Digital Commons Network^™

Sept9 And Pai-1 Are Immunohistochemical Biomarkers Of The Hepatocellular Carcinoma Immune Microenvironment, Eundong Park, Xin Wang, Nusret Bekir Subasi, Michel Kmeid, Paul J Higgins, Anne Chen, Hwajeong Lee

2020-Current year OA Pubs

BACKGROUND: Septin 9 (SEPT9) interacts with multiple oncogenic proteins and is expressed abnormally in several cancers, including hepatocellular carcinoma (HCC). Plasminogen activator inhibitor-1 (PAI-1) promotes tumor formation and progression by modulating the tumor immune microenvironment. CXCR2+ immune cells play a crucial role in HCC formation, progression, and prognosis. The relationship between SEPT9 and PAI-1, and their impact on the HCC immune microenvironment remains unclear.

METHODS: Expression levels of SEPT9 and PAI-1 were evaluated by immunohistochemistry (IHC) in HCC and background benign liver (n = 76). Their IHC results were examined for relationships with immune cell markers (CXCR2, CD3, CD15, CD68, …

Loss Of Atg7 In Microglia Impairs Upr, Triggers Ferroptosis, And Weakens Amyloid Pathology Control, Zhangying Cai, Shoutang Wang, Siyan Cao, Yun Chen, Silvia Penati, Vincent Peng, Carla M Yuede, Wandy L Beatty, Kent Lin, Yiyang Zhu, Yingyue Zhou, Marco Colonna

2020-Current year OA Pubs

Microglia impact brain development, homeostasis, and pathology. One important microglial function in Alzheimer's disease (AD) is to contain proteotoxic amyloid-β (Aβ) plaques. Recent studies reported the involvement of autophagy-related (ATG) proteins in this process. Here, we found that microglia-specific deletion of Atg7 in an AD mouse model impaired microglia coverage of Aβ plaques, increasing plaque diffusion and neurotoxicity. Single-cell RNA sequencing, biochemical, and immunofluorescence analyses revealed that Atg7 deficiency reduces unfolded protein response (UPR) while increasing oxidative stress. Cellular assays demonstrated that these changes lead to lipoperoxidation and ferroptosis of microglia. In aged mice without Aβ buildup, UPR reduction and …

Backbone-Mediated Weakening Of Pairwise Interactions Enables Percolation In Peptide-Based Mimics Of Protein Condensates, Xiangze Zeng, Rohit V Pappu

2020-Current year OA Pubs

Biomolecular condensates formed by intrinsically disordered proteins (IDPs) are semidilute solutions. These can be approximated as solutions of blob-sized segments, which are peptide-sized motifs. We leveraged the blob picture and molecular dynamics simulations to quantify differences between inter-residue interactions in model compound and peptide-based mimics of dense versus dilute phases. The all-atom molecular dynamics simulations use a polarizable forcefield. In model compound solutions, the interactions between aromatic residues are stronger than interactions between cationic and aromatic residues. This holds in dilute and dense phases. Cooperativity within dense phases enhances pairwise interactions leading to finite-sized nanoscale clusters. The results for peptide-based …

Comparing Analgesic Regimen Effectiveness And Safety After Surgery (Cares): Protocol For A Pragmatic, International Multicentre Randomised Trial, Mark C Bicket, Karim Shiraz Ladha, Simon Haroutounian, Kellie Mcfarlin, Mary Neff, Rachel L Mcduffie, Jennifer F Waljee, Duminda Nalaka Wijeysundera, Chad Brummet, Yi Li, Cares Investigators

2020-Current year OA Pubs

INTRODUCTION: Acute pain is commonly experienced by millions of patients who undergo outpatient surgical procedures. Moreover, an increasing number of procedures are performed on an outpatient basis, requiring greater postoperative planning to ensure effective pain management. Analgesic approaches commonly involve prescription opioids and non-steroidal anti-inflammatory drugs (NSAIDs), but an optimal regimen that balances pain and adverse effects has not been identified. In addition, critical gaps in evidence exist regarding how opioids and NSAIDs compare as analgesic regimens after surgery.

