Digital Commons Network^™

Association Of Self-Rated Health And Risk Of Incident Atrial Fibrillation: Findings From Three Cohorts, Parveen K Garg, Aniqa Alam, Harpreet S Bhatia, Jens Horn, Vegard Malmo, Jan Pal Loennechen, Scott Mu, Randi Foraker, Elizabeth Selvin, Imre Janszky, Susan R Heckbert, Alvaro Alonso

2020-Current year OA Pubs

BACKGROUND: Self-rated health (SRH) is easy to obtain and is known to be a good predictor for mortality and several comorbidities, including cardiovascular disease, but its relation to atrial fibrillation (AF) is largely unknown. We determined the association of SRH with risk of developing AF.

METHODS: We conducted a pooled cohort analysis of participants in the Atherosclerosis Risk in Communities Study (ARIC) (

RESULTS: Over a mean of 16±6, 9 ± 2, and 10±4 years of follow-up, 2340 (22.8 %), 1525 (3.5 %), and 879 (17.4 %) incident AF events occurred in ARIC, HUNT-3, and MESA respectively. Lower SRH categories …

Risk Factors For Anticoagulant-Related Bleeding In Cancer: Traditional And Cancer-Specific Factors, Alexa Loncharich, Brian F Gage, Suhong Luo, Martin Schoen, Amber Afzal, Amir Mahmoud, Kenneth Carson, Su-Hsin Chang, Yan Yan, Kristen M Sanfilippo

2020-Current year OA Pubs

Managing anticoagulant therapy in cancer-associated venous thromboembolism (VTE) is challenging due to risks of recurrent VTE and anticoagulant-related bleeding. Existing clinical risk models for bleeding are limited by discriminatory ability in patients with cancer, perhaps due to the omission of cancer-specific risk factors for bleeding. This study estimated the associations of traditional and cancer-specific risk factors with bleeding requiring hospitalization in patients with cancer-associated VTE prescribed anticoagulant therapy. We conducted a retrospective cohort study using the Veterans Health Administration database to identify patients with cancer-associated VTE between 2012 and 2020. Cancer-associated VTE was defined by diagnostic International Classification of Diseases …

Skida1 Sustains Mll::Enl-Expressing Hematopoietic Progenitors During Neonatal Stages And Promotes B-Lineage Priming, Jonny Mendoza-Castrejon, Wei Yang, Elisabeth Denby, Rohini Muthukumar, Emily B Casey, Riddhi M Patel, Sarah K Tasian, Jeffrey A Magee

2020-Current year OA Pubs

Infant leukemias arise as B-cell acute lymphoblastic or acute myeloid leukemia. Most are driven by chromosomal rearrangements of the

Plasma Ceramides Levels In Severe Covid-19 Disease: Correlations With Survival, Tri Pham, Andrea M Heredia Castillo, Andrew Atkinson, Linda R Peterson, M Cristina Vazquez Guillamet

2020-Current year OA Pubs

BACKGROUND: Dysregulated inflammatory processes have been associated with severe COVID-19 disease. Ceramides, bioactive lipids involved in inflammatory signaling, have been utilized to predict outcomes in chronic cardiometabolic diseases and pancreatic cancer, but their role in COVID-19 remains unknown.

METHODS: This observational study prospectively enrolled patients with COVID-19 disease who required intubation and mechanical ventilation at a Midwestern academic hospital between August 2020 and March 2021. Plasma ceramides 16:0 (C16), 22:0 (C22), and 24:0 (C24) and inflammatory markers (CRP, ESR, D-Dimer, and ferritin) were collected and organized weekly from symptom onset for up to 6 weeks. Patients were grouped by in-hospital …

The Sport Publication Observational Research Tool (Sport): An Objective Tool To Score The Methodological Quality Of Observational Clinical Sports Medicine Research, Andrew W Kuhn, Paul M Inclan, Ameer A Haider, Michele N Christy, Robert Brophy, Matthew Smith, Matthew J Matava, Et Al.

