Digital Commons Network^™

Characterization Of Tlr9 Responsiveness In Cell Subsets Derived From In Vitro Pdc Differentiation Of Hematopoietic Stem And Progenitor Cells, Sabina Sánchez Hernández, Tobias Wang Bjerg, Ian Helstrup Nielsen, Anders Laustsen, Hai Q Tang, Lars Henning Pedersen, Eynav Klechevsky, Martin R Jakobsen, Rasmus O Bak

2020-Current year OA Pubs

Plasmacytoid dendritic cells (pDCs) are multifunctional immune cells with roles in both the innate and adaptive immune system. Their hallmark function is production of large amounts of type I interferons in response to viral infections, but they are also capable of producing a range of other cytokines, antigen presentation, and cytotoxicity. Their potential as an immunotherapy for cancer and infectious disease is being explored, but broad application of these cells is challenged by low frequency in the blood and low viability during

The Gut Microbiome And Gastrointestinal Cancers: Mechanisms, Biomarkers And Therapeutic Opportunities, Sarbjeet Kaur Makkar, Kumar S Bishnupuri

2020-Current year OA Pubs

Gastrointestinal (GI) cancers remain a leading global cause of cancer-related mortality, significantly impacting public health and healthcare systems worldwide. Emerging evidence underscores the critical role of gut microbiome dysbiosis-characterized by disrupted microbial diversity and function-in GI carcinogenesis. Utilizing recent advancements in multi-omics technologies and sophisticated computational biology, researchers have elucidated distinct microbial signatures associated with colorectal, gastric, hepatobiliary, pancreatic, and esophageal cancers. This review comprehensively analyzes the primary mechanisms through which gut microbes contribute to cancer development and progression, encompassing genotoxicity, chronic inflammation, metabolic dysregulation, epigenetic modifications, and immunomodulation. Moreover, we explore innovative microbiome-derived biomarkers for potential clinical applications, including …

Uncovering A Novel Binding Trench In Errα: Insights From Molecular Simulations, Lamees Hegazy

2020-Current year OA Pubs

Although estrogen-related receptor α (ERRα) holds significant therapeutic potential for treating various disorders, developing selective agonists remains challenging due to the poor pharmacokinetics and limited selectivity of current ligands. This study presents unconstrained molecular dynamics simulations of ERRα bound to an agonist ligand, uncovering dynamic ligand-binding behavior as the ligand shifts between two orientations: one in the orthosteric pocket and another in a newly identified trench adjacent to this site. The free energy landscape reveals that both binding orientations are comparably populated, with an accessible transition pathway between them. The identification of this novel binding trench expands our understanding of …

The Stabilizing Potential Of The Supraspinatus Is Inhibited In Tear-Associated Scapula Shapes But Can Be Modulated By Kinematic Adjustments, Erin C S Lee, Nathan M Young, Ellen Y Li, Rebekah L Lawrence, Michael J Rainbow

2020-Current year OA Pubs

INTRODUCTION: Specific scapula shapes are associated with full-thickness tears of the supraspinatus tendon. A primary role of the supraspinatus is to actively stabilize the glenohumeral joint against muscles that generate destabilizing shear forces. Mechanisms that increase the supraspinatus load required to perform this stabilizing function may increase an individual's susceptibility to tears. Previous work has shown that tear-associated scapula shapes increase the destabilizing action of the deltoid during arm-raising, but no work has investigated whether tear-associated shapes inhibit the stabilizing potential of the supraspinatus itself.

METHODS: We combined statistical shape modeling, kinematics-driven simulations of the glenohumeral joint, and a finite …

Expanding The Spectrum Of White Matter Abnormalities In Wolfram Syndrome: A Retrospective Review, Justin Simo, Heather M Lugar, Tamara Hershey, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Wolfram syndrome (WFS) is a genetic disorder mainly caused by pathogenic variants in the

METHODS: We conducted an international multicenter retrospective study of the clinical, genetic, and radiological data from 17 unrelated WFS subjects.

