (45.7%, N = 191 vs 28.0%, N = 118; Plt; .0001), non-White race (62.7%, N = 262 vs 29.1%, N = 123; Plt; .0001), and low-income and low-food access populations (39.8%, N = 147 vs 30.4%, N = 116; P = .007). Low-food access Black populations showed increased scald injury (18% [interquartile range 6-35] vs 10% [interquartile range 4-25]), whereas all other populations showed no association. The patients with scalds had a higher overall social vulnerability index (0.67 vs 0.62, P = .008).Often related to poverty, health access, and health equity, population-level social determinants of health like social vulnerability and food access have significant impact on health care and should influence health outreach and systems improvement.
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- 2022
14. Retrospective study on the pharyngeal airspace in the lateral cephalogram - A mathematical model to predict changes due to bimaxillary orthognathic surgery
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F.B. Warwas, N. Heim, M. Berger, F.-J. Kramer, and V. Wiedemeyer
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Otorhinolaryngology ,Surgery ,Oral Surgery - Abstract
The aim of this study was the development of a statistical model for reliable prediction of Posterior Airway Space (PAS) changes in lateral cephalograms (LCR) of patients after bimaxillary orthognathic surgery. The LCRs of patients who underwent bimaxillary orthognathic surgery were retrospectively analyzed. The anteroposterior dimension of the PAS was measured at three levels in the pre-operative and postoperative LCR: On the nasopharyngeal (SPAS), oropharyngeal (MAS), and hypopharyngeal level (IAS). The data of 139 patients were collected. The following changes of the PAS were measured: in class II patients SPAS: 0.291 mm (SD = 2.570 mm); MAS: 2.444 mm (SD = 2.986 mm); IAS: 0.750 mm (SD = 3.017 mm); in class III patients SPAS: 1.377 mm (SD 3.212 mm); MAS: 0.962 (SD: = 3.135 mm); IAS: 0.370 mm (SD = 3.468 mm). Linear regression analysis showed for class II patients, a significant influence of mandibular movement on MAS (p = 0.049) and a significant effect of maxillary and mandibular movements on SPAS (p = 0.001) and MAS (p = 0.022) in class III patients. The other jaw displacements had no significant impact on the investigated PAS levels. While the presented method does not permit exact prediction of the dimension of the PAS, it is still an easily accessible method of orientation for the surgeon. The surgeon can initiate three-dimensional examinations to provide exact three-dimensional prediction based on this calculation.
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- 2022
15. Teaching self-regulation
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Daniel Schunk, Eva M. Berger, Henning Hermes, Kirsten Winkel, and Ernst Fehr
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Behavioral Neuroscience ,Social Psychology ,Experimental and Cognitive Psychology - Published
- 2022
16. Computer customization errors compromised the optimization of trace element repletion dose after major burns
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Céline Jina Dusapin, Olivier Pantet, Pierre Voirol, Mélanie Charrière, Pauline Thomann, and Mette M. Berger
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Selenium ,Zinc ,Nutrition and Dietetics ,Computers ,Humans ,Salts ,Burns ,Critical Care and Intensive Care Medicine ,Copper ,Retrospective Studies ,Trace Elements - Abstract
Major burns develop acute trace element (TE) deficiencies due to exudative losses of copper, selenium, and zinc from the wounds. A repletion strategy has been shown to decrease infectious and surgical complications. The TE doses have been adapted over time and the last adaptation, was not followed by the expected changes. The study aims at identifying the causes of the failure.Retrospective cohort study including critically ill major burns patients admitted to intensive care with burns exceeding 20% of body surface area (BSA). Period A (2011-2015) included patients admitted before the dose change, and Period B patients after (2017-2020). Demographic variables, daily TE delivery, and weekly TE blood levels were extracted from the computerized information system (CIS).Altogether 71 patients completed the inclusion criteria (Periods A and B: 42 and 29 patients respectively). They were aged 38 (32) years and burned 35 (30) % BSA, with no severity differences. Comparing periods A and B, copper (p = 0.046) and selenium (p = 0.031) blood levels were significantly lower in B. The dose value extracted from CIS was as planned. Customization error was found: TE salts' weight had been entered instead of elemental weight in molar units.The lower TE repletion doses administered since 2017 resulted in a significant decrease in blood levels of Cu and Se. A CIS customisation error, confusing salt weight and elemental weight was the source of the error. A systematic quality control is crucial to identify systemic errors, as is the use of the standard international units.
