Trypanosoma cruzi infection in dogs along the US-Mexico border: R changes with vector species composition.

Infection with Trypanosoma cruzi, etiological agent of Chagas disease, is common in US government working dogs along the US-Mexico border. This 3145 km long border comprises four states: Texas (TX), New Mexico (NM), Arizona (AZ) and California (CA) with diverse ecosystems and several triatomine (a.k.

Pembrolizumab With R-CHOP in Previously Untreated DLBCL: Sustained, High Efficacy, and Safety With Long-Term Follow-Up.

Background: While generally ineffective in relapsed diffuse large B cell lymphoma (DLBCL), immune checkpoint inhibitors (ICIs) may hold greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (PR-CHOP) in a phase I trial of untreated DLBCL, noting responses in 90% of patients (complete response 77%) and a 2-year progression-free survival (PFS) of 83%. We herein report long-term safety and efficacy at 5-year follow up.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

Background: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values.

Methods: SPRINT data were linked with EHR data from 49 (of 102) study sites.

Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

Background: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

Methods: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines.

The role of aspirin, statins, colchicine, and IL-1 inhibitors in prevention of cardiovascular events: a systematic integrative review.

Context: Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse cardiovascular events (CVEs). Specifically, identifying drugs that can reduce the progression of CVD and serious adverse events is much needed.

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.

Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.

Methods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level.

Noncontact Infant Apnea Detection for Hypoxia Prevention With a K-Band Biomedical Radar.

Annually, a significant number of premature infants suffer from apnea, which can easily cause a drop in oxygen saturation levels, leading to hypoxia. However, infant cardiopulmonary monitoring using conventional methods often necessitates skin contact, and they are not suitable for long-term monitoring. This article introduces a non-contact technique for infant cardiopulmonary monitoring and an adjustable apnea detection algorithm.

A recombinant virus-like particle vaccine against adenovirus-7 induces a potent humoral response.

Adenoviruses (AdVs) cause infections in humans that range from mild to severe, and can cause outbreaks particularly in close contact settings. Several human AdV types have been identified, which can cause a wide array of clinical manifestations. AdV types 4 and 7 (AdV-4 and AdV-7), which are among the most commonly circulating types in the United States, are known to cause acute respiratory disease that can result in hospitalization and rarely, death.

Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

Background: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy.

Methods: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy.

Machine Learning-Enabled Quantitative Analysis of Optically Obscure Scratches on Nickel-Plated Additively Manufactured (AM) Samples.

Additively manufactured metal components often have rough and uneven surfaces, necessitating post-processing and surface polishing. Hardness is a critical characteristic that affects overall component properties, including wear. This study employed K-means unsupervised machine learning to explore the relationship between the relative surface hardness and scratch width of electroless nickel plating on additively manufactured composite components.

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.

Factors influencing behavioral cough suppression therapy in children with nonspecific chronic cough.

Background: Behavioral cough suppression therapy (BCST) with a speech-language pathologist is a common treatment for chronic nonspecific cough (a.k.a.

Development of Electronic Health Record-Based Machine Learning Models to Predict Barrett's Esophagus and Esophageal Adenocarcinoma Risk.

Introduction: Screening for Barrett's esophagus (BE) is suggested in those with risk factors, but remains underutilized. BE/esophageal adenocarcinoma (EAC) risk prediction tools integrating multiple risk factors have been described. However, accuracy remains modest (area under the receiver-operating curve [AUROC] ≤0.

Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension.

Background: Epigenetic regulation of vascular remodeling in pulmonary hypertension (PH) is poorly understood. Transcription regulating, histone acetylation code alters chromatin accessibility to promote transcriptional activation. Our goal was to identify upstream mechanisms that disrupt epigenetic equilibrium in PH.

Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction.

Background: Clonal hematopoiesis (CH), which results from an array of nonmalignant driver gene mutations, can lead to altered immune cell function and chronic disease, and has been associated with worse outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the role of CH in the prognosis of HF with preserved ejection fraction (HFpEF) has been understudied. This study aimed to characterize CH in patients with HFpEF and elucidate its causal role in a murine model.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1.

Selection of viral capsids and promoters affects the efficacy of rescue of -deficient cochlea.

Adeno-associated virus (AAV)-mediated gene transfer has shown promise in rescuing mouse models of genetic hearing loss, but how viral capsid and promoter selection affects efficacy is poorly characterized. Here, we tested combinations of AAVs and promoters to deliver , mutations in which are associated with hearing loss in humans. mice display severe cochlear hair cell degeneration, loss of auditory brainstem responses, and delayed loss of spiral ganglion neurons.

Correlation of Manifest Refraction and Simulated Keratometry to Tomography Characteristics in Patients With Keratoconus.

Objectives: To report on baseline refractive and keratometric values and their correlation with tomographic characteristics of eyes with keratoconus (KC).

Methods: Retrospective chart review of patients treated in a single-center cornea and refractive surgery practice. Baseline topographic measurements were reviewed for 1,012 keratoconic eyes of 586 patients between 2008 and 2018.

Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are part of the standard of care for patients with chronic kidney disease (CKD), both with and without type 2 diabetes. Endothelin A (ETA) receptor antagonists have also been shown to slow progression of CKD. Differing mechanisms of action of SGLT2 and ETA receptor antagonists may enhance efficacy.

Three-dimensional echocardiographic evaluation of longitudinal and non-longitudinal components of right ventricular contraction: results from the World Alliance of Societies of Echocardiography study.

Aims: Right ventricular (RV) functional assessment is mainly limited to its longitudinal contraction. Dedicated three-dimensional echocardiography (3DE) software enabled the separate assessment of the non-longitudinal components of RV ejection fraction (EF). The aims of this study were (i) to establish normal values for RV 3D-derived longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their relative contributions to global RVEF, (ii) to calculate 3D RV strain normal values, and (iii) to determine sex-, age-, and race-related differences in these parameters in a large group of normal subjects (WASE study).

Transcriptomic Maps of Colorectal Liver Metastasis: Machine Learning of Gene Activation Patterns and Epigenetic Trajectories in Support of Precision Medicine.

The molecular mechanisms of the liver metastasis of colorectal cancer (CRLM) remain poorly understood. Here, we applied machine learning and bioinformatics trajectory inference to analyze a gene expression dataset of CRLM. We studied the co-regulation patterns at the gene level, the potential paths of tumor development, their functional context, and their prognostic relevance.