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Full-Text Articles in Medicine and Health Sciences

Predictive Modeling Of Hematoma Expansion From Non-Contrast Computed Tomography In Spontaneous Intracerebral Hemorrhage Patients, Natasha Ironside, Shinjini Kundu, Et Al. Dec 2025

Predictive Modeling Of Hematoma Expansion From Non-Contrast Computed Tomography In Spontaneous Intracerebral Hemorrhage Patients, Natasha Ironside, Shinjini Kundu, Et Al.

2020-Current year OA Pubs

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for …


Simultaneous Initiation Of Finerenone And Empagliflozin Across The Spectrum Of Kidney Risk In The Confidence Trial, Muthiah Vaduganathan, Jennifer B Green, Hiddo J L Heerspink, Sung Gyun Kim, Johannes F E Mann, Janet B Mcgill, Amy Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Li Li, Na Li, Katja Rohwedder, Charlie Scott, Rajiv Agarwal Dec 2025

Simultaneous Initiation Of Finerenone And Empagliflozin Across The Spectrum Of Kidney Risk In The Confidence Trial, Muthiah Vaduganathan, Jennifer B Green, Hiddo J L Heerspink, Sung Gyun Kim, Johannes F E Mann, Janet B Mcgill, Amy Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Li Li, Na Li, Katja Rohwedder, Charlie Scott, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and type 2 diabetes using a UACR Endpoint) trial investigated the safety and efficacy of simultaneously initiating finerenone and empagliflozin for patients with chronic kidney disease (CKD) and type 2 diabetes. This prespecified analysis aimed to determine if the predicted risk of kidney disease progression, based on KDIGO risk categories, influenced the benefits and safety of this combination therapy.

METHODS: The double-blind, double-dummy trial randomized 818 adults with CKD and type 2 diabetes [urine albumin-creatinine ratio (UACR) ≥100 to < 5000 mg/g] to receive once-daily finerenone plus empagliflozin, finerenone alone or empagliflozin alone, all in addition to a renin-angiotensin system inhibitor. The relative change in UACR from baseline to day 180 (primary endpoint) and a >30% reduction in UACR (secondary endpoint) across KDIGO …


Association Of Shock Index And Variants With Mortality In Acute Pulmonary Embolism, Cameron P Upchurch, Kristen Sanfilippo, Daphne Lew, Maanasi Samant, Rachel Mcdonald Dec 2025

Association Of Shock Index And Variants With Mortality In Acute Pulmonary Embolism, Cameron P Upchurch, Kristen Sanfilippo, Daphne Lew, Maanasi Samant, Rachel Mcdonald

2020-Current year OA Pubs

INTRODUCTION: Pulmonary embolism (PE) is common with potential for morbidity and mortality. Several PE risk-stratification tools exist; however, more granular and patient-specific indicators of potential decompensation or short-term mortality that can be easily obtained are needed for the bedside clinician to further sub-stratify risk and inform management decisions. We sought to determine the association of early emergency department (ED) measurement of the shock index (SI) and SI variants (modified SI, SI to peripheral oxygen saturation ratio, age-adjusted SI, respiratory-adjusted SI, and double product) and mortality among patients with acute PE.

METHODS: This was an observational case-control study of adult patients …


Soluble Urokinase Plasminogen Activator Receptor And Acute Kidney Injury In Hematopoietic Cell Transplantation, Bhavna Bhasin-Chhabra, Tao Wang, John E Levine, Shalini Shenoy, Miguel-Angel Perales, Asad Bashey, Hershel Raff, Wael Saber Dec 2025

Soluble Urokinase Plasminogen Activator Receptor And Acute Kidney Injury In Hematopoietic Cell Transplantation, Bhavna Bhasin-Chhabra, Tao Wang, John E Levine, Shalini Shenoy, Miguel-Angel Perales, Asad Bashey, Hershel Raff, Wael Saber

2020-Current year OA Pubs

Acute kidney injury (AKI) frequently follows hematopoietic cell transplantation (HCT). Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker of AKI in the general population. We evaluated suPAR and its association with AKI requiring dialysis (AKI-D) in patients undergoing allogeneic HCT (alloHCT). Performance of suPAR was compared with serum creatinine (sCr) and neutrophil gelatinase-associated lipocalin (NGAL). Data were obtained from the Blood and Marrow Transplant Clinical Trials Network 1202 cohort, an observational study of 1709 alloHCT recipients. Adults aged ≥18 years with AKI-D after HCT were included. Adults who did not develop AKI were included as controls and matched 1:1. …