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- 2022
17. Oceans of plenty? Challenges, advancements, and future directions for the provision of evidence-based fisheries management advice
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Daniel R. Goethel, Kristen L. Omori, André E. Punt, Patrick D. Lynch, Aaron M. Berger, Carryn L. de Moor, Éva E. Plagányi, Jason M. Cope, Natalie A. Dowling, Richard McGarvey, Ann L. Preece, James T. Thorson, Milani Chaloupka, Sarah Gaichas, Eric Gilman, Sybrand A. Hesp, Catherine Longo, Nan Yao, and Richard D. Methot
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Aquatic Science - Abstract
Marine population modeling, which underpins the scientific advice to support fisheries interventions, is an active research field with recent advancements to address modern challenges (e.g., climate change) and enduring issues (e.g., data limitations). Based on discussions during the 'Land of Plenty' session at the 2021 World Fisheries Congress, we synthesize current challenges, recent advances, and interdisciplinary developments in biological fisheries models (i.e., data-limited, stock assessment, spatial, ecosystem, and climate), management strategy evaluation, and the scientific advice that bridges the science-policy interface. Our review demonstrates that proliferation of interdisciplinary research teams and enhanced data collection protocols have enabled increased integration of spatiotemporal, ecosystem, and socioeconomic dimensions in many fisheries models. However, not all management systems have the resources to implement model-based advice, while protocols for sharing confidential data are lacking and impeding research advances. We recommend that management and modeling frameworks continue to adopt participatory co-management approaches that emphasize wider inclusion of local knowledge and stakeholder input to fill knowledge gaps and promote information sharing. Moreover, fisheries management, by which we mean the end-to-end process of data collection, scientific analysis, and implementation of evidence-informed management actions, must integrate improved communication, engagement, and capacity building, while incorporating feedback loops at each stage. Increasing application of management strategy evaluation is viewed as a critical unifying component, which will bridge fisheries modeling disciplines, aid management decision-making, and better incorporate the array of stakeholders, thereby leading to a more proactive, pragmatic, transparent, and inclusive management framework-ensuring better informed decisions in an uncertain world.The online version contains supplementary material available at 10.1007/s11160-022-09726-7.
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- 2022
18. Challenges of variant reinterpretation: Opinions of stakeholders and need for guidelines
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Sara M. Berger, Paul S. Appelbaum, Karolynn Siegel, Julia Wynn, Akilan M. Saami, Elly Brokamp, Bridget C. O’Connor, Rizwan Hamid, Donna M. Martin, and Wendy K. Chung
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Counselors ,Surveys and Questionnaires ,Humans ,Genetic Testing ,Focus Groups ,Laboratories ,Genetics (clinical) - Abstract
The knowledge used to classify genetic variants is continually evolving, and the classification can change on the basis of newly available data. Although up-to-date variant classification is essential for clinical management, reproductive planning, and identifying at-risk family members, there is no consistent practice across laboratories or clinicians on how or under what circumstances to perform variant reinterpretation.We conducted exploratory focus groups (N = 142) and surveys (N = 1753) with stakeholders involved in the process of variant reinterpretation (laboratory directors, clinical geneticists, genetic counselors, nongenetic providers, and patients/parents) to assess opinions on key issues, including initiation of reinterpretation, variants to report, termination of the responsibility to reinterpret, and concerns about consent, cost, and liability.Stakeholders widely agreed that there should be no fixed termination point to the responsibility to reinterpret a previously reported genetic variant. There were significant concerns about liability and lack of agreement about many logistical aspects of variant reinterpretation.Our findings suggest a need to (1) develop consensus and (2) create transparency and awareness about the roles and responsibilities of parties involved in variant reinterpretation. These data provide a foundation for developing guidelines on variant reinterpretation that can aid in the development of a low-cost, scalable, and accessible approach.
