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Premarket Clinical Evidence Strength And Recalls Of High-Risk Therapeutic Medical Devices, Maryam Mooghali, Faaizah Arshad, Vinay K Rathi, Kushal T Kadakia, Alexander O Everhart, Joseph S Ross, Sanket S Dhruva Aug 2026

Premarket Clinical Evidence Strength And Recalls Of High-Risk Therapeutic Medical Devices, Maryam Mooghali, Faaizah Arshad, Vinay K Rathi, Kushal T Kadakia, Alexander O Everhart, Joseph S Ross, Sanket S Dhruva

2020-Current year OA Pubs

IMPORTANCE: High-risk medical devices approved through the US Food and Drug Administration (FDA) premarket approval (PMA) pathway may be supported by limited premarket clinical evidence, leaving uncertainties about safety. Whether device, premarket clinical evidence, or regulatory characteristics are associated with subsequent device recalls is unknown.

OBJECTIVE: To examine the association between device, premarket clinical evidence, and regulatory characteristics and serious recalls among high-risk therapeutic devices.

DESIGN AND SETTING: This cross-sectional study reviewed 193 high-risk therapeutic medical devices approved through the FDA's PMA pathway between January 1, 2014, and December 31, 2023. Data were analyzed between August 2025 and December 2025. …


Acute Opioid Responses Are Modulated By Dynamic Interactions Of Oprm1 And Fgf12, Paige M Lemen, Alexander S Hatoum, Arpana Agrawal, Et Al. Jul 2026

Acute Opioid Responses Are Modulated By Dynamic Interactions Of Oprm1 And Fgf12, Paige M Lemen, Alexander S Hatoum, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

We generated time-series data for 105 morphine- and naloxone-related traits across ~700 BXD mice (64 diverse strains for both sexes) for 3 hr after a single morphine injection. Variations in responses were mapped using genome sequencing-based genotypes. The locomotor responses to morphine mapped to the µ opioid receptor gene (


Tgf-Β Drives The Conversion Of Conventional Nk Cells Into Uterine Tissue-Resident Nk Cells To Support Murine Pregnancy, Josselyn D Barahona, Liping Yang, D Michael Nelson, Wayne M Yokoyama Jul 2026

Tgf-Β Drives The Conversion Of Conventional Nk Cells Into Uterine Tissue-Resident Nk Cells To Support Murine Pregnancy, Josselyn D Barahona, Liping Yang, D Michael Nelson, Wayne M Yokoyama

2020-Current year OA Pubs

Tissue microenvironments shape lymphocyte differentiation to align immune function with local physiological demands. Uterine natural killer (NK) cells are critical for reproductive success, yet the molecular cues in the uterus that instruct their specialized identities remain incompletely understood. Here, we identify a TGF-β-dependent differentiation pathway by which circulating conventional NK cells convert into uterine tissue-resident NK cells during murine pregnancy. Loss of TGF-β receptor II expression in


Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks Jul 2026

Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high


Subunit Composition Of The Katp Channels That Modulate Contractility Of Skeletal Muscle During Fatigue, Rosa Scala, Yuezhou Chen, Berk Mizrak, Gretchen A Meyer, Colin G Nichols Jul 2026

Subunit Composition Of The Katp Channels That Modulate Contractility Of Skeletal Muscle During Fatigue, Rosa Scala, Yuezhou Chen, Berk Mizrak, Gretchen A Meyer, Colin G Nichols

2020-Current year OA Pubs

ATP-sensitive potassium (KATP) channels are among the most expressed ion channels in skeletal muscle sarcolemma. While all KATP subunits can be detected in skeletal muscles, transcripts are enriched for KCNJ11 and ABCC9, suggesting that noncanonical Kir6.2/SUR2A assembly may constitute the majority of sarcolemmal KATP channels, but there has been no systematic dissection of KATP makeup in skeletal muscles. Here, we used a unique collection of murine lines selectively lacking specific channel-forming subunits (knockout, KO), and combined a genetic and pharmacological approach to determine which subunits of KATP channels are functionally relevant for skeletal muscle contraction. Under fatiguing conditions, isometric tetanic …


Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle Jul 2026

Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle

2020-Current year OA Pubs

A-isoforms of cytosolic growth factor homologous factors (FGF11-14) mediate long-term inactivation (LTI) of voltage-dependent sodium (NaV) channels. LTI is a rapid onset process that is competitive with the fast inactivation (IF) intrinsic to NaV channels, with little or no interconversion between inactivated states. Since recovery from LTI is orders of magnitude slower than recovery from IF, repetitive depolarizations lead to use-dependent accumulation of NaV channels in slow recovery states, thereby limiting NaV availability during trains of action potentials. Of the two or more N-terminal splice variants of the various FGF homologues, LTI specifically arises only from the A-isoform of each …


Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al. Jul 2026

Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Endotracheal aspirate culture (EAC) practices for evaluation of ventilator-associated infections (VAI) vary widely across pediatric hospitals, and overuse can contribute to overdiagnosis and overtreatment for VAI. Diagnostic stewardship strategies to optimize EAC testing practices may reduce overtesting and unnecessary antibiotic treatment.

OBJECTIVE: To evaluate the association of diagnostic stewardship of EACs using clinical decision support with culture rates, antibiotic use, and patient outcomes across a multicenter collaborative of pediatric intensive care units (PICUs).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study with a pre-post study design among the BrighT STAR (Testing Stewardship for Antibiotic Reduction) Quality Improvement …


Prescribed Short-Acting Hormonal Contraceptive Use Among Premenopausal Females, Israel Bacha, Suleepon Uttamapinan, Hannah Harsanyi, Abigail Liberty, Lin Yang, Adetunji T Toriola Jul 2026

Prescribed Short-Acting Hormonal Contraceptive Use Among Premenopausal Females, Israel Bacha, Suleepon Uttamapinan, Hannah Harsanyi, Abigail Liberty, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Hormonal contraceptive use has important implications for both reproductive and general health. However, the patterns and trends of short-acting hormonal contraceptive use among US premenopausal females remain insufficiently characterized.

OBJECTIVE: To evaluate trends in and factors associated with prescribed short-acting hormonal contraceptive use among US premenopausal females.

DESIGN, SETTING, AND PARTICIPANTS: Serial, cross-sectional analyses were conducted using US nationally representative data from the National Health and Nutrition Examination Survey (NHANES), including 10 survey cycles between 1999 to 2000 and 2017 to 2020 (before the COVID-19 pandemic). Participants included noninstitutionalized premenopausal females aged 15 years to younger than 60 years …


Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al. Jul 2026

Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Inferior petrosal sinus sampling (IPSS) is important for confirming Cushing's Disease (CD). Due to lack of corticotropin releasing hormone (CRH) availability, desmopressin/DDAVP is being used as the alternative stimulating agent but has limited data regarding testing cutoffs.

DESIGN: We compared the stimulation profiles of desmopressin and CRH in patients with CD.

METHODS: Data from the multi-center Registry of Adenomas of the PItuitary and Related Disorders (RAPID) was evaluated. 93 patients with CD confirmed by pathology or biochemical remission that underwent IPSS testing prior to surgical resection (desmopressin [n = 57], CRH [n = 36] or both [n = 1]). …


Patient-Centered Approach To Surgical Prevention Of Ovarian Cancer: A Nonrandomized Clinical Trial, Karen H Lu, Andrea R Hagemann, Et Al. Jul 2026

Patient-Centered Approach To Surgical Prevention Of Ovarian Cancer: A Nonrandomized Clinical Trial, Karen H Lu, Andrea R Hagemann, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative.

OBJECTIVE: To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October …


Maternal Health And Sociodemographic Characteristics Influence Infant Growth To 24 Months In The Tunza Mwana Cohort: A Prospective Cohort Study, David Taylor Hendrixson, Mark J Manary, Et Al. Jul 2026

Maternal Health And Sociodemographic Characteristics Influence Infant Growth To 24 Months In The Tunza Mwana Cohort: A Prospective Cohort Study, David Taylor Hendrixson, Mark J Manary, Et Al.

