Medicine and Health Sciences Commons^™

Computationally Driven Discovery Of Sars-Cov-2 M Pro Inhibitors: From Design To Experimental Validation, Léa El Khoury, Jay W Ponder, Et Al

2020-Current year OA Pubs

We report a fast-track computationally driven discovery of new SARS-CoV-2 main protease (M

Stronger Microstructural Damage Revealed In Multiple Sclerosis Lesions With Central Vein Sign By Quantitative Gradient Echo Mri, Victoria A Levasseur, Biao Xiang, Amber Salter, Dmitriy A Yablonskiy, Anne H Cross

2020-Current year OA Pubs

BACKGROUND: Multiple sclerosis (MS) lesions typically form around a central vein that can be visualized with FLAIR* MRI, creating the central vein sign (CVS) which may reflect lesion pathophysiology. Herein we used gradient echo plural contrast imaging (GEPCI) MRI to simultaneously visualize CVS and measure tissue damage in MS lesions. We examined CVS in relation to tissue integrity in white matter (WM) lesions and among MS subtypes.

OBJECTIVE: We aimed to determine if CVS positive lesions were specific to MS subtype, if CVS can be detected consistently among readers using the GEPCI method, and if there were differences in tissue …

Prospectively Defined Patterns Of Apobec3a Mutagenesis Are Prevalent In Human Cancers, Rachel A Deweerd, Eszter Németh, Ádám Póti, Nataliya Petryk, Chun-Long Chen, Olivier Hyrien, Dávid Szüts, Abby M Green

2020-Current year OA Pubs

Mutational signatures defined by single base substitution (SBS) patterns in cancer have elucidated potential mutagenic processes that contribute to malignancy. Two prevalent mutational patterns in human cancers are attributed to the APOBEC3 cytidine deaminase enzymes. Among the seven human APOBEC3 proteins, APOBEC3A is a potent deaminase and proposed driver of cancer mutagenesis. In this study, we prospectively examine genome-wide aberrations by expressing human APOBEC3A in avian DT40 cells. From whole-genome sequencing, we detect hundreds to thousands of base substitutions per genome. The APOBEC3A signature includes widespread cytidine mutations and a unique insertion-deletion (indel) signature consisting largely of cytidine deletions. This …

Rationally Designed Immunogens Enable Immune Focusing Following Sars-Cov-2 Spike Imprinting, Blake M Hauser, Maya Sangesland, Kerri J St Denis, Evan C Lam, James Brett Case, Ian W Windsor, Jared Feldman, Timothy M Caradonna, Ty Kannegieter, Michael S Diamond, Alejandro B Balazs, Daniel Lingwood, Aaron G Schmidt

2020-Current year OA Pubs

Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased …

Btla Signaling In Conventional And Regulatory Lymphocytes Coordinately Tempers Humoral Immunity In The Intestinal Mucosa, Caroline Stienne, Richard Virgen-Slane, Lisa Elmén, Marisol Veny, Sarah Huang, Jennifer Nguyen, Elizabeth Chappell, Mary Olivia Balmert, Jr-Wen Shui, Michelle A Hurchla, Mitchell Kronenberg, Scott N Peterson, Kenneth M Murphy, Carl F Ware, John R Šedý

2020-Current year OA Pubs

The Btla inhibitory receptor limits innate and adaptive immune responses, both preventing the development of autoimmune disease and restraining anti-viral and anti-tumor responses. It remains unclear how the functions of Btla in diverse lymphocytes contribute to immunoregulation. Here, we show that Btla inhibits activation of genes regulating metabolism and cytokine signaling, including Il6 and Hif1a, indicating a regulatory role in humoral immunity. Within mucosal Peyer's patches, we find T-cell-expressed Btla-regulated Tfh cells, while Btla in T or B cells regulates GC B cell numbers. Treg-expressed Btla is required for cell-intrinsic Treg homeostasis that subsequently controls GC B cells. Loss of …

