Assessment of Bendopnea and Its Association With Clinical and Para-Clinical Findings in Systolic Heart Failure: A Cross-Sectional Study.

Background And Aims: Bendopnea is a symptom found in patients with heart failure (HF) defined as shortness of breath when bending forward. The present study examined the correlation between bendopnea with other cardiac symptoms, echocardiographic findings, and cardiac function parameters.

Methods: This was a single-center prospective cross-sectional study of patients diagnosed with systolic HF.

Engineering of CRISPR-Cas PAM recognition using deep learning of vast evolutionary data.

CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, significantly limiting the range of targetable sequences in a genome. Machine learning-based protein engineering provides a powerful solution to efficiently generate Cas protein variants tailored to recognize specific PAMs. Here, we present Protein2PAM, an evolution-informed deep learning model trained on a dataset of over 45,000 CRISPR-Cas PAMs.

Development of an algorithm impacting COPD care through personalized nutrition and IoT-based monitoring.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by high morbidity and mortality rates. This study aims to assess the clinical outcomes of COPD patients after implementing an algorithm within the MyTatva app.

Methods: The study involved a sample of 10 COPD patients, evaluating key parameters such as Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity, Weight, Body Mass Index (BMI), Fat-Free Mass Index, and Distance Covered during the 6-Minute Walk Test (6MWT) before and after the algorithm's implementation in the MyTatva app.

Site-Specific Competitive Kinase Inhibitor Target Profiling Using Phosphonate Affinity Tags.

Protein kinases are prime targets for drug development due to their involvement in various cancers. However, selective inhibition of kinases, while avoiding off-target effects remains a significant challenge for the development of protein kinase inhibitors. Activity-based protein profiling (ABPP), in combination with pan-kinase activity-based probes (ABPs) and mass spectrometry-based proteomics, enables the identification of kinase drug targets.

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.

Trends in Obesity Care Among US Adults, 2010-2021.

Background: Obesity is a major contributor to mortality in the United States. Clinical guidelines emphasize the need for multimodal treatment, but novel treatments may be changing care-seeking behavior.

Objective: To characterize obesity treatment access patterns and factors associated with obesity care from 2010 to 2021 in the United States.

Enhancing single-cell transcriptomics using interposed anchor oligonucleotide sequences.

Single-cell transcriptomics, which utilises barcodes and unique molecular identifiers (UMIs) for polyA+ mRNA capture, is compromised by oligonucleotide synthesis errors. To address this, we modified the oligonucleotide capture design and integrated an interposed anchor between the barcode and the UMI. This design significantly reduces the need to discard reads due to synthesis inaccuracies.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Correlation of fecal microbiome dysregulation to synovial transcriptome in an equine model of obesity associated osteoarthritis.

Background: Osteoarthritis (OA) is increasingly thought to be a multifactorial disease in which sustained gut inflammation serves as a continued source of inflammatory mediators driving degenerative processes at distant sites such as joints. The objective of this study was to use the equine model of naturally occurring obesity associated OA to compare the fecal microbiome in OA and health and correlate those findings to differential gene expression synovial fluid (SF) cells, circulating leukocytes and cytokine levels (plasma, SF) towards improved understanding of the interplay between microbiome and immune transcriptome in OA pathophysiology.

Methods: Feces, peripheral blood mononuclear cells (PBMCs), and SF cells were isolated from healthy skeletally mature horses (n=12; 6 males, 6 females) and those with OA (n=6, 2 females, 4 males).

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.

Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Selected microwave irradiation effectively inactivates airborne avian influenza A(H5N1) virus.

The highly pathogenic avian influenza A(H5N1) virus threatens animal and human health globally. Innovative strategies are crucial for mitigating risks associated with airborne transmission and preventing outbreaks. In this study, we sought to investigate the efficacy of microwave inactivation against aerosolized A(H5N1) virus by identifying the optimal frequency band for a 10-min exposure and evaluating the impact of varying exposure times on virus inactivation.

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.

The effects of anodization and instrumentation on titanium abutment surface characteristics and biofilm formation.

Purpose: To assess the impact of anodization and instrumentation on titanium abutment surface characteristics (surface roughness and wettability) and biofilm formation (viability and mass).

Materials And Methods: Titanium discs were obtained from pre-milled abutment blanks made of titanium-6aluminum-7niobium alloy. Polished samples were divided into three groups: un-anodized, gold-anodized, and pink-anodized.

Molecular-targeted Therapy for Precision Medicine in Gastrointestinal Cancer: Advancement in Cancer Targeting Strategies.

Gastrointestinal (GI) cancer represent significant health challenges, affecting the digestive system with often subtle symptoms that can delay diagnosis. GI cancers account for a higher global mortality rate than any other cancer, largely due to the limited availability of highly effective treatment options." Due to next-generation sequencing and new preclinical model tools, that we have learned more regarding its pathophysiology and molecular changes.

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study.

Background: Perinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.

Changes in Sleep Quality in Patients Older than 60 Years, Post-COVID Pandemic.

Background: COVID-19 is a disease that had a great impact in the world, generating lifestyle changes; among these are changes in sleep quality, with the elderly being one of the most affected age groups. Objective: To identify sleep alterations in Mexican people older than 60 years post COVID-19 pandemic. Methods: We performed a descriptive study on subjects older than 60 years from the aging cohort of the National Institute of Respiratory Diseases.

Vitritis following intravitreal faricimab: a retrospective monocentric analysis.

Purpose: Intravitreal injections of anti-VEGF agents are considered as safe, with a very low rate of intraocular inflammations (IOI). Faricimab is a novel intravitreal bispecific antibody targeting both VEGF-A and angiopoietin-Tie2 independently. Despite a safe profile in randomized clinical trials, several real-life studies have reported cases of IOI.

Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

α-Amylase inhibitory potential of dihydropyrano coumarins: In silico and DFT analysis.

Unlabelled: Coumarin derivatives are one of the naturally occurring bioactive molecule. Dihydropyrano coumarins are one of the medicinally important derivatives of coumarin which have been reported to exhibit various bioactivity. However, there are no reports on their antihyperglycemic activities.

Association between preoperative exercise tolerance and unplanned readmission in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma: a retrospective analysis.

Background: Despite advances in treatment, the incidence of postoperative complications following pancreatectomy remains high, leading to frequent hospital readmissions. Therefore, this study aimed to investigate the relationship between preoperative exercise tolerance and the likelihood of unplanned readmission in patients with pancreatic ductal adenocarcinoma.

Methods: This retrospective analysis included 88 patients who underwent pancreatectomy at a single institution between July 2019 and September 2022 and focused on patients with pancreatic ductal adenocarcinoma.

Amelioration and Immuno-modulation by Ashwagandha on Wi-fi Induced Oxidative Stress in Regulating Reproduction Via Estrogen Receptor Alpha in Male Japanese Quail.

As global change threatens avian biodiversity, understanding species responses to environmental perturbations due to radiation emitted by enormous increase in the application of wireless communication is very urgent. The study investigates the effect of MW radiation on redox balance, stress level, male fertility and the efficacy of Withania somnifera (WS) root extract (100 mg/kg body weight) orally administered in 8 weeks old mature male Japanese quail exposed to 2.4 GHz MW radiation for 2 h/day for 30 days with power density = 0.