Medicine and Health Sciences Commons^™

Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, And Cost Of The Audiovisual-Assisted Therapeutic Ambience In Radiation Therapy Prospective Multi-Institutional Trial, Justin Oh, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost.

METHODS AND MATERIALS: The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, …

Evaluating The Interaction Between Hemorrhagic Transformation And Cerebral Edema On Functional Outcome After Ischemic Stroke, Amrit Avula, Quoc Bui, Atul Kumar, Yasheng Chen, Ali Hamzehloo, Julien Cifarelli, Laura Heitsch, Agnieszka Slowik, Daniel Strbian, Jin-Moo Lee, Rajat Dhar

2020-Current year OA Pubs

BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation.

METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately.

RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001].

CONCLUSIONS: Most stroke patients with HT also have measurable CED. …

Agreement Between Three Noninvasive Temperature Monitoring Devices During Spinal Anaesthesia For Caesarean Delivery: A Prospective Observational Study, D O Vawda, Christopher King, L Du Toit, R A Dyer, N J Masuku, D G Bishop

2020-Current year OA Pubs

Hypothermia during obstetric spinal anaesthesia is a common and important problem, yet temperature monitoring is often not performed due to the lack of a suitable, cost-effective monitor. This study aimed to compare a noninvasive core temperature monitor with two readily available peripheral temperature monitors during obstetric spinal anaesthesia. We undertook a prospective observational study including elective and emergency caesarean deliveries, to determine the agreement between affordable reusable surface temperature monitors (Welch Allyn SureTemp® Plus oral thermometer and the Braun 3-in-1 No Touch infrared thermometer) and the Dräger T-core© (using dual-sensor heat flux technology), in detecting thermoregulatory changes during obstetric spinal …

Generation Of An Induced Pluripotent Stem Cell Line (Biortci001-A) From A Healthy Adult Indigenous Nigerian Participant, Zaid Muhammad, Phoebe W Brown, Larema Babazau, Abdulrahman I Alkhamis, Baba W Goni, Haruna A Nggada, Kefas M Mbaya, Selina Wray, Isa H Marte, Celeste M Karch, Louise C Serpell, Mahmoud B Maina

2020-Current year OA Pubs

Genetic backgrounds influence cellular phenotypes, drug responses, and health outcomes, yet most human iPSC lines are derived from individuals of European descent, with lines from indigenous Africans particularly scarce. Addressing this gap, we generated iPSCs from dermal fibroblasts of a healthy 60-year-old indigenous Nigerian male of the Babur ethnic group using Sendai virus. The iPSC line displayed a normal karyotype, was characterized for pluripotency markers and differentiated into neural progenitor cells and astrocytes. To enhance African representation in research, this iPSC line will be available to the scientific community, with ongoing efforts focused on creating an open-access African iPSC biobank. …

Western Diet Reduces Small Intestinal Intraepithelial Lymphocytes Via Fxr-Interferon Pathway, Chen-Ting Hung, Changqing Ma, Santosh K Panda, Tihana Trsan, Miki Hodel, Jennifer Frein, Amanda Foster, Shengxiang Sun, Hung-Ting Wu, Justin Kern, Richa Mishra, Umang Jain, Marco Colonna, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL …

Metabolically Active Neutrophils Represent A Permissive Niche For Mycobacterium Tuberculosis, J Tucker Andrews, G V R Krishna Prasad, Jennifer A Philips, Et Al.

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils …

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …

Leveraging Gpt-4 For Identifying Cancer Phenotypes In Electronic Health Records: A Performance Comparison Between Gpt-4, Gpt-3.5-Turbo, Flan-T5, Llama-3-8b, And Spacy's Rule-Based And Machine Learning-Based Methods, Kriti Bhattarai, Inez Y Oh, Jonathan Moran Sierra, Jonathan Tang, Philip R O Payne, Zach Abrams, Albert M Lai

2020-Current year OA Pubs

OBJECTIVE: Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients' health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI's Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy.

MATERIALS AND METHODS: Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected …

Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: We aimed to develop and validate a novel multimodal framework

MATERIALS AND METHODS: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal …

Immune Checkpoint Markers And Tumour Mutation Burden In Wilms Tumour: A Study Of 59 Cases, Aidas J Mattis, Jie-Fu Chen, Ivan A Gonzalez, Rehan Rais, Louis P Dehner, John Pfeifer, Mai He

2020-Current year OA Pubs

Wilms tumour (WT) is the most common renal tumour in children, and studies of immune checkpoint inhibitors (ICIs) treatment and markers are limited in number. In this study we investigated the ICIs' related immune landscape by examining the expression of PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) proteins by immunohistochemistry (IHC), tumour mutation burden (TMB), and correlations with histology and clinical outcome. Positive PD-L1 (SP263) expression was defined as modified combined positive score (CPS) ≥1. A total of 59 WTs (from 2000 to 2017), including eight (14.0%) with anaplasia, from 46 patients were analysed (45 primary and 14 metastatic). …

Evaluation Of Forces Applied To Tissues During Robotic-Assisted Surgical Tasks Using A Novel Force Feedback Technology, Michael M Awad, Mathew C Raynor, Mika Padmanabhan-Kabana, Lana Y Schumacher, Jeffrey A Blatnik

2020-Current year OA Pubs

BACKGROUND: The absence of force feedback (FFB) is considered a technical limitation in robotic-assisted surgery (RAS). This pre-clinical study aims to evaluate the forces applied to tissues using a novel integrated FFB technology, which allows surgeons to sense forces exerted at the instrument tips.

