545 results on '"Hoth, P."'
Search Results
2. Die WHO-Klassifikation von Hörverlusten: Ein Konsens zu einer deutschen Fassung
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Holube, I., Dziemba, O., Fedtke, T., Hoth, S., Michel, O., Neumann, K., Rahne, T., Veraguth, D., von Gablenz, P., Wesarg, T., and Baljić, I.
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- 2024
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3. Innerklinische Erstversorgung von Patienten mit penetrierendem Trauma nach Gewalt und Krieg
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Achatz, Gerhard, Franke, Axel, Friemert, Benedikt, Hoth, Patrick, Hube, Philipp, and Bieler, Dan
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- 2024
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4. Surgical and procedural antibiotic prophylaxis in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document.
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Farrell, Michael, Agapian, John, Appelbaum, Rachel, Filiberto, Dina, Gelbard, Rondi, Hoth, Jason, Jawa, Randeep, Kirsch, Jordan, Kutcher, Matthew, Nohra, Eden, Pathak, Abhijit, Paul, Jasmeet, Robinson, Bryce, Cuschieri, Joseph, and Stein, Deborah
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antibiotic prophylaxis ,infections - Abstract
The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy).
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- 2024
5. Availability and use of institutional support programs for emergency department healthcare personnel during the COVID-19 pandemic.
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Hoth, Karin, Ten Eyck, Patrick, Harland, Karisa, Krishnadasan, Anusha, Wendt, Linder, Mower, William, Wallace, Kelli, Santibañez, Scott, Talan, David, Mohr, Nicholas, Rodriguez, Robert, and Montoy, Juan Carlos
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Humans ,United States ,COVID-19 ,Pandemics ,COVID-19 Testing ,Cross-Sectional Studies ,Health Personnel ,Delivery of Health Care ,Emergency Service ,Hospital - Abstract
OBJECTIVES: The COVID-19 pandemic placed health care personnel (HCP) at risk for stress, anxiety, burnout, and post-traumatic stress disorder (PTSD). To address this, hospitals developed programs to mitigate risk. The objectives of the current study were to measure the availability and use of these programs in a cohort of academic emergency departments (EDs) in the United States early in the pandemic and identify factors associated with program use. METHODS: Cross-sectional survey of ED HCP in 21 academic EDs in 15 states between June and September 2020. Site investigators provided data on the availability of 28 programs grouped into 9 categories. Individual support programs included: financial, workload mitigation, individual COVID-19 testing, emotional (e.g., mental health hotline), and instrumental (e.g., childcare) Clinical work support programs included: COVID-19 team communication (e.g., debriefing critical incident), patient-family communication facilitation, patient services (e.g., social work, ethics consultation), and system-level exposure reduction. Participants provided corresponding data on whether they used the programs. We used generalized linear mixed models clustered on site to measure the association between demographic and facility characteristics and program use. RESULTS: We received 1,541 survey responses (96% response rate) from emergency physicians or advanced practice providers, nurses, and nonclinical staff. Program availability in each of the 9 categories was high (>95% of hospitals). Program use was variable, with clinical work support programs used more frequently (28-50% of eligible HCP across categories) than individual employee support programs (6-13% of eligible HCP across categories). Fifty-seven percent of respondents reported that the COVID-19 pandemic had affected their stress and anxiety, and 12% were at elevated risk for PTSD. Program use did not significantly differ for HCP who reported symptoms of anxiety and/or stress compared to those who did not. CONCLUSIONS: Early in the pandemic, support programs were widely available to ED HCP, but program use was low. Future work will focus on identifying barriers and facilitators to use and specific programs most likely to be effective during periods of highest occupational stress.
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- 2024
6. CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients
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Sylvia Zöphel, Nadja Küchler, Johanna Jansky, Cora Hoxha, Gertrud Schäfer, Julius J. Weise, Joanne Vialle, Lea Kaschek, Gebhard Stopper, Hermann Eichler, Daniela Yildiz, Alina Moter, Philipp Wendel, Evelyn Ullrich, Claudia Schormann, Torben Rixecker, Onur Cetin, Frank Neumann, Patrick Orth, Moritz Bewarder, Markus Hoth, Lorenz Thurner, and Eva C. Schwarz
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aggressive B-NHL (non-Hodgkin B cell lymphoma) ,diffuse large B cell lymphoma (DLBCL) ,CD16+ T cell ,CD16+ monocyte ,antibody-dependent cellular cytotoxicity (ADCC) ,rituximab ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes. Kaplan-Meier survival curves show a superior progression-free survival (PFS) for patients having more than 1.6% CD16+ T cells (p = 0.02; HR = 0.13 (0.007–0.67)) but an inferior PFS having more than 10.0% CD16+ monocytes (p = 0.0003; HR = 16.0 (3.1-291.9)) at diagnosis. Surprisingly, no correlation with NK cells was found. The increased risk of relapse in the presence of > 10.0% CD16+ monocytes is reversed by the simultaneous occurrence of > 1.6% CD16+ T cells. The unexpectedly strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity as quantified by real-time killing assays and single-cell imaging. The combined analysis of CD16+ monocytes (> 10%) and CD16+ T cells (
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- 2024
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7. CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients
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Zöphel, Sylvia, Küchler, Nadja, Jansky, Johanna, Hoxha, Cora, Schäfer, Gertrud, Weise, Julius J., Vialle, Joanne, Kaschek, Lea, Stopper, Gebhard, Eichler, Hermann, Yildiz, Daniela, Moter, Alina, Wendel, Philipp, Ullrich, Evelyn, Schormann, Claudia, Rixecker, Torben, Cetin, Onur, Neumann, Frank, Orth, Patrick, Bewarder, Moritz, Hoth, Markus, Thurner, Lorenz, and Schwarz, Eva C.
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- 2024
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8. Elementary School Students' Length Estimation Skills--Analyzing a Multidimensional Construct in a Cross-Country Study
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Hoth, Jessica, Heinze, Aiso, Huang, Hsin-Mei E., Weiher, Dana Farina, Niedermeyer, Inga, and Ruwisch, Silke
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Measurement estimation skills are relevant for our everyday life and should be addressed in the mathematics classroom. Although students' measurement estimation skills were examined in several empirical studies, a structure model to describe these skills is still missing. The current research aimed at analyzing the structure of length estimation skills as one basic measurement estimation skill. Taking into account the different kinds of estimation situations, a test on length estimation skills was developed and administered in two contrasting samples of 3rd- and 4th-grade students from Germany and Taiwan in two studies. Study 1 (N = 248) followed an exploratory approach to analyze the structure of length estimation skills (research question 1). Exploratory factor analysis suggested a 3-dimensional model of length estimation skills, dividing the dimensions (1) estimating lengths of small objects, (2) estimating lengths of objects that are not small but touchable, and (3) estimating lengths of objects that are not small and not touchable. This 3-dimensional structure could be confirmed using confirmatory factor analyses in study 2 (N = 903). In addition, the test on students' length estimation skills proved to be partially measurement invariant across the two groups (research question 2). The cross-national comparison (research question 3) revealed differences between Taiwanese and German students' length estimation skills that correspond to the educational traditions in each country. Taiwanese students reached better results on the dimensions small as well as not small and touchable while German students were ahead in the dimension not small and not touchable.