Investigating The Relationship Between Breast Cancer Risk Factors And An Ai-Generated Mammographic Texture Feature In The Nurses' Health Study Ii, Xueyao Wu, Shu Jiang, Aaron Ge, Constance Turman, Graham Colditz, Rulla M Tamimi, Peter Kraft Dec 2025

Investigating The Relationship Between Breast Cancer Risk Factors And An Ai-Generated Mammographic Texture Feature In The Nurses' Health Study Ii, Xueyao Wu, Shu Jiang, Aaron Ge, Constance Turman, Graham Colditz, Rulla M Tamimi, Peter Kraft

2020-Current year OA Pubs

The mammogram risk score (MRS), an AI-driven mammographic texture feature, strongly predicts breast cancer risk independently of breast density, though underlying mechanisms remain unclear. Using data from the Nurses' Health Study II (292 cases, 561 controls), we validated MRS's association with breast cancer and evaluated its relationships with established breast cancer risk factors through observational analyses, polygenic score analyses, and Mendelian randomization. MRS was significantly associated with breast cancer risk before (OR=1.92 per SD increase; 95% CI:1.57 to 2.35; 10-year AUC=0.69) and after adjustment for predicted BI-RADS density (OR=1.85; 95% CI:1.49 to 2.30). Early life body size and adult body …


Epidemiology And Screening Of Traumatic Vertebral Artery Injuries At A Large Scandinavian Level 1 Trauma Center, Paulina Cewe, Victor E. Staartjes, Victor Gabriel El-Hajj, Ihab Ahmad Al-Rikabi, Basel Musmar, Joana M. Roy, Dennis Troung, Mats Beckman, Marcus Ohlsson, Pascal Jabbour, Adrian Elmi-Terander, Erik Edström Dec 2025

Epidemiology And Screening Of Traumatic Vertebral Artery Injuries At A Large Scandinavian Level 1 Trauma Center, Paulina Cewe, Victor E. Staartjes, Victor Gabriel El-Hajj, Ihab Ahmad Al-Rikabi, Basel Musmar, Joana M. Roy, Dennis Troung, Mats Beckman, Marcus Ohlsson, Pascal Jabbour, Adrian Elmi-Terander, Erik Edström

Jefferson Hospital Staff Papers and Presentations

OBJECTIVE: Traumatic vertebral artery injuries (tVAIs) are uncommon but potentially devastating if missed. While computed tomography angiography (CTA) is routinely used for diagnosis, data on the number needed to image (NNI) remain limited. We hence analyzed tVAI epidemiology and imaging practices at a major Scandinavian level 1 trauma center.

METHODS: A retrospective study (2013-2020) was performed based on a single-center trauma registry. Patients were grouped based on CTA imaging protocol used; selective screening (2013-2017) and universal screening (2018-2020). Imaging protocols, treatment strategies, and outcomes were analyzed.

RESULTS: Among 2,843 patients admitted with level 1 trauma and receiving CTA imaging, 62 …


Cv: Ann Guernon (Speech-Language Pathology), Ann Guernon Dec 2025

Cv: Ann Guernon (Speech-Language Pathology), Ann Guernon

Rehabilitation and Health Sciences Department Faculty Curricula Vitae

No abstract provided.


Systems Level Analysis Of Gene, Pathway And Phytochemical Associations With Psoriasis, Sonalika Ray, Ojasvi Dutta, Neoklis Apostolopoulos, Konstantin G. Kousoulas, Jean Christopher Chamcheu, Rishemjit Kaur Dec 2025

Systems Level Analysis Of Gene, Pathway And Phytochemical Associations With Psoriasis, Sonalika Ray, Ojasvi Dutta, Neoklis Apostolopoulos, Konstantin G. Kousoulas, Jean Christopher Chamcheu, Rishemjit Kaur

Faculty Publications

Psoriasis is an inflammatory skin disorder driven by abnormal immune activation that promotes excessive proliferation and accelerated turnover of epidermal keratinocytes. IL-17 and TNF pathways are well known in psoriasis, but the other mechanisms that keep the disease active and link it to systemic comorbidities are not yet fully understood. A combined transcriptomic and systems biology framework was applied to map regulatory circuits in psoriatic lesions and to identify phytochemical candidates capable of multi-target modulation for topical intervention. Differential gene expressions between lesional and healthy skin was analyzed, followed by pathway enrichment, upstream regulator inference, protein-protein interaction network, and chemical-gene …


Cv: Ann Guernon (Speech-Language Pathology), Ann Guernon Dec 2025

Cv: Ann Guernon (Speech-Language Pathology), Ann Guernon

Rehabilitation Sciences Department Curricula Vitae

No abstract provided.


