The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats.

Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( = 12), healthy cats ( = 9), and cats with tooth resorption or periodontitis ( = 11).

Trophectoderm biopsy of blastocysts following IVF and embryo culture increases epigenetic dysregulation in a mouse model.

Study Question: Does trophectoderm biopsy (TEBx) of blastocysts for preimplantation genetic testing in the clinic affect normal placental and embryo development and offspring metabolic outcomes in a mouse model?

Summary Answer: TEBx impacts placental and embryonic health during early development, with some alterations resolving and others worsening later in development and triggering metabolic changes in adult offspring.

What Is Known Already: Previous studies have not assessed the epigenetic and morphological impacts of TEBx either in human populations or in animal models.

Study Design, Size, Duration: We employed a mouse model to identify the effects of TEBx during IVF.

Machine learning prediction of hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the United States.

Background And Purpose: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining.

Incident Asthma, Asthma Exacerbations, and Asthma-Related Hospitalizations in Patients With Atopic Dermatitis.

Background: Atopic dermatitis (AD) is thought to induce asthma via the "atopic march," but the effects of AD on incident asthma and asthma severity have not been fully characterized.

Objective: To determine risk of asthma, asthma exacerbations, and asthma-related hospitalizations among patients fwith AD.

Methods: A cohort study was conducted using electronic health records data from UK general practices from 1994 to 2015.

Associations Between End-Tidal Carbon Dioxide During Pediatric Cardiopulmonary Resuscitation, Cardiopulmonary Resuscitation Quality, and Survival.

Background: Supported by laboratory and clinical investigations of adult cardiopulmonary arrest, resuscitation guidelines recommend monitoring end-tidal carbon dioxide (ETCO) as an indicator of cardiopulmonary resuscitation (CPR) quality, but they note that "specific values to guide therapy have not been established in children."

Methods: This prospective observational cohort study was a National Heart, Lung, and Blood Institute-funded ancillary study of children in the ICU-RESUS trial (Intensive Care Unit-Resuscitation Project; NCT02837497). Hospitalized children (≤18 years of age and ≥37 weeks postgestational age) who received chest compressions of any duration for cardiopulmonary arrest, had an endotracheal or tracheostomy tube at the start of CPR, and evaluable intra-arrest ETCO data were included.

RAB1A haploinsufficiency phenocopies the 2p14-p15 microdeletion and is associated with impaired neuronal differentiation.

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.

Regulation of eDHFR-tagged proteins with trimethoprim PROTACs.

Temporal control of protein levels in cells and living animals can be used to improve our understanding of protein function. In addition, control of engineered proteins could be used in therapeutic applications. PRoteolysis-TArgeting Chimeras (PROTACs) have emerged as a small-molecule-driven strategy to achieve rapid, post-translational regulation of protein abundance via recruitment of an E3 ligase to the target protein of interest.

Changes in the burden of medications that may impair driving among older adults before and after a motor vehicle crash.

Background: Medications are one of the most easily modifiable risk factors for motor vehicle crashes (MVCs) among older adults, yet limited information exists on how the use of potentially driver-impairing (PDI) medications changes following an MVC. Therefore, we examined the number and types of PDI medication classes dispensed before and after an MVC.

Methods: This observational study included Medicare fee-for-service beneficiaries aged ≥67 years who were involved in a police-reported MVC in New Jersey as a driver between 2008 and 2017.

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5).

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.

Outcomes in High-Risk Pulmonary Embolism Patients Undergoing FlowTriever Mechanical Thrombectomy or Other Contemporary Therapies: Results From the FLAME Study.

Background: Hemodynamically unstable high-risk, or massive, pulmonary embolism (PE) has a reported in-hospital mortality of over 25%. Systemic thrombolysis is the guideline-recommended treatment despite limited evidence. The FLAME study (FlowTriever for Acute Massive PE) was designed to generate evidence for interventional treatments in high-risk PE.

Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline.

Background And Objectives: The purpose of this guideline is to update the 2010 American Academy of Neurology (AAN) brain death/death by neurologic criteria (BD/DNC) guideline for adults and the 2011 American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine guideline for infants and children and to clarify the BD/DNC determination process by integrating guidance for adults and children into a single guideline. Updates in this guideline include guidance related to conducting the BD/DNC evaluation in the context of extracorporeal membrane oxygenation, targeted temperature management, and primary infratentorial injury.

Methods: A panel of experts from multiple medical societies developed BD/DNC recommendations.

Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Association of Breast Cancer Odds with Background Parenchymal Enhancement Quantified Using a Fully Automated Method at MRI: The IMAGINE Study.

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer.

A new method for multiancestry polygenic prediction improves performance across diverse populations.

Polygenic risk scores (PRSs) increasingly predict complex traits; however, suboptimal performance in non-European populations raise concerns about clinical applications and health inequities. We developed CT-SLEB, a powerful and scalable method to calculate PRSs, using ancestry-specific genome-wide association study summary statistics from multiancestry training samples, integrating clumping and thresholding, empirical Bayes and superlearning. We evaluated CT-SLEB and nine alternative methods with large-scale simulated genome-wide association studies (~19 million common variants) and datasets from 23andMe, Inc.

mTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.

Background: Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endothelial cells. Gain-of-function mutations in (encoding the enzymatic subunit of the PI3K (phosphoinositide 3-kinase) pathway associated with cell growth) synergize with CCM gene loss-of-function to generate rapidly growing lesions.

Nuclear speckles regulate HIF-2α programs and correlate with patient survival in kidney cancer.

Nuclear speckles are membrane-less bodies within the cell nucleus enriched in RNA biogenesis, processing, and export factors. In this study we investigated speckle phenotype variation in human cancer, finding a reproducible speckle signature, based on RNA expression of speckle-resident proteins, across >20 cancer types. Of these, clear cell renal cell carcinoma (ccRCC) exhibited a clear correlation between the presence of this speckle expression signature, imaging-based speckle phenotype, and clinical outcomes.

Multilevel Community Engagement to Inform a Randomized Clinical Trial.

Objective: To explore how patients, community-based perinatal support professionals, and health system clinicians and staff perceived facilitators and barriers to implementation of a randomized clinical trial (RCT) designed to optimize Black maternal heart health.

Methods: This article describes the formative work that we believed needed to occur before the start of the Change of H.E.

Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19.

Background: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear.

Methods: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 μg once daily for 14 days or placebo.

mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis.

Background And Objective: In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens.

Methods: This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine.

Midlife Hemostasis Measures, 20-Year Cognitive Decline, and Incident Dementia.

Background And Objectives: Blood concentrations of hemostatic factors affect thrombosis and bleeding diathesis and may contribute to cognitive impairment through modifiable vascular pathologies. Whether hemostasis, assessed in middle age, is associated with late-life cognitive impairment remains largely unknown in a community-dwelling population.

Methods: Using data from 14,128 participants with cognitive function measurements in 1990-1992 from the Atherosclerosis Risk in Communities study, we assessed the associations of hemostasis measures with 20-year changes in cognitive performance and incident dementia.

The Impact of Unexpected Billing in Spine Surgery and How the Price Calculator Can Improve Patient Care.

Study Design: Survey study.

Objective: The objective of this study was to determine the impact of unexpected in-network billing on the patient experience after spinal surgery.

Summary Of Background Data: The average American household faces difficulty paying unexpected medical bills.

Clinical Classification of Variants in the Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy.

Background And Objectives: Pathogenic variants in the valosin-containing protein () gene cause a phenotypically heterogeneous disorder that includes myopathy, motor neuron disease, Paget disease of the bone, frontotemporal dementia, and parkinsonism termed multisystem proteinopathy. This hallmark pleiotropy makes the classification of novel variants challenging. This retrospective study describes and assesses the effect of 19 novel or nonpreviously clinically characterized variants identified in 28 patients (26 unrelated families) in the retrospective VCP International Multicenter Study.