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- 2023
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9. Assessing petroleum contamination in parts of the Niger Delta based on a sub-catchment delineated field assessment
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Ola, Ibukun, Drebenstedt, Carsten, Burgess, Robert M., Mensah, Martin, Hoth, Nils, Okoroafor, Precious, and Külls, Christoph
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- 2024
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10. Environmental impacts of artisanal and small-scale gold mining within Kambele and Pater gold mining sites, East Cameroon
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Fonshiynwa, Mark Monyuy, Fuanya, Christopher, Hoth, Nils, Ouabo, Romaric Emmanuel, Tangko, Tangko Emmanuel, Günther, Juliane, Eseya, Mengu Emmanuel, and Drebenstedt, Carsten
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- 2024
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11. Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function
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Zhang, Yuankai, Liu, Xue, Wiggins, Kerri L, Kurniansyah, Nuzulul, Guo, Xiuqing, Rodrigue, Amanda L, Zhao, Wei, Yanek, Lisa R, Ratliff, Scott M, Pitsillides, Achilleas, Aguirre Patiño, Juan Sebastian, Sofer, Tamar, Arking, Dan E, Austin, Thomas R, Beiser, Alexa S, Blangero, John, Boerwinkle, Eric, Bressler, Jan, Curran, Joanne E, Hou, Lifang, Hughes, Timothy M, Kardia, Sharon LR, Launer, Lenore J, Levy, Daniel, Mosley, Thomas H, Nasrallah, Ilya M, Rich, Stephen S, Rotter, Jerome I, Seshadri, Sudha, Tarraf, Wassim, González, Kevin A, Ramachandran, Vasan, Yaffe, Kristine, Nyquist, Paul A, Psaty, Bruce M, DeCarli, Charles S, Smith, Jennifer A, Glahn, David C, González, Hector M, Bis, Joshua C, Fornage, Myriam, Heckbert, Susan R, Fitzpatrick, Annette L, Liu, Chunyu, Satizabal, Claudia L, Aguilera, Norma, Ament, Seth, Ammous, Farah, Arnett, Donna K, Becker, Diane, Bis, Joshua, Blue, Elizabeth, Breaux, Camille, Chaar, Dima, MHI, Clarkson-Townsend, Danielle, Cooper, Brigidann, Coresh, Josef, Correa, Adolfo, DeStefano, Anita, Ding, Jingzhong, Fardo, David, Fitzpatrick, Annette, French, Jennifer, Glahn, David, Gonzalez, Hector, Granot-Hershkovitz, Einat, Hanly, Patrick, Hayden, Kathleen, Heckbert, Susan, Heemann, Scott, Horvath, Steve, Hoth, Karin, Hughes, Timothy, Jaiswal, Sidd, Jian, Xueqiu, Katsumata, Yuriko, Kho, Minjung, Kooperberg, Charles, Launer, Lenore, Lin, Honghuang, Litkowski, Elizabeth, Longstreth, Will, Martin, Alexandra, Mayeux, Richard, Mikulla, Julie, Miller, Amy, Misra, Biswapriya, Mosley, Thomas, Nyquist, Paul, O'Connell, Jeff, Olivier, Michael, Peloso, Gina, Perry, James, Psaty, Bruce, Purcell, Shaun, and Raffield, Laura
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Alzheimer's Disease ,Neurodegenerative ,Dementia ,Aging ,Biomedical Imaging ,Acquired Cognitive Impairment ,Behavioral and Social Science ,Brain Disorders ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Clinical Research ,Precision Medicine ,Genetics ,4.1 Discovery and preclinical testing of markers and technologies ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,Good Health and Well Being ,Middle Aged ,Humans ,Female ,Aged ,Male ,DNA ,Mitochondrial ,DNA Copy Number Variations ,Prospective Studies ,Cross-Sectional Studies ,Alzheimer Disease ,Magnetic Resonance Imaging ,Cognition ,Brain ,NHLBI Trans-Omics for Precision Medicine (TOPMed) program ,Mitochondrial and Neurocognitive Working Groups ,Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences - Abstract
Background and objectivesPrevious studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.MethodsWe included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (
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- 2023
12. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease.
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Tran, Thuonghien, Kinney, Gregory, Comellas, Alejandro, Hoth, Karin, Baldomero, Arianne, Mamary, A, Curtis, Jeffrey, Hanania, Nicola, Casaburi, Richard, Young, Kendra, Kim, Victor, Make, Barry, Wan, Emily, Diaz, Alejandro, Hokanson, John, Crapo, James, Silverman, Edwin, Bhatt, Surya, Regan, Elizabeth, and Fortis, Spyridon
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Chronic obstructive pulmonary disease ,Diagnosis ,Humans ,Female ,Prevalence ,Pulmonary Disease ,Chronic Obstructive ,Lung ,Smoking ,Risk Factors ,Spirometry - Abstract
INTRODUCTION: Recent evidence suggests a high prevalence of undiagnosed chronic obstructive pulmonary disease (COPD). These individuals are at risk of exacerbations and delayed treatment. We analyzed an at-risk population for the prevalence of abnormal spirometry to provide clarity into who should undergo early spirometry. METHODS: We analyzed data from the COPDGene study. Participants with ≥10 pack-years of smoking were included. Individuals with self-reported or physician-diagnosed COPD, asthma, chronic bronchitis, emphysema and/or were on inhalers were excluded. Parsimonious multivariable logistic regression models identified factors associated with abnormal spirometry, defined as either airflow obstruction (AFO) or preserved ratio impaired spirometry. Variables were selected for the final model using a stepwise backward variable elimination process which minimized Akaike information criterion (AIC). Similarly, during the 5-year follow-up period, we assessed factors associated with incident diagnosis of COPD. RESULTS: Of 5055 individuals, 1064 (21%) had undiagnosed AFO. Age, pack-years, current smoking and a history of acute bronchitis were associated with AFO while body mass index, female sex, and Black race were inversely associated. Among 2800 participants with 5-year follow-up, 532 (19%) had an incident diagnosis of COPD. Associated risk factors included mMRC ≥2, chronic productive cough, respiratory exacerbations during the follow-up period, and abnormal spirometry. Age was inversely associated. CONCLUSIONS: The prevalence of undiagnosed COPD is high in at-risk populations. We found multiple factors associated with undiagnosed COPD and incident diagnosis of COPD at follow up. These results can be used to identify those at risk for undiagnosed COPD to facilitate earlier diagnosis and treatment.
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- 2023
13. Presence of symptoms 6 weeks after COVID-19 among vaccinated and unvaccinated US healthcare personnel: a prospective cohort study.
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Mohr, Nicholas, Plumb, Ian, Harland, Kari, Pilishvili, Tamara, Fleming-Dutra, Katherine, Krishnadasan, Anusha, Hoth, Karin, Saydah, Sharon, Mankoff, Zachary, Haran, John, Briggs-Hagen, Melissa, León, Eliezer, and Talan, David
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COVID-19 ,EPIDEMIOLOGY ,INFECTIOUS DISEASES ,Humans ,COVID-19 ,COVID-19 Vaccines ,Prospective Studies ,SARS-CoV-2 ,Vaccination ,mRNA Vaccines ,Delivery of Health Care - Abstract
OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work. DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. SETTING: Health systems in 12 US states. PARTICIPANTS: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset. EXPOSURES: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. MAIN OUTCOME MEASURES: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work. RESULTS: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79). CONCLUSIONS: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work.
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- 2023
14. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure: A Longitudinal Follow-up Study of the COPDGene Cohort.
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Adviento, Brigid, Regan, Elizabeth, Make, Barry, Han, MeiLan, Foreman, Marilyn, Iyer, Anand, Bhatt, Surya, Kim, Victor, Bon, Jessica, Soler, Xavier, Kinney, Gregory, Hanania, Nicola, Lowe, Katherine, Holm, Kristen, Yohannes, Abebaw, Shinozaki, Gen, Hoth, Karin, and Fiedorowicz, Jess
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COPD ,overdose ,prospective cohort study ,suicide deaths ,tobacco smoking ,Humans ,Female ,Middle Aged ,Aged ,Male ,Follow-Up Studies ,Pulmonary Disease ,Chronic Obstructive ,Prospective Studies ,Smoking ,Risk Factors ,Dyspnea ,Biomarkers ,Drug Overdose ,Forced Expiratory Volume - Abstract
BACKGROUND: Studies have shown that COPD and smoking are associated with increased suicide risk. To date, there are no prospective studies examining suicide risk among individuals with smoking exposure along a spectrum of pulmonary diseases ranging from normal spirometry to severe COPD. RESEARCH QUESTION: Which clinical variables predict death by suicide or overdose of indeterminate intent in a large cohort of individuals with smoking exposure within the Genetic Epidemiology of COPD (COPDGene) study? STUDY DESIGN AND METHODS: We studied data from 9,930 participants involved in COPDGene, a multisite, prospective cohort study of individuals with smoking exposure. Primary cause of adjudicated deaths was identified by using death certificates, family reports, and medical records. Time to death by suicide/overdose was examined as the primary outcome in Cox regression models including age, sex, race, BMI, pack-years, current smoking status, airflow limitation (FEV1 % predicted), dyspnea (modified Medical Research Council scale score ≥ 2), 6-min walk distance, supplemental oxygen use, and severe exacerbations in the prior year with time-varying covariates and other causes of death as a competing risk. RESULTS: The cohort was 47% female and 33% Black (67% White); they had a mean ± SD age of 59.6 ± 9.0 years and a mean FEV1 % predicted of 76.1 ± 25.5. Sixty-three individuals died by suicide/overdose. Factors associated with risk of suicide/overdose were current smoking (hazard ratio [HR], 6.44; 95% CI, 2.64-15.67), use of sedative/hypnotics (HR, 2.33; 95% CI, 1.24-4.38), and dyspnea (HR, 2.23; 95% CI, 1.34-3.70). Lower risk was associated with older age (per-decade HR, 0.45; 95% CI, 0.31-0.67), higher BMI (HR, 0.95; 95% CI, 0.91-0.99), and African-American race (HR, 0.41; 95% CI, 0.23-0.74). Severity of airflow limitation (FEV % predicted) was not associated with suicide risk. INTERPRETATION: In this well-characterized cohort of individuals with smoking exposure with and without COPD, risk factors for suicide/overdose were identified that emphasize the subjective experience of illness over objective assessments of lung function.