Charters In Patient-Engaged Research: A Scoping Review Of Current Evidence, Jenny Martínez, Catherine V. Piersol, Richard W. Hass, Felicia Chew, Amy Cunningham, Sharon L. Larson Dec 2025

Charters In Patient-Engaged Research: A Scoping Review Of Current Evidence, Jenny Martínez, Catherine V. Piersol, Richard W. Hass, Felicia Chew, Amy Cunningham, Sharon L. Larson

College of Population Health Faculty Papers

AIMS: Research study charters facilitate shared governance and power sharing with research partners when developed collaboratively and early on in a study. Study charters are negotiated and developed on a study-by-study basis, offering insight into study-specific dynamics between research partners and investigators, as well as the factors that each identify as important for their collaboration. This review aimed to map and synthesize existing evidence on the development, structure, and implementation of research study charters used in patient-engaged research.

METHODS: We searched peer-reviewed literature published worldwide in English between January 2019 and January 2025.

RESULTS: Our final sample consisted of 17 …


Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan Dec 2025

Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan

School of Graduate Studies Faculty Publications

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …


Multiple Sclerosis: An Ethnically Diverse Disease With Worldwide Equity Challenges Accessing Care, Victor M Rivera Dec 2025

Multiple Sclerosis: An Ethnically Diverse Disease With Worldwide Equity Challenges Accessing Care, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) affects approximately 2.9 million people in the world, exerting a significant economic and societal burden. The disease is increasingly identified among populations considered as uncommonly affected. MS is reported in all regions of the World Health Organization (WHO) member states in Africa, the Americas, South-East Asia, Europe, the Eastern Mediterranean and the Western Pacific, affecting all ethnicities while exhibiting substantially variable prevalences. Countries with high MS prevalence and some with moderate frequencies generally have economically better structured healthcare systems. Nevertheless, health disparities in these countries are accentuated by suboptimal accessibility of care for their minorities, immigrants and …


Titin-Related Familial Dilated Cardiomyopathy: Factors Associated With Disease Onset, Renee Johnson, Robert A Fletcher, Stacey Peters, Monique Ohanian, Magdalena Soka, Andrei Smolnikov, Katherine E Abihider, Michael J Ackerman, Flavie Ader, Mohammed M Akhtar, Ahmad S Amin, Euan A Ashley, John J Atherton, Rachel Austin, Annette F Baas, Richard D Bagnall, Samantha Barratt Ross, Jean-Louis Blouin, Emily E Brown, Henning Bundgaard, Douglas Cannie, Przemyslaw Chmielewski, Gemma Correnti, Maria Generosa Crespo-Leiro, Matteo Dal Ferro, Lisa M Dellefave-Castillo, Fernando Dominguez, Dennis Dooijes, Anne M Dybro, Youssef Ed Demri, Mohamed El Hachmi, Luis Escobar-Lopez, Sarah Jajesnica Foye, Maria Franaszczyk, Marta Gigli, Esther Gonzalez Lopez, Adeline Goudal, Sharon Graw, Michel Guipponi, Eric Haan, Jan Haas, Daniel J Hammersley, Frederikke G Hansen, Christopher S Hayward, Thomas Morris Hey, Stephane Heymans, Carolyn Y Ho, Arjan C Houweling, Jodie Ingles, Angela Ingrey, Andrew Jabbour, Paul A James, Joeri A Jansweijer, Jan D H Jongbloed, Anne M Keogh, Jose M Larrañaga-Moreira, Ronald H Lekanne Deprez, Ivan Macciocca, Peter S Macdonald, Nicolas Mansencal, Julia Mansour, Cristina Martinez-Veira, Barbara Mcdonough, Julie Mcgaughran, Kristen Medo, Marco Merlo, Ewa Michalak, Lorenzo Monserrat, Helen Mountain, Steven A Muller, Anne M Murphy, Brittney Murray, Emily C Oates, Elizabeth Ormondroyd, Nicholas Pachter, Alessia Paldino, Aurélien Palmyre, Naveen L Pereira, Kermshlise C Picard, Nicola Poplawski, Sanjay Prasad, Julie Proukhnitzky, Jean-Francois Pruny, Patricia Reant, Pascale Richard, Anne Ronan, Farbod Sedaghat-Hamedani, Christopher Semsarian, Garrett Storm, Sophie Stroeks, Petros Syrris, Matthew R G Taylor, Kate Thomson, Tina Thompson, J Peter Van Tintelen, Christoffer Rasmus Vissing, Kathryn E Waddell-Smith, Mathew Wallis, Dominica Zentner, Clare Arnott, Ali J Marian, Jaewon Oh, Siv Fokstuen, Cynthia A James, Roberto Barriales-Villa, Benjamin Meder, Karim Wahbi, John R Giudicessi, Victoria N Parikh, James S Ware, Nicolas Piriou, Caroline Rooryck, Neal K Lakdawala, Luisa Mestroni, Gianfranco Sinagra, Perry M Elliott, Hugh Watkins, Elizabeth M Mcnally, Philippe Charron, Karin Y Van Spaendonck-Zwarts, Pablo Garcia-Pavia, Maria Luisa Peña-Peña, Jens Mogensen, Alex Hoerby Christensen, Zofia T Bilińska, Torsten B Rasmussen, Jonathan G Seidman, Christine E Seidman, Anneline S J M Te Riele, Job A J Verdonschot, Yigal M Pinto, Imke Christiaans, Diane Fatkin Dec 2025