METHODS: Twenty-eight surgeons with varying experience levels employed FFB instruments to perform three robotic-assisted surgical tasks, including retraction, dissection, and suturing, on inanimate or ex-vivo models, while the instrument sensors recorded and conveyed the applied forces to the surgeon hand controllers of the robotic system. Generalized Estimating Equations (GEE) models were used to analyze the mean …

Neuroimmune Interactions In The Development And Chronification Of Migraine Headache, Jintao Zhang, Roli Simoes, Tingting Guo, Yu-Qing Cao

2020-Current year OA Pubs

Migraine is highly prevalent and debilitating. The persistent headaches in this condition are thought to arise from the activation and sensitization of the trigeminovascular pathway. Both clinical and animal model studies have suggested that neuroimmune interactions contribute to the pathophysiology of migraine headache. In this review, we first summarize the findings from human studies implicating the dysregulation of the immune system in migraine, including genetic analyses, measurement of circulatory factors, and neuroimaging data. We next discuss recent advances from rodent studies aimed at elucidating the neuroimmune interactions that manifest at various levels of the trigeminovascular pathway and lead to the …

Role Of The Card8 Inflammasome In Hiv Pathogenesis, Qiankun Wang, Liang Shan

2020-Current year OA Pubs

Human immunodeficiency virus (HIV) continues to be a significant global health challenge despite decades of research and advances in treatment. Substantial gaps in our understanding of the mechanisms of HIV pathogenesis and the host immune responses still exist. The interaction between HIV and these immune responses is pivotal in the disease progression to acquired immunodeficiency syndrome (AIDS). Recently, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome has emerged as a crucial factor in orchestrating innate immune responses to HIV infection and exerting a substantial impact on viral pathogenesis. CARD8 restricts viral replication by detecting the activity of HIV protease. Conversely, …

Multi-Site Eeg Studies In Early Infancy: Methods To Enhance Data Quality, Abigail Dickinson, John Zempel, Natasha Marrus, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as …

Clinical And Research Application Of Fluid Biomarkers In Autosomal Dominant Alzheimer's Disease And Down Syndrome, María Carmona-Iragui, Antoinette O'Connor, Jorge Llibre-Guerra, Patrick Lao, Nicholas J Ashton, Juan Fortea, Raquel Sánchez-Valle

2020-Current year OA Pubs

Autosomal dominant Alzheimer's disease (ADAD) and Down syndrome (DS) constitute genetic forms of Alzheimer's disease (AD). The study of these forms has been crucial in understanding the biomarker changes and disease progression, notably in advancing our knowledge of the natural history of AD. However, some specific characteristics of biomarkers in genetically determined forms and, most importantly, the near full penetrance and predictability of disease onset lead to a very different context of use for biomarkers in these populations. This article delves into the similarities and differences in biomarker profiles between genetically determined AD and sporadic cases, discussing the implications for …

Assessing The Response Results Of An Mhealth-Based Patient Experience Survey Among People Receiving Hiv Care In Lusaka, Zambia: Cohort Study, Jacob Mutale, Kombatende Sikombe, Boroma Mwale, Mwansa Lumpa, Sandra Simbeza, Chama Bukankala, Njekwa Mukamba, Aaloke Mody, Laura K Beres, Charles B Holmes, Carolyn Bolton Moore, Elvin H Geng, Izukanji Sikazwe, Jake M Pry

2020-Current year OA Pubs

BACKGROUND: This pilot study evaluates the effectiveness of mobile talk-time incentives in maintaining participation in a longitudinal mobile health (mHealth) data collection program among people living with HIV in Lusaka, Zambia. While mHealth tools, such as mobile phone surveys, provide vital health feedback, optimal incentive strategies to ensure long-term engagement remain limited. This study explores how different incentive levels affect response rates in multiple survey rounds, providing insights into effective methods for encouraging ongoing participation, especially in the context of Zambia's prepaid mobile system and multi-SIM usage, a common practice in sub-Saharan Africa.

OBJECTIVE: This study aimed to assess the …

Continuous Adaptation Of Conversation Aids For Uterine Fibroids Treatment Options In A Four-Year Multi-Center Implementation Project, Danielle Schubbe, Tessa Madden, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred.

