Digital Commons Network^™

A Physician Survey On Research And Implementation Priorities For Caffeine Citrate Use In Newborn Care In Sub-Saharan Africa, Olufunke Bolaji, Osayame Ekhaguere, Franck Houndjahoue, Nicholas Embleton, Helen Nabwera

Centre of Excellence in Women and Child Health

Background:Evidence on caffeine citrate (CC) for apnoeaof prematurity (AOP) originate from high-income countries. This study aimed to develop consensus on research design for evidence in sub-Saharan Africa (SSA).

Methods:We surveyed physicians in newborn units across SSA to assess their opinions on CC research and their preferred study designs.

Participants rated four study designs:a) an observational before-and-after study; a randomized controlled trial (RCT) of b) caffeine versus placebo; c) caffeine versus aminophylline; d) a traditional or stepped wedge cluster trial.  They  assessed  each  design  using  a  Likert  scale  for  evidence, feasibility, and ethics considerations.

Results:Ninety-two   newborn   physicians …

Transcatheter Aortic Valve Replacement In Systemic Sclerosis: A Case Series And Review Of Short- And Long-Term Outcomes, Chris T. Derk, Ahmadreza Badali, Esra Mehmetoglu, Anvitha Mummadisetty, Amit Syal, Konstantinos Parperis

Student Papers, Posters & Projects

Objectives: A higher frequency of valvular heart disease is seen among Systemic Sclerosis (SSc) patients. Advanced aortic valve stenosis leads to significant morbidity in these patients with multiple other comorbidities. In this study, we aim to define the short- and long-term outcomes of transcatheter aortic valve replacement (TAVR) procedures in SSc patients. Methods: We undertook a retrospective chart review of all patients with SSc who underwent a TAVR procedure at our institution over a defined 11-year period. Demographics as well as short- and long-term outcomes were identified. Results: Fourteen SSc patients underwent a TAVR procedure between 2012 and 2023. They …

Improving Vaccination In People With Ckd: Report From A National Kidney Foundation Working Group, Susan F. Massengill, Kenneth A. Andreoni, Keith A. Bellovich, Cheryl Courtlandt, Vimal K. Derebail, David L. Feldman, Gia J. Oh, John W. Sleasman, Kristina A. Bryant, Improving Vaccination In Ckd Working Group

Department of Surgery Faculty Papers

People with chronic kidney disease (CKD) are particularly vulnerable to vaccine-preventable infections. Therefore, the National Kidney Foundation organized a multidisciplinary working group, including people with CKD and family care partners, to develop recommendations to improve vaccination rates, vaccination effectiveness, and health care for the CKD population. A modified Delphi process was used to achieve consensus on the recommendations. Recommendations on vaccination in CKD patients were organized into these categories: (1) patient preferences; (2) assessing the vaccination status of patients with CKD; (3) assessing vaccine response in patients with CKD; (4) vaccination of immunocompromised patients; (5) vaccination in posttransplant patients; (6) …

Effect Of Dental Treatments On Reduction Of Preterm Birth: A Systematic Review And Meta-Analysis, Camille Thomas, Shakil Ahmed, Vincenzo Berghella, Romina Brignardello-Petersen, Mohamed El-Rabbany, Catherine Devion, Stefania Ronzoni

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Periodontal disease is associated with increased risk of preterm birth. Effective management during pregnancy may reduce preterm birth, though clinical trial evidence has been inconsistent. This study aimed to assess whether treating dental disease during pregnancy reduces preterm birth.

DATA SOURCES: A systematic search was performed of EMBASE, MEDLINE, PubMed, Cochrane Library, and trial registries up to December 2023 and re-run in January 2025.

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) enrolling pregnant persons with any dental disease randomized to receive dental treatment vs no treatment were included. No language restriction was applied.