2020-Current year OA Pubs

Upstream pathways influencing child growth are complex. Weight-for-age z-score (WAZ) reflects both ponderal and linear growth and can identify children at high mortality risk. Using data from a prospective cohort of 326 mother-child pairs in Kenya, we evaluated whether associations between maternal exposures and child growth outcomes in early and later childhood. Growth trajectories were examined using locally weighted scatterplot smoothing and piecewise linear mixed-effect models with a knot at age 3 months. Poisson regression models examined associations between maternal characteristics and child underweight (WAZ <  -2) and stunting (LAZ <  -2) before and after 3 months. Mean WAZ increased to a peak at 3 months before declining steadily through 24 months. Lower maternal education (adjusted β [aβ] -0.18; 95% CI: -0.24, -0.13), household crowding (aβ -0.2; 95% CI: -0.28, -0.11), lower wealth quintile (aβ -0.04; 95% CI: -0.06, -0.02) and multiparity (aβ -0.16; 95% CI: -0.23, -0.1) were associated with lower monthly rate of change in WAZ prior to age 3 months. Younger maternal age was associated with an increased monthly rate of change in WAZ (aβ = 0.13; 95% CI: 0.08, 0.18) before 3 months and decreased monthly WAZ (aβ -0.02; 95% CI: -0.03, -0.01) after 3 months. Preterm birth was associated with increased risk of underweight in both periods (aRR 2.77; 95% CI: 1.39-5.50). Maternal mental health, intimate partner violence and adverse childhood experiences were not significantly associated with child growth. Maternal nutritional, socio-economic and household-level factors shape early growth, emphasising the need for cross-sectoral programs to support growth.


Patterns Of Brain-Wide Associations Reflect Socioeconomics, Scott Marek, Meghan Rose Donohue, Nicole R Karcher, Caroline P Hoyniak, Roselyne J Chauvin, Ashley C Meyer, John Miller, Andrew N Van, Anxu Wang, Noah J Baden, Vahdeta Suljic, Kristen M Scheidter, Julia Monk, Forrest I Whiting, Nadeshka J Ramirez-Perez, Samuel R Krimmel, Athanasia Metoki, Rebecca F Schwarzlose, Steven E Petersen, Joan Luby, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Et Al. Jun 2026

Patterns Of Brain-Wide Associations Reflect Socioeconomics, Scott Marek, Meghan Rose Donohue, Nicole R Karcher, Caroline P Hoyniak, Roselyne J Chauvin, Ashley C Meyer, John Miller, Andrew N Van, Anxu Wang, Noah J Baden, Vahdeta Suljic, Kristen M Scheidter, Julia Monk, Forrest I Whiting, Nadeshka J Ramirez-Perez, Samuel R Krimmel, Athanasia Metoki, Rebecca F Schwarzlose, Steven E Petersen, Joan Luby, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Previous brain-wide association studies (BWAS) have linked specific environmental and behavioral variables to brain variability. In this work, we mapped 649 variables to children's brains and compared the resultant BWAS maps with each other and with neurobiological reference patterns. Socioeconomic status (SES) showed the strongest brain-wide associations. The SES associations were strongest in motor and sensory but not cognitive regions, a pattern shared across many BWAS maps, including intelligence quotient (IQ). A single, common BWAS brain pattern existed across variables that was most reflective of a child's socioeconomics. Adjusting for SES weakened brain-IQ associations, eliminating the BWAS motor and sensory …


Opposing Regulation By Rev1 Of Dna Polymerase Zeta Activity On Damaged Versus Undamaged Dna, Rachel Bezalel-Buch, Carrie Stith, Alena V Makarova, Sara K Binz, Peter M Burgers Jun 2026

Opposing Regulation By Rev1 Of Dna Polymerase Zeta Activity On Damaged Versus Undamaged Dna, Rachel Bezalel-Buch, Carrie Stith, Alena V Makarova, Sara K Binz, Peter M Burgers

2020-Current year OA Pubs

The Rev1 deoxycytidyl transferase functions as a scaffold protein for DNA polymerase ζ (Pol ζ)-mediated translesion synthesis (TLS). Biochemical studies with yeast enzymes indicate that Rev1 plays a dual regulatory role in TLS, stimulating Pol ζ activity at sites of damage but inhibiting its activity on undamaged DNA. An evolutionary conserved N-terminal alpha-helical motif (M1), located 10-20 amino acids upstream of Rev1's single BRCT domain, is required for the inhibitory activity of Rev1 on undamaged DNA. Mutations in the M1 motif result in a stimulation of Pol ζ replication activity on both undamaged and damaged DNA. Yeast cells carrying a …


