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Articles 151 - 180 of 20184

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Gut Microbiota Modulation Of Regulatory Dna Elements Revealed By Massively Parallel Functional Characterization, Chadmirah Zaratiana, Adheet Ganesh, Yang E Li, Et Al. May 2026

Gut Microbiota Modulation Of Regulatory Dna Elements Revealed By Massively Parallel Functional Characterization, Chadmirah Zaratiana, Adheet Ganesh, Yang E Li, Et Al.

2020-Current year OA Pubs

Cis-regulatory elements (CREs) are central to dynamic gene regulation in hepatocytes, yet most functional annotations derive from in vitro models that poorly capture physiological regulation. We systematically profiled 109,386 human liver-derived CREs using massively parallel reporter assays in hepatocytes under matched in vitro and in vivo conditions. In vivo-active functional CREs (fCREs) were enriched for H3K27ac and chromatin accessibility and were regulated by diverse transcription factors in the human liver. We further demonstrate that gut microbiota-derived signals modulate fCRE activity and target gene expression in vivo, in part via the KEAP1/NFE2L2 antioxidant pathway. Specific microbial metabolites directly altered the activity …


+Cd49a+Cd103+ Cytotoxic Tissue-Resident Natural Killer Cells Infiltrate And Control Solid Epithelial Tumor Growth In Mice, Nina B Horowitz, Jennifer A Foltz, Et Al. May 2026

+Cd49a+Cd103+ Cytotoxic Tissue-Resident Natural Killer Cells Infiltrate And Control Solid Epithelial Tumor Growth In Mice, Nina B Horowitz, Jennifer A Foltz, Et Al.

2020-Current year OA Pubs

Human tissue-resident natural killer (NK) cells (trNK cells), broadly defined by markers of tissue residency, such as CD49a [


Early-Life Wnt4 Expressing Colon Stromal Cells Orchestrate Lifelong Mucosal Homeostasis Via Bmp-Driven Inkt Cell Imprinting, Xi Lin, Chloe Hyun-Jung Lee, Ting Zhang, Agne Antanaviciute, Thomas Hanley, Jonathan N Glickman, Nikhila S Bharadwaj, Vicki Rosen, Jenny E Gumperz, Matthew K Waldor, Alison Simmons, Thomas Gensollen, Richard S Blumberg May 2026

Early-Life Wnt4 Expressing Colon Stromal Cells Orchestrate Lifelong Mucosal Homeostasis Via Bmp-Driven Inkt Cell Imprinting, Xi Lin, Chloe Hyun-Jung Lee, Ting Zhang, Agne Antanaviciute, Thomas Hanley, Jonathan N Glickman, Nikhila S Bharadwaj, Vicki Rosen, Jenny E Gumperz, Matthew K Waldor, Alison Simmons, Thomas Gensollen, Richard S Blumberg

2020-Current year OA Pubs

The early-life intestinal microenvironment plays a pivotal role in shaping immune cell development. Here, we identify a colonic Wnt4-expressing stromal cell, enriched during early-life, that promotes iNKT cell proliferation via BMP-MAPK signaling. These stromal cells are spatially associated with iNKT cells and macrophages and exhibit high Bmp2 expression during the neonatal period. Depletion of BMP2 in Wnt4


Genealogy-Based Trait Association With Locater Boosts Power At Loci With Allelic Heterogeneity, Xinxin Wang, Ryan Christ, Erica Young, Chul Joo Kang, Indraniel Das, Edward A Belter, Markku Laakso, Louis J M Aslett, David Steinsaltz, Nathan O Stitziel, Ira M Hall May 2026

Genealogy-Based Trait Association With Locater Boosts Power At Loci With Allelic Heterogeneity, Xinxin Wang, Ryan Christ, Erica Young, Chul Joo Kang, Indraniel Das, Edward A Belter, Markku Laakso, Louis J M Aslett, David Steinsaltz, Nathan O Stitziel, Ira M Hall