STUDY APPRAISAL AND SYNTHESIS METHODS: Data …

Non-Synaptic Function And Localization Of Syntaxin-Binding Protein 1 In A Mouse Model Of Stxbp1-Related Epileptic Encephalopathy, Tao Yang, Rajat Banerjee, Yamei Deng, Sheetal Jahagirdar, Joo Hyun Kim, Wu Chen, Mingshan Xue, Alexey I Nesvizhskii, Michael D Uhler, Jack M Parent, Yu Wang

Duncan NRI Faculty and Staff Publications

Objective: De novo mutations in the syntaxin-binding protein 1 (STXBP1), encoded by STXBP1, are among the most prevalent causes of variable neurodevelopmental disorders, including epileptic encephalopathy, developmental delay, and movement disorders. Although STXBP1 has been proposed as a critical presynaptic protein controlling synaptic vesicle exocytosis, clinical phenotypes also suggest that its biological function could be more diverse.

Methods: The expression pattern of STXBP1 was studied using immunostaining in vitro and in vivo. Synaptosome isolation was performed to investigate the synaptic and non-synaptic localization of STXBP1 in the brain. STXBP1 immunoprecipitation followed by mass spectrometry (MS) was conducted to identify protein …

Low-Dose Aspirin For Preventing Intrauterine Growth Restriction And Pre-Eclampsia In Sickle Cell Pregnancy, Lydia Pecker, Sophie Lanzkron

Cardeza Foundation for Hematologic Research

No abstract provided.

Screening Ptsd In Clinical Populations Within East Africa: Results From The First Follow-Up Study Of Neurogap-Psychosis, Shaili Jha, Rocky Stroud, Ana Lucia Dice, Joseph Kyebuzibwa, Stella Gichuru, Fredrick Ochieng, Manasi Sharma, Hayden Mountcastle, Lydia Marshall, Lukoye Atwoli

Brain and Mind Institute

Background: Given the high burden of trauma in Sub-Saharan Africa, there is a critical need for scalable tools to screen for trauma and posttraumatic stress disorder (PTSD) symptoms, especially in low-resource settings.

Objective: This study aimed to evaluate the utility, reliability, and validity of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) administered over the telephone to individuals previously enrolled in the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) study in Uganda (N = 4,921) and Kenya (N = 3,149).

Method: Cases with psychosis and controls without psychosis (patients, caretakers, or employees) were recontacted from the NeuroGAP-Psychosis …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Children’s Nutrition Research Center Staff Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Perceptions And Use Of Behaviour Change Interventions For Physical Activity In Chronic Respiratory Disease In The Republic Of Ireland, Ciara Hanrahan, Joseph G Mcveigh, Terence M O'Connor, Thierry Troosters, Julie Broderick

Children’s Nutrition Research Center Staff Publications

Objectives: Behaviour change interventions may support physical activity behaviour in people with chronic respiratory disease. The most effective interventions for long-term physical activity behaviour change in this cohort remains unclear. This aim of this study was to explore the use and perceptions of behaviour change interventions by both providers of physical activity programmes for people with chronic respiratory disease and by people living with chronic obstructive pulmonary disease (COPD) in The Republic of Ireland.

Design: Two anonymous online and paper-copy cross-sectional surveys, piloted and mapped to the COM-B model of behaviour change, were distributed via social media and relevant gate-keepers …