Growth In Early Infancy Drives Optimal Brain Functional Connectivity Which Predicts Cognitive Flexibility In Later Childhood, Chiara Bulgarelli, Anna Blasi, Samantha Mccann, Bosiljka Milosavljevic, Giulia Ghillia, Ebrima Mbye, Ebou Touray, Tijan Fadera, Lena Acolatse, Sophie E Moore, Sarah Lloyd-Fox, Clare E Elwell, Adam T Eggebrecht, Bright Study Team Jun 2026

Growth In Early Infancy Drives Optimal Brain Functional Connectivity Which Predicts Cognitive Flexibility In Later Childhood, Chiara Bulgarelli, Anna Blasi, Samantha Mccann, Bosiljka Milosavljevic, Giulia Ghillia, Ebrima Mbye, Ebou Touray, Tijan Fadera, Lena Acolatse, Sophie E Moore, Sarah Lloyd-Fox, Clare E Elwell, Adam T Eggebrecht, Bright Study Team

2020-Current year OA Pubs

Functional brain network organisation, measured by functional connectivity (FC), reflects key neurodevelopmental processes for healthy development. Early exposure to adversity, for example undernutrition, affects neurodevelopment, observable via disrupted FC, and leads to poorer outcomes from preschool age onwards. We assessed longitudinally the impact of early growth trajectories on developmental FC in a rural Gambian population from age 5-24 months. To investigate how these early trajectories relate to later childhood outcomes, we assessed cognitive flexibility at 3-5 years. We observed that early physical growth before the fifth month of life drove optimal developmental trajectories of FC that in turn predicted cognitive …


Autoregulation Of Three Yeast Ribosomal Protein Genes By Splicing Inhibition, David Granas, Anirudh Kesanapally, Michael A White, Gary D Stormo Jun 2026

Autoregulation Of Three Yeast Ribosomal Protein Genes By Splicing Inhibition, David Granas, Anirudh Kesanapally, Michael A White, Gary D Stormo

2020-Current year OA Pubs

Yeast ribosomal protein genes RPL18B, RPL28, and RPS22B are autoregulated by inhibition of splicing. This is demonstrated by inserting their introns into a chromosomal copy of GFP and observing repression upon induction of the cognate protein. In RPL18B and RPS22B, a predicted conserved secondary structure within the intron is required for regulation, while in RPL28, it is not.


Role Of Households With Children In Community Spread Of Multidrug-Resistant Enterobacterales, St. Louis, Missouri, Usa, Barrett Breeze, Ahmed Babiker, Sreenivas Konda, Alaina L Robinson, Stefan J Green, Catherine C Babbs, Federico Cunha, Katherine Y Shen, India Shepherd Hammond, Stephanie A Fritz, Latania K Logan Jun 2026

Role Of Households With Children In Community Spread Of Multidrug-Resistant Enterobacterales, St. Louis, Missouri, Usa, Barrett Breeze, Ahmed Babiker, Sreenivas Konda, Alaina L Robinson, Stefan J Green, Catherine C Babbs, Federico Cunha, Katherine Y Shen, India Shepherd Hammond, Stephanie A Fritz, Latania K Logan

2020-Current year OA Pubs

Community-acquired multidrug-resistant (MDR) Enterobacterales bacteria are an increasing public health concern, yet whether households play a role in community spread remains unclear. We investigated 150 households with children in St. Louis, Missouri, USA, for MDR Enterobacterales. We cultured swab specimens from household members and environmental surfaces for identification and antimicrobial susceptibility testing. We also performed whole-genome sequencing in the 53 (35%) households where >1 MDR Enterobacterales species were recovered. Enterobacter hormaechei predominated, followed by Klebsiella pneumoniae and Pantoea species. Whole-genome sequencing revealed closely related strains shared between persons and environmental surfaces, suggesting potential intra-household transmission. We identified >1 horizontal gene …


