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Landscape Of Pharmacogenetic Variants Associated With Non-Insulin Antidiabetic Drugs In The Indian Population, Ambily Sivadas, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Arpita Mukhopadhyay, Greg Gibson, Km Venkat Narayan, Sridhar Sivasubbu, Vinod Scaria, Anura V Kurpad

Faculty, Staff and Student Publications

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.

RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with …

Distributed Neural Representations Of Conditioned Threat In The Human Brain, Zhenfu Wen, Edward F Pace-Schott, Sara W Lazar, Jörgen Rosén, Fredrik Åhs, Elizabeth A Phelps, Joseph E Ledoux, Mohammed R Milad

Faculty, Staff and Student Publications

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety …

Author Correction: Hypomorphic Brca2 And Rad51c Double Mutant Mice Display Fanconi Anemia, Cancer And Polygenic Replication Stress, Karl-Heinz Tomaszowski, Sunetra Roy, Carolina Guerrero, Poojan Shukla, Caezaan Keshvani, Yue Chen, Martina Ott, Xiaogang Wu, Jianhua Zhang, Courtney D Dinardo, Detlev Schindler, Katharina Schlacher

Faculty, Staff and Student Publications

No abstract provided.

Incidence And Risk Factors Of Early Onset Vod/Sos Differ In Younger Vs Older Adults After Stem Cell Transplantation, Curtis Marcoux, Rima M Saliba, Whitney Wallis, Sajad Khazal, Dristhi Ragoonanan, Gabriela Rondon, Priti Tewari, Uday Popat, Betul Oran, Amanda Olson, Qaiser Bashir, Muzaffar Qazilbash, Amin Alousi, Chitra Hosing, Yago Nieto, Gheath Alatrash, David Marin, Katayoun Rezvani, Issa Khouri, Samer Srour, Richard Champlin, Elizabeth Shpall, Partow Kebriaei

Faculty, Staff and Student Publications

Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Although increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with posttransplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single-center analysis of adult patients aged ≥18 years undergoing allo-SCT (N = 1561) using predominately PTCy as graft-versus-host disease (GVHD) prophylaxis (72%). We found a higher rate of VOD at 16.8% (20 of 119) in those aged ≤25 years compared with 3.8% (55 of 1442) in those aged >25 years, with unique predictors …

A Biogeographical Appraisal Of The Threatened South East Africa Montane Archipelago Ecoregion, Julian Bayliss, Gabriela B Bittencourt-Silva, William R Branch, Carl Bruessow, Steve Collins, T Colin E Congdon, Werner Conradie, Michael Curran, Savel R Daniels, Iain Darbyshire, Harith Farooq, Lincoln Fishpool, Geoffrey Grantham, Zacharia Magombo, Hermenegildo Matimele, Ara Monadjem, Jose Monteiro, Jo Osborne, Justin Saunders, Paul Smith, Claire N Spottiswoode, Peter J Taylor, Jonathan Timberlake, Krystal A Tolley, Érica Tovela, Philip J Platts

Faculty, Staff and Student Publications

Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the 'South East Africa Montane Archipelago' (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates …

Evaluation Of Treatment Parameters For Focused-Extracorporeal Shock Wave Therapy In Knee Osteoarthritis Patients With Bone Marrow Lesions: A Pilot Study, Hani Al-Abbad, Jacqueline E Reznik, Erik Biros, Bruce Paulik, Rob Will, Samuel Gane, Penny Moss, Anthony Wright

Faculty, Staff and Student Publications

OBJECTIVES: To evaluate the effect of different dosage parameters of focused-extracorporeal shock wave therapy on pain and physical function in knee osteoarthritis patients with bone marrow lesions. In addition, to investigate pathophysiological changes based on imaging and biomarker measures.

METHODS: Using a single-case experimental design, a total of 12 participants were randomly allocated in 4 equal groups of 3 to receive different dosages of focused-extracorporeal shock wave therapy. Each group received either 4 or 6 sessions of 1500 or 3000 shocks over 4 or 6 weekly sessions. Participants underwent repeated measurements during the baseline, intervention, and post-intervention phases for Western …

Draft Genome Sequences Of Pseudomonas Strains Zfem001–005 Isolated From The Intestine Of Larval Zebrafish Danio Rerio, Sabona B Simbassa, Justin Clark, Keiko Salazar, Anthony Maresso, Anne-Marie Krachler

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Here, we report the draft genome sequences of Pseudomonas strains zfem001–005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

