Medicine and Health Sciences Commons^™

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 …

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, …

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, …

Shared Brain And Genetic Architectures Between Mental Health And Physical Activity, Wei Zhang, Sarah E Paul, Anderson Winkler, Ryan Bogdan, Janine D Bijsterbosch

2020-Current year OA Pubs

Physical activity is correlated with, and effectively treats various forms of psychopathology. However, whether biological correlates of physical activity and psychopathology are shared remains unclear. Here, we examined the extent to which the neural and genetic architecture of physical activity and mental health are shared. Using data from the UK Biobank (N = 6389), we applied canonical correlation analysis to estimate associations between the amplitude and connectivity strength of subnetworks of three major neurocognitive networks (default mode, DMN; salience, SN; central executive networks, CEN) with accelerometer-derived measures of physical activity and self-reported mental health measures (primarily of depression, anxiety disorders, …

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 …

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 …

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

Six-Year Results From Relevance: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed By Rituximab Maintenance In Untreated Advanced Follicular Lymphoma, Franck Morschhauser, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

No abstract provided.

Targeting Pim2 By Jp11646 Results In Significant Antitumor Effects In Solid Tumors, Eriko Katsuta, Malgorzata Gil-Moore, Justine Moore, Mohamed Yousif, Alex A Adjei, Yi Ding, Justin Caserta, Carmen M Baldino, Kelvin P Lee, Irwin H Gelman, Kazuaki Takabe, Mateusz Opyrchal

2020-Current year OA Pubs

Proviral integration of Moloney virus 2 (PIM2) is a pro‑survival factor of cancer cells and a possible therapeutic target in hematological malignancies. However, the attempts at inhibiting PIM2 have yielded underwhelming results in early clinical trials on hematological malignancies. Recently, a novel pan‑PIM inhibitor, JP11646, was developed. The present study examined the utility of targeting PIM2 in multiple solid cancers and investigated the antitumor efficacy and the mechanisms of action of JP11646. When PIM2 expression was compared between normal and cancer tissues in publicly available datasets, PIM2 was found to be overexpressed in several types of solid cancers. PIM2 ectopic …

The Gut Microbial Metabolic Capacity Of Microbiome-Humanized Vs. Wild Type Rodents Reveals A Likely Dual Role Of Intestinal Bacteria In Hepato-Intestinal Schistosomiasis, Alba Cortés, John Martin, Bruce A. Rosa, Klara A. Stark, Simon Clare, Catherine Mccarthy, Katherine Harcourt, Cordelia Brandt, Charlotte Tolley, Trevor D. Lawley, Makedonka Mitreva, Matthew Berriman, Gabriel Rinaldi, Cinzia Cantacessi

2020-Current year OA Pubs

Increasing evidence shows that the host gut microbiota might be involved in the immunological cascade that culminates with the formation of tissue granulomas underlying the pathophysiology of hepato-intestinal schistosomiasis. In this study, we investigated the impact of Schistosoma mansoni infection on the gut microbial composition and functional potential of both wild type and microbiome-humanized mice. In spite of substantial differences in microbiome composition at baseline, selected pathways were consistently affected by parasite infection. The gut microbiomes of infected mice of both lines displayed, amongst other features, enhanced capacity for tryptophan and butyrate production, which might be linked to the activation …

Multi-Modulated Frequency Domain High Density Diffuse Optical Tomography, Guy A. Perkins, Adam T. Eggebrecht, Hamid Dehghani

2020-Current year OA Pubs

No abstract provided.