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- 2022
19. Rare pathogenic variants in WNK3 cause X-linked intellectual disability
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Sébastien Küry, Jinwei Zhang, Thomas Besnard, Alfonso Caro-Llopis, Xue Zeng, Stephanie M. Robert, Sunday S. Josiah, Emre Kiziltug, Anne-Sophie Denommé-Pichon, Benjamin Cogné, Adam J. Kundishora, Le T. Hao, Hong Li, Roger E. Stevenson, Raymond J. Louie, Wallid Deb, Erin Torti, Virginie Vignard, Kirsty McWalter, F. Lucy Raymond, Farrah Rajabi, Emmanuelle Ranza, Detelina Grozeva, Stephanie A. Coury, Xavier Blanc, Elise Brischoux-Boucher, Boris Keren, Katrin Õunap, Karit Reinson, Pilvi Ilves, Ingrid M. Wentzensen, Eileen E. Barr, Solveig Heide Guihard, Perrine Charles, Eleanor G. Seaby, Kristin G. Monaghan, Marlène Rio, Yolande van Bever, Marjon van Slegtenhorst, Wendy K. Chung, Ashley Wilson, Delphine Quinquis, Flora Bréhéret, Kyle Retterer, Pierre Lindenbaum, Emmanuel Scalais, Lindsay Rhodes, Katrien Stouffs, Elaine M. Pereira, Sara M. Berger, Sarah S. Milla, Ankita B. Jaykumar, Melanie H. Cobb, Shreyas Panchagnula, Phan Q. Duy, Marie Vincent, Sandra Mercier, Brigitte Gilbert-Dussardier, Xavier Le Guillou, Séverine Audebert-Bellanger, Sylvie Odent, Sébastien Schmitt, Pierre Boisseau, Dominique Bonneau, Annick Toutain, Estelle Colin, Laurent Pasquier, Richard Redon, Arjan Bouman, Jill. A. Rosenfeld, Michael J. Friez, Helena Pérez-Peña, Syed Raza Akhtar Rizvi, Shozeb Haider, Stylianos E. Antonarakis, Charles E. Schwartz, Francisco Martínez, Stéphane Bézieau, Kristopher T. Kahle, Bertrand Isidor, Clinical Genetics, Clinical sciences, Medical Genetics, Reproduction and Genetics, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Exeter, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Greenwood Genetic Center, GeneDx [Gaithersburg, MD, USA], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE), Yale School of Medicine [New Haven, Connecticut] (YSM), This work was granted by the French network of University Hospitals HUGO ('Hôpitaux Universitaires du Grand Ouest'), the French Ministry of Health, and and the Health Regional Agencies from Poitou-Charentes (represented by Frédérique Allaire), Bretagne, Pays de la Loire, and Centre-Val de Loire (HUGODIMS, 2013, RC14_0107). W.K.C. was supported by grants from Simons Foundation Autism Research Initiative, United
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MESH: Symporters ,Exome sequencing ,Male ,KCC2 ,Mutation, Missense ,MESH: Catalytic Domain ,Neurodevelopmental disease ,Protein Serine-Threonine Kinases ,X-linked intellectual disability ,MESH: Brain ,WNK3 ,SDG 3 - Good Health and Well-being ,Loss of Function Mutation ,Catalytic Domain ,MESH: Mental Retardation, X-Linked ,Humans ,Phosphorylation ,MESH: Hemizygote ,Genetics (clinical) ,Hemizygote ,MESH: Mutation, Missense ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Phosphorylation ,Symporters ,Brain ,MESH: Loss of Function Mutation ,MESH: Protein Serine-Threonine Kinases ,MESH: Male ,Mental Retardation, X-Linked ,Maternal Inheritance ,MESH: Maternal Inheritance - Abstract
PURPOSE: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. METHOD: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). RESULTS: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had identifier with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. CONCLUSION: Pathogenic WNK3 variants cause a rare form of human X-linked identifier with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.
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- 2022
20. Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis
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Yu Imai, Glenn Hauk, Jeffrey Quigley, Libang Liang, Sangkeun Son, Meghan Ghiglieri, Michael F. Gates, Madeleine Morrissette, Negar Shahsavari, Samantha Niles, Donna Baldisseri, Chandrashekhar Honrao, Xiaoyu Ma, Jason J. Guo, James M. Berger, and Kim Lewis
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DNA Gyrase ,Antitubercular Agents ,Humans ,Topoisomerase II Inhibitors ,Tuberculosis ,Mycobacterium tuberculosis ,Thiophenes ,Cell Biology ,Molecular Biology ,Article ,Poisons ,Anti-Bacterial Agents - Abstract
The antimicrobial resistance crisis requires the introduction of novel antibiotics. The use of conventional broad-spectrum compounds selects for resistance in off-target pathogens and harms the microbiome. This is especially true for Mycobacterium tuberculosis, where treatment requires a 6-month course of antibiotics. Here we show that a novel antimicrobial from Photorhabdus noenieputensis, which we named evybactin, is a potent and selective antibiotic acting against M. tuberculosis. Evybactin targets DNA gyrase and binds to a site overlapping with synthetic thiophene poisons. Given the conserved nature of DNA gyrase, the observed selectivity against M. tuberculosis is puzzling. We found that evybactin is smuggled into the cell by a promiscuous transporter of hydrophilic compounds, BacA. Evybactin is the first, but likely not the only, antimicrobial compound found to employ this unusual mechanism of selectivity.