2020-Current year OA Pubs

BACKGROUND: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases.

PURPOSE: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research.

STUDY DESIGN: Consensus statement.

METHODS: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the …

Nested Ecosystems Theory For Conceptualizing Brain Tumors, Lori A Forster, David H Gutmann

2020-Current year OA Pubs

The application of advanced multi-omic methodologies to studying brain tumors has culminated in the appreciation that these cancers function as ecosystems that depend on the interactions of a diverse collection of cell types and signals. This connectivity operates not only at the level of the cancer cell, in which variants create new growth dependencies, but also between tumor cells and the immediate tumor microenvironment, between tumor cells and cell populations residing elsewhere in the brain tissue or body, and in response to extracorporeal factors. The cellular and molecular relationships within these four interrelated strata (intracellular, extracellular, intracorporeal and extracorporeal) act …

Phase 1 Study Of Inbrx-105, A Tnfrsf9 (4-1bb) And Pd-L1 Bispecific Antibody, In Patients With Select Solid Tumors, Jong Chul Park, Doug R Adkins, Et Al.

2020-Current year OA Pubs

PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R …

Divergent Humoral Immune Signatures In Response To Klebsiella Pneumoniae Bacteremia, Paeton L Wantuch, Nadia Wattad, David A Rosen

2020-Current year OA Pubs

OBJECTIVES: Klebsiella pneumoniae is an increasingly threatening global pathogen with high rates of antibiotic resistance and no licensed vaccines available. Despite its worldwide importance, little is known about the human adaptive immune response to K. pneumoniae infection.

METHODS: Herein we observed the longitudinal antibody responses of three immunocompetent patients hospitalized with K. pneumoniae bacteremia. We analyzed the human serum for antibody titers and in vitro functionality. Further, serum function was evaluated via an in vivo mouse model.

RESULTS: We found that in each case, anti-K. pneumoniae antibodies against the infecting strain were still detectable a year after the initial infection. …

Clinical Presentation, Risk Factors And Outcome Of Non-Tuberculous Mycobacteria Infection In Hematopoietic Stem-Cell Transplantation: A Multinational Case-Control Study, Mario Fernández-Ruiz, Sasinuch Rutjanawech, Carlos Mejía-Chew, Et Al.

2020-Current year OA Pubs

BACKGROUND: The clinical and microbiological features of infection due to non-tuberculous mycobacteria (NTM) after hematopoietic stem-cell transplantation (HSCT) remain poorly understood.

METHODS: We performed a retrospective, multinational case-control study that included HSCT recipients (≥12 years) diagnosed with NTM disease between January 2008 and December 2018. Controls were HSCT recipients with no evidence of NTM disease, matched (1:2 ratio) by participating center and post-transplant survival. Logistic regression on matched pairs was used to investigate risk factors for NTM disease.

RESULTS: We included 25 cases of NTM disease. The most common HSCT type was allogeneic from unrelated donor (72.0%) after myeloablative conditioning …

Multi-Modal Pediatric Critical Care Datamart For Extracorporeal Support Prediction And Decision Support, Miranda Edmunds, Aditi Gupta, Inez Oh, Levi Kaster, Jonathan Sagel, Andrew Michelson, Yuyao Zhuge, Philip Payne, Ahmed Said

2020-Current year OA Pubs

OBJECTIVES: To develop a multimodal pediatric critical care datamart supporting predictive modeling and decision support tool development, integrating high-resolution physiologic and clinical data and future clinical deployment.

MATERIALS AND METHODS: We developed a continuously expanding datamart integrating electronic health record data, high-resolution telemetry, and extracorporeal membrane oxygenation (ECMO)-domain datasets. The platform links static and longitudinal time-series variables with expert-curated neurologic outcomes for both ECMO and non-ECMO patients, enabling trajectory-based analyses.