Pre- And Postnatal Exposure To Pm2.5 And No2 And Blood Pressure In Children: Results From The Echo Cohort, Yu Ni, Andrew Law, Xingyu Gao, Adam A Szpiro, Christine T Loftus, Miranda Jones, Logan C Dearborn, Marnie F Hazlehurst, Allison R Sherris, Sindana Ilango, Kaja Z Lewinn, Nicole R Bush, Qi Zhao, Leonardo Trasande, Joseph T Flynn, Daniel A Enquobahrie, Ruby H N Nguyen, Tom O'Connor, Arpita K Vyas, Mingyu Zhang, Hooman Mirzakhani, Alison Hipwell, Anne Starling, Alicia K Peterson, Akhgar Ghassabian, Assiamira Ferrara, Judy Aschner, Scott Collingwood, Margaret R Karagas, Michelle Katzow, Annemarie Stroustrup, Mehtap Haktnair, Tina V Hartert, Brittney M Snyder, Sophia Jan, Anne Marie Singh, Dana Dabelea, Angela M Malek, Jennifer K Straughen, Carlos A Camargo, Miatta A Buxton, Rosalind Wright, Kecia Carroll, Keia Sanderson, Daphne Koinis Mitchell, Viren D'Sa, Christine Hockett, Anne L Dunlop, Shohreh F Farzen, Sunni L Mumford, Akram N Alshawabkeh, Hudson P Santos, Xueying Zhang, Zhongzheng Niu, Nan Ji, Carrie Breton, Donghai Liang, Catherine J Karr, Echo Cohort Consortium

Children’s Nutrition Research Center Staff Publications

Background: There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive.

Methods: We examined the association between exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and blood pressure measured at age 5-12 years in 4863 U.S. children from 20 pregnancy cohorts of the NIH ECHO cohort. Point-based residential exposures were derived from spatiotemporal models with a biweekly resolution and averaged over each trimester, the whole pregnancy, and child age 0-2 years. We converted systolic (SBP) and diastolic blood …

Breast Cancer Awareness And Preferences For Screening Messaging On Menstrual Hygiene Products In Ghana And Tanzania, Tingting Mo, Elisabeth Msoka, Clement Narh, Blandina Mmbaga, Modesta Mitao, Getrude Mshana, Janeth Kiwia, Huruma Sapheli, Frank Baiden, Miriam Mutebi

General Surgery, East Africa

Background Menstrual hygiene products (MHPs) may offer a high-reach, frequent, long-lasting yet underutilized channel for health education, particularly in low-resource settings. This study aimed to explore women’s breast health awareness (BHA) and their attitudes towards and preferences for BHA messages on MHPs.

Methods Women aged 18–49 years in Ghana and Tanzania (n = 438; 216 Ghana, 222 Tanzania), stratified by age and urban/rural setting, completed a questionnaire assessing socio-demographics, BHA, and preferences for BHA messages with MHP. BHA was assessed with an adapted 31-item Breast Cancer Awareness Measure Tool covering 4 domains: breast cancer signs and symptoms, confidence, skills, and …

Severe Bilateral Retinal Degeneration Following A Twenty-Six-Year Pentosan Polysulfate Sodium Exposure: A Case Report., Aaron T. Zhao, Turner D. Wibbelsman, Martin Calotti, Collin J Richards, Tamara R. Vrabec

Wills Eye Hospital Papers

PURPOSE: To describe an advanced case of pentosan polysulfate sodium (PPS)-associated retinopathy with extensive macular and peripheral retinal involvement following prolonged high-dose exposure.

OBSERVATIONS: An 86-year-old male presented with bilateral hand motion visual acuity and a 26-year history of PPS use (400mg daily, ∼3769g cumulative dose) for treatment of interstitial cystitis. Fundus examination revealed widespread retinal degeneration characterized by confluent nummular patches of retinal atrophy in a radial distribution from the optic nerves. Ocular coherence tomography (OCT) demonstrated severe outer retinal disorganization, and fundus autofluorescence (FAF) showed extensive RPE loss and absence of the Robson Holder ring. Genetic testing excluded …

Undergraduate Health And Wellbeing Course And Study Away Program To Alaska, Lorraine S. Wallace, Steven J. Mousetes, Jennifer Bickley

Journal of Global Education and Research

High-impact practices, such as diversity/global education, have been shown to positively contribute to student development, engagement, and success. As the US is both culturally and linguistically diverse, domestic study away programs can offer students impactful multicultural educational experiences without leaving the country. The purpose of this study was to describe the design of a health and well-being academic course and accompanying study away program to Alaska for undergraduates at The Ohio State University (OSU). The authors (1) describe the application of the backward design process in guiding ELOs development, (2) provide a sample of course assignments and student responses, and …

Pharmacokinetic Modeling Strategies For Dynamic Hyperpolarized Urea Imaging, Keith A Michel, Collin J Harlan, Christopher M Walker, Matthew E Merritt, Yunyun Chen, Stephen Y Lai, James A Bankson

Faculty, Staff and Student Publications

Purpose: To evaluate pharmacokinetic modeling methods for quantification of tissue perfusion/permeability with hyperpolarized 13C urea.

