Digital Commons Network^™

Development And Internal Validation Of A Pretransplant Biomarker Panel For Mortality Prediction Following Liver Transplant, Guergana G Panayotova, Sopio Simonishvili, Lianhua Jin, Duc T Nguyen, Edward A Graviss, Yong Qin, Anastasia Xynogala, Tumininu Ayorinde, Laurie J Minze, Alexander Lemenze, Krupa R Mysore, Julie M Corkrean, Linda W Moore, Flavio Paterno, Ashish Saharia, Constance M Mobley, Arpit Amin, Mark J Hobeika, Xian C Li, Paul J Gaglio, R Mark Ghobrial, James V Guarrera, Keri E Lunsford

Faculty, Staff and Students Publications

Importance: Current pretransplant clinical scoring systems fail to accurately estimate post-liver transplant (LT) survival, making recipient selection challenging. Persistent immune dysfunction contributes to early LT recipient mortality but is not captured by existing models.

Objective: To identify plasma biomarkers of pretransplant immune dysfunction and to develop a biomarker-based pre-LT risk stratification tool to predict post-LT mortality.

Design, setting, and participants: Prospective biomarker analysis of consecutively enrolled adult LT recipients was conducted. Healthy controls were included for baseline comparison. Patients undergoing LT at Houston Methodist Hospital (October 1, 2013, to December 31, 2017) and Rutgers/University Hospital (January 1, 2019, to March …

The International Pediatric Headache Didactic Series: A Novel Curriculum Innovation, Sara Pavitt, Sruthi Ilangovan, Zoë Allen, Samantha L Irwin, Irene Patniyot

Faculty, Staff and Students Publications

Objectives: The International Pediatric Headache Didactic Series (IPHDS) was developed to provide free, comprehensive pediatric headache education to healthcare professionals worldwide. The objective of this study was to describe the design, implementation, and impact of this prospective educational intervention.

Background: Headache is the most common neurological symptom within the pediatric population. Yet, only nine fellowships are offered in pediatric headache medicine. Limitations in access to education and training are often cited as reasons for diagnostic and management barriers. To address this gap, the IPHDS was established in July 2022.

Methods: IPHDS is a recurring series consisting of 23 biweekly lectures. …

Confessions In Cases Of Child Physical Abuse-A Capnet Study, Margaret R Russell, Antoinette L Laskey, Henry T Puls, Suzanne P Starling, Joanne N Wood, Daniel M Lindberg, Nancy S Harper, Caitlin R Mcnamara, Angela N Bachim, Farah W Brink, Lori D Frasier, James D Anderst, Porcia Vaughn, Kristine A Campbell

Faculty, Staff and Students Publications

Objective: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

Methods: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

Results: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

Conclusions: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Fronto-Cerebellar Features Associate With Cognitive Dysfunction In Childhood-Onset Systemic Lupus Erythematosus, Hanne Van Der Heijden, Gabrielle Alonzi, Amanda Cao, Raquel Van Gool, Merve Koç Yekedüz, Lise Vrolix, Itamar Ronen, Vanessa Rameh, Kyle Mcbrearty, Aditi Deokar, Robert P Sundel, Eyal Muscal, Joseph Gonzalez-Heydrich, Andrea Knight, Joyce C Chang, Jaymin Upadhyay

Faculty, Staff and Students Publications

Objective: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE.

Methods: Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI.

Results: cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients …

Kidney Disease And Heart Failure: Recent Advances And Current Challenges: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Carolyn S P Lam, Biykem Bozkurt, David Z I Cherney, Justin A Ezekowitz, Meg J Jardine, Sadiya S Khan, Magdalena Madero, Mark J Sarnak, Jozine M Ter Maaten, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Nisha Bansal

Faculty, Staff and Students Publications

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, which elevates the risks of hospitalization, disease progression, and death. Despite advances in treating each condition independently, many challenges remain in diagnosing and managing them in combination. In March 2024, Kidney Disease: Improving Global Outcomes (KDIGO) held the Controversies Conference on Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Discussions highlighted the complex, bidirectional relationship between HF and CKD, including shared risk factors and overlapping pathophysiology as well as nuances in interpreting biomarkers such as natriuretic peptides and serum creatinine. Sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and emerging …

A Comprehensive Review Of Tear Fluid Proteome Alterations In Dry Eye Disease: Insights Into Pathophysiology And Biomarker Potential, Saleh Ahmed, Steven Safille, Victoria Clifton, Shruti Sharma, Cintia S De Paiva, Ashok Sharma