RESULTS: The datamart currently includes 25 762 pediatric patients, of whom 395 received ECMO support. The datamart captures granular longitudinal physiologic, laboratory, medication, and telemetry data suitable for dynamic predictive …

Associations Of Child Amygdala Development With Borderline Personality Symptoms During Adolescence, Anna Constantino-Pettit, Kirsten Gilbert, Kiran Boone, Katherine Luking, Benjamin Geselowitz, Rebecca Tillman, Diana Whalen, Joan Luby, Deanna M Barch, Alecia Vogel

2020-Current year OA Pubs

BACKGROUND: The current understanding of the neural correlates of borderline personality disorder (BPD) is limited, but some evidence suggests that alterations in limbic structures play a role in adult BPD. The developmental course of structural neural differences in BPD is unknown. Whether there is specificity for structural alterations in BPD compared to other psychiatric presentations, such as major depressive disorder (MDD), remains unexplored. In the current study, we examined childhood trajectories of 2 limbic regions that have been implicated in BPD, hippocampal and amygdala volume, as they relate to adolescent BPD symptoms compared to MDD symptoms.

METHODS: Participants (n = …

Patient-Reported Outcomes In The Serena-6 Trial Of Camizestrant Plus Cdk4/6 Inhibitor In Patients With Advanced Breast Cancer And Emergent Esr1 Mutations During First-Line Endocrine-Based Therapy, E L Mayer, C Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: In SERENA-6, switching from aromatase inhibitor (AI) to camizestrant with continuation of CDK4/6 inhibitor (CDK4/6i) guided by emergence of ESR1 mutations (ESR1-mut) during first-line AI-CDK4/6i in patients with hormone receptor (HR)-positive advanced breast cancer (ABC) resulted in statistically significant and clinically meaningful improvement in progression-free survival compared with AI-CDK4/6i and reduction in the risk of deterioration in global health status (GHS)/quality of life (QoL) (hazard ratio 0.54). Here we report additional data from patient-reported outcomes (PROs).

PATIENTS AND METHODS: Patients completed PRO questionnaires at pre-specified timepoints, including the European Organisation for Research and Treatment of Cancer (EORTC) oncology-specific EORTC …

Palbociclib With Adjuvant Endocrine Therapy In Early Breast Cancer: 5-Year Follow-Up Analysis Of The Global Multicenter, Open-Label, Randomized Phase Iii Pallas Trial (Abcsg-42/Aft-05/Pre0109/Big-14-13), E L Mayer, K Clifton, Et Al.

2020-Current year OA Pubs

BACKGROUND: In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS).

PATIENTS AND METHODS: PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS.

RESULTS: The trial enrolled …

Intersecting Challenges: Substance Use And Mental Health Disparities Across Self-Reported Disability Status, Jessica Williams, Xiao Li, Hannah S Szlyk, Erin Kasson, Nathaniel A Dell, Alex Ramsey, Patricia A Cavazos-Rehg

2020-Current year OA Pubs

PURPOSE: Substance use and substance use disorders (SUD) disproportionately affect people with disabilities (PWD), yet PWD remain under-represented in addiction treatment literature. While recent work has begun to address SUD prevalence and recovery service gaps, little is known about how disability status shapes substance use outcomes. The present study is the first to our knowledge to investigate how recovery, mental health comorbidities, and barriers to care differ across disability status using structured survey data from people who use substances.

METHODS: 333 participants who use substances and provided information about their disability status in the baseline survey for a digital intervention …

"Another One Bite The Dust-It Happens So Much In Black Neighborhoods": Structural Barriers And Grassroots Resources Among Black Men Who Use Drugs Facing Fentanyl-Era Overdose And Treatment Disparities, Devin E Banks, Kaytryn D Campbell, Maria E Paschke, Rashmi Ghonasgi, Bridget Coffey, Jameala Jones, Brittany Blanchard, Ryan W Carpenter, Daje Bradshaw, Rachel P Winograd

2020-Current year OA Pubs

INTRODUCTION: Black men in the United States have been disproportionately impacted by fatal drug overdose since the proliferation of synthetic opioids like fentanyl. This community based participatory research study examined determinants of overdose risk and substance use treatment disparities among Black men based on their lived experience.