Lingo4 Coordinates Ilc3-Intrinsic Il-22 Production And Microbiota-Mediated Ilc3 Homeostasis, José L Fachi, Tihana Trsan, Cristiane Sécca, Sarah De Oliveira, Vinícius R Rodovalho, Patrick Fernandes Rodrigues, Wandy L Beatty, Raki Sudan, Shitong Wu, Bishan Bhattarai, Santosh K Panda, Marina Cella, Susan Gilfillan, Marco Colonna Jun 2026

Lingo4 Coordinates Ilc3-Intrinsic Il-22 Production And Microbiota-Mediated Ilc3 Homeostasis, José L Fachi, Tihana Trsan, Cristiane Sécca, Sarah De Oliveira, Vinícius R Rodovalho, Patrick Fernandes Rodrigues, Wandy L Beatty, Raki Sudan, Shitong Wu, Bishan Bhattarai, Santosh K Panda, Marina Cella, Susan Gilfillan, Marco Colonna

2020-Current year OA Pubs

LINGO4 is a leucine-rich repeat and immunoglobulin-like domain-containing transmembrane protein encoded immediately adjacent to Rorc, the gene for RORγt, raising the possibility that it contributes to the biology of RORγt+ lymphocytes. However, its impact on these cells and resistance to enteric infections has remained unknown. Here, we identify LINGO4 as a critical regulator of group 3 innate lymphoid cells (ILC3s). Lingo4-/- ILC3s exhibit a profound, cell-intrinsic defect in IL-22 production linked to impaired STAT3 activation, mitochondrial dysfunction, elevated ROS, and increased apoptosis. In vivo, Lingo4 deficiency also drives a dysbiotic gut microbiota, resulting in an additional, microbiota-dependent loss of ILC3s. …


Viscoelastic And Morphologic Changes In The Lumbar Intervertebral Discs Of The 5xfad Mouse Model Of Alzheimer's Disease, C E Gonzalez, C A Schurman, K A Wilson, B Schilling, L M Ellerby, S Y Tang Jun 2026

Viscoelastic And Morphologic Changes In The Lumbar Intervertebral Discs Of The 5xfad Mouse Model Of Alzheimer's Disease, C E Gonzalez, C A Schurman, K A Wilson, B Schilling, L M Ellerby, S Y Tang

2020-Current year OA Pubs

BACKGROUND: Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD.

AIMS: The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD.

MATERIALS AND METHODS: Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we …


Noninvasive Enrichment Of Circulating Tumor Biomarkers In A Mouse Model Of Diffuse Midline Glioma Using Focused Ultrasound, Dingyue Zhang, Yimei Yue, Yan Gong, Leqi Yang, Kevin Xu, Jinyun Yuan, Hong Chen Jun 2026

Noninvasive Enrichment Of Circulating Tumor Biomarkers In A Mouse Model Of Diffuse Midline Glioma Using Focused Ultrasound, Dingyue Zhang, Yimei Yue, Yan Gong, Leqi Yang, Kevin Xu, Jinyun Yuan, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Diagnosing diffuse midline glioma (DMG) through invasive tissue biopsies is challenging due to the tumor's eloquent location at the pons. Liquid biopsies offer a promising noninvasive alternative; however, their limited detection sensitivity and lack of information on the source of biomarkers pose great challenges. This study aimed to evaluate the feasibility and safety of using focused ultrasound (FUS) with microbubbles to enrich circulating DMG tumor biomarkers in blood and cerebrospinal fluid (CSF) using a mouse model.

METHODS: Murine DMG cells, transfected with enhanced green fluorescent protein (EGFP) and firefly luciferase (Fluc) genes, were orthotopically injected into the mouse brain. …


Trastuzumab Deruxtecan In Hormone Receptor-Positive, Her2-Low/-Ultralow Metastatic Breast Cancer (Destiny-Breast06): Outcome Analyses By Time To Progression On Prior First-Line Endocrine Therapy With Cdk4/6 Inhibitor And Baseline Burden Of Disease, G Curigliano, N A Bagegni, Et Al. Jun 2026

Trastuzumab Deruxtecan In Hormone Receptor-Positive, Her2-Low/-Ultralow Metastatic Breast Cancer (Destiny-Breast06): Outcome Analyses By Time To Progression On Prior First-Line Endocrine Therapy With Cdk4/6 Inhibitor And Baseline Burden Of Disease, G Curigliano, N A Bagegni, Et Al.

