Medicine and Health Sciences Commons^™

Systematic Computer-Aided Disulfide Design As A General Strategy To Stabilize Prefusion Class I Fusion Proteins, Karen J Gonzalez, Kevin C Yim, Jorge C G Blanco, Marina S Boukhvalova, Eva-Maria Strauch

2020-Current year OA Pubs

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricate task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric …

Unmet Patient Needs In Monocarboxylate Transporter 8 (Mct8) Deficiency: A Review, Andrew J Bauer, Bethany Auble, Amy L Clark, Tina Y Hu, Amber Isaza, Kyle P Mcnerney, Daniel L Metzger, Lindsey Nicol, Samuel R Pierce, Richard Sidlow

2020-Current year OA Pubs

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the

Isoflurane Conditioning Improves Functional Outcomes After Peripheral Nerve Injury In A Sciatic Cut Repair Murine Model, Yameng Xu, Ying Yan, Gregory J Zipfel, Matthew Macewan, Wilson Z Ray, Umeshkumar Athiraman

2020-Current year OA Pubs

INTRODUCTION: Anesthetic conditioning has been shown to provide neuroprotection in several neurological disorders. Whether anesthetic conditioning provides protection against peripheral nerve injuries remains unknown. The aim of our current study is to investigate the impact of isoflurane conditioning on the functional outcomes after peripheral nerve injury (PNI) in a rodent sciatic nerve injury model.

METHODS: Adult male Lewis rats underwent sciatic nerve cut and repair and exposed to none (Group 1, sham), single isoflurane exposure (Group 2), three-time isoflurane exposure (Group 3), and six-time isoflurane exposure (Group 4). Isoflurane conditioning was established by administration of 2% isoflurane for 1 hour, …

Co-Occurring Autism, Adhd, And Gender Dysphoria In Children, Adolescents, And Young Adults With Eating Disorders: An Examination Of Pre- Vs. Post-Covid Pandemic Outbreak Trends With Real-Time Electronic Health Record Data, Tashalee R Brown, Madeline O Jansen, A Ning Zhou, Dominic Moog, Hui Xie, Katherine V Liebesny, Kevin Y Xu, Binx Y Lin, Wisteria Y Deng

2020-Current year OA Pubs

BACKGROUND: Incidence rates of autism, attention-deficit/hyperactivity disorder (ADHD), and gender dysphoria (GD) are rising not only in the general population, but particularly among children, adolescents, and young adults with eating disorders (EDs). While ED rates have risen during the COVID pandemic, trends in co-occurring autism, ADHD, and GD have yet to be investigated in detail or at scale by way of large electronic medical record data.

OBJECTIVES: To investigate trends in rates of co-occurring autism, ADHD, and GD among children, adolescents, and young adults with EDs in years prior to and during the COVID-19 pandemic.

METHODS: We utilized a de-identified …

Case Report: Deep Sequencing And Long-Read Genome Sequencing Refine Prior Genetic Analyses In Families With Apparent Gonadal Mosaicism In Pik3cd-Related Activated Pi3k Delta Syndrome, Halyn Orellana, Alex Paul, Nermina Saucier, Megan Cooper, Et Al.

2020-Current year OA Pubs

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently

Assessment Of Sociodemographic And Psychiatric Characteristics Of Transgender Adults Seen At A Midwest Tertiary Medical Center, Samuel Cortez, Dominic Moog, Elizabeth Baranski, Kelley Williams, Jinli Wang, Ginger Nicol, Thomas Baranski, Cynthia J Herrick

2020-Current year OA Pubs

BACKGROUND: The National Academy of Medicine has formally identified transgender adults as an understudied population in critical need of health research. While national surveys, like the US Transgender survey, have characterized higher rates of depression, anxiety, suicidality and socioeconomic need in the transgender community, studies have not examined the impact of sociodemographic and clinical characteristics on mental health related outcomes.

OBJECTIVE: To describe the sociodemographic and mental health characteristics of transgender adults seen at a large Midwest transgender clinic and to determine factors associated with self-reported mental health conditions.

METHODS: Descriptive, retrospective, cross-sectional study of new transgender patients 18 years …

Recarving The Future: Bridging Car T-Cell Therapy Gaps With Synthetic Biology, Engineering, And Economic Insights, Alaa Ali, John F Dipersio

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and …

Molecular Characterization Of Gliomas And Glioneuronal Tumors Amid Noonan Syndrome: Cancer Predisposition Examined, Margaret Shatara, Mohamed S Abdelbaki, Et Al

2020-Current year OA Pubs

INTRODUCTION: In the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease.

