Digital Commons Network^™

The Next-Generation Dna Vaccine Platforms And Delivery Systems: Advances, Challenges And Prospects, Siyuan Song, Praveen Neeli, Navid Sobhani, Pavithra K, Srinivasa Reddy Bonam, Rajendra Kurapati, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. …

A Multi-Institutional Natural Language Processing Pipeline To Extract Performance Status From Electronic Health Records, Danielle Guffey, Huili Zhu, Sudha R Yarlagadda, Ang Li, Javad Razjouyan

Faculty, Staff and Students Publications

PURPOSE: Performance status (PS), an essential indicator of patients' functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes.

PATIENTS AND METHODS: We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair's corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train …

Treatment Guidelines For Hyponatremia: Stay The Course, Tomas Berl, Volker Burst, David M Cohen, Mirjam Christ-Crain, Martin Cuesta, Guy Decaux, Michael Emmett, Aoife Garrahy, Fabrice Gankam-Kengne, John K Hix, Ewout J Hoorn, Kamel S Kamel, Nicolaos E Madias, Alessandro Peri, Julie Refardt, Mitchell H Rosner, Mark Sherlock, Stephen M Silver, Alain Soupart, Chris J Thompson, Joseph G Verbalis

Faculty, Staff and Students Publications

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting …

Spatial Transcriptomics Resolve An Emphysema-Specific Lymphoid Follicle B Cell Signature In Chronic Obstructive Pulmonary Disease, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J Mckenna, Francesca Polverino

Faculty, Staff and Students Publications

Rationale

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.

Objectives

To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema.

Methods

Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. …

Idppub: Illuminating The Dark Phosphoproteome Through Pubmed Mining, Yuxing Liao, Zhiao Shi, Huy Anh Pham, Hua Xu, Bing Zhang

Faculty, Staff and Students Publications

Global phosphoproteomics experiments quantify tens of thousands of phosphorylation sites. However, data interpretation is hampered by our limited knowledge on functions, biological contexts, or precipitating enzymes of the phosphosites. This study establishes a repository of phosphosites with associated evidence in biomedical abstracts, using deep learning-based natural language processing techniques. Our model for illuminating the dark phosphoproteome through PubMed mining (IDPpub) was generated by fine-tuning BioBERT, a deep learning tool for biomedical text mining. Trained using sentences containing protein substrates and phosphorylation site positions from 3000 abstracts, the IDPpub model was then used to extract phosphorylation sites from all MEDLINE abstracts. …

Neutrophil-Derived Activin-A Moderates Their Pro-Netotic Activity And Attenuates Collateral Tissue Damage Caused By Influenza A Virus Infection, Ariana Gavriil, Christina C Giannouli, Anastasia Apostolidou, Martyn L Foster, Martin M Matzuk, Panagiotis Skendros, Ioanna-Evdokia Galani, Paschalis Sideras

Faculty, Staff and Students Publications

BACKGROUND: Pre-neutrophils, while developing in the bone marrow, transcribe the Inhba gene and synthesize Activin-A protein, which they store and release at the earliest stage of their activation in the periphery. However, the role of neutrophil-derived Activin-A is not completely understood.

METHODS:To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model (S100a8-Cre/Inhba fl/fl mice) and analyzed the immune response to Influenza A virus (IAV) infection. More specifically, evaluation of body weight and lung mechanics, molecular and cellular analyses of bronchoalveolar lavage fluids, flow cytometry and cell sorting of lung cells, as well as histopathological analysis of lung tissues, …

Structure And Funding Of Clinical Informatics Fellowships: A National Survey Of Program Directors, Kunal P Patel, Karl M Kochendorfer, Richard J Medford, Dara E Mize, Edward R Melnick, Jonathan D Hron, Kenneth Youens, Deepti Pandita, Michael G Leu, Gregory A Ator, Feliciano Yu, Nicholas Genes, Carrie K Baker, Douglas S Bell, Joshua M Pevnick, Steven A Conrad, Aarti R Chandawarkar, Kendall M Rogers, David C Kaelber, Ila R Singh, Bruce P Levy, John T Finnell, Joseph Kannry, Natalie M Pageler, Vishnu Mohan, Christoph U Lehmann

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.

OBJECTIVES: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses.

METHODS: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, …

Spatial Transcriptomics Resolve An Emphysema-Specific Lymphoid Follicle B Cell Signature In Chronic Obstructive Pulmonary Disease, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J Mckenna, Francesca Polverino

Faculty, Staff and Students Publications

Rationale

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.

Objectives

To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema.