2020-Current year OA Pubs

A key methodological challenge for genome-wide association studies is how to leverage haplotype diversity and allelic heterogeneity to improve trait association power, especially in noncoding regions where it is difficult to predict variant impacts and define functional units for variant aggregation. Genealogy-based association methods have the potential to bridge this gap by testing combinations of common and rare haplotypes based purely on their ancestral relationships. In parallel work, we have developed an efficient local ancestry inference engine and a novel statistical method (LOCATER) for combining signals present on different branches of a locus-specific haplotype tree. Here, we develop a genome-wide …


Large-Scale Genetic Characterization Of Parkinson's Disease In The African And African Admixed Populations, Fulya Akçimen, Scott A Norris, Erin R Foster, Et Al. May 2026

Large-Scale Genetic Characterization Of Parkinson's Disease In The African And African Admixed Populations, Fulya Akçimen, Scott A Norris, Erin R Foster, Et Al.

2020-Current year OA Pubs

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …


Logistic Regression For Estimating Functional Effects With Spatial Transcriptomics, Michael Barkasi, Cody Nhan Pham, Demetrios Neophytou, Hysell V Oviedo May 2026

Logistic Regression For Estimating Functional Effects With Spatial Transcriptomics, Michael Barkasi, Cody Nhan Pham, Demetrios Neophytou, Hysell V Oviedo

2020-Current year OA Pubs

Spatial transcriptomics (ST) unlocks potential for studying gene functions in processes that depend on orchestration of transcription across space. However, analysis tools for ST remain aimed at data exploration, with few resources for hypothesis testing. What's missing is a way to test whether a factor of interest affects functionally relevant parameters of a gene's spatial distribution. We present a tool to fill this gap, which we call a warped sigmoidal Poisson-process mixed-effects (WSP, pronounced "wisp") model. WSP models are the first ST tool allowing researchers to test critical questions without bespoke preprocessing pipelines for identifying key spatial parameters. By aligning …


Mitochondrial Etf Insufficiency Drives Neoplastic Growth By Selectively Optimizing Cancer Bioenergetics, David Papadopoli, Sergej Djuranovic, Et Al. May 2026

Mitochondrial Etf Insufficiency Drives Neoplastic Growth By Selectively Optimizing Cancer Bioenergetics, David Papadopoli, Sergej Djuranovic, Et Al.

2020-Current year OA Pubs

Mitochondrial electron transport flavoprotein (ETF) insufficiency causes metabolic diseases known as a multiple acyl-CoA dehydrogenase deficiency (MADD). In contrast to muscle, ETFDH is a non-essential gene in acute lymphoblastic leukemia NALM6 cells, and its expression is reduced across human cancers. In various human cancer cell lines and mouse models, ETF insufficiency caused by decreased ETFDH expression limits flexibility of OXPHOS fuel utilisation but paradoxically increases bioenergetics and accelerates neoplastic growth via activation of the mTORC1/BCL-6/4E-BP1 axis. Collectively, these findings reveal that while ETF insufficiency is rare and has detrimental effects in non-malignant tissues, it is common in neoplasia, where ETFDH …


Transcriptome Predictors Of Second Breast Events In Ductal Carcinoma In Situ: A Case‒Control Study Including Black And White Women, Aditi Hazra, Emma Berdan, Thomas Walsh, Sarah Humble, Jen Tappenden, Katherine Deschryver, Deborah Veis, Kiran Vij, Shannan Ho Sui, Graham A Colditz May 2026

Transcriptome Predictors Of Second Breast Events In Ductal Carcinoma In Situ: A Case‒Control Study Including Black And White Women, Aditi Hazra, Emma Berdan, Thomas Walsh, Sarah Humble, Jen Tappenden, Katherine Deschryver, Deborah Veis, Kiran Vij, Shannan Ho Sui, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Black women diagnosed with ductal carcinoma in situ (DCIS) experience disproportionately higher risk of second breast cancer events (SBEs), including both ipsilateral and contralateral recurrences, yet remain underrepresented in molecular biomarker studies compared to non-Hispanic White women.