METHODS AND ANALYSIS: The Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES) trial is a pragmatic, international, multicentre randomised trial …

Year 1 Of Medicare's Accountable Care Organization Realizing Equity, Access, And Community Health Model, Gmerice Hammond, Sunny Lin, Sukruth A Shashikumar, R J Waken, Fengxian Wang, Khavya Avula, Vi-Anh Hoang, Kenton J Johnston, Karen Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: The US Centers for Medicare & Medicaid Services launched the Accountable Care Organization (ACO) Realizing Equity, Access, and Community Health (REACH) payment model in January 2023. In contrast to prior ACO initiatives, such as the Medicare Shared Savings Program (MSSP), ACO REACH includes equity-focused measures and payment adjustments, including an equity plan and financial risk adjustment for ACOs with higher proportions of underserved beneficiaries. However, it is unknown whether these changes have incented participation from organizations that serve beneficiaries from marginalized communities.

OBJECTIVE: To compare characteristics between participants in ACO REACH with those in MSSP and the broader pool …

Responsible Sharing Of Qualitative Research Data: Insights From A Pioneering Project In The United States, Heidi A. Walsh, Meredith V. Parsons, Jessica Mozersky, Aditi Gupta, Albert M. Lai, Annie B. Friedrich, James M. Dubois

2020-Current year OA Pubs

No abstract provided.

Nitrous Oxide Activates Layer 5 Prefrontal Neurons Via Sk2 Channel Inhibition For Antidepressant Effect, Joseph Cichon, Thomas T Joseph, Xinguo Lu, Andrzej Z Wasilczuk, Max B Kelz, Steven J Mennerick, Charles F Zorumski, Peter Nagele

2020-Current year OA Pubs

Nitrous oxide (N

A Mapping Review And Critique Of The Literature On Translation, Dissemination, And Implementation Capacity Building Initiatives For Different Audiences, Ana A Baumann, Danielle R Adams, Laura-Mae Baldwin, Rachel G Tabak, Sara Malone, Maura M Kepper, Anita D Misra-Hebert, Kathleen R Stevens, Maria E Fernandez, Sunil Kripalani

2020-Current year OA Pubs

BACKGROUND: Capacity building is critical for research and practice as the fields of dissemination, implementation and translation science continue to grow. Some scholars state that capacity building should be grounded in competencies. However, the fields are unclear in determining which competencies are relevant for whom, including the content and appropriate level of information and skills for different roles. The goal of this study was to catalogue competencies across current D&I capacity building initiatives.

METHODS: We conducted a mapping review to examine to what extent are theories or frameworks used to guide capacity building, who is being trained, to what extent …

Open Access Dataset And Common Data Model For Pulse Oximeter Performance Data, Nicholas Fong, Leonid Shmuylovich, Et Al.

2020-Current year OA Pubs

The OpenOximetry Dataset stores clinical and lab pulse oximetry data. It supports measurements of arterial oxygen saturation (SaO2) by arterial blood gas co-oximetry and pulse oximetry (SpO2), alongside processed and unprocessed photoplethysmography (PPG) data and other metadata. This includes skin color measurements, finger diameter, vital signs (e.g., arterial blood pressure, end-tidal carbon dioxide), and arterial blood gas parameters (e.g., acid-base balance, hemoglobin concentration). All data, from desaturation studies to clinical trials, are collected prospectively to ensure accuracy. A common data model and standardized protocols for consistent archival and interpretation ensure consistent data archival and interpretation. The dataset aims to facilitate …

Cross-Ancestry Genome-Wide Association Study Identifies Implications Of Sorl1 In Cerebral Beta-Amyloid Deposition, Jun Pyo Kim, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