2020-Current year OA Pubs

BACKGROUND: In DESTINY-Breast06, trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) versus physician's choice of chemotherapy (TPC) for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low/-ultralow metastatic breast cancer (mBC), without new safety signals. We report additional analyses exploring outcomes for patients with characteristics that affect prognosis.

PATIENTS AND METHODS: Patients were randomly assigned 1 : 1 to receive T-DXd (5.4 mg/kg) once every 3 weeks or TPC. Subgroups were specified post hoc from the intent-to-treat population (N = 866). Outcomes were PFS, objective response rate (ORR), and duration of response (DOR) by blinded independent central review …


Cabozantinib Plus Nivolumab And Ipilimumab In Previously Untreated, Advanced Renal Cell Carcinoma: Final Results And Biomarker Analyses From The Phase Iii Cosmic-313 Study, R J Motzer, M A Reimers, Et Al. Jun 2026

Cabozantinib Plus Nivolumab And Ipilimumab In Previously Untreated, Advanced Renal Cell Carcinoma: Final Results And Biomarker Analyses From The Phase Iii Cosmic-313 Study, R J Motzer, M A Reimers, Et Al.

2020-Current year OA Pubs

BACKGROUND: Primary results from COSMIC-313 demonstrated significantly longer progression-free survival (PFS) with first-line cabozantinib plus nivolumab and ipilimumab versus placebo plus nivolumab and ipilimumab in patients with advanced renal cell carcinoma. Final efficacy and safety results, as well as data from exploratory biomarker analyses, are reported here.

PATIENTS AND METHODS: The design, participants, and primary-endpoint PFS outcomes have been reported previously for this phase III, double-blind, randomized (1 : 1) study of cabozantinib or placebo plus nivolumab and ipilimumab in adults with previously untreated, advanced clear cell renal cell carcinoma. The secondary endpoint was overall survival (OS) in the intention-to-treat …


Biomedgraphica: An All-In-One Platform For Joint Textual Biomedical Prior Knowledge And Numeric Graph Generation, Heming Zhang, Shunning Liang, Tim Xu, Wenyu Li, Di Huang, Yuhan Dong, Philip Miller, Peter Goedegebuure, Marco Sardiello, Jonathan Cooper, William Buchser, Patricia Dickson, Ryan C Fields, Carlos Cruchaga, Yixin Chen, Michael Province, Philip Payne, Fuhai Li, Et Al. Jun 2026

Biomedgraphica: An All-In-One Platform For Joint Textual Biomedical Prior Knowledge And Numeric Graph Generation, Heming Zhang, Shunning Liang, Tim Xu, Wenyu Li, Di Huang, Yuhan Dong, Philip Miller, Peter Goedegebuure, Marco Sardiello, Jonathan Cooper, William Buchser, Patricia Dickson, Ryan C Fields, Carlos Cruchaga, Yixin Chen, Michael Province, Philip Payne, Fuhai Li, Et Al.

2020-Current year OA Pubs

MOTIVATION: Multiomics data analysis is essential for scientific discovery in precision medicine. However, translating analysis results of omics data analysis into novel scientific hypotheses remains a significant challenge. Human experts must manually review analysis results and generate new hypotheses based on extensive and interconnected biomedical prior knowledge, which is subjective and not scalable. While large language models can accelerate the discovery, their reasoning improves when grounded in structured, auditable, and comprehensive biomedical prior knowledge. However, biomedical knowledge is scattered across heterogeneous databases that use diverse and inconsistent nomenclature systems, making it difficult to integrate resources into a unified format for …


Short Autoinhibitory Sequences Control Phase Separation Of An Essential Bacterial Transcription Termination Factor, Emilia Krypotou, Kiersten M Ruff, Leah K Mckinney, Guy E Townsend Ii, Jue D Wang, Rohit V Pappu, Eduardo A Groisman Jun 2026