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- 2023
15. Evaluation of bone density and hand grip strength in the course of drug treatment for osteoporosis: A real-world study
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Schröder, Guido, Hoth, Ivonne, Flachsmeyer, Dirk, Dutzke, Mario, Andresen, Julian Ramin, Andresen, Reimer, and Schober, Hans-Christof
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- 2023
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16. Faculty Publication Productivity and Collaboration in Pakistan: Using Mixed Methods to Compare Foreign and Domestic Doctoral Degree Holders
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Baloch, Niamatullah, Luo, Siming, Shen, Hong, and Hoth, Mir Dosteen
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In higher education research, publication productivity and collaboration of foreign doctoral degree holders have been thoroughly examined in developed countries. However, they have been given less attention in developing countries such as Pakistan, despite their growing visibility and significance in HEIs. The purpose of this study was to examine faculty publication productivity and collaboration differences between foreign and domestic doctoral degree holders. The theoretical premise of the study was based on knowledge recombination theory and mobility approaches, and the study used a convergent parallel mixed methods design. The empirical data consist of 232 faculty members and 17 semi-structured interviews with university administrators collected from 14 public universities. The findings of the study revealed that foreign doctoral degree holders had not produced a greater total of refereed journal articles than their domestic doctoral holder colleagues. Qualitative findings also supported the quantitative findings of the study, as well as made a theoretical contribution to knowledge recombination theory and mobility approaches. Our findings suggested that mobility helps knowledge flows and knowledge gained from distant sources is significantly more creative when compared to domestic knowledge. Additionally, analysis demonstrated that certain foreign doctoral holders are particularly productive and could have benefited from unique knowledge not accessible to their domestic doctoral colleagues. The findings also recognized that those who move internationally and opt for foreign study could be beneficial for home countries and undoubtedly help institutions achieve their research excellence goals. Further discussion and implications are provided.
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- 2021
17. High-Performance Silicon Photonic Single-Sideband Modulators for Cold Atom Interferometry
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Kodigala, Ashok, Gehl, Michael, Hoth, Gregory W., Lee, Jongmin, DeRose, Christopher, Pomerene, Andrew, Dallo, Christina, Trotter, Douglas, Starbuck, Andrew L., Biedermann, Grant, Schwindt, Peter D. D., and Lentine, Anthony L.
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Physics - Optics ,Physics - Atomic Physics ,Quantum Physics - Abstract
The most complicated and challenging system within a light-pulse atom interferometer (LPAI) is the laser system, which controls the frequencies and intensities of multiple laser beams over time to configure quantum gravity and inertial sensors. The main function of an LPAI laser system is to perform cold-atom generation, state-preparation, state-selective detection and to generate coherent two-photon process for the light-pulse sequence. Substantial miniaturization and ruggedization of the laser system can be achieved by bringing most key functions of the laser system onto photonic integrated circuit (PIC). We demonstrate a high-performance silicon photonic suppressed-carrier single-sideband (SC-SSB) modulator at 1560 nm, which can dynamically frequency shift within the LPAI. With independent RF-channel control, we study the imbalances in both the optical and RF phases/amplitudes to reach 30 dB carrier-suppression, unprecedented 47.8 dB sideband-suppression at peak conversion-efficiency: -6.846 dB (20.7 %). Using a silicon photonic SSB-modulator, we demonstrate cold-atom generation, state-selective detection, and atom interferometer fringes to estimate gravitational acceleration, $g \approx 9.77 \pm 0.01 \,\rm{m/s^2}$, in a Rubidium ($^{87}$Rb) atom system., Comment: 25 pages, 14 figures
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- 2022
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18. Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document
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Seshadri, Anupamaa, Appelbaum, Rachel, Carmichael, Samuel P, Cuschieri, Joseph, Hoth, Jason, Kaups, Krista L, Kodadek, Lisa, Kutcher, Matthew E, Pathak, Abhijit, Rappold, Joseph, Rudnick, Sean R, and Michetti, Christopher P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Physical Injury - Accidents and Adverse Effects ,Digestive Diseases ,Liver Disease ,Clinical Research ,Chronic Liver Disease and Cirrhosis ,cirrhosis ,critical care ,liver ,practice guideline - Abstract
Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.
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- 2022
19. Use of the Spirometric “Fixed-Ratio” Underdiagnoses COPD in African-Americans in a Longitudinal Cohort Study
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Regan, Elizabeth A., Lowe, Melissa E., Make, Barry J., Curtis, Jeffrey L., Chen, Quan (Grace), Cho, Michael H., Crooks, James L., Lowe, Katherine E., Wilson, Carla, O’Brien, James K., Oates, Gabriela R., Baldomero, Arianne K., Kinney, Gregory L., Young, Kendra A., Diaz, Alejandro A., Bhatt, Surya P., McCormack, Meredith C., Hansel, Nadia N., Kim, Victor, Richmond, Nicole E., Westney, Gloria E., Foreman, Marilyn G., Conrad, Douglas J., DeMeo, Dawn L., Hoth, Karin F., Amaza, Hannatu, Balasubramanian, Aparna, Kallet, Julia, Watts, Shandi, Hanania, Nicola A., Hokanson, John, Beaty, Terri H., Crapo, James D., Silverman, Edwin K., Casaburi, Richard, and Wise, Robert
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- 2023
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20. Elementary School Students’ Length Estimation Skills—Analyzing a Multidimensional Construct in a Cross-Country Study
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Hoth, Jessica, Heinze, Aiso, Huang, Hsin-Mei E., Weiher, Dana Farina, Niedermeyer, Inga, and Ruwisch, Silke
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- 2023
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21. Curcumin Supplementation and Vascular and Cognitive Function in Chronic Kidney Disease: A Randomized Controlled Trial
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Colin J. Gimblet, Nicholas T. Kruse, Katharine Geasland, Jeni Michelson, Mingyao Sun, Patrick Ten Eyck, Cari Linkenmeyer, Safur Rehman Mandukhail, Matthew J. Rossman, Meenakshi Sambharia, Michel Chonchol, Manjula Kurella Tamura, Douglas Seals, Karin F. Hoth, and Diana Jalal
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CKD ,curcumin ,vascular function ,oxidative stress ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid–femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was −0.7 (−2.1, 1.1) and −0.1 (−1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.
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- 2024
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22. Microbial hydrogen consumption leads to a significant pH increase under high-saline-conditions: implications for hydrogen storage in salt caverns
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Dopffel, Nicole, Mayers, Kyle, Kedir, Abduljelil, Alagic, Edin, An-Stepec, Biwen Annie, Djurhuus, Ketil, Boldt, Daniel, Beeder, Janiche, and Hoth, Silvan
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- 2023
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23. Surgical and procedural antibiotic prophylaxis in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document
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Deborah M Stein, John Varujan Agapian, Bryce Robinson, Matthew E Kutcher, Joseph Cuschieri, Michael Steven Farrell, Dina M Filiberto, Abhijit Pathak, Rondi Gelbard, Jason Hoth, Randeep Jawa, Jasmeet Paul, Rachel D Appelbaum, Eden Nohra, and Jordan Kirsch
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Surgery ,RD1-811 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy).
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- 2024
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24. Antibiotic prophylaxis in injury: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document
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Deborah M Stein, Randeep S Jawa, Joseph Cuschieri, J Jason Hoth, Samuel Mandell, Tanya Rinderknecht, Rachel D Appelbaum, Michael S Farrell, Rondi B Gelbard, Jordan M Kirsch, Eden A Nohra, and Susan Rowell
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Surgery ,RD1-811 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Published
- 2024
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25. Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease.