Clinical Outcomes Of Patients With Unresectable Primary Liver Cancer Treated With Yttrium-90 Radioembolization With An Escalated Dose, Re-I Chin, Anirudh Bommireddy, Tyler J Fraum, Daniel R Ludwig, Yi Huang, Jacqueline E Zoberi, Jose L Garcia-Ramirez, Nichole M Maughan, William Chapman, Kevin Korenblat, Lauren E Henke, Hyun Kim, Shahed N Badiyan

2020-Current year OA Pubs

PURPOSE: Yttrium-90 (90Y) radioembolization with an escalated dose has been shown to improve clinical outcomes compared with standard dose radioembolization, but there are few data on the local control of primary liver tumors. We reported the clinical outcomes of patients with unresectable primary liver tumors treated with 90Y radioembolization with an escalated dose.

METHODS AND MATERIALS: Clinical data of patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and biphenotypic tumors (cHCC-CC) treated with radioembolization with an escalated dose (≥150 Gy) between 2013 and 2020 with >3 months follow-up were retrospectively reviewed. The primary endpoint was freedom from local progression. Clinical …

Domain-General Cognitive Motivation: Evidence From Economic Decision-Making - Final Registered Report, Jennifer L Crawford, Sarah A Eisenstein, Jonathan E Peelle, Todd S Braver

2020-Current year OA Pubs

Stable individual differences in cognitive motivation (i.e., the tendency to engage in and enjoy effortful cognitive activities) have been documented with self-report measures, yet convergent support for a trait-level construct is still lacking. In the present study, we used an innovative decision-making paradigm (COG-ED) to quantify the costs of cognitive effort, a metric of cognitive motivation, across two distinct cognitive domains: working memory (an N-back task) and speech comprehension (understanding spoken sentences in background noise). We hypothesized that cognitive motivation operates similarly within individuals, regardless of domain. Specifically, in 104 adults aged 18-40 years, we tested whether individual differences in …

Prevalence And Perception Of Substance Abuse And Associated Economic Indicators And Mental Health Disorders In A Large Cohort Of Kenyan Students: Towards Integrated Public Health Approach And Clinical Management, Victoria N Mutiso, David M Ndetei, Esther N Muia, Christine Musyimi, Tom L Osborn, Rita Kasike, Lydia Onsinyo, Jane Mbijjiwe, Pamela Karambu, Andre Sounders, John R Weisz, Monica H Swahn, Daniel Mamah

2020-Current year OA Pubs

BACKGROUND: The earlier younger people begin to use drugs, the more vulnerable they become to both their short term and long-term harmful effects. The overall aim of this study is to determine the prevalence of alcohol and drug abuse, the socio-demographic characteristic, perception of abuse and associated economic indicators and mental disorders and how they inform potential intervention in a cohort of Kenyan students.

METHODS: This was a cross-sectional study on a total of 9742 high school, college and university students. We used tools to document socio-demographic characteristics, economic indicators, drug and alcohol use and related perceptions and Diagnostic and …

Impact Of The Covid-19 Pandemic On Patients Without Covid-19 With Acute Myocardial Infarction And Heart Failure, Daniel K Fox, R J Waken, Daniel Y Johnson, Gmerice Hammond, Jonathan Yu, Erika Fanous, Thomas M Maddox, Karen E Joynt Maddox

2020-Current year OA Pubs

Background Excess mortality from cardiovascular disease during the COVID-19 pandemic has been reported. The mechanism is unclear but may include delay or deferral of care, or differential treatment during hospitalization because of strains on hospital capacity. Methods and Results We used emergency department and inpatient data from a 12-hospital health system to examine changes in volume, patient age and comorbidities, treatment (right- and left-heart catheterization), and outcomes for patients with acute myocardial infarction (AMI) and heart failure (HF) during the COVID-19 pandemic compared with pre-COVID-19 (2018 and 2019), controlling for seasonal variation. We analyzed 27 427 emergency department visits or …

Metronidazole Treatment Rapidly Reduces Genital Inflammation Through Effects On Bacterial Vaginosis-Associated Bacteria Rather Than Lactobacilli, Eric Armstrong, Hilary Reno, Et Al.