Methods

Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. …

Human Plcg2 Haploinsufficiency Results In A Novel Natural Killer Cell Immunodeficiency, Annelise Y Mah-Som, Allyssa L Daugherty, Stephanie Li, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Albert Yao, Ivan K Chinn, James R Lupski, Mohammad Ehlayel, Michael Keller, Greg R Bowman, Megan A Cooper, Jordan S Orange, Anthony R French

Faculty, Staff and Students Publications

Background:

Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. A subset of these patients possess defects in NK cells, lymphocytes which recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK cell and B cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported to date.

Objective:

We aimed to identify the genetic cause of NK cell immunodeficiency in two families, and herein describe the functional consequences of two novel loss-of-function …

Adolescent/Young Adult Self-Management And Independence Self-Report Scale: Preliminary Psychometric Findings, Timothy J Brei, Ellen Fremion, Grayson N Holmbeck, Audrey J Roach, Kathleen J Sawin, Eileen Sherburne

Faculty, Staff and Students Publications

Purpose: This study examined preliminary psychometrics of the Adolescent/Young Adult Self-Management and Independence Self-Report Scale (AMIS II SR).

Methods: Adolescents and adults (N = 159; 13-38 years old) with spina bifida from two clinics and one community sample completed the AMIS II SR. The majority (83%) had myelomeningocele, and about half were female (51.6%). The sample included 44.7% White, 11.3% Black and over one-third Hispanic/Latino (38.4%) participants. Descriptive analyses and reliability were assessed; a confirmatory factor analysis (CFA) was conducted.

Results: Item-to-total correlations support the AMIS II SR total scale (r = .38-.79) and its two subscales: condition (r = …

Crystal Structure Of Trichinella Spiralis Calreticulin And The Structural Basis Of Its Complement Evasion Mechanism Involving C1q, Mingming Zhang, Bin Zhan, Liming Yan, Zhenhua Ming, Yuli Cheng, Xiaolin Tian, Shuai Shao, Jingjing Huang, Xinping Zhu

Faculty, Staff and Students Publications

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT …

Achieving Surgical, Obstetric, Trauma, And Anesthesia (Sota) Care For All In South Asia, Natalie Sheneman, Chaitrali Patil, Anveshi Nayan, Himanshu Iyer, Arti Raj Kumar, Arun Prasad, G Allen Finley, Chellapuram Raja Krishna Prasad, Chintamani, Dhananjaya Sharma, Dhruva Ghosh, Gnanaraj Jesudian, Irum Fatima, Jogi Pattisapu, Justin Sangwook Ko, Lovenish Bains, Mashal Shah, Mohammed Shadrul Alam, Narmada Hadigal, Naveen Malhotra, Nilmini Wijesuriya, Prateek Shukla, Sadaf Khan, Sunil Pandya, Tariq Khan, Tashi Tenzin, Venkat Raja Hadiga, Daniel Peterson

Faculty, Staff and Students Publications

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions-initiatives and innovations-toward addressing these …

Diminished Tmem100 Expression In A Newborn With Acinar Dysplasia And A Novel Tbx4 Variant: A Case Report, Bushra Afzal, Emily Schlotterbeck, Justyna A Karolak, Gail Deutsch, Drucilla Roberts, Paweł Stankiewicz

Faculty, Staff and Students Publications

Acinar dysplasia (AcDys) of the lung is a rare lethal developmental disorder in neonates characterized by severe respiratory failure and pulmonary arterial hypertension refractory to treatment. Recently, abnormalities of TBX4-FGF10-FGFR2-TMEM100 signaling regulating lung development have been reported in patients with AcDys due to heterozygous single-nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving TBX4, FGF10, or FGFR2. Here, we describe a female neonate who died at 4 hours of life due to severe respiratory distress related to AcDys diagnosed by postmortem histopathologic evaluation. Genomic analyses revealed a novel deleterious heterozygous missense variant c.728A>C (p.Asn243Thr) in TBX4 that arose …

Ginkgo Biloba For Tardive Dyskinesia And Plasma Mnsod Activity: Association With Mnsod Ala-9val Variant: A Randomized, Double-Blind Trial, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.

Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded …

Effects Of Blood Flow Restriction Resistance Training On Autonomic And Endothelial Function In Persons With Parkinson's Disease, Lindsay Spindler, Pricilla Wyatt, Darryn Willoughby

Faculty, Staff and Students Publications

Background: Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD).