METHODS: We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group …

Negative Effect Of Treatment With Mglur5 Negative Allosteric Modulator Afq056 On Blood Biomarkers In Young Individuals With Fragile X Syndrome, Dragana Protic, Stephanie Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show …

Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Primary Advanced Or Recurrent Endometrial Cancer In A Phase Iii, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Annika Auranen, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

OBJECTIVES: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

DESIGN: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared …

A Multicenter, Randomized, Non-Comparative, Phase Ii Study Of Nivolumab ± Ipilimumab For Patients With Metastatic Sarcoma (Alliance A091401): Expansion Cohorts And Correlative Analyses, Nathan D Seligson, James L Chen, Austin C Goodrich, Brian A Van Tine, Jordan D Campbell, Allison L Richards, Cristina R Antonescu, David A Liebner, Mohammed M Milhem, Howard Streicher, William D Tap, Gary K Schwartz, Suzanne George, Sandra P D'Angelo

2020-Current year OA Pubs

BACKGROUND: In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers.

METHODS: Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts.

RESULTS: A total of 66 patients were …

How To Utilize Current Guidelines To Manage Patients With Cancer At High Risk For Heart Failure, Michelle Bloom, Jose A Alvarez-Cardona, Sarju Ganatra, Ana Barac, Iskra Pusic, Daniel Lenihan, Susan Dent

2020-Current year OA Pubs

Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout …

A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay

2020-Current year OA Pubs

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism …

Length-Scale Study In Deep Learning Prediction For Non-Small Cell Lung Cancer Brain Metastasis, Haowen Zhou, Siyu Lin, Mark Watson, Cory T Bernadt, Oumeng Zhang, Ling Liao, Ramaswamy Govindan, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN's predictive power. We applied this method to analyze a DNN's capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This …

Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from …

Massively Parallel Characterization Of Insulator Activity Across The Genome, Clarice K Y Hong, Yawei Wu, Alyssa A Erickson, Jie Li, Arnold J Federico, Barak A Cohen

2020-Current year OA Pubs

A key question in regulatory genomics is whether cis-regulatory elements (CREs) are modular elements that can function anywhere in the genome, or whether they are adapted to certain genomic locations. To distinguish between these possibilities we develop MPIRE (Massively Parallel Integrated Regulatory Elements), a technology for recurrently assaying CREs at thousands of defined locations across the genome in parallel. MPIRE allows us to separate the intrinsic activity of CREs from the effects of their genomic environments. We apply MPIRE to assay three insulator sequences at thousands of genomic locations and find that each insulator functions in locations with distinguishable properties. …

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …

Durations Of Antibiotic Treatment For Acute Otitis Media And Variability In Prescribed Durations Across Two Large Academic Health Systems, Sophie E Katz, Timothy C Jenkins, Amy B Stein, Gale Thomas, Nancy Koenig, Gary Lucas Starnes, Jason G Newland, Ritu Banerjee, Holly M Frost

2020-Current year OA Pubs

BACKGROUND: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system.

METHODS: Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a …

Treatment Outcomes Among Patients With A Positive Candida Culture Close To Randomization Receiving Rezafungin Or Caspofungin In The Restore Study, Alex Soriano, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.

METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before …

Spatiotemporal Relationships Between Neuronal, Metabolic, And Hemodynamic Signals In The Awake And Anesthetized Mouse Brain, Xiaodan Wang, Jonah A Padawer-Curry, Annie R Bice, Byungchan Kim, Zachary P Rosenthal, Jin-Moo Lee, Manu S Goyal, Shannon L Macauley, Adam Q Bauer

2020-Current year OA Pubs

Neurovascular coupling (NVC) and neurometabolic coupling (NMC) provide the basis for functional magnetic resonance imaging and positron emission tomography to map brain neurophysiology. While increases in neuronal activity are often accompanied by increases in blood oxygen delivery and oxidative metabolism, these observations are not the rule. This decoupling is important when interpreting brain network organization (e.g., resting-state functional connectivity [RSFC]) because it is unclear whether changes in NMC/NVC affect RSFC measures. We leverage wide-field optical imaging in Thy1-jRGECO1a mice to map cortical calcium activity in pyramidal neurons, flavoprotein autofluorescence (representing oxidative metabolism), and hemodynamic activity during wake and ketamine/xylazine anesthesia. …

Conformational Ensembles In Klebsiella Pneumoniae Fimh Impact Uropathogenesis, Edward D B Lopatto, Jerome S Pinkner, Denise A Sanick, Robert F Potter, Lily X Liu, Jesús Bazán Villicaña, Kevin O Tamadonfar, Yijun Ye, Maxwell I Zimmerman, Nathaniel C Gualberto, Karen W Dodson, James W Janetka, David A Hunstad, Scott J Hultgren

2020-Current year OA Pubs

No abstract provided.