Titin-Related Familial Dilated Cardiomyopathy: Factors Associated With Disease Onset, Renee Johnson, Robert A Fletcher, Stacey Peters, Monique Ohanian, Magdalena Soka, Andrei Smolnikov, Katherine E Abihider, Michael J Ackerman, Flavie Ader, Mohammed M Akhtar, Ahmad S Amin, Euan A Ashley, John J Atherton, Rachel Austin, Annette F Baas, Richard D Bagnall, Samantha Barratt Ross, Jean-Louis Blouin, Emily E Brown, Henning Bundgaard, Douglas Cannie, Przemyslaw Chmielewski, Gemma Correnti, Maria Generosa Crespo-Leiro, Matteo Dal Ferro, Lisa M Dellefave-Castillo, Fernando Dominguez, Dennis Dooijes, Anne M Dybro, Youssef Ed Demri, Mohamed El Hachmi, Luis Escobar-Lopez, Sarah Jajesnica Foye, Maria Franaszczyk, Marta Gigli, Esther Gonzalez Lopez, Adeline Goudal, Sharon Graw, Michel Guipponi, Eric Haan, Jan Haas, Daniel J Hammersley, Frederikke G Hansen, Christopher S Hayward, Thomas Morris Hey, Stephane Heymans, Carolyn Y Ho, Arjan C Houweling, Jodie Ingles, Angela Ingrey, Andrew Jabbour, Paul A James, Joeri A Jansweijer, Jan D H Jongbloed, Anne M Keogh, Jose M Larrañaga-Moreira, Ronald H Lekanne Deprez, Ivan Macciocca, Peter S Macdonald, Nicolas Mansencal, Julia Mansour, Cristina Martinez-Veira, Barbara Mcdonough, Julie Mcgaughran, Kristen Medo, Marco Merlo, Ewa Michalak, Lorenzo Monserrat, Helen Mountain, Steven A Muller, Anne M Murphy, Brittney Murray, Emily C Oates, Elizabeth Ormondroyd, Nicholas Pachter, Alessia Paldino, Aurélien Palmyre, Naveen L Pereira, Kermshlise C Picard, Nicola Poplawski, Sanjay Prasad, Julie Proukhnitzky, Jean-Francois Pruny, Patricia Reant, Pascale Richard, Anne Ronan, Farbod Sedaghat-Hamedani, Christopher Semsarian, Garrett Storm, Sophie Stroeks, Petros Syrris, Matthew R G Taylor, Kate Thomson, Tina Thompson, J Peter Van Tintelen, Christoffer Rasmus Vissing, Kathryn E Waddell-Smith, Mathew Wallis, Dominica Zentner, Clare Arnott, Ali J Marian, Jaewon Oh, Siv Fokstuen, Cynthia A James, Roberto Barriales-Villa, Benjamin Meder, Karim Wahbi, John R Giudicessi, Victoria N Parikh, James S Ware, Nicolas Piriou, Caroline Rooryck, Neal K Lakdawala, Luisa Mestroni, Gianfranco Sinagra, Perry M Elliott, Hugh Watkins, Elizabeth M Mcnally, Philippe Charron, Karin Y Van Spaendonck-Zwarts, Pablo Garcia-Pavia, Maria Luisa Peña-Peña, Jens Mogensen, Alex Hoerby Christensen, Zofia T Bilińska, Torsten B Rasmussen, Jonathan G Seidman, Christine E Seidman, Anneline S J M Te Riele, Job A J Verdonschot, Yigal M Pinto, Imke Christiaans, Diane Fatkin

