Digital Commons Network^™

Clinical And Molecular Response To Tebentafusp In Previously Treated Patients With Metastatic Uveal Melanoma: A Phase 2 Trial, Richard D Carvajal, Leonel Hernandez-Aya, Et Al.

2020-Current year OA Pubs

In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% with a median overall survival of 7.8 months. We conducted a multicenter, single-arm, open-label phase 2 study of tebentafusp, a soluble T cell receptor bispecific (gp100×CD3), in 127 patients with treatment-refractory metastatic uveal melanoma (NCT02570308). The primary endpoint was the estimation of objective response rate based on RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Secondary objectives included safety, overall survival, progression-free survival and disease control rate. All patients had at least one treatment-related adverse event, with rash (87%), pyrexia (80%) and pruritus …

Ho'ouna Pono Implementation: Applying Concept Mapping To A Culturally Grounded Substance Use Prevention Curriculum In Rural Hawai'i Schools, Kelsie H Okamura, Scott K Okamoto, Sarah Momilani Marshall, Steven Keone Chin, Pamela M Garcia, Byron J Powell, Kelly A Stern, Sara J Becker, David S Mandell

2020-Current year OA Pubs

BACKGROUND: Despite their potential to ameliorate health disparities and address youth substance use, prevention programs have been poorly disseminated and implemented across Hawai'i, which begs the question: Why are effective prevention programs not being used in communities most in need of them? Implementing and sustaining culturally grounded prevention programs is critical to address equitable healthcare and minimize health disparities in communities. The field of implementation science provides frameworks, theories, and methods to examine factors associated with community adoption of these programs.

METHOD: Our project applies concept mapping methods to a culturally grounded youth drug prevention program with state level educational …

Collaborative Quality Improvement Strategy In Secondary Prevention Of Cardiovascular Disease In India: Findings From A Multi-Stakeholder, Qualitative Study Using Consolidated Framework For Implementation Research (Cfir), Kavita Singh, Mark D. Huffman, Leslie C M Johnson, Nikhil Tandon, Dorairaj Prabhakaran, Emily Mendenhall

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care.

OBJECTIVE: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India.

METHODS: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to …

Mesoscale Structure-Function Relationships In Mitochondrial Transcriptional Condensates, Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V Pappu, Tom Misteli

2020-Current year OA Pubs

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters …

Association Of Α-Klotho With Subclinical Carotid Atherosclerosis In Subjects With Type 1 Diabetes Mellitus, Esmeralda Castelblanco, Marta Hernández, Nuria Alonso, Aina Ribes-Betriu, Jordi Real, Minerva Granado-Casas, Joana Rossell, Marina Idalia Rojo-López, Adriana Silvia Dusso, Josep Julve, Didac Mauricio

2020-Current year OA Pubs

BACKGROUND: Compelling evidence suggests that the fibroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects.

METHODS: This cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque-matched, non-diabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine the presence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, …

Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, Margaret Sunitha Selvaraj, Lisa De Las Fuentes, Susan K. Dutcher, Et Al.

2020-Current year OA Pubs

No abstract provided.

Amyloid Β, Lipid Metabolism, Basal Cholinergic System, And Therapeutics In Alzheimer's Disease, Victoria Campos-Peña, Pavel Pichardo-Rojas, Talía Sánchez-Barbosa, Emma Ortíz-Islas, Citlali Ekaterina Rodríguez-Pérez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios

2020-Current year OA Pubs

The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each …

Blood Culture Utilization Practices Among Febrile And/Or Hypothermic Inpatients, Kap Sum Foong, Satish Munigala, Stephanie Kern-Allely, David K Warren

2020-Current year OA Pubs

BACKGROUND: Predictors associated with the decision of blood culture ordering among hospitalized patients with abnormal body temperature are still underexplored, particularly non-clinical factors. In this study, we evaluated the factors affecting blood culture ordering in febrile and hypothermic inpatients.

METHODS: We performed a retrospective study of 15,788 adult inpatients with fever (≥ 38.3℃) or hypothermia (< 36.0℃) from January 2016 to December 2017. We evaluated the proportion of febrile and hypothermic episodes with an associated blood culture performed within 24h. Generalized Estimating Equations were used to determine independent predictors associated with blood culture ordering among febrile and hypothermic inpatients.