Congenital Aneurysm Of The Muscular Interventricular Septum Associated With Bifascicular Block, Hoang H. Nguyen, Patrick Y. Jay

2020-Current year OA Pubs

Isolated congenital aneurysm of the muscular interventricular septum is rare. We present a patient with congenital aneurysm of the basal muscular ventricular septum, who also develops conduction abnormalities with first-degree heart block, right bundle branch block, and left posterior fascicular block. The case details the natural history of the aneurysm over a 10-year period follow-up during which the patient remained asymptomatic with evidence of regression of the aneurysm. Given the aneurysm's location close to the proximal right bundle and left posterior fascicle, we believe that the cause for the aneurysm also injured both fascicles resulting in bifascicular block. The diagnosis …

The Inner Nuclear Membrane Protein Nemp1 Supports Nuclear Envelope Openings And Enucleation Of Erythroblasts, Didier Hodzic, Jun Wu, Karen Krchma, Andrea Jurisicova, Yonit Tsatskis, Yijie Liu, Peng Ji, Kyunghee Choi, Helen Mcneill

2020-Current year OA Pubs

Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show …

Health-Related Quality Of Life In Older Patients With Heart Failure From Before To Early After Advanced Surgical Therapies: Findings From The Sustain-It Study, Kathleen L. Grady, Justin Hartupee, Et Al.

2020-Current year OA Pubs

BACKGROUND: Restoring health-related quality of life (HRQOL) is a therapeutic goal for older patients with advanced heart failure. We aimed to describe change in HRQOL in older patients (60-80 years) awaiting heart transplantation (HT) with or without pretransplant mechanical circulatory support (MCS) or scheduled for long-term MCS, if ineligible for HT, from before to 6 months after these surgeries and identify factors associated with change.

METHODS: Patients from 13 US sites completed the EuroQol 5-dimension 3L questionnaire and Kansas City Cardiomyopathy Questionnaire-12 at baseline and 3 and 6 months after HT or long-term MCS. Analyses included univariate comparisons and multivariable …

Choline, Dha, And Diarrheal Disease Associated With Growth Faltering In A Case-Control Study, Jenna N Diaz, Sherlie Jean Louis Dulience, Noah Wolthausen, Xuntian Jiang, Emmanuel Gyimah, Francesca J Marhône Pierre, F Matthew Kuhlmann, Lora L Iannotti

2020-Current year OA Pubs

BACKGROUND: Children with recurrent infectious diarrhea are susceptible to growth faltering. DHA and choline may play a role in this relationship due to their involvement in lipid metabolism, gut immunity, and inflammatory pathways.

OBJECTIVES: This study aimed to characterize the contributions made by DHA and choline status and enteric damage in young children in the association between diarrheal illness and child growth.

METHODS: A longitudinal case-control study was conducted among children aged 6-36 mo (

RESULTS: At baseline, mean plasma DHA concentrations (1.03 µg/mL; 95% CI: 0.91, 1.15) were not significantly different between cases and controls, nor was there a …

Evaluating Brain Damage In Multiple Sclerosis With Simultaneous Multi-Angular-Relaxometry Of Tissue, Biao Xiang, Jie Wen, Robert E Schmidt, Alexander L Sukstanskii, Daniel Mamah, Dmitriy A Yablonskiy, Anne H Cross

2020-Current year OA Pubs

OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination.

METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric …

Paediatrician's Guide To Post-Operative Care For Functionally Univentricular Chd: A Review, Christina Ronai, Sarosh P Batlivala, Quang-Tuyen Nguyen, Markus S Renno, Lindsay Arthur, Julie Glickstein, Jonathan N Johnson, Jacob R Miller, Carolyn A Altman, Elif Seda Selamet Tierney

2020-Current year OA Pubs

IMPORTANCE: Single ventricle CHD affects about 5 out of 100,000 newborns, resulting in complex anatomy often requiring multiple, staged palliative surgeries. Paediatricians are an essential part of the team that cares for children with single ventricle CHD. These patients often encounter their paediatrician first when a complication arises, so it is critical to ensure the paediatrician is knowledgeable of these issues to provide optimal care.

OBSERVATIONS: We reviewed the subtypes of single ventricle heart disease and the various palliative surgeries these patients undergo. We then searched the literature to detail the general paediatrician's approach to single ventricle patients at different …

A Saturated Map Of Common Genetic Variants Associated With Human Height, Loïc Yengo, E Warwick Daw, Lihua Wang, Mary F. Feitosa, Michael A. Province, Dabeeru C. Rao, Adam E. Locke, Et Al.