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O’Toole, Jacqueline, Woo, Han, Putcha, Nirupama, Cooper, Christopher B, Woodruff, Prescott, Kanner, Richard E, Paine, Robert, Bowler, Russell P, Comellas, Alejandro, Hoth, Karin F, Krishnan, Jerry A, Han, Meilan, Dransfield, Mark, Iyer, Anand S, Couper, David, Peters, Stephen P, Criner, Gerard, Kim, Victor, Barr, R Graham, Martinez, Fernando J, Hansel, Nadia N, Eakin, Michelle N, Alexis, Neil E, Anderson, Wayne H, Arjomandi, Mehrdad, Barjaktarevic, Igor, Bateman, Lori A, Bhatt, Surya P, Bleecker, Eugene R, Boucher, Richard C, Christenson, Stephanie A, Comellas, Alejandro P, Couper, David J, Criner, Gerard J, Crystal, Ronald G, Curtis, Jeffrey L, Doerschuk, Claire M, Dransfield, Mark T, Drummond, Brad, Freeman, Christine M, Galban, Craig, Han, MeiLan K, Hastie, Annette T, Hoffman, Eric A, Huang, Yvonne, Kaner, Robert J, Kleerup, Eric C, LaVange, Lisa M, Lazarus, Stephen C, Meyers, Deborah A, Moore, Wendy C, Newell, John D, Paulin, Laura, Pirozzi, Cheryl, Oelsner, Elizabeth C, O’Neal, Wanda K, Ortega, Victor E, Raman, Sanjeev, Rennard, Stephen I, Tashkin, Donald P, Wells, J Michael, Wise, Robert A, and Woodruff, Prescott G
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Clinical Research ,Behavioral and Social Science ,Depression ,Chronic Obstructive Pulmonary Disease ,Mental Health ,Lung ,Respiratory ,Good Health and Well Being ,Female ,Forced Expiratory Volume ,Humans ,Pulmonary Disease ,Chronic Obstructive ,Quality of Life ,Respiratory Function Tests ,Smoking ,Surveys and Questionnaires ,depression ,COPD ,patient reported outcome measures ,SPIROMICS Investigators - Abstract
Rationale: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives: Examine the impact of depressive symptoms compared with FEV1% on COPD morbidity. Methods: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV1% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. Results: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV1% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV1% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV1%, explaining 30-67% of heterogeneity. FEV1% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16-32% of heterogeneity. Depressive symptoms accounted for 3-17% variance in change over time in PROs. In contrast, FEV1% accounted for 1-4% variance over time in PROs. Conclusions: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.
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- 2022
26. Schwerstverletztenversorgung beim Massenanfall von Verletzten: Worin besteht der Unterschied zum Schockraummanagement?
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Franke, Axel, Bieler, Dan, Achatz, Gerhard, Suda, Arnold J., Hoth, Patrick, Paffrath, Thomas, and Friemert, Benedikt
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- 2023
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27. A passively pumped vacuum package sustaining cold atoms for more than 200 days
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Little, Bethany J., Hoth, Gregory W., Christensen, Justin, Walker, Chuck, De Smet, Dennis J., Biedermann, Grant W., Lee, Jongmin, and Schwindt, Peter D. D.
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Physics - Atomic Physics ,Physics - Applied Physics - Abstract
Compact cold-atom sensors depend on vacuum technology. One of the major limitations to miniaturizing these sensors are the active pumps -- typically ion pumps -- required to sustain the low pressure needed for laser cooling. Although passively pumped chambers have been proposed as a solution to this problem, technical challenges have prevented successful operation at the levels needed for cold-atom experiments. We present the first demonstration of a vacuum package successfully independent of ion pumps for more than a week; our vacuum package is capable of sustaining a cloud of cold atoms in a magneto-optical trap (MOT) for greater than 200 days using only non-evaporable getters and a rubidium dispenser. Measurements of the MOT lifetime indicate the package maintains a pressure of better than $2\times10^{-7}$ Torr. This result will significantly impact the development of compact atomic sensors, including those sensitive to magnetic fields, where the absence of an ion pump will be advantageous., Comment: 6 pages, 5 figures. (This replacement corrects cross-section value.)
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- 2021
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28. Education and training as a key enabler of successful patient care in mass-casualty terrorist incidents
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Hoth, Patrick, Roth, Johanna, Bieler, Dan, Friemert, Benedikt, Franke, Axel, Paffrath, Thomas, Blätzinger, Markus, and Achatz, Gerhard
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- 2023
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29. Evaluation of the decision-making process within the table-top exercise of the Terror and Disaster Surgical Care (TDSC®) course
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Achatz, Gerhard, Reckziegel, Alexander, Friemert, Benedikt, Blätzinger, Markus, Hinz-Bauer, Simone, Franke, Axel, Bieler, Dan, Paffrath, Thomas, and Hoth, Patrick
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- 2023
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30. Microbial hydrogen consumption leads to a significant pH increase under high-saline-conditions: implications for hydrogen storage in salt caverns
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Nicole Dopffel, Kyle Mayers, Abduljelil Kedir, Edin Alagic, Biwen Annie An-Stepec, Ketil Djurhuus, Daniel Boldt, Janiche Beeder, and Silvan Hoth
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Medicine ,Science - Abstract
Abstract Salt caverns have been successfully used for natural gas storage globally since the 1940s and are now under consideration for hydrogen (H2) storage, which is needed in large quantities to decarbonize the economy to finally reach a net zero by 2050. Salt caverns are not sterile and H2 is a ubiquitous electron donor for microorganisms. This could entail that the injected H2 will be microbially consumed, leading to a volumetric loss and potential production of toxic H2S. However, the extent and rates of this microbial H2 consumption under high-saline cavern conditions are not yet understood. To investigate microbial consumption rates, we cultured the halophilic sulphate-reducing bacteria Desulfohalobium retbaense and the halophilic methanogen Methanocalculus halotolerans under different H2 partial pressures. Both strains consumed H2, but consumption rates slowed down significantly over time. The activity loss correlated with a significant pH increase (up to pH 9) in the media due to intense proton- and bicarbonate consumption. In the case of sulphate reduction, this pH increase led to dissolution of all produced H2S in the liquid phase. We compared these observations to a brine retrieved from a salt cavern located in Northern Germany, which was then incubated with 100% H2 over several months. We again observed a H2 loss (up to 12%) with a concurrent increase in pH of up to 8.5 especially when additional nutrients were added to the brine. Our results clearly show that sulphate-reducing microbes present in salt caverns consume H2, which will be accompanied by a significant pH increase, resulting in reduced activity over time. This potentially self-limiting process of pH increase during sulphate-reduction will be advantageous for H2 storage in low-buffering environments like salt caverns.
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- 2023
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31. Structural and functional analysis of a plant nucleolar RNA chaperone-like protein
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Rita Fernandes, Anna Ostendorp, Steffen Ostendorp, Judith Mehrmann, Sven Falke, Melissa Ann Graewert, Magdalena Weingartner, Julia Kehr, and Stefan Hoth
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Medicine ,Science - Abstract
Abstract Ribosome biogenesis is a key process in all eukaryotic cells that requires hundreds of ribosome biogenesis factors (RBFs), which are essential to build the mature ribosomes consisting of proteins and rRNAs. The processing of the required rRNAs has been studied extensively in yeast and mammals, but in plants much is still unknown. In this study, we focused on a RBF from A. thaliana that we named NUCLEOLAR RNA CHAPERONE-LIKE 1 (NURC1). NURC1 was localized in the nucleolus of plant cell nuclei, and other plant RBF candidates shared the same localization. SEC-SAXS experiments revealed that NURC1 has an elongated and flexible structure. In addition, SEC-MALLS experiments confirmed that NURC1 was present in its monomeric form with a molecular weight of around 28 kDa. RNA binding was assessed by performing microscale thermophoresis with the Arabidopsis internal transcribed spacer 2 (ITS2) of the polycistronic pre-rRNA precursor, which contains the 5.8S, 18S, and 25S rRNA. NURC1 showed binding activity to the ITS2 with a dissociation constant of 228 nM and exhibited RNA chaperone-like activity. Our data suggested that NURC1 may have a function in pre-rRNA processing and thus ribosome biogenesis.
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- 2023
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32. Availability and use of institutional support programs for emergency department healthcare personnel during the COVID-19 pandemic
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Karin F. Hoth, Patrick Ten Eyck, Karisa K. Harland, Anusha Krishnadasan, Robert M. Rodriguez, Juan Carlos C. Montoy, Linder H. Wendt, William Mower, Kelli Wallace, Scott Santibañez, David A. Talan, and Nicholas M. Mohr
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Medicine ,Science - Published
- 2024
33. Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices
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Sadjadi, Z., Zhao, R., Hoth, M., Qu, B., and Rieger, H.