Faculty, Staff and Students Publications

Tear fluid is a highly specialized and dynamic biofluid composed of proteins, lipids, mucins, and electrolytes that is essential for maintaining ocular surface integrity, immune defense, and tear film stability. Growing evidence from tear proteomic studieshas revealed extensive alterations in protein composition in dry eye disease (DED), reflecting a complex interplay between local ocular surface pathology and systemic inflammatory influences. This review summarizes proteomic findings from 50 published studies to identify tear proteins that are consistently upregulated or downregulated in DED and to interpret their biological relevance in the context of ocular surface homeostasis. Across studies, proteins upregulated in DED …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …

Long-Term Outcomes Of Left Bundle-Branch Pacing Vs Biventricular Pacing In Heart Failure: The Heartsync-Lbbp Randomized Clinical Trial, Xueying Chen, Xi Liu, Ruogu Li, Zhongkai Wang, Yixiu Liang, Lei Zhang, Wei Wang, Jin Bai, Jingfeng Wang, Shengmei Qin, Weiwei Zhang, Tianbao Yao, Dong Huang, Ting Chen, Xianxian Zhao, Dening Liao, Jingbo Li, Jialiang Mao, Mihail G Chelu, Yangang Su, Kenneth A Ellenbogen, Junbo Ge

Faculty, Staff and Students Publications

Importance: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking.

Objective: To evaluate the long-term clinical outcomes of LBBP and BiVP.

Design, setting, and participants: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 …

Novel Variants Identified In Families With Snx27 -Related Neurodevelopmental Disorder, Aiding In Characterizing Its Genotypic And Phenotypic Spectrum, Tayyaba Shan, Abrar Hussain, Anushree Acharya, Mulazim Hussain, Yumei Li, Hafiz Muhammad Jafar Hussain, Kiran Afshan, Suzanne M Leal, Rui Chen, Asif Mir, Isabelle Schrauwen, Sabika Firasat

Faculty, Staff and Students Publications

Background:

Sorting Nexin 27 (SNX27), a key regulator of synaptic receptor trafficking and endosomal recycling, has been implicated in maintaining synaptic homeostasis and cognitive function. To date, variants in SNX27 have been reported in a small number of patients across three publications with severe neurodevelopmental phenotypes. However, the genetic and functional landscape of SNX27-related disorders remains poorly understood, and further evidence is needed to confirm its association with disease and to better delineate the associated phenotype.

Methods and Results:

Two unrelated Pakistani families with a total of five affected individuals segregating a neurodevelopmental disorder were investigated via exome …

Black Equality In Ocd Neurogenomics (Belong): Study Protocol, Iasha J Williams, Dalia Y Marquez, Kara E Lopez-Lengowski, Malini Bommiasamy, Ogechi Cynthia Onyeka, Slayton J Underwood, Juliana E Avery, Jacob Gluckman, Thariana Pichardo, Rhea Chandler, Yulu Brown, Katie Mangen, Emma Grace Choplin, Black Equality In Ocd Neurogenomics (Belong) Study Team, Sonyia C Richardson, Joseph D Buxbaum, Eric A Storch, James J Crowley, Sidney H Hankerson, Dorothy E Grice

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a chronic, serious psychiatric disorder that affects 2%-3% of the population and is associated with high personal and societal costs. Genetic factors are estimated to explain roughly half the risk of developing OCD, and genomic studies are just beginning to identify common and rare genetic variants mediating this risk. A major goal of genomic studies is to yield insights into the etiology of OCD and identify molecular targets for the development of novel therapeutics. However, the overwhelming majority of subjects in existing genetic studies are of European ancestry, limiting the generalizability of these findings. To address …

Efficient In Vivo Pharmacological Inhibition Of Δfosb, An Ap-1 Transcription Factor, In The Brain, Sean Mcneme, Anil Kumar, Yun Young Yim, Brandon W Hughes, Corey St Romain, Yi Li, Ashwani Kumar, Qichao Bao, Molly Estill, Shanghua Fan, Nadeen Takatka, Earnest P Chen, Matthew Rivera, Haiying Chen, Alfred J Robison, Mischa Machius, Stephen J Haggarty, Jeannie Chin, Eric J Nestler, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, an unusually stable member of the AP-1 family of transcription factors, mediates long-term maladaptations that play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesia, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitro in cell-based assays, and one such compound, JPC0661, disrupts ΔFOSB binding to genomic DNA in vivo in the mouse brain with partial efficiency. JPC0661 binds to a groove outside of the DNA-binding cleft of the ΔFOSB/JUND bZIP heterodimer in a cocrystal structure. Here, we generated a …

Robotic Single-Incision Laparoscopic Surgery For The Management Of Endometriosis: First Experience Via The Da Vinci Sp Platform, Qiannan Yang, Daniel Y Lovell, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the feasibility and mid-term outcomes of Robotic single-port single-incision laparoscopic surgery (RSP-SILS) for endometriosis management.

