Digital Commons Network^™

Characterization Of Mettl3/14-Mediated M6a Modification In Human Transcriptome Using Nanopore Direct Rna Sequencing, Emily Kurtyan, Andrew J. Stein, Kelly J. Abdalla, Zhangerjiao Yuan, Miten Jain, Fadia Ibrahim

Department of Biochemistry and Molecular Biology Faculty Papers

Post-transcriptional RNA modifications modulate diverse aspects of RNA metabolism. N6-methyladenosine (m6A), one of the most abundant internal RNA modifications, is deposited by the core methyltransferase complex, METTL3 and METTL14. Oxford Nanopore Technologies (ONT) platform permits direct, single RNA molecule sequencing while preserving native modifications. However, without rigorous benchmarking, the accuracy and reproducibility of modification detection remain uncertain. Here, we leveraged ONT to comprehensively profile bona fide m6A modifications in cellular RNAs at single-nucleotide resolution by integrating two direct RNA sequencing chemistries (RNA002 and RNA004) with the m6Anet and Dorado modification-detection models. We independently depleted METTL3 and METTL14 in human cells …

Towards Human-Centered Digital Health Interventions, Kristin M Kostick-Quenet, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

This article discusses the potential of digital health interventions (DHIs) in mental health care, emphasizing the importance of designing them to foster genuine humanistic care. It highlights current challenges in measuring engagement and outcomes, advocating for integrating human-centered endpoints such as dignity, autonomy, and therapeutic alliance into evaluation frameworks. The authors call for mechanistic research to identify effective engagement strategies and context-specific implementation approaches. Ultimately, successful DHIs should demonstrate both clinical efficacy and the preservation of humane, person-centered care, ensuring ethical and meaningful mental health support through technology.

Nf1 Loss In Estrogen Receptor-Positive Breast Cancer Induces Osteoclast Formation And Immunosuppression To Promote Bone Metastasis, Zifan Zhao, Ze-Yi Zheng, Jonathan T Lei, Matthew J Baik, Yi-Hsuan Wu, Lauren K Somes, Andres F Mosquera Paternina, Omar A Harb, Owen A Chang, Fengshuo Liu, Matthew V Holt, Junkai Wang, Igor Bado, Hai Wang, George Miles, Zbigniew Gugala, Meenakshi Anurag, Ahmed Elkhanany, Yi Li, Valentina Hoyos, Xiang H-F Zhang, Eric C Chang

Faculty, Staff and Students Publications

Estrogen receptor-positive (ER+) breast cancer exhibits a marked propensity for skeletal metastasis; however, the molecular drivers of bone colonization remain incompletely defined. We investigated the tumor suppressor neurofibromin (NF1), a dual repressor for RAS and ER signaling, whose inactivation promotes endocrine therapy (ET) resistance and is associated with inferior relapse-free survival. NF1 copy number loss was detected in 62% of ER+ patients who subsequently developed metastases and was associated with an increased likelihood of bone metastases at initial diagnosis. In mouse xenograft models, NF1-depleted ER+ breast cancer cells demonstrated enhanced dissemination to skeletal sites following surgical resection of primary tumors. …

Cerebellar Atrophy In Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study, Rebecca Macrae, Kierstin Hederstedt, Christopher Cortina, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman

Faculty, Staff and Students Publications

Background and objectives: Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.

Methods: This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.

Results: Of participants with follow-up imaging, cerebellar atrophy …

Genomic Analysis Of Oesophageal Carcinoma (Ec) Identifies Recurrent Mutations In Histone Methyltransferases As A Distinctive Subset, Jingyuan Wang, Moh'd Khushman, Et Al.

2020-Current year OA Pubs

Histone-lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility. We aimed to identify the molecular profile of KMT2-MT oesophageal cancer (EC) and associations with patient outcomes. In our study, KMT2 mutations were significantly associated with longer immunotherapy-related overall survival (OS) in the esophageal adenocarcinoma (EA) (21.42 vs 13.42 months, HR = 0.66, 95% CI: 0.50-0.88, P = 0.004), but not in the esophageal squamous cell carcinoma (ESCC). KMT2 mutations were significantly associated with microsatellite instability-high and …

Abundance And Balance Of Circulating Leukocyte Subsets And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Catherine M Bulka, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Mingxiang Teng, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Cancer immunology research has traditionally focused on tumor-infiltrating leukocytes, but the role of the peripheral leukocytes remains understudied. Since tumor-infiltrating leukocytes are recruited from the blood, circulating immune profiles may provide prognostic insights obtainable before surgery, reflecting overall immune competence.