Automating Data Analysis For Hydrogen/Deuterium Exchange Mass Spectrometry Using Data-Independent Acquisition Methodology, Frantisek Filandr, Vladimir Sarpe, Shaunak Raval, D Alex Crowder, Morgan F Khan, Pauline Douglas, Stephen Coales, Rosa Viner, Aleem Syed, John A Tainer, Susan P Lees-Miller, David C Schriemer

Faculty, Staff and Student Publications

We present a hydrogen/deuterium exchange workflow coupled to tandem mass spectrometry (HX-MS2) that supports the acquisition of peptide fragment ions alongside their peptide precursors. The approach enables true auto-curation of HX data by mining a rich set of deuterated fragments, generated by collisional-induced dissociation (CID), to simultaneously confirm the peptide ID and authenticate MS1-based deuteration calculations. The high redundancy provided by the fragments supports a confidence assessment of deuterium calculations using a combinatorial strategy. The approach requires data-independent acquisition (DIA) methods that are available on most MS platforms, making the switch to HX-MS2 straightforward. Importantly, we find that HX-DIA enables …

Urban-Rural Differences In School Districts' Local Wellness Policies And Policy Implementation Environments, Swati Iyer, Timothy J Walker, Alexandra L Macmillan Uribe, Chad D Rethorst, Rebecca A Seguin-Fowler, Jacob Szeszulski

Faculty, Staff and Student Publications

Higher rates of obesity in rural compared to urban districts suggest environmental differences that affect student health. This study examined urban-rural differences in districts' local wellness policies (LWPs) and LWP implementation environments. Cross-sectional data from two assessments in Texas were analyzed. In assessment one, each district's LWP was reviewed to see if 16 goals were included. In assessment two, an audit was conducted to identify the presence of a wellness plan (a document with recommendations for implementing LWPs), triennial LWP assessment, and school health advisory councils (SHACs) on the district website. Rural districts' LWPs had a smaller number of total …

Immune Heterogeneity In Small-Cell Lung Cancer And Vulnerability To Immune Checkpoint Blockade, Barzin Y Nabet, Habib Hamidi, Myung Chang Lee, Romain Banchereau, Stefanie Morris, Leah Adler, Velimir Gayevskiy, Ahmed M Elhossiny, Minu K Srivastava, Namrata S Patil, Kiandra A Smith, Rajiv Jesudason, Caleb Chan, Patrick S Chang, Matthew Fernandez, Sandra Rost, Lisa M Mcginnis, Hartmut Koeppen, Carl M Gay, John D Minna, John V Heymach, Joseph M Chan, Charles M Rudin, Lauren A Byers, Stephen V Liu, Martin Reck, David S Shames

Faculty, Staff and Student Publications

Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I). Deeper investigation into the immune heterogeneity uncovers two subsets with differing neuroendocrine (NE) versus non-neuroendocrine (non-NE) phenotypes, demonstrating immune cell infiltration hallmarks. The NE tumors with low tumor-associated macrophage (TAM) but …

Learning From The Implementation Of A Surgical Opioid Reduction Initiative In An Integrated Health System: A Qualitative Study Among Providers And Patients, Willemijn L A Schäfer, Julie K Johnson, Meagan S Ager, Cassandra B Iroz, Reiping Huang, Salva N Balbale, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Surgical opioid overprescribing can result in long-term use or misuse. Between July 2018 and March 2019, the multicomponent intervention, Minimizing Opioid Prescribing in Surgery (MOPiS) was implemented in the general surgery clinics of five hospitals and successfully reduced opioid prescribing. To date, various studies have shown a positive outcome of similar reduction initiatives. However, in addition to evaluating the impact on clinical outcomes, it is important to understand the implementation process of an intervention to extend sustainability of interventions and allow for dissemination of the intervention into other contexts. This study aims to evaluate the contextual factors impacting intervention …

Metabolomic Profiles In Jamaican Children With And Without Autism Spectrum Disorder, Akram Yazdani, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Amirali Tahanan, Megan L Grove, Tanja Gangnus, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls.