Methods: A retrospective analysis was conducted on 50 adult women with endometriosis who underwent RSP-SILS via the da Vinci SP platform between November 2023 and July 2025.

Results: Median total operative time was 142 min, robot dock time was 3 min, and robot console time was 99 min. Median estimated blood loss was 25 mL. No conversion occurred. Reported mid-term outcomes included 1 case each of pelvic haematoma, Clostridioides difficile colitis, and umbilical surgical site infection, as well as 3 cases of …

Aht Diagnoses: The Influences Of Clinical Presentation And Evidence Of Impact, Ruairi Smith-Dewey, Angela Bachim, Colleen Bressler, Kristine Campbell, Lori Frasier, Christopher Greeley, Danielle Horton, Nicole Johnson, Jan Leonard, Megan M Letson, Caitlin Mcnamara, Ashley Sherman, Shalon Nienow, Stuart Sommers, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Background: The frequency of abusive head trauma (AHT) diagnoses by child abuse pediatricians (CAPs), especially regarding external evidence of head impact, has been questioned.

Objectives: To compare CAP diagnoses in subjects with subdural hemorrhage (SDH) across clinical presentations, including subgroups with and without external evidence of head impact. Additionally, we aimed to describe subjects with SDH and concomitant suspicious injuries (CSI) without evidence of head impact.

Participants and setting: Multicenter retrospective study including subjects < 24 months old with SDH.

Methods: Subjects were divided into groups based on clinical presentations: Ill SDH only, Non-ill SDH only, and SDH + CSI. Groups were subcategorized based on presence/absence …

Yield Of Injury Testing For Contacts Of Children Evaluated For Physical Abuse, Lígia Batista, Joanne N Wood, Tagrid M Ruiz-Maldonado, M Katherine Henry, Jan Leonard, Angela Bachim, James D Anderst, Farah W Brink, Hannah B Sahud, Lori D Frasier, Nancy S Harper, Natalie Laub, Colleen J Bressler, Daniel M Lindberg

Faculty, Staff and Students Publications

Background: Siblings and household contacts of physically abused children are at increased risk for physical abuse and may have injuries that are not clinically apparent. However, injury testing recommendations for contact children remain debated.

Objective: Our objective was to describe testing practices and yield for contacts of physically abused children.

Participants and settings: This is a cross-sectional study of children < 10 years old evaluated for physical abuse at 10 US pediatric referral centers in the CAPNET research network.

Methods: We report the proportion of contact children who had a skeletal survey (SS) or neuroimaging and describe the proportion of tests that identified injuries.

Results: Among 6256 index evaluations, 4863 contacts were identified. Among 794 contacts with physical examinations, …

Trauma-Related Compulsions In Obsessive-Compulsive Disorder: Functional Insights From Factor Analysis, Caitlin M Pinciotti, Max Thorsson, Gregor Horvath, Matti Cervin

Faculty, Staff and Students Publications

Resisting obsessive-compulsive disorder (OCD) compulsions is a key predictor of exposure and response prevention (ERP) effectiveness, yet trauma-exposed individuals with OCD endorse more severe compulsions and are more likely to be labelled 'treatment resistant.' Among trauma-exposed individuals, compulsions are theorised to function to prevent future trauma and cope with trauma-related responses. Recent findings suggest that certain compulsions in the context of trauma exposure differentially impact treatment outcomes, yet missing from extant literature is a larger empirically derived conceptualisation for how trauma may impact the underlying function of compulsions. In a sample of 662 adult patients enroled in intensive OCD treatment …

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

Developing A Novel Index For Neighborhood Social Determinants Of Cardiovascular Diseases In The Cardia Study, Tao Gao, Yinan Zheng, Brian T Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Penny Gordon-Larsen, Chunyu Liu, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

2020-Current year OA Pubs

Neighborhood social determinants of health have been shown to influence cardiovascular risk and the development of cardiovascular disease, but few studies have been done about early-life exposure as well as the combined effect of multiple neighborhood social determinants of health measures. Each 1-standard-deviation increase in the neighborhood social determinants of health index is associated with increased risk of coronary artery calcification at the year 7, year 15, and year 20 visits (Odds Ratios range from 1.15 to 1.17). The area under the Receiver Operating Characteristics curve ranges between 0.718 (year 7) and 0.719 (year 20). Compared to White participants, Black …