RESULTS: Seven subjects (7/17; 41%) showed at least one focal white matter lesion evocative of MS. Among these seven, three fulfilled the McDonald radiological criteria of dissemination in space and time, suggesting an inflammatory demyelinating process. All subjects reviewed in the study had at least one of the classical WFS MRI features.

CONCLUSION: Our report expands the WFS spectrum of white matter involvement …

Cluster Randomized Multilevel Intervention For Promoting Physical Activity In Rural Communities, Alan M Beck, Natalicio Serrano, Dixie Duncan, Amy A Eyler, Amanda Gilbert, Fatemeh Naghiloo, Rodrigo Reis, Rachel G Tabak, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: Rural areas of the United States have lower levels of physical activity (PA) as compared to their urban and suburban counterparts, leading to higher levels of chronic diseases. The objective of the study was to increase PA in rural communities via a multilevel intervention.

METHODS: We implemented a cluster randomized controlled trial of a community-based multilevel PA intervention between 2019 and 2022 in 14 rural communities. The intervention consisted of (1) text messaging (i.e., individual level), (2) encouragement of walking groups (i.e., interpersonal level), and (3) community-based marketing (i.e., community level).

RESULTS: Participants meeting the 2018 PA guidelines for …

Barriers And Facilitators Of Integrating Cervical Cancer Screening Into Routine Hiv Care And Acceptability Of Self-Sampling For Hpv Dna Testing Among People With Hiv: An Exploratory Study In Southern Ghana, Evelyn Yayra Bonney, Emmanuel Frimpong Gyekye, Jonathan Klutse, Dzidzor Aku Attoh, Yeena Abla Tay, Nicholas Ekow Thomford, Mary Amoakoh-Coleman, Kwadwo Ansah Koram, George Boateng Kyei, Collins Stephen Ahorlu

2020-Current year OA Pubs

BACKGROUND: Cervical cancer poses a substantial global health challenge, disproportionately affecting low- and middle-income nations. Women living with HIV are disproportionately affected compared to the general population. Our study explored the acceptance and preferences of participants regarding cervical cancer screening procedures during their HIV clinic visits.

METHODS: Using the Consolidated Framework for Implementation Research (CFIR) to inform questions, we conducted semi-structured in-depth qualitative interviews with 85 people with HIV (PWH), across six southern Ghana sites, to identify factors that could promote or impede the integration of cervical cancer screening into HIV care in Ghana. We also explored the acceptability of …

Factors Affecting Viral Suppression Or Rebound In People Living With Hiv And Receiving Antiretroviral Therapy In Ghana, Anthony T Boateng, James O Aboagye, Helena Lamptey, Christopher Z-Y Abana, Araba Abaidoo-Myles, Darius N K Quansah, Seth Agyemang, Yaw Awuku-Larbi, Gloria Ansa, Joseph Oliver-Commey, Vincent Ganu, George B Kyei, Peter Puplampu, Evelyn Y Bonney

2020-Current year OA Pubs

INTRODUCTION: Regular viral load (VL) testing for people living with HIV (PLWH) is key to attaining the Joint United Nations Program on HIV/AIDS (UNAIDS) Fast-Track 95-95-95 target to end the HIV epidemic by 2030. However, VL testing remains sporadic in routine HIV care in the majority of resource-limited settings, including Ghana, except when provided through research initiatives. In this study, we measured VL among PLWH in Ghana at regular intervals and investigated factors affecting viral suppression (VS) and rebound.

METHODS: We analyzed data from a hospital-based cohort enrolled in our HIV cure research. Participants were recruited from three hospitals in …

Articles That May Change Your Practice: Reviewing Intraosseous Or Intravenous? Reviewing Intraosseous Versus Intravenous First Approach To Access In Out-Of-Hospital Cardiac Arrest Data From Randomized Controlled Trials, Blaise Loughman, Fatou Ndaw, Aaron J Lacy, James L Li

2020-Current year OA Pubs

No abstract provided.