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- 2022
21. Influence of meat batter addition in ground beef on structural properties and quality parameters
- Author
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Lisa M. Berger, Monika Gibis, Franziska Witte, Nino Terjung, and Jochen Weiss
- Subjects
General Chemistry ,Biochemistry ,Industrial and Manufacturing Engineering ,Food Science ,Biotechnology - Abstract
The determination of the amount of non-intact cells (ANIC) in ground beef products is usually performed using a time-consuming and subjective histometric approach neglecting structural properties, which is why more objective and faster methods including evaluation of quality parameters are needed. To determine, whether the addition of meat batter increases the histologically determined ANIC ground beef samples containing increasing shares of meat batter (non-intact cells) were investigated histologically and results were compared to other methodological approaches, namely lactate dehydrogenase activity (LDH), soluble protein content, metmyoglobin content, drip loss, firmness, and cooking loss. Histological measurements showed that ANIC increased linearly with the addition of meat batter to ground beef. The quality parameters drip loss (r = − 0.834, p r = − 0.499, p r = 0.924, p
- Published
- 2022
22. The Challenge of Genetic Variants of Uncertain Clinical Significance
- Author
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Wylie Burke, Erik Parens, Wendy K. Chung, Sara M. Berger, and Paul S. Appelbaum
- Subjects
Uncertainty ,Internal Medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,General Medicine ,Probability - Abstract
Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUSs). Only a minority of VUSs are likely to prove pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision making and can result in harms and costs to patients and the health care system, including the time-consuming analysis required to interpret a VUS and the potential for unnecessary treatment and adverse psychological effects. Current efforts to improve variant interpretation will help reduce the scope of the problem, but the high prevalence of rare and novel variants in the human genome points to VUSs as an ongoing challenge. Additional strategies can help mitigate the potential harms of VUSs, including testing protocols that limit identification or reporting of VUSs, subclassification of VUSs according to the likelihood of pathogenicity, routine family-based evaluation of variants, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance of measures is likely to vary for different test uses and clinical settings. Cross-specialty deliberation and public input could contribute to systematic and broadly supported policies for managing VUSs.
- Published
- 2022
23. Causes and clinical consequences of inappropriate shocks experienced by patients wearing a cardioverter-defibrillator
- Author
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Justin M. Berger, Jay D. Sengupta, Alan J. Bank, Susan A. Casey, Dawn Witt, Scott W. Sharkey, Larissa I. Stanberry, and Robert G. Hauser
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Published
- 2023
24. Nutrition during the acute phase of critical illness: discussions on NUTRIREA-3
- Author
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Zheng-Yii Lee, Charles Chin Han Lew, Mette M Berger, Aileen Hill, and Christian Stoppe
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2023
25. Authors of Their Own Lives
- Author
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Reinhard Bendix, Bennett M. Berger, Jessie Bernard, James S. Coleman, Donald R. Cressey, Cynthia Fuchs Epstein, John Gagnon, Herbert J. Gans, Nathan Glazer, Andrew M. Greeley, Joseph Gusfield, Dean MacCannell, Gary T. Marx, David Riesman, Barbara Rosenblum, Alice S. Rossi, Guenther Roth, Pepper Schwartz, Pierre L. van den Berghe, and Dennis Wrong
- Published
- 2023
26. Preface
- Author
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Bennett M. Berger
- Published
- 2023
27. Looking for the Interstices
- Author
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Bennett M. Berger
- Published
- 2023
28. Stage‐specific drivers of Pacific hake ( <scp> Merluccius productus </scp> ) recruitment in the California Current Ecosystem
- Author
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Cathleen D. Vestfals, Kristin N. Marshall, Nick Tolimieri, Mary E. Hunsicker, Aaron M. Berger, Ian G. Taylor, Michael G. Jacox, and Brendan D. Turley
- Subjects
Aquatic Science ,Oceanography - Published
- 2023
29. IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings
- Author
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Mercedes Spínola-Amilibia, Lidia Araújo-Bazán, Álvaro de la Gándara, James M. Berger, Ernesto Arias-Palomo, Ministerio de Ciencia e Innovación (España), Spínola-Amilibia, Mercedes, Araújo-Bazán, Lidia, Gándara, Álvaro de la, Berger, James M., and Arias-Palomo, Ernesto
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
14 p.-8 fig., Transposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transposase present in the widespread IS21 family of mobile elements, catalyzes efficient DNA transposition. Solution studies show that IstA engages the transposon terminal sequences to form a high-molecular weight complex and promote DNA integration. A 3.4 Å resolution structure of the transposase bound to transposon ends corroborates our biochemical findings and reveals that IstA self-assembles into a highly intertwined tetramer that synapses two supercoiled terminal inverted repeats. The three-dimensional organization of the IstA•DNA cleaved donor complex reveals remarkable similarities with retroviral integrases and classic transposase systems, such as Tn7 and bacteriophage Mu, and provides insights into IS21 transposition., This work was supported by grant GM071747 (to J.M.B.), grants PID2020-120275GB-I00 and BFU2017-89143-P funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” (to E.A.-P.), and grant PRE2018-086026 funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future” (to E.A.-P. and A.G.).
