Genomic analysis of surgical patients to identify patients at risk for postoperative sepsis and surgical site infection.

Background: Early and accurate diagnosis of sepsis and the ensuing organ dysfunction remain a challenge in the postoperative setting. Susceptibility to infections, as well as the subsequent immunological response, are driven to some extent by the genetic predisposition of the patient. The purpose of this study was to identify novel genetic variants associated with postoperative sepsis (POS) and surgical site infections (SSIs).

Point of No Return-What Is the Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death.

Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes by various triggers, known as permeability transition pore (mPTP) leads to the release of proapoptotic proteins and acts as an initial step in initiation of apoptosis. However, a role for mPTP was also suggested for physiology and it is unclear if there is a threshold in number of mitochondria with mPTP which induces cell death and how this mechanism is regulated in different tissues.

Specific inhibition of fibroblast growth factor receptor 1 signaling by a DNA aptamer.

Impaired fibroblast growth factor receptor (FGFR) signaling is associated with many human conditions, including growth disorders, degenerative diseases, and cancer. Current FGFR therapeutics are based on chemical inhibitors of FGFR tyrosine kinase activity (TKIs). However, FGFR TKIs are limited in their target specificity as they generally inhibit all FGFRs and other receptor tyrosine kinases.

TCCbuilder: An open-source tool for the analysis of thermal switches, thermal diodes, thermal regulators, and thermal control circuits.

In the area of thermal management, thermal control elements (TCEs) and thermal control circuits (TCCs) are proving to be innovative solutions to the challenges of temperature control and heat dissipation in various applications, ranging from electronic cooling to energy conversion and temperature control in buildings. Their integration promises to improve power density, energy efficiency, system reliability and system life expectancy. With the aim of connecting researchers in the field of thermal management and accelerating the development of TCEs and TCCs, we have developed an open-source TCC simulation tool called TCCbuilder that enables a quick and easy time-dependent 1D numerical analysis of the behavior of TCEs and TCCs.

Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat.

Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been proposed to underlie the pathophysiology of schizophrenia, suggesting that promoting NMDAR activity may alleviate the negative or cognitive symptoms associated with schizophrenia. To circumvent excitotoxicity that may accompany direct agonism of the glutamate binding site on the NMDAR, therapeutic trials have focused on targeting the glycine binding site on the NMDAR. Direct administration of either glycine or D-serine, both of which are endogenous coagonists at the NMDAR glycine site, has yielded mixed outcomes across an array of clinical trials investigating different doses or patient populations.

Pharmacological Management of IgG4-Related Disease: From Traditional to Mechanism-Based Targeted Therapies.

IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by organ enlargement and dysfunction. The formation of tertiary lymphoid tissues (TLTs) in affected organs is crucial for understanding IgG4-RD, as T follicular helper (Tfh) 2 cells within TLTs drive IgG4+B cell differentiation, contributing to mass formation. Key cytokines IL-4 and IL-10, produced by Tfh2 cells, are essential for this process.

Nanobody-based indirect competitive ELISA for the detection of aflatoxin M1 in dairy products.

Aflatoxin M1 (AFM1) is known to be carcinogenic, mutagenic, and teratogenic and poses a serious threat to food safety and human health, which makes its surveillance critical. In this study, an indirect competitive ELISA (icELISA) based on a nanobody (Nb M4) was developed for the sensitive and rapid detection of AFM1 in dairy products. In our previous work, Nb M4 was screened from a Bactrian-camel-immunized phage-displayed library.

Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors.

A series of novel phenylamino quinazolinone derivatives were designed and synthesized as potential tyrosinase inhibitors. Among these compounds, 9r emerged as the most potent derivative, exhibiting IC values of 17.02 ± 1.

Statistical optimization of pectinases from thermophilic Aspergillus fumigatus BT-4 employing response surface methodology through submerged fermentation using agricultural wastes.

Background: In this study, thermophilic pectinase-producing strains were isolated. Among all the isolates, strain No. 4 was identified as Aspergillus fumigatus BT-4 based on its morphology and 18 S rDNA analysis.

A novel peptide CP29L, selected from the phage displayed cyclic random heptapeptide library, demonstrates its potent inhibitory effects to liver cancer HCCLM3 cells by targeting FOXM1.

FOXM1 is the "Achilles' heel" of cancers and hence the potential therapeutic target for anticancer drug discovery. In this work, we selected high affinity peptides against the protein of human DNA binding domain of FOXM1 (FOXM1-DBD) from the disulfide-constrained, phage displayed random cyclic heptapeptide library Ph.D.

Ca²⁺ signaling in myenteric interstitial cells of Cajal (ICC-MY) and their role as conditional pacemakers in the colon.

Interstitial cells of Cajal in the plane of the myenteric plexus (ICC-MY) serve as electrical pacemakers in the stomach and small intestine. A similar population of cells is found in the colon, but these cells do not appear to generate regular slow wave potentials, as characteristic in more proximal gut regions. Ca handling mechanisms in ICC-MY of the mouse proximal colon were studied using confocal imaging of muscles from animals expressing GCaMP6f exclusively in ICC.

Salvage pathway of vitamin B absorption in chickens with mutant tumor virus a receptor.