Methods: Three models for quantitative analysis of dynamic HP urea imaging data were proposed and evaluated in numerical simulations and a thyroid cancer mouse model. A multicompartment model resembling the extended Tofts model for DCE-MRI (Model I) and two simplified models were used. The simplified models each eliminate a volume parameter representing vascular (Model II) or impermeable cellular space (Model III). Signal curves were generated from Model I, and models were fit to these synthetic data to quantify the effects of acquisition settings, bias in …

Analysis Of Patients With Monocytic And Monocytic-Like Acute Myeloid Leukemia, Including Aml-M4 And Aml-M5, Treated With Venetoclax Plus Azacitidine, Marina Konopleva, Courtney D Dinardo, Yan Sun, Paul Jung, Sanam Loghavi, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Mutational Landscape And Burden On Rbc Transfusion Response In Patients With Lower-Risk Myelodysplastic Syndromes (Lr-Mds) In The Commands Study, Rami S Komrokji, Sheida Hayati, Manuel Ugidos, Guillermo Garcia-Manero, Matteo Giovanni Della Porta, Amer M Zeidan, Valeria Santini, Uwe Platzbecker, Anita K Gandhi, Rajasekhar N V S Suragani

Faculty, Staff and Student Publications

The COMMANDS trial established luspatercept as a first‐line treatment for anemia in transfusion‐dependent lower‐risk (LR) myelodysplastic syndromes (MDS). Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%–59%. Mutation profiles were similar in the treatment groups. Luspatercept …

Clemastine Ameliorates Cognitive Deficits In An Experimental Rat Model Of Chronic Cerebral Hypoperfusion, Xuemei Zong, Zhihai Huang, Fanfei Kong, Yu Feng, Yulan Zhang, Peibin Zou, Hung Wen Lin, David C Hess, Quanguang Zhang

Faculty, Staff and Student Publications

Chronic cerebral hypoperfusion (CCH) profoundly affects patient well-being and has been proposed as a risk factor for cognitive impairment and dementia. However, due to the limited understanding of the pathophysiology of CCH, there are currently no effective preventive or therapeutic approaches for CCH-associated cognitive impairment. Therefore, identifying new targets for CCH is essential to bridge this knowledge gap. In this study, we sought to determine whether enhanced myelination could prevent cognitive impairment associated with CCH. Experimental CCH was induced via bilateral common carotid artery occlusion (BCCAO) in rats, and clemastine, a well-established pro-myelinating agent, was administered to boost myelin renewal. …

Beyond Short Microhomologies: Mismatch-Compatible Pol Θ-Mediated Dna Damage Repair, Yuzhen Li, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ)-mediated end-joining (TMEJ), one of several pathways for repairing DNA double-strand breaks, is traditionally thought to initiate via anchoring at short, consecutive, and perfectly matched microhomologies (MHs). Emerging evidence indicates that Pol θ can utilize MHs containing mismatches both in vitro and in vivo. This revised definition of MH provides a mechanistic explanation for a broader spectrum of Pol θ-dependent repair outcomes. Here, we summarize recent findings on the revised definition of MHs utilized by Pol θ, assess the applicability of this concept across species, and compare TMEJ with other (micro)hom(e)ology-mediated repair pathways. We explore how …

Clinicopathologic And Molecular Characteristics Of High-Grade Appendiceal Mucinous Neoplasms, Ashlee N Seldomridge, Michael G White, Christopher Scally, Richard E Royal, Mark Routbort, Jbryan Iorgulescu, Michael J Overman, Sun Mi Lee, Wai Chin Foo, Melissa W Taggart, Yun Song, Paul F Mansfield, Keith F Fournier, John Paul Shen, Beth A Helmink

Faculty, Staff and Student Publications

Background: Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized. Comparative data with low-grade appendiceal mucinous neoplasms (LAMNs) are limited. This study aims to detail the clinical management and outcomes of patients with HAMN and those with LAMN.

