Medical Sciences Commons^™

From Relapse To Restoration: Insights Into The Immunopathology Of Bacterial Vaginosis (Bv) In Women Of Reproductive Age, Nhi To, Ms

Student Papers, Posters & Projects

Bacterial vaginosis (BV) has been a subject of study for decades, yet its complex pathogenesis remains poorly understood. BV affects most women of reproductive age, with significant associations to gynecological and obstetric complications. A deeper understanding of the complicated host-microbiota dynamic is crucial for advancing treatment options, as BV continues to pose challenges in effective management. This review aims to explore the current research on vaginal microbiota as well as potential mechanisms of BV-associated bacteria (BVAB) and their interaction with the host immune system, altogether sheds light on the complex interplay within the human reproductive tract. While Lactobacillus-dominant communities support …

Maackia Amurensis Seed Lectin Structure And Sequence Comparison With Other M. Amurensis Lectins, Ashok R. Nayak, Cayla J. Holdcraft, Ariel C. Yin, Rachel E. Nicoletto, Caifeng Zhao, Haiyan Zheng, Dmitry Temiakov, Gary S. Goldberg

Department of Biochemistry and Molecular Biology Faculty Papers

Maackia amurensis lectins, including MASL, MAA, and MAL2, are widely utilized in biochemical and medicinal research. However, the structural and functional differences between these lectins have not been defined. Here, we present a high-resolution cryo-EM structure of MASL revealing that its tetrameric assembly is directed by two intersubunit disulfide bridges. These bridges, formed by C272 residues, are central to the dimer-of-dimers assembly of a MASL tetramer. This cryo-EM structure also identifies residues involved in stabilizing the dimer interface, multiple glycosylation sites, and calcium and manganese atoms in the sugar-binding pockets of MASL. Notably, our analysis reveals that Y250 in the …

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

Dependence Of Mitochondrial Calcium Signalling And Dynamics On The Disaggregase, Clpb, Donato D'Angelo, Víctor H. Sánchez-Vázquez, Benjamín Cartes-Saavedra, Denis Vecellio Reane, Ryan R. Cupo, Hilda Delgado De La Herran, Giorgia Ghirardo, James Shorter, Ron A. Wevers, Saskia B. Wortmann, Fabiana Perocchi, Rosario Rizzuto, Anna Raffaello, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cells utilize protein disaggregases to avoid abnormal protein aggregation that causes many diseases. Among these, caseinolytic peptidase B protein homolog (CLPB) is localized in the mitochondrial intermembrane space and linked to human disease. Upon CLPB loss, MICU1 and MICU2, regulators of the mitochondrial calcium uniporter complex (mtCU), and OPA1, a main mediator of mitochondrial fusion, become insoluble but the functional outcome remains unclear. In this work we demonstrate that CLPB is required to maintain mitochondrial calcium signalling and fusion dynamics. CLPB loss results in altered mtCU composition, interfering with mitochondrial calcium uptake independently of cytosolic calcium and mitochondrial membrane potential. …

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …

Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John

College of Health Professions Faculty Papers

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al., Sci. Rep. 7, 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple …

A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink

Department of Medicine Faculty Papers

Introduction: We present the first published case of turmeric-associated drug-induced liver injury (DILI) accompanied by significant ferritin elevation. Case Presentation: Our patient, a 59-year-old female with DILI caused by long-term ingestion of oral turmeric supplements, presented with painless jaundice on an annual exam. The patient’s liver function tests exhibited a hepatocellular pattern and hyperferritinemia (>2,000 ng/dL). Additional testing was negative except for heterozygosity for the H63D allele associated with hemochromatosis. A liver biopsy indicated acute hepatitis without fibrosis or stainable iron. Conclusion: Upon discontinuation of the supplement, liver enzymes normalized within a month. This case highlights the potential for …

Impact Of Chromatin On Hiv-1 Latency: A Multi-Dimensional Perspective, Joanna E. Jones, Chelsea E. Gunderson, Brian Wigdahl, Michael R. Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that infects multiple immune cell types and integrates into host cell DNA termed provirus. Under antiretroviral control, provirus in cells is able to evade targeting by both host immune surveillance and antiretroviral drug regimens. Additionally, the provirus remains integrated for the life of the cell, and clonal expansion establishes a persistent reservoir. As host cells become quiescent following the acute stage of infection, the provirus also enters a latent state characterized by low levels of transcription and virion production. Proviral latency may last years or even decades, but stimuli such as …

A Randomized Phase Ii/Iii Study Of Paclitaxel/Carboplatin/Metformin Versus Paclitaxel/Carboplatin/Placebo As Initial Therapy For Measurable Stage Iii Or Iva, Stage Ivb, Or Recurrent Endometrial Cancer: An Nrg Oncology/Gog Study, Victoria L. Bae-Jump, Michael W. Sill, Paola A. Gehrig, Jason D. Merker, David L. Corcoran, Adam D. Pfefferle, Michele C. Hayward, Joan L. Walker, Andrea R. Hagemann, Steven E. Waggoner, Roisin E. O'Cearbhaill, Megan E. Mcdonald, Mitchell I. Edelson, Paul A. Disilvestro, Amy L. Mcnally, Aimee Fleury, Ramey D. Littell, Frederick R. Ueland, Heather A. Lankes, Carol Aghajanian

Abington Jefferson Health Papers

INTRODUCTION: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).

METHODS: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary …

Changes In Brain Functional Connectivity Associated With Transcutaneous Auricular Vagus Nerve Stimulation In Healthy Controls, Daniel A. Monti, Nancy Wintering, Faezeh Vedaei, Alicia Steinmetz, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

PURPOSE: A growing number of research studies have explored the potential effects of vagus nerve stimulation (VNS) on brain physiology as well as clinical effects particularly related to stress and anxiety. However, there currently are limited studies showing functional changes during different frequencies of stimulation and laterality effects transcutaneous auricular VNS (TaVNS). In this study, we evaluated whether TaVNS alters functional connectivity in the brain of healthy controls. We hypothesized that TaVNS would significantly alter connectivity in areas involved with emotional processing and regulation including the limbic areas, insula, frontal lobe regions, and cerebellum.

METHODS: We enrolled 50 healthy controls. …

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

The Heterogeneity Of 13q Deletions In Chronic Lymphocytic Leukemia: Diagnostic Challenges And Clinical Implications, Changqing Xia, Guang Liu, Jinglan Liu, Arash Ronaghy, Saber Tadros, Wei Wang, Hong Fang, Shanxiang Zhang, Joseph D. Khoury, Zhenya Tang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, particularly in Western countries. CLL can present indolently or aggressively, influenced by various factors, including chromosomal alterations. Fluorescent in situ hybridization (FISH), targeting specific genes/loci frequently affected in CLL patients, has established a standard for stratifying five CLL prognostic groups: del(11q)/ATM, trisomy 12, del(13q) as a sole aberration, del(17p)/TP53, and normal CLL FISH panel results. Among these, del(13q) as a sole aberration is associated with a favorable prognosis, while the others are considered intermediate (normal CLL FISH panel result and trisomy 12) or unfavorable (del(11q)/ATM and del(17p)/TP53) prognostic …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Axl Signaling In Cancer: From Molecular Insights To Targeted Therapies, Monika Yadav, Akansha Sharma, Ketki Patne, Saba Tabasum, Jyoti Suryavanshi, Laxminarayan Rawat, Marc Machaalani, Marc Eid, Rana Singh, Toni Choueiri, Soumitro Pal, Akash Sabarwal

Department of Microbiology and Immunology Faculty Papers

AXL, a member of the TAM receptor family, has emerged as a potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays a significant role in various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, and inflammatory responses. Beyond oncology, AXL also facilitates viral infections, including SARS-CoV-2 and Zika highlighting its importance in both cancer and virology. In preclinical models, small-molecule kinase inhibitors targeting AXL have shown promising anti-tumorigenic potential. This review primarily focuses on the induction, regulation and biological functions of AXL …

Multimorbidity And Peak Oxygen Uptake In Patients Undergoing Cardiac Rehabilitation, Pauline F. Gomes, Audry Chacin-Suarez, Sophie A. Miller, Karen M. Fischer, Thomas P. Olson

Einstein Health Papers

No abstract provided.

Notch3 Deletion Regulates Hiv-1 Gene Expression And Systemic Inflammation To Ameliorate Chronic Kidney Disease, Mackenzie Thornton, Nicole Sommer, Mercedes Mcgonigle, Anil Kumar Ram, Sireesha Yerrathota, Henrietta Ehirim, Aakriti Chaturvedi, Johnny Dinh Phan, Anubhav Chakraborty, V. Praveen Chakravarthi, Sumedha Gunewardena, Mudit Tyagi, Jaya Talreja, Tao Wang, Pravin Singhal, Pamela V. Tran, Timothy A. Fields, Patricio E. Ray, Navneet K. Dhillon, Madhulika Sharma

Center for Translational Medicine Faculty Papers

Anti-retroviral therapy (ART) has decreased human immunodeficiency virus (HIV)-1-associated morbidity. However, despite ART, immune cells remain latently infected, leading to chronic inflammation and HIV-1-associated comorbidities. New strategies are needed to target viral proteins and inflammation. We found activation of Notch3 in renal cells of the HIV-1 transgenic mouse model (HIV-Tg26) and in patients with HIV-associated nephropathy. We hypothesized that targeting NOTCH3 activation constitutes an effective therapy for HIV-related chronic kidney disease. We generated HIV-Tg26 mice with Notch3 knocked out (Tg-N3KO). Compared to HIV-Tg26 mice at 3 months, Tg-N3KO mice showed a marked reduction in renal injury, skin lesions and mortality …

Nrf2/Cyclooxygenase 2 Signaling In Cr(Vi)-Induced Carcinogenesis, Lei Zhao, Yi-Fang Wang, Andrea Adamcakova-Dodd, Peter Thorne, Ranakul Islam, Ke Jian Liu, Fei Chen, Jia Luo, Ling-Zhi Liu

