Digital Commons Network^™

Decreasing Barriers To The Utilization Of Cryopreserved Sperm In Male Cancer Survivors: An Expert Review And Guide, Megan V Alexander, Hailie Ciomperlik, Anna Claire Reynolds, Allyson Nevins, Luwam Ghidei, Jordan Kassab, Kevin Campbell, John Sullivan, Michael D Jochum, Laura Detti, Terri L Woodard, Larry I Lipshultz, Laurie J Mckenzie

Faculty, Staff and Students Publications

Background: Sperm cryopreservation offers male cancer patients a critical opportunity to preserve fertility prior to gonadotoxic therapy, yet utilization of banked sperm remains modest, typically under 10%. A structured understanding of barriers across the cancer survivorship continuum is needed to support patients in utilization of cryopreserved sperm in alignment with their reproductive goals.

Materials and methods: This expert review synthesizes current evidence and clinical experience to explore the multifaceted barriers to cryopreserved sperm use and propose specific solutions. Key intervention timepoints are examined, including the post-treatment fertility return visit, long-term cryopreservation while remote from family building, readiness for family building, …

How Well Can Commonly Used Anxiety Scales Detect Treatment Outcomes In The Context Of Autism?, Huilin Chen, Jeffrey J Wood, Connor M Kerns, Eric A Storch, Philip C Kendall, Gaia Scerif, Cathy Creswell

Faculty, Staff and Students Publications

Anxiety is one of the most prevalent mental health challenges in autistic children, yet there is limited evidence on effective tools to measure treatment outcomes. Previous research with non-autistic children has found that the Child Anxiety Impact Scale, Parent Version achieved good diagnostic accuracy when measuring treatment outcomes and performed better than a commonly used symptom measure. However, this has not been evaluated for autistic children. The present study examined the psychometric properties of the Child Anxiety Impact Scale, Parent Version in autistic children and compared its utility against other anxiety symptom measures, to detect treatment outcomes as assessed by …

Fibroblasts Are The Primary Contributors To A Disrupted Micro-Environment In End-Stage Pediatric Hypertrophic Cardiomyopathy, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

Results: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes …

Group Concept Mapping To Develop A Salon-Based Hpv Self-Collection Intervention, Kelly N B Palmer, Namoonga M Mantina, Adebola Adegboyega, Itunu O Sokale, Kathleen Pryor, Azaria Suero-Davis, Trevon Brooks, Jennifer Hatcher

Faculty, Staff and Students Publications

Background: Black women in the US face higher cervical cancer mortality rates due to delayed diagnoses linked to lower screening rates. Contributing factors include provider bias, costs, and limited access, particularly affecting women aged 40-64. While innovative approaches like clinical and home-based HPV self-collection exist, equitable dissemination remains challenging. Distributing HPV self-collection kits in unconventional sites like hair salons may offer a solution. Using concept mapping, we gathered community insights to design a salon-based cervical cancer screening intervention.

Methods: We employed groupwisdom™ and REDCap platforms for community-based participatory intervention development. Participants included members of the Black Community Advisory Council of …

Implications Of Cooccurring Adhd For The Cognitive Behavioural Treatment Of Anxiety In Autistic Children, Elise Ng-Cordell, Eric A Storch, Philip C Kendall, Jeffrey J Wood, Amori Yee Mikami, Connor M Kerns

Faculty, Staff and Students Publications

Background: Childhood mental health conditions commonly cooccur, with potential treatment implications. Autistic children frequently experience anxiety and attention deficit/hyperactivity disorder (ADHD). We investigated the implications of this cooccurrence for Cognitive Behavioural Therapy (CBT), a front-line treatment for anxiety in autistic children. We tested whether (1) ADHD predicts anxiety treatment response, (2) ADHD improves in response to anxiety treatment and (3) ADHD improvement is related to reductions in anxiety.