OBJECTIVE: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. …

Nanofibrous Multidomain Peptide Hydrogels Provide T Cells A 3d, Cytocompatible Environment For Cell Expansion And Antigen-Specific Killing, Viridiana Leyva-Aranda, Shailbala Singh, Maria J Telesforo, Simon Young, Cassian Yee, Jeffrey D Hartgerink

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T cells have the ability to recognize and kill specific target cells, giving therapies based on their potential for treating infection, diabetes, cancer, and other diseases. However, the advancement of T cell-based treatments has been hindered by difficulties in their ex vivo activation and expansion, the number of cells required for sustained in vivo levels, and preferential localization following systemic delivery. Biomaterials may help to overcome many of these challenges by providing a combined means of proliferation, antigen presentation, and cell localization upon delivery. In this work, we studied self-assembling Multidomain Peptides (MDPs) as scaffolds for T cell culture, activation, …

Methodological Advances In Patient-Centered Rare Disease Research: The Uthealth Houston Turner Syndrome Society Of The United States Research Registry, Sara Mansoorshahi, Cindy Scurlock, Scientific Advisory Board Of The Turner Syndrome Society Of The United States Research Registry, Siddharth K Prakash

Faculty, Staff and Student Publications

BACKGROUND: Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers.

RESULTS: To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston …

High Response Rate With Extended Dosing Of Cemiplimab In Advanced Cutaneous Squamous Cell Carcinoma, Danny Rischin, Brett G M Hughes, Nicole Basset-Séguin, Dirk Schadendorf, Samantha Bowyer, Sabiha Trabelsi Messai, Friedegund Meier, Thomas K Eigentler, Victoria Casado Echarren, Brian Stein, Marie Beylot-Barry, Sophie Dalac, Brigitte Dréno, Michael R Migden, Axel Hauschild, Chrysalyne D Schmults, Annette M Lim, Suk-Young Yoo, Anne J Paccaly, Apostolos Papachristos, Jenny-Hoa Nguyen, Emmanuel Okoye, Frank Seebach, Jocelyn Booth, Israel Lowy, Matthew G Fury, Alexander Guminski

Faculty, Staff and Student Publications

BACKGROUND: Cemiplimab (Libtayo

METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review.

RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n

CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W …

Ape-Gen20: Expanding Rapid Class I Peptide-Major Histocompatibility Complex Modeling To Post-Translational Modifications And Noncanonical Peptide Geometries, Romanos Fasoulis, Mauricio M Rigo, Gregory Lizée, Dinler A Antunes, Lydia E Kavraki

Faculty, Staff and Student Publications

The recognition of peptides bound to class I major histocompatibility complex (MHC-I) receptors by T-cell receptors (TCRs) is a determinant of triggering the adaptive immune response. While the exact molecular features that drive the TCR recognition are still unknown, studies have suggested that the geometry of the joint peptide–MHC (pMHC) structure plays an important role. As such, there is a definite need for methods and tools that accurately predict the structure of the peptide bound to the MHC-I receptor. In the past few years, many pMHC structural modeling tools have emerged that provide high-quality modeled structures in the general case. …

Toward Generalizable Machine Learning Models In Speech, Language, And Hearing Sciences: Estimating Sample Size And Reducing Overfitting, Hamzeh Ghasemzadeh, Robert E Hillman, Daryush D Mehta

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PURPOSE: Many studies using machine learning (ML) in speech, language, and hearing sciences rely upon cross-validations with single data splitting. This study's first purpose is to provide quantitative evidence that would incentivize researchers to instead use the more robust data splitting method of nested

METHOD: First, the significant impact of different cross-validations on ML outcomes was demonstrated using real-world clinical data. Then, Monte Carlo simulations were used to quantify the interactions among the employed cross-validation method, the discriminative power of features, the dimensionality of the feature space, the dimensionality of the model, and the sample size. Four different cross-validation methods …

Grb2 Stabilizes Rad51 At Reversed Replication Forks Suppressing Genomic Instability And Innate Immunity Against Cancer, Zu Ye, Shengfeng Xu, Yin Shi, Xueqian Cheng, Yuan Zhang, Sunetra Roy, Sarita Namjoshi, Michael A Longo, Todd M Link, Katharina Schlacher, Guang Peng, Dihua Yu, Bin Wang, John A Tainer, Zamal Ahmed

Faculty, Staff and Student Publications

Growth factor receptor-bound protein 2 (GRB2) is a cytoplasmic adapter for tyrosine kinase signaling and a nuclear adapter for homology-directed-DNA repair. Here we find nuclear GRB2 protects DNA at stalled replication forks from MRE11-mediated degradation in the BRCA2 replication fork protection axis. Mechanistically, GRB2 binds and inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks. In GRB2-depleted cells, PARP inhibitor (PARPi) treatment releases DNA fragments from stalled forks into the cytoplasm that activate the cGAS-STING pathway to trigger pro-inflammatory cytokine production. Moreover in a syngeneic mouse metastatic ovarian cancer model, GRB2 depletion in the context of PARPi treatment …