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Physics - Biological Physics ,Quantitative Biology - Cell Behavior - Abstract
To fulfill their killing functions, cytotoxic T lymphocytes (CTLs) need to migrate to search for their target cells in complex biological microenvironments, a key component of which is extracellular matrix (ECM). The mechanisms underlying CTL's navigation are not well understood so far. Here we use a collagen assay as a model for the ECM and analyze the migration trajectories of primary human CTLs in collagen matrices with different concentrations. We observe different migration patterns for individual T cells. Three different motility types can be distinguished: slow, fast and mixed motilities. Slow CTLs remain nearly stationary within the collagen matrix and show slightly anti-persistent motility, while the fast ones move quickly and persistent (i.e. with not too large turning angles). The dynamics of the mixed type consists of periods of slow and fast motions; both states are persistent, but they have different persistencies. The dynamics can be well described by a two-state persistent random walk model. We extract the parameters of the model by analyzing experimental data. The mean square displacements predicted by the model and those measured experimentally are in very good agreement, without any fitting parameter. Potential reasons for the observed two-state motility are discussed. T cells dig the collagen during their migration and form channels, which facilitate the movement of other CTLs in the collagen network., Comment: 9 pages, 9 figures, 4 tables
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- 2020
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34. Factors associated with the decision to receive bivalent COVID-19 booster vaccination among health care personnel
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Nicholas M. Mohr, Ian D. Plumb, Eliezer Santos León, Karisa K. Harland, Anusha Krishnadasan, Utsav Nandi, Karin F. Hoth, Howard A. Smithline, and David A. Talan
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COVID-19 vaccines ,vaccination hesitancy ,health personnel ,public health ,occupational health ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
ABSTRACTCOVID-19 vaccination is effective at reducing SARS-CoV-2 complications, but uptake has been low. Our objective in this study was to compare the importance of factors reported to influence the decision to receive a bivalent COVID-19 booster vaccine among health care personnel (HCP) tested for SARS-CoV-2 between October 2022 and April 2023 in a 20-hospital vaccine effectiveness study in the United States (n = 1656). Compared with those who had not received the booster, the factors most likely to be reported to be important were concerns about contracting COVID-19 (84.0% of those who had received the bivalent booster vs. 47.5% of those who had not, difference 36.6% points (PP), 95% confidence interval [CI] 32.1 to 41.1%), spreading infection to family members (89.2% vs. 62.8%, difference 26.3 PP, 95% CI 22.3 to 30.4%), and spreading infection to colleagues at work (85.5% vs. 59.4%, difference 26.1 PP, 95% CI 21.7 to 30.5%). HCP who had received the booster more frequently cited the primary literature (61.7% vs. 31.8%, difference 29.9 PP, 95% CI 24.6 to 35.2%) and employer recommendations (48.3% vs. 29.8%, difference 18.5 PP, 95% CI 13.2 to 23.9%) as influencing their decision. This analysis provides insight into factors for targeting future vaccine messaging.
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- 2023
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35. Symptoms of Anxiety, Burnout, and PTSD and the Mitigation Effect of Serologic Testing in Emergency Department Personnel During the COVID-19 Pandemic
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Rodriguez, Robert M, Montoy, Juan Carlos C, Hoth, Karin F, Talan, David A, Harland, Karisa K, Eyck, Patrick Ten, Mower, William, Krishnadasan, Anusha, Santibanez, Scott, Mohr, Nicholas, Network, Project COVERED Emergency Department, Bahamon, Monica, Carlson, Jestin N, Chisolm-Straker, Makini, Driver, Brian, Faine, Brett, Pharm, D, Galbraith, James, Giordano, Philip A, Haran, John P, Higgins, Amanda, Hinson, Jeremiah, House, Stacey, Idris, Ahamed H, Kean, Efrat, Krebs, Elizabeth, Kurz, Michael C, Lee, Lilly, Liang, Stephen Y, Lim, Stephen C, Moran, Gregory, Nandi, Utsav, Pathmarajah, Kavitha, Paxton, James H, Perez, Yesenia, Rothman, Richard, Schrading, Walter A, Shuck, Jessica, Slev, Patricia, Smithline, Howard A, Souffront, Kimberly, Steele, Mark, St. Romain, Michelle, Stubbs, Amy, Swanson, Morgan, Tiao, Josh, Torres, Jesus R, Trent, Stacy, Uribe, Lisandra, Venkat, Arvind, Volturo, Gregory, Wallace, Kelli, and Weber, Kurt D
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Mind and Body ,Brain Disorders ,Behavioral and Social Science ,Anxiety Disorders ,Infectious Diseases ,Prevention ,Clinical Research ,Health Services ,Mental Health ,Post-Traumatic Stress Disorder (PTSD) ,Good Health and Well Being ,Anxiety ,Burnout ,Professional ,COVID-19 ,COVID-19 Testing ,Emergency Service ,Hospital ,Female ,Health Personnel ,Humans ,Male ,Pandemics ,Prospective Studies ,SARS-CoV-2 ,Stress Disorders ,Post-Traumatic ,United States ,Project COVERED Emergency Department Network ,Clinical Sciences ,Emergency & Critical Care Medicine - Abstract
Study objectiveAmong a comprehensive range of frontline emergency department health care personnel, we assessed symptoms of anxiety and burnout, specific coronavirus disease 2019 (COVID-19) work-related stressors, and risk for post-traumatic stress disorder (PTSD). We also determined whether COVID-19 serologic testing of HCP decreased their self-reported anxiety.MethodsIn a prospective cohort study from May 13, 2020, to July 8, 2020, we used electronic surveys to capture participant self-reported symptoms before and after serologic testing for anti-SARS-CoV-2 immunoglobulin G antibodies. Participants were physicians, nurses, advanced practice providers, and nonclinical ED personnel at 20 geographically diverse United States EDs. We evaluated these domains: 1) the effects of the COVID-19 pandemic on overall stress and anxiety; 2) COVID-19-related work stressors; 3) burnout; and 4) PTSD risk (measured using the Primary Care-PTSD Screen for DSM-5, a 5-item screening instrument in which a score of ≥3 signifies high risk for PTSD). We also assessed perceptions of whether results of COVID-19 antibody testing decreased participants' self-reported anxiety.ResultsOf 1,606 participants, 100% and 88% responded to the baseline and follow-up surveys, respectively. At baseline, approximately half (46%) reported symptoms of emotional exhaustion and burnout from their work, and 308 (19.2%, 95% confidence interval [CI] 17.3% to 21.1%) respondents screened positive for increased PTSD risk. Female respondents were more likely than males to screen positive (odds ratio [OR] 2.03, 95% CI 1.49 to 2.78). Common concerns included exposing their family and the health of coworkers diagnosed with COVID-19. After receiving antibody test results, 54% (95% CI 51.8 to 56.7) somewhat agreed, agreed, or strongly agreed that knowledge of their immune status had decreased their anxiety. A positive serology result indicating prior SARS-CoV-2 infection was associated with a higher likelihood of reporting decreased anxiety (2.83, 95% CI 1.37 to 5.83).ConclusionSymptoms of anxiety and burnout were prevalent across the spectrum of ED staff during the COVID-19 pandemic. One-fifth of ED personnel appeared to be at risk for PTSD. Increased provision of serologic testing may help to mitigate anxiety.
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- 2021
36. Ars2‐containing bispecific, Fab‐ and IgG1‐format BAR‐bodies to target DLBCL cells
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Maximilian Kiefer, Lorenz Thurner, Theresa Bock, Onur Cetin, Igor Kos, Vadim Lesan, Dominic Kaddu‐Mulindwa, Joerg Thomas Bittenbring, Natalie Fadle, Evi Regitz, Markus Hoth, Frank Neumann, Klaus‐Dieter Preuss, Michael Pfreundschuh, Konstantinos Christofyllakis, and Moritz Bewarder
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autoantigen ,BAR‐bodies ,B cells ,B‐cell receptor ,lymphoid malignancies ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Despite recent advances in the therapy of diffuse large B‐cell lymphoma, not otherwise specified (DLBCL), around 30% of patients develop refractory disease or relapse after first‐line treatment. Recently, Ars2 was reported as the auto‐antigenic target of the B‐cell receptor (BCR) in approximately 25% of activated B‐cell DLBCL cases. Ars2 could be used to specifically target B cells expressing Ars2‐reactive BCRs. However, the optimal therapeutic format to integrate Ars2 into has yet to be determined. To mimic therapeutic antibody formats, Ars2‐containing bispecific and IgG1‐like constructs (BCR antigens for reverse [BAR]‐bodies) were developed. Two bispecific BAR‐bodies connecting single‐chain antibodies against CD16 or CD3 to the BCR‐binding epitope of Ars2 were constructed. Both constructs showed strong binding to U2932 cells and induced effector cell‐dependent and selective cytotoxicity against U2932 cells of up to 44% at concentrations of 20 μg/ml. Additionally, IgG1‐format Ars2 BAR‐bodies were constructed by replacing the variable heavy‐ and light‐chain regions of a full‐length antibody with the Ars2 epitope. IgG1‐format Ars2 BAR‐bodies also bound selectively to U2932 and OCI‐Ly3 cells and induced selective cytotoxicity of up to 60% at 10 μg/ml. In conclusion, Ars2‐containing bispecific and IgG1‐format BAR‐bodies both are new therapeutic formats to target DLBCL cells.
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- 2023
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37. Examining the Effect of Genes on Depression as Mediated by Smoking and Modified by Sex
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Kirsten Voorhies, Julian Hecker, Sanghun Lee, Georg Hahn, Dmitry Prokopenko, Merry-Lynn McDonald, Alexander C. Wu, Ann Wu, John E. Hokanson, Michael H. Cho, Christoph Lange, Karin F. Hoth, and Sharon M. Lutz
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depression ,mediation analysis ,smoking ,sex moderation ,Genetics ,QH426-470 - Abstract
Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [LOC105378800] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 4.0 × 10−4) among all participants and a marginally significant indirect effect among females (p = 0.02) and males (p = 4.0 × 10−3). Moreover, rs10501696 [GRM5] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 0.01) among all participants and a significant indirect effect among females (p = 2.2 × 10−3). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [GRM5] on broad depression through the log of pack-years of cigarette smoking (p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years (p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [LOC105378800, GRM5] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex.