2020-Current year OA Pubs

BackgroundBacterial vaginosis (BV) causes genital inflammation and increases HIV risk, whereas a vaginal microbiota dominated by Lactobacillus species is associated with immune quiescence and relative HIV protection. BV treatment reduces genital inflammation, but it is unclear whether this reduction is driven by a decrease in BV-associated bacteria or an increase in Lactobacillus species.METHODSTo evaluate the short-term effect of standard BV treatment on genital immunology and the vaginal microbiota, vaginal swabs were collected immediately before and after metronidazole treatment for BV and analyzed with multiplex ELISA, metagenomic sequencing, and quantitative PCR.RESULTSTopical metronidazole treatment rapidly reduced vaginal levels of proinflammatory cytokines, chemokines, …

L-Plastin Enhances Nlrp3 Inflammasome Assembly And Bleomycin-Induced Lung Fibrosis, Hemant Joshi, Alison Almgren-Bell, Edgar P Anaya, Elizabeth M Todd, Steven J Van Dyken, Anushree Seth, Katherine M Mcintire, Srikanth Singamaneni, Fayyaz Sutterwala, Sharon C Morley

2020-Current year OA Pubs

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions …

Durable Reduction Of Clostridioides Difficile Infection Recurrence And Microbiome Restoration After Treatment With Rbx2660: Results From An Open-Label Phase 2 Clinical Trial, Robert Orenstein, Erik R Dubberke, Sahil Khanna, Christine H Lee, David Yoho, Stuart Johnson, Gail Hecht, Herbert L Dupont, Dale N Gerding, Ken F Blount, Sarah Mische, Adam Harvey

2020-Current year OA Pubs

BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.

METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered …

The Targeted Smac Mimetic Sw Iv-134 Augments Platinum-Based Chemotherapy In Pre-Clinical Models Of Ovarian Cancer, Pratibha S Binder, Yassar M Hashim, James Cripe, Tommy Buchanan, Abigail Zamorano, Suwanna Vangveravong, David G Mutch, William G Hawkins, Matthew A Powell, Dirk Spitzer

2020-Current year OA Pubs

BACKGROUND: Ovarian cancer is initially responsive to frontline chemotherapy. Unfortunately, it often recurs and becomes resistant to available therapies and the survival rate for advanced and recurrent ovarian cancer is unacceptably low. We thus hypothesized that it would be possible to achieve more durable treatment responses by combining cisplatin chemotherapy with SW IV-134, a cancer-targeted peptide mimetic and inducer of cell death. SW IV-134 is a recently developed small molecule conjugate linking a sigma-2 ligand with a peptide analog (mimetic) of the intrinsic death pathway activator SMAC (second-mitochondria activator of caspases). The sigma-2 receptor is overexpressed in ovarian cancer and …

Towards A Biological Definition Of Ards: Are Treatable Traits The Solution?, Lieuwe D J Bos, John G Laffey, Lorraine B Ware, Nanon F L Heijnen, Pratik Sinha, Brijesh Patel, Matthieu Jabaudon, Julie A Bastarache, Daniel F Mcauley, Charlotte Summers, Carolyn S Calfee, Manu Shankar-Hari

2020-Current year OA Pubs

The pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation of protein-rich pulmonary edema in the air spaces and interstitial areas of the lung, variable degrees of epithelial injury, variable degrees of endothelial barrier disruption, transmigration of leukocytes, alongside impaired fluid and ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range of pharmacological interventions targeting these pathophysiological processes have failed to improve patient outcomes. In this manuscript, our goal is to provide a narrative summary of the potential methods to capture the underlying …

Agrobacterium Species Bacteraemia, Switzerland, 2008 To 2019: A Molecular Epidemiological Study, Lisa Balmer, Helena M B Seth-Smith, Adrian Egli, Carlo Casanova, Andreas Kronenberg, Jacques Schrenzel, Jonas Marschall, Rami Sommerstein

2020-Current year OA Pubs

BACKGROUND: Agrobacterium spp. are infrequent agents of bloodstream infections linked to healthcare-associated outbreaks. However, it is unclear if outbreaks also occur across larger geographic areas. Triggered by two local clusters from putative point sources, our aim was to detect potential additional clusters in Switzerland.