The tumor virus A receptor (TVA), a member of the low-density lipoprotein receptor (LDLR) family, serves as an entry receptor for Avian Leukosis Virus (ALV) subgroups A and K, as well as a receptor for vitamin B bound to transcobalamin. Naturally occurring genetic variants in the TVA gene determine susceptibility or resistance to ALV-A and -K, but the effects of these mutated TVA on vitamin B uptake have not been investigated systemically. We found four TVA variants comprising the wild type (TVA), a single nucleotide polymorphism variant (TVA), and two partial deletions in the splicing branch point region (TVA).

AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides.

Design, synthesis, in vitro, and in silico studies of 4-fluorocinnamaldehyde based thiosemicarbazones as urease inhibitors.

Clinically significant problems such as kidney stones and stomach ulcers are linked to the activation of the urease enzyme. At low pH, this enzyme gives an ideal environment to Helicobacter pylori in the stomach which is the cause of gastric ulcers and peptic ulcers. In recent work, we have developed a library of 4-fluorocinnamaldehyde base thiosemicarbazones and assessed them for their potential against urease enzyme.

Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update.

Since the first derivation of human pluripotent stem cells (hPSCs) 27 years ago, technologies to control their differentiation and manufacturing have advanced immensely, enabling increasing numbers of clinical trials with hPSC-derived products. Here, we revew the landscape of interventional hPSC trials worldwide, highlighting available data on clinical safety and efficacy. As of December 2024, we identify 116 clinical trials with regulatory approval, testing 83 hPSC products.

Genetic factors shaping the plasma lipidome and the relations to cardiometabolic risk in children and adolescents.

Background: Lipid species are emerging as biomarkers for cardiometabolic risk in both adults and children. The genetic regulation of lipid species and their impact on cardiometabolic risk during early life remain unexplored.

Methods: Using mass spectrometry-based lipidomics, we measured 227 plasma lipid species in 1149 children and adolescents (44.

Incidence of Adjacent Synchronous Ipsilateral Infiltrating Carcinoma and/or Ductal Carcinoma In Situ in Patients Diagnosed with Flat Epithelial Atypia by Core Needle Biopsy (TBCRC 034).

Background: Flat epithelial atypia (FEA), a rare breast proliferative lesion, is often diagnosed following core biopsy (CB) of mammographic microcalcifications. In the prospective multi-institution TBCRC 034 trial, we investigate the upgrade rate to ductal carcinoma in situ (DCIS) or invasive cancer following excision for patients diagnosed with FEA on CB.

Patients And Methods: Patients with a breast imaging reporting and data system (BI-RADS) ≤ 4 imaging abnormality and a concordant CB diagnosis of FEA were identified for excision.

Umbilical Cord Amniotic Membrane Graft as a Skin Substitute in Periocular Reconstruction: A Case Series.

Loss of periocular skin due to cancer, trauma, or surgery is a major reconstructive challenge; resultant tissue contracture can cause eyelid malposition with poor functional and aesthetic outcomes. We describe the successful use of cryopreserved umbilical cord amniotic membrane as a wound covering and scaffold for periorbital anterior lamellar defects. This is a retrospective case series of 4 patients (mean 21 years, range 9-30 years, 3 male) who underwent periocular reconstruction with umbilical cord amniotic membrane of 9 different sites.

Production performance, serum lipid profile and gut health in Indian native Kadaknath chickens fed diet incorporated with liquorice root powder.

The principal constituent of liquorice root () is glycyrrhizin, a triterpene saponin that is approximately many times sweeter than sucrose, the main active component. This study aimed to investigate the dietary liquorice root powder (LRP) on production performance, serum biochemical, gut health and carcass characteristics of Kadaknath (KN) birds as replacement of antibiotic growth promoter. Day-old Kadaknath chicks (n = 240) with uniform body weight were selected randomly and divided into six different treatments, each one with five replicates and eight birds per replicate, and raised in battery brooder cages for 15 weeks.

Education Research: Utilization of Simulation in Residency Programs: A Survey of Adult Neurology Residency Program Directors.

Background And Objectives: Previous research has demonstrated that simulation-based medical education (SBME) can improve neurology trainees' confidence, knowledge, and competence. However, a general needs assessment and review of current SBME used within neurology are needed to guide SBME curriculum development. The objective of this study was to describe the current use of SBME in resident education and to assess perceived barriers to expanding SBME interventions.

A new peptide inhibitor of C1QBP exhibits potent anti-tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair.

C1QBP exhibits heightened expression across a spectrum of tumours, thereby fostering their proliferation and metastasis, rendering it a pivotal therapeutic target. Nevertheless, to date, no pharmacological agents capable of directly targeting and inducing the degradation of C1QBP have been identified. In this study, we have unveiled a new peptide, PDBAG1, derived from the precursor protein GPD1, employing a peptidomics-based drug screening strategy.

pACP-HybDeep: predicting anticancer peptides using binary tree growth based transformer and structural feature encoding with deep-hybrid learning.

Worldwide, Cancer remains a significant health concern due to its high mortality rates. Despite numerous traditional therapies and wet-laboratory methods for treating cancer-affected cells, these approaches often face limitations, including high costs and substantial side effects. Recently the high selectivity of peptides has garnered significant attention from scientists due to their reliable targeted actions and minimal adverse effects.

Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective.

The standard dengue virus (DENV) neutralization assay inconsistently predicts dengue protection. We compare how IgG ELISA, envelope domain III (EDIII), or non-structural protein 1 (NS1) binding antibodies, and titers from plaque reduction neutralization tests (PRNTs) using standard and mature viruses are associated with dengue. The ELISA measures IgG antibodies that bind to inactivated DENV1-4.