Articles That May Change Your Practice: Double-Sequential External Defibrillation In Out-Of-Hospital Cardiac Arrest, Michael J Defilippo, Christianne L Jafari, James L Li, Aaron J Lacy

2020-Current year OA Pubs

No abstract provided.

Articles That May Change Your Practice: Prehospital Extracorporeal Membrane Oxygenation Alerts And Extracorporeal Cardiopulmonary Resuscitation In Out-Of-Hospital Cardiac Arrest, James L Li, Aaron J Lacy, Bridgette B Svancarek

2020-Current year OA Pubs

No abstract provided.

An Exploratory Graphical Analysis Of The Montgomery-Åsberg Depression Rating Scale Pre- And Post-Treatment Using Pooled Antidepressant Trial Secondary Data, David Byrne, Arunangshu Ghoshal, Fiona Boland, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth E Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Vincent Mcdarby, Emma Wallace, Frank Doyle

2020-Current year OA Pubs

BACKGROUND: The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) is a commonly used measure of depression in antidepressant clinical trials. Numerous studies have adopted classical test theory perspectives to assess the psychometric properties of this scale, finding generally positive results. However, its network configural structure and stability is unexplored across different time-points and treatment groups.

AIMS: To assess the network structure and stability of the MADRS in clinical settings pre- and post-treatment, and to determine a configurally invariant and stable model across time-points and treatment groups (placebo and intervention).

METHOD: Individual participant data for 6440 participants from 14 clinical trials of …

Association Of Item-Level Responses To Cognitive Function Index With Tau Pathology And Hippocampal Volume In The A4 Study, Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.

METHODS: In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau

RESULTS: Higher tau

DISCUSSION: These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.

HIGHLIGHTS: Higher …

Early Alzheimer's Disease Patient Care Pathway And Health System Readiness: A Framework For Integrated Care, Ilya M Nasrallah, Erik S Musiek, Et Al.

2020-Current year OA Pubs

UNLABELLED: Alzheimer's disease (AD) is often underdiagnosed, especially at early stages when symptoms are mild, and patients may benefit from new and recently approved anti-amyloid therapies. An updated patient care pathway may facilitate timely diagnosis and intervention. We conducted a scan of published information and convened an expert panel of health care professionals to gain insights on early AD care pathways. We developed an Early AD Patient Care Pathway as an implementation guide that includes new diagnostic and treatment modalities and addresses needs and opportunities. The Early AD Patient Care Pathway focuses on patient identification, assessment, diagnosis, treatment, and management …

Variations In Greater Trochanter Height As A Relation To Patient Demographics: Implications For Femoral Nail Design, Jordan A Haber, Amogh I Iyer, Matthew Dulas, Douglas Weaver, Jason A Strelzow

2020-Current year OA Pubs

Intramedullary nail fixation is the "gold standard" for surgical intervention of femoral fractures. While many aspects of nail design and patient anatomy have received specific focus, anatomic variations in proximal femoral geometry and greater trochanteric height variation have been poorly studied. Understanding the potential relationship of the greater trochanter to patient demographics may provide an opportunity to improve implant placement. Retrospective review of x-ray and computed tomography images of the proximal femur was performed. Inclusion criteria consisted of skeletally mature patients over 18 years old with imaging of the proximal femur. Inclusion criteria identified 296 patients. Mean age of included …

Domain-Specific Customization For Language Models In Otolaryngology: The Ent Gpt Assistant, Brenton T Bicknell, Nicholas J Rivers, Adam Skelton, Delaney Sheehan, Charis Hodges, Stevan C Fairburn, Benjamin J Greene, Bharat Panuganti

2020-Current year OA Pubs

OBJECTIVE: To develop and evaluate the effectiveness of domain-specific customization in large language models (LLMs) by assessing the performance of the ENT GPT Assistant (E-GPT-A), a model specifically tailored for otolaryngology.