RESULTS: We identified 21,383 abnormal body temperature episodes among 15,788 inpatients (13,093 febrile and 8,290 hypothermic episodes). Blood cultures were performed in 36.7% (7,850/ 21,383) of these episodes. Predictors for blood culture ordering among inpatients with abnormal body temperature included fever ≥ 39℃ (adjusted …

Occupational Characteristics Associated With Sars-Cov-2 Infection In The Uk Biobank During August-November 2020: A Cohort Study, Elizabeth L Yanik, Bradley A Evanoff, Ann Marie Dale, Yinjiao Ma, Karen E Walker-Bone

2020-Current year OA Pubs

BACKGROUND: Occupational exposures may play a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk. We used a job-exposure matrix linked to the UK Biobank to measure occupational characteristics and estimate associations with a positive SARS-CoV-2 test.

METHODS: People reporting job titles at their baseline interview in England who were < 65 years of age in 2020 were included. Healthcare workers were excluded because of differential access to testing. Jobs were linked to the US Occupational Information Network (O*NET) job exposure matrix. O*NET-based scores were examined for occupational physical proximity, exposure to diseases/infection, working outdoors exposed to weather, and working outdoors under cover (score range = 1-5). Jobs were classified as remote work using two algorithms. SARS-CoV-2 test results were evaluated between August 5th-November 10th, 2020, when the UK was released from lockdown. Cox regression was used to calculate adjusted hazard ratios (aHRs), accounting for age, sex, race, education, neighborhood deprivation, assessment center, household size, and income.

RESULTS: We included 115,451 people with job titles, of whom 1746 tested positive for SARS-CoV-2. A one-point increase in physical proximity score was associated with 1.14 times higher risk of SARS-CoV-2 (95%CI = 1.05-1.24). A one-point increase in the exposure to diseases/infections score was associated with 1.09 …

Global Variation In Isolated Posterior Cruciate Ligament Reconstruction, Derrick M Knapik, Varun Gopinatth, Garrett R Jackson, Jorge Chahla, Matthew V Smith, Matthew J Matava, Robert H Brophy

2020-Current year OA Pubs

PURPOSE: In the setting of persistent instability or failed non-operative management, surgical reconstruction is commonly recommended for isolated posterior cruciate ligament (PCL) tears. The purpose of this study was to systematically review published studies to evaluate regional variation in the epidemiology of and surgical approaches to primary, isolated PCL reconstruction.

METHODS: A systematic review was performed in June 2022 to identify studies examining operative techniques during primary, isolated PCL reconstruction. Collected variables consisted of reconstruction technique, graft type, graft source, tibial reconstruction technique, femoral and tibial drilling and fixation methods, and whether the remnant PCL was preserved or debrided. Studies …

Cellular Sources And Neuroprotective Roles Of Interleukin-10 In The Facial Motor Nucleus After Axotomy, Elizabeth M Runge, Deborah O Setter, Abhirami K Iyer, Eric J Regele, Felicia M Kennedy, Virginia M Sanders, Kathryn J Jones

2020-Current year OA Pubs

Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA.

Integrating A Patient Decision Aid Into The Electronic Health Record: A Case Report On The Implementation Of Breastchoice At 2 Sites, Clara N Lee, Janessa Sullivan, Randi Foraker, Terence M Myckatyn, Margaret A Olsen, Crystal Phommasathit, Jessica Boateng, Katelyn L Parrish, Milisa Rizer, Tim Huerta, Mary C Politi

2020-Current year OA Pubs

UNLABELLED: Patient decision aids can support shared decision making and improve decision quality. However, decision aids are not widely used in clinical practice due to multiple barriers. Integrating patient decision aids into the electronic health record (EHR) can increase their use by making them more clinically relevant, personalized, and actionable. In this article, we describe the procedures and considerations for integrating a patient decision aid into the EHR, based on the example of BREASTChoice, a decision aid for breast reconstruction after mastectomy. BREASTChoice's unique features include 1) personalized risk prediction using clinical data from the EHR, 2) clinician- and patient-facing …

Why Tic Severity Changes From Then To Now And From Here To There, Ann M Iverson, Kevin J. Black

2020-Current year OA Pubs

Much of the research regarding Tourette's syndrome (TS) has focused on why certain individuals develop tics while others do not. However, a separate line of research focuses on the momentary influences that cause tics to increase or decrease in patients who are already known to have TS or another chronic tic disorder (CTD). Environmental and internal variables such as fatigue, anxiety, and certain types of thoughts all have been shown to worsen tic severity and may even overcome the positive effects of treatment. Other influences such as stress, distraction, and being observed have had mixed effects in the various studies …

Multi-Trait Genome-Wide Association Study Of Opioid Addiction: Oprm1 And Beyond, Nathan Gaddis, Arpana Agrawal, Paul W Jeffries, Kathleen Bucholz, Elliot C Nelson, Laura Bierut, Et Al.

