A genetically based computational drug repurposing framework for rapid identification of candidate compounds: application to COVID-19.

Background: The development and approval of novel drugs are typically time-intensive and expensive. Leveraging a computational drug repurposing framework that integrates disease-relevant genetically regulated gene expression (GReX) and large longitudinal electronic medical record (EMR) databases can expedite the repositioning of existing medications. However, validating computational predictions of the drug repurposing framework remains a challenge.

The potential synergistic effect of combining doxorubicin with vorinostat in urothelial carcinoma therapy.

Bladder cancer ranks as the 9th most common type of cancer worldwide. Approximately 70 % of bladder cancers are diagnosed as non-muscle invasive, and they are treated with transurethral resection followed by intravesical therapy. Doxorubicin is one of the effective cytotoxic drugs used in intravesical and systemic therapy, but its cardiotoxicity and nephrotoxicity limit therapeutic dosages.

Characterization of Broad Spectrum Bacteriophage vB ESM-pEJ01 and Its Antimicrobial Efficacy Against Shiga Toxin-Producing in Green Juice.

Shiga toxin-producing (STEC) infections have increased in humans, animals, and the food industry, with ready-to-eat (RTE) food products being particularly susceptible to contamination. The prevalence of multidrug-resistant strains has rendered the current control strategies insufficient to effectively control STEC infections. Herein, we characterized the newly isolated STEC phage vB_ESM-pEJ01, a polyvalent phage capable of infecting and species, and assessed its efficacy in reducing STEC in vitro and food matrices.

Optimizing the graft size in the Evans osteotomy to minimize the calcaneocuboid joint pressure by highly realistic in-silico analysis.

This contribution details a new high-fidelity finite element analysis (FEA) methodology for the investigation of the effect of the graft size on the pressure distribution developing at the calcaneocuboid joint after the Evans osteotomy procedure. The FEA model includes all 28 bones of the foot up to the distal end of fibula and tibia as well as soft tissues, tendons, and muscles. The developed FEA model was validated by comparing the in-vivo pressure distribution on the foot plantar with the in-silico results, resulting in a low deviation equal to 7.

Perforator-Based Propeller Flap Application in Pressure Ulcer Reconstruction: A Comparative Analysis With Advancement Flaps.

Background: Pressure ulcers are a prevalent and debilitating condition, often necessitating surgical reconstruction. Various flap techniques, such as Advancement Flaps (AF) and Perforator-based Propeller Flaps (PBPF), are commonly used for pressure sore reconstruction. While both techniques have proven effective, there is limited research comparing their outcomes in different clinical scenarios.

Therapeutic blockade of CCL17 in obesity-exacerbated osteoarthritic pain and disease.

Objectives: We previously reported that CCL17 gene-deficient mice are protected from developing pain-like behaviour and exhibit less disease in destabilization of medial meniscus (DMM)-induced OA, as well as in high-fat diet (HFD)-exacerbated DMM-induced OA. Here, we explored if therapeutic neutralization of CCL17, using increasing doses of a neutralizing monoclonal antibody (mAb), would lead to a dose-dependent benefit in these two models.

Design: DMM-induced OA was initiated in male mice either fed with a control diet (7% fat) or 8 weeks of a 60% HFD, followed by therapeutic intraperitoneal administration (i.

Wildlife policy, the food system and One Health: a complex systems analysis of unintended consequences for the prevention of emerging zoonoses in China, the Democratic Republic of the Congo and the Philippines.

Introduction: Evolving human-wildlife interactions have contributed to emerging zoonoses outbreaks, and pandemic prevention policy for wildlife management and conservation requires enhanced consideration from this perspective. However, the risk of unintended consequences is high. In this study, we aimed to assess how unrecognised complexity and system adaptation can lead to policy failure, and how these dynamics may impact zoonotic spillover risk and food system outcomes.

Pre-disability resilience and well-being following the onset of functional impairments.