The Acceptance And Use Of Digital Technologies For Self-Reporting Medication Safety Events After Care Transitions To Home In Patients With Cancer: Survey Study, Yun Jiang, Misun Hwang, Youmin Cho, Christopher R Friese, Sarah T Hawley, Milisa Manojlovich, John C Krauss, Yang Gong

Faculty, Staff and Student Publications

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in …

Observation On Efficacy And Underlying Mechanism Of Cheek Acupuncture On Ovulation Induction For Infertile Women With Pcos: Case Series, Yi Yang, Lihua Jin, Shasha Xu, Huijun Ye, Xi Luo, Ruilan Li, Yuebing Yue

Faculty, Staff and Student Publications

RATIONALE: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth …

Transmembrane Domain-Driven Pd-1 Dimers Mediate T Cell Inhibition, Elliot A Philips, Jia Liu, Audun Kvalvaag, Alexander M Mørch, Anna S Tocheva, Charles Ng, Hong Liang, Ian M Ahearn, Ruimin Pan, Christina C Luo, Alexander Leithner, Zhihua Qin, Yong Zhou, Antonio Garcia-España, Adam Mor, Dan R Littman, Michael L Dustin, Jun Wang, Xiang-Peng Kong

Faculty, Staff and Student Publications

Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers, but PD-1 has been considered monomeric. Here, we show that PD-1 and its ligands form dimers as a consequence of transmembrane domain interactions and that propensity for dimerization correlates with the ability of PD-1 to inhibit immune responses, antitumor …

Commentary On 2022 Guidelines On Clinical Trial Design In Cluster Headache And Further Suggestions, Ioana Medrea, Stewart J Tepper, Donliang Wang, Paul G Mathew, Mark Burish

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BACKGROUND: New guidelines for cluster headache clinical trials were recently published. We welcome these new guidelines and raise additional considerations in trial methodologies.

MAIN BODY: We present non-inferiority trials to overcome ethical issues with placebo use, and additionally discuss issues with trial recruitment.

CONCLUSIONS: We highlight some possible issues and solutions to be considered with the recently published cluster headache trial guidelines.

Final Results Of Urelumab, An Anti-Cd137 Agonist Monoclonal Antibody, In Combination With Cetuximab Or Nivolumab In Patients With Advanced Solid Tumors, Nikhil I Khushalani, Patrick A Ott, Robert L Ferris, Tina Cascone, Dirk Schadendorf, Dung T Le, Manish R Sharma, Fabrice Barlesi, William Sharfman, Jason J Luke, Ignacio Melero, Deanne Lathers, Jaclyn Neely, Satyendra Suryawanshi, Abanti Sanyal, James L Holloway, Rasika Suryawanshi, Scott Ely, Neil H Segal

Faculty, Staff and Student Publications

BACKGROUND: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors.

METHODS: CA186-018: Patients with metastatic colorectal cancer or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated in a dose-evaluation phase with urelumab 0.1 mg/kg (urelumab-0.1) every 3 weeks (Q3W)+cetuximab 250 mg/m

RESULTS: CA186-018: 66 patients received study treatment. The most frequent …

Rehabilitation Treatment Specification System For Voice Therapy: Application To Everyday Clinical Care, Jeremy Wolfberg, John Whyte, Patricia Doyle, Shirley Gherson, Jason Muise, Brian Petty, Carol Jorgensen Tolejano, Robert E Hillman, Tara Stadelman-Cohen, Jarrad H Van Stan

Faculty, Staff and Student Publications

PURPOSE: Rehabilitation intervention descriptions often do not explicitly identify active ingredients or how those ingredients lead to changes in patient functioning. The Rehabilitation Treatment Specification System (RTSS) provides guidance to identify the critical aspects of any rehabilitation therapy and supported the development of standardly named ingredients and targets in voice therapy (Rehabilitation Treatment Specification System for Voice Therapy [RTSS-Voice]). This study sought to test the content validity of the RTSS-Voice and determine if the RTSS-Voice can be used to identify commonalities and differences in treatment (criterion validity) across clinicians in everyday clinical practice.