METHODS: Within an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease-germline comparator exome analysis, RNA sequencing, and tumor classification …

Changing Hearts And Minds: Theorizing How, When, And Under What Conditions Three Social Influence Implementation Strategies Work, Bryan J Weiner, Rosemary D Meza, Predrag Klasnja, Rebecca Lengnick-Hall, Gretchen J Buchanan, Aaron R Lyon, Kayne D Mettert, Marcella H Boynton, Byron J Powell, Cara C Lewis

2020-Current year OA Pubs

BACKGROUND: Opinion leadership, educational outreach visiting, and innovation championing are commonly used strategies to address barriers to implementing innovations and evidence-based practices in healthcare settings. Despite voluminous research, ambiguities persist in how these strategies work and under what conditions they work well, work poorly, or work at all. The current paper develops middle-range theories to address this gap.

METHODS: Conceptual articles, systematic reviews, and empirical studies informed the development of causal pathway diagrams (CPDs). CPDs are visualization tools for depicting and theorizing about the causal process through which strategies operate, including the mechanisms they activate, the barriers they address, and …

Role Of Endogenous T1Ρ And Its Dispersion Imaging In Differential Diagnosis Of Cardiac Amyloidosis, Keyan Wang, Yong Zhang, Wenbo Zhang, Hongrui Jin, Jing An, Jingliang Cheng, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Cardiovascular magnetic resonance (CMR) has demonstrated excellent performance in the diagnosis of cardiac amyloidosis (CA). However, misdiagnosis occasionally occurs because the morphological and functional features of CA are non-specific. This study was performed to determine the value of non-contrast CMR T1ρ in the diagnosis of CA.

METHODS: This prospective study included 45 patients with CA, 30 patients with hypertrophic cardiomyopathy (HCM), and 10 healthy controls (HCs). All participants underwent cine (whole heart), T1ρ mapping, pre- and post-contrast T1 mapping imaging (three slices), and late gadolinium enhancement using a 3T whole-body magnetic resonance imaging system. All participants underwent T1ρ at …

Preteen Suicide Risk Screening In The Pediatric Outpatient Setting: A Clinical Pathway, Laura Hennefield, Ellen-Ge Denton, Peggy G Chen, Arielle H Sheftall, Lynsay Ayer

2020-Current year OA Pubs

We are in a youth mental health crisis with unprecedented and staggeringly high rates of suicidal ideations and suicide behaviors in preteens. In the United States, 14.5% of children aged 9-10 have experienced suicidal thoughts and behaviors, including 1.3% with a suicide attempt. American Academy of Pediatrics guidelines call for universal suicide risk screening of youth aged 12 years and older during preventative health care visits and screening in preteens aged 8-11 years when clinically indicated. However, what constitutes a clinical indication at 8-11 years can be difficult to systematically detect, and pediatric practitioners may not be equipped with necessary …

First-In-Human Assessment Of Gut Permeability In Crohn's Disease Patients Using Fluorophore Technology, Lori R Holtz, B Darren Nix, Sewuese E Akuse, Carla Hall-Moore, Rodney D Newberry, Matthew A Ciorba, Parakkal Deepak, Maria Zulfiqar, Jeng-Jong Shieh, James R Johnson, I Rochelle Riley, Richard B Dorshow

2020-Current year OA Pubs

BACKGROUND AND AIMS: The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn's disease (CD).

METHODS: We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 …

Usability Testing Of A Web Tool For Dissemination And Implementation Science Models, Rebekah Natalie Gomes, Bryan S Ford, Rachel G Tabak, Ross C Brownson, Sara Malone, Maggie Padek, Russell E Glasgow, Borsika Rabin

2020-Current year OA Pubs

UNLABELLED: Dissemination and Implementation science is dedicated to increasing the speed of evidence-based research translated into practice as guided by one or multiple D&I theories, models, and frameworks. The Dissemination and Implementation Models in Health Research and Practice web tool guides users on how to plan, select, combine, adapt, use, and assess theories, models, and frameworks. This paper describes usability testing to update the web tool. Iterative user testing was conducted with implementation science research and clinical participants to facilitate updates and optimize the functionality of the tool. A multi-step protocol involved quantitative and qualitative data collection including a survey, …

Tourette Syndrome Research Highlights From 2023 [Version 2; Peer Review: 3 Approved], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Mol Debes, Simon Morand-Beaulieu, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers.