METHODS: We performed a nationwide descriptive study of cases in Switzerland based on a prospective surveillance system (Swiss Centre for Antibiotic Resistance, anresis.ch), from 2008 to 2019. We identified patients with Agrobacterium spp. isolated from blood cultures and used a survey to collect clinical-epidemiological information and susceptibility testing results. We performed whole genome sequencing (WGS) of …

A Stakeholder-Driven Method For Selecting Implementation Strategies: A Case Example Of Pediatric Hypertension Clinical Practice Guideline Implementation, Ashley A Knapp, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: This article provides a generalizable method, rooted in co-design and stakeholder engagement, to identify, specify, and prioritize implementation strategies. To illustrate this method, we present a case example focused on identifying strategies to promote pediatric hypertension (pHTN) Clinical Practice Guideline (CPG) implementation in community health center-based primary care practices that involved meaningful engagement of pediatric clinicians, clinic staff, and patients/caregivers. This example was chosen based on the difficulty clinicians and organizations experience in implementing the pHTN CPG, as evidenced by low rates of guideline-adherent pHTN diagnosis and treatment.

METHODS: We convened a Stakeholder Advisory Panel (SAP), comprising 6 pediatricians …

Strainge: A Toolkit To Track And Characterize Low-Abundance Strains In Complex Microbial Communities, Lucas R Van Dijk, Bruce J Walker, Timothy J Straub, Colin J Worby, Alexandra Grote, Henry L Schreiber 4th, Christine Anyansi, Amy J Pickering, Scott J Hultgren, Abigail L Manson, Thomas Abeel, Ashlee M Earl

2020-Current year OA Pubs

Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.

Circular Rna Detection Identifies Circpsen1 Alterations In Brain Specific To Autosomal Dominant Alzheimer's Disease, Hsiang-Han Chen, Abdallah Eteleeb, Ciyang Wang, Maria Victoria Fernandez, John P Budde, Kristy Bergmann, Joanne Norton, Fengxian Wang, Curtis Ebl, John C Morris, Richard J Perrin, Randall J Bateman, Eric Mcdade, Chengjie Xiong, Alison Goate, Martin Farlow, Jasmeer Chhatwal, Peter R Schofield, Helena Chui, Oscar Harari, Carlos Cruchaga, Laura Ibanez, Dominantly Inherited Alzheimer Network

2020-Current year OA Pubs

BACKGROUND: Autosomal-dominant Alzheimer's disease (ADAD) is caused by pathogenic mutations in APP, PSEN1, and PSEN2, which usually lead to an early age at onset (<  65). Circular RNAs are a family of non-coding RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD.

METHODS: We obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts for PSEN1, PSEN2 and APP genes. Only circPSEN1 passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performed in-silico functional analyses using the Circular RNA interactome website and DIANA mirPath …

Sex-Based Differences In Functional Brain Activity During Working Memory In Survivors Of Pediatric Acute Lymphoblastic Leukemia, Kellen Gandy, Matthew A Scoggins, Nicholas Phillips, Ellen Van Der Plas, Slim Fellah, Lisa M Jacola, Ching-Hon Pui, Melissa M Hudson, Wilburn E Reddick, Ranganatha Sitaram, Kevin R Krull

2020-Current year OA Pubs

BACKGROUND: Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone.

METHODS: Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, …

Prediagnosis Leisure-Time Physical Activity And Lung Cancer Survival: A Pooled Analysis Of 11 Cohorts, Jae Jeong Yang, Yikyung Park, Et Al.

2020-Current year OA Pubs

BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients.

METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum …

Health-Related Quality Of Life, Symptoms, And Tolerability Of Loncastuximab Tesirine In Patients With Relapsed Or Refractory Diffuse Large B-Cell Lymphoma, Alexander Spira, Xiaolei Zhou, Lei Chen, Ari Gnanasakthy, Luqiang Wang, David Ungar, Rafael Curiel, Laura Liao, John Radford, Brad Kahl

2020-Current year OA Pubs

BACKGROUND: Loncastuximab tesirine has shown antitumor activity with an acceptable toxicity profile in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were relapsed or refractory after ≥2 prior therapies, including activity in patients with high-risk disease characteristics. This analysis examined health-related quality of life (HRQoL), symptoms, and tolerability in patients receiving loncastuximab tesirine for relapsed or refractory DLBCL.