2020-Current year OA Pubs

Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (r

Spontaneous Activity Patterns In Human Motor Cortex Replay Evoked Activity Patterns For Hand Movements, Tomer Livne, Dohyun Kim, Nicholas V Metcalf, Lu Zhang, Lorenzo Pini, Gordon L Shulman, Maurizio Corbetta

2020-Current year OA Pubs

Spontaneous brain activity, measured with resting state fMRI (R-fMRI), is correlated among regions that are co-activated by behavioral tasks. It is unclear, however, whether spatial patterns of spontaneous activity within a cortical region correspond to spatial patterns of activity evoked by specific stimuli, actions, or mental states. The current study investigated the hypothesis that spontaneous activity in motor cortex represents motor patterns commonly occurring in daily life. To test this hypothesis 15 healthy participants were scanned while performing four different hand movements. Three movements (Grip, Extend, Pinch) were ecological involving grip and grasp hand movements; one control movement involving the …

A Bioresorbable Peripheral Nerve Stimulator For Electronic Pain Block, Geumbee Lee, Emily Ray, Sabrina Genovese, Ying Yan, Arman Odabas, Umang Khandpur, Wilson Z Ray, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, …

Integrating Transcriptomics, Metabolomics, And Gwas Helps Reveal Molecular Mechanisms For Metabolite Levels And Disease Risk, Xianyong Yin, Adam E Locke, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated. We performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results for 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from the FinnGen study. We found that genetic variants that regulate metabolite …

Continuous Npwt Regulates Fibrosis In Murine Diabetic Wound Healing, Mengfan Wu, Dany Y Matar, Zhen Yu, Ziyu Chen, Samuel Knoedler, Brian Ng, Oliver A Darwish, Sadaf Sohrabi, Leigh Friedman, Valentin Haug, George F Murphy, Yuval Rinkevich, Dennis P Orgill, Adriana C Panayi

2020-Current year OA Pubs

Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (

A Living Database Of Hiv Implementation Research (Live Project): Protocol For Rapid Living Reviews, Ingrid Eshun-Wilson, Nathan Ford, Noelle Le Tourneau, Stefan Baral, Sheree Schwartz, Christopher Kemp, Elvin Geng

2020-Current year OA Pubs

BACKGROUND: HIV implementation research evolves rapidly and is often complex and poorly characterized, which makes the synthesis of data on HIV implementation strategies inherently difficult. This is further compromised by prolonged data abstraction processes due to variable interventions, outcomes, and context, and delays in the publication of review findings; this can all result in outdated and irrelevant systematic reviews.

OBJECTIVE: The LIVE project (A Living Database of HIV Implementation Research) aims to overcome these challenges by applying an implementation science lens to the conduct of rapid living systematic reviews and meta-analyses to inform HIV service delivery priorities and guideline development. …

Unravelling The Reservoirs For Colonisation Of Infants With Campylobacter Spp. In Rural Ethiopia: Protocol For A Longitudinal Study During A Global Pandemic And Political Tensions, Arie H Havelaar, Mark J Manary, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for

METHODS AND ANALYSIS: This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water …

Antidepressant Use And Its Association With 28-Day Mortality In Inpatients With Sars-Cov-2: Support For The Fiasma Model Against Covid-19, Nicolas Hoertel, Angela M Reiersen, Eric J Lenze, Bradley A Fritz, Et Al.

2020-Current year OA Pubs

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant …

Association Between The Affordable Care Act Medicaid Expansion And Receipt Of Cardiac Resynchronization Therapy By Race And Ethnicity, Hunter Mwansa, Ibrahim Barry, Shannon M Knapp, Sula Mazimba, Elizabeth Calhoun, Nancy K Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

Background Black and Hispanic patients are less likely to receive cardiac resynchronization therapy (CRT) than White patients. Medicaid expansion has been associated with increased access to cardiovascular care among racial and ethnic groups with higher prevalence of underinsurance. It is unknown whether the Medicaid expansion was associated with increased receipt of CRT by race and ethnicity. Methods and Results Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington, DC, we analyzed 1061 patients from early-adopter states (Medicaid expansion by January 2014) and 745 patients from nonadopter states (no implementation 2013-2014). Estimates of change in …