- Published
- 2023
30. Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case-control study
- Author
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Antoine Equey, Mette M. Berger, Semira Gonseth-Nusslé, Marc Augsburger, Serge Rezzi, Andrew C.C. Hodgson, Sandrine Estoppey, Giuseppe Pantaleo, Céline Pellaton, Maïwenn Perrais, Sébastien Lenglet, Valentin Rousson, Valérie D'Acremont, and Murielle Bochud
- Subjects
Nutrition and Dietetics ,Copper ,Deficiency ,Immunity ,Micronutrients ,Public health ,Vitamin D ,Critical Care and Intensive Care Medicine - Abstract
Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D 3 (25(OH)D 3 ) with LC-MS/MS and explored associations using multiple logistic regression. The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m 2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log 2 (Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D 3 with anti-SARS-CoV-2 IgG or IgA seropositivity. Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. CORONA IMMUNITAS:: ISRCTN18181860.
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- 2023
31. Data from Three-Year Interval for the Multi-Target Stool DNA Test for Colorectal Cancer Screening: A Longitudinal Study
- Author
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Barry M. Berger, Anas Daghestani, Seth Sweetser, Paul J. Limburg, Folasade P. May, Steven H. Itzkowitz, Debbie Jakubowski, Tara N. Marti, Philip T. Lavin, and Thomas F. Imperiale
- Abstract
Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention Relevance:Understanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.
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- 2023
32. Supplementary Tables S1-S2 from Three-Year Interval for the Multi-Target Stool DNA Test for Colorectal Cancer Screening: A Longitudinal Study
- Author
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Barry M. Berger, Anas Daghestani, Seth Sweetser, Paul J. Limburg, Folasade P. May, Steven H. Itzkowitz, Debbie Jakubowski, Tara N. Marti, Philip T. Lavin, and Thomas F. Imperiale
- Abstract
Supplemental Table S1: Distribution of colorectal lesions among subjects at baseline (T0) and year 3 (T3). Supplemental Table S2: Study subject accountability in the baseline negative population
- Published
- 2023
33. Supplementary Text from Three-Year Interval for the Multi-Target Stool DNA Test for Colorectal Cancer Screening: A Longitudinal Study
- Author
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Barry M. Berger, Anas Daghestani, Seth Sweetser, Paul J. Limburg, Folasade P. May, Steven H. Itzkowitz, Debbie Jakubowski, Tara N. Marti, Philip T. Lavin, and Thomas F. Imperiale
- Abstract
This Supplemental Text file provides additional information regarding the clinical procedures and sample processing/lab procedures, as well as an explanation of the sensitivity and robustness analyses.
- Published
- 2023
34. Data from Specificity of the Multi-Target Stool DNA Test for Colorectal Cancer Screening in Average-Risk 45–49 Year-Olds: A Cross-Sectional Study
- Author
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Paul J. Limburg, Barry M. Berger, Sandra Statz, Emma Kate Duimstra, Bradley Scheu, Steven H. Itzkowitz, John B. Kisiel, and Thomas F. Imperiale
- Abstract
High-specificity colorectal cancer screening is desirable to triage patients P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9–47.5%), with most APL (83.7%) measuring 10–19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64–0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening.Prevention Relevance:This study shows that mt-sDNA has high specificity among average-risk 45–49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.
- Published
- 2023
35. Supplementary Tables from Specificity of the Multi-Target Stool DNA Test for Colorectal Cancer Screening in Average-Risk 45–49 Year-Olds: A Cross-Sectional Study
- Author
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Paul J. Limburg, Barry M. Berger, Sandra Statz, Emma Kate Duimstra, Bradley Scheu, Steven H. Itzkowitz, John B. Kisiel, and Thomas F. Imperiale
- Abstract
Supplementary Tables
- Published
- 2023
36. Micronutrients: A low blood concentration is not equivalent to deficiency
- Author
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Alan Shenkin and Mette M. Berger
- Subjects
Selenium ,Nutrition and Dietetics ,Humans ,Micronutrients ,Critical Care and Intensive Care Medicine ,Trace Elements - Published
- 2022
37. Neural Flow Map Reconstruction
- Author
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S. Sahoo, Y. Lu, and M. Berger
- Subjects
Computer Graphics and Computer-Aided Design - Published
- 2022
38. Research priorities to reduce risks from work hours and fatigue in the healthcare and social assistance sector
- Author
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Claire C. Caruso, Megan W. Arbour, Ann M. Berger, Beverly M. Hittle, Sharon Tucker, Patricia A. Patrician, Alison M. Trinkoff, Ann E. Rogers, Laura K. Barger, J. Cole Edmonson, Christopher P. Landrigan, Nancy S. Redeker, and Eileen R. Chasens
- Subjects
Sleep Disorders, Circadian Rhythm ,Research ,Work Schedule Tolerance ,Public Health, Environmental and Occupational Health ,Humans ,Sleep ,Delivery of Health Care ,Fatigue ,Article - Abstract
BACKGROUND: The services of Healthcare and Social Assistance (HCSA) workers are needed by society around the clock. As a result, these workers are exposed to shift work and long work hours. The combination of demanding work schedules and other hazards in the HCSA work environment increases the health and safety risks to these workers, as well as to their patients/clients and the public. METHODS: This paper has three aims: (1) provide an overview of the burden of shift work, long hours, and related sleep and fatigue problems in this sector; (2) suggest research priorities that would improve these ; and (3) discuss potential positive impacts of addressing these research priorities for the health and safety of workers and the public. The authors used a modified Delphi approach to anonymously rank-order priorities for improving HCSA worker health and safety and public safety. Input was also obtained from attendees at the 2019 National Institute for Occupational Safety and Health (NIOSH) Work Hours, Sleep, and Fatigue Forum. RESULTS: The highest rated research priorities were developing better designs for work schedules, and improving the HCSA culture and leadership approaches to shift work and long work hours. Additional priorities are identified. CONCLUSION: Research in these priority areas has the potential to benefit HCSA workers as well as their patients/clients, employers, and society.