STUDY DESIGN: Comparative analysis using multiple-choice questions (MCQs) from established otolaryngology resources.

SETTING: Tertiary care academic hospital.

METHODS: Two hundred forty clinical-vignette style MCQs were sourced from BoardVitals Otolaryngology and OTOQuest, covering a range of otolaryngology subspecialties (n = 40 for each). The E-GPT-A was developed using targeted instructions and customized to otolaryngology. The performance of E-GPT-A was compared against top-performing and widely used artificial intelligence (AI) LLMs, including …

Vagus Nerve Stimulation In Treatment-Resistant Depression: A One-Year, Randomized, Sham-Controlled Trial, Charles R Conway, Christopher L Kriedt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

OBJECTIVE: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

METHODS: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3-12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated.

RESULTS: Overall, 88.4 % of participants completed the trial. Percent …

Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Acquired Ductopenia: An Insight Into Imaging Findings, Rachita Khot, Nathan R Shelman, Daniel R Ludwig, Rashmi T Nair, Mark A Anderson, Sudhakar K Venkatesh, Raj Mohan Paspulati, Rex A Parker, Christine O Menias

2020-Current year OA Pubs

Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These …

Head-To-Head Preclinical Treatment Design Prioritizes Promising Therapies For Neurofibromatosis Type 1 Optic Glioma Clinical Translation, Talia Eligator, Jit Chatterjee, Shintaro Yamada, Anthony Kirchner, Hareesh B Nair, Jason R Fangusaro, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (

METHODS:

RESULTS: While all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards …

Assessing The Clinical Meaningfulness Of Slowing Cdr-Sb Progression With Disease-Modifying Therapies For Alzheimer's Disease, Sarah M Hartz, Suzanne E Schindler, Marissa L Streitz, Krista L Moulder, Jessica Mozersky, Guoqiao Wang, Chengjie Xiong, John C Morris

2020-Current year OA Pubs

INTRODUCTION: For many patients and caregivers, a major goal of disease-modifying treatments (DMTs) for Alzheimer's disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.

METHODS: Participants at the Knight Alzheimer Disease Research Center (Knight ADRC) who met eligibility criteria for recent DMT trials were studied: age ≥60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating [CDR] score 0.5 or 1), biomarker confirmation …

System Readiness And The Patient Care Pathway For Alzheimer's Disease Diagnosis And Treatment, B Joy Snider, Et Al.

2020-Current year OA Pubs

Promising therapeutic interventions that target the underlying pathophysiology are changing the landscape of Alzheimer's disease (AD) research. The AD care pathway must be transformed to meet the challenge of bringing these new therapies to the increasing number of people living with AD within the existing healthcare framework. Challenges include identifying patients who may benefit from treatment interventions early in the course of the disease, ensuring that diagnostic tools are accessible and accurate, and developing capabilities to monitor the effectiveness of interventions over time. These challenges must be addressed at all levels, from primary care settings to tertiary treatment centers; this …

Qualitative And Quantitative Analysis Of A Novel Dental Health Education Program To Improve Dental Care Utilization By Bhutanese-, Burmese-, And Swahili-Speaking Refugees In A Midwestern United States City, Chandra Swanson, Katherine Gordon, Kelly Kreisler, Elizabeth Montgomery Collins

2020-Current year OA Pubs

No abstract provided.

Impact Of Genetic Counseling And Testing In Individuals At High Risk Of Familial Alzheimer's Disease From Latin America: A Non-Randomized Controlled Trial, Pablo M Bagnati, Ellen Ziegemeier, Eric Mcdade, Randall J Bateman, Jorge J Llibre-Guerra, Et Al.