Short Autoinhibitory Sequences Control Phase Separation Of An Essential Bacterial Transcription Termination Factor, Emilia Krypotou, Kiersten M Ruff, Leah K Mckinney, Guy E Townsend Ii, Jue D Wang, Rohit V Pappu, Eduardo A Groisman

2020-Current year OA Pubs

Within cells, across diverse organisms, macromolecular condensation enables spatial and temporal organization of biochemical reactions by organizing proteins and nucleic acids into compositionally distinct membraneless biomolecular condensates. In the gut bacterium Bacteroides thetaiotaomicron, condensate formation by the transcription termination factor Rho (BtRho) increases its termination activity and promotes B. thetaiotaomicron fitness in the mammalian gut. Here, we elucidate the molecular mechanism governing carbon starvation-induced BtRho phase separation. We establish that short, specific amino acid sequences within BtRho's intrinsically disordered region (IDR) control BtRho condensation via complex coacervation. The identified sequences participate in RNA and intra-IDR regulatory interactions that drive condensate …


Initial Injury Type And Violent Reinjury, Nicholas Szoko, Daphne Lew, Taylor Kaser, Zoe M Miller, Matt Vogel, Michael A Mancini, Lindsay M Kranker, Christopher Behr, Vicki Moran, Rachel Ancona, Kristen Mueller Jun 2026

Initial Injury Type And Violent Reinjury, Nicholas Szoko, Daphne Lew, Taylor Kaser, Zoe M Miller, Matt Vogel, Michael A Mancini, Lindsay M Kranker, Christopher Behr, Vicki Moran, Rachel Ancona, Kristen Mueller

2020-Current year OA Pubs

IMPORTANCE: Violent injuries are the leading cause of death among children and young adults in the United States. Violent injury may increase the risk of subsequent injury (ie, violent reinjury), but it is unclear how this risk varies across different injury types (eg, blunt assault, stabbing, firearm).

OBJECTIVE: To describe patterns of violent reinjury across different injury types to inform tailored prevention strategies.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study included patients who presented with violent injuries to 2 adult and 2 pediatric level I trauma centers in St Louis, Missouri, from January 2016 to December 2023.

EXPOSURES: Violent …


Chronic Conditions And Mortality In Medicare Beneficiaries Before And After The Covid-19 Pandemic, R J Waken, Fengxian Wang, Jose F Figueroa, Rishi K Wadhera, Khavya Avula, E John Orav, Anne Mobley Butler, Karen E Joynt Maddox Jun 2026

Chronic Conditions And Mortality In Medicare Beneficiaries Before And After The Covid-19 Pandemic, R J Waken, Fengxian Wang, Jose F Figueroa, Rishi K Wadhera, Khavya Avula, E John Orav, Anne Mobley Butler, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: There were well-documented changes in health care use during the COVID-19 pandemic. Little is known about whether there were any associated decreases in claims-based comorbidity ascertainment that might have relevance to health services and policy research.

OBJECTIVE: To quantify differences in claims-based comorbidity assessment in Medicare beneficiaries pre- vs post-COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the 30 Chronic Conditions Warehouse 1- or 2-year lookback claims algorithms to ascertain each comorbidity with exact date ranges for all fee-for-service (FFS) and Medicare Advantage (MA) beneficiaries. Data were analyzed from April 2025 to April 2026.

EXPOSURES: The …


Natural History Of Limb Girdle Muscular Dystrophy R1 (Lgmdr1): A Grasp Consortium Study, Stephanie M Hunn, Andrew R Findlay, Amanda Clause, Conrad C Weihl, Et Al. Jun 2026

Natural History Of Limb Girdle Muscular Dystrophy R1 (Lgmdr1): A Grasp Consortium Study, Stephanie M Hunn, Andrew R Findlay, Amanda Clause, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

Identifying clinical outcome assessments (COAs) that are able to detect change in functional abilities over time in the limb girdle muscular dystrophy (LGMD) population is critical for managing disease progression in addition to determining drug efficacy in the context of anticipated therapeutic trials. Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 participants with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each participant completed a battery of COAs, including the North Star Assessment for Limb Girdle-Type Muscular Dystrophies (NSAD), 100-meter timed test (100 m), Performance of the Upper Limb (PUL), …


Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease, Mike Seed, Cynthia Ortinau, Caroline Lee, Et Al. Jun 2026

Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease, Mike Seed, Cynthia Ortinau, Caroline Lee, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Neurodevelopmental impairments are common in children with congenital heart disease.