Objectives: Tested the prospective relationship of a resilient personality prototype determined prior to disability onset to well-being among persons with and without debilitating functional impairments nine to 10 years later. A resilient profile was expected to predict well-being through its beneficial associations with positive affect, perceived control and social support.

Design: Longitudinal, prospective observation study.

Cycle Effects Are Not Universal: A Case Study of Urinary C-Reactive Protein Concentrations in Rural Polish and Polish American Samples.

Objectives: We need to better understand how the menstrual cycle interacts with other biological systems, such the inflammation and immune response. One way to study this interaction is through C-reactive protein (CRP). Studies of CRP concentrations across the menstrual cycle have been inconsistent.

Identification of Sulcal Hyperintense Vessel (Vessel Wall MR Ivy Sign) in Adult Moyamoya Disease with High-resolution Vessel Wall Imaging : A Pilot Study.

Objective: The leptomeningeal ivy sign is a distinctive finding of moyamoya disease (MMD), characterized by a linear high signal intensity along the cortical sulci on contrast-enhanced T1 magnetic resonance imaging (MRI) and fluid-attenuated inversion-recovery MRI. We recently identified a similar linear enhancement along the cortical sulci using gadolinium-enhanced vessel wall MRI (VWMR) in patients with MMD. The aim of this study was to introduce the concept of the "VWMR ivy sign (VIS)".

Ionic Diode-Based Drug Delivery System.

Drug delivery systems hold promise for delivering cytotoxic drugs by controlling the timing and location of the drug release. However, conventional delivery mechanisms often fall short of achieving spatiotemporally controlled yet sustained release, which is crucial for ensuring drug efficacy and minimizing impact on surrounding tissues. Here, an ionic diode-based drug delivery system is reported that is controlled by an electric potential and capable of releasing drugs at scales ranging from nanogram to microgram.

Zwitterion Interlocked Diarylethene Molecules Order, Unconnected Diarylethene Molecules Disorder.

A diarylethene-based zwitterionic molecule (DZM) is newly synthesized for the development of smart films exhibiting reversible color change and switchable ionic conductivity in response to external light stimuli. This dual molecular building block is constructed through zwitterionic interlocking and strong phase separation between the dendron-shaped aliphatic tails and the diarylethene head. Uniaxial shear coating and molecular self-assembly result in anisotropically oriented nanostructures, which are further solidified through photopolymerization.

Interpretable Multi-Label Classification for Tibiofibula Fracture 2D CT Images with Selective Attention and Data Augmentation.

Background: Tibiofibula fractures occur across all age groups, and postoperative complications are frequent. An accurate and rapid classification methodology for these fractures could significantly assist physicians. Clinically, tibiofibula fractures occur at various locations, and the fracture types are not evenly distributed.

Simultaneous analysis of residual prohibited doping substances in foods using gas chromatography-tandem mass spectrometry.

The continuous consumption of various foods increases the risk of unintentional exposure to residual contaminants. Thus, improving premonitoring procedures to ensure food safety is critical. Herein, a rapid and efficient assay was developed to monitor residual contaminants in food, with a focus on banned doping substances.

Associations Between Big-Five Personality Traits and Attitudes and Perception Towards Health Behaviours.

Despite efforts to promote exercise and healthy diets, global prevalence of obesity continues to rise. This pervasiveness of obesity is alarming as it is a key contributing factor of ischemic heart disease, a leading cause of death worldwide. The issue of obesity is exacerbated in Malaysia, where 50.

Lupus Mastitis Manifesting as Extensive Calcification in the Retromammary Area: A Case Report.

Lupus mastitis is a presentation of lupus panniculitis that involves subcutaneous fat in patients with systemic lupus erythematosus (SLE). Moreover, lupus mastitis is a rare condition that typically presents as a palpable breast mass. Here, we report the case of a 29-year-old woman with a prior diagnosis of SLE who presented with palpable lumps in both breasts.

A novel tape-free sample preparation method for human osteochondral cryosections for high throughput hyperspectral imaging.

Understanding the osteochondral junction, where non-mineralised cartilage and mineralised bone converge, is crucial for joint health. Current sample preparation techniques are insufficient for detailed spatial hyperspectral imaging analysis. Using the enhanced Kawamoto method, we used the super cryo embedding medium's temperature-dependent properties to transfer high-quality tissue samples onto slides for spatial imaging analysis.

Validation of an interferon-gamma enzyme-linked immunosorbent spot assay to evaluate cell-mediated immunity against severe acute respiratory syndrome coronavirus 2.

The COVID-19 pandemic forced the rapid development of methods to measure humoral and cellular immunity against SARS-CoV-2. The lack of a global standardized protocol and the high variability of intra- and inter-assay precision of the T-cell response made it difficult to compare T-cell assay results with those of other laboratories. The interferon-gamma enzyme-linked immunosorbent spot (IFN-γ ELISpot) assay for immunogenicity evaluation was validated using naturally infected donor peripheral blood mononuclear cells, a commercially available IFN-γ ELISpot kit, and a SARS-CoV-2 specific peptide pool.

Modulating radiative efficiency in -carboranyl luminophores through electron-donating substituents: insights from intramolecular-charge-transfer-based emissions.

In this study, we introduce six -carboranyl compounds derived from 9,9-dimethyl-9-fluorene 1CH-6CP, each possessing substituents with varying electron-donating capabilities. Their geometric features were comprehensively characterised through single X-ray crystallography. In rigid states (solutions at 77 K, films, aggregates, and crystals), these compounds exhibited intense intramolecular charge-transfer (ICT)-based emissions in the bluish-green spectrum.

Judicious Molecular Design of 5H‑Dithieno[3,2‑b:2',3'‑d]Pyran-based Hole-Transporting Materials for Highly Efficient and Stable Perovskite Solar Cells.

The structural modification of hole-transporting materials (HTMs) is an effective strategy for enhancing photovoltaic performance in perovskite solar cells (PSCs). Herein, a series of dithienopyran (DTP)-based HTMs (Me-H, Ph-H, CF3-H, CF3-mF, and CF3-oF) is designed and synthesized by substituting different functional groups on the DTP unit and are used fabricating PSCs. In comparison with Me-H having two methyl substituents on the dithienopyrano ring, the Ph-H having two phenyl substituents on the ring exhibits higher PCEs.

Biochemical, structural, and single-molecule characterization of LIG1 active site mutants demonstrate role of F635 and F872 residues for faithful ligation.

Human DNA ligase 1 (LIG1) finalizes DNA repair pathways by an ultimate ligation step and discriminates against nicks containing unusual ends, yet the contribution of the conserved active site residues for faithful end joining remains unknown. Here, using biochemistry, X-ray crystallography, and single-molecule approaches, we comprehensively characterized LIG1 mutants carrying Ala(A) and Leu(L) substitutions at the active site residues Phe(F)635 and Phe(F)872. Our results showed an abolished ligation of nick DNA substrates with all 12 non-canonical mismatches, while the mutagenic nick sealing of oxidatively damaged ends by wild-type enzyme is significantly reduced by F635A/L and F872A/L substitutions.

Thicker is better? Impact of food consistencies on aspiration detection using IDDSI levels.

Background/purpose: Water is the most commonly, and often the only tested material in swallow screening. Our objective is to assess the impact of food consistencies on the reliability of trial swallows in predicting aspiration in dysphagic patients, utilizing the International Dysphagia Diet Standardisation Initiative (IDDSI) levels.

Methods: All trial swallows were evaluated using 5 ml of standardized test food with IDDSI levels of 0, 2, 4, 5.

Protein Involved in Tip Elongation (PITE) regulates root hair growth in rice.

Polar tip growth in plants occurs only in root hairs and pollen tubes. In particular, root hair growth is considered very important in the growth of plants, as it is critical for water and nutrient absorption. Polar tip growth is regulated by various factors, including plant hormones such as abscisic acid (ABA) and gibberellin (GA) and cell wall modifications.