METHODS: We analyzed treatment-naïve blood samples from 134 stage I-III colorectal cancer (CRC) patients using a nested case-control design (33 recurrences, 45 deaths; median follow-up: 7.4 years). Circulating leukocyte subsets were estimated using methylation cytometry applied to genome-wide methylation profiles. Cox regression models estimated associations between leukocyte metrics and disease-free and overall survival, adjusting for clinical factors.

RESULTS: Higher …

Cracking The Code: Genotype-Phenotype Correlation Models In Sarcoglycanopathies, Leonela Luce, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sarcoglycanopathies are among the most severe limb-girdle muscular dystrophies (LGMD), though milder presentations have been described. These diseases are primarily caused by missense variants, but the limited predictability of their effect on protein maturation, complex formation, and transport has hindered reliable genotype-phenotype correlations. This study aimed to establish accurate genotype-phenotype correlations for LGMDR3, LGMDR4, and LGMDR5.

METHODS: We analyzed the largest sarcoglycanopathy cohort to date (n = 541). Clinical data, including age at symptom onset and loss of ambulation, were collected and used to define phenotype severity. Predictive models were developed considering the impact of non-truncating variants on secondary …

Opioid Dispensing Volume And Per-Patient Intensity In Sickle Cell Disease, Kevin Y Xu, Brandon K Attell, Joanna L Buss, Tashalee R Brown, Charles R Jonassaint, Richard A Grucza, Allison A King, Max Jordan Nguemeni Tiako

2020-Current year OA Pubs

IMPORTANCE: Opioids remain central to management of acute and chronic pain in sickle cell disease (SCD). Opioid dispensing declined over the 2010s amid opioid stewardship efforts, but patterns since 2020 are less clear. Analyses aggregating opioids into morphine milligram equivalents (MME) may obscure agent-specific patterns.

OBJECTIVE: To characterize opioid dispensing volume and per-recipient frequency, duration, and dose among individuals with SCD.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of commercially insured and Medicaid-enrolled patients with SCD using the Merative MarketScan databases across 3 periods from January 2011 to February 2016, March 2016 to December 2020, and January 2021 to …

Spinal Cord Imaging For Multiple Sclerosis: Advances, Priorities, And Opportunities, Cornelia Laule, Matthew R Brier, Et Al.

2020-Current year OA Pubs

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of …

Energy Conservation In Mri: Sequence Selection And Operational Strategies, Nathan Scherer, Felicia Wang, Andrew L Chang, Mariam Malik, Anna Schroeder, Heather Craig, Benjamin E Northrup

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: The healthcare system accounts for approximately 9.8% of the United States' (U.S.) greenhouse gas emissions, much of which is due to imaging, particularly magnetic resonance imaging (MRI). This study investigates the components of MRI energy consumption and compares sequences that may be interchangeable in clinical practice. Although the greatest potential for decreasing energy expenditure lies in reduction of inappropriate imaging and optimizing energy consumption of idle MRI equipment, sequence substitution offers an underexplored solution that can potentially be implemented without changing practice patterns or capital expenditure.

MATERIALS AND METHODS: MRI energy expenditure of one machine was monitored …

Implementation Of A New Mri Contrast Policy At A Large Hospital System: Access To Contrast-Enhanced Mri And Development Of Nsf In Patients With Renal Insufficiency, Daniel R Ludwig, Fan Zhang, Brittany Minor, Tammie L S Benzinger, Anup S Shetty

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: To evaluate access to contrast-enhanced MRI among patients with acute or chronic renal failure after implementation of a more permissive contrast policy and determine whether any patients developed nephrogenic systemic fibrosis (NSF).

