stormTB: a web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments.

Introduction: Tuberculosis (TB) poses a significant threat to global health, with millions of new infections and approximately one million deaths annually. Various modeling efforts have emerged, offering tailored data-driven and physiologically-based solutions for novel and historical compounds. However, this diverse modeling panorama may lack consistency, limiting result comparability.

Arcuate fasciculus cortico-cortical evoked potentials and direct cortico-subcortical stimulation during awake craniotomy for debulking of left dominant temporal oligodendroglioma.

Electrophysiological mapping and monitoring techniques permit the objective measurement of eloquent cortical regions and accompanying white matter tracts to reduce the incidence of iatrogenic injury in glioma surgery. Recently, there has been increased interest in mapping and monitoring of the human arcuate fasciculus via cortico-cortical evoked potentials (CCEPs) during awake and asleep craniotomy. The authors present the case of a 27-year-old female who underwent a hypnosis-assisted awake craniotomy with cortico-subcortical language mapping and arcuate fasciculus CCEPs.

Factors Influencing Iron Levels Among Women of Reproductive Age and Children 6-48 Months in Livestock-Keeping Communities in Narok County, Kenya.

Proper nutrition is vital for maintaining good health for all people across their lifespan, especially children and mothers, who are especially vulnerable due to their specific nutrient needs. Despite the necessity of improved nutrition for these groups, some members do not fully meet their recommended daily micronutrient needs, a challenge exacerbated by different socioeconomic, cultural, and communal constraints resulting in malnutrition. Iron deficiency anaemia is a major concern among children and mothers, especially in pastoralist communities, due to poor nutrition and other related factors.

A Comprehensive Review on the Application of Artificial Intelligence for Predicting Postsurgical Recurrence Risk in Early-Stage Non-Small Cell Lung Cancer Using Computed Tomography, Positron Emission Tomography, and Clinical Data.

Introduction: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Despite advancements in early detection and treatment, postsurgical recurrence remains a significant challenge, occurring in 30%-55% of patients within 5 years after surgery. This review analysed existing studies on the utilisation of artificial intelligence (AI), incorporating CT, PET, and clinical data, for predicting recurrence risk in early-stage NSCLCs.

Chlorogenic Acid Ameliorates CCl4-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.

Background: Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.

Objective: Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.

Methods: Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks.

The Kids Pain Collaborative: A Hybrid Type 3 Implementation Effectiveness Study Transforming Paediatric Pain Care in the Emergency Department.

Aim: To evaluate the impact of a participatory, action-oriented implementation study, guided by the integrated Promoting Action on Research Implementation in Health Services framework, for optimising pain care processes in a tertiary paediatric emergency department.

Design: Hybrid type 3 implementation effectiveness.

Methods: A collaborative appraisal of the context and culture of pain care informed two interdependent action cycles: Enabling nurse-initiated analgesia and involving families in pain care.

Methionine Sulfoximine as a Tool for Studying Temporal Lobe Epilepsy: Initiator, Developer, Attenuator.

Methionine sulfoximine (MSO) is a compound originally discovered as a byproduct of agene-based milled flour maturation. MSO irreversibly inhibits the astrocytic enzyme glutamine synthase (GS) but also interferes with the transport of glutamine (Gln) and of glutamate (Glu), and γ-aminobutyric acid (GABA) synthesized within the Glu/Gln-GABA cycle, in this way dysregulating neurotransmission balance in favor of excitation. No wonder that intraperitoneal administration of MSO has long been known to induce behavioral and/or electrographic seizures.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.

Acute liver failure is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates.

Immune Checkpoint Inhibitors +/- Chemotherapy for Patients With NSCLC and Brain Metastases: A Systematic Review and Network Meta-Analysis.

Background: Multiple studies have demonstrated the intracranial efficacy of immune checkpoint inhibitors (ICI) +/- chemotherapy. The efficacy of chemoimmunotherapy compared to ICI alone in patients with metastatic NSCLC and brain metastases (BM) remains unknown.

Methods: A systematic review and network meta-analysis were performed to evaluate ICI efficacy and the influence of additional chemotherapy on survival outcomes in treatment-naïve metastatic NSCLC with BM.

When multiple instance learning meets foundation models: Advancing histological whole slide image analysis.

Deep multiple instance learning (MIL) pipelines are the mainstream weakly supervised learning methodologies for whole slide image (WSI) classification. However, it remains unclear how these widely used approaches compare to each other, given the recent proliferation of foundation models (FMs) for patch-level embedding and the diversity of slide-level aggregations. This paper implemented and systematically compared six FMs and six recent MIL methods by organizing different feature extractions and aggregations across seven clinically relevant end-to-end prediction tasks using WSIs from 4044 patients with four different cancer types.