A Pathogenic Tau Mutation Drives Autophagy-Lysosome Dysfunction That Limits Tau Degradation In A Model Of Frontotemporal Dementia, Farzaneh S Mirfakhar, Jacob A Marsh, Chihiro Sato, Kylie J Schache, Miguel A Minaya, Roland E Dolle, Stephen C Pak, Gary A Silverman, David H Perlmutter, Shannon L Macauley, Celeste M Karch

2020-Current year OA Pubs

Tau accumulates in a group of neurodegenerative diseases known as tauopathies. A prevailing hypothesis has been that Tau degradation is impaired due to an age-related imbalance in the autophagy-lysosome pathway, but whether these defects are a cause or consequence of Tau accumulation remains unclear. Here we show that a disease-causing mutation in the MAPT gene, which encodes Tau, p.R406W, is sufficient to disrupt multiple steps of the autophagy-lysosome pathway in human neurons. Using Airyscan super-resolution imaging, we find that mutant Tau neurons accumulate Tau and phosphorylated Tau in dysfunctional lysosomes, exhibit reduced lysosome motility, impaired fusion of autophagosomes and lysosomes, …

Post-Hemorrhagic Hydrocephalus Of Prematurity Is Associated With Disruption Of Tight Junctions And Increased Macrophage Activity In The Choroid Plexus, Maria Garcia-Bonilla, Rajiv Swarup, Owen W Limbrick, Habeebah Z Vohra, Ayodamola Otun, Konrad Mckalip, William Bernhardt, Kirill Shumilov, Marie Michenkova, Jayne Crouthamel, Mackenzie Newman, Krikor Dikranian, James P Mcallister Ii, David D Limbrick

2020-Current year OA Pubs

BACKGROUND: Previous studies on intraventricular hemorrhage (IVH), a common and severe complication of preterm birth, and subsequent post-hemorrhagic hydrocephalus (PHH), have predominantly concentrated on the secretory function of the choroid plexus (ChP), with considerably less emphasis on its barrier function. We hypothesized that PHH is associated with immune-related alterations in the junction biology of ChP. METHODS: We examined differences in tight junctions and macrophages using a neonatal mouse model of PHH (n = 40) and in vitro ChP explants (n = 22), as well as human post-mortem samples (n = 6). To test our hypothesis, we employed histology, immunofluorescence, magnetic …

Provider And Caregiver Perspectives On Vision Services For Childhood Cancer Survivors: A Qualitative Study, Asha Parvathaneni, Luke Zabotka, Jacob Strelnikov, Allison J L'Hotta, Matthew J Ehrhardt, Maria Montoya, Kyathi Thallapureddy, Robert J Hayashi, Margaret Reynolds, Sara Malone

2020-Current year OA Pubs

PURPOSE: This study qualitatively explored barriers and facilitators to accessing supportive vision services for childhood cancer survivors with vision deficits and identified current service-delivery contexts from the perspectives of community professionals and caregivers. METHODS: Participants included caregivers and professionals who completed semi-structured interviews. Provider questions focused on patient identification and assessment, follow-up protocols, and available resources, while caregiver questions addressed navigating survivorship care, academic needs, and goals for their children. Transcripts were thematically analyzed following inductive and deductive coding. RESULTS: Six caregivers and 10 professionals completed interviews. Thematic analysis resulted in three contexts for barriers and facilitators: school settings, community …

Free Versus In Situ Right Internal Mammary Artery As A Conduit In Coronary Artery Bypass Surgery: A Meta-Analysis, Yuta Kikuchi, Tomoki Sakata, Tomonari Shimoda, Shinichi Fukuhara, Junichi Shimamura, Makoto Hibino, Tsuyoshi Kaneko, Hiroo Takayama, Hisato Takagi, Michel Pompeu Sa, Toshiki Kuno

Department of Medicine Faculty Papers

OBJECTIVES: There is debate regarding the optimal choice for a second conduit in coronary artery bypass grafting. The right internal mammary artery (RIMA) is commonly employed as a second conduit; however, it is unclear whether the free (fRIMA) or in situ (isRIMA) configuration yields superior outcomes. We performed a systematic review and meta-analysis to compare clinical outcomes between fRIMA and isRIMA as the second conduit.