Pan-Cancer Analysis Reveals Recurrent Bcar4 Gene Fusions Across Solid Tumors, Andrew Nickless, Jin Zhang, Ghofran Othoum, Jace Webster, Matthew J Inkman, Emily Coonrod, Sherron Fontes, Emily B Rozycki, Christopher A Maher, Nicole M White

2020-Current year OA Pubs

UNLABELLED: Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient …

A Non-Canonical Retina-Iprgcs-Scn-Pvt Visual Pathway For Mediating Contagious Itch Behavior, Fang Gao, Jun Ma, Yao-Qing Yu, Xiao-Fei Gao, Yang Bai, Yi Sun, Juan Liu, Xianyu Liu, Devin M Barry, Steven Wilhelm, Tyler Piccinni-Ash, Na Wang, Dongyang Liu, Yan Hao, Jin-Jing Jia, Qianyi Yang, Johan Van Nispen, Zhou-Feng Chen, Et Al.

2020-Current year OA Pubs

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival of social animals. Gastrin-releasing peptide (GRP) and its receptor (GRPR) in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates contagious itch behavior in mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual itch information, independently of melanopsin, from the retina to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR neurons relay itch information to the paraventricular nucleus of the thalamus (PVT). Surprisingly, neither the visual cortex nor superior colliculus is involved in contagious itch. In vivo calcium imaging and extracellular recordings reveal contagious …

Global Longitudinal Strain And Biomarkers Of Cardiac Damage And Stress As Predictors Of Outcomes After Transcatheter Aortic Valve Implantation, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (

The Transcription Factor Bach2 Negatively Regulates Murine Natural Killer Cell Maturation And Function, Shasha Li, Michael D Bern, Benpeng Miao, Changxu Fan, Xiaoyun Xing, Takeshi Inoue, Sytse J Piersma, Ting Wang, Marco Colonna, Tomohiro Kurosaki, Wayne M Yokoyama

2020-Current year OA Pubs

BTB domain And CNC Homolog 2 (Bach2) is a transcription repressor that actively participates in T and B lymphocyte development, but it is unknown if Bach2 is also involved in the development of innate immune cells, such as natural killer (NK) cells. Here, we followed the expression of Bach2 during murine NK cell development, finding that it peaked in immature CD27

Current Communication Practices Between Obstetrics And Gynecology Residency Applicants And Program Directors, Helen Kang Morgan, Abigail Ford Winkel, Karen George, Eric Strand, Erika Banks, Fiona Byrne, David Marzano, Maya M Hammoud

2020-Current year OA Pubs

Importance: In order to equitably improve the residency application process, it is essential to understand the problems we need to address.

Objective: To determine how obstetrics and gynecology (OBGYN) applicants and faculty communicate applicants' interest to residency programs, and how program directors report being influenced by these communications.

Design, Setting, and Participants: This survey study was conducted with email surveys of OBGYN application stakeholders in 2022. Included participants were OBGYN applicants, clerkship directors, and residency program directors in medical education associations' email listservs.

Exposures: Surveys sent by the American Association of Medical Colleges, Association of Professors of Gynecology and Obstetrics, …

Reprogramming Alveolar Macrophage Responses To Tgf-Β Reveals Ccr2+ Monocyte Activity That Promotes Bronchiolitis Obliterans Syndrome, Zhiyi Liu, Fuyi Liao, Jihong Zhu, Dequan Zhou, Gyu Seong Heo, Hannah P. Leuhmann, Davide Scozzi, Antanisha Parks, Ramsey Hachem, Derek E. Byers, Laneshia K. Tague, Hrishikesh S. Kulkarni, Marlene Cano, Brian W. Wong, Wenjun Li, Daniel Kreisel, Andrew E Gelman, Et Al.

2020-Current year OA Pubs

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway …

Effectiveness Of The Ad26.Cov2.S (Johnson & Johnson) Coronavirus Disease 2019 (Covid-19) Vaccine For Preventing Covid-19 Hospitalizations And Progression To High Disease Severity In The United States, Nathaniel M Lewis, Hilary M Babcock, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, …

Entrectinib In Children And Young Adults With Solid Or Primary Cns Tumors Harboring Ntrk, Ros1, Or Alk Aberrations (Startrk-Ng), Ami V Desai, Karen Gauvain, Amy E Armstrong, Et Al.

2020-Current year OA Pubs

BACKGROUND: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.

METHODS: STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D.

RESULTS: At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 …