An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.

Adjuvant strategies to tackle -mediated polymyxin resistance.

The emergence of the () gene is a demonstrable threat contributing to the worldwide antibiotic resistance crisis. The gene is encoded on plasmids and can easily spread between different bacterial strains. encodes a phosphoethanolamine (pEtN) transferase, which catalyses the transfer of the pEtN moiety from phosphatidylethanolamine to lipid A, the head group of lipopolysaccharides (LPS).

Deep generative design of RNA aptamers using structural predictions.

RNAs represent a class of programmable biomolecules capable of performing diverse biological functions. Recent studies have developed accurate RNA three-dimensional structure prediction methods, which may enable new RNAs to be designed in a structure-guided manner. Here, we develop a structure-to-sequence deep learning platform for the de novo generative design of RNA aptamers.

Drivers and Impacts of the Record-Breaking 2023 Wildfire Season in Canada.

The 2023 wildfire season in Canada was unprecedented in its scale and intensity, spanning from mid-April to late October and across much of the forested regions of Canada. Here, we summarize the main causes and impacts of this exceptional season. The record-breaking total area burned (~15 Mha) can be attributed to several environmental factors that converged early in the season: early snowmelt, multiannual drought conditions in western Canada, and the rapid transition to drought in eastern Canada.

Small molecules targeting GRP78 mitigate anti-GRP78 autoantibody-mediated tissue factor procoagulant activity in cultured endothelial cells.

Background: The 78-kDa glucose-regulated protein (GRP78) expressed on the cell surface (csGRP78) has been reported to regulate tissue factor (TF) procoagulant activity (PCA) in lesion-resident endothelial cells (ECs), which is further enhanced by circulating anti-GRP78 autoantibodies that bind to the Leu-Leu epitope in GRP78.

Objectives: Determine the effects of the engagement of the anti-GRP78 autoantibody to csGRP78 on ECs and the underlying mechanisms that impact TF PCA.

Methods: Immunofluorescent staining was used to determine the presence of csGRP78 in tumor necrosis factor α-treated ECs.

Medicaid long-term services and supports and caregiving needs of caregivers of individuals with intellectual and developmental disabilities.

Background: Long-term care services are funded primarily by Medicaid long-term services and support in the United States, where eligibility is based on care needs of the individual with intellectual and developmental disability alone. Impact of Medicaid waiver services on self-reported caregiver needs is not well understood.

Method: Caregivers (n = 405) of individuals with intellectual and developmental disabilities across four states (NY, OH, TX, and PA) completed an online survey.

Discovery of a new class of cell-penetrating peptides by novel phage display platform.

The primary hurdles for small interference RNA (siRNA) in clinical use are targeted and cytosolic delivery. To overcome both challenges, we have established a novel platform based on phage display, called NNJA. In this approach, a lysosomal cathepsin substrate is engineered within the flexible loops of PIII, that is displaying a unique random sequence at its N-terminus.

Performance of HER2 DAKO HercepTest and Ventana 4B5 immunohistochemical assays on detecting HER2 gene-amplification in uterine serous carcinomas.

We compared the performance of two commonly-used HER2 immunohistochemistry (IHC) assays in uterine serous carcinomas (USC), correlating with HER2 gene amplification by fluorescence in-situ hybridization (FISH). Sixty-five USCs were stained by both HercepTest™ and PATHWAY 4B5 assays. FISH was performed by HER2 IQFISH pharmDx.

Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

Objective: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice.

Patients And Methods: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT.

Utilization and Patient-Reported Outcomes of Direct-to-Consumer Telemedicine During the First 6 Weeks of the COVID-19 Pandemic in the Largest Pediatric Ambulatory Network in New York State.

We aimed to (1) describe telemedicine utilization and usability during the first 6 weeks of the pandemic and (2) determine if usability varied by individual- or visit-level characteristics. We conducted a retrospective cohort study of ambulatory pediatric telemedicine visits occurring between March 10, 2020, and April 18, 2020, across a large academic health system. We performed manual chart review to assess individual- and visit-level characteristics and invited caregivers to respond to an adapted Telehealth Usability Questionnaire (TUQ).