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- 2024
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38. Integrated Hydrological and Hydrochemical Analysis of Arsenic and Iron Behavior in Waters of a Decommissioned Tin Mine in Ehrenfriedersdorf, Germany
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Viktoria Rafique, Marlies Grimmer, Florian Scheermann, Marco Roscher, and Nils Hoth
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arsenic ,iron ,mine water ,climatic water balance ,decommissioned mine ,Science - Abstract
Arsenic contamination poses significant challenges to environmental and public health, with mining activities contributing to its wider distribution. This study investigates the fate of arsenic and iron in mine waters at a decommissioned tin mine, now a visitor mine, located in Ehrenfriedersdorf, Germany, situated in the Free State of Saxony. Despite the general shortage of data, which is common for old mining sites, we explored the complex interplay of climatic conditions, hydrological processes, and arsenic and iron behavior in the mine waters through a comprehensive approach encompassing general site characterization, mine water monitoring, and analysis of local weather data. Over a period of three years, we conducted 14 sampling campaigns, collecting a total of 95 water samples, each consisting of three filtration subsamples, resulting in the analysis of 285 water samples. These samples were collected both aboveground and underground. Aboveground samples included mine outflows, a tailing outflow, and an adjacent creek, while underground sampling points were scattered throughout the mine initially and later focused on the identified “main” mine water system. The chemical data from the analyses were correlated with local climatic water balances to reveal distinctive patterns in arsenic and iron concentrations at various locations within the mine system. Our findings shed light on the hydrological behavior of the mine, helping to elucidate the impact of precipitation and potential evapotranspiration on arsenic and iron concentrations in a tailing outflow, in the flooded mine body, and at the portal of the main dewatering gallery. Our findings emphasize the importance of sustained monitoring and the utilization of local weather data to comprehend metalloid and metal contamination risks in similar mining environments.
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- 2024
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39. Vehicle-Integrated Photovoltaics—A Case Study for Berlin
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Philipp Hoth, Ludger Heide, Alexander Grahle, and Dietmar Göhlich
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vehicle-integrated photovoltaics ,VIPV ,urban environment ,solar simulation ,trees ,GIS ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Transportation engineering ,TA1001-1280 - Abstract
Recent developments in vehicle-integrated photovoltaics (VIPV) offer prospects for enhancing electric vehicle range, lowering operating costs, and supporting carbon-neutral transport, particularly in urban settings. This study evaluates the solar energy potential of parking spaces in Berlin, considering challenges like building and tree shading using digital surface models and weather data for solar simulations. Utilizing open datasets and software, the analysis covered 48,827 parking spaces, revealing that VIPV could extend vehicle range by 7 to 14 km per day, equating to a median annual increase of 2527 km. The findings suggest median yearly cost savings of 164 euros from reduced grid charging. However, the environmental benefits of solar vehicle charging were found to be less than those of traditional grid-connected photovoltaic systems. The study introduces a method to pinpoint parking spaces that are most suitable for solar charging.
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- 2024
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40. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthmaResearch in context
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Kathryn Recto, Priyadarshini Kachroo, Tianxiao Huan, David Van Den Berg, Gha Young Lee, Helena Bui, Dong Heon Lee, Jessica Gereige, Chen Yao, Shih-Jen Hwang, Roby Joehanes, Scott T. Weiss, George T. O’Connor, Daniel Levy, Dawn L. DeMeo, Namiko Abe, Gonçalo Abecasis, Francois Aguet, Christine Albert, Laura Almasy, Alvaro Alonso, Seth Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum-Bowden, Kristin Ardlie, Dan Arking, Donna K. Arnett, Allison Ashley-Koch, Stella Aslibekyan, Tim Assimes, Paul Auer, Dimitrios Avramopoulos, Najib Ayas, Adithya Balasubramanian, John Barnard, Kathleen Barnes, R. Graham Barr, Emily Barron-Casella, Lucas Barwick, Terri Beaty, Gerald Beck, Diane Becker, Lewis Becker, Rebecca Beer, Amber Beitelshees, Emelia Benjamin, Takis Benos, Marcos Bezerra, Larry Bielak, Joshua Bis, Thomas Blackwell, John Blangero, Nathan Blue, Eric Boerwinkle, Donald W. Bowden, Russell Bowler, Jennifer Brody, Ulrich Broeckel, Jai Broome, Deborah Brown, Karen Bunting, Esteban Burchard, Carlos Bustamante, Erin Buth, Brian Cade, Jonathan Cardwell, Vincent Carey, Julie Carrier, April P. Carson, Cara Carty, Richard Casaburi, Juan P. Casas Romero, James Casella, Peter Castaldi, Mark Chaffin, Christy Chang, Yi-Cheng Chang, Daniel Chasman, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Yii-Der Ida Chen, Michael Cho, Seung Hoan Choi, Lee-Ming Chuang, Mina Chung, Ren-Hua Chung, Clary Clish, Suzy Comhair, Matthew Conomos, Elaine Cornell, Adolfo Correa, Carolyn Crandall, James Crapo, L. Adrienne Cupples, Joanne Curran, Jeffrey Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sean David, Colleen Davis, Michelle Daya, Mariza de Andrade, Lisa de las Fuentes, Paul de Vries, Michael DeBaun, Ranjan Deka, Dawn DeMeo, Scott Devine, Huyen Dinh, Harsha Doddapaneni, Qing Duan, Shannon Dugan-Perez, Ravi Duggirala, Jon Peter Durda, Susan K. Dutcher, Charles Eaton, Lynette Ekunwe, Adel El Boueiz, Patrick Ellinor, Leslie Emery, Serpil Erzurum, Charles Farber, Jesse Farek, Tasha Fingerlin, Matthew Flickinger, Myriam Fornage, Nora Franceschini, Chris Frazar, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Stacey Gabriel, Weiniu Gan, Shanshan Gao, Yan Gao, Margery Gass, Heather Geiger, Bruce Gelb, Mark Geraci, Soren Germer, Robert Gerszten, Auyon Ghosh, Richard Gibbs, Chris Gignoux, Mark Gladwin, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, Sharon Graw, Kathryn J. Gray, Daniel Grine, Colin Gross, C. Charles Gu, Yue Guan, Xiuqing Guo, Namrata Gupta, Jeff Haessler, Michael Hall, Yi Han, Patrick Hanly, Daniel Harris, Nicola L. Hawley, Jiang He, Ben Heavner, Susan Heckbert, Ryan Hernandez, David Herrington, Craig Hersh, Bertha Hidalgo, James Hixson, Brian Hobbs, John Hokanson, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Jianhong Hu, Yi-Jen Hung, Haley Huston, Chii Min Hwu, Marguerite Ryan Irvin, Rebecca Jackson, Deepti Jain, Cashell Jaquish, Jill Johnsen, Andrew Johnson, Craig Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert Kaplan, Sharon Kardia, Shannon Kelly, Eimear Kenny, Michael Kessler, Alyna Khan, Ziad Khan, Wonji Kim, John Kimoff, Greg Kinney, Barbara Konkle, Charles Kooperberg, Holly Kramer, Christoph Lange, Ethan Lange, Leslie Lange, Cathy Laurie, Cecelia Laurie, Meryl LeBoff, Jiwon Lee, Sandra Lee, Wen-Jane Lee, Jonathon LeFaive, David Levine, Joshua Lewis, Xiaohui Li, Yun Li, Henry Lin, Honghuang Lin, Xihong Lin, Simin Liu, Yongmei Liu, Yu Liu, Ruth J.F. Loos, Steven Lubitz, Kathryn Lunetta, James Luo, Ulysses Magalang, Michael Mahaney, Barry Make, Ani Manichaikul, Alisa Manning, JoAnn Manson, Lisa Martin, Melissa Marton, Susan Mathai, Rasika Mathias, Susanne May, Patrick McArdle, Merry-Lynn McDonald, Sean McFarland, Stephen McGarvey, Daniel McGoldrick, Caitlin McHugh, Becky McNeil, Hao Mei, James Meigs, Vipin Menon, Luisa Mestroni, Ginger Metcalf, Deborah A. Meyers, Emmanuel Mignot, Julie Mikulla, Nancy Min, Mollie Minear, Ryan L. Minster, Braxton D. Mitchell, Matt Moll, Zeineen Momin, May E. Montasser, Courtney Montgomery, Donna Muzny, Josyf C. Mychaleckyj, Girish Nadkarni, Rakhi Naik, Take Naseri, Pradeep