GWAS of Alzheimer's disease have been predominantly based on European ancestry cohorts with clinically diagnosed patients. Increasing the ancestral diversity of GWAS and focusing on imaging brain biomarkers for Alzheimer's disease may lead to the identification of new genetic loci. Here, we perform a GWAS on cerebral β-amyloid deposition measured by PET imaging in 3,885 East Asians and a cross-ancestry GWAS meta-analysis with data from 11,816 European participants. Our GWAS analysis replicates known loci (APOE4, CR1, and FERMT2) and identifies a novel locus near SORL1 that is significantly associated with β-amyloid deposition. Single-nucleus expression analysis shows that SORL1 is differentially …

Unraveling The Complexities Of Myeloid-Derived Suppressor Cells In Inflammatory Bowel Disease, Yangzhuangzhuang Zhu, Siyan Cao

2020-Current year OA Pubs

Myeloid-derived suppressor cells (MDSCs) regulate immune responses in many pathological conditions, one of which is inflammatory bowel disease (IBD), an incurable chronic disorder of the digestive tract and beyond. The pathophysiology of IBD remains unclear, likely involving aberrant innate and adaptive immunity. Studies have reported altered population of MDSCs in patients with IBD. However, their distribution varies among patients and different preclinical models of IBD. The expansion and activation of MDSCs are likely driven by various stimuli during intestinal inflammation, but the in-depth mechanisms remain poorly understood. The role of MDSCs in the pathogenesis of IBD appears to be paradoxical. …

Capitalizing On Natural Language Processing (Nlp) To Automate The Evaluation Of Coach Implementation Fidelity In Guided Digital Cognitive-Behavioral Therapy (Gdcbt), Nur Hani Zainal, Regina Eckhardt, Gavin N Rackoff, Ellen E Fitzsimmons-Craft, Elsa Rojas-Ashe, Craig Barr Taylor, Burkhardt Funk, Daniel Eisenberg, Denise E Wilfley, Michelle G Newman

2020-Current year OA Pubs

BACKGROUND: As the use of guided digitally-delivered cognitive-behavioral therapy (GdCBT) grows, pragmatic analytic tools are needed to evaluate coaches' implementation fidelity.

AIMS: We evaluated how natural language processing (NLP) and machine learning (ML) methods might automate the monitoring of coaches' implementation fidelity to GdCBT delivered as part of a randomized controlled trial.

METHOD: Coaches served as guides to 6-month GdCBT with 3,381 assigned users with or at risk for anxiety, depression, or eating disorders. CBT-trained and supervised human coders used a rubric to rate the implementation fidelity of 13,529 coach-to-user messages. NLP methods abstracted data from text-based coach-to-user messages, and …

Systemic Inflammation Is Associated With Worse Outcomes From Sars-Cov-2 Infection But Not Neutralizing Antibody, Christopher W Farnsworth, Brittany Roemmich, John Prostko, Gerard Davis, Gillian Murtagh, Laurel Jackson, Christopher Jacobson, Nicolette Jeanblanc, Timothy Griffiths, Edwin Frias, David J Daghfal

2020-Current year OA Pubs

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation …

Statistical Properties Of Functional Connectivity Mri Enrichment Analysis In School-Age Autism Research, Austin S Ferguson, Tomoyuki Nishino, Natasha Marrus, John R Pruett Jr, Alexandre A Todorov, Et Al.

2020-Current year OA Pubs

Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations. However, there has not yet been a rigorous examination of the statistical properties of enrichment analysis when applied to fcMRI data. Establishing power for fcMRI enrichment analysis will be important for future neuropsychiatric and cognitive neuroscience study designs that plan to include this method. Here, we use realistic …

Tenapanor Improves Abdominal Symptoms Irrespective Of Changes In Complete Spontaneous Bowel Movement Frequency In Adults With Irritable Bowel Syndrome With Constipation, Darren M Brenner, Gregory S Sayuk, Brooks D Cash, Lucinda A Harris, Nitin K Ahuja, Jill K Deutsch, Yang Yang, Suling Zhao, David P Rosenbaum, Anthony J Lembo

2020-Current year OA Pubs

INTRODUCTION: Tenapanor is a first-in-class, minimally absorbed intestinal sodium/hydrogen exchanger isoform 3 inhibitor approved by the US Food and Drug Administration for adults with irritable bowel syndrome with constipation (IBS-C). Pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies examined the effects of tenapanor on abdominal symptoms independent of tenapanor's effect on complete spontaneous bowel movement (CSBM) frequency in adults with IBS-C.