Method: Autistic children with elevated anxiety (N = 167) enrolled in a multisite, randomised controlled trial comparing standard CBT, autism-adapted CBT and treatment as usual. ADHD symptoms and severity were assessed via …

Insights From A Survey Of School Nurses: Assessing The Challenges Of Constipation In Schools, Andrew S Chu, Eric H Chiou

Faculty, Staff and Students Publications

Objectives: School nurses are key responders to students with constipation, yet their experiences are underreported. This study surveyed their observations regarding constipation, identified barriers to student restroom access, and assessed educational needs.

Methods: In this descriptive, cross-sectional survey study, an anonymous online survey was distributed to school nurses participating in a virtual education series. The survey assessed nurse demographics, frequency of encounters with constipation and encopresis, school restroom policies, barriers to restroom use, accommodation requests, and training in constipation management.

Findings: Of 125 respondents, 95% encountered students with constipation at least monthly and 55% reported ≥ 6 encounters monthly. Commonly …

Phenotypic Variability And Paternal Inheritance Of A Chd8 Variant Causing Intellectual Developmental Disorder With Autism And Macrocephaly Confirmed By Epigenetic And Structural Analyses, Yutaka Furuta, Jonathan H Sheehan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intellectual developmental disorder with autism and macrocephaly (IDDAM, OMIM #615032) is an autosomal dominant neurodevelopmental disorder characterized primarily by intellectual disability, autism spectrum disorder, macrocephaly, tall stature, gastrointestinal symptoms, and variable neurological manifestations. Most cases result from de novo pathogenic variants in CHD8.

METHODS: We conducted genome sequencing through the Undiagnosed Diseases Network (UDN) in a female proband harboring a CHD8 variant of uncertain significance (VUS), whose clinical presentation was consistent with IDDAM but included atypical features such as ptosis and hearing loss. Variant pathogenicity was further evaluated using EpiSign DNA methylation analysis and structural biology modeling.

RESULTS: Genome …

A Roadmap To Scale Up Person-Centred Care In The Hiv Response: Recommendations From A Global Consensus-Building Process, Lina Golob, Elvin H Geng, Et Al.

2020-Current year OA Pubs

INTRODUCTION: World Health Organization global normative guidance recommends person-centred care (PCC) approaches to reduce HIV-related mortality and morbidity and to improve health-related quality of life (HrQoL). However, consensus on the priority PCC elements and guidance on how different stakeholders can realize PCC principles at the health systems, service delivery and individual client-healthcare worker (HCW) levels are lacking. We conducted a global consensus-building process to define core PCC elements and develop recommendations for implementation at scale.

METHODS: We used a multi-phase process to build consensus and prioritize recommendations, consisting of a literature review, five stakeholder consultations (34-43 participants each) between July …

Fast And Accurate Measurement Of Small Field Dosimetry Using A Novel Scintillation Detector, Yiding Han, Jingzhu Xu, Yao Hao, Baozhou Sun

2020-Current year OA Pubs

BACKGROUND: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.

PURPOSE: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD …

Telemedicine Preexposure Prophylaxis Prescribing From A Large Online Us Company, Aaron J Siegler, Shi Hao Ernest Koh, Tristan Schukraft, Simon Mazzoni, Edwin Corbin-Gutierrez, Rupa R Patel, Patrick S Sullivan, Wenting Huang

2020-Current year OA Pubs

IMPORTANCE: HIV preexposure prophylaxis (PrEP) is highly effective in HIV prevention; telemedicine is a promising avenue for delivering PrEP care.

OBJECTIVE: To explore telemedicine delivery of PrEP care (telePrEP) by the largest telePrEP company in the US.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, single-arm cohort study used health record data of patients receiving telePrEP from MISTR LLC, a for-profit telehealth company, from November 27, 2018, to March 5, 2025. Patient characteristics and AIDSVu data were assessed to determine levels of PrEP use nationally. Retention in care was assessed for persons initiating PrEP in 2020, 2021, and 2022. Data were analyzed …

Impact Of Silencing Automated Penicillin Cross-Reactivity Alerts On Perioperative Antibiotic Prescribing And Surgical Site Infection Rates, Michael J Durkin, Joshua Nordman, Alice Bewley, Andrew Atkinson, Jonas Marschall, Helen Newland, Kimberly G Blumenthal