METHODS: We performed RNA sequencing on 200 archival DCIS samples from the Resource of Archival Breast Tissue cohort, including 33% self-reported Black women. We correlated transcriptomic and clinical data to identify predictors of SBEs. Cases (n = 100) who developed SBEs between 1999 and 2019 were matched 1:1 to controls (n = 100) on age, race, and margin status, who remained event-free …


Recommendations Made And Accepted By A Telehealth-Enabled Antimicrobial Stewardship Program Implemented At Rural Veterans Affairs Medical Centers, Taissa A Bej, Jason P Burnham, Joshua D. Nordman, Et Al. May 2026

Recommendations Made And Accepted By A Telehealth-Enabled Antimicrobial Stewardship Program Implemented At Rural Veterans Affairs Medical Centers, Taissa A Bej, Jason P Burnham, Joshua D. Nordman, Et Al.

2020-Current year OA Pubs

BACKGROUND: To support Antimicrobial Stewardship programs (ASPs) as well as the clinical care of patients with infections, we disseminated and implemented a Videoconference Antimicrobial Stewardship Team (VAST) to connect multidisciplinary teams from rural Veterans Affairs (VA) medical centers with geographically distant ID experts. Here, we describe the clinical syndromes discussed and the response to recommendations made during VAST sessions.

METHODS: Between September 2021 to February 2024, eight ID consultants established VASTs with ten rural VAMCs, holding regularly scheduled videoconference sessions to discuss clinical cases and provide recommendations. Data were collected on patient demographics, clinical syndromes, and recommendations. Acceptance of recommendations …


Securepose: Automated Face Blurring And Human Movement Kinematics Extraction From Videos Recorded In Clinical Settings, Rishabh Bajpai, Bhooma Aravamuthan May 2026

Securepose: Automated Face Blurring And Human Movement Kinematics Extraction From Videos Recorded In Clinical Settings, Rishabh Bajpai, Bhooma Aravamuthan

2020-Current year OA Pubs

Movement disorder diagnosis often relies on expert evaluation of patient videos, but sharing these videos poses privacy risks. Current methods for de-identifying videos, such as blurring faces, are often manual, inconsistent, or inaccurate. Furthermore, these methods can compromise automated kinematics extraction-a valuable aid to movement analysis. To address these challenges, we developed SecurePose, open-source software that provides both reliable de-identification and automated body kinematic extraction from videos recorded in clinic settings using smartphones/tablets. We validated SecurePose on gait videos recorded in outpatient clinic visits of 116 children with cerebral palsy, assessing both the accuracy of its de-identification compared to the …


Spleen Volume Reduction And Transfusion Independence With Momelotinib Versus Ruxolitinib And Associated Overall Survival With Momelotinib In Jak Inhibitor-Naive Patients With Myelofibrosis And Anemia: Subgroup Analyses Of Simplify-1, Francesca Palandri, Stephen T Oh, Et Al. May 2026

Spleen Volume Reduction And Transfusion Independence With Momelotinib Versus Ruxolitinib And Associated Overall Survival With Momelotinib In Jak Inhibitor-Naive Patients With Myelofibrosis And Anemia: Subgroup Analyses Of Simplify-1, Francesca Palandri, Stephen T Oh, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Improvements in splenomegaly, anemia, and overall survival (OS) are key considerations in the management of patients with myelofibrosis. In the phase III SIMPLIFY-1 trial (NCT01969838), momelotinib was noninferior to ruxolitinib for spleen volume reduction ≥ 35% (SVR35) and nominally superior for transfusion independence (TI) at week 24 in Janus kinase (JAK) inhibitor-naive patients. However, the relative impact of these endpoints on OS in anemic patients has not been described.

MATERIALS AND METHODS: The present post hoc analysis evaluated week 24 SVR35, TI, and dual responses (SVR35 + TI) in patients with baseline hemoglobin < 10 g/dL.

RESULTS: SVR35 rates were similar overall …


A Covalent Allosteric Molecular Glue Suppresses Nrf2-Dependent Cancer Growth, Nilotpal Roy, Ilah Bok, Harit Panda, Dhaval P Bhatt, Emily M Wilkerson, Soma Saeidi, Paul Zolkind, Michael B Major, Et Al. May 2026

A Covalent Allosteric Molecular Glue Suppresses Nrf2-Dependent Cancer Growth, Nilotpal Roy, Ilah Bok, Harit Panda, Dhaval P Bhatt, Emily M Wilkerson, Soma Saeidi, Paul Zolkind, Michael B Major, Et Al.