MATERIALS AND METHODS: This retrospective study included all patients who had an order for contrast-enhanced MRI in our healthcare system between July 1st, 2023 and June 30th, 2025. Each exam was categorized as completed or cancelled, and multivariable analysis was performed to identify factors associated with exam cancellation. Potential diagnoses of NSF were identified by searching the problem list and encounter diagnoses using ICD-10 codes. …

Perioperative Depression And Anxiety Care In Older Patients: A Randomized Clinical Trial, Joanna Abraham, Katherine J Holzer, Simon Haroutounian, Bethany Pennington, Ana Baumann, Ryan Calfee, Theresa Cordner, Kenneth E Freedland, Thomas Kannampallil, Benjamin Kozower, Emily Lenard, J Philip Miller, Mary Politi, Michael Yingling, Michael S Avidan, Eric J Lenze

2020-Current year OA Pubs

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking.

OBJECTIVE: To evaluate a perioperative intervention to optimize mental health.

DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety …

Comparison Of Safety And Efficacy Of Lower-Intensity Versus Standard Unfractionated Heparin Infusion Nomograms For Extracranial Venous Thromboembolism In The Neurological Intensive Care Unit, Abdullah M Hakoun, Megha Gupta, Rajat Dhar, Mahta Mardani, Fatih Koc, Salah G Keyrouz

2020-Current year OA Pubs

BACKGROUND: Anticoagulation for acute venous thromboembolism (VTE) in the neurological intensive care unit is challenging because patients with acute brain injury or recent neurosurgery are at high risk for hemorrhagic complications. Unfractionated heparin infusions are commonly used, sometimes with lower activated partial thromboplastin time targets, but the safety and effectiveness of lower-intensity UFH nomograms remain poorly defined.

METHODS: We performed a retrospective single-center study of patients diagnosed with acute extracranial VTE, including deep venous thrombosis and/or pulmonary embolism, between June 2018 and April 2024. Patients were grouped by treatment strategy: standard-intensity UFH targeting aPTT 60-100 s, lower-intensity UFH targeting aPTT …

Pediatric Hypertension Prevalence With 1 Vs. 2 Vs. 3 Within-Visit Blood Pressure Readings (Nhanes 2013-2020), Sandeep K Riar, Donald L Batisky, Scott Gillespie, Andrew M South

2020-Current year OA Pubs

To compare hypertension prevalence using 'initial' blood pressure (BP), 'subsequent' BP (averaged second and third readings) and 'total' BP (averaged three readings), we included 8-17-year-old youth with three BP readings from NHANES 2013-2020. From 2013-2016, BP was obtained using auscultation (manual protocol, MP) and subsequently, using oscillometry (automated protocol, AP). We excluded subjects with 'zero' diastolic blood pressure (DBP). In 5656 subjects, clinical hypertension (high systolic blood pressure [SBP] and/or DBP) prevalence was highest with 'initial' BP (350/5 642, 6.2% [95% CI 5.6-6.9%]), lower with 'subsequent' BP (289/5 642, 5.1% [4.6-5.7%], p <  0.001), and lowest with 'total' BP (251/5 642, 4.4% [3.9-5.0%], p <  0.001). Both MP and AP groups maintained this trend with a significantly lower hypertension prevalence with 'total' vs. 'subsequent' BP. An exception to the trend occurred in the AP group for three conditions: diastolic hypertension, hypertension in high BMI and Hispanic subjects. Diastolic hypertension prevalence with 'subsequent' DBP (86/2 285, 3.8% [3.1-4.6%]) exceeded that with 'initial' DBP (83/2 285, 3.6% [2.9-4.5%]) and was lowest with 'total' DBP (59/2 285, 2.6% [2.0-3.3%]). Diastolic hypertension prevalence was higher (126/5 642, 2.2% [1.9 - 2.7%]) with the 2016 European guidelines (same as 'subsequent' DBP) than with 'total' DBP (94/5 642, 1.7% [1.4 - 2.0%]). Our findings support the inclusion of the first BP reading in BP categorization, as 'total BP' leads to lower hypertension classification than 'subsequent' BP.