Stat1 Employs Myeloid Cell-Extrinsic Mechanisms To Regulate The Neutrophil Response And Provide Protection Against Invasive Klebsiella Pneumoniae Lung Infection, Shekina Gonzalez-Ferrer, Zeyu Xiong, Atish Gheware, Janet S Lee, Et Al.

2020-Current year OA Pubs

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread …

Efficacy And Health-Related Quality Of Life Impact Of Fecal Microbiota, Live-Jslm: A Post Hoc Analysis Of Punch Cd3 Patients At First Recurrence Of Clostridioides Difficile Infection, Paul Feuerstadt, Jessica R Allegretti, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana Garcia-Horton, Mirko Fillbrunn, Glenn Tillotson, Lindy L Bancke, Kerry Laplante, Kevin W Garey, Sahil Khanna

2020-Current year OA Pubs

INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3.

METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea …

Cep120 Is Essential For Kidney Stromal Progenitor Cell Growth And Differentiation, Ewa Langner, Tao Cheng, Eirini Kefaloyianni, Charles Gluck, Baolin Wang, Moe R Mahjoub

2020-Current year OA Pubs

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the ciliopathy gene Cep120, which is essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of interstitial lineages including pericytes, fibroblasts and mesangial cells. These phenotypes were caused by a combination of delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, …

Disruption Of The Nascent Polypeptide-Associated Complex Leads To Reduced Polyglutamine Aggregation And Toxicity, Leeran B. Dublin-Ryan, Ankan K. Bhadra, Heather L. True

2020-Current year OA Pubs

The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone complex that binds near the ribosome exit tunnel and is the first point of chaperone contact for newly synthesized proteins. Deletion of the NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown that the deletion of the NAC rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize that NAC disruption would improve viability in cells expressing human misfolding proteins. Here, we show that NAC disruption improves viability in cells expressing expanded polyglutamine and also leads to delayed and reduced aggregation of expanded polyglutamine and changes …

Characterization And Individual-Level Prediction Of Cognitive State In The First Year After 'Mild' Stroke, Juan Pablo Saa, Tamara Tse, Gerald Choon-Huat Koh, Philip Yap, Carolyn M. Baum, David E. Uribe-Rivera, Saras M. Windecker, Henry Ma, Stephen M. Davis, Geoffrey A. Donnan, Leeanne M. Carey

2020-Current year OA Pubs

BACKGROUND: Mild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.

METHODS: In this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCA<24 points) were compared between assessment time-points. Trajectory clusters were identified using variations of ≥1 point in MoCA scores. To further compare clusters, additional assessments administered at 3- and 12-months were included. Gamma and Quantile mixed-effects regression were used to predict individual MoCA scores over time, using baseline clinical and demographic variables. Model predictions were fitted for each stroke survivor and evaluated using model cross-validation to identify the overall best predictors of cognitive recovery.

RESULTS: Participants' (n = 119) MoCA scores improved from baseline to 3-months …

Translatability Of Findings From Cynomolgus Monkey To Human Suggests A Mechanistic Role For Il-21 In Promoting Immunogenicity To An Anti-Pd-1/Il-21 Mutein Fusion Protein, Mark A Kroenke, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were …

Graceful Gait: Virtual Ballet Classes Improve Mobility And Reduce Falls More Than Wellness Classes For Older Women, Elinor C Harrison, Allison M Haussler, Lauren E Tueth, Sidney T Baudendistel, Gammon M Earhart

2020-Current year OA Pubs

INTRODUCTION: Dance is an effective and motivating form of exercise for older women, but few studies have quantified the benefits of virtual dance classes nor, specifically, ballet. This study tested the effectiveness of virtual ballet compared to virtual wellness classes, with the goal of reaching underserved populations. It is among the first to explore the effects of virtual classical ballet on functional gait mobility, balance, and quality of life measures in older women.

METHODS: Older women were recruited in two waves and randomized to two groups: a ballet class modified for older adults and a wellness-based control class. Both groups …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Samuel Klein, Et Al.