METHODS: Between February and December 2023, we enrolled 35 Black men reporting past-30-day opioid use to complete semi-structured qualitative interviews. Interviews were analyzed by a team of academic and community-based coders with lived experience using an inductive-deductive approach to thematic analysis.

RESULTS: Six key themes were identified. Four themes described racism-related inequities posing …

Objective Selection Of Bone Mimetic Materials Using Impact Microindentation, Lucas R Budd, Rachana S Vaidya, Babak Jahani, Saideep Nakka, Alexander Proctor, Peter T Burks, Blake K Montgomery, Simon Y Tang

2020-Current year OA Pubs

BACKGROUND: Research and development for orthopedic medical devices, implants, surgical technique, and surgical education all require the appropriate selection of bone mimetic materials to align with the physiologic conditions. There is a critical need for an objective measure of material strength that can be collected, practically, on both bone mimetic materials and living human bone to improve mimetic material selection.

METHODS: This study stratifies commonly used synthetic materials in orthopedic research, as well as animal and human bone, using impact microindentation. The impact microindentation is performed with the OsteoProbe, an FDA-approved handheld medical device that can quantify material strength via …

Risk Factors For Complication And Reoperation In The Treatment Of Discoid Lateral Meniscus In Children And Adolescents: A Multicenter Study, Suzanna Ohlsen, Jeffrey J Nepple, Et Al.

2020-Current year OA Pubs

BACKGROUND: The discoid lateral meniscus (DLM) is a common congenital abnormality of the meniscus. Tears are common, and initial treatment is often not definitive, leading to a spectrum of complications, including persistent symptoms, meniscal insufficiency, osteochondral defects, and recurrent tears potentially requiring reoperation.

PURPOSE: To determine demographic, injury, and perioperative risk factors that increase the likelihood of complications and reoperation after treatment in patients with DLM.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Patients surgically treated for DLM from 9 institutions between 2000 and 2020 were reviewed. Data on demographics, presenting symptoms and signs, surgical findings and treatments, …

Ultrasound Applications In The Treatment Of Major Depressive Disorder: A Systematic Review Of Techniques And Therapeutic Potentials In Clinical Trials And Animal Model Studies, Gansheng Tan, Hong Chen, Eric C Leuthardt

2020-Current year OA Pubs

OBJECTIVE: Major depressive disorder (MDD) is a debilitating condition that inflicts significant personal and economic burdens and affects approximately 8% of the US population. Approximately 30% of patients with MDD do not respond to conventional antidepressant and psychotherapeutic treatments. Current treatment options for refractory MDD include transcranial magnetic stimulation (TMS) and invasive surgical procedures such as surgical ablation, vagus nerve stimulation, and deep brain stimulation. In this context, therapeutic ultrasound emerges as a promising alternative for treating refractory MDD, which has the unique advantage of combining noninvasiveness with selective targeting. Over the past ten years, there has been growth in …

Silent Messengers In The Nano-World: Harnessing Extracellular Vesicles As Theranostic Tools For Neonatal Surgical Conditions, Augusto Zani

2020-Current year OA Pubs

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles secreted by all cells that mediate intercellular communication by transferring proteins, lipids, and nucleic acids. Among their cargo, microRNAs are key post-transcriptional regulators of organogenesis. In fetal lung development, EV-mediated signaling is essential for the coordination of epithelial, mesenchymal, endothelial, and immune cells. In congenital diaphragmatic hernia (CDH), disruption of these interactions leads to pulmonary hypoplasia and pulmonary hypertension, the primary causes of morbidity and mortality. Amniotic fluid stem cell-derived EVs (AFSC-EVs) have emerged as a promising cell-free therapy to restore this impaired communication. In rodent, rabbit, and human models of pulmonary hypoplasia, …

Association Of Sleep Disturbance With Survival After Colorectal Cancer Diagnosis: Results From The Colocare Study, Anita R Peoples, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sleep problems are common among cancer patients. The relationship between sleep disruption and clinical outcomes after colorectal cancer (CRC) diagnosis remains poorly understood. We investigated associations of sleep disruption with survival and recurrence in patients with CRC.