2020-Current year OA Pubs

We evaluated the impact of silencing penicillin cross-reactivity alerts on perioperative antibiotic prescribing and surgical site infections (SSIs) in 6 hospitals using an interrupted time series analysis. Silencing the alerts minimally increased cefazolin prescribing among penicillin allergy labeled patients (sensitivity analysis only;

Introducing The Outpace Framework For Health Care Quality Improvement, Michele Bolles, Heather M. Alger, Mitchell S. V. Elkind, Howard Haft, Sabra C. Lewsey, Mariell Jessup, Karen E. Joynt Maddox, Chiadi E. Ndumele, Clyde W. Yancy, Christine Rutan, Michelle Congdon, Katherine Overton, Lynn Serdynski, Kathie Thomas, Gregg C. Fonarow

2020-Current year OA Pubs

Equitable, timely, and evidence-based care remains a central goal across health care ecosystems, yet significant quality gaps, care variability, and health disparities persist. Professional societies, including the American Heart Association, have long developed clinical practice guidelines to provide standardized, evidence-based recommendations across the cardiovascular care continuum. These guidelines are operationalized into quality measures to monitor care, identify gaps, and guide improvement. Professional societies, agencies, and health systems have applied implementation science strategies, such as education, data sharing, and evaluation, to improve care quality and achieve quality measures defined in the clinical practice guidelines. American Heart Association's Get With The Guidelines …

Does Health Insurance Coverage Improve Cardiometabolic Risk Factor Levels? Quasi-Experimental Evidence From India, Kavita Singh, Anubha Agarwal, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored.

OBJECTIVE: To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India.

METHODS: Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality …

Long-Term Illness In Adults Hospitalized For Respiratory Syncytial Virus Disease, United States, February 2022-September 2023, Aleda M Leis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

Respiratory syncytial virus (RSV) can cause severe illness, but little is known about long-term consequences in hospitalized adults. We surveyed adults (>18 years of age) who survived hospitalization for RSV or COVID-19 during February 2022-September 2023 about physical functioning and quality of life; surveys were conducted 6-12 months after hospitalization. We compared outcomes after RSV hospitalization by age (< 60 vs. >60 years) and to those hospitalized for COVID-19 by using multivariable regression models. Among 146 adults hospitalized with RSV, 27.4% reported severe breathlessness and 21.9% poor quality of life at follow-up. Few differences were seen in posthospital illness by age. …

Impact Of Common Variants On Brain Gene Expression From Rna To Protein To Schizophrenia Risk, Qiuman Liang, Yi Jiang, Annie W Shieh, Dan Zhou, Rui Chen, Feiran Wang, Meng Xu, Mingming Niu, Xusheng Wang, Dalila Pinto, Yue Wang, Lijun Cheng, Ramu Vadukapuram, Chunling Zhang, Kay Grennan, Gina Giase, Kevin P White, Junmin Peng, Bingshan Li, Chunyu Liu, Chao Chen, Sidney H Wang

The Brown Foundation: Institute of Molecular Medicine

Genetic variants influencing gene expression have been extensively studied at the transcriptional level. How these variants affect downstream processes remains unclear. We quantitated ribosome occupancy in prefrontal cortex samples from the BrainGVEX cohort and integrated these data with transcriptomic and proteomic profiles from the same individuals. Through cis-QTL mapping, we identified genetic variants associated with transcript level (eQTLs), ribosome occupancy (rQTLs), and protein level (pQTLs). Notably, only 34% of eQTLs have their effects propagated to the protein levels, suggesting widespread post-transcriptional attenuation. Using both a gene-based approach and a variant-based approach we identified omics-specific QTLs that associated with brain disorder …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

Faculty, Staff and Student Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Structure Of An Lgr Dimer, An Evolutionary Predecessor Of Glycoprotein Hormone Receptors, Zhen Gong, Shuobing Chen, Ziao Fu, Brian Kloss, Chi Wang, Jonathan Kim, Oliver B Clarke, Qing R Fan, Wayne A Hendrickson