PATIENTS AND METHODS: The single-arm, open-label phase II LOTIS-2 study (ADCT-402-201; NCT03589469) enrolled 145 patients aged ≥18 years. Patients received loncastuximab tesirine as a 30-minute intravenous infusion on day 1 of each 3-week treatment cycle. Patient-reported outcomes were measured …

Segmental Colitis Associated With Diverticulosis Masquerading As Polyploid-Appearing Mucosa In The Rectosigmoid Area On Endoscopy And As Focal Thickening On Imaging, Eugene C. Nwankwo Jr, Gebran Khneizer, Gregory Sayuk, Jill Elwing, Necat Havlioglu, Michael Presti

Open Access Publications

Segmental colitis associated with diverticulosis (SCAD) is an inflammatory disease affecting segments of the large bowel with diverticular disease. SCAD presents several challenges in diagnoses and treatment because it often mimics a range of disorders including inflammatory bowel disease and malignancy. Here, we present the case of a 72-year-old man with lower abdominal pain and bloody stools whose initial abdominal workup showed nonspecific large bowel thickening and concerns for malignancy. Ultimately, the patient was diagnosed with mild SCAD and treated conservatively with a resolution of symptoms. He had no symptoms at the three-month and 1-year follow-ups. This case highlights the …

Enhanced Immunoprecipitation Techniques For The Identification Of Rna-Binding Protein Partners: Igf2bp1 Interactions In Mammary Epithelial Cells, Saja A Fakhraldeen, Scott M Berry, David J Beebe, Avtar Roopra, Celia M Bisbach, Vladimir S Spiegelman, Natalie M Niemi, Caroline M Alexander

2020-Current year OA Pubs

RNA-binding proteins (RBPs) regulate the expression of large cohorts of RNA species to produce programmatic changes in cellular phenotypes. To describe the function of RBPs within a cell, it is key to identify their mRNA-binding partners. This is often done by crosslinking nucleic acids to RBPs, followed by chemical release of the nucleic acid fragments for analysis. However, this methodology is lengthy, which involves complex processing with attendant sample losses, thus large amounts of starting materials and prone to artifacts. To evaluate potential alternative technologies, we tested "exclusion-based" purification of immunoprecipitates (IFAST or SLIDE) and report here that these methods …

Outcomes Of Acute Versus Subacute Scapholunate Ligament Repair, Raymond E Chen, Ryan P Calfee, Jeffrey G Stepan, Daniel A Osei

2020-Current year OA Pubs

PURPOSE: This study investigated the long-term outcomes of direct scapholunate ligament (SLL) repairs with or without dorsal capsulodesis performed within 6 weeks (acute repair) of a SLL tear versus 6 to 12 weeks following injury (subacute repair).

METHODS: A review of medical records from April 1996 to April 2012 identified 24 patients who underwent SLL repair (12 acute, 12 subacute). Patients returned to the clinic for radiographic examinations of the injured wrist, standardized physical examinations, and validated questionnaires.

RESULTS: The mean follow-up times for the acute and subacute groups were 7.2 and 6.2 years, respectively. At the final examination, patients …

Longitudinal And Cross-Sectional Validation Of The Wercap Screen For Assessing Psychosis Risk And Conversion, Daniel Mamah, Victoria N Mutiso, David M Ndetei

2020-Current year OA Pubs

BACKGROUND: The Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen was developed to assess risk for developing psychosis. Its validity has not been investigated in a large population-based study or with longitudinal analyses.