2020-Current year OA Pubs

No abstract provided.

Calciphylaxis Arising Following Bariatric Surgery: A Case Series, Bethany Cucka, Bianca Biglione, Lauren Ko, Emily D Nguyen, Charbel C Khoury, Sagar U Nigwekar, Malcolm K Robinson, Daniela Kroshinsky

2020-Current year OA Pubs

No abstract provided.

Lung Allograft Standardized Histological Analysis (Lasha) Template: A Research Consensus Proposal, Fiorella Calabrese, Chieh-Yu Lin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Routine monitoring of lung-transplanted patients is crucial for the identification of immunological and non-immunological complications. Determining the etiology of acute allograft dysfunction, particularly in alloimmune-mediated disorders, relies heavily on the lung biopsy with histopathologic analysis. Standardization of the pathologic diagnosis of rejection (e.g., cellular and antibody-mediated) is based on consensus statements and guidelines, indicating the importance of a multidisciplinary approach to achieve a definitive etiological diagnosis. In addition to these statements and guidelines, refinements and standardizations are feasible through systematic analysis morphological, immunophenotypic and molecular alterations observed in transbronchial biopsies. This study is to identify key morphologic features to …

High Polygenic Risk Scores Are Associated With Early Age Of Onset Of Alcohol Use Disorder In Adolescents And Young Adults At Risk, John I Nurnberger Jr, Kathleen Bucholz, Laura Bierut, Vivia Mccutcheon, Andrey P Anokhin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations.

METHODS: A total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using …

Variability In Energy Expenditure Is Much Greater In Males Than Females, Lewis G Halsey, Susan B Racette, Et Al.

2020-Current year OA Pubs

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether …

Incisionless Targeted Adeno-Associated Viral Vector Delivery To The Brain By Focused Ultrasound-Mediated Intranasal Administration, Dezhuang Ye, Jinyun Yuan, Yaoheng Yang, Yimei Yue, Zhongtao Hu, Siaka Fadera, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Adeno-associated viral (AAV) vectors are currently the leading platform for gene therapy with the potential to treat a variety of central nervous system (CNS) diseases. There are numerous methods for delivering AAVs to the CNS, such as direct intracranial injection (DI), intranasal delivery (IN), and intravenous injection with focused ultrasound-induced blood-brain barrier disruption (FUS-BBBD). However, non-invasive and efficient delivery of AAVs to the brain with minimal systemic toxicity remain the major challenge. This study aims to investigate the potential of focused ultrasound-mediated intranasal delivery (FUSIN) in AAV delivery to brain.

METHODS: Mice were intranasally administered with AAV5 encoding enhanced …

Newborn Mid-Upper Arm Circumference Identifies Low-Birth Weight And Vulnerable Infants: A Secondary Analysis, D Taylor Hendrixson, Patrick N Lasowski, Aminata Shamit Koroma, Mark J Manary

2020-Current year OA Pubs

BACKGROUND: Low birth weight (LBW) infants are at increased risk of morbidity and mortality. Identification of LBW may not occur in settings where access to reliable scales is limited. Mid-upper arm circumference (MUAC) may be an accessible, low-cost measure to identify LBW and vulnerable infants.

OBJECTIVES: We explored the validity of newborn MUAC in identifying LBW and vulnerable newborns in rural Sierra Leone.

METHODS: This study was a secondary analysis of infant data from a randomized controlled clinical trial of supplementary food and anti-infective therapies compared with standard care for undernourished pregnant women. Data for singleton liveborn infants with birth …

Semiautomated Analysis Of An Optical Atp Indicator In Neurons, Taher Dehkharghanian, Arsalan Hashemiaghdam, Ghazaleh Ashrafi

2020-Current year OA Pubs

No abstract provided.