METHOD: Five speech-language pathologists from different institutions …

Protein Biomarkers And Alternatively Methylated Cell-Free Dna Detect Early Stage Pancreatic Cancer, Roni Ben-Ami, Qiao-Li Wang, Jinming Zhang, Julianna G Supplee, Johannes F Fahrmann, Roni Lehmann-Werman, Lauren K Brais, Jonathan Nowak, Chen Yuan, Maureen Loftus, Ana Babic, Ehsan Irajizad, Tal Davidi, Aviad Zick, Ayala Hubert, Daniel Neiman, Sheina Piyanzin, Ofer Gal-Rosenberg, Amit Horn, Ruth Shemer, Benjamin Glaser, Natalia Boos, Kunal Jajoo, Linda Lee, Thomas E Clancy, Douglas A Rubinson, Kimmie Ng, John A Chabot, Fay Kastrinos, Michael Kluger, Andrew J Aguirre, Pasi A Jänne, Nabeel Bardeesy, Ben Stanger, Mark H O'Hara, Jacob Till, Anirban Maitra, Erica L Carpenter, Andrea J Bullock, Jeanine Genkinger, Samir M Hanash, Cloud P Paweletz, Yuval Dor, Brian M Wolpin

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.

Design: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.

Results: Comparative methylome analysis identified nine loci that were differentially …

Safety, Tolerability, And Dose-Limiting Toxicity Of Lacosamide In Patients With Painful Chronic Pancreatitis: Protocol For A Phase 1 Clinical Trial To Determine Safety And Identify Side Effects, Evan L Fogel, Jeffrey J Easler, Ying Yuan, Dhiraj Yadav, Darwin L Conwell, Santhi Swaroop Vege, Samuel Y Han, Walter Park, Vanessa Patrick, Fletcher A White

Faculty, Staff and Student Publications

Background: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control.

Objective: In this phase 1 trial, we aim to determine the safety, …

One Form And Two Functions: Mbd Of Setdb2 Is A Protein-Interacting Domain, Jujun Zhou, Taiping Chen, Xiaodong Cheng

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In this issue of Structure, Mahana et al.1 present their structural characterization of an annotated methyl-CpG-binding domain (MBD) from the histone H3 lysine 9 methyltransferase SETDB2. This study reveals that, rather than binding DNA as previously hypothesized, this domain instead interacts with a cystine-rich domain from C11orf46, highlighting its involvement in protein-protein interactions.

Deep Learning Model For Personalized Prediction Of Positive Mrsa Culture Using Time-Series Electronic Health Records, Masayuki Nigo, Laila Rasmy, Bingyu Mao, Bijun Sai Kannadath, Ziqian Xie, Degui Zhi

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Methicillin-resistant Staphylococcus aureus (MRSA) poses significant morbidity and mortality in hospitals. Rapid, accurate risk stratification of MRSA is crucial for optimizing antibiotic therapy. Our study introduced a deep learning model, PyTorch_EHR, which leverages electronic health record (EHR) time-series data, including wide-variety patient specific data, to predict MRSA culture positivity within two weeks. 8,164 MRSA and 22,393 non-MRSA patient events from Memorial Hermann Hospital System, Houston, Texas are used for model development. PyTorch_EHR outperforms logistic regression (LR) and light gradient boost machine (LGBM) models in accuracy (AUROC

Neuronal Npr-15 Modulates Molecular And Behavioral Immune Responses Via The Amphid Sensory Neuron-Intestinal Axis In C Elegans, Benson Otarigho, Anna Frances Butts, Alejandro Aballay

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The survival of hosts during infections relies on their ability to mount effective molecular and behavioral immune responses. Despite extensive research on these defense strategies in various species, including the model organism

Single-Cell Cd4 And Cd8 T-Cell Secretome Profiling Reveals Temporal And Niche Differences In Acute Myeloid Leukemia Following Immune Checkpoint Blockade Therapy, Jessica L Root, Poonam N Desai, Christopher Ly, Bofei Wang, Fatima Zahra Jelloul, Jing Zhou, Sean Mackay, Mansour Alfayez, Jairo Matthews, Sherry Pierce, Patrick K Reville, Naval Daver, Hussein A Abbas

Faculty, Staff and Student Publications

UNLABELLED: Acute myeloid leukemia (AML) is a heterogeneous malignancy of the blood primarily treated with intensive chemotherapy. The allogeneic T-cell antileukemic activity via donor lymphocyte infusions and stem cell transplantation suggests a potential role for checkpoint blockade therapy in AML. While clinical trials employing these treatments have fallen short of expected results, a deeper exploration into the functional states of T cells in AML could bridge this knowledge gap. In this study, we analyzed the polyfunctional activity of T cells in a cohort of patients with relapsed/refractory (RelRef) AML treated on the clinical trial (ClinicalTrials.gov identifier: NCT02397720) of combination therapy …