Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5.

Background: Right ventricular dysfunction (RVD) is common in patients with heart failure with reduced ejection fraction, and it is associated with poor prognosis. However, no biomarker reflecting RVD is available for routine clinical use.

Methods: Proteomic analysis of myocardium from the left ventricle and right ventricle (RV) of patients with heart failure with reduced ejection fraction with (n=10) and without RVD (n=10) who underwent heart transplantation was performed.

Prevalence of "weak B" phenotypes and their evaluation and differentiation in healthy blood donor population in Eastern India.

Background: Examples of group B red cells that react weakly or not at all with anti-B have been described. Subgroups of B such as B, B, B, and B are rare and are less frequently reported. We studied the frequency of subgroups of B in our healthy blood donor population and serologically characterized and differentiated these subgroups.

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.

Short-Term Warm-Water Immersion for Improving Whole-Body Heat Loss in Older Men.

Purpose: Exercise-induced heat acclimation can mitigate age-related reductions in heat-loss capacity, though performing repeated bouts of strenuous exercise in the heat may be untenable for many older adults. While short-term passive heat acclimation (e.g.

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.

Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial.

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no.

Language and Attention Networks Have Distinct Roles in Language Improvement Following an Intensive Comprehensive Aphasia Program.

Background: Attention is known to play an important role in language, and attentional deficits have been associated with language impairments in people with aphasia (PWA). A prior study by our laboratory indicated that behavioral measures for PWA participating in an intensive comprehensive aphasia program (ICAP) clustered into 1 language and 1 attention-related factor, with each factor correlated with independent resting state functional connectivity (rsFC) networks. The present study includes additional attention measures and participants to better assess the relationship between attention, language, and rsFC.

Evaluation of a Deep Learning Denoising Algorithm for Dose Reduction in Whole-Body Photon-Counting CT Imaging: A Cadaveric Study.

Rationale And Objectives: Photon Counting CT (PCCT) offers advanced imaging capabilities with potential for substantial radiation dose reduction; however, achieving this without compromising image quality remains a challenge due to increased noise at lower doses. This study aims to evaluate the effectiveness of a deep learning (DL)-based denoising algorithm in maintaining diagnostic image quality in whole-body PCCT imaging at reduced radiation levels, using real intraindividual cadaveric scans.

Materials And Methods: Twenty-four cadaveric human bodies underwent whole-body CT scans on a PCCT scanner (NAEOTOM Alpha, Siemens Healthineers) at four different dose levels (100%, 50%, 25%, and 10% mAs).

Photodegradation, kinetics and non-linear error functions of methylene blue dye using SrZrO perovskite photocatalyst.

The degradation of methylene blue dye-contaminated wastewater via photocatalysis is an efficient approach towards environmental remediation. The SrZrO perovskite photocatalyst was synthesized using the modified Pechini sol-gel method, and characterized using XRD, FESEM, FTIR, and UV-visible spectrophotometer. Crystallite size obtained by the Scherrer and Williamson-Hall methods were 45.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Targeting protein-ligand neosurfaces with a generalizable deep learning tool.

Molecular recognition events between proteins drive biological processes in living systems. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

Unveiling Baseline Clinical Divergence in VA ECMO vs. ECPELLA: Tailoring Treatment for Distinct Patient Profiles. A Systematic Review and Meta-analysis.

Objectives: The benefit of combining multiple mechanical circulatory support (MCS) systems in patients with cardiogenic shock (CS) is debated. This review examines patient characteristics across studies to identify differences and assesses if patients with a higher-risk clinical profile receive Impella unloading.

Design: A systematic review and meta-analysis was conducted to examine if there were significant differences in baseline clinical parameters among patients receiving MCS in addition to venoarterial extracorporeal membrane oxygenation (VA ECMO).

Mortality in patients with Sjögren Disease: A Prospective Cohort Study Identifying Key Predictors.

Objective: To quantify the mortality risk in a large, well-characterized cohort of Sjögren's disease (SjD) patients and to identify independent predictors of mortality in this population.

Methods: We included 314 patients diagnosed with SjD according to the 2002 American-European Consensus Group criteria from a prospective, multicenter SjögrenSER-PROS cohort. Detailed data on systemic manifestations, serological markers, disease activity, and mortality was collected after 9 years of follow up.

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

In Silico Structural Insights into a Glucanase from Clostridium perfringens and Prediction of Structural Stability Improvement Through Hydrophobic Interaction Network and Aromatic Interaction.

Glucanases are widely applied in industrial applications such as brewing, biomass conversion, food, and animal feed. Glucanases catalyze the hydrolysis of glucan to produce the sugar hemiacetal through hydrolytic cleavage of glycosidic bonds. Current study aimed to investigate structural insights of a glucanase from Clostridium perfringens through blind molecular docking, site-specific molecular docking, molecular dynamics (MD) simulation, and binding energy calculation.

An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive.

Background: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential.

Frontal plane mechanical leg alignment estimation from knee x-rays using deep learning.

Objective: Lower limb malalignment can complicate symptoms and accelerate knee osteoarthritis (OA), necessitating consideration in study population selection. In this study, we develop and validate a deep learning model that classifies leg alignment as "normal" or "malaligned" from knee antero-posterior (AP)/postero-anterior (PA) radiographs alone, using an adjustable hip-knee-ankle (HKA) angle threshold.

Material And Methods: We utilized 8878 digital radiographs, including 6181 AP/PA full-leg x-rays (LLRs) and 2697 AP/PA knee x-rays (2292 with positioning frame, 405 without).

Importance of Computer-Aided Drug Design in Modern Pharmaceutical Research.

Background: Computer-Aided Drug Design (CADD) approaches are essential in the drug discovery and development process. Both academic institutions and pharmaceutical and biotechnology corporations utilize them to enhance the efficacy of bioactive compounds.

Objective: This study aims to entice researchers by investigating the benefits of Computer-Aided Drug and Design (CADD) and its fundamental principles.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Adsorption of sulfamethoxazole in an aqueous environment onto a novel magnetic sporopollenin-cellulose triacetate.

Antibiotics are emerging environmental contaminants posing critical health risks due to their tendency to concentrate in living things and eventually infiltrate the human body. Sulfamethoxazole (SMZ) is among the commonly detected antibiotics in wastewater requiring effective removal approach. A sustainable, thermally stable and easily separable magnetic sporopollenin-cellulose triacetate (Msp-CTA) was developed via a simple step synthesis for eliminating SMZ from aqueous solution.

Exploring the synergistic effect of NaOH/NaClO absorbent in a novel wet FGD scrubber to control SOx/NOx emissions.

Escalating SOx and NOx emissions from industrial plants necessitates customized scrubbing solutions to improve removal efficiency and tackle cost limitations in existing wet FGD units. This work investigates the real-time intensified removal pathways via an innovative two-stage countercurrent spray tower configuration strategically integrating NaOH (M) and NaOH/NaClO (M/M) to remove SOx and NOx emissions simultaneously from the industrial stack through a comprehensive parametric study of absorbents concentration, reaction temperature, gas flow rate, liquid to gas ratio (F/F), and absorbent showering head. Flue gas stream comprising SO bearing 4500 ppm, SO bearing 300 ppm, 70 ppm NO, and 50 ppm NO brought into contact with two scrubbing solutions as M, and a complex absorbent of M/M at varying respective ratios.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.