2020-Current year OA Pubs

UNLABELLED: The NRF2 transcription factor is constitutively active in cancer, in which it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2 dependency and resistance to chemotherapy/radiotherapy (RT). In this study, we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the Kelch-like ECH-associated protein 1 (KEAP1)-cullin3 (CUL3) ubiquitin-ligase complex. VVD-065 specifically and covalently engages Cys151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported Cys151-directed compounds decrease KEAP1-CUL3 interactions …


Computational Fluid Dynamics-Based Risk Stratification Of Modified Blalock-Taussig-Thomas Shunt Thrombogenicity, Yi Qiao, Ethan Penn, Jacob Miller, Scott Bugenhagen, Ram Rohatgi, Kelsey Mercer, Blaire Kulp, Jinli Wang, Pirooz Eghtesady, Guy M Genin, Edon J Rabinowitz, David Bark May 2026

Computational Fluid Dynamics-Based Risk Stratification Of Modified Blalock-Taussig-Thomas Shunt Thrombogenicity, Yi Qiao, Ethan Penn, Jacob Miller, Scott Bugenhagen, Ram Rohatgi, Kelsey Mercer, Blaire Kulp, Jinli Wang, Pirooz Eghtesady, Guy M Genin, Edon J Rabinowitz, David Bark

2020-Current year OA Pubs

BACKGROUND: The modified Blalock-Taussig-Thomas shunt (mBTTS) is a critical palliative procedure for infants with single-ventricle physiology, but thrombosis-related occlusion affects 8% to 12% of infants and carries nearly 50% mortality. Meanwhile, existing antithrombotic strategies fail to address the hemodynamic factors driving thrombosis, highlighting the need for a deeper understanding of flow dynamics in shunt failure.

OBJECTIVES: This study aims to identify how mBTTS geometry influences hemodynamics and thrombosis risk, providing quantitative guidance for surgical planning and shunt design optimization.

METHODS: We used patient-specific imaging data to test 54 idealized mBTTS configurations, systematically varying key geometric factors: pulmonary artery diameter, shunt …


Sustainment Of Hydroxyurea Adherence In Patients With Sickle Cell Disease, Andrew M Heitzer, Zachary Wooten, Guangjin Luo, Marsha Treadwell, Allison A King, Victor R Gordeuk, Nirmish Shah, Christina M Abrams, Sarah Mccuskee, Siera Gollan, Jennifer Longoria, Jane S Hankins, Sickle Cell Disease Implementation Consortium May 2026

Sustainment Of Hydroxyurea Adherence In Patients With Sickle Cell Disease, Andrew M Heitzer, Zachary Wooten, Guangjin Luo, Marsha Treadwell, Allison A King, Victor R Gordeuk, Nirmish Shah, Christina M Abrams, Sarah Mccuskee, Siera Gollan, Jennifer Longoria, Jane S Hankins, Sickle Cell Disease Implementation Consortium

2020-Current year OA Pubs

IMPORTANCE: Despite established treatment guidelines and strong therapeutic benefit, hydroxyurea remains underused among patients with sickle cell disease.

OBJECTIVE: To assess the change in self-reported hydroxyurea use (ie, taking the medication at all) and adherence (ie, the number of days taken per week) over time and to examine factors associated with the trajectory of hydroxyurea use and adherence.

DESIGN, SETTING, AND PARTICIPANTS: Data were collected through the Sickle Cell Disease Implementation Consortium, a longitudinal, multicenter, observational cohort study that recruited patients from 8 centers across the US. Data collection occurred from 2017 to 2022, and analyses were performed from January …


Cognitive Behavioral Therapy For Individuals With Low Literacy And Perinatal Depression: A Randomized Clinical Trial, Eliza Kleban, Ashleen Lee, Aminata Koroma, D Taylor Hendrixson, Joshua Duncan, Mark J Manary, Kevin B Stephenson May 2026

Cognitive Behavioral Therapy For Individuals With Low Literacy And Perinatal Depression: A Randomized Clinical Trial, Eliza Kleban, Ashleen Lee, Aminata Koroma, D Taylor Hendrixson, Joshua Duncan, Mark J Manary, Kevin B Stephenson

2020-Current year OA Pubs

IMPORTANCE: Perinatal depression is common in sub-Saharan Africa, yet treatment gaps are substantial. Cognitive behavioral therapy (CBT) is effective but relies on written materials.