Objective: To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and …

Role Of Apolipoprotein B In The Clinical Management Of Cardiovascular Risk In Adults: An Expert Clinical Consensus From The National Lipid Association, Terry A Jacobson, Vera A Bittner, Jessica M Peña, George Thanassoulis, Seth S Martin, Carol F Kirkpatrick, Salim S Virani, Dave L Dixon, Christie M Ballantyne, Alan T Remaley

Faculty, Staff and Students Publications

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when …

Ispad Clinical Practice Consensus Guidelines 2024: Screening, Staging, And Strategies To Preserve Beta-Cell Function In Children And Adolescents With Type 1 Diabetes, Kristina Casteels, Jenny J Couper, Maria E Craig, Helena Elding Larsson, Laura Jacobsen, Karin Lange, Tal Oron, Emily K Sims, Cate Speake, Mustafa Tosur, Francesca Ulivi, Anette-G Ziegler, Diane K Wherrett, M Loredana Marcovecchio

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 …

Validation Of A New Patient-Reported Outcome Measure Of The Functional Impact Of Essential Tremor On Activities Of Daily Living, Alfonso Fasano, Sheng-Han Kuo, Kelly E Lyons, Henry Moore, Holly A Shill, Aparna Wagle Shukla, Carlos Singer, Rodger J Elble

Faculty, Staff and Students Publications

BACKGROUND: The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines.

OBJECTIVE: Develop and validate a TETRAS PRO subscale.

METHODS: Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for …

Understanding Prescribing Practices And Patient Experiences With Renin Angiotensin System Inhibitors Use In Chronic Kidney Disease: A Qualitative Study, Michael A Herrera, Peter A Richardson, Michael E Matheny, Julia M Akeroyd, Glenn T Gobbel, Adriana Hung, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve outcomes but are underutilized in patients with chronic kidney disease (CKD). Little is known about reasons for discontinuation and lack of reinitiating these medications. We aimed to explore clinicians' and patients' experiences and perceptions of ACEI/ARB use in CKD.

Methods: A multi-profession sample of health care clinicians and patients with documented ACEI/ARB-associated side effects in the past 6 months. Participants were recruited from 2 Veterans Affairs healthcare systems in Texas and Tennessee. A total of 15 clinicians and 10 patients completed interviews. We used inductive and deductive qualitative data …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Self-Correcting Method For Highly Effective Office-Based Helicobacter Pylori Therapy Using Cumulative Test Of Cure Data

Faculty, Staff and Students Publications

Background and aim: Helicobacter pylori infections have become resistant to many previously highly effective antimicrobial regimens resulting in clarithromycin, metronidazole, or fluoroquinolone-containing therapies becoming unsuccessful. Pretreatment susceptibility testing is only widely available in the United States but is still rarely done. Here, we propose a framework to monitor H. pylori eradication in small clinical settings by routinely assessing the effectiveness of therapy.

Methods: Because of the small sample size in individual practice's, we assume an acceptable cure rate of ≥80% (preferred cure rate ≥85%) in adherent patients, with a dichotomous outcome (cured vs. failed) and consecutive patient enrollment. To obtain …

Rates And Predictors Of Rapid Eye Movement Sleep Behavior Disorder Symptoms Among Post-9/11 Veterans, Ruosha Li, Audri Villalon, Ritwick Agrawal, Ricardo E Jorge

Faculty, Staff and Students Publications

Objective: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and degenerative synucleinopathy. Rates and predictors of RBD symptoms were investigated by screening post-9/11 veterans for RBD with a validated questionnaire.

Methods: In this cross-sectional analysis, consecutive patients in the Houston Translational Research Center for TBI and Stress Disorders (TRACTS) were screened with the English translation of the RBD Questionnaire-Hong Kong (RBDQ-HK). In addition to data from the standard TRACTS battery, systematic chart review was used to identify known sleep disorders mimicking …

Protein Biomarkers Gdf15 And Fgf21 To Differentiate Mitochondrial Hepatopathies From Other Pediatric Liver Diseases, Roxanne A Van Hove, Kristen R Miller, Rohit Sharma, Hardik Shah, Jane Estrella, Linda Gabel, Simon Horslen, Rohit Kohli, Mark A Lovell, Alexander G Miethke, Jean P Molleston, Rene Romero, James E Squires, Estella M Alonso, Stephen L Guthery, Binita M Kamath, Kathleen M Loomes, Philip Rosenthal, Krupa R Mysore, Laurel A Cavallo, Pamela L Valentino, John C Magee, Shikha S Sundaram, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children.

METHODS: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls.