2020-Current year OA Pubs

INTRODUCTION: This study involved evaluating a tailored genetic counseling and testing (GCT) protocol for families at risk of autosomal dominant Alzheimer's disease (ADAD) in Latin America (LatAm), focusing on essential cultural and regional adaptations.

METHODS: We conducted a non-randomized controlled trial among ADAD families in Colombia and Argentina. Participants were categorized based on their decision to learn their genetic status (GS), with further comparisons between mutation-positive versus mutation-negative participants who learned their status. Psychological impacts were measured using validated scales for anxiety and depression.

RESULTS: Of the 122 eligible participants, 97 completed the GCT protocol, and 87 opted to learn …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Carissa W. Tomas, Evan M. Gordon, Et Al

2020-Current year OA Pubs

No abstract provided.

Wireless Modular Implantable Neural Device With One-Touch Magnetic Assembly For Versatile Neuromodulation, Inho Kang, John Bilbily, Choong Yeon Kim, Chuanqian Shi, Manish K Madasu, Eun Young Jeong, Kyle E Parker, Do A Kwon, Bum-Joon Jung, Jae-Soon Yang, Juhyun Lee, Noah D L Kabbaj, Wonhee Lee, Jun-Bo Yoon, Ream Al-Hasani, Jianliang Xiao, Jordan G Mccall, Jae-Woong Jeong

2020-Current year OA Pubs

Multimodal neural interfaces open new opportunities in brain research by enabling more sophisticated and systematic neural circuit dissection. Integrating complementary features across distinct functional domains, these multifunctional neural probes have greatly advanced the interrogation of complex neural circuitry. However, introducing multiple functionalities into a compact form factor for freely behaving animals presents substantial design hurdles that complicate the device or require more than one device. Moreover, fixed functionality poses challenges in meeting the dynamic needs of chronic neuroscience inquiry, such as replacing consumable parts like batteries or drugs. To address these limitations, the modular implantable neural device (MIND) is introduced …

Psychosocial Behavioral Phenotypes Of Racially/Ethnically Minoritized Older Adults Enrolled In Habs-Hd Differ On Neuroimaging Measures Of Brain Age Gap, Hippocampal Volume, And Cortical Thickness, Alexandra L Clark, Makenna B Mcgill, Alexandra J Weigand, Julie K Wisch, Kalen Petersen, Beau Ances, Meredith N Braskie, Sid O'Bryant, Kelsey R Thomas, Habs‐Hd Study Team

2020-Current year OA Pubs

INTRODUCTION: This study examined whether previously identified psychosocial behavioral phenotypes differed on structural neuroimaging markers.

METHODS: Latent profile analysis (LPA) employed in a sample of 1820 community-dwelling older adults (1118 Hispanic and 702 Black) replicated previous Low Resource/Low Distress, High Resource/Low Distress, and Low Resource/High Distress phenotype classifications. Analyses of covariance (ANCOVAs) adjusting for relevant factors examined phenotype differences on neuroimaging outcomes of predicted brain age gap (BAG) (DeepBrainNet

RESULTS: The Low Resource/Low Distress and Low Resource/High Distress phenotypes had significantly higher predicted BAGs relative to the High Resource/Low Distress phenotype, and the Low Resource/High Distress group displayed significantly lower …

A Clinical Practice Review Of Optimizing The Approach For Correction Of Thoracolumbar Deformity— When And How To Perform Anterior Releases And Fusion, Brian M. Phelps, Munish C. Gupta

2020-Current year OA Pubs

No abstract provided.

Caregiver Worry About Covid-19 As A Predictor Of Social Mitigation Behaviours And Sars-Cov-2 Infection In A 12-City U.S. Surveillance Study Of Households With Children, Steven M Brunwasser, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

METHODS: Data were drawn from a surveillance study of households with children (

RESULTS: Caregivers with high enrollment levels of worry about COVID-19 illness were more likely to reduce direct social contact outside the household, particularly during the U.S.'s most deadly pandemic wave. Households of caregivers with …

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …