Medicine and Health Sciences Commons^™

Brain-Derived Neurotrophic Factor In Fibromyalgia: A Systematic Review And Meta-Analysis Of Its Role As A Potential Biomarker, Amir Hossein Behnoush, Amirmohammad Khalaji, Shaghayegh Khanmohammadi, Parsa Alehossein, Behrad Saeedian, Parnian Shobeiri, Antonio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM.

METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant …

Non-Invasive Brain Stimulation For Fatigue In Post-Acute Sequelae Of Sars-Cov-2 (Pasc), Kelly Santana, Eduardo França, João Sato, Ana Silva, Maria Queiroz, Julia De Farias, Danniely Rodrigues, Iara Souza, Vanessa Ribeiro, Egas Caparelli-Dáquer, Antonio L Teixeira, Leigh Charvet, Abhishek Datta, Marom Bikson, Suellen Andrade

Faculty, Staff and Student Publications

BACKGROUND: and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue.

METHODS: Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact …

“It’S Hard To Feel A Part Of Something When You’Ve Never Met People”: Defining “Learning Community” In An Online Era, Lucy Prodgers, Elizabeth Travis, Madeleine Pownall

Faculty, Staff and Student Publications

Feeling part of a community of learners has been shown to foster students' engagement and sense of belonging, leading to higher retention and achievement of learning outcomes. The pivot to online teaching caused by the COVID-19 pandemic has prompted a reappraisal of all aspects of the student experience, including students' capacity and opportunity to engage in meaningful learning communities online. There has been some emergent literature which considers how to facilitate online learning communities in the emergency remote teaching context prompted by COVID-19. However, there is a notable lack of literature which considers how learning communities are defined, understood, and …

Transcriptome-Wide Profiling Of Acute Stress Induced Changes In Ribosome Occupancy Level Using External Standards, Annie W Shieh, Sandeep K Bansal, Zhen Zuo, Sidney H Wang

Faculty, Staff and Student Publications

Acute cellular stress is known to induce a global reduction in mRNA translation through suppression of cap dependent translation. Selective translation in response to acute stress has been shown to play important roles in regulating the stress response. However, accurately profiling translational changes transcriptome-wide in response to acute cellular stress has been challenging. Commonly used data normalization methods operate on the assumption that any systematic shifts are experimental artifacts. Consequently, if applied to profiling acute cellular stress-induced mRNA translation changes, these methods are expected to produce biased estimates. To address this issue, we designed, produced, and evaluated a panel of …

Fgf Signaling In Cranial Suture Development And Related Diseases, Xiaolei Zhao, Shannon Erhardt, Kihan Sung, Jun Wang

Faculty, Staff and Student Publications

Suture mesenchymal stem cells (SMSCs) are a heterogeneous stem cell population with the ability to self-renew and differentiate into multiple cell lineages. The cranial suture provides a niche for SMSCs to maintain suture patency, allowing for cranial bone repair and regeneration. In addition, the cranial suture functions as an intramembranous bone growth site during craniofacial bone development. Defects in suture development have been implicated in various congenital diseases, such as sutural agenesis and craniosynostosis. However, it remains largely unknown how intricate signaling pathways orchestrate suture and SMSC function in craniofacial bone development, homeostasis, repair and diseases. Studies in patients with …

Association Of Immune-Related Adverse Events With The Outcomes Of Immune Checkpoint Inhibitors In Patients With Dmmr/Msi-H Metastatic Colorectal Cancer, Vincenzo Nasca, Francesco Barretta, Francesca Corti, Sara Lonardi, Monica Niger, Maria Elena Elez, Marwan Fakih, Priya Jayachandran, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Chiara Cremolini, Javier Ros, Margherita Ambrosini, Giacomo Mazzoli, Rossana Intini, Michael J Overman, Rosalba Miceli, Filippo Pietrantonio

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

METHODS: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by …

Wnt Signaling In Liver Regeneration, Disease, And Cancer, Gengyi Zou, Jae-Il Park

Faculty, Staff and Student Publications

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. …

Gankyrin-Mediated Interaction Between Cancer Cells And Tumor-Associated Macrophages Facilitates Prostate Cancer Progression And Androgen Deprivation Therapy Resistance, Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yongwei Yu, Yuquan Jiang, Sishun Gan, Xu Gao

Faculty, Staff and Student Publications

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions.

Bayesian Feature Selection For Radiomics Using Reliability Metrics, Katherine Shoemaker, Rachel Ger, Laurence E Court, Hugo Aerts, Marina Vannucci, Christine B Peterson

Faculty, Staff and Student Publications

Introduction: Imaging of tumors is a standard step in diagnosing cancer and making subsequent treatment decisions. The field of radiomics aims to develop imaging based biomarkers using methods rooted in artificial intelligence applied to medical imaging. However, a challenging aspect of developing predictive models for clinical use is that many quantitative features derived from image data exhibit instability or lack of reproducibility across different imaging systems or image-processing pipelines. Methods: To address this challenge, we propose a Bayesian sparse modeling approach for image classification based on radiomic features, where the inclusion of more reliable features is favored via a probit …

Characteristics Of Pediatric Covid-19 Infections And The Impact Of Influenza And Covid-19 Vaccinations During The First Two Years Of The Pandemic, Mahmoud Ali, Lynette Phillips, David C Kaelber, Hulya Bukulmez

Faculty, Staff and Student Publications

The data regarding the demographics of SARS-CoV-2 in the pediatric population has been published based on several single-center experiences or on metanalyses over short time frames. This article reports data on the demographics of pediatric patients with COVID-19 on a global scale using the TriNetX COVID-19 Research Network. In addition, we examined the risk of COVID-19 infection in relation to the body mass index (BMI) category and the protective value of influenza and COVID-19 immunization against COVID-19 infection. The incidence of COVID-19 infection was higher in the younger age group (≤6 years old), but no gender differences. The incidence of …

Protein Translation Paradox: Implications In Translational Regulation Of Aging, Harper S Kim, Andrew M Pickering

Faculty, Staff and Student Publications

Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age. Conversely, lifelong reductions in protein translation have been found to extend lifespan and healthspan in multiple animal models. These findings raise the protein synthesis paradox: age-related declines in protein synthesis should be detrimental, but life-long reductions in protein translation paradoxically slow down aging and prolong …

Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale, Tanzin Dikid

Faculty, Staff and Student Publications

INTRODUCTION: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps.

MATERIAL AND METHODS: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system …

How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students' Selecting Pathology As A Specialty?, Cindy B Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R George, Ashley M Holloman, Bronwyn Bryant, Mary P Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E C Knollmann-Ritschel, Victor Gerardo Prieto, Charles F Timmons, Robert D Hoffman

Faculty, Staff and Student Publications

There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school's historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences …

Tuning The Thermodynamic, Optical, And Rheological Properties Of Thermoresponsive Polymer Solutions Via Silica Nanoparticle Shape And Concentration, Christopher A P Neal, Valeria León, Michelle C Quan, Nondumiso O Chibambo, Michelle A Calabrese

Faculty, Staff and Student Publications

HYPOTHESIS: The shape and quantity of hydrophilic silica nanoparticles (NPs) can be used to tune the microstructure, rheology, and stability of phase-separating polymer solutions. In thermoresponsive polymer systems, silica nanospheres are well-studied whereas anisotropic NPs have little literature precedent. Here, we hypothesize that NP shape and concentration lower the onset of rheological and turbidimetric transitions of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions.

EXPERIMENTS: Differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), turbidimetry, and oscillatory rheology are utilized to examine interactions between NPs, PNIPAM, and water and to track changes in phase separation and rheological properties due to NP concentration and shape. …

Next-Generation Ctla-4 Targeting Molecules And Combination Therapy: Promising Strategies For Improving Cancer Immunotherapy, Nils-Petter Rudqvist, Manushak Avagyan, Dhan Chand

Faculty, Staff and Student Publications

Radiation therapy and anti-CTLA-4 combination therapy can induce meaningful responses in some patients. Adding CD40 may provide additional benefit. Next-generation anti-CTLA-4 antibodies, such as botensilimab, are showing promise in clinical trials. Combining botensilimab with RT and/or CD40 agonist may offer additional benefits for challenging tumor types.

Stereotactic Body Proton Therapy For Early Stage Non-Small Cell Lung Cancer – Technical Challenges And Solutions: The Md Anderson Experience, X Ronald Zhu, Yuting Li, Ming Yang, Thomas J Whitaker, Paige A Taylor, Xiaodong Zhang, Falk Poenisch, Narayan Sahoo, Zhongxing Liao, Joe Y Chang

Faculty, Staff and Student Publications

Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better …

A Randomized Double-Blind Prospective Study Comparing The Efficacy Of Subperiosteal And Periarticular Injections Of A Local Anesthetic For Postoperative Pain Management After Total Knee Arthroplasty, Reza Minaei, Mohammad Salehpour, Emad Kouhestani, Mahshid Ghasemi

Faculty, Staff and Student Publications

OBJECTIVES: Total knee arthroplasty (TKA) serves as an effective surgical treatment method for advanced osteoarthritis (OA). Nonetheless, it is associated with postoperative pain that can influence patients' functional outcome. This study aimed to compare the analgesic effect of subperiosteal and periarticular injection methods of a special local anesthetic in patients who underwent TKA.

METHODS: This double-blind prospective clinical study was conducted on patients with advanced knee OA who underwent TKA. Patients were randomly divided into two groups, with a local anesthetic (21 ml) administered either in periarticular (P group) or subperiosteal (S group) forms prior to wound closure. The local …

Multi-Faceted Role Of Lrp1 In The Immune System, Olga Sizova, Lisa St John, Qing Ma, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Graft versus host disease (GVHD) represents the major complication after allogeneic hematopoietic stem cell transplantation (Allo-SCT). GVHD-prone patients rely on GVHD prophylaxis (e.g. methotrexate) and generalized anti-GVHD medical regimen (glucocorticoids). New anti-GVHD therapy strategies are being constantly explored, however there is an urgent need to improve current treatment, since GVHD-related mortality reaches 22% within 5 years in patients with chronic GVHD. This review is an attempt to describe a very well-known receptor in lipoprotein studies - the low-density lipoprotein receptor related protein 1 (LRP1) - in a new light, as a potential therapeutic target for GVHD prevention and treatment. Our …

Colorectal Surveillance Outcomes From An Institutional Longitudinal Cohort Of Lynch Syndrome Carriers, Gabriel Del Carmen, Laura Reyes-Uribe, Daniel Goyco, Kyera Evans, Charles M Bowen, Jennifer L Kinnison, Valerie O Sepeda, Diane M Weber, Julie Moskowitz, Maureen E Mork, Selvi Thirumurthi, Patrick M Lynch, Miguel A Rodriguez-Bigas, Melissa W Taggart, Y Nancy You, Eduardo Vilar

Faculty, Staff and Student Publications

OBJECTIVE: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for

DESIGN: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to …

Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar

Faculty, Staff and Student Publications

Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited …

Fanconi Anemia Caused By Biallelic Inactivation Of Brca2 Can Present With An Atypical Cancer Phenotype In Adulthood, Kara N Maxwell, Vishal Patel, Kevin T Nead, Shana Merrill, Dana Clark, Qinqin Jiang, Bradley Wubbenhorst, Kurt D'Andrea, Roger B Cohen, Susan M Domchek, Jennifer J D Morrissette, Roger A Greenberg, Daria V Babushok, Katherine L Nathanson

Faculty, Staff and Student Publications

Inherited biallelic pathogenic variants (PVs) in BRCA2 cause Fanconi Anemia complementation group D1 (FA-D1), a severe pediatric bone marrow failure and high-risk cancer syndrome. We identified biallelic BRCA2 PVs in a young adult with multiple basal cell carcinomas, adult-onset colorectal cancer and small cell neuroendocrine carcinoma, without bone marrow failure. No PVs were identified in any other known cancer susceptibility gene, and there was no evidence of reversion mosaicism. The proband's deceased sister had a classic FA-D1 presentation and was shown to carry the same biallelic BRCA2 PVs. A lymphoblastoid cell line derived from the proband demonstrated hypersensitivity to DNA …

Uncovering The Role Of Fat-Infiltrated Axillary Lymph Nodes In Obesity-Related Diseases With Statistical And Machine Learning Analyses, Qingyuan Song

Dartmouth College Ph.D Dissertations

The link between obesity and pathogenesis is a complex and multifaceted area of research that is yet to be fully understood. Ample evidence exists to demonstrate the direct relationship between excessive internal fat and various health conditions such as cancer, and metabolic and cardiovascular diseases. The infiltration of ectopic fat into axillary lymph nodes, observable on breast cancer screening images, has been shown to be correlated with body mass index (BMI) in women undergoing screening. This study aimed to explore the relationship between fat-infiltrated axillary lymph nodes (FIN) and obesity-related diseases, with the goal of evaluating the clinical value of …

An Explainable Deep Learning Prediction Model For Severity Of Alzheimer's Disease From Brain Images, Godwin O. Ekuma

Graduate Theses/Dissertations

Deep Convolutional Neural Networks (CNNs) have become the go-to method for medical imaging classification on various imaging modalities for binary and multiclass problems. Deep CNNs extract spatial features from image data hierarchically, with deeper layers learning more relevant features for the classification application. The effectiveness of deep learning models are hampered by limited data sets, skewed class distributions, and the undesirable "black box" of neural networks, which decreases their understandability and usability in precision medicine applications. This thesis addresses the challenge of building an explainable deep learning model for a clinical application: predicting the severity of Alzheimer's disease (AD). AD …

Expanding Medicaid To Reduce Human Immunodeficiency Virus Transmission In Houston, Texas: Insights From A Modeling Study, Francis Lee, Aditya S Khanna, Camden J Hallmark, Richa Lavingia, Marlene Mcneese, Jing Zhao, Melanie L Mcneese, Salma Khuwaja, Babak M Ardestani, Nicholson Collier, Jonathan Ozik, Anna L Hotton, Nina T Harawa, John A Schneider, Kayo Fujimoto

Faculty, Staff and Student Publications

CONTEXT: Medicaid expansion has been nationally shown to improve engagement in the human immunodeficiency virus (HIV) treatment and prevention continua, which are vital steps to stopping the HIV epidemic. New HIV infections in the United States are disproportionately concentrated among young Black men who have sex with men (YBMSM). Houston, TX, is the most populous city in the Southern United States with a racially/ethnically diverse population that is located in 1 of 11 US states that have not yet expanded Medicaid coverage as of 2021.

METHODS: An agent-based model that incorporated the sexual networks of YBMSM was used to simulate …

A Student-Designed Multimodal Sex- And Gender-Based Women's Health Elective Program: Advocacy Curriculum For Medical Students, Lauren M Conroy, Danna Ghafir, Maitreyi Narayan, Hunter Mcspedden, Samuel Neher, S Shahrukh Hashmi, Rebecca Lunstroth

Faculty, Staff and Student Publications

OBJECTIVES: The objective of this article is to describe the design and implementation of a multimodal, student-driven, sex- and gender-based women's health (SGBWH) elective with a curricular focus on patient and legislative advocacy. In this single arm, pre/post design, interventional study, we detail and evaluate the use of social media, newsletters, and round-table discussions in conjunction with a traditional lecture-based educational format to engage medical students in a virtual learning environment.