The Brown Foundation: Institute of Molecular Medicine

Background and aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM.

Results: A total of 3158 subjects in 1043 …


Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel Dec 2025

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …


Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu Dec 2025

Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu

Faculty, Staff and Student Publications

Background: Epithelial cell adhesion molecule (EpCAM) is a pleotropic transmembrane glycoprotein comprising an extracellular domain (EpEX), a single transmembrane domain, and an intracellular domain (EpICD). For several types of cancer, high EpCAM expression is associated with tumor progression, metastasis, immune evasion, and overall poor prognosis. A rare but aggressive form of thyroid cancer, anaplastic thyroid cancer (ATC), has a mean survival time of only 3–6 months after diagnosis.

Methods: The levels of EpEX and EpICD cleavage in clinical patient samples was evaluated by using tissue microarray. Capture enzyme-linked immunosorbent assay (ELISA) was conducted to explore the of shedding EpEX and …


Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko Dec 2025

Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, a member of the AP-1 family of transcription factors, mediates long-term neuroadaptations underlying drug addiction, seizure-related cognitive decline, dyskinesias, and several other chronic conditions. AP-1 transcription factors are notoriously difficult to modulate pharmacologically due to the absence of well-defined binding pockets. Here, we identify a novel site on ΔFOSB, located outside the DNA-binding cleft, that accommodates small molecules. We show that sulfonic acid-containing compounds bind to this site via an induced-fit mechanism, reorienting side chains critical for DNA binding, and that they may hinder the ΔFOSB bZIP α-helix from binding to the major groove of DNA. In vivo, direct …


Clair3-Rna: A Deep Learning-Based Small Variant Caller For Long-Read Rna Sequencing Data, Zhenxian Zheng, Xian Yu, Lei Chen, Yan-Lam Lee, Cheng Xin, Angel On Ki Wong, Miten Jain, Rupesh K Kesharwani, Fritz J Sedlazeck, Ruibang Luo Dec 2025

Clair3-Rna: A Deep Learning-Based Small Variant Caller For Long-Read Rna Sequencing Data, Zhenxian Zheng, Xian Yu, Lei Chen, Yan-Lam Lee, Cheng Xin, Angel On Ki Wong, Miten Jain, Rupesh K Kesharwani, Fritz J Sedlazeck, Ruibang Luo

Faculty, Staff and Students Publications

Variant calling with long-read RNA sequencing (lrRNA-seq) helps to analyze full-length isoforms and gene expression but is complicated by high error rates, transcript diversity, RNA editing events, etc. Here, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data. Building upon Clair series' pipelines, Clair3-RNA enhances lrRNA-seq variant calling using optimized techniques, such as uneven coverage normalization, refined training data, editing site discovery, and haplotype phasing to enhance performance. Clair3-RNA supports various platforms, including PacBio, ONT complementary DNA sequencing (cDNA), and ONT direct RNA sequencing (dRNA). Clair3-RNA achieved a ~ 91% SNP F1-score on the ONT platform …


Current Controversies On Adequate Circulating Vitamin D Levels In Ckd, Adriana S Dusso, Daniela J Porta, Carlos Bernal-Mizrachi Dec 2025

Current Controversies On Adequate Circulating Vitamin D Levels In Ckd, Adriana S Dusso, Daniela J Porta, Carlos Bernal-Mizrachi

2020-Current year OA Pubs

Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) has evolved dramatically over the past five decades, driven by discoveries that have fundamentally reshaped our understanding of the vitamin D endocrine system and its role in disease progression. This review synthesizes the key pathophysiological insights and clinical evidence underlying three critical paradigm shifts. The first shift moved beyond simple calcitriol replacement with the development of selective vitamin D receptor activators (VDRAs) designed to minimize hypercalcemia while maximizing PTH suppression. Crucially, these analogs revealed unexpected survival benefits, suggesting protective VDR actions extending beyond mineral metabolism. The second shift recognized the …


Video Conversation Aids To Assist In Goals-Of-Care Discussions With Older Adults In A Medical Setting: A Systematic Review, Ashna S Karpe, Mokunfayo O Fajemisin, Stephanie Martinez Ugarte, Lara Ouellette, Martin L Blakely, Gina H Khraish, Shreyans V Sanghvi, Min J Kwak, Jessica L Lee, Lillian S Kao, Thaddeus J Puzio Dec 2025

Video Conversation Aids To Assist In Goals-Of-Care Discussions With Older Adults In A Medical Setting: A Systematic Review, Ashna S Karpe, Mokunfayo O Fajemisin, Stephanie Martinez Ugarte, Lara Ouellette, Martin L Blakely, Gina H Khraish, Shreyans V Sanghvi, Min J Kwak, Jessica L Lee, Lillian S Kao, Thaddeus J Puzio

Library Staff Publications

Background

Goals-of-care (GOC) discussions align medical treatment with older adults’ preferences, yet are hindered by communication barriers, provider discomfort, and misinformation. Video-based decision aids improve understanding and reduce decision conflict, though data on their use in older populations remain limited. This review aimed to determine the effectiveness of video-based decision aids in improving GOC discussions and decision-making outcomes among older adults.

Methods

For this systematic review, a medical librarian conducted a literature search of Medline, Embase, Web of Science, CINAHL, PsychINFO, and Cochrane from database inception through April 2025. Eligible studies evaluated a video-based aid in US adults aged ≥65 …


Implementation Of Single-Pill Combination Medication For Hypertension Treatment By Nonphysician Health Care Workers At Primary Healthcare Facilities In Nigeria: An Explanatory Mixed Methods Study, Emmanuel I Okpetu, Chisom Obiezu-Umeh, Boni M Ale, Abigail S Baldridge, Rosemary C B Okoli, Grace J Shedul, Gabriel L Shedul, Nanna R Ripiye, Ikechukwu A Orji, Lisa R Hirschhorn, Dike B Ojji, Mark D Huffman, Hypertension Treatment In Nigeria Program Investigators Dec 2025

Implementation Of Single-Pill Combination Medication For Hypertension Treatment By Nonphysician Health Care Workers At Primary Healthcare Facilities In Nigeria: An Explanatory Mixed Methods Study, Emmanuel I Okpetu, Chisom Obiezu-Umeh, Boni M Ale, Abigail S Baldridge, Rosemary C B Okoli, Grace J Shedul, Gabriel L Shedul, Nanna R Ripiye, Ikechukwu A Orji, Lisa R Hirschhorn, Dike B Ojji, Mark D Huffman, Hypertension Treatment In Nigeria Program Investigators

2020-Current year OA Pubs

BACKGROUND: Single-pill combination (SPC) therapy improves hypertension control; however, its implementation in primary care settings remains limited. In Nigeria, there is insufficient evidence on factors influencing SPC uptake, particularly from the perspective of healthcare workers (HCWs). This study examined the implementation of SPC medications for hypertension treatment by nonphysician HCWs at primary healthcare facilities (PHCs) in Nigeria.

METHODS: An explanatory sequential mixed methods study was conducted, building on a cluster randomized controlled trial embedded within the Hypertension Treatment in Nigeria Program. The trial compared SPC medications with free-equivalent combination therapies across 60 PHCs (January-June 2021). A subsequent qualitative component (September-December …


Acl Injuries In Major League Soccer: A 10-Year Analysis Of Injury Rate And Return To Play, And Performance Metrics By Player Position, Brian Forsythe, Catherine Hand, Camden Bohn, Francis Hand, Vahram Gamsarian, Daanish Khazi-Syed, Joshua Chang, Vikranth Mirle, Eric Giza, Robert Brophy, Danyal Nawabi, Bert Mandelbaum Dec 2025

Acl Injuries In Major League Soccer: A 10-Year Analysis Of Injury Rate And Return To Play, And Performance Metrics By Player Position, Brian Forsythe, Catherine Hand, Camden Bohn, Francis Hand, Vahram Gamsarian, Daanish Khazi-Syed, Joshua Chang, Vikranth Mirle, Eric Giza, Robert Brophy, Danyal Nawabi, Bert Mandelbaum

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) injuries are among the most debilitating injuries in professional soccer, often leading to extended recovery times and performance impacts. While much is known about ACL injury outcomes in European leagues, data specific to the Major League Soccer (MLS) remains limited.

PURPOSE/HYPOTHESIS: This study aimed to assess the return to play (RTP) times, RTP rates, and performance outcomes after ACL reconstruction in MLS athletes. It was hypothesized that RTP times would improve over the study period and that player performance would stabilize by the third post-injury season, consistent with findings from other professional soccer leagues.

STUDY …


Enteric Nervous System Degeneration In Human And Murine Cln3 Disease, Is Ameliorated By Gene Therapy In Mice, Ewa A Ziółkowska, Letitia L Williams, Matthew J Jansen, Sophie H Wang, Elizabeth M Eultgen, Jaiprakash Sharma, Marco Sardiello, Rebecca P Bradley, Ineka T Whiteman, Mark S Sands, Robert O Heuckeroth, Jonathan D Cooper Dec 2025

Enteric Nervous System Degeneration In Human And Murine Cln3 Disease, Is Ameliorated By Gene Therapy In Mice, Ewa A Ziółkowska, Letitia L Williams, Matthew J Jansen, Sophie H Wang, Elizabeth M Eultgen, Jaiprakash Sharma, Marco Sardiello, Rebecca P Bradley, Ineka T Whiteman, Mark S Sands, Robert O Heuckeroth, Jonathan D Cooper

2020-Current year OA Pubs

Severe gastrointestinal (GI) symptoms occur in people with CLN3 disease, a neurodegenerative disorder. If left untreated these GI symptoms compromise life quality and may contribute to death. We hypothesized GI symptoms in CLN3 disease are at least partially due to neurodegeneration in the enteric nervous system (ENS), the master regulator of bowel function. We examined the integrity of the ENS in human CLN3 autopsy small bowel and colon, and in CLN3 deficient (Cln3Δex7/8) mice. We performed detailed immunohistological analyses of enteric neurons and glia and assessed bowel transit times at multiple disease stages. We then tested the therapeutic potential of …


Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube Dec 2025

Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube

Faculty, Staff and Student Publications

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer …


Efficacy Of Intravenous Immunoglobulin In Patients With Chronic Inflammatory Demyelinating Polyneuropathy With Or Without Diabetes: Insights From A Multicenter Prospective Comparative Study., Samir P. Macwan, Shalini Mahajan, Peter Novak, Khosro Farhad, Ericka Wong, Thomas H. Brannagan, Sohail Masood, Fawad Piracha, Marinos C. Dalakas Dec 2025

Efficacy Of Intravenous Immunoglobulin In Patients With Chronic Inflammatory Demyelinating Polyneuropathy With Or Without Diabetes: Insights From A Multicenter Prospective Comparative Study., Samir P. Macwan, Shalini Mahajan, Peter Novak, Khosro Farhad, Ericka Wong, Thomas H. Brannagan, Sohail Masood, Fawad Piracha, Marinos C. Dalakas

Department of Neurology Faculty Papers

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most frequently observed autoimmune neuropathy in patients with diabetes mellitus (DM). While intravenous immune globulin (IVIG) is a well-established treatment for CIDP, its efficacy in diabetic patients remains uncertain due to their exclusion from prior randomized trials, largely because of concerns about confounding diabetic axonal neuropathy.

OBJECTIVES: To evaluate the effectiveness of IVIG therapy in CIDP patients with diabetes mellitus (CIDP-DM) compared to those without diabetes (CIDP).

DESIGN: Multi-center, prospective, observational study after at least 3 monthly infusions of IVIG therapy.

METHODS: Thirty-six patients meeting diagnostic criteria for CIDP were enrolled and …


A Protein Complex In The Extreme Distal Tip Of Vertebrate Motile Cilia Controls Their Organization, Length, And Function, Juyeon Hong, Jiehong Pan, Amjad Horani, Steven L Brody, Et Al. Dec 2025

A Protein Complex In The Extreme Distal Tip Of Vertebrate Motile Cilia Controls Their Organization, Length, And Function, Juyeon Hong, Jiehong Pan, Amjad Horani, Steven L Brody, Et Al.

2020-Current year OA Pubs

The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33, occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization …


Imlunestrant, An Oral Selective Estrogen Receptor Degrader, In Combination With Her2 Directed Therapy, With Or Without Abemaciclib, In Er-Positive, Her2-Positive Advanced Breast Cancer: Results From The Phase 1a/1b Ember Study, Manali Bhave, Cynthia X Ma, Et Al. Dec 2025

Imlunestrant, An Oral Selective Estrogen Receptor Degrader, In Combination With Her2 Directed Therapy, With Or Without Abemaciclib, In Er-Positive, Her2-Positive Advanced Breast Cancer: Results From The Phase 1a/1b Ember Study, Manali Bhave, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hormone receptor-positive (HR+), human epithelial growth factor receptor 2 (HER2) overexpressed breast cancer (BC) represents the more aggressive subtype of HR + BC, typically associated with poor clinical outcomes. Despite significant advancements in the treatment of estrogen receptor-positive (ER+)/HER2 + BC, resistance to endocrine therapy (ET) poses a continued challenge. Imlunestrant is a next-generation, oral, brain-penetrant, pure antagonistic ER degrader designed to deliver continuous ER target inhibition. It has shown favorable clinical benefit, safety, and pharmacokinetics (PK) when used as monotherapy or with targeted therapy in patients with ER+/HER2- advanced BC (ABC). Here, we present the safety and efficacy …


Cv: Catherine Bohlin (Exercise Science), Catherine Bohlin Dec 2025

Cv: Catherine Bohlin (Exercise Science), Catherine Bohlin

Rehabilitation and Health Sciences Department Faculty Curricula Vitae

No abstract provided.


Cv: Catherine Bohlin (Exercise Science), Catherine Bohlin Dec 2025

Cv: Catherine Bohlin (Exercise Science), Catherine Bohlin

Health Sciences Department Curricula Vitae

No abstract provided.


Optimization Of Actuator Stiffness And Actuation Timing Of A Passive Ankle Exoskeleton: A Case Study Using A Musculoskeletal Modeling Approach, Jania Williams, Cody P. Anderson, Arash Mohammadzadeh Gonabad, Farahnaz Fallahtafti, Sara A. Myers, Hafizur Rahman Dec 2025

Optimization Of Actuator Stiffness And Actuation Timing Of A Passive Ankle Exoskeleton: A Case Study Using A Musculoskeletal Modeling Approach, Jania Williams, Cody P. Anderson, Arash Mohammadzadeh Gonabad, Farahnaz Fallahtafti, Sara A. Myers, Hafizur Rahman

School of Podiatric Medicine Publications

Objective: A modeling and simulation tool, OpenSim, was used to determine the optimal relationship between actuator stiffness and actuation timing of a passive ankle exoskeleton for reducing metabolic costs during walking. We hypothesized that the absolute minimum in total metabolic cost would exist at an actuation timing of 15% of stance and at a spring stiffness of 7.5 kN/m. We also hypothesized that a local minimum in total metabolic cost would exist at an actuation timing of 50% of stance. Methods: Bilateral kinematics and kinetics data were collected on a healthy male walking overground wearing his regular tennis shoe. The …


Changes In Sleep Quality During The 12 Months Following Medical Cannabis Initiation., Megan M. Short, Michelle R. Lent, Thomas R. Mccalmont, Karen L Dugosh Dec 2025

Changes In Sleep Quality During The 12 Months Following Medical Cannabis Initiation., Megan M. Short, Michelle R. Lent, Thomas R. Mccalmont, Karen L Dugosh

PCOM Scholarly Works

BACKGROUND: Poor sleep quality is a commonly reported reason for medical cannabis (MC) use, yet evidence regarding its long-term impact on sleep remains limited. This study evaluated changes in subjective sleep quality over a 12-month period among adults initiating MC treatment in Pennsylvania and explored whether preferred route of administration and referring condition were associated with observed changes.

METHODS: A total of 137 adults newly referred for MC in PA completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and at 3, 6, 9, and 12 months. Linear mixed effects models assessed changes in PSQI global and subscale scores over …