METHODS: This post hoc analysis was performed for patients with no CSBMs in ≥6 of the first 12 weeks of treatment (no-CSBM subgroup). The three-item abdominal score (AS3; the average of …

Sexually Dimorphic Cardiovascular Impacts Of Prenatal Exposure To A Real-Life Environmental Chemical Mixture In Adult Offspring, Noor Muhammad Khan, Victoria Scott, Mohammad Ghasemzadeh-Hasankolaei, Vasantha Padmanabhan, Arpita Vyas, Neil P Evans, Michelle Bellingham

2020-Current year OA Pubs

Cardiovascular disease (CVD) is a leading cause of death that is sexually dimorphic. This study used an ovine model to investigate whether maternal exposure to an environmental chemical (EC) mixture (biosolids) prior to and throughout pregnancy, affected offspring cardiovascular (CV) structure and function in adulthood. CV function of male and female offspring from ewes grazed on either conventionally fertilised (control, C) or biosolids-treated pasture (B) was assessed. Males exhibited higher blood pressure compared to females with no significant effect of EC exposure. Heart rate variability in females suggested reduced autonomic regulation in the B group. EC-exposed males, but not females, …

Antibody Responses In Klebsiella Pneumoniae Bloodstream Infection: A Prospective Cohort Study, Wontae Hwang, Paeton L Wantuch, David A Rosen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function.

METHODS: In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream …

Multi-Omic Analysis Of Biological Aging Biomarkers In Long-Term Calorie Restriction And Endurance Exercise Practitioners: A Cross-Sectional Study, Giovanni Fiorito, Valeria Tosti, Silvia Polidoro, Beatrice Bertozzi, Nicola Veronese, Edda Cava, Francesco Spelta, Laura Piccio, Dayna S Early, Daniel Raftery, Paolo Vineis, Luigi Fontana

2020-Current year OA Pubs

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of …

Linear Growth During Treatment With A Simplified, Combined Protocol: Secondary Analyses Of Severely Wasted Children 6-59 Months In The Compas Cluster Randomized Controlled Trial, Grace Heymsfield, Kevin Stephenson, Zachary Tausanovitch, André Briend, Marko Kerac, Heather Stobaugh, Jeanette Bailey, Suvi T Kangas

2020-Current year OA Pubs

A simplified, combined protocol treats children with moderate acute malnutrition (MAM), defined by mid-upper arm circumference (MUAC) of <  125 and ≥ 115 mm and no oedema, with 1 daily sachet of ready-to-use therapeutic food (RUTF) and those with severe acute malnutrition (SAM), defined by MUAC <  115 mm and/or oedema, with two daily sachets of RUTF. This protocol was previously shown to result in non-inferior recovery compared to standard treatment that used higher, weight-based RUTF dosing among children with SAM and ready-to-use supplementary food (RUSF) for MAM in a cluster-based randomised controlled trial in Kenya and South Sudan. We conducted a secondary analysis of this trial to compare linear growth among children admitted with MUAC <  115 mm. Linear and ponderal growth were calculated from admission to discharge and visualised using aggregate growth curves. HAZ change adjusted for admission characteristics was negative across the course of treatment but similar across arms [-0.21 ± 0.18 SE in the standard arm, -0.24 ± 0.18 SE in simplified; difference (95% confidence interval) 0.03 (-0.12, 0.18)]. The unadjusted mean ± SE linear growth velocity from admission to discharge was 1.8 ± 0.7 mm/week in the standard arm compared to 1.7 ± 0.7 mm/week in the simplified arm [difference = 0.09 (-0.36, 0.53)] and similar in adjusted analysis. MUAC and weight gain velocities were not significantly different by treatment arm. Reducing the RUTF dose prescribed to children during SAM treatment does not appear to affect linear growth or other growth velocities during treatment.