METHODS: We developed a 22-week SGBWH curriculum for pre-clinical and clinical medical students, which included a series of lectures on multi-specialty and gender-inclusive topics related to SGBWH, small group …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M Willems, Natasha H J Ng, Juan Fernandez, Rebecca S Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Xueling Sim, Hanieh Yaghootkar, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Niels Grarup, Ruifang Li-Gao, Tibor V Varga, Jennifer L Asimit, Shuang Feng, Rona J Strawbridge, Erica L Kleinbrink, Tarunveer S Ahluwalia, Ping An, Emil V Appel, Dan E Arking, Juha Auvinen, Lawrence F Bielak, Nathan A Bihlmeyer, Jette Bork-Jensen, Jennifer A Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Järvelin, Richard A Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Man Li, Yingchang Lu, Jian'an Luan, Alisa K Manning, Jonathan Marten, Karina Meidtner, Dennis O Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M Rice, Serena Sanna, Albert Vernon Smith, Jennifer A Smith, Lorraine Southam, Heather M Stringham, Vinicius Tragante, Sander W Van Der Laan, Helen R Warren, Jie Yao, Andrianos M Yiorkas, Weihua Zhang, Wei Zhao, Mariaelisa Graff, Heather M Highland, Anne E Justice, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W Asselbergs, Lori L Bonnycastle, Michiel L Bots, Ivan Brandslund, Ji Chen, John Danesh, Renée De Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, Epic-Interact Consortium, Aliki-Eleni Farmaki, Jessica D Faul, Paul W Franks, Steve Franks, Andreas Fritsche, Anette P Gjesing, Mark O Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B Harris, Karl-Heinz Herzig, Marie-France Hivert, Torben Jørgensen, Marit E Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L R Kardia, Leena Kinnunen, Heikki A Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Lenore J Launer, Aaron Leong, Jaana Lindström, Jocelyn E Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A Nalls, Matthew Neville, James S Pankow, Alison Pattie, Eva R B Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D Taylor, Betina H Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group;, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P Bottinger, Mark J Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Francis S Collins, Josef Coresh, Francesco Cucca, Gert J De Borst, Ian J Deary, George Dedoussis, Panos Deloukas, Hester M Den Ruijter, Josée Dupuis, Michele K Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Torben Hansen, Andrew T Hattersley, Caroline Hayward, Joel N Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J F Loos, Patrick E Macdonald, Karen L Mohlke, Andrew D Morris, Patricia B Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A Peyser, Ozren Polasek, David Porteous, Michael A Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M Starr, Michael Stumvoll, Cornelia M Van Duijn, Mark Walker, Nick J Wareham, David R Weir, James G Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B Zonderman, Jerome I Rotter, Andrew P Morris, Michael Boehnke, Jose C Florez, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Robert A Scott, Anna L Gloyn, Inês Barroso

Faculty, Staff and Student Publications

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network …

Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls

Faculty, Staff and Student Publications

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6-12 months after an index ischemic stroke.

Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6-12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate …

Leveraging Informative Missing Data To Learn About Acute Respiratory Distress Syndrome And Mortality In Long-Term Hospitalized Covid-19 Patients Throughout The Years Of The Pandemic, Emily Getzen, Amelia Lm Tan, Gabriel Brat, Gilbert S Omenn, Zachary Strasser, Qi Long, John H Holmes, Danielle Mowery

Faculty, Staff and Student Publications

Electronic health records (EHRs) contain a wealth of information that can be used to further precision health. One particular data element in EHRs that is not only under-utilized but oftentimes unaccounted for is missing data. However, missingness can provide valuable information about comorbidities and best practices for monitoring patients, which could save lives and reduce burden on the healthcare system. We characterize patterns of missing data in laboratory measurements collected at the University of Pennsylvania Hospital System from long-term COVID-19 patients and focus on the changes in these patterns between 2020 and 2021. We investigate how these patterns are associated …

Dental Claires: Contrastive Language Image Retrieval Search For Dental Research, Tanjida Kabir, Luyao Chen, Muhammad F Walji, Luca Giancardo, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

Learning about diagnostic features and related clinical information from dental radiographs is important for dental research. However, the lack of expert-annotated data and convenient search tools poses challenges. Our primary objective is to design a search tool that uses a user's query for oral-related research. The proposed framework,

Coevolution Combined With Molecular Dynamics Simulations Provides Structural And Mechanistic Insights Into The Interactions Between The Integrator Complex Subunits, Bernard Fongang, Yannick N Wadop, Yingjie Zhu, Eric J Wagner, Andrzej Kudlicki, Maga Rowicka

Faculty, Staff and Student Publications

Finding the 3D structure of large, multi-subunit complexes is difficult, despite recent advances in cryo-EM technology, due to remaining challenges to expressing and purifying subunits. Computational approaches that predict protein-protein interactions, including Direct Coupling Analysis (DCA), represent an attractive alternative for dissecting interactions within protein complexes. However, they are readily applicable only to small proteins due to high computational complexity and a high number of false positives. To solve this problem, we proposed a modified DCA approach, a powerful tool to predict the most likely interfaces of protein complexes. Since our modified approach cannot provide structural and mechanistic details of …