- Published
- 2022
39. Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma
- Author
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Barry M. Berger, Glenn J. Hanna, Marshall R. Posner, Eric M. Genden, Julio Lautersztain, Stephen P. Naber, Catherine Del Vecchio Fitz, and Charlotte Kuperwasser
- Subjects
Oropharyngeal Neoplasms ,Cancer Research ,Oncology ,Head and Neck Neoplasms ,Squamous Cell Carcinoma of Head and Neck ,DNA, Viral ,Papillomavirus Infections ,Humans ,Alphapapillomavirus ,Papillomaviridae ,Biomarkers ,Retrospective Studies - Abstract
Purpose: Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging and are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine posttreatment surveillance among a large population of real-world patients. Experimental Design: This retrospective clinical case series included 1,076 consecutive patients across 108 U.S. sites who were ≥ 3 months posttreatment for HPV-driven OPSCC and who had one or more TTMV-HPV DNA tests (NavDx, Naveris Laboratories) obtained during surveillance between February 6, 2020, and June 29, 2021. Test results were compared with subsequent clinical evaluations. Results: Circulating TTMV-HPV DNA was positive in 80 of 1,076 (7.4%) patients, with follow-up available on all. At first positive surveillance testing, 21 of 80 (26%) patients had known recurrence while 59 of 80 (74%) patients were not known to have recurrent disease. Among these 59 patients, 55 (93%) subsequently had a confirmed recurrence, 2 patients had clinically suspicious lesions, and 2 had clinically “no evidence of disease” (NED) at last follow-up. To date, the overall positive predictive value of TTMV-HPV DNA testing for recurrent disease is 95% (N = 76/80). In addition, the point-in-time negative predictive value is 95% (N = 1,198/1,256). Conclusions: These findings highlight the clinical potential for circulating TTMV-HPV DNA testing in routine practice. As a surveillance tool, TTMV-HPV DNA positivity was the first indication of recurrence in the majority of cases, pre-dating identification by routine clinical and imaging exams. These data may inform future clinical and guideline-endorsed strategies for HPV-driven malignancy surveillance. See related commentary by Colevas, p. 4171
- Published
- 2022
40. Warum Urbanisierung Allergien begünstigt – eine Umweltbetrachtung
- Author
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M. Berger, M. Bastl, L. Dirr, and U.E. Berger
- Subjects
Immunology and Allergy - Published
- 2022
41. Supplementary Figure 1 from Dendritic Cell–Activating Vaccine Adjuvants Differ in the Ability to Elicit Antitumor Immunity Due to an Adjuvant-Specific Induction of Immunosuppressive Cells
- Author
-
Mary L. Disis, Gregory E. Holt, Carmen M. Berger, Lauren Rastetter, Ekram Gad, Wolfgang M. Wagner, and Yushe Dang
- Abstract
PDF file, 86KB, The administration of anti-Gr-1 and anti-CD25 mAb can deplete MDSC and Treg cells respectively.