Dynein Light Chains 1 And 2 Are Auxiliary Proteins Of Ph-Sensitive Kir4.1 Channels, Sun-Joo Lee, Jian Gao, Ellen Thompson, Jonathan Mount, Colin G Nichols

2020-Current year OA Pubs

Inward rectifier Kir4.1 potassium channels are abundantly expressed in cells that are important for electrolyte homeostasis. Dysregulation of Kir4.1 underlies various neurological disorders. Here, through biochemical and structural studies of full-length Kir4.1, we show that dynein light chain 1 and 2 proteins, also as known as LC8, copurify with Kir4.1 at stoichiometric levels. Direct interaction between Kir4.1 and LC8 is supported by in vitro binding assays and reiterated with native Kir4.1 proteins from mouse brain. Notably, we identify a LC8 binding motif in the unstructured N terminus of Kir4.1. Among Kir subtypes, the motif is unique to Kir4.1 and is …

Racial Disparities In Utilization Of Medications And Disease Outcomes In Inflammatory Bowel Disease Patients, Khaled Alsabbagh Alchirazi, Osama Hamid, Thabet Qapaja, Mohammad Aldiabat, Nour Azzouz, Motasem Alkhayyat, Miguel Regueiro

2020-Current year OA Pubs

BACKGROUND: Although traditionally associated with White European ancestry, inflammatory bowel disease (IBD) has increased among different races and ethnicities. Large studies conducted in the United States and Canada have identified more complex disease phenotypes among Black patients. Our study aimed to investigate disparities in IBD treatments and outcomes between Black and White patients in the United States.

METHODS: Using the TriNetX database, adult IBD patients were divided into 2 groups based on race: Black and White patients with IBD, Crohn's disease (CD), or ulcerative colitis (UC). Medical therapy and disease outcomes were evaluated in both groups with 1:1 propensity-score matching. …

Dynamic Femoral Head Coverage Following Periacetabular Osteotomy For Developmental Dysplasia Of The Hip, Christina A Bourantas, Emma C Behrman, Molly C Shepherd, Keith R Lohse, John C Clohisy, Michael D Harris

2020-Current year OA Pubs

BACKGROUND: Developmental dysplasia of the hip reduces hip stability due to insufficient femoral head coverage. Periacetabular osteotomy surgery aims to increase this coverage. Typically measured using radiographs, most coverage assessments are limited to static hip positions and cannot capture 3D anatomy. This study quantified how dynamic 3D femoral coverage changes during gait and squat after periacetabular osteotomy surgery and compared dynamic coverage to static measures.

METHODS: Pre- and post-surgery CT scans from 38 patients with hip dysplasia were used to reconstruct 3D femur and pelvis bones with which gait and squat were simulated. Models of 38 control subjects were also …

The Cognitive Profile Of Older Adults With Treatment-Resistant Depression: An Analysis Of The Optimum Randomized Controlled Trial, Nicholas J Ainsworth, Hanadi Oughli, Helen Lavretsky, Daniel M Blumberger, Patrick J Brown, Meryl A Butters, Jordan F Karp, Emily Lenard, Eric J Lenze, Mary Pat Mcandrews, J Philip Miller, Bruce G Pollock, Charles F Reynolds, Benoit H Mulsant

2020-Current year OA Pubs

OBJECTIVE: Major depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy.

DESIGN: Secondary analysis of baseline cognitive data from OPTIMUM, a multicenter RCT evaluating pharmacotherapy strategies for TR-LLD.

SETTING: Five outpatient academic medical centers (4 US, 1 Canada).