Natarajan, Sergei Nekhai, Sarah C. Nelson, Bonnie Neltner, Caitlin Nessner, Deborah Nickerson, Osuji Nkechinyere, Kari North, Jeff O'Connell, Tim O'Connor, Heather Ochs-Balcom, Geoffrey Okwuonu, Allan Pack, David T. Paik, Nicholette Palmer, James Pankow, George Papanicolaou, Cora Parker, Gina Peloso, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Patricia Peyser, Lawrence S. Phillips, Jacob Pleiness, Toni Pollin, Wendy Post, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuss, Bruce Psaty, Pankaj Qasba, Dandi Qiao, Zhaohui Qin, Nicholas Rafaels, Laura Raffield, Mahitha Rajendran, Vasan S. Ramachandran, D.C. Rao, Laura Rasmussen-Torvik, Aakrosh Ratan, Susan Redline, Robert Reed, Catherine Reeves, Elizabeth Regan, Alex Reiner, Muagututi‘a Sefuiva Reupena, Ken Rice, Stephen Rich, Rebecca Robillard, Nicolas Robine, Dan Roden, Carolina Roselli, Jerome Rotter, Ingo Ruczinski, Alexi Runnels, Pamela Russell, Sarah Ruuska, Kathleen Ryan, Ester Cerdeira Sabino, Danish Saleheen, Shabnam Salimi, Sejal Salvi, Steven Salzberg, Kevin Sandow, Vijay G. Sankaran, Jireh Santibanez, Karen Schwander, David Schwartz, Frank Sciurba, Christine Seidman, Jonathan Seidman, Frédéric Sériès, Vivien Sheehan, Stephanie L. Sherman, Amol Shetty, Aniket Shetty, Wayne Hui-Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin Silverman, Robert Skomro, Albert Vernon Smith, Jennifer Smith, Josh Smith, Nicholas Smith, Tanja Smith, Sylvia Smoller, Beverly Snively, Michael Snyder, Tamar Sofer, Nona Sotoodehnia, Adrienne M. Stilp, Garrett Storm, Elizabeth Streeten, Jessica Lasky Su, Yun Ju Sung, Jody Sylvia, Adam Szpiro, Daniel Taliun, Hua Tang, Margaret Taub, Kent Taylor, Matthew Taylor, Simeon Taylor, Marilyn Telen, Timothy A. Thornton, Machiko Threlkeld, Lesley Tinker, David Tirschwell, Sarah Tishkoff, Hemant Tiwari, Catherine Tong, Russell Tracy, Michael Tsai, Dhananjay Vaidya, Peter VandeHaar, Scott Vrieze, Tarik Walker, Robert Wallace, Avram Walts, Fei Fei Wang, Heming Wang, Jiongming Wang, Karol Watson, Jennifer Watt, Daniel E. Weeks, Joshua Weinstock, Bruce Weir, Lu-Chen Weng, Jennifer Wessel, Cristen Willer, Kayleen Williams, L. Keoki Williams, Scott Williams, Carla Wilson, James Wilson, Lara Winterkorn, Quenna Wong, Baojun Wu, Joseph Wu, Huichun Xu, Lisa Yanek, Ivana Yang, Ketian Yu, Seyedeh Maryam Zekavat, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiaofeng Zhu, Elad Ziv, Michael Zody, and Sebastian Zoellner
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EWAS ,DNA methylation ,IgE ,Asthma ,RNA-Sequencing ,Mendelian randomization ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P
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- 2023
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41. Cold-atom clock based on a diffractive optic
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Elvin, Rachel, Hoth, Gregory W., Wright, Michael, Lewis, Ben, McGilligan, James P., Arnold, Aidan S., Griffin, Paul F., and Riis, Erling
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Physics - Atomic Physics - Abstract
Clocks based on cold atoms offer unbeatable accuracy and long-term stability, but their use in portable quantum technologies is hampered by a large physical footprint. Here, we use the compact optical layout of a grating magneto-optical trap (gMOT) for a precise frequency reference. The gMOT collects $10^7$ $^{87}$Rb atoms, which are subsequently cooled to $20\,\mu$K in optical molasses. We optically probe the microwave atomic ground-state splitting using lin$\perp$lin polarised coherent population trapping and a Raman-Ramsey sequence. With ballistic drop distances of only $0.5\,$mm, the measured short-term fractional frequency stability is $2 \times 10 ^{-11} /\sqrt{\tau}$., Comment: 8 pages, 4 figures
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- 2019
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42. Multi-axis atom interferometer gyroscope with a single source of atoms
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Chen, Yun-Jhih, Hansen, Azure, Hoth, Gregory W., Ivanov, Eugene, Pelle, Bruno, Kitching, John, and Donley, Elizabeth A.
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Physics - Atomic Physics - Abstract
Using the technique of point source atom interferometry, we characterize the sensitivity of a multi-axis gyroscope based on free-space Raman interrogation of a single source of cold atoms in a glass vacuum cell. The instrument simultaneously measures the acceleration in the direction of the Raman laser beams and the component of the rotation vector in the plane perpendicular to that direction. We characterize the sensitivities for the magnitude and direction of the rotation vector measurement, which are 0.033 $^{\circ}/\mathrm{s}$ and 0.27 $^{\circ}$ with one second averaging time, respectively. The sensitivity could be improved by increasing the Raman interrogation time, allowing the cold-atom cloud to expand further, correcting the fluctuations in the initial cloud shape, and reducing sources of technical noise. The unique ability of the PSI technique to measure the rotation vector in a plane may permit applications of atom interferometry such as tracking the precession of a rotation vector and gyrocompassing.
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- 2018
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43. COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.
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Lowe, Katherine E, Regan, Elizabeth A, Anzueto, Antonio, Austin, Erin, Austin, John HM, Beaty, Terri H, Benos, Panayiotis V, Benway, Christopher J, Bhatt, Surya P, Bleecker, Eugene R, Bodduluri, Sandeep, Bon, Jessica, Boriek, Aladin M, Boueiz, Adel Re, Bowler, Russell P, Budoff, Matthew, Casaburi, Richard, Castaldi, Peter J, Charbonnier, Jean-Paul, Cho, Michael H, Comellas, Alejandro, Conrad, Douglas, Costa Davis, Corinne, Criner, Gerard J, Curran-Everett, Douglas, Curtis, Jeffrey L, DeMeo, Dawn L, Diaz, Alejandro A, Dransfield, Mark T, Dy, Jennifer G, Fawzy, Ashraf, Fleming, Margaret, Flenaugh, Eric L, Foreman, Marilyn G, Fortis, Spyridon, Gebrekristos, Hirut, Grant, Sarah, Grenier, Philippe A, Gu, Tian, Gupta, Abhya, Han, MeiLan K, Hanania, Nicola A, Hansel, Nadia N, Hayden, Lystra P, Hersh, Craig P, Hobbs, Brian D, Hoffman, Eric A, Hogg, James C, Hokanson, John E, Hoth, Karin F, Hsiao, Albert, Humphries, Stephen, Jacobs, Kathleen, Jacobson, Francine L, Kazerooni, Ella A, Kim, Victor, Kim, Woo Jin, Kinney, Gregory L, Koegler, Harald, Lutz, Sharon M, Lynch, David A, MacIntye, Neil R, Make, Barry J, Marchetti, Nathaniel, Martinez, Fernando J, Maselli, Diego J, Mathews, Anne M, McCormack, Meredith C, McDonald, Merry-Lynn N, McEvoy, Charlene E, Moll, Matthew, Molye, Sarah S, Murray, Susan, Nath, Hrudaya, Newell, John D, Occhipinti, Mariaelena, Paoletti, Matteo, Parekh, Trisha, Pistolesi, Massimo, Pratte, Katherine A, Putcha, Nirupama, Ragland, Margaret, Reinhardt, Joseph M, Rennard, Stephen I, Rosiello, Richard A, Ross, James C, Rossiter, Harry B, Ruczinski, Ingo, San Jose Estepar, Raul, Sciurba, Frank C, Sieren, Jessica C, Singh, Harjinder, Soler, Xavier, Steiner, Robert M, Strand, Matthew J, Stringer, William W, Tal-Singer, Ruth, Thomashow, Byron, Vegas Sánchez-Ferrero, Gonzalo, and Walsh, John W
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COPD Genetic Epidemiology study ,preserved ratio-impaired spirometry ,COPD diagnosis ,COPD diagnosis ,COPDGene ,GOLD ,Global initiative for chronic Obstructive Lung Dis ,PRISm ,chronic obstructive pulmonary disease ,copd ,preserved ratio-impaired spirometry ,spirometry ,Prevention ,Tobacco Smoke and Health ,Tobacco ,Lung ,Chronic Obstructive Pulmonary Disease ,Biomedical Imaging ,Clinical Research ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Respiratory ,Good Health and Well Being ,COPD ,COPD Genetic Epidemiology study ,Global initiative for chronic Obstructive Lung Disease - Abstract
BackgroundChronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.MethodsFour key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.ResultsUsing smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.ConclusionsA substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.
