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Technical Trends In Management Of Acl Reconstructions In 2025: A Major League Soccer Team Physicians Survey, Matthew Varano, Henry Eilen, Catherine Hand, Camden Bohn, Yining Lu, Rachel Frank, Danyal Nawabi, Robert Brophy, Bert Mandelbaum, Brian Forsythe Jun 2026

Technical Trends In Management Of Acl Reconstructions In 2025: A Major League Soccer Team Physicians Survey, Matthew Varano, Henry Eilen, Catherine Hand, Camden Bohn, Yining Lu, Rachel Frank, Danyal Nawabi, Robert Brophy, Bert Mandelbaum, Brian Forsythe

2020-Current year OA Pubs

BACKGROUND: The optimal graft choice for anterior cruciate ligament reconstruction (ACLR) remains a subject of ongoing debate. In practice, graft selection in ACLR is multifactorial, with patient characteristics, activity level, and surgeon preference/training background all playing a crucial role in the clinical decision-making process. While graft trends have been reported across select professional sports leagues, none have focused specifically on professional soccer.

PURPOSE: To report current trends in graft preference for ACLR among Major League Soccer (MLS) surgeons.

STUDY DESIGN: Cross-sectional study.

METHODS: A 39-question survey was distributed to 27 orthopaedic surgeons affiliated with MLS teams in January 2025. The …


Synergistic Effects Of Diabetic Neuropathy And Kidney Function Decline On Second Metatarsal Skeletal Health And Foot Function: A Pilot Study, Victor A Cheuy, Saghi Sadoughi, Hasung Moon, Jalen Ellis, Rodney Gross, David R Sinacore, Mary K Hastings, Richard B Souza, Galateia J Kazakia Jun 2026

Synergistic Effects Of Diabetic Neuropathy And Kidney Function Decline On Second Metatarsal Skeletal Health And Foot Function: A Pilot Study, Victor A Cheuy, Saghi Sadoughi, Hasung Moon, Jalen Ellis, Rodney Gross, David R Sinacore, Mary K Hastings, Richard B Souza, Galateia J Kazakia

2020-Current year OA Pubs

A discouraging increase in diabetes-related nontraumatic lower-extremity amputations (NLEA) has occurred over the last decade. Individuals with diabetic neuropathy (DMPN) and CKD are at the highest risk for NLEA. Despite the critical implications, little is known about the factors that initiate the cascade of events leading to NLEA, limiting early and effective interventions. We aimed to develop and implement a technique for quantifying metatarsal bone density and microstructure using HR-pQCT. Twelve participants were enrolled:


Toward Better Response Assessment Of Cutaneous Chronic Graft-Versus-Host Disease: A Report From The National Institutes Of Health Consensus Project Task Force, Alina Markova, Iskra Pusic, Et Al. Jun 2026

Toward Better Response Assessment Of Cutaneous Chronic Graft-Versus-Host Disease: A Report From The National Institutes Of Health Consensus Project Task Force, Alina Markova, Iskra Pusic, Et Al.

2020-Current year OA Pubs

The National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) Consensus Project established response criteria that enabled clinical trials and facilitated regulatory approval of multiple therapies. Nonetheless, organ-specific assessments have limitations, particularly for severe sclerotic skin involvement. Cutaneous manifestations occur in approximately half of patients with chronic GVHD but are difficult to evaluate due to heterogeneous clinical features. To address these challenges, the NIH Consensus Skin Task Force convened from 2024 to 2025 to refine skin response measures for use in clinical trials. This report (1) summarizes current diagnosis and scoring of skin chronic GVHD, (2) reviews existing response assessments, …


Expanding The Omop Common Data Model To Support Extracorporeal Life Support Research, Clemens Rieder, Ahmed Said, Et Al. Jun 2026

Expanding The Omop Common Data Model To Support Extracorporeal Life Support Research, Clemens Rieder, Ahmed Said, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Despite the increased availability of electronic health records, open-source standardized data collection to facilitate high-resolution data during extracorporeal life support (ECLS) is lacking. This project aimed to assess the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) for interoperability to store data sufficiently generated in the context of ECLS and to develop a custom data model expansion in case the OMOP CDM proved insufficient.