OBJECTIVE: To evaluate the efficacy of a culturally adapted CBT intervention delivered by lay counselors to women with perinatal depression in rural Sierra Leone.

DESIGN, SETTING, AND PARTICIPANTS: This study was an individually randomized, outcomes assessor- and investigator-blinded, clinical trial of an adapted CBT intervention vs enhanced usual care. The trial was conducted in 6 government-run antenatal clinics in Pujehun District, Sierra Leone, which has limited infrastructure, low literacy, high maternal undernutrition, and no perinatal mental …


Hematopoietic Cell Transplant Access And Patient Diversity, Rachel Cusatis, Ramzi Abboud, Et Al. May 2026

Hematopoietic Cell Transplant Access And Patient Diversity, Rachel Cusatis, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Allogeneic hematopoietic cell transplant (HCT) is curative for hematologic cancers, yet access remains inequitable for racially and ethnically underrepresented and socioeconomically disadvantaged populations, making the goal of having a suitable donor for every patient who needs a transplant challenging. The ACCESS trial broadened access by enrolling patients without matched donors, who instead received an HCT from a mismatched unrelated donor.

OBJECTIVE: To compare baseline characteristics of ACCESS trial participants with participants enrolled in a similar clinical trial and a patient-reported outcome (PRO) protocol cohort.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included adult participants (aged ≥18 years) from 3 …


Androgen Loss Accelerates Brain Tumour Growth Via Hpa Axis Activation, Juyeun Lee, Joshua B Rubin, Et Al. May 2026

Androgen Loss Accelerates Brain Tumour Growth Via Hpa Axis Activation, Juyeun Lee, Joshua B Rubin, Et Al.

2020-Current year OA Pubs

Many cancers, including glioblastoma (GBM), show a male-biased incidence and associated worse outcomes


Adaptive Evolution Of Gene Regulatory Networks In Mammalian Neocortex, Zhuo Li, Linda J Richards, Et Al. May 2026

Adaptive Evolution Of Gene Regulatory Networks In Mammalian Neocortex, Zhuo Li, Linda J Richards, Et Al.

2020-Current year OA Pubs

Mammals have evolved a more complex brain, exemplified by the transformation of the single-layer dorsal cortex of excitatory projection neurons (ExNs) in ancestors into a multilayered cerebral neocortex


Single-Cell Spatiotemporal Dissection Of The Human Maternal-Fetal Interface, Cheng Wang, Sarah K England, David K Stevenson, Gary M Shaw, Et Al. May 2026

Single-Cell Spatiotemporal Dissection Of The Human Maternal-Fetal Interface, Cheng Wang, Sarah K England, David K Stevenson, Gary M Shaw, Et Al.

2020-Current year OA Pubs

The human maternal-fetal interface is characterized by mosaic intermingling of maternal and fetal cells


Synovial Fluid Biomarkers Associated With Anterior Cruciate Ligament Injury And Reconstruction: A Systematic Review, Daniel C Touhey, Derrick M Knapik, Sina Tartibi, Varun Gopinatth, Tanya Boghosian, Matthew J Matava, Matthew V Smith, Robert H Brophy May 2026

Synovial Fluid Biomarkers Associated With Anterior Cruciate Ligament Injury And Reconstruction: A Systematic Review, Daniel C Touhey, Derrick M Knapik, Sina Tartibi, Varun Gopinatth, Tanya Boghosian, Matthew J Matava, Matthew V Smith, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Synovial fluid biomarkers reflect the inflammatory response after joint injury and surgery. Previous studies have identified synovial fluid biomarker concentrations in the knee after both anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR).

PURPOSE: To systematically review the literature to summarize reported changes in synovial fluid biomarkers and their concentrations after acute ACL injury/ACLR.