METHODS: 825 participants, aged 14-25, were recruited from Kenya. Symptoms were assessed using the WERCAP Screen, as experienced over the prior 3-months (3MO), 12-months (12MO) or lifetime (LIF). ROC curve analysis was used to determine the validity of the WERCAP Screen against the Structured Interview of Psychosis-Risk Syndromes. Longitudinal validity was assessed by comparing baseline p-WERCAP scores in psychotic disorder converters and non-converters, and using ROC …

Pharmacological Chaperones For The Oxytocin Receptor Increase Oxytocin Responsiveness In Myometrial Cells, Manasi Malik, Yingye Fang, Monali Wakle-Prabagaran, Michelle Roh, Kevin Prifti, Antonina I Frolova, Princess I Imoukhuede, Sarah K England

2020-Current year OA Pubs

Oxytocin is a potent uterotonic agent administered to nearly all patients during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin. Previously, we showed that the V281M variant in the oxytocin receptor (OXTR) gene impairs OXTR trafficking to the cell surface, leading to a decreased oxytocin response in cells. Here, we sought to identify pharmacological chaperones that increased oxytocin response in cells expressing WT or …

Treatment Patterns And Overall Survival Outcomes Among Patients Aged 80 Yr Or Older With High-Risk Prostate Cancer, Benjamin W Fischer-Valuck, Brian C. Baumann, Ryan Mueller, Randall J. Brenneman, Jeff M. Michalski, Hiram A. Gay, Et Al.

2020-Current year OA Pubs

BACKGROUND: Elderly patients diagnosed with high-risk prostate cancer (PCa) present a therapeutic dilemma of balancing treatment of a potentially lethal malignancy with overtreatment of a cancer that may not threaten life expectancy.

OBJECTIVE: To investigate treatment patterns and overall survival outcomes in this group of patients.

DESIGN SETTING AND PARTICIPANTS: A retrospective cohort study was conducted. We queried the National Cancer Database for high-risk PCa in patients aged 80 yr or older diagnosed during 2004-2016.

INTERVENTION: Eligible patients underwent no treatment following biopsy (ie, observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or surgery.

OUTCOME …

Comparison Of Performance Of Psychiatrists Vs Other Outpatient Physicians In The 2020 Us Medicare Merit-Based Incentive Payment System, Andrew C Qi, Karen E Joynt Maddox, Laura J Bierut, Kenton J Johnston

2020-Current year OA Pubs

Importance: Medicare's Merit-Based Incentive Payment System (MIPS) is a new, mandatory, outpatient value-based payment program that ties reimbursement to performance on cost and quality measures for many US clinicians. However, it is currently unknown how the program measures the performance of psychiatrists, who often treat a different patient case mix with different clinical considerations than do other outpatient clinicians.

Objective: To compare performance scores and value-based reimbursement for psychiatrists vs other outpatient physicians in the 2020 MIPS.

Design Setting and Participants: In this cross-sectional study, the Centers for Medicare & Medicaid Services Provider Data Catalog was used to identify outpatient …

Reproducible Brain-Wide Association Studies Require Thousands Of Individuals, Scott Marek, David F Montez, Benjamin P Kay, Alexander S Hatoum, Meghan Rose Donohue, Ryland L Miller, Sridhar Kandala, Dillan J Newbold, Annie Zheng, Nicole A Seider, Andrew N Van, Athanasia Metoki, Timothy O Laumann, Steven E Petersen, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions

Trabecular Meshwork Mitochondrial Function And Oxidative Stress: Clues To Racial Disparities Of Glaucoma, Hongli Wu, Ying-Bo Shui, Ying Liu, Xiaobin Liu, Carla J Siegfried

2020-Current year OA Pubs

PURPOSE: To identify racial differences of oxidative damage and stress and mitochondrial function in human trabecular meshwork (TM).

DESIGN: Experimental study.

PARTICIPANTS: One hundred seventy-three eyes of 173 patients undergoing intraocular surgery provided aqueous humor (AH) for analysis. Trabecular meshwork tissues from eye bank donors were used as healthy controls for primary cell culture.

METHODS: Enzyme-linked immunosorbent assay methods were used to measure 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative damage marker, in AH comparing Black and White Americans. Human TM primary cultured cells from Black and White donors were used for adenosine triphosphate (ATP) measurement under high and low oxygen culture conditions. …