DESIGN AND SETTING: The OMOP CDM was analyzed qualitatively by expert consensus for its capability to capture data relative to ECLS as well as the presence of fitting ECLS-related concepts. Database entries necessary to …


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


Comprehensive Mass Spectrometry Screening-Derived Atlas Of Hdac Inhibitors Reveals Histone-Specific Acetylation Changes, Rashmi Karki, Francisca N De Luna Vitorino, Richard M Searfoss, Joanna K Lempiäinen, Cheryl H Arrowsmith, Benjamin A Garcia May 2026

Comprehensive Mass Spectrometry Screening-Derived Atlas Of Hdac Inhibitors Reveals Histone-Specific Acetylation Changes, Rashmi Karki, Francisca N De Luna Vitorino, Richard M Searfoss, Joanna K Lempiäinen, Cheryl H Arrowsmith, Benjamin A Garcia

2020-Current year OA Pubs

Histone deacetylase inhibitors (HDACis) have emerged as valuable therapeutics for cancer and other diseases; however, their effects on histone post-translational modification remain poorly characterized. Here, we applied quantitative mass spectrometry and high-throughput sequencing to systematically profile site-specific changes in histone modifications in response to a panel of HDACis. This platform enabled mapping of histone modification changes across hundreds of sites, including low-abundance histone marks. Furthermore, an integrative analysis of chromatin immunoprecipitation followed by sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data identified genome-wide binding sites for the low-abundance histone modification of H2A.Z acetylation in HeLa and MDA-MB-231 breast cancer cells, highlighting the …


Patterns Of Care And Clinical Outcomes In Systemic Peripheral T-Cell Lymphoma: The Leo-Mer Prospective Cohort Study, Jia Ruan, Neha Mehta-Shah, Brad Kahl, Et Al. May 2026

Patterns Of Care And Clinical Outcomes In Systemic Peripheral T-Cell Lymphoma: The Leo-Mer Prospective Cohort Study, Jia Ruan, Neha Mehta-Shah, Brad Kahl, Et Al.

2020-Current year OA Pubs

Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for peripheral T-cell lymphoma (PTCL). We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in 2 related prospective cohort studies, Lymphoma Epidemiology of Outcomes (LEO) from 2015 to 2020 and Molecular Epidemiology Resource (MER) from 2002 to 2015, both followed to 2024. The primary end points were event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimator and Cox regression model. Secondary end points included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP (cyclophosphamide, …


Inflammaging In Aged Tissues Drives Remodeling Of The Cd8+ T Cell Compartment, Irina Shchukina, Carlos J Rodriguez-Hernandez, Heather S Ruiz, Maksim Kleverov, Rachel L Mintz, Katsutaka Mineura, Subhadra C Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A Mogilenko, Rachael L Field, Tran H Nguyen, Quazim A Alayo, Christopher G Huckstep, Barbora Vander Wielen, Jonathan R Brestoff, Sheila A Stewart, David W Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J Randolph, Maxim N Artyomov May 2026

Inflammaging In Aged Tissues Drives Remodeling Of The Cd8+ T Cell Compartment, Irina Shchukina, Carlos J Rodriguez-Hernandez, Heather S Ruiz, Maksim Kleverov, Rachel L Mintz, Katsutaka Mineura, Subhadra C Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A Mogilenko, Rachael L Field, Tran H Nguyen, Quazim A Alayo, Christopher G Huckstep, Barbora Vander Wielen, Jonathan R Brestoff, Sheila A Stewart, David W Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J Randolph, Maxim N Artyomov