RESULTS: GDF15 levels compared to controls were …

Optimizing Immunogenicity And Product Presentation Of A Sars-Cov-2 Subunit Vaccine Composition: Effects Of Delivery Route, Heterologous Regimens With Self-Amplifying Rna Vaccines, And Lyophilization, Brian Keegan, Leroy Versteeg, Ulrich Strych, Wen-Hsiang Chen, Raodoh Mohamath, Gabi Ramer-Denisoff, Sierra Reed, Christina Renshaw, Samuel Beaver, Alana Gerhardt, Emily A Voigt, Mark A Tomai, Robert Sitrin, Robert K M Choy, Frederick J Cassels, Peter J Hotez, Maria Elena Bottazzi, Christopher B Fox

Faculty, Staff and Students Publications

INTRODUCTION: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.) route has been shown to improve protective mucosal responses in comparison to intramuscular (i.m.) delivery. As we gain knowledge of the limitations of existing vaccines, it is of interest to understand if changes in product presentation or combinations of multiple vaccine modalities can further improve immunological outcomes.

METHODS: We investigated a commercial-stage SARS-CoV-2 receptor binding domain (RBD) antigen adjuvanted with a clinical-stage TLR-7/8 agonist …

International Society For Pediatric And Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive …

Sccad: Cluster Decomposition-Based Anomaly Detection For Rare Cell Identification In Single-Cell Expression Data, Yunpei Xu, Shaokai Wang, Qilong Feng, Jiazhi Xia, Yaohang Li, Hong-Dong Li, Jianxin Wang

Computer Science Faculty Publications

Single-cell RNA sequencing (scRNA-seq) technologies have become essential tools for characterizing cellular landscapes within complex tissues. Large-scale single-cell transcriptomics holds great potential for identifying rare cell types critical to the pathogenesis of diseases and biological processes. Existing methods for identifying rare cell types often rely on one-time clustering using partial or global gene expression. However, these rare cell types may be overlooked during the clustering phase, posing challenges for their accurate identification. In this paper, we propose a Cluster decomposition-based Anomaly Detection method (scCAD), which iteratively decomposes clusters based on the most differential signals in each cluster to effectively separate …

Triphlapan: Predicting Hla Molecules Binding Peptides Based On Triple Coding Matrix And Transfer Learning, Meng Wang, Chuqi Lei, Jianxin Wang, Yaohang Li, Min Li

Computer Science Faculty Publications

Human leukocyte antigen (HLA) recognizes foreign threats and triggers immune responses by presenting peptides to T cells. Computationally modeling the binding patterns between peptide and HLA is very important for the development of tumor vaccines. However, it is still a big challenge to accurately predict HLA molecules binding peptides. In this paper, we develop a new model TripHLApan for predicting HLA molecules binding peptides by integrating triple coding matrix, BiGRU + Attention models, and transfer learning strategy. We have found the main interaction site regions between HLA molecules and peptides, as well as the correlation between HLA encoding and binding …

Hite: A Fast And Accurate Dynamic Boundary Adjustment Approach For Full-Length Transposable Element Detection And Annotation, Kang Hu, Peng Ning, Minghua Xu, You Zou, Jianye Chang, Xin Gao, Yaohang Li, Jue Ruan, Bin Hu, Jianxin Wang

Computer Science Faculty Publications

Recent advancements in genome assembly have greatly improved the prospects for comprehensive annotation of Transposable Elements (TEs). However, existing methods for TE annotation using genome assemblies suffer from limited accuracy and robustness, requiring extensive manual editing. In addition, the currently available gold-standard TE databases are not comprehensive, even for extensively studied species, highlighting the critical need for an automated TE detection method to supplement existing repositories. In this study, we introduce HiTE, a fast and accurate dynamic boundary adjustment approach designed to detect full-length TEs. The experimental results demonstrate that HiTE outperforms RepeatModeler2, the state-of-the-art tool, across various species. Furthermore, …

It Is Time To Screen For Homozygous Familial Hypercholesterolemia In The United States, Sarah De Ferranti, Lisa Hudgins, Allison Jamison, Mary P Mcgowan, Amy L Peterson, Robert D Steiner, Melissa K Uveges, Yunshu Wang

Faculty, Staff and Students Publications

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated.

Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9–11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive …

Assessing The Potential Of Gpt-4 To Perpetuate Racial And Gender Biases In Health Care: A Model Evaluation Study, Jorge A Rodriguez, Leo Anthony Celi, Judy Gichoya, Dan Jurafsky, Peter Szolovits, David W Bates, Raja-Elie E Abdulnour, Atul J Butte, Emily Alsentzer

Faculty, Staff and Students Publications

Background: Large language models (LLMs) such as GPT-4 hold great promise as transformative tools in health care, ranging from automating administrative tasks to augmenting clinical decision making. However, these models also pose a danger of perpetuating biases and delivering incorrect medical diagnoses, which can have a direct, harmful impact on medical care. We aimed to assess whether GPT-4 encodes racial and gender biases that impact its use in health care.

Methods: Using the Azure OpenAI application interface, this model evaluation study tested whether GPT-4 encodes racial and gender biases and examined the impact of such biases on four potential applications …