OBJECTIVES: To compare neurodevelopmental outcomes by cardiac diagnosis and identify associations between medical and social factors and early neurodevelopmental outcomes among children with congenital heart disease.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used neurodevelopmental follow-up data obtained between May 1, 2019, and June 30, 2022, and entered into the Cardiac Neurodevelopmental Outcome Collaborative (CNOC) registry, with linkage to the Pediatric Cardiac Critical Care Consortium registry. Children younger than 30 months from 25 CNOC sites were studied. Data analysis was performed between January 2023 and December 2024.

EXPOSURES: Patients …


Frame-Wise Multi-Echo Distortion Correction For Superior Functional Mri, Andrew N Van, David F Montez, Timothy O Laumann, Philip N Cho, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Roselyne J Chauvin, Samuel R Krimmel, Athanasia Metoki, Aishwarya Rajesh, Jarod L Roland, Anxu Wang, Aristeidis Sotiras, Joshua S Shimony, Benjamin P Kay, Scott A Marek, Evan M Gordon, Nico U F Dosenbach, Et Al. May 2026

Frame-Wise Multi-Echo Distortion Correction For Superior Functional Mri, Andrew N Van, David F Montez, Timothy O Laumann, Philip N Cho, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Roselyne J Chauvin, Samuel R Krimmel, Athanasia Metoki, Aishwarya Rajesh, Jarod L Roland, Anxu Wang, Aristeidis Sotiras, Joshua S Shimony, Benjamin P Kay, Scott A Marek, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities, which currently must be corrected using separately acquired field map data. However, changes in the head position of a participant across fMRI frames cause changes in the B0 field, preventing accurate correction of geometric distortions. Movement during field map acquisitions corrupts field maps, preventing distortion correction altogether. In this study, we use multi-echo (ME) fMRI data to dynamically sample and correct for magnetic field image distortions caused by head motion. Our distortion correction pipeline, MEDIC (Multi-Echo DIstortion Correction), leverages magnetic field inhomogeneity information found in the difference between …


Regulation Of Pfh1 Helicase Activity By Nucleic Acid Interactions And Mitochondrial Ssb, María Ortiz-Rodríguez, Saurabh P Singh, Francisco J Cao-García, Roberto Galletto, Borja Ibarra May 2026

Regulation Of Pfh1 Helicase Activity By Nucleic Acid Interactions And Mitochondrial Ssb, María Ortiz-Rodríguez, Saurabh P Singh, Francisco J Cao-García, Roberto Galletto, Borja Ibarra

2020-Current year OA Pubs

Pif1-family helicases are essential for proper nuclear and mitochondrial genome maintenance, yet the regulation of their activities remains incompletely understood. Here, we use single-molecule manipulation and visualization techniques to dissect the real-time mechanochemical behavior of Pfh1, the sole Pif1-family helicase in


Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: 4-Year Follow-Up Of The Pathfinder Study, Jason Gotlib, Stephen T Oh, Et Al. May 2026

Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: 4-Year Follow-Up Of The Pathfinder Study, Jason Gotlib, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Advanced systemic mastocytosis (AdvSM), a clonal hematologic neoplasm driven predominantly by D816V-mutant KIT, is often characterized by organ damage. Associated hematologic neoplasms (AHNs; usually myeloid) are often present, leading to poor survival. We report on the oral, highly selective, potent KIT D816V inhibitor avapritinib (200 mg once daily, starting dose) with >4 years follow-up from the fully enrolled PATHFINDER study. End points included overall response rate (ORR; primary), duration of response (DOR), progression-free survival (PFS), overall survival (OS), changes in objective biomarkers of disease, and safety (all secondary). Of 107 patients with AdvSM (including 71 [66%] with SM-AHN; overall population …