2020-Current year OA Pubs

Aging strongly impacts CD8


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 …


Isg15 Negatively Regulates Ripk3-Mediated Cell Death And Viral Pathogenesis, Yi-Chieh Perng, Jessica M C Warsaw, Sachendra S Bais, Bradley E Hiller, Marissa C Locke, David J Morales-Heil, Chaoqun Li, Alissa R Young, Kristen J Monte, Robert E Schmidt, Douglas R Green, Yi-Nan Gong, Deborah J Lenschow May 2026

Isg15 Negatively Regulates Ripk3-Mediated Cell Death And Viral Pathogenesis, Yi-Chieh Perng, Jessica M C Warsaw, Sachendra S Bais, Bradley E Hiller, Marissa C Locke, David J Morales-Heil, Chaoqun Li, Alissa R Young, Kristen J Monte, Robert E Schmidt, Douglas R Green, Yi-Nan Gong, Deborah J Lenschow

2020-Current year OA Pubs

Necroptosis, a form of programmed, inflammatory necrosis, plays an important role in viral-host defense and inflammation. The receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway mediates necroptosis. Yet, the mechanisms that control necroptosis to limit immunopathology are poorly understood. Here, we report that interferon-stimulated gene 15 (ISG15) negatively regulates RIPK3-mediated cell death, including necroptosis, and limits immunopathology during chikungunya virus (CHIKV) infection. ISG15-deficient mice infected with CHIKV display increased levels of necroptosis, resulting in elevated proinflammatory cytokine and chemokine production, leading to increased lethality. This dysregulated host response is fully prevented when MLKL or RIPK3 is ablated …


Real-World Evidence For Pembrolizumab Gemcitabine Vinorelbine And Liposomal Doxorubicin In Classical Hodgkin Lymphoma, Grace Baek, Nancy L Bartlett, Marcus Watkins, Et Al. May 2026

Real-World Evidence For Pembrolizumab Gemcitabine Vinorelbine And Liposomal Doxorubicin In Classical Hodgkin Lymphoma, Grace Baek, Nancy L Bartlett, Marcus Watkins, Et Al.

2020-Current year OA Pubs

No abstract provided.


Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E Irmen, Nicholas J Constantino, Chanung Wang, Michael F Kanan, Marco Colonna, Shannon L Macauley, Jocelyn Y Cheng, Ken Hatanaka, Margaret Moline, Erik S Musiek May 2026

Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E Irmen, Nicholas J Constantino, Chanung Wang, Michael F Kanan, Marco Colonna, Shannon L Macauley, Jocelyn Y Cheng, Ken Hatanaka, Margaret Moline, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer's disease (AD). The orexin/hypocretin system regulates sleep-wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice.

METHODS: PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed …


Generalizability Of An Ai-Based Mammogram Risk Score (Mrs) For Breast Cancer Among Diverse Populations Of Women, Shu Jiang, Debbie L Bennett, Peter Kraft, Graham A Colditz May 2026

Generalizability Of An Ai-Based Mammogram Risk Score (Mrs) For Breast Cancer Among Diverse Populations Of Women, Shu Jiang, Debbie L Bennett, Peter Kraft, Graham A Colditz

2020-Current year OA Pubs

Conventional prediction models incorporating genetic and clinical factors including breast density underperform in non-European populations. We investigated an artificial intelligence-derived mammogram risk score (MRS), a summary of texture features that captures intrinsic breast-tissue characteristics-the substrate for cancer development. This study leveraged data from two North American screening cohorts totaling >226,000 women, including non-Hispanic white, non-Hispanic Black, East Asian, South Asian, and Indigenous women. MRS distributions showed nonsignificant shifts (and similar SDs) between cohorts and across race and ethnic subgroups. MRS increased with age and was significantly associated with breast cancer risk, with hazard ratios per SD ranging from 2.24 [95% …


Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances May 2026

Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

METHODS: Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of …


Quantification Of Sarm1 Nadase Activity In Human Peripheral Blood Mononuclear Cells, Lila F Dabill, Ivana R Shen, Jennifer M Brazill, Alicia Neiner, Yo Sasaki, Erica L Scheller May 2026

Quantification Of Sarm1 Nadase Activity In Human Peripheral Blood Mononuclear Cells, Lila F Dabill, Ivana R Shen, Jennifer M Brazill, Alicia Neiner, Yo Sasaki, Erica L Scheller

2020-Current year OA Pubs

SARM1 (sterile α and TIR motif-containing protein-1) is an NADase enzyme that serves as the central executioner of Wallerian axon degeneration. Given this, SARM1 is of high interest as a candidate therapeutic target, and SARM1 inhibitors are currently in clinical trials for treatment of neurodegeneration. Beyond neuroscience, emerging studies reveal that SARM1 may also drive aspects of bone fragility, liver pathology, adipose expansion, and insulin resistance in metabolic disease. However, we lack methods to quantify SARM1 activation in humans to better define patients at high risk of SARM1-mediated tissue damage. Unlike neurons, peripheral blood mononuclear cells (PBMCs) represent an easily …


Subclinical Neuropsychiatric Trait Variation In Parents Of Children With Autism Spectrum Disorder: A Cohort Study, Lindsay J Mullin, Carolyn Lasch, Natasha Marrus, Et Al. May 2026

Subclinical Neuropsychiatric Trait Variation In Parents Of Children With Autism Spectrum Disorder: A Cohort Study, Lindsay J Mullin, Carolyn Lasch, Natasha Marrus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism.

METHODS: Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were …


Abl Kinases Regulate Fgf Signaling Independent Of Crk Phosphorylation To Prevent Peters Anomaly Type Ii, Hao Wu, Yingyu Mao, Qian Wang, Honglian Yu, Michael Bouaziz, Neoklis Makrides, Enpeng Wang, Zhipeng Ding, Anthony J Koleske, Glenn L Radice, Jerry Hsu, Xin Zhang May 2026

Abl Kinases Regulate Fgf Signaling Independent Of Crk Phosphorylation To Prevent Peters Anomaly Type Ii, Hao Wu, Yingyu Mao, Qian Wang, Honglian Yu, Michael Bouaziz, Neoklis Makrides, Enpeng Wang, Zhipeng Ding, Anthony J Koleske, Glenn L Radice, Jerry Hsu, Xin Zhang

2020-Current year OA Pubs

Peters anomaly is an anterior segment dysgenesis and a leading cause of congenital corneal opacity. Here, we show that loss of ABL kinases restores lens induction in the absence of FGF signaling but induces Peters anomaly type II independently of ERK signaling, a phenotype also observed with elevated FGF-Ras activity. This defect is rescued by allelic deletion of the ABL substrates CRK and CRKL. Contrary to prevailing models, ABL kinases do not act through direct phosphorylation of CRK proteins; instead, they phosphorylate PTPN12, suppressing p130CAS phosphorylation and CRK recruitment required for RHO GTPase activation. ABL kinase deficiency reduces actomyosin contractility …


Hierarchical Small Molecule Inhibition Of Myst Acetyltransferases, Xuemin Chen, Alexandra Castroverde, Minervo Perez, Ronald Holewinski, Kiall F Suazo, Rashmi Karki, Thorkell Andresson, Benjamin A Garcia, Jordan L Meier May 2026

Hierarchical Small Molecule Inhibition Of Myst Acetyltransferases, Xuemin Chen, Alexandra Castroverde, Minervo Perez, Ronald Holewinski, Kiall F Suazo, Rashmi Karki, Thorkell Andresson, Benjamin A Garcia, Jordan L Meier