Gynecologic Oncology Patient Perspectives And Knowledge On Advance Care Planning: A Quality Improvement Intervention, Sarah P. Huepenbecker, Sophia Lewis, Mark C. Valentine, Marguerite L. Palisoul, Premal H. Thaker, Andrea R. Hagemann, Carolyn K. Mccourt, Katherine C. Fuh, Matthew A. Powell, David G. Mutch, Lindsay M. Kuroki

2020-Current year OA Pubs

OBJECTIVES: Assess and improve advance care planning (ACP) awareness and uptake among gynecologic oncology patients.

METHODS: Using a quality improvement Plan-Do-Check-Act framework, we completed a single institution needs assessment and intervention. The needs assessment was a 26-question survey assessing baseline ACP knowledge and preferences of gynecologic oncology patients. We used this survey to implement an outpatient intervention in which patients were offered ACP resources (pamphlet, discussion with their gynecologic oncologist, and/or social work referral). We conducted a post-intervention survey among patients who had and had not received ACP resource(s) to assess whether our intervention increased ACP knowledge, discussions, or uptake. …

Stress Radiography Is A Reliable Method To Quantify Posterior Cruciate Ligament Insufficiency: A Systematic Review, J. Jared Guth, Robert H. Brophy, Matthew J. Matava, R. Garrett Steinmetz, Matthew V. Smith

2020-Current year OA Pubs

PURPOSE: To perform a systematic review of posterior tibial stress radiography techniques and radiographic measurement methods to compare their accuracy and efficacy to aid clinicians in quantifying posterior cruciate ligament laxity.

METHODS: Electronic databases, including PubMed, MEDLINE, Embase.com 1947- , Ovid Medline 1946- , Scopus 1823- , Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov 1997- were queried in December 2020. The abstracts of articles were reviewed by 2 authors for published studies comparing posterior tibial stress radiography techniques, describing, and comparing radiographic measurement methods, and comparing stress radiographs with instrumented knee testing.

RESULTS: The systematic review included 13 …

Treatment Of Stage I Lung Cancer Detected By Computed Tomography Screening, David S. Gierada, Yun Zhu Bai, Matthew B. Spraker, Anne Stilinovic, Ruben G. Nava

2020-Current year OA Pubs

INTRODUCTION: Reducing lung cancer deaths through early detection by computed tomography (CT) screening requires delivery of effective treatment. We performed this retrospective study to determine the types of treatment used for screen-detected stage I lung cancer at our academic center and to compare the demographic and clinical characteristics of patients by type of treatment.

METHODS: All persons screened in the lung cancer screening program at our institution through June 16, 2021, were included. Those with screening CT findings needing follow-up were managed through a thoracic surgery clinic. Demographic and clinical characteristics of patients diagnosed with having stage I lung cancer …

Tnfr1 Contributes To Activation-Induced Cell Death Of Pathological Cd4+ T Lymphocytes During Ischemic Heart Failure, Vinay Kumar, Rachel Rosenzweig, Suman Asalla, Sarita Nehra, Sumanth D Prabhu, Shyam S Bansal

2020-Current year OA Pubs

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Antimicrobial Stewardship For Sepsis In The Intensive Care Unit: Survey Of Critical Care And Infectious Diseases Physicians, M Cristina Vazquez Guillamet, Jason P Burnham, Maria Pérez, Marin H Kollef, Constantine A Manthous, Donna B Jeffe

2020-Current year OA Pubs

OBJECTIVE: To evaluate the attitudes of infectious diseases (ID) and critical care physicians toward antimicrobial stewardship in the intensive care unit (ICU).

DESIGN: Anonymous, cross-sectional, web-based surveys.

SETTING: Surveys were completed in March-November 2017, and data were analyzed from December 2017 to December 2019.

PARTICIPANTS: ID and critical care fellows and attending physicians.

METHODS: We included 10 demographic and 17 newly developed, 5-point, Likert-scaled items measuring attitudes toward ICU antimicrobial stewardship and transdisciplinary collaboration. Exploratory principal components analysis (PCA) was used for data reduction. Multivariable linear regression models explored demographic and attitudinal variables.

RESULTS: Of 372 respondents, 315 physicians had …