Kimmel Cancer Center Faculty Papers

Long-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upre- gulated in Cr(VI)-exposed lung tissues, as well as in the …

Genetic Ancestry Concordant Rna Splicing In Prostate Cancer Involves Oncogenic Genes And Associates With Recurrence, Muthana Al Abo, Wen-Chi Foo, Lauren Howard, Shannon Mcgue, Bonnie Lacroix, Julie Kephart, Angela Clayton, Blair Thornburg, Monika Anand, Michael Rothberg, Shannon Mccall, Jiaoti Huang, Thomas Esther, Judd Moul, Michael Ferrandino, Thomas Polascik, Cary Robertson, Brant Inman, Andrew Armstrong, Yuan Wu, Terry Hyslop, Daniel George, Steven Patierno, Jennifer Freedman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant …

Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and …

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …

Does Body Mass Index Influence Intraoperative Costs And Operative Times For Open Transforaminal Lumbar Interbody Fusion? A Time-Driven Activity-Based Costing Analysis, Danyal A. Quraishi, Advith Sarikonda, Dwight M. Self, Emily Isch, Steven R. Glener, Arbaz A. Momin, Ashmal Sami, Nicholas Clark, Joshua Pelta-Heller, Srinivas Prasad, Ashwini Sharan, Jack Jallo, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan

Department of Neuroscience Faculty Papers

BACKGROUND: The increasing prevalence of obesity has raised concerns about its impact on surgical outcomes and healthcare costs. This study evaluates the influence of Body Mass Index (BMI) on intraoperative costs and operative times during open Transforaminal Lumbar Interbody Fusion (TLIF) procedures using a Time-Driven Activity-Based Costing (TDABC) approach.

METHODS: A retrospective analysis was conducted on 279 patients who underwent TLIF between 2019 and 2022. Patients were categorized into 5 BMI cohorts: healthy weight (BMI 18.5-24.99), overweight (BMI 25.0-29.99), Class I obese (BMI 30.0-34.99), Class II obese (BMI 35.0-39.99), and Class III obese (BMI >40). Intraoperative costs were calculated using …

Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase

Kimmel Cancer Center Faculty Papers

Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and noncoding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived …

Expansion Of Genotypic And Phenotypic Findings In Adamts18-Related Ocular Pathology, Ari August, Rebecca Procopio, Christopher Rapuano, Jose Pulido

Wills Eye Hospital Papers

Purpose: ADAMTS18-related ocular pathology is rare with few described cases. Features include distinctive facies, refractive error, anterior segment dysgenesis, and retinal dystrophy. Previous patients were found to have ho- mozygous variants in ADAMTS18. Here, we present a patient with compound heterozygous ADAMTS18-related pathology and its associated findings. Observations: A 37-year-old male with a history of bilateral congenital nasolacrimal duct obstruction, dry eye syndrome, mild myopia, and accommodative esotropia presented to the Retina Service. He was found to have multiple features of anterior segment dysgenesis and retinal dystrophy, some of which have not been previously reported in association with ADAMTS18 variants. …

Adenosine-Sensitive Upper Septal Fascicular Ventricular Tachycardia Associated With Takotsubo Syndrome, Parker O'Neill, Daniel Underberg, Reginald Ho, Darius Farzad, Gregary Marhefka

Department of Medicine Faculty Papers

We describe a rare case of upper septal fascicular ventricular tachycardia (VT) associated with takotsubo syndrome that failed to convert with synchronized shock but converted to normal sinus rhythm after intravenous adenosine administration. The excess catecholamine state of takotsubo syndrome likely provided substrate for cyclic adenosine monophosphate–mediated triggered activity, causing fascicular VT.

Skeletal And Dental Tissue Mineralization: The Potential Role Of The Endoplasmic Reticulum/Golgi Complex And The Endolysosomal And Autophagic Transport Systems, Irving M. Shapiro, Makarand V. Risbud, Tengteng Tang, William J. Landis

Department of Orthopaedic Surgery Faculty Papers

This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

Pivotal Roles Of Biglycan And Decorin In Regulating Bone Mass, Water Retention, And Bone Toughness, Rui Hua, Yan Han, Qingwen Ni, Roberto J. Fajardo, Renato V. Iozzo, Rafay Ahmed, Jeffry S. Nyman, Xiaodu Wang, Jean X. Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet their distinct roles in bone remain largely elusive. In this study, we utilized single knockout (KO) mouse models and successfully generated double KO (dKO) models despite challenges with low yield. Bgn deficiency, but not Dcn deficiency, decreased trabecular bone mass, with more pronounced bone loss in dKO mice. Low-field nuclear magnetic resonance measurements showed a marked decrease in bound water among all KO groups, especially in Bgn KO and dKO …

Clinical Significance Of "S" Isoform Of Dclk1 In Different Gastric Cancer Subtypes Using Newly Produced Monoclonal Antibody, Mahdieh Razmi, Ali-Ahmad Bayat, Nafiseh Mortazavi, Elham Kalantari, Leili Saeednejad Zanjani, Sima Saki, Roya Ghods, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Materials and methods