A harmonized river-ocean coupled database for the northern Gulf of Mexico.

The northern Gulf of Mexico (nGoM) receives water from over 50 rivers which are highly influenced by humans and include the largest river in the United States, the Mississippi River. To support large-scale data-driven research centered on the dynamic river-ocean system in the region, this study consolidated hydrogeochemical river and ocean data from across the nGoM. In particular, we harmonized 35 chemical solute parameters from 54 rivers and incorporated river discharge data to derive daily solute concentration and flux estimates throughout the nGoM.

Safety and tolerability of the M2 muscarinic acetylcholine receptor modulator BAY 2413555 in heart failure with reduced ejection fraction in the REMOTE-HF study.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.

A simple model of the rheological curve of HPAM solutions at different temperatures.

The oil and gas industry faces two significant challenges, including rising global temperatures and depletion of reserves. Enhanced recovery techniques such as polymer flooding have positioned themselves as an alternative that attracts international attention thanks to increased recovery factors with low emissions. However, existing physical models need further refinement to improve predictive accuracy and prevent design failures in polymer flooding projects.

Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

Strontium isoscape of sub-Saharan Africa allows tracing origins of victims of the transatlantic slave trade.

Strontium isotope (Sr/Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving Sr/Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the Sr/Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression.

Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array.

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation.

NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.

High-performance 2D electronic devices enabled by strong and tough two-dimensional polymer with ultra-low dielectric constant.

As the feature size of microelectronic circuits is scaling down to nanometer order, the increasing interconnect crosstalk, resistance-capacitance (RC) delay and power consumption can limit the chip performance and reliability. To address these challenges, new low-k dielectric (k < 2) materials need to be developed to replace current silicon dioxide (k = 3.9) or SiCOH, etc.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Three Decades of Outpatient Plastic Surgery Safety: A Review of 42,720 Consecutive Cases.

Background: Outpatient plastic surgery offers cost-effective solutions and enhanced privacy but demands careful patient assessment for suitability and vigilant anticipation of adverse events. This study provides recommendations to enhance patient safety in outpatient settings by analyzing over 40,000 consecutive cases spanning across three decades.

Methods: We retrospectively reviewed all consecutive cases completed by board-certified plastic surgeons at an accredited outpatient surgical center between 1995-2023.

I-CONECT intervention effects on weekly time spent outside of home and social contacts among socially isolated older adults.

Background: Socially isolated individuals tend to have less access to cognitively stimulating activities, which could adversely impact their cognitive health. The Internet-Based Conversational Engagement Clinical Trial (I-CONECT) intervention was designed to deliver online conversation sessions to socially isolated older old adults to prevent cognitive decline. The current study examined the intervention efficacy on participants' weekly time spent out-of-home and their social interaction with family and friends.

Evaluating the effect of VersaWrap tendon protector on functional outcomes in operative tendon repairs.

Background: Tendon repairs often result in adhesion formation which can cause persisting functional deficits. Close proximity of healing tissues increases friction during tendon excursion, often leading to tendon tethering postoperatively. Despite continued improvements in techniques for tendon repairs, there is currently no consensus on the most effective modality to reduce adhesion formation.

Knowledge, Perception, and Practices of Hand Hygiene Among Medical and Paramedical Students at a Tertiary Care Institute in Uttarakhand.

Background: Healthcare-associated infections or nosocomial infections are considered to be one of the leading causes of increased morbidity and mortality in patients. Hand hygiene is one of the simplest and most effective infection control measures to prevent nosocomial infections. Medical and paramedical students are the foundation of any healthcare system.

Optimizing immunogenicity and product presentation of a SARS-CoV-2 subunit vaccine composition: effects of delivery route, heterologous regimens with self-amplifying RNA vaccines, and lyophilization.

Introduction: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.

Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis.

Background: The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.

Methods: Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science.

Novel variant alters splicing of in family with features of Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder representing a wide spectrum of phenotypes, ranging from isolated thoracic aortic aneurysm or dissection to a more severe syndromic presentation with multisystemic involvement. Significant clinical variability has been noted for both related and unrelated individuals with the same pathogenic variant. We report a family of five affected individuals with notable phenotypic variability who appear to have two distinct molecular causes of LDS, one attributable to a missense variant in and the other an intronic variant 6 bp upstream from a splice junction in .

Phylogeography, taxonomy, and conservation of the endangered brown howler monkey, (Primates, Atelidae), of the Atlantic Forest.

The brown howler, , endemic to the Atlantic Forest of Brazil and Argentina, is threatened by habitat loss and fragmentation, hunting, and its susceptibility to yellow fever. Two subspecies have been recognized, but their names, validity, and geographic ranges have been controversial. We obtained samples covering the species' entire distribution in Brazil and Argentina to clarify these issues by investigating their genetic diversity and structure and assessing their evolutionary history.

Non-adrenergic vasopressors for vasodilatory shock or perioperative vasoplegia: a meta-analysis of randomized controlled trials.

Background: Excessive exposure to adrenergic vasopressors may be harmful. Non-adrenergic vasopressors may spare adrenergic agents and potentially improve outcomes. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of non-adrenergic vasopressors in adult patients receiving vasopressor therapy for vasodilatory shock or perioperative vasoplegia.

Predicting kidney graft function and failure among kidney transplant recipients.

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history.

Genetics of Cerebral Palsy: Diagnosis, Differential Diagnosis, and Beyond.

Cerebral palsy (CP) is the most common motor disability in children, characterized by diverse clinical manifestations and often uncertain etiology, which has spurred increasing interest in genetic diagnostics. This review synthesizes findings from various studies to enhance understanding of CP's genetic underpinnings. The discussion is structured around five key areas: monogenic causes and copy number variants directly linked to CP, differential genetic disorders including atypical CP and mimics, ambiguous genetic influences, co-occurrence with other neurodevelopmental disorders, and polygenic risk factors.

Anticoagulation therapy for the prevention of subclinical leaflet thrombosis after transcatheter aortic valve replacement: A comprehensive literature review and future directions.

Leaflet thrombosis after transcatheter aortic valve replacement (TAVR) presents a significant challenge, leading to adverse clinical outcomes. Subclinical leaflet thrombosis (SLT) is increasingly recognized, and there is a growing concern about its role in clinical events and hemodynamic valve deterioration. Current recommendations for prophylactic anticoagulation or antiplatelet therapy following TAVR are primarily based on expert consensus rather than definitive evidence from randomized trials, resulting in a variety of antithrombotic strategies in clinical practice.

Uncontrolled Diabetes is a Strong Predictor of Amputation in End Stage Renal Disease Patients on Hemodialysis.

Background: Diabetic nephropathy remains a strong risk factor for chronic kidney disease progression. Hemoglobin A1C (HBA1C) has historically been used as a marker for complications related to diabetes.

Objectives: The purpose of this study is to examine the relationship between HBA1C and clinical complications in a patient population with end stage renal disease.