2020-Current year OA Pubs

Glycoprotein hormones (GpHs) produced in the human pituitary act through receptors (GpHRs) in the gonads to support reproduction and in the thyroid for metabolism. GpHs are heterodimeric cystine-knot proteins; their receptors bind cognate hormones at an extracellular domain and signal through a transmembrane domain to heterotrimeric G proteins. GpHs and GpHRs have co-evolved from invertebrate counterparts. Structures of the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers. Here we characterize the homologous receptor from Caenorhabditis elegans. Its biochemical properties are notably similar to those of the thyroid stimulating …

“I Missed My Other Oncologist”: Established Relationships As Barriers And Facilitators To Accessing Car-T And Autologous Transplantation, Zachary A. K. Frosch, Clark Meshack, Caitlin Meeker, Asya Varshavsky-Yanovsky, Rashmi Khanal, Michael Bromberg, Ashwin Chandar, Emmanuel Quien, Jordan Carter, Shazia K. Nakhoda, Marcus Messmer, Charissa Montgomery, Jason A. Incorvati, Nadia D. Ali, Michael J. Styler, Carolyn Y. Fang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) can provide significant clinical benefit, but are not equally available to all patients. Oncologist continuity and trust are important to patients, and may act as barriers to receipt of therapy. However, detailed data are lacking on the mechanism by which these might affect receipt of therapy, or how this barrier may be overcome.

METHODS: We conducted a qualitative interview study with patients with non-Hodgkin lymphoma (NHL), classic Hodgkin lymphoma (cHL) or multiple myeloma (MM) eligible for or treated with ASCT/CAR-T. Participants were recruited from a multi-site academic …

Non-Invasive Ultrasonic Neuromodulation Of The Human Nucleus Accumbens Impacts Reward Sensitivity, Siti N Yaakub, John Eraifej, Nadège Bault, Mathilde Lojkiewiez, Elouan Bellec, Jamie Roberts, Noah S Philip, Amir Puyan Divanbeighi Zand, Alexander L Green, Matthew F S Rushworth, Elsa F Fouragnan

School of Psychology

Precisely neuromodulating deep brain regions could bring transformative advancements in both neuroscience and treatment. We demonstrate that non-invasive transcranial ultrasound stimulation (TUS) can selectively modulate deep brain activity and affect learning and decision making, comparable to deep brain stimulation (DBS). We tested whether TUS could causally influence neural and behavioural responses by targeting the nucleus accumbens (NAcc) using a reinforcement learning task. Twenty-six healthy adults completed a within-subject TUS-fMRI experiment with three conditions: TUS to the NAcc, dorsal anterior cingulate cortex (dACC), or Sham. After TUS, participants performed a probabilistic learning task during fMRI. TUS-NAcc altered BOLD responses to reward …

Developing Ehealth Interventions To Improve Diabetes Management In Emerging Adulthood: Qualitative Formative Study, April Idalski Carcone, Deepika Baskar, Aishah Mahmood, Karen Macdonell, Susan Eggly, Samiran Ghosh, Colleen Buggs-Saxton, Steven J Ondersma, Deborah A Ellis

Faculty, Staff and Student Publications

Background: Emerging adulthood is a high-risk period during which many with type 1 diabetes demonstrate suboptimal diabetes management and glycemic control. There is a need for effective, scalable interventions designed specifically for this population. Technology-based approaches are readily accessible to this age group. Furthermore, interventions consistent with self-determination theory-which posits that the fulfillment of psychological needs for autonomy, self-efficacy, and relatedness promotes intrinsic motivation for change-may resonate well with emerging adults' developmental needs for establishing independence and autonomy, and growing their social network.

Objective: This study aimed to enhance the potential relevance, sustainability, and efficacy of 3 self-determination theory-informed mobile …

Human Plasma Proteomic Profile Of Clonal Hematopoiesis, Zhi Yu, Amélie Vromman, Ngoc Quynh H Nguyen, Art Schuermans, Linke Li, Thiago Rentz, Tetsushi Nakao, Shamsudheen K Vellarikkal, Md Mesbah Uddin, Abhishek Niroula, Gabriel Griffin, Michael C Honigberg, Amy E Lin, Christopher J Gibson, Daniel H Katz, Usman A Tahir, Shi Fang, Jacqueline S Dron, Michael Pan, Sara Haidermota, Shriienidhie Ganesh, Tajmara Antoine, Joshua Weinstock, Thomas R Austin, Ramachandran S Vasan, Gina M Peloso, Whitney Hornsby, Peter Ganz, Joann E Manson, Bernhard Haring, Charles Kooperberg, Alexander P Reiner, Joshua C Bis, Bruce M Psaty, Yuan-I Min, Adolfo Correa, Leslie A Lange, Wendy S Post, Jerome I Rotter, Stephen S Rich, James G Wilson, Benjamin L Ebert, Bing Yu, Christie M Ballantyne, Josef Coresh, Vijay G Sankaran, Alexander G Bick, Siddhartha Jaiswal, Robert E Gerszten, Nhlbi Trans-Omics For Precision Medicine, Peter Libby, Rajat M Gupta, Pradeep Natarajan

Faculty, Staff and Student Publications

Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer insights into downstream clinical consequences. Here we explore these patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 participants (3881 with CHIP) from TOPMed and UK Biobank (UKB) with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2917 proteins by Olink in UKB), we identify 32 and 345 proteins from TOPMed and UKB, respectively, associated with CHIP and most prevalent driver genes (DNMT3A, TET2, and ASXL1). These …

Investigating The Neuronal Role Of The Proteasomal Atpase Subunit Gene Psmc5 In Neurodevelopmental Proteasomopathies, Sébastien Küry, Janelle E Stanton, Geeske M Van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most, Tianyun Wang, Jonas J Papendorf, Charlotte De Konink, Wallid Deb, Virginie Vignard, Maja Studencka-Turski, Thomas Besnard, Anna M Hajdukowicz, Franziska G Thiel, Sophie Wolfgramm, Laëtitia Florenceau, Silvestre Cuinat, Sylvain Marsac, Yann Verrès, Audrey Dangoumau, Léa Poirier, Ingrid M Wentzensen, Annabelle Tuttle, Cara Forster, Johanna Striesow, Richard Golnik, Damara Ortiz, Laura Jenkins, Jill A Rosenfeld, Alban Ziegler, Clara Houdayer, Dominique Bonneau, Erin Torti, Amber Begtrup, Kristin G Monaghan, Sureni V Mullegama, Catharina M L Nienke Volker-Touw, Koen L I Van Gassen, Renske Oegema, Mirjam S De Pagter, Katharina Steindl, Anita Rauch, Ivan Ivanovski, Kimberly Mcdonald, Emily Boothe, Andrew Dauber, Janice Baker, Noelle Andrea V Fabie, Raphael A Bernier, Tychele N Turner, Siddharth Srivastava, Kira A Dies, Lindsay C Swanson, Carrie Costin, Alali Abdulrazak, Rebekah K Jobling, John Pappas, Rachel Rabin, Dmitriy Niyazov, Anne Chun-Hui Tsai, Karen Kovak, David B Beck, May Christine V Malicdan, David R Adams, Lynne Wolfe, Rebecca D Ganetzky, Colleen C Muraresku, Davit Babikyan, Zdeněk Sedláček, Miroslava Hančárová, Andrew T Timberlake, Hind Al Saif, Berkley Nestler, Kayla King, M J Hajianpour, Gregory Costain, D'Arcy Prendergast, Chumei Li, David Geneviève, Antonio Vitobello, Arthur Sorlin, Christophe Philippe, Tamar Harel, Ori Toker, Ataf Sabir, Derek Lim, Mark J Hamilton, Lisa J Bryson, Elaine Cleary, Sacha Weber, Trevor L Hoffman, Anna M Cueto-González, Eduardo F Tizzano, David Gómez-Andrés, Marta Codina-Solà, Athina Ververi, Efterpi Pavlidou, Alexandros Lambropoulos, Kyriakos Garganis, Marlène Rio, Jonathan Levy, Sarah J Langas, Anne M Mcrae, Mathieu K Lessard, Maria Daniela D'Agostino, Isabelle De Bie, Meret Wegler, Rami Abou Jamra, Susanne B Kamphausen, Viktoria Bothe, Lorraine Potocki, Eric Olinger, Yves Sznajer, Elsa Wiame, Michelle L Thompson, Molly C Schroeder, Catherine Gooch, Raphael A Smith, Arti Pandya, Larissa M Busch, Uwe Völker, Elke Hammer, Kristian Wende, Benjamin Cogné, Bertrand Isidor, Jens Meiler, Clémentine Ripoll, Stéphanie Bigou, Frédéric Laumonnier, Peter W Hildebrand, Evan E Eichler, Kirsty Mcwalter, Peter M Krawitz, Florence Roux-Dalvai, Ype Elgersma, Julien Marcoux, Marie-Pierre Bousquet, Arnaud Droit, Jeremie Poschmann, Andreas M Grabrucker, Francois V Bolduc, Stéphane Bézieau, Frédéric Ebstein, Elke Krüger