METHODS: CRC patients with stages I-IV (N = 895) were included in this study. Self-reported sleep disturbance was assessed presurgery using the sleep item from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core-30 and classified into "no/mild" or "moderate/severe" sleep disturbance. Cox-proportional hazard models were computed (HRs and 95% confidence intervals) to investigate associations of sleep disturbance …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

Accelerated Diffusion Basis Spectrum Imaging With Tensor Computations, Kainen L Utt, Jacob S Blum, Donsub Rim, Sheng-Kwei Song

2020-Current year OA Pubs

This paper introduces an advanced framework for accelerated processing of diffusion-weighted imaging (DWI) data that utilizes an entire-image modeling approach to optimize the estimation of diffusion parameters from DWIs by mapping input diffusion data to predicted signals and estimating parameter values via a stochastic gradient descent optimizer (Adam). To validate this approach, we applied this framework to diffusion basis spectrum imaging (DBSI) and analyzed in vivo human brain and ex vivo mouse brain DWIs. Results demonstrate significant improvements to computational speed and signal-to-noise ratio (SNR) in estimated parameter maps compared to standard DBSI. Our approach is applicable to any diffusion …

A Systemic Selective Modified Mrna Delivery Platform For Preventing Chemotherapy-Induced Cardiotoxicity, Jimeen Yoo, Mengcheng Shen, Et Al.

2020-Current year OA Pubs

Doxorubicin (Dox) is a widely employed chemotherapeutic agent, but its use is clinically limited by dose-accumulative cardiotoxicity. More specifically, Dox induces oxidative stress and causes pro-apoptotic ceramide accumulation in cardiomyocytes (CMs). Acid ceramidase (AC) modified mRNA (modRNA) has been shown to reduce ceramide levels and protect the heart following ischemic injury; however, therapeutic modRNA applications have been hindered by the need for invasive delivery. Here, we present a platform for minimally intrusive transmission of modRNA to the heart. This CM-selective modRNA translational system (cmSMRTs) is encapsulated in lipid nanoparticles for intravenous (IV) delivery to enable systemic administration with high cardiac …

Loss Of Beta-Cell Identity And Function As A Mechanism Of Secondary Failure Of Sulfonylurea Therapy In Diabetes, Sumit Patel, Zihan Yan, Maria S Remedi

2020-Current year OA Pubs

Sulfonylureas, commonly used to treat type 2 diabetes (T2D), often lose effectiveness over time when used as monotherapy; however, the underlying mechanisms remain unclear. To investigate the mechanisms of sulfonylurea failure, glibenclamide-releasing pellets were implanted in KK mice, a polygenic model that spontaneously develops T2D. KK mice receiving placebo pellets (KK-Placebo) developed hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Notably, KK mice implanted with glibenclamide (KK-Glib) showed improved blood glucose levels during the first 7 days, returning to KK-Placebo levels thereafter. KK-Glib mice exhibited reduced plasma insulin levels and insulin secretion in response to a glucose challenge compared with the …

Blood Dna Methylation-Predicted Plasma Protein Levels And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Esther Jean-Baptiste, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.

METHODS: We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with …

Lightweight Open-Source Large Language Models Versus Ctakes For Information Extraction From Discharge Summaries: Tobacco Smoking Status Test Case, David M Dávila-García, Matthew J Schuelke, Adam B Wilcox

2020-Current year OA Pubs

OBJECTIVES: To compare lightweight open-source large language models (LLMs) with cTAKES, a state-of-the-art natural language processing (NLP) system, in an information extraction task from hospitalization discharge summaries.