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: Studies published in the PubMed, EMBASE, and the Cochrane Library databases reporting in English on humans sustaining ACL tears and undergoing ACLR from inception to August 2025 were identified and included if postinjury/preoperative and/or postoperative …


Adapt-On-Demand: Enabling Flexible And Scalable Adaptive Radiotherapy Through Workflow Automation, Sean Domal, Min Geon Choi, Justin Visak, Ruiqi Li, Taoran Li, Boon-Keng Kevin Teo, Xiaodong Zhao, Matthew Schmidt, Eric Laugeman, David Parsons, Yang Kyun Park, Shahed Badiyan, David Sher, Mu-Han Lin May 2026

Adapt-On-Demand: Enabling Flexible And Scalable Adaptive Radiotherapy Through Workflow Automation, Sean Domal, Min Geon Choi, Justin Visak, Ruiqi Li, Taoran Li, Boon-Keng Kevin Teo, Xiaodong Zhao, Matthew Schmidt, Eric Laugeman, David Parsons, Yang Kyun Park, Shahed Badiyan, David Sher, Mu-Han Lin

2020-Current year OA Pubs

PURPOSE: CT-guided adaptive radiotherapy (CTgART) offers significant clinical benefits, but its utilization is often limited by resource demands and rigid workflows. This study presents a flexible and scalable "Adapt-on-Demand" (AOD) framework that integrates the adaptive capabilities of the Varian Ethos platform with the high-throughput IGRT delivery of the Varian Halcyon, supported by automated scripting.

METHODS: We developed an end-to-end dual-platform workflow that dynamically transitions between ART and IGRT delivery based on patient needs. Key components include Eclipse Scripting API (ESAPI) automation to streamline adapted plan ingestion from the Ethos Treatment Planning and Management System (TPMS) export directory, compatibility conversion for …


Preterm Birth Increases Susceptibility To Hyperglycemia-Induced Kidney Injury With Sex-Specific Differences In Structural And Molecular Responses, Rachel K Dailey, Aleksandra Cwiek, Logan C Hamil, Sage Timberline, Ayyappa Kumar Sista Kameshwar, Masako Suzuki, Jaya Isaac, Kimberly Deronde, Mark Conaway, Kevin M Bennett, Edwin J Baldelomar, Matthew R Hoch, Kimberly J Reidy, Jennifer R Charlton May 2026

Preterm Birth Increases Susceptibility To Hyperglycemia-Induced Kidney Injury With Sex-Specific Differences In Structural And Molecular Responses, Rachel K Dailey, Aleksandra Cwiek, Logan C Hamil, Sage Timberline, Ayyappa Kumar Sista Kameshwar, Masako Suzuki, Jaya Isaac, Kimberly Deronde, Mark Conaway, Kevin M Bennett, Edwin J Baldelomar, Matthew R Hoch, Kimberly J Reidy, Jennifer R Charlton

2020-Current year OA Pubs

BACKGROUND: Preterm birth increases the long-term risk of diabetes and chronic kidney disease (CKD), yet its impact on diabetic kidney disease (DKD) is unclear. We previously showed that male preterm mice with diabetes develop early features of DKD, including reduced podocyte density, decreased renin expression, activation of angiogenesis pathways, and impaired endothelial-podocyte signaling. Here, we examine whether preterm birth similarly accelerates DKD progression in female mice and compare structural and transcriptomic outcomes in the females to the prior male cohort to assess sex-specific differences.

METHODS: Preterm mice were delivered by Caesarean section at 19 days post conception (dpc) and term …


A Prospective, Multi-Center, Observational Study Of The Safety, Tolerability And Effectiveness Of Nusinersen In Adult Patients With Spinal Muscular Atrophy, Craig M Zaidman, Crystal Proud, Bing Liao, Nassim Rad, Doreen Ho, Mary-Lynn Chu, Shafeeq Ladha, Thomas O Crawford, Shakti Nayar, Angela Genge, Margaret Frey, Chad Heatwole, Daphne Lew May 2026