Methods: This retrospective cohort study was conducted at a large academic cancer center. An internal database was queried to identify patients with LAMN or HAMN who underwent appendectomy between 2016 and 2024. Kaplan-Meier survival analyses were used to assess the impact of primary tumor type and peritoneal …

Shiny-Magec: A Bayesian R Shiny Application For Meta-Analysis Of Censored Adverse Events, Zihan Zhou, Zizhong Tian, Christine Peterson, Le Bao, Shouhao Zhou

Faculty, Staff and Student Publications

Accurate assessment of adverse event (AE) incidence is critical in clinical research for drug safety. While meta-analysis serves as an essential tool to comprehensively synthesize the evidence across multiple studies, incomplete AE reporting in clinical trials remains a persistent challenge. In particular, AEs occurring below study-specific reporting thresholds are often omitted from publications, leading to left-censored data. Failure to account for these censored AE counts can result in biased AE incidence estimates. We present an R Shiny application that implements a Bayesian meta-analysis model specifically designed to incorporate censored AE data into the estimation process. This interactive tool provides a …

Classification Of Major Depressive Disorder Using Vertex-Wise Brain Sulcal Depth, Curvature, And Thickness With A Deep And A Shallow Learning Model, Roberto Goya-Maldonado, Tracy Erwin-Grabner, Ling-Li Zeng, Christopher R K Ching, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Katharina Brosch, Robin Bülow, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Kathryn Cullen, Udo Dannlowski, Christopher G Davey, Annemiek Dols, Jan Ernsting, Jennifer W Evans, Lukas Fisch, Paola Fuentes-Claramonte, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke A Groenewold, Dominik Grotegerd, Tim Hahn, J Paul Hamilton, Laura K M Han, Ben J Harrison, Tiffany C Ho, Neda Jahanshad, Alec J Jamieson, Andriana Karuk, Tilo Kircher, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Ramona Leenings, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Susanne Meinert, Elisa Melloni, Bryon A Mueller, Benson Mwangi, Igor Nenadić, Amar Ojha, Yasumasa Okamoto, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Elena Rodríguez-Cano, Matthew D Sacchet, Raymond Salvador, Anouk Schrantee, Kang Sim, Jair C Soares, Aleix Solanes, Dan J Stein, Frederike Stein, Aleks Stolicyn, Sophia I Thomopoulos, Yara J Toenders, Aslihan Uyar-Demir, Eduard Vieta, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Heather C Whalley, Sarah Whittle, Nils Winter, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used …

Impact Of Intra- And Interfractional Motion On The Dose Distribution And Urinary Adverse Events For Magnetic Resonance-Guided Prostate Cancer Radiotherapy, Shu Xing, Sarah Burleson, Xiao Tan, Qijie Huang, Nima Hassan-Razein, Chengcheng Gui, Ergys Subashi, Himanshu Nagar, Victoria Brennan, Neelam Tyagi

Faculty, Staff and Student Publications

Purpose: To evaluate the impact of intra- and interfractional motion on dose distribution and clinical outcome in prostate magnetic resonance (MR)-guided adaptive radiotherapy.