Faculty, Staff and Students Publications

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor …

Exploring Experiences Of Mental Health Challenges In Under-Represented Young People (Aged 16–24 Years) In England: A Narrative Inquiry Protocol, Rebecca Syed Sheriff, Jason Arday, Rohit Shankar, Roisin Mooney, Louise Chandler, Helen Adams, Lili Z Nagy, Roger Farrell, Daisy Fancourt, Scott Weich, Catherine Henderson, Shaima Hassan, Joe Langley, Kamaldeep Bhui

Peninsula Medical School

Introduction Three-quarters of mental health problems start before the age of 25. However, young people are the least likely to receive mental healthcare. Some young people (such as those from ethnic minorities) are even less likely to receive mental healthcare than others. Long-term impacts of mental health problems include poorer physical health, relationships, education and employment. We aim to elicit the views, experiences and needs of diverse young people (aged 16–24 years), to better understand (1) their experiences of under-representation, mental health and coping, (2) mechanisms that shape mental health trajectories and (3) how online arts and culture might be …

Turning Patients' Open-Ended Narratives Of Chronic Pain Into Quantitative Measures: Natural Language Processing Study, Raquel Norel, Jennifer Gewandter, Zhengwu Zhang, Anika Tahsin, Chadi G Abdallah, John Markman, Zhiyao Duan, Guillermo Cecchi, Paul Geha

Faculty, Staff and Students Publications

Background: Subjective report of pain remains the gold standard for assessing symptoms in patients with chronic pain and their response to analgesics. This subjectivity underscores the importance of understanding patients' personal narratives, as they offer an accurate representation of the illness experience.

Objective: In this pilot study involving 20 patients with chronic low back pain (CLBP), we applied emerging tools from natural language processing (NLP) to derive quantitative measures that captured patients' pain narratives.

Methods: Patients' narratives were collected during recorded semistructured interviews in which they spoke about their lives in general and their experiences with CLBP. Given that NLP …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

The Global Hypophosphatasia Registry: Lessons Learned From A Decade Of Real-World Data., Priya S. Kishnani, Lothar Seefried, Keiichi Ozono, Gabriel Ángel Martos-Moreno, Cheryl Rockman-Greenberg, Deborah Fowler, Luke K. Burke, William R. Mowrey, Eric T. Rush, Peter R. Ebeling, Wolfgang Högler, Agnès Linglart, Shona Fang, Anna Petryk, Kathryn M. Dahir

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Hypophosphatasia (HPP) is an inherited, metabolic, rare disease characterized by a high level of clinical heterogeneity. In response to this robust heterogeneity, the Global HPP Registry was formed to characterize the types of manifestations that patients may experience, as well as to compile information on genetic underpinnings of the disease, overall impact on patient quality of life, and safety and effectiveness of enzyme replacement therapy. The objective of this review was to synthesize key learnings gained from the Global HPP Registry, which is now in its tenth year of enrolling patients.