METHODS: A comprehensive search of PubMed (MEDLINE), EMBASE, and CENTRAL was performed through May 2025 to identify studies comparing outcomes in patients undergoing coronary artery bypass grafting with either fRIMA or isRIMA as a second …

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …

Pathogenic Variants In The Cohesin Loader Subunit Mau2 Underlie A Distinct Cornelia De Lange Syndrome Subtype., Ilaria Parenti, Alina Hesters, Marta Gil-Salvador, Laura Duffy, Deniz Kanber, Jasmin Beygo, Jennifer Kerkhof, Laura Steenpaß, Elsa Leitão, Julia Woestefeld, Philip M. Boone, Emeline M. Kao, Lama Alabdi, Hesham M. Aldhalaan, Fowzan S. Alkuraya, Muneera J. Alshammari, Stylianos E. Antonarakis, Donald Basel, Kevin Cassinari, Laurana De Polli Cellin, Amanda R. Clause, Alexander Augusto De Lima Jorge, Andréa De Castro Leal, Stephan C. Collins, Benjamin Durand, Juliane Eckhold, Mais O. Hashem, Parul Jayakar, Arif O. Khan, Kohji Kato, Regina Kubica, Gholson J. Lyon, Elaine Marchi, Julie Mccarrier, Lara K. Kimmig, Seiji Mizuno, Gael Nicolas, Yosuke Nishio, Tomoo Ogi, Juan Pié, Jordyn Prell, Beatriz Puisac, Feliciano J. Ramos, Emmanuelle Ranza, Claire Redin, Eric T. Rush, Shinji Saitoh, Hanan E. Shamseldin, Susan Starling, Esteban Astiazaran-Symonds, Sara H. Eltahir, Alma Kuechler, Bekim Sadikovic, Binnaz Yalcin, Kerstin S. Wendt, Frank J. Kaiser

Manuscripts, Articles, Book Chapters and Other Papers

The role of the cohesin complex depends on the cohesin loader proteins NIPBL and MAU2. While NIPBL variants are a major cause of Cornelia de Lange Syndrome (CdLS), the role of MAU2 in disease is unclear. We describe 18 individuals carrying 15 heterozygous MAU2 variants and demonstrate pathogenicity through functional analyses. In-frame MAU2 variants predominantly impair NIPBL-MAU2 interaction, whereas truncating variants cause MAU2 haploinsufficiency and lead to NIPBL reduction. Most individuals exhibit a DNA methylation profile compatible with the CdLS episignature. We also describe two MAU2-specific episignatures that reflect variant-dependent molecular consequences. Affected individuals display a wide range of phenotypes, …

Physical Rehabilitation For Older Patients With Acute Hfpef (Rehab-Hfpef) Trial: Design And Rationale, Amy M. Pastva, Gordon R. Reeves, David J. Whellan, Robert J. Mentz, Haiying Chen, Alain G. Bertoni, Pamela W. Duncan, Mark A. Espeland, Shelby D. Reed, M. Benjamin Nelson, Christopher M. O'Connor, Dalane W. Kitzman

Department of Medicine Faculty Papers

RATIONALE: Older patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF) experience persistently poor outcomes, including physical disability, cognitive impairment, depression, impaired health-related quality of life (HRQOL), rehospitalizations, loss of independence, and mortality. In our previous phase 2 REHAB-HF trial, an innovative physical rehabilitation intervention, delivered across three phases-inpatient, 12-week outpatient, and 3-month home-based maintenance-produced large improvements in physical function and HRQOL, with signals of reduced clinical events among patients with acute HFpEF. These findings provide a compelling rationale for a definitive, event-powered trial to evaluate clinical outcomes.

HYPOTHESIS: Targeting physical frailty and multisystem functional impairments using …

Cilia Dynamics In Primary Ciliary Dyskinesia: A Biophysical Characterization Of The Rsph4a Founder Variant, Gabriel Rosario-Ortiz, José Muñiz-Hernández, Natalia M Ortiz-Pérez, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is a rare ciliopathy resulting in chronic oto-sino-pulmonary disease. PCD diagnosis can be achieved by a combination of different diagnostic and adjuvant tools, including high-speed video-microscopy analysis (HSVA). A founder variant has been described in Puerto Rico as the most common cause of PCD in the island. Background/Objectives: In HSVA, objective parameters such as ciliary beat frequency (CBF) and subjective parameters such as ciliary beat pattern (CBP) shed light on the biophysical properties of cilia. However, the subjective nature of CBP creates a gap in knowledge; characteristics such as the length, angle, and bending index of …