MATERIALS AND METHODS: Two readers annotated 250 randomly sampled adult discharge summaries (BJC HealthCare, 2018-2023) for tobacco smoking status as "Smoker," "Never smoker," "Unknown." Six LLMs (Llama-3 [1B-70B], gpt-oss-20B, MedGemma-27B) and cTAKES extracted smoking status from summaries. Performance was benchmarked against consensus annotations using weighted F1-score, macro F1-score, and per-class F1-scores and a noninferiority test.

RESULTS: Inter-reader agreement was excellent (κ = 0.91). LLM size (2.3-47.3 GB) and inference time (2.5-14.5 s/note) varied. …

Effects Of Dual-Eligible Integrated Care Plans On Medicaid Enrollment And Retention: Evidence From The Implementation Of Medicare-Medicaid Plans, Eric T Roberts, Eliza Macneal, Kenton J Johnston, José F Figueroa

2020-Current year OA Pubs

Medicare and Medicaid are separate programs that together cover 13 million low-income older adults and people with disabilities, known as dual-eligible individuals. Concern about a lack of coordination across Medicare and Medicaid has prompted the development of Integrated Care Programs (ICPs). Although the primary goal of ICPs is to coordinate financing and care across Medicare and Medicaid, ICPs may also influence whether low-income individuals obtain or keep Medicaid. We evaluated whether the rollout of Medicare-Medicaid Plans (MMPs)-one of the largest ICPs-was associated with changes in Medicaid take-up and retention among Medicare beneficiaries residing in high-poverty zip codes. Using a stacked …

Seeg-Guided Responsive Neurostimulation To Treat Neocortical Epilepsy: A Multicenter Retrospective Study Of The Efficacy And Safety Of Depth Electrode-Mediated Neuromodulation, Sina Sadeghzadeh, Jon T Willie, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)-guided depth leads to provide responsive stimulation to neocortical gray matter.

METHODS: Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti-responders (≤0%) based on percent seizure reduction at 1 year post-implant (1-Y). …

Neural Cells Are Susceptible To Historic And Recently Emerged Oropouche Virus Strains, Kaleigh A. Connors, Maris R. Pedlow, Zachary D. Frey, Marjorie Cornejo Pontelli, Sean P. J. Whelan, W. Paul Duprex, Leonardo D'Aiuto, Zachary P. Wills, Amy L. Hartman

2020-Current year OA Pubs

Oropouche fever is a re-emerging global viral threat caused by infection with Oropouche virus (OROV). While disease is generally self-limiting, historical and recent reports of neurologic involvement highlight the importance of understanding the neuropathogenesis of OROV. In this study, we characterize viral replication kinetics in neurons, microglia, and astrocytes derived from immortalized, primary, and induced pluripotent stem cell-derived cells, which are all permissive to infection with the prototypic OROV BeAn19991. We demonstrate cell-type dependent replication kinetics with both historic and recently emerged viral strains. Further, we show that ex vivo rat brain slice cultures can be infected by all OROV …

Serine/Threonine Protein Kinase Phosphorylation Of Dosr Alters Target Gene Transcription Mechanics And Regulates Mycobacterium Tuberculosis Response To Nitric Oxide Stress, Natalie R. Sontag, Ana Ruiz Manzano, Alwyn M. V. Ecker, Eric A. Galburt, Shumin Tan

2020-Current year OA Pubs

Successful host colonization by bacterial pathogens requires appropriate response and adaptation to environmental signals encountered during infection, with two-component systems (TCSs) and serine/threonine protein kinases (STPKs) being two important signal transduction mechanisms. Mycobacterium tuberculosis (Mtb) possesses similar numbers of STPKs (11) and TCSs (12), but if and how these two regulatory systems coordinate to enable Mtb adaptation in response to key environmental cues remains poorly understood. Here, we identify extensive interactions between STPKs and TCSs, with a subset of STPKs demonstrating interactions with multiple TCS response regulators. STPK phosphorylation of purified DosR, the response regulator of the key nitric oxide …