A Prospective, Multi-Center, Observational Study Of The Safety, Tolerability And Effectiveness Of Nusinersen In Adult Patients With Spinal Muscular Atrophy, Craig M Zaidman, Crystal Proud, Bing Liao, Nassim Rad, Doreen Ho, Mary-Lynn Chu, Shafeeq Ladha, Thomas O Crawford, Shakti Nayar, Angela Genge, Margaret Frey, Chad Heatwole, Daphne Lew

2020-Current year OA Pubs

Nusinersen, an antisense oligonucleotide, modulates pre-mRNA splicing to produce full length survival motor neuron protein in spinal muscular atrophy (SMA). It was approved in the US for SMA in all ages based on evidence in children. In adults, studies of nusinersen rely on real-world observational data and show stability or small improvements over time. We performed a prospective, 30 month longitudinal, observational multi-center study of adults initiating nusinersen with SMA types II/III to examine its safety, tolerability, and effectiveness. 43 participants (20 female; 14 ambulatory; 3, 17, and 23 with 2, 3, and ≥4 SMN2 copies, respectively), mean (SD) age …


Defining The Qualities Of A Surgical Resident Who "Gets It": A Qualitative Analysis Of Faculty And Resident Perceptions, Shaleen V Sathe, Ravi R Agrawal, Jennifer Yu, Paul E Wise, Michael Awad, Kevin Y Pei May 2026

Defining The Qualities Of A Surgical Resident Who "Gets It": A Qualitative Analysis Of Faculty And Resident Perceptions, Shaleen V Sathe, Ravi R Agrawal, Jennifer Yu, Paul E Wise, Michael Awad, Kevin Y Pei

2020-Current year OA Pubs

BACKGROUND: The phrase "getting it" is frequently used in surgical trainee assessment, yet its meaning remains undefined. This study explores how residents and faculty define the concept and whether perceptions align.

METHODS: Semi-structured interviews were conducted with 11 residents and 13 faculty at a single institution and analyzed using reflexive thematic analysis.

RESULTS: Residents described "getting it" as clinical competence, social awareness, feedback responsiveness, and team integration, while noting challenges with interpreting implicit expectations and the influence of faculty bias. Faculty described "getting it" as a gestalt recognition of initiative, insight, and sound clinical judgment. Both agreed that the concept …


Utility Of Routine Histopathologic And Culture Analysis In Wrist Tenosynovectomy, Andrew Straszewski, Stockton Troyer, Martin I Boyer, Charles A Goldfarb May 2026

Utility Of Routine Histopathologic And Culture Analysis In Wrist Tenosynovectomy, Andrew Straszewski, Stockton Troyer, Martin I Boyer, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Routine practices without a clear impact on patient care merit continuous reassessment. This retrospective study evaluated the value of routine histopathologic and culture analysis in patients who underwent flexor or extensor tendon tenosynovectomy.

METHODS: Current Procedural Terminology codes for isolated tenosynovectomy procedures were queried from an institutional database from 2018 to 2023, including all patients aged ≥18 treated by one of seven fellowship-trained hand surgeons. Demographics, past medical and surgical history, clinic notes, operative notes, imaging, pathology, and culture data were reviewed. We assessed for changes to the treatment course of each patient based on the pathology and culture …


Vustruct: A Compute Pipeline For High Throughput And Personalized Structural Biology, Christopher W. Moth, Jonathan H. Sheehan, Abdullah Al Mamun, R. Michael Sivley, Alican Gulsevin, David C. Rinker, Zenab F. Mchaourab, Undiagnosed Disease Network, John A. Capra, Jens Meiler May 2026

Vustruct: A Compute Pipeline For High Throughput And Personalized Structural Biology, Christopher W. Moth, Jonathan H. Sheehan, Abdullah Al Mamun, R. Michael Sivley, Alican Gulsevin, David C. Rinker, Zenab F. Mchaourab, Undiagnosed Disease Network, John A. Capra, Jens Meiler

2020-Current year OA Pubs

Effective diagnosis and treatment of rare genetic disorders requires the interpretation of a patient's genetic variants of unknown significance (VUSs). Today, clinical decision-making is primarily guided by gene-phenotype association databases and DNA-based scoring methods. Our web-accessible variant analysis pipeline, VUStruct, supplements these established approaches by deeply analyzing the downstream molecular impact of variation in context of 3D protein structure. VUStruct's growing impact is fueled by the co-proliferation of protein 3D structural models, gene sequencing, compute power, and artificial intelligence. Contextualizing VUSs in protein 3D structural models also illuminates longitudinal genomics studies and biochemical bench research focused on VUS, and we …