Methods: Seventy-six patients were treated with five-fraction stereotactic radiotherapy on a 1.5 T MR linear accelerator. Cine MR images were acquired during treatment and exported to a motion monitoring research package, to generate motion traces in the anterior-posterior (AP), superior-inferior (SI) and left-right (LR) directions. Planned dose distributions were shifted according to motion trace to reconstruct intrafraction motion-blurred dose. Intrafraction motion-blurred doses were deformably registered to fraction one motion-blurred dose to obtain interfraction accumulated dose. The impact …

Frontotemporal Network Interactions Causally Support Rapid Concreteness Judgments During Reading, Elliot Murphy, Oscar Woolnough, Cale W Morse, Xavier Scherschligt, Nitin Tandon

Faculty, Staff and Student Publications

Neurobiological models of conceptual processing have been limited in spatiotemporal resolution, and uncertainty remains about the causal role of specific regions in concept representation. We utilized intracranial recordings in human neurosurgical patients with epilepsy (n = 19) during a concreteness judgement paradigm of single word reading. Concrete concepts showed greater high-frequency activation across a frontal and ventrotemporal network, while greater activation for abstract words was found in lateral posterior middle temporal cortex. Intercortical communications, measured by high-frequency partial direct coherence, revealed bidirectional frontal and ventral plus lateral temporal interactions. Words occupying the middle range of the concreteness scale (e.g., "profit") …

Trends And Challenges: A 15-Year Review Of Imaging And Radiation Oncology Core Anthropomorphic Phantom Audits For Proton Therapy, Lian Duan, Hunter S Mehrens, Stephen F Kry, Jessica R L Lowenstein, Nadia Hernandez, Lucas B Acuna Scafati, Paige A Taylor

Faculty, Staff and Student Publications

Purpose: This study aims to analyze the trends in institutional performance on Imaging and Radiation Oncology Core (IROC) proton phantoms and to investigate the impact of treatment parameters on proton therapy delivery accuracy.

Materials and methods: We analyzed 402 IROC anthropomorphic phantom audits performed by 57 institutions worldwide between 2009 and 2024, including brain, head and neck (H&N), spine, prostate, lung, and liver phantoms. Dosimetric assessments included thermoluminescent dosimeters (TLDs) for dose comparison and gamma analysis of radiochromic film. The lung and liver phantoms were irradiated with simulated motion. Univariate analysis was performed to evaluate the relationships between treatment parameters …

Selective Deletion Of Fgfr1 In Agrp Neurons Impairs Energy Homeostasis Under High-Fat Diet In Mice, Daniel Shookster, Shea O'Connell, Patel Darshan, Taylor Landry, Wyatt Bunner, Zhiying Jiang, Qingchun Tong, Hu Huang

Faculty, Staff and Student Publications

Background: The global obesity crisis and the limited success of current treatments underscore the need to identify novel regulatory pathways. While central administration of α-Klotho exerts anti-obesity effects in rodents through AgRP neurons, the intracellular signaling mechanisms that mediate this process remain undefined.

Methods: To define the role of FGFR1 within the α-Klotho signaling pathway in AgRP neurons, we performed a targeted deletion of the receptor in adult mice using an AAV-mediated CRISPR/Cas9 system alongside transgenic models.

Results: Deletion of FGFR1 in AgRP neurons disrupted energy homeostasis, promoting weight gain induced by a high-fat diet. Electrophysiological recordings revealed that FGFR1 …

Quantifying Rate-Limiting Genetic Variation In Breast And Ovarian Tumourigenesis, Kathleen E Houlahan, Mahad Bihie, Yves Greatti, Julián Grandvallet Contreras, Daniel J Fulop, Gonzalo Lopez, Marc Williams, Hsin-Hsiung Huang, Peter Van Loo, Paul C Boutros, Kuan-Lin Huang

Faculty, Staff and Student Publications

Background: The number and type of genetic alterations required to initiate breast and ovarian cancer remain unclear. While germline BRCA1/2 carriers show markedly elevated cancer risk, it is uncertain whether point mutations or copy number alterations constitute the rate-limiting events of tumourigenesis.

