Aprocitentan for Blood Pressure Reduction in Black Patients.

Background: Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).

Methods: Patients with confirmed resistant hypertension were randomized to aprocitentan 12.

Reproducibility of automatic adipose tissue segmentation using proton density fat fraction images between 1.5 and 3.0 T magnetic resonance.

Background: Deep learning (DL)-based adipose tissue segmentation methods have shown great performance and efficacy for adipose tissue distribution analysis using magnetic resonance (MR) images, an important indicator of metabolic health and disease. The aim of this study was to evaluate the reproducibility of whole-body adipose tissue distribution analysis using proton density fat fraction (PDFF) images at different MR strengths.

Methods: A total of 24 volunteers were imaged using both 1.

Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis.

Background And Objective: N,N-Dimethyltryptamine (DMT) is currently being studied for its therapeutic potential in various psychiatric disorders. An understanding of its pharmacokinetics (PK) is essential to determine appropriate dose ranges in future clinical studies. We conducted a systematic literature review on the PK of DMT.

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

Tumour growth rate and invasive interval cancer characteristics in a UK breast cancer screening population.

Objectives: To estimate tumour volume doubling time (TVDT) of interval cancers (ICs).

Methods: Two radiologists retrospectively reviewed prior screening and diagnostic mammograms and measured mean diameter on "visible" ICs. Univariate analyses of clinicopathological variables (ER, HER2, grade, age at diagnosis, and breast density) were undertaken, and those with p < 0.

Differentiation of Atherosclerotic Carotid Plaque Components With Dual-Energy Computed Tomography.

Objectives: Carotid plaque vulnerability is a strong predictor of recurrent ipsilateral stroke, but differentiation of plaque components using conventional computed tomography (CT) is suboptimal. The aim of our study was to evaluate the ability of dual-energy CT (DECT) to characterize atherosclerotic carotid plaque components based on the effective atomic number and effective electron density using magnetic resonance imaging (MRI) and, where possible, histology as the reference standard.

Materials And Methods: Patients with recent cerebral ischemia and a ≥2-mm carotid plaque underwent computed tomography angiography and MRI.

2021 European Society of Cardiology guidelines on cardiac pacing and cardiac resynchronisation therapy : Statement of endorsement by the NVVC.

The European Society of Cardiology (ESC) has updated its guidelines on cardiac pacing and cardiac resynchronisation. As the majority are class II recommendations (61%) and based on expert opinion (59%), a critical appraisal for the Dutch situation was warranted. A working group has been established, consisting of specialists in cardiology, cardiothoracic surgery, geriatrics, allied professionals in cardiac pacing, and patient organisations with support from the Knowledge Institute of the Dutch Association of Medical Specialists.

The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured.

Background: Tissue-plasminogen activator-challenged thromboelastography (tPA-TEG) predicts massive transfusion and mortality better than conventional rapid thromboelastography (rTEG), with little concordance between their lysis values (LY30). We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.

Methods: Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval.

Self-Activated Energy Release Cascade from Anthracene-Based Solid-State Molecular Solar Thermal Energy Storage Systems.

We introduce donor-acceptor substituted anthracenes as effective molecular solar thermal energy storage compounds that operate exclusively in the solid state. The donor-acceptor anthracenes undergo visible light-induced [4+4] cycloaddition reaction, producing metastable cycloadducts, dianthracenes with quaternary carbons, and storing photon energy. The triggered cycloreversion of dianthracenes to anthracenes discharges the stored energy as heat in the order of 100 kJ/mol (200 J/g).

Two thermochromic laminated veneer cellulose-based alizarin/stearic acid/nano‑silicon dioxide/hexagonal boron nitride composites encapsulated with xanthan gum and wood wax oil films, that have excellent temperature-responsive and thermal-storing capabilities.

Thermochromic wood-based phase change material (TWPCM) is a temperature-responsive, smart material that actively manages thermal energy in response to ambient temperature fluctuations. The material has become a central focus in research on thermal energy storage and temperature sensing in recent years. A key research direction is the incorporation of delignified veneer impregnated with thermochromic phase change material (TPCM) into a multi-layered structure to enhance the thermal energy storage capacity of TWPCM.

State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment.

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Simulated deep space exposure on seeds utilizing the MISSE flight facility.

The MISSE-Seed project was designed to investigate the effects of space exposure on seed quality and storage. The project tested the Multipurpose Materials International Space Station Experiment-Flight Facility (MISSE-FF) hardware as a platform for exposing biological samples to the space environment outside the International Space Station (ISS). Furthermore, it evaluated the capability of a newly designed passive sample containment canister as a suitable exposure unit for biological samples for preserving their vigor while exposing to the space environment to study multi-stressor effects.

Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics.

Background: Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed.

Objective: We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset.

RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia.

Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation.

Investigative genetic genealogy practices warranting policy attention: Results of a modified policy Delphi.

A technique known as investigative genetic genealogy (IGG) was first introduced to criminal investigations in 2018, and it has since been used by U.S. law enforcement to help identify hundreds of criminal perpetrators and unidentified human remains.

HEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions.

What happens when you turn weed management off? A long-term appraisal of the effectiveness of Pteridium aquilinum (L.) kuhn control treatments and the role of sheep grazing.

Long-term strategies are needed for the ecological restoration of land invaded by perennial weed species comprising of two parts: (1) control of the invasive species and (2) restoration of native vegetation meeting agricultural/conservation objectives. We investigated this within a statistically-rigorous, 28-year experiment at a site where Pteridium aquilinum had invaded an acid-grass/heathland. Where P.

Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment.

Introduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.

Osseointegration and fixation opportunities of sacroiliac instrumentation: a preclinical evaluation in a large animal model.

Background: Implant fixation is often the cornerstone of musculoskeletal surgical procedures performed to provide bony fixation and/or fusion. The aim of this study was to evaluate how different design features and manufacturing methods influence implant osseointegration and mechanical properties associated with fixation in a standardized model in cancellous bone of adult sheep.

Methods: We evaluated the performance of three titanium alloy implants: (A) iFuse-TORQ implant; (B) Fenestrated Sacroiliac Device; and (C) Standard Cancellous Bone Screw in the cancellous bone of the distal femur and proximal tibia in 8 sheep.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Bifunctional NiCo-CuO Nanostructures: A Promising Catalyst for Energy Conversion and Storage.

This investigation explores the potential of co-incorporating nickel (Ni) and cobalt (Co) into copper oxide (CuO) nanostructures for bifunctional electrochemical charge storage and oxygen evolution reactions (OER). A facile wet chemical synthesis method is employed to co-incorporate Ni and Co into CuO, yielding diverse nanostructured morphologies, including rods, spheres, and flake. The X-ray diffraction (XRD) and Raman analyses confirmed the formation of NiCo-CuO nanostructure, with minor phases of nickel oxide (NiO) and cobalt tetraoxide (CoO).

Small molecule inhibits KCNQ channels with a non-blocking mechanism.

Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.

Orthogonalized human protease control of secreted signals.

Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. Although protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a potential immunogenic risk. In this study, we developed Humanized Drug Induced Regulation of Engineered CyTokines (hDIRECT) as a platform to control cytokine activity exclusively using human-derived proteins.