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- 2019
44. B‐cell receptors of EBV‐negative Burkitt lymphoma bind modified isoforms of autoantigens
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Theresa Bock, Moritz Bewarder, Onur Cetin, Natalie Fadle, Evi Regitz, Eva C. Schwarz, Jana Held, Sophie Roth, Stefan Lohse, Thorsten Pfuhl, Rabea Wagener, Sigrun Smola, Sören L. Becker, Rainer Maria Bohle, Lorenz Trümper, Reiner Siebert, Martin‐Leo Hansmann, Michael Pfreundschuh, Hans G. Drexler, Markus Hoth, Boris Kubuschok, Klaus Roemer, Klaus‐Dieter Preuss, Sylvia Hartmann, and Lorenz Thurner
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atypical post‐translationally modified isoforms ,autoantigens ,BCR ,Burkitt lymphoma ,immunotoxins ,neoantigens ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Burkitt lymphoma (BL) represents the most aggressive B‐cell‐lymphoma. Beside the hallmark of IG‐MYC‐translocation, surface B‐cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra‐nodal sites suggest antigenic triggers. To explore this hypothesis, BCRs of BL cell lines and cases were screened for reactivities against a panel of bacterial lysates, lysates of Plasmodium falciparum, a custom‐made virome array and against self‐antigens, including post‐translationally modified antigens. An atypically modified, SUMOylated isoform of Bystin, that is, SUMO1‐BYSL was identified as the antigen of the BCR of cell line CA46. SUMO1‐BYSL was exclusively expressed in CA46 cells with K139 as site of the SUMOylation. Secondly, an atypically acetylated isoform of HSP40 was identified as the antigen of the BCR of cell line BL41. K104 and K179 were the sites of immunogenic acetylation, and the acetylated HSP40 isoform was solely present in BL41 cells. Functionally, addition of SUMO1‐BYSL and acetylated HSP40 induced BCR pathway activation in CA46 and BL41 cells, respectively. Accordingly, SUMO1‐BYSL‐ETA’ immunotoxin, produced by a two‐step intein‐based conjugation, led to the specific killing of CA46 cells. Autoantibodies directed against SUMO1‐BYSL were found in 3 of 14 (21.4%), and autoantibodies against acetylated HSP40 in 1/14(7.1%) patients with sporadic Burkitt‐lymphoma. No reactivities against antigens of the infectious agent spectrum could be observed. These results indicate a pathogenic role of autoreactivity evoked by immunogenic post‐translational modifications in a subgroup of sporadic BL including two EBV‐negative BL cell lines.
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- 2022
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45. Artisanal gold mine spoil types within a common geological area and their variations in contaminant loads and human health risks
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Mensah, Martin Kofi, Drebenstedt, Carsten, Hoth, Nils, Ola, Ibukun Momoriola, Okoroafor, Precious Uchenna, and Wiafe, Edward Debrah
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- 2023
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46. Fencing affects movement patterns of two large carnivores in Southern Africa
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Dipanjan Naha, Stéphanie Périquet, J. Werner Kilian, Caitlin A. Kupferman, Tammy Hoth-Hanssen, and James C. Beasley
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carnivore ,conservation ,human–wildlife conflicts ,spatial ecology ,movement ,lion ,Evolution ,QH359-425 ,Ecology ,QH540-549.5 - Abstract
The erection of peripheral fences around protected areas has been shown to adversely affect the movement behavior, genetic connectivity and long-term viability of animal populations. However, fencing is also used extensively to reduce human encroachment, limit poaching activities, and mitigate human–wildlife conflicts. Limited information on the movement behavior of carnivores is available along the periphery of protected areas, particularly in semi-arid environments. To quantify the potential effects of the 824 km perimeter fence surrounding the Etosha National Park (Etosha, Namibia) on the movement and space use of carnivores, we collected GPS movement data from 36 lions (Panthera leo) and seven spotted hyenas (Crocuta crocuta) over a 14-year period. For these two apex carnivores, we measured the impact of the Etosha fence on their movements (step lengths and path straightness), calculated the likelihood of fence crossings, and evaluated the spatial–temporal characteristics of these crossings. Our results indicated that lions and hyenas moved faster (longer step lengths) when closer to the fence. Lions showed no variation in path straightness with respect to the fence but hyenas had straighter movement paths when closer to the fence. When moving within the vicinity of the fence, lions had a 9% likelihood of crossing the fence, while hyenas were much more likely (18%) to do so, which suggests that the Etosha fence was more permeable for hyenas than for lions. Fence crossings predominantly occurred at night for both species. Lions were more likely to cross the fence during the cold dry season (May–August) whereas hyenas crossed more often during the warm wet season (December–April). Female and adult lions had a higher probability of crossing the fence than males and subadults. These findings could be useful in the development of appropriate strategies to mitigate human–carnivore conflicts and thus promote the conservation of carnivores in multiple-use areas along the periphery of the park. Further research is needed to better elucidate the impact of perimeter fences on a broader suite of carnivores and other large mammals, including species-specific variation in the response to fences, as well as the economic benefits of fencing provided to local communities.
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- 2023
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47. B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma
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Lorenz Thurner, Natalie Fadle, Evi Regitz, Sophie Roth, Onur Cetin, Igor Age Kos, Simon Mauro Hess, Julia Bein, Rainer Maria Bohle, Martine Vornanen, Christer Sundström, Laurence de Leval, Enrico Tiacci, Peter Borchmann, Andreas Engert, Viola Poeschel, Gerhard Held, Eva C. Schwarz, Frank Neumann, Klaus-Dieter Preuss, Markus Hoth, Ralf Küppers, Karola Lehman, Martin-Leo Hansmann, Sören L. Becker, Moritz Bewarder, and Sylvia Hartmann
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA’-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.
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- 2023
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48. Cognitive function and inhaler technique following recovery from exacerbations of COPD
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Benjamin E. Henkle, Rebecca L. Freese, Mary Dahlheimer, Catherine Kane, Karin F. Hoth, and Ken M. Kunisaki
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Medicine - Published
- 2023
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49. The calcium channel modulator 2-APB hydrolyzes in physiological buffers and acts as an effective radical scavenger and inhibitor of the NADPH oxidase 2
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Ewa Jasmin Slowik, Katerina Stankoska, Nhat Nguyen Bui, Bastian Pasieka, David Conrad, Josef Zapp, Markus Hoth, Ivan Bogeski, and Reinhard Kappl
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2-APB ,Ca-signaling ,Reactive oxygen species (ROS) ,Hydrolysis ,Degradation ,NOX inhibition ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
2-aminoethoxydiphenyl borate (2-APB) is commonly used as a tool to modulate calcium signaling in physiological studies. 2-APB has a complex pharmacology and acts as activator or inhibitor of a variety of Ca2+ channels and transporters. While unspecific, 2-APB is one of the most-used agents to modulate store-operated calcium entry (SOCE) mediated by the STIM-gated Orai channels. Due to its boron core structure, 2-APB tends to readily hydrolyze in aqueous environment, a property that results in a complex physicochemical behavior. Here, we quantified the degree of hydrolysis in physiological conditions and identified the hydrolysis products diphenylborinic acid and 2-aminoethanol by NMR. Notably, we detected a high sensitivity of 2-APB/diphenylborinic acid towards decomposition by hydrogen peroxide to compounds such as phenylboronic acid, phenol, and boric acid, which were, in contrast to 2-APB itself and diphenylborinic acid, insufficient to affect SOCE in physiological experiments. Consequently, the efficacy of 2-APB as a Ca2+ signal modulator strongly depends on the reactive oxygen species (ROS) production within the experimental system. The antioxidant behavior of 2-APB towards ROS and its resulting decomposition are inversely correlated to its potency to modulate Ca2+ signaling as shown by electron spin resonance spectroscopy (ESR) and Ca2+ imaging. Finally, we observed a strong inhibitory effect of 2-APB, i.e., its hydrolysis product diphenylborinic acid, on NADPH oxidase (NOX2) activity in human monocytes. These new 2-APB properties are highly relevant for Ca2+ and redox signaling studies and for pharmacological application of 2-APB and related boron compounds.
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- 2023
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50. Sicherheitsaspekte und Vorbereitung zur Notfallvorsorge und Gefahrenabwehr in Kliniken bei MANV/TerrorMANV: Ausblick auf zukünftige Herausforderungen anhand von Umfrageergebnissen zur 3. Notfallkonferenz der DGU
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Hoth, Patrick, Bieler, Dan, Friemert, Benedikt, Franke, Axel, Blätzinger, Markus, and Achatz, Gerhard
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- 2022
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