METHODS: Registry data were analyzed to provide up-to-date …

Live-Cell Quantitative Monitoring Reveals Distinct, High-Affinity Gβγ Regulations Of Girk2 And Girk1/2 Channels, Reem Handklo-Jamal, Tal Keren Raifman, Boris Shalomov, Patrick Hofer, Uri Kahanovitch, Theres Friesacher, Galit Tabak, Vladimir Tsemakhovich, Haritha P Reddy, Orna Chomsky-Hecht, Debi Ranjan Tripathy, Kerstin Zuhlke, Carmen W Dessauer, Enno Klussmann, Yoni Haitin, Joel A Hirsch, Anna Stary-Weinzinger, Daniel Yakubovich, Nathan Dascal

Faculty, Staff and Student Publications

Gi/o protein-coupled receptors (GPCRs) inhibit cardiac and neuronal excitability via G protein-activated K+ channels (GIRK), assembled by combinations of GIRK1 - GIRK4 subunits. GIRKs are activated by direct binding of the Gβγ dimer of inhibitory Gi/o proteins. However, key aspects of this textbook signaling pathway remain debated. Recent studies suggested no Gi/o-GIRK pre-coupling and low (>250 µM) Gβγ-GIRK interaction affinity, contradicting earlier sub-µM estimates and implying low signaling efficiency. We show that Gγ prenylation, which mediates Gβγ membrane attachment required for GIRK activation, also contributes to the Gβγ-GIRK interaction, explaining the poor affinity obtained with non-prenylated Gβγ. Using quantitative …

Cohort Profile: The Pharmacogenomics And Pharmacokinetics Study In Ghanaian Hiv Patients (Genopharm-Gh), Nicholas Ekow Thomford, Oksana Ryabinina, Joel Adu Twum, John Anyimadu, Samuel Badu Nyarko, Akwasi Anyanful, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: The GenoPharm-GH project initiated in 2019, as a longitudinal, multi-site observational cohort study aimed at bridging gaps in understanding the influence of host genetics, pharmacokinetics and comorbidities on treatment outcome among persons living with HIV (PLWH) in Ghana.

METHODS: The study is ongoing prospective, longitudinal, multi-site cohort associated with diverse projects being conducted throughout health facilities across Ghana. So far 2044 persons living with HIV (PLWH) aged ≥ 8 years have been registered. These participants are on treatment with antiretroviral therapies (ART). Viral suppression, treatment adherence (self-reported and pill count), clinical data, genetic variations, coinfections, and comorbidities are being …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025., Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Emily R. Levy, Tamara T. Bradford, Stephanie P. Schwartz, Tracie C. Walker, Melissa S. Stockwell, Austin Biggs, Alexander H. Hogan, Katherine Lindsey, Angela P. Campbell, Adrienne G. Randolph, Overcoming Rsv Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < 1 year) in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Mu-Glioma Post: A Comprehensive Dataset Of Automated Mr Multi-Sequence Segmentation And Clinical Features, Esmat Mahmoud, Jaime Gass, Yaseen Dhemesh, Josh Greaser, Karolina Pogorzelski, Edvin Isufi, Filip Garrett, Jonathan Thacker, Nourel Hoda Tahon, Jason Sinclair, Lester Layfield, Talissa Altes, Ayman Nada

2020-Current year OA Pubs

Gliomas represent a heterogenous group of primary brain tumors with overlapping imaging phenotypes. Treatment typically includes surgery and/or chemoradiation, however this varies based on the overall lesion and clinical presentation. This heterogeneity in both lesion characteristics and management strategies contributes to a lack of reliable findings when evaluating treatment outcomes with conventional MRI. The overlapping imaging features of radiation necrosis and tumor progression post-treatment can be particularly challenging for radiologists. We present a dataset of 203 glioma patients with 594 post-treatment timepoints of relevant clinical history and routine T1, T1 postcontrast, T2, and FLAIR weighted MR sequences. Preprocessing of the …