2020-Current year OA Pubs

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

The Ithildin Library For Efficient Numerical Solution Of Anisotropic Reaction-Diffusion Problems In Excitable Media, Desmond Kabus, Marie Cloet, Christian Zemlin, Olivier Bernus, Hans Dierckx

2020-Current year OA Pubs

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this …

Janus Kinase Inhibition In The Treatment And Prevention Of Graft-Versus-Host Disease, Elisa De Togni, Oladipo Cole, Ramzi Abboud

2020-Current year OA Pubs

Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For many years, corticosteroids have been the mainstay treatment for GVHD, but cases of steroid-refractory GVHD and the severe adverse effects of high-dose corticosteroids have increased the need for preventative and therapeutic strategies for GVHD. Due to the nature of alloreactive T cells, GVHD is inherently linked to the graft-versus-leukemia (GVL) effect, the therapeutic driving force behind stem cell transplantation. A considerable clinical challenge is to preserve GVL while suppressing GVHD. The field of GVHD research has greatly expanded over the past …

Analyses Of Patients Who Self-Administered Diazepam Nasal Spray For Acute Treatment Of Seizure Clusters, Sunita N Misra, Michael R Sperling, Vikram R Rao, Jurriaan M Peters, Patricia Penovich, James Wheless, R Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase …

Predicting Cognitive Decline: Which Is More Useful, Baseline Amyloid Levels Or Longitudinal Change?, Gengsheng Chen, Nicole S Mckay, Brian A Gordon, Jingxia Liu, Nelly Joseph-Mathurin, Suzanne E Schindler, Jason Hassenstab, Andrew J Aschenbrenner, Qing Wang, Stephanie A Schultz, Yi Su, Pamela J Lamontagne, Sarah J Keefe, Parinaz Massoumzadeh, Carlos Cruchaga, Chengjie Xiong, John C Morris, Tammie L S Benzinger

2020-Current year OA Pubs

The use of biomarkers for the early detection of Alzheimer's disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.,2021). However, it is still unclear whether longitudinal Aβ-PET may have additional value for predicting time to cognitive impairment in AD. The current study aims to evaluate the ability of baseline- versus longitudinal rate of change in-

Everything But The Kitchen Sink: An Analysis Of Bacterial And Chemical Contaminants Found In Syringe Residue From People Who Inject Drugs, John A Wildenthal, Drew J Schwartz, Nathanial S Nolan, Lingxia Zhao, John I Robinson, Erin Jones, Raagini Jawa, Jeffrey P Henderson, Laura R Marks

2020-Current year OA Pubs

BACKGROUND: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants.

METHODS: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography-mass spectrometry.

RESULTS: Bacteria were cultured from 58.75% of 160 syringes …

Sc2menetdrug: A Computational Tool To Uncover Inter-Cell Signaling Targets And Identify Relevant Drugs Based On Single Cell Rna-Seq Data, Jiarui Feng, S. Peter Goedegebuure, Amanda Zeng, Ye Bi, Ting Wang, Philip Payne, Li Ding, David Denardo, William Hawkins, Ryan C. Fields, Fuhai Li

2020-Current year OA Pubs

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling …

Ddr2-Regulated Arginase Activity In Ovarian Cancer-Associated Fibroblasts Promotes Collagen Production And Tumor Progression, Favour A Akinjiyan, Zainab Ibitoye, Peinan Zhao, Leah P Shriver, Gary J Patti, Gregory D Longmore, Katherine C Fuh

2020-Current year OA Pubs

Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, …

Patient-Reported Treatment Response In Chronic Graft-Versus-Host Disease, Annie Im, Iskra Pusic, Et Al.

2020-Current year OA Pubs

Chronic graft-versus-host disease (GvHD) treatment response is assessed using National Institutes of Health (NIH) Consensus Criteria in clinical trials, and by clinician assessment in routine practice. Patient-reported treatment response is central to the experience of chronic GvHD manifestations as well as treatment benefit and toxicity, but how they correlate with clinician- or NIH-responses has not been well-studied. We aimed to characterize 6-month patientreported response, determine associated chronic GvHD baseline organ features and changes, and evaluate which patientreported quality of life and chronic GvHD symptom burden measures correlated with patient-reported response. From two nationally representative Chronic GVHD Consortium prospective observational studies, …