Advancing Peripheral Nerve Regeneration (Nerve Space 2025), Ken Porche, Tara Sara Saffari, Hollie Power, Wesley P Thayer, S Shelby Burks, John C Elfar, Alexander Y Shin, David M Brogan May 2026

Advancing Peripheral Nerve Regeneration (Nerve Space 2025), Ken Porche, Tara Sara Saffari, Hollie Power, Wesley P Thayer, S Shelby Burks, John C Elfar, Alexander Y Shin, David M Brogan

2020-Current year OA Pubs

UNLABELLED: Peripheral nerve injuries remain a major clinical challenge due to slow axonal regeneration, rapid Wallerian degeneration (WD), and degeneration of target organs prior to reinnervation.

WHERE ARE WE NOW?: Strategies to enhance regeneration can be broadly divided into three categories: preventing or delaying WD, speeding up axonal regeneration, and improving the molecular environment at the injury site. Approaches to delay WD include polyethylene glycol-mediated axonal fusion, which may restore early axonal continuity and conduction, and inhibition of sterile alpha and TIR motif-containing 1, the central executioner of WD, with small-molecule inhibitors now in clinical trials. Methods to accelerate axon …


Use And Public Reporting Of Predetermined Change Control Plans For Ai-Enabled Medical Devices, Patryk A Dabek, Florence T Bourgeois, Ariel D Stern, Yi Zhu, Alexander O Everhart May 2026

Use And Public Reporting Of Predetermined Change Control Plans For Ai-Enabled Medical Devices, Patryk A Dabek, Florence T Bourgeois, Ariel D Stern, Yi Zhu, Alexander O Everhart

2020-Current year OA Pubs

No abstract provided.


Primary Cilia Regulate Glp-1 Signaling In Pancreatic Β Cells, Isabella Melena, Jeong Hun Jo, Shannon E Townsend, Samantha Adamson Digruccio, Xinhang Dong, Lifei Zhu, Jonathan Campbell, Jing W Hughes May 2026

Primary Cilia Regulate Glp-1 Signaling In Pancreatic Β Cells, Isabella Melena, Jeong Hun Jo, Shannon E Townsend, Samantha Adamson Digruccio, Xinhang Dong, Lifei Zhu, Jonathan Campbell, Jing W Hughes

2020-Current year OA Pubs

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are mainstay therapies for diabetes and obesity, acting in part by enhancing glucose-dependent insulin secretion. While the primary cilium is a known signaling compartment for certain G-protein coupled receptors (GPCRs), its role in the β-cell response to incretins remains undefined. Here, we show that primary cilia are essential for full GLP-1R signaling. Loss of β-cell cilia in mouse and human islets severely impaired GLP-1-potentiated insulin secretion, an effect preceded by blunted whole-cell cAMP and Ca


From Low Field To High Value: Robust Cortical Mapping From Low-Field Mri, Karthik Gopinath, Timothy Coalson, Matthew F Glasser, David Van Essen, Et Al. May 2026

From Low Field To High Value: Robust Cortical Mapping From Low-Field Mri, Karthik Gopinath, Timothy Coalson, Matthew F Glasser, David Van Essen, Et Al.

2020-Current year OA Pubs

Three-dimensional reconstruction of cortical surfaces from MRI for subsequent morphometric analysis is fundamental for understanding brain structure. While high-field Magnetic Resonance Imaging (HF-MRI) is the standard in research and clinical settings, its relatively limited availability hinders widespread use. Low-field MRI (LF-MRI), particularly portable systems, offers a cost-effective and accessible alternative. However, existing cortical surface analysis tools, such as FreeSurfer, are optimized for high-resolution HF-MRI and struggle with the lower signal-to-noise ratio (SNR) and resolution of LF-MRI. In this work, we present a machine learning method for 3D reconstruction and analysis of portable LF-MRI scans over a range of contrasts and …