From Fair To Cure: Guidelines For Computational Models Of Biological Systems, Herbert M. Sauro, Eran Agmon, Michael L. Blinov, John H. Gennari, Joseph L. Hellerstein, Adel Heydarabadipour, Bartholomew E. Jardine, Elebeoba May, David P. Nickerson, Lucian P. Smith, Gary D. Bader, Frank T. Bergmann, Patrick M. Boyle, Andreas Dräger, James R. Faeder, Song Feng, Juliana Freire, Fabian Fröhlich, James A. Glazier, Thomas E. Gorochowski, Tomas Helikar, Henning Hermjakob, Stefan Hoops, Peter Hunter, Princess I. Imoukhuede, Sarah M. Keating, Matthias König, Reinhard Laubenbacher, Leslie M. Loew, Carlos F. Lopez, William W. Lytton, Rahuman S. Malik-Sheriff, Andrew Mcculloch, Pedro Mendes, Lealem Mulugeta, Chris J. Myers, Jerry G. Myers, Anna Niarakis, David D. Van Niekerk, Brett G. Olivier, Alexander A. Patrie, Ellen M. Quardokus, Nicole Radde, Johann M. Rohwer, Sven Sahle, James C. Schaff, Falk Schreiber, T. J. Sego, Janis Shin, Jacky L. Snoep, Rajanikanth Vadigepalli, H. Steven Wiley, Dagmar Waltemath, Ion I. Moraru

Computational Medicine Center Faculty Papers

Guidelines for managing scientific data have been established under the FAIR principles, requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model …

Associations Between Caregiver-Provider Communication Quality And Unmet Care Needs Among Older Adults, Jiaming Liang, Rafael Samper-Ternent, Brian Downer, Zhigang Xie

Faculty, Staff and Student Publications

BACKGROUND: Unmet care needs (lack of assistance with daily activities) among older adults are common and linked to adverse health outcomes, greater healthcare utilization, and caregiver burden. While effective patient-provider communication is known to improve care quality, less is understood about the role of caregiver-provider communication, particularly across sociodemographic, health, and caregiving contexts. METHODS: We conducted a cross-sectional secondary analysis of pooled 2021–2023 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) data, restricted to community-dwelling older adults (65 + years) who received assistance from caregivers due to difficulty with daily activities, and had at least …

Social Isolation And Firearm Secure Storage In The Usa: Results From The 2022 Brfss, Alexander Testa, Daniel Semenza, Dylan B Jackson, Karyn Fu, Sandra Mckay, Kyle T Ganson, Jason M Nagata, Jack Tsai

Faculty, Staff and Student Publications

Background: Firearm secure storage (ie, storing firearms unloaded and locked) is recommended to reduce unintentional injuries and suicides. However, the relationship between psychological states, such as social isolation, and firearm secure storage practices is under-researched.

Methods: Data are from 7136 individuals with firearms in their households from the 2022 Behavioral Risk Factor Surveillance System. Multinomial logistic regression was used to explore the relationship between social isolation and firearm storage.

Results: Among respondents, 71.6% reported storing firearms unloaded, 14.2% stored firearms loaded and locked and 14.2% stored firearms loaded and unlocked. Most respondents reported feeling 'never' (40.7%) or 'rarely' (33.3%) socially …

Impact Of Who Aware Antibiotic Handbook Training On Antibiotics Prescribing Knowledge Among Private Primary Care Providers: A Vignette-Based, Prep-Post Pilot Study In Patna, India, Poshan Thapa, Prachi Shukla, Chandrashekhar Joshi, Sena Sayood, Pradeep Kumar Sinha, Diwash Timilsina, Mili Dutta, Madhukar Pai, Samira Abbasgholizadeh Rahimi, Sumanth Gandra

2020-Current year OA Pubs

INTRODUCTION: Inappropriate antibiotic prescribing is a major concern in low- and middle-income countries (LMICs), particularly at the primary care level. The WHO AWaRe Antibiotic Handbook was introduced to promote rational antibiotic use, yet its real-world feasibility and potential impact remain underexplored. Our study evaluated the impact and usefulness of the WHO AWaRe Handbook training among private primary care providers (PCPs) in Patna, India.

METHODS: We conducted a pre-post pilot study among 145 private PCPs (40 formal PCPs (FPs) and 105 informal PCPs (IPs) in Patna, India. Participants received training from an infectious disease physician on the WHO AWaRe Antibiotic Handbook. …