Methods: We developed a statistical framework extending prior incidence-mutation models to estimate the minimal number and type of driver events required for cancer initiation. Somatic mutation and copy-number data from >3000 breast and ovarian cancers in TCGA and METABRIC were compared between germline BRCA1/2 carriers and non-carriers matched on subtypes. Results were validated through analyses of evolutionary timing …

Large Language Models For Bioinformatics, Wei Ruan, Yanjun Lyu, Jing Zhang, Jiazhang Cai, Peng Shu, Yang Ge, Yao Lu, Shang Gao, Yue Wang, Peilong Wang, Lin Zhao, Tao Wang, Yufang Liu, Luyang Fang, Ziyu Liu, Zhengliang Liu, Yiwei Li, Zihao Wu, Junhao Chen, Hanqi Jiang, Yi Pan, Zhenyuan Yang, Jingyuan Chen, Shizhe Liang, Wei Zhang, Terry Ma, Yuan Dou, Jianli Zhang, Xinyu Gong, Qi Gan, Yusong Zou, Zebang Chen, Yuanxin Qian, Shuo Yu, Jin Lu, Kenan Song, Xianqiao Wang, Andrea Sikora, Gang Li, Xiang Li, Quanzheng Li, Yingfeng Wang, Lu Zhang, Yohannes Abate, Lifang He, Wenxuan Zhong, Rongjie Liu, Chao Huang, Wei Liu, Ye Shen, Ping Ma, Hongtu Zhu, Yajun Yan, Dajiang Zhu, Tianming Liu

Faculty, Staff and Student Publications

With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and …

Tuscan: Tumor Segmentation And Classification Analysis In Spatial Transcriptomics, Chenxuan Zang, Charles C Guo, Yaohong Wang, Peng Wei, Ziyi Li

Faculty, Staff and Student Publications

The identification of tumor cells is pivotal for understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method to study gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. A common strategy for identifying tumor cells is via tumor-specific marker gene expression signatures, which are highly dependent on marker accuracy. Another effective approach is through aneuploid copy …

Defining A Quantitative Threshold For Adaptive Re-Planning Using A Percentile-Based Scoring System, Alexandra O Leone, Christine B Peterson, Anna Lee, Adam S Garden, G Brandon Gunn, Lauren L Mayo, Amy C Moreno, Steven J Frank, C David Fuller, Jay P Reddy, Karen Hoffman, Ivan Vazquez, Ming Yang, Joshua S Niedzielski, Laurence E Court, Thomas J Whitaker

Faculty, Staff and Student Publications

Background: Despite the frequent need for adaptive planning in head and neck proton therapy, no quantitative indicators have been identified to determine when a plan should be adapted. Here, we aimed to determine a quantitative threshold for the change in plan quality between the primary treatment plan and verification plans that correlates with the physician's decision to adapt.

Methods: Primary treatment and verification plans were extracted from the clinical treatment planning system for 167 patients who underwent intensity-modulated proton therapy for base of tongue, tonsillar, or oropharyngeal cancers, with and without nodal involvement, between 2016 and 2021. All plans were …

Optimizing Feasibility And Acceptability Of An Online Expressive Writing Intervention For Survivors Of Adolescent And Young Adult Cancer: A Pilot Randomized Trial Of Iterative Modifications And Outcomes, Eunju Choi, Yusi Aveva Xu, Celia Cy Wong-Meli, Michael E Roth, Yisheng Li, Qian Lu

Faculty, Staff and Student Publications

Objective: To evaluate the feasibility of an online expressive writing (EW) intervention for survivors of adolescent and young adult (AYA) cancer and determine whether iterative, theory-driven modifications can enhance response, adherence, and completion rates.

Methods: In this randomized pilot trial, survivors of AYA cancer were recruited through a hospital-based AYA oncology clinic and an online community. Forty participants were randomly assigned to the EW intervention or control group. To improve on lower-than-expected adherence and completion rates in a previous cohort, the protocol was iteratively revised using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Modifications included …