Quality of Web-Based Sickle Cell Disease Resources for Health Care Transition: Website Content Analysis.

Background: Adolescents and young adults with sickle cell disease (SCD) transitioning from pediatric to adult health care face a high-risk period associated with increased use of acute health care services and mortality. Although 59% of American citizens report using the internet for health care information, the quality of web-based, patient-facing resources regarding transition in SCD care has not been evaluated.

Objective: This study aimed to evaluate the quality and readability of web-based health information on SCD, especially as it pertains to the transition to adulthood for inidividuals with SCD.

The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1.

Increasing the therapeutic potential and reducing the side effects of U.S. Food and Drug Administration-approved glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat obesity require complete characterization of the central mechanisms that mediate both the food intake-suppressive and illness-like effects of GLP-1R signaling.

Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion.

Caregiver support, burden, and long-term planning among caregivers of individuals with intellectual and developmental disabilities: A cross-sectional study.

Background: Long-term care planning (LTCP) is critical for individuals with intellectual/developmental disabilities. Objectives of this study were to investigate progression through LTCP, and associations between social support and: (1) LTCP and (2) burden among family caregivers.

Methods: A cross-sectional survey was distributed to caregivers of individuals with intellectual/developmental disabilities in NY, OH, PA, and TX, exploring demographics, supports, burden, and LTCP behaviours.

Consensus Statements on Precision Oncology in the China Greater Bay Area.

Background: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA.

Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding.

Background: There is great interest to engineer in vitro models that allow the study of complex biological processes of the microvasculature with high spatiotemporal resolution. Microfluidic systems are currently used to engineer microvasculature in vitro, which consists of perfusable microvascular networks (MVNs). These are formed through spontaneous vasculogenesis and exhibit the closest resemblance to physiological microvasculature.

Maternal Anti-Ro Antibody Titers Obtained With Commercially Available Immunoassays Are Strongly Associated With Immune-Mediated Fetal Heart Disease.

Objective: Anti-Ro antibody-positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti-Ro antibody titers and fetal CNL.

Autocatalytic base editing for RNA-responsive translational control.

Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. To this end, here we engineer programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. Dubbed DART VADAR (Detection and Amplification of RNA Triggers via ADAR), our system amplifies the signal from editing by endogenous ADAR through a positive feedback loop.

A Repeat Pattern of Founder Events for SARS-CoV-2 Variants in Alaska.

Alaska is a unique US state because of its large size, geographically disparate population density, and physical distance from the contiguous United States. Here, we describe a pattern of SARS-CoV-2 variant emergence across Alaska reflective of these differences. Using genomic data, we found that in Alaska, the Omicron sublineage BA.

Acceptance of a computer vision facilitated protocol to measure adherence to face mask use: a single-site, observational cohort study among hospital staff.

Objectives: Mask adherence continues to be a critical public health measure to prevent transmission of aerosol pathogens, such as SARS-CoV-2. We aimed to develop and deploy a computer vision algorithm to provide real-time feedback of mask wearing among staff in a hospital.

Design: Single-site, observational cohort study.

Mechanism of Action of Sodium Caprate for Improving the Intestinal Absorption of a GLP1/GIP Coagonist Peptide.

Sodium caprate (C10) has been widely evaluated as an intestinal permeation enhancer for the oral delivery of macromolecules. However, the effect of C10 on the intestinal absorption of peptides with different physicochemical properties and its permeation-enhancing effect remains to be understood. Here, we evaluated the effects of C10 on intestinal absorption in rats with a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP-GLP1) dual agonist peptide (LY) and semaglutide with different enzymatic stabilities and self-association behaviors as well as the oral exposure of the LY peptide in minipigs.

Cost-Effective Solution of Remote Photoplethysmography Capable of Real-Time, Multi-Subject Monitoring with Social Distancing.

Recent advances in remote-photoplethysmography (rPPG) have enabled the measurement of heart rate (HR), oxygen saturation (SpO), and blood pressure (BP) in a fully contactless manner. These techniques are increasingly applied clinically given a desire to minimize exposure to individuals with infectious symptoms. However, accurate rPPG estimation often leads to heavy loading in computation that either limits its real-time capacity or results in a costly setup.