Irs: Iterative Reference Selection Improves Normalization Of Microbiome Sequencing Data, Yiming Shi, Lili Liu, Jun Chen, Kristine M Wylie, Todd N Wylie, Sung Hee Park, Ruiwen Zhou, Yin Cao, Stephanie A Fritz, Molly J Stout, Maria Cristina Vazquez Guillamet, Lei Liu

2020-Current year OA Pubs

Microbiome studies often seek to determine how the absolute abundances of individual taxa change across biological conditions, yet sequencing read counts are sample-specific scaled representations of those abundances. Because sampling depth can differ across samples, fold changes calculated directly from sequencing read counts do not generally represent absolute-abundance fold changes. Normalization methods attempt to account for these between-sample differences in sampling depth, but their accuracy depends on the reference used. In particular, total-sum scaling uses all taxa as the reference and can introduce compositional bias. Reference-based methods instead rely on taxa that are stable across conditions, but contamination of the …

Unlocking Cis-Regulatory Landscapes Across 500 Million Years Of Evolution And Disease Mechanisms, Tássia Mangetti Gonçalves, Casey L Stewart, Samantha D Baxley, Jason Xu, Kevin Boyer, Bijesh George, Daofeng Li, Chengran Yang, Harrison W Gabel, Xianhua Piao, Carlos Cruchaga, Yang E Li, Ting Wang, Oshri Avraham, Guoyan Zhao

2020-Current year OA Pubs

Genomic DNA encodes regulatory information that determines where, when, and to what extent genes are expressed. Theoretically, we should be able to identify these transcriptional "instructions" by examining genomic DNA sequence alone, yet this has remained challenging. Here we present the Vertebrate Regulatory MOdule Detector (VRMOD), a method that accurately predicts gene regulatory sequences using only the query genomic sequences. We applied VRMOD to 309 Ensembl genomes, generating a compendium of high-resolution, genome-position-fixed

Responding To Medetomidine In Philadelphia: Narrative Summary Of The Public Health Response To A New Psychoactive Substance, Tareva Warrick-Stone, Serge-Emile Simpson, Phil Durney, Dennis Goodstein, Catherine Abrams, Raymond Bobb, Kory London, Daniel Teixeira Da Silva

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Despite the emergence of medetomidine as the dominant adulterant in Philadelphia's illicit opioid supply, coordinated public health responses are limited or non-existent in the literature. Thus, we summarize a recent Summit in Philadelphia of outpatient and inpatient service providers who specialize in the care of persons who use drugs to discuss medetomidine response readiness and building ongoing community readiness for potential destabilizing drug supply changes.

PURPOSE: Describe a public health intervention that distributed information about practices across health care settings and mobilized key informants to identify and address barriers to treatment.

METHODS: Descriptive summary of the in-person Summit organized …

Gamclust: Identification Of Regulated Metabolic Modules In Bulk, Single Cell And Spatial Gene Expression Data, Anastasiia Gainullina, Evgeniia Chikina, Maxim N Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

MOTIVATION: Metabolism operates as a highly interconnected biochemical network, and its regulation emerges from coordinated changes across many reactions and metabolites. The integration of gene expression profiling data with organism-scale metabolic networks has proven to be a valuable tool for understanding cellular metabolic regulation. However, the increasing complexity of profiling technologies and experimental designs requires the development of specialized tools.

RESULTS: Here, we present GAMclust, an R package implementing and extending the previously published GAM-clustering pipeline for identifying transcriptionally regulated metabolic modules in complex gene expression datasets. GAMclust supports bulk, single-cell, and spatial gene expression profiling. It includes built-in KEGG …

Heritable Transgenic Schistosomes As A Living Platform For Sars-Cov-2 Neutralizing Antibody Secretion, Wannaporn Ittiprasert, Bruce A Rosa, Sergej Djuranovic, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH-IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring …

Allograft Tendon Pretensioning Technique Guide., Joseph R Brown, Robert W Mendicino

Surgery Articles

In foot and ankle surgery, allograft tendons are frequently used in both primary and revision cases to enhance stability and function. However, postoperative complications, such as creep, can compromise the intended correction and stability over time. This paper presents a practical guide on pretensioning techniques prior to implantation, aiming to reduce creep and improve long-term outcomes. Using two common allograft specimens, we demonstrate pretensioning methods with specific focus on tendon stitching, techniques for securing the allograft to the graft board, optimal tensioning and time parameters. We recommend pretensioning at 80 N for approximately 30 min to effectively decrease creep and …

Valvular Heart Failure Is A Distinct Heart Transplant Phenotype With Comparable Adjusted Survival To Other Heart Failure Etiologies, Devon Kelley, Varun Kathawate, Joyce Ho, Andrew Belec, Takahiro Tashima, Kazuhiro Ueno, Jessica Dominic, Pavan Atluri

Division of Cardiology Faculty Papers

PURPOSE: Valvular heart failure (VHF) accounts for 1-5% of heart transplant listings. Comparative outcomes relative to other heart failure etiologies remain poorly characterized. This study defines the VHF phenotype and compares waitlist and transplant outcomes to other heart failure recipients.

METHODS: This retrospective cohort study uses the UNOS thoracic transplant database to analyze adult, first-time, heart-only listings with a diagnosis of heart disease. Patients were grouped by diagnosis as VHF or non-VHF. The primary outcome was waitlist events; post-transplant survival and outcomes were secondary analyses. Subgroup analysis was performed in the post-2018 allocation era.

RESULTS: VHF recipients were older (55.3 …

Donor-Specific Transplant Outcomes From Bmt Ctn 1702: A Multicenter Prospective Biologic Assignment Trial, Asad Bashey, Iskra Pusic, Et Al.

2020-Current year OA Pubs

Newer approaches to control alloreactivity may produce similar transplant outcomes using HLA-mismatched donors vs HLA-matched unrelated donors (MUD). However, prospective comparisons are lacking. BMT CTN 1702 used a donor search prognosis score to assign patients to an 8/8 HLA MUD or the center's preference of haploidentical related donors (HAPLO), mismatched unrelated donors (MMUD), or umbilical cord blood (UCB). Outcomes of MUD were compared to HAPLO, MMUD, and UCB transplantation after adjusting for covariates. Patients (n = 1179 [93% adults]) underwent transplantation with MUD (n = 772), HAPLO (n = 254), MMUD (n = 112), and UCB (n = 41) at …

Machine Learning For Functional Outcome Prediction After Vestibular Schwannoma Surgery: A Systematic Review And Diagnostic Test Accuracy Meta-Analysis, Shiva Nischal, Shaan Patel, Musa China, Kush Kale, Yi Hein Chai, Santosh Guru, William Muirhead, Patrick Grover

Department of Neurosurgery Faculty Papers

PURPOSE: Machine learning (ML) models have been increasingly applied to predict postoperative facial nerve dysfunction and hearing preservation after vestibular schwannoma (VS) surgery. However, reported performance varies substantially, and the overall diagnostic accuracy and clinical reliability of these models remain uncertain. We conducted a systematic review and diagnostic test accuracy meta-analysis to characterise the current state and methodological readiness of ML-based prediction of these outcomes.

METHODS: PubMed, Embase, and CENTRAL were searched from inception to February 2026. Studies evaluating ML-based prediction of facial nerve function or hearing preservation following VS surgery were included. Diagnostic performance metrics were pooled using random-effects …

Redo-Transcatheter Aortic Valve Replacement With Self-Expanding Valves: A U.S. Registry Analysis., Toby Rogers, Vinayak N Bapat, Stanley J Chetcuti, Harold L Dauerman, John K Forrest, Sachin S Goel, Kendra J Grubb, Wah Wah Htun, Rishi Puri, Michael J Reardon, Gilbert H L Tang, Amit N Vora, Steven J Yakubov, Ruth Eisenberg, Guilherme F Attizzani

Heart and Vascular Articles

BACKGROUND: Redo-transcatheter aortic valve replacement (TAVR) for failed transcatheter heart valves is expected to increase, but data on outcomes with self-expanding valves remain limited.

OBJECTIVES: The aims of this study were to evaluate procedural, clinical, and quality-of-life outcomes following redo-TAVR using self-expanding Evolut valves and to compare these outcomes with those among a contemporary native TAVR cohort.

METHODS: Outcomes after redo-TAVR with Evolut R, Evolut PRO, and Evolut PRO+ valves in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry were analyzed and compared with outcomes after native-valve TAVR using the same valve platform during the …

Compbio And Miras-A Multi-Omic Analysis Platform Built On A Memory-Based Intelligence Engine, Ruteja A Barve, Chad E Storer, Wayne D Hoxsie, Curtis Marcum, Joshua F Mcmichael, Jared M Lalmansingh, Brittany K Smith, Mark R Johnson, Daniel J Kuster, Richard D Head

2020-Current year OA Pubs

As molecular and cellular technologies have advanced, the need to analyze and interpret the resulting vast and multi-modal data into actionable intelligence has become a rate-limiting factor in scientific advancement. While traditional knowledgebase-pathway tools and LLM-based AI tools provide a degree of support in data interpretation, both exhibit known limitations. Presented here is the CompBio multi-omic analysis platform built upon Memory-based Intelligent Reasoning System (MIRaS), an associative reasoning engine grounded in episodic and semantic memory, capable of inferring biological relationships directly from stored knowledge rather than from model training. The MIRaS system is not dependent on human-curated pathway knowledgebases, provides …

Predictors Of Adalimumab Durability In Hidradenitis Suppurativa: A Multicenter Cohort Study, Albert T. Young, Arashleen Pannu, Alexander Velaoras, Roland Leyson, Rayad B. Shams, Alexandra Turfe, Andrea Dai, Mohsen Mokhtari, Sarah Bassett, Joshua Vazhappilly, Richard W. Hass, Iltefat Hamzavi, Christopher J. Sayed, Qing-Sheng Mi, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Adalimumab is widely used for hidradenitis suppurativa (HS), but treatment durability varies and predictors of sustained benefit remain uncertain.

OBJECTIVE: To identify clinical and laboratory factors associated with adalimumab treatment durability in HS.

METHODS: We retrospectively studied 135 adults with HS who initiated adalimumab as first biologic therapy across three academic centers from 2013 to 2023. Outcomes were categorized as primary failure (12-24 weeks), secondary failure (24 weeks-2 years), or sustained response (>2 years) based on discontinuation for inefficacy. Predictors of treatment durability were evaluated using ordinal logistic regression.

RESULTS: In univariable analyses, Hurley stage 3, higher body …

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

Implementation Readiness For National Cancer Survivorship Care Standards, Christiane J. El Khoury, Meera Gupta, Maryem Shirzadi, Heidi Dowst, Martha Mims, Maysa Abu-Khalaf, Hoda Badr

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Cancer survivorship care is a growing public health priority, yet delivery remains variable across health systems. The National Standards for Cancer Survivorship Care provide a framework for high-quality care, but little empirical evidence exists regarding health system readiness to implement these standards in routine practice.

OBJECTIVE: To assess implementation readiness for the National Standards for Cancer Survivorship Care and identify perceived barriers to implementation.

DESIGN, SETTING, AND PARTICIPANTS: This real-time Delphi survey study was conducted from January to March 2025 at a National Cancer Institute-designated comprehensive cancer center. Participants were multidisciplinary experts involved in cancer survivorship care delivery, care …

7th International Workshop On Sox Transcription Factors., Aya Uchida

Faculty Research 2026

Marking the 20th anniversary of a well-established meeting series focused on the biological and clinical importance of SOX genes as regulators of cell fate, the 7th International Workshop on SOX Transcription Factors held from 8-11 September 2025 at the Prince Resort MICE Karuizawa in Nagano, Japan, brought together 83 participants from 17 countries. The meeting showcased the foundations of SOX gene research and recent technological and conceptual breakthroughs across diverse model systems and human research, illustrating the field's evolution and emerging directions for future research. Reflecting the breadth of SOX biology - from early embryonic development and sex determination to …

Integrative Rna-Seq Analysis Reveals Stress Type-Dependent Lncrna-Centered Co-Expression Networks Across Human Cellular Stress Contexts, Christina Anastasiadi, Aggeliki Kasapi, Ioannis Sentementes, Vasileios Gouzouasis, Margaritis Tsifintaris, Antonis Giannakakis

Computational Medicine Center Faculty Papers

Long non-coding RNAs (lncRNAs) are emerging as important regulators of cellular adaptation to environmental and molecular stress, but the extent to which their responses remain reproducible and stress-type-dependent across human stress conditions remains unclear. Here, we performed an integrative transcriptomic meta-analysis of human stress-response datasets from ASTRA and GEO, focusing on normal, non-cancerous, wild-type human cell lines exposed to oxidative stress (H2O2), hypoxia, heat stress, or UV-induced DNA damage. Gene Ontology (GO) enrichment analysis of differentially expressed (DE) protein-coding mRNAs confirmed that the resulting stress-stratified comparison captured biologically coherent transcriptional programmes to oxidative stress signaling, hypoxic and metabolic adaptation, heat-induced …