2020-Current year OA Pubs

MYST lysine acetyltransferases (KATs) are a class of epigenetic enzymes critical for cellular function that constitute an emerging therapeutic target in cancer. Recently, several drug-like MYST inhibitors have been reported that show promise in preclinical models as well as in clinical trials of breast cancer. Understanding the specificity of these molecules is critical for their effective use as chemical probes. Here we apply an integrated profiling strategy to systematically define the potency and selectivity of drug-like MYST KAT inhibitors. First, we use optimized chemoproteomic profiling and histone acetylation biormarkers to study the industry-developed KAT inhibitor PF-9363. This reveals dose-dependent engagement …


Mosunetuzumab Monotherapy Is Active And Tolerable In Patients With Relapsed/Refractory Richter Transformation, Katharine L Lewis, Nancy L Bartlett, Et Al. May 2026

Mosunetuzumab Monotherapy Is Active And Tolerable In Patients With Relapsed/Refractory Richter Transformation, Katharine L Lewis, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Richter transformation (RT) to diffuse large B-cell lymphoma is an aggressive lymphoma that arises from underlying chronic lymphocytic leukemia or small lymphocytic lymphoma. RT is often chemorefractory, resulting in poor clinical outcomes with standard chemoimmunotherapy. Mosunetuzumab, a bispecific CD20/CD3 T-cell-engaging antibody, was investigated in a cohort of 20 patients with relapsed/refractory RT. Cytokine release syndrome occurred in 65% of patients, almost exclusively grade 1 (20%) or grade 2 (40%), and occurring during the first treatment cycle. Other adverse events included infections, neutropenia, thrombocytopenia, tumor flare, and low-grade neurotoxicity, with no adverse events leading to treatment discontinuation. Mosunetuzumab resulted in an …


Simultaneous Multielectrode Recordings Along The Human Scala Tympani: Evidence For Level-Dependent Place Coding, Amit Walia, Matthew A Shew, Shannon M Lefler, Amanda J Ortmann, Patrick Ioerger, Jordan Varghese, Jacques A Herzog, Craig A Buchman May 2026

Simultaneous Multielectrode Recordings Along The Human Scala Tympani: Evidence For Level-Dependent Place Coding, Amit Walia, Matthew A Shew, Shannon M Lefler, Amanda J Ortmann, Patrick Ioerger, Jordan Varghese, Jacques A Herzog, Craig A Buchman

2020-Current year OA Pubs

The cochlea systematically encodes sound frequency and intensity via a precisely organized tonotopic map, in which traveling waves peak at specific cochlear locations. A fundamental but incompletely understood aspect of auditory coding involves how stimulus intensity shapes this tonotopic organization. In animal models, increasing intensity shifts the cochlear traveling wave peak basally; however, physiological evidence for such intensity-dependent shifts in human cochlear processing is limited. Here, we performed simultaneous multielectrode electrocochleography recordings along the human scala tympani to characterize how cochlear place coding varies as a function of stimulus intensity. In subjects with preserved cochlear mechanics, including individuals with auditory …


Making Process Evaluations More Explanatory - Key Opportunities To Advance Implementation Research, Michel Wensing, Elvin H Geng May 2026

Making Process Evaluations More Explanatory - Key Opportunities To Advance Implementation Research, Michel Wensing, Elvin H Geng

2020-Current year OA Pubs

Process evaluation of implementation strategies is increasingly common, but a review by Bracci et al. showed that room for improvement exists. In this contribution, we complement their recommendations by ideas on the design of process evaluations. Process evaluations are meant to provide explanations for why implementation strategies were effective, or not effective. Therefore, they are best guided by theory or frameworks, but the frequent focus on intervention acceptability reflects a lack of imagination on moderators and mediators that influence outcomes. Intervention fidelity is relevant in all process evaluations. Meaningful synthesis of process evaluation studies requires a homogeneous outcome, such as …


Developmental Origins Of Exceptional Health And Survival: A Four-Generation Family Cohort Study, Matthew Thomas Keys, Søren Netra, Dorthe Almind Pedersen, Pernille Stemann Larsen, Alexander Kulminski, Mary F Feitosa, Mary Wojczynski, Michael Province, Kaare Christensen May 2026

Developmental Origins Of Exceptional Health And Survival: A Four-Generation Family Cohort Study, Matthew Thomas Keys, Søren Netra, Dorthe Almind Pedersen, Pernille Stemann Larsen, Alexander Kulminski, Mary F Feitosa, Mary Wojczynski, Michael Province, Kaare Christensen

2020-Current year OA Pubs

Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (N = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These associations in fourth-generation great-grandchildren (N = 14,908) were attenuated and less consistent (e.g., infant mortality, Hazard Ratio = 0.90, [0.70, 1.17]). Dilatory patterns across successive generations were independent of …


Tunable Tripcides Suppress Virulence Factor Secretion During Staphylococcus Aureus Infection And Kill Dormant Cells, Hasan Tükenmez, Taylor M Nye, Suzanne Hickerson, Chloe L P Obernuefemann, Jerome S Pinkner, Karen W Dodson, Michael G Caparon, Scott J Hultgren, Et Al. May 2026

Tunable Tripcides Suppress Virulence Factor Secretion During Staphylococcus Aureus Infection And Kill Dormant Cells, Hasan Tükenmez, Taylor M Nye, Suzanne Hickerson, Chloe L P Obernuefemann, Jerome S Pinkner, Karen W Dodson, Michael G Caparon, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Antimicrobial resistance (AMR) in common bacterial pathogens, including methicillin-resistant


Nivolumab Plus Ipilimumab For Chemotherapy-Refractory Metastatic Castration-Resistant Prostate Cancer: Results From The Randomized Portion Of The Phase 2 Checkmate 650 Trial, Padmanee Sharma, Russell K Pachynski, Et Al. May 2026

Nivolumab Plus Ipilimumab For Chemotherapy-Refractory Metastatic Castration-Resistant Prostate Cancer: Results From The Randomized Portion Of The Phase 2 Checkmate 650 Trial, Padmanee Sharma, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

We report on the randomized portion of the phase 2, open-label CheckMate 650 trial (NCT02985957), in which docetaxel-experienced, biologically male patients with chemotherapy-refractory metastatic castration-resistant prostate cancer were randomized 2:2:1:2 to nivolumab 3 mg /kg plus ipilimumab 1 mg /kg (n = 73), nivolumab 1 mg /kg plus ipilimumab 3 mg /kg (n = 74), ipilimumab 3 mg /kg (n = 38), or cabazitaxel (n = 74). Primary endpoints were objective response rate and radiographic progression-free survival; key secondary endpoints included overall survival, prostate-specific antigen response rate, and safety. This portion of CheckMate 650 was not designed to statistically compare …


Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Stacey L House, Et Al. May 2026

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …


Cellular And Molecular Basis Of Pfcoronin Function In Artemisinin Resistance In Plasmodium Falciparum, Imran Ullah, Eva S Istvan, Et Al. May 2026

Cellular And Molecular Basis Of Pfcoronin Function In Artemisinin Resistance In Plasmodium Falciparum, Imran Ullah, Eva S Istvan, Et Al.

2020-Current year OA Pubs

Artemisinin combination therapies are central to malaria control, but their efficacy is threatened by the emergence of resistant Plasmodium falciparum strains. While the role of Pfkelch13 mutations is well established, mutations in Pfcoronin have also been implicated in treatment failure, revealing layers of resistance complexity. Here, we define the cellular mechanism of Pfcoronin‑mediated artemisinin resistance. PfCoronin interacts with PfActin and localizes to the parasite plasma membrane, the digestive vacuole membrane, and small vesicles containing host cell material. Mutations in PfCoronin disrupt its localization and perturb PfActin homeostasis, altering the distribution of ring‑stage morphologies, including a reduced proportion of parasites adopting …


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 …


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


+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 [