PARTICIPANTS: About 369 …

Long-Term Results Of Bone-Patellar Tendon-Bone Versus Hamstring Tendon Autograft For Primary Anterior Cruciate Ligament Reconstruction: A Meta-Analysis Of Randomized Controlled Trials, Varun Gopinatth, Sina Tartibi, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik

2020-Current year OA Pubs

BACKGROUND: Bone-patellar tendon-bone (BTB) and hamstring tendon (HT) autografts are the most commonly utilized grafts for primary anterior cruciate ligament reconstruction (ACLR). While previous studies have compared outcomes using BTB and HT grafts for ACLR at short- and mid-term follow-ups, outcomes at long-term follow-ups remain unclear.

PURPOSE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating BTB versus HT autografts for primary ACLR at a minimum 10-year follow-up.

STUDY DESIGN: Systematic review; Level of evidence, 2.

METHODS: A systematic review was performed in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …

Lyset Facilitates Integration Of Both The N- And C-Terminal Transmembrane Helices/Cytoplasmic Domains Of Glcnac-1-Phosphotransferase, Baraj Doray, Benjamin C Jennings, Xi Yang, Lin Liu, Varsha Venkatarangan, Stuart Kornfeld, Ming Li

2020-Current year OA Pubs

LYSET is a recently identified Golgi transmembrane (TM) protein, and inactivating mutations in the

Transcriptome Meta-Analysis Uncovers Cell-Specific Regulatory Relationships In Embryonic, Juvenile, Adult, And Aged Mouse Lens Epithelium And Fibers, Matthieu Duot, Sarah Y Coomson, Sanjaya K Shrestha, M V Murali Krishna Nagulla, Yann Audic, Ruteja A Barve, Hongzhan Huang, Carole Gautier-Courteille, Luc Paillard, Salil A Lachke

2020-Current year OA Pubs

PURPOSE: The lens transcriptome has been examined using microarrays and RNA-sequencing (RNA-seq). These omics data are the basis of the bioinformatics web-resource iSyTE that has identified new genes involved in lens development and cataract. The lens predominantly contains epithelial and fiber cells, and yet, presently, iSyTE is based on whole lens data. To gain cell-specific regulatory insights, we meta-analyzed isolated epithelium and fiber transcriptomes from embryonic/postnatal, adult and aged lenses.

METHODS: Mouse lens epithelium and fiber transcriptome public datasets at embryonic (E) and postnatal (P) stages E12.5, E14.5, E16.5, E18.5, P0.5, P0, P5, P13, and age one month, three months, …

Enhancing Human Nk Cell Antitumor Function By Knocking Out Smad4 To Counteract Tgfβ And Activin A Suppression, Anna Rea, Bishan Bhattarai, Marco Colonna, Et Al.

2020-Current year OA Pubs

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR-Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4

Patient- And Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.

OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.

DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional …

Patients' Attitudes To Magnetic Resonance Imaging In Perianal Fistulizing Crohn's Disease: A Global Survey, Easan Anand, Jalpa Devi, Anna Antoniou, Shivani Joshi, Jaap Stoker, Phillip Lung, Ailsa Hart, Phil Tozer, David H Ballard, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: There is limited patient involvement in radiological research for perianal fistulizing Crohn's disease (pfCD), despite magnetic resonance imaging (MRI)'s critical role in diagnosis and management. Patient and public involvement is essential for aligning research with patient priorities. This study aimed to gather patient perspectives on the use of MRI in pfCD.

METHODS: A mixed-methods approach was used, following Guidance for Reporting Involvement of Patients and the Public (GRIPP2) guidelines. An online survey, co-developed with a patient representative, included open and closed questions on MRI experiences, advantages, challenges, and the potential for Artificial Intelligence (AI)-generated reports. This was followed by …

Applying Results Of Extended Genotyping To Management Of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines, L. Stewart Massad, Megan A. Clarke, Rebecca B. Perkins, Francisco Garcia, David Chelmow, Li C. Cheung, Teresa M. Darragh, Didem Egemen, Thomas S. Lorey, Ritu Nayar, Morgan Newman, Carolann Risley, Robert A. Smith, Nicolas Wentzensen, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee

2020-Current year OA Pubs

OBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs.

METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through …