- Published
- 2023
42. Data from Dendritic Cell–Activating Vaccine Adjuvants Differ in the Ability to Elicit Antitumor Immunity Due to an Adjuvant-Specific Induction of Immunosuppressive Cells
- Author
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Mary L. Disis, Gregory E. Holt, Carmen M. Berger, Lauren Rastetter, Ekram Gad, Wolfgang M. Wagner, and Yushe Dang
- Abstract
Purpose: We questioned whether the vaccine adjuvant combination of TLR-7 ligand agonist, imiquimod, with granulocyte macrophage colony-stimulating factor (GM-CSF) would result in enhanced dendritic cell recruitment and activation with increased antigen-specific immunity as compared with either adjuvant used alone.Experimental Design: The adjuvant effects of GM-CSF and imiquimod were studied in ovalbumin (OVA) and MMTVneu transgenic mice using peptide-based vaccines. Type I immunity, serum cytokines, myeloid-derived suppressive cells (MDSC), and regulatory T cells (Treg) levels were examined.Results: Both GM-CSF and imiquimod equally induced local accumulation and activation of dendritic cells. Both adjuvants effectively enhanced OVA-specific T-cell responses. We further evaluated the antitumor efficacy of adjuvant GM-CSF and imiquimod immunizing against murine insulin-like growth factor–binding protein-2 (IGFBP-2), a nonmutated oncoprotein overexpressed in the tumors of MMTVneu transgenic mice. Tumor growth was significantly inhibited in the mice receiving IGFBP-2 peptides with GM-CSF (P = 0.000), but not in imiquimod vaccine-treated groups (P = 0.141). Moreover, the addition of imiquimod to GM-CSF negated the antitumor activity of the vaccine when GM-CSF was used as the sole adjuvant. While GM-CSF stimulated significant levels of antigen-specific T-helper cell (TH)1, imiquimod induced elevated serum interleukin (IL)-10. Both MDSC and Tregs were increased in the imiquimod-treated but not GM-CSF–treated groups (P = 0.000 and 0.006, respectively). Depleting MDSC and Treg in animals immunized with imiquimod and IGFBP-2 peptides restored antitumor activity to the levels observed with vaccination using GM-CSF as the sole adjuvant.Conclusion: Adjuvants may induce regulatory responses in the context of a self-antigen vaccine. Adjuvant triggered immunosuppression may limit vaccine efficacy and should be evaluated in preclinical models especially when contemplating combination approaches. Clin Cancer Res; 18(11); 3122–31. ©2012 AACR.
- Published
- 2023
43. Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily
- Author
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Marcel Rak, Roberta Tesch, Lena M. Berger, Ekaterina Shevchenko, Monika Raab, Amelie Tjaden, Rezart Zhubi, Dimitrios-Ilias Balourdas, Andreas C. Joerger, Antti Poso, Andreas Krämer, Lewis Elson, Aleksandar Lučić, Thales Kronenberger, Thomas Hanke, Klaus Strebhardt, Mourad Sanhaji, and Stefan Knapp
- Subjects
Pharmacology ,Organic Chemistry ,Drug Discovery ,General Medicine - Abstract
Salt-inducible kinases 1-3 (SIK1-3) are key regulators of the LKB1-AMPK pathway and play an important role in cellular homeostasis. Dysregulation of any of the three isoforms has been associated with tumorigenesis in liver, breast, and ovarian cancers. We have recently developed the dual pan-SIK/group I p21-activated kinase (PAK) chemical probe MRIA9. However, inhibition of p21-activated kinases has been associated with cardiotoxicityin vivo, which complicates the use of MRIA9 as a tool compound. Here, we present a structure-based approach involving the back-pocket and gatekeeper residues, for narrowing the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one-based inhibitors towards SIK kinases, eliminating PAK activity. Optimization was guided by high-resolution crystal structure analysis and computational methods, resulting in a pan-SIK inhibitor, MR22, which no longer exhibited activity on STE group kinases and displayed excellent selectivity in a representative kinase panel. MR22-dependent SIK inhibition led to centrosome dissociation and subsequent cell-cycle arrest in ovarian cancer cells, as observed with MRIA9, conclusively linking these phenotypic effects to SIK inhibition. Taken together, MR22 represents a valuable tool compound for studying SIK kinase function in cells.
- Published
- 2023
44. Entwicklung eines Fragebogens zur Therapieadhärenz und -komfort bei nicht-invasiver Heimbeatmung: Ein einfaches Instrument für die Erfassung patientenrelevanter Parameter
- Author
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D Kroppen, M Wollsching-Strobel, D Majorski, F Magnet, M Berger, W Windisch, and S Schwarz
- Published
- 2023
45. Erfassung von und Einflussfaktoren auf die Therapieadhärenz bei Patient:innen mit schwerer COPD
- Author
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M Wollsching-Strobel, A Werner, D Kroppen, D Majorski, F Magnet, M Berger, T Mathes, S Schwarz, and W Windisch
- Published
- 2023
46. Phenomenological Approaches in the History of Ethnomusicology
- Author
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Harris M. Berger, David VanderHamm, and Friedlind Riedel
- Abstract
Beginning in the late 1970s, ethnomusicologists began to engage with ideas from phenomenology (a movement within Continental European philosophy). This article discusses key concepts from phenomenology and explores how ethnomusicologists developed them to address fundamental issues in the study of music and culture—the problem of musical meaning and musical interpretation, the nature of the performance event, and questions of music and being. Tracing the intellectual history of phenomenological ethnomusicology, the article synthesizes findings from research on a broad range of musical traditions and offers new insights into a variety of topics of interest to contemporary music scholars, including embodiment, self-reflexivity, flow and musical involvement, trance, time and temporality, research methods, and the politics of music. The article closes by discussing the explosion of phenomenological work in ethnomusicology that has occurred in recent years and suggests new directions for research.
- Published
- 2023
47. Vulnerability to climate change of managed stocks in the California Current large marine ecosystem
- Author
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Michelle M. McClure, Melissa A. Haltuch, Ellen Willis-Norton, David D. Huff, Elliott L. Hazen, Lisa G. Crozier, Michael G. Jacox, Mark W. Nelson, Kelly S. Andrews, Lewis A.K. Barnett, Aaron M. Berger, Sabrina Beyer, Joe Bizzarro, David Boughton, Jason M. Cope, Mark Carr, Heidi Dewar, Edward Dick, Emmanis Dorval, Jason Dunham, Vladlena Gertseva, Correigh M. Greene, Richard G. Gustafson, Owen S. Hamel, Chris J. Harvey, Mark J. Henderson, Chris E. Jordan, Isaac C. Kaplan, Steven T. Lindley, Nathan J. Mantua, Sean E. Matson, Melissa H. Monk, Peter Moyle, Colin Nicol, John Pohl, Ryan R. Rykaczewski, Jameal F. Samhouri, Susan Sogard, Nick Tolimieri, John Wallace, Chantel Wetzel, and Steven J. Bograd
- Subjects
Global and Planetary Change ,Ocean Engineering ,Aquatic Science ,Oceanography ,Water Science and Technology - Abstract
IntroductionUnderstanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes.MethodsThis study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions.ResultsOverall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges.DiscussionAs climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore.
- Published
- 2023
48. Comment: Early nutrition prescription in critically ill patients—learnings from the FRANS study
- Author
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Mette M. Berger and Pierre Singer
- Subjects
Critical Care and Intensive Care Medicine - Published
- 2023
49. Post-Shock Asystole in Patients Dying Out of Hospital While Wearing a Cardioverter Defibrillator
- Author
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Justin M. Berger, Jay D. Sengupta, Alan J. Bank, Susan A. Casey, Scott W. Sharkey, Larissa I. Stanberry, and Robert G. Hauser
- Published
- 2023
50. Dimensional Reduction for Single Molecule Imaging of DNA and Nucleosome Condensation by Polyamines, HP1α and Ki-67
- Author
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Nils A. Benning, Jacob Kæstel-Hansen, Fahad Rashid, Sangwoo Park, Raquel Merino Urteaga, Ting-Wei Liao, Jingzhou Hao, James M. Berger, Nikos S. Hatzakis, and Taekjip Ha
- Abstract
Macromolecules organize themselves into discrete membrane-less compartments. Mounting evidence has suggested that nucleosomes as well as DNA itself can undergo clustering or condensation to regulate genomic activity. Current in vitro condensation studies provide insight into the physical properties of condensates, such as surface tension and diffusion. However, such studies lack the resolution needed for complex kinetic studies of multicomponent condensation. Here, we use a supported lipid bilayer platform in tandem with total internal reflection microscopy to observe the 2-dimensional movement of DNA and nucleosomes at the single-molecule resolution. This dimensional reduction from 3-dimensional studies allows us to observe the initial condensation events and dissolution of these early condensates in the presence of physiological condensing agents. Using polyamines, we observed that the initial condensation happens on a timescale of minutes while dissolution occurs within seconds upon charge inversion. Polyamine valency, DNA length and GC content affect threshold polyamine concentration for condensation. Protein-based nucleosome condensing agents, HP1α and Ki-67, have much lower threshold concentration for condensation than charge-based condensing agents, with Ki-67 being the most effective as low as 100 pM for nucleosome condensation. In addition, we did not observe condensate dissolution even at the highest concentrations of HP1α and Ki-67 tested. We also introduce a two-color imaging scheme where nucleosomes of high density labeled in one color is used to demarcate condensate boundaries and identical nucleosomes of another color at low density can be tracked relative to the boundaries after Ki-67 mediated condensation. Our platform should enable the ultimate resolution of single molecules in condensation dynamics studies of chromatin components under defined physicochemical conditions.Abstract Figure
- Published
- 2023
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