Therapeutic gene target prediction using novel deep hypergraph representation learning.

Identifying therapeutic genes is crucial for developing treatments targeting genetic causes of diseases, but experimental trials are costly and time-consuming. Although many deep learning approaches aim to identify biomarker genes, predicting therapeutic target genes remains challenging due to the limited number of known targets. To address this, we propose HIT (Hypergraph Interaction Transformer), a deep hypergraph representation learning model that identifies a gene's therapeutic potential, biomarker status, or lack of association with diseases.

PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.

BRAF mutations drive initiation and progression of various tumors. While BRAF inhibitors are effective in BRAF-mutant melanoma patients, intrinsic or acquired resistance to these therapies is common. Here, we identify non-receptor-type protein tyrosine phosphatase 23 (PTPN23) as an alternative effective target in BRAF-mutant cancer cells.

A systematic review to determine the effect of strategies to sustain chronic disease prevention interventions in clinical and community settings.

This review assessed the effect of strategies designed to sustain the delivery of evidenced based interventions (EBIs) which target behavioural risk factors linked to leading causes of chronic disease in clinical and community settings. Seven electronic databases were searched for randomised controlled studies published from earliest record to November 2022. Studies were included if they tested a strategy to sustain the delivery of an EBI within clinical or community settings.

South Korean study to prevent cognitive impairment and protect brain health through multidomain interventions via face-to-face and video communication platforms in mild cognitive impairment (SUPERBRAIN-MEET): A randomized controlled trial.

Introduction: We investigated the efficacy of a multidomain intervention (MI) via face-to-face and video communication platforms using a tablet personal computer application in patients with mild cognitive impairment (MCI).

Methods: Three hundred participants with MCI and ≥ 1 modifiable dementia risk factor, aged 60-85 years, were randomly assigned to either the MI group, who underwent a 24-week intervention, or the control group, who received usual care.

Results: The overall adherence rate to MI was 84.

The PKM2 activator TEPP-46 suppresses cellular senescence in hydrogen peroxide-induced proximal tubular cells and kidney fibrosis in CD-1 mice.

Aim/introduction: Senescence is a key driver of age-related kidney dysfunction, including diabetic kidney disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and is associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to cellular senescence have not been elucidated. We hypothesized that PKM2 activation by TEPP-46 could suppress oxidative stress-induced renal tubular cell injury and cellular senescence.

Ischemic Area-Targeting and Self-Monitoring Nanoprobes Ameliorate Myocardial Ischemia/Reperfusion Injury by Scavenging ROS and Counteracting Cardiac Inflammation.

Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real-time monitoring of drug aggregation in the MIRI region remains an open question. Herein, a drug delivery system, hesperadin and ICG assembled in PLGA-Se-Se-PEG-IMTP (HI@PSeP-IMTP), is designed to deliver hesperadin and ICG to the MIRI region for in vivo optical imaging tracking and to ameliorate MIRI.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

ASA Class Is a Stronger Predictor of Early Revision Risk Following Primary Total Knee Arthroplasty than BMI.

Background: Although there is a known correlation between obesity and revision risk following total knee arthroplasty (TKA), there is an ongoing debate regarding the appropriateness of denying TKA solely based on the body mass index (BMI) of a patient. Our aim was to determine whether a patient's American Society of Anesthesiologists (ASA) class predicts their risks of early all-cause revision and revision for periprosthetic joint infection (PJI) following primary TKA, independent of their BMI.

Methods: Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) were obtained regarding all patients who underwent primary TKA for osteoarthritis in Australia from January 1, 2015, to December 31, 2022.

Integrative genomic analyses combined with molecular dynamics simulations reveal the impact of deleterious mutations of Bcl-2 gene on the apoptotic machinery and implications in carcinogenesis.

Objectives: Unlike other diseases, cancer is not just a genome disease but should broadly be viewed as a disease of the cellular machinery. Therefore, integrative multifaceted approaches are crucial to understanding the complex nature of cancer biology. Bcl-2 (B-cell lymphoma 2), encoded by the human BCL-2 gene, is an anti-apoptotic molecule that plays a key role in apoptosis and genetic variation of Bcl-2 proteins and is vital in disrupting the apoptotic machinery.

Clinical phenotype and trio whole exome sequencing data from a patient with glycogen storage disease IV in Indonesia.

Glycogen storage disease type IV (GSD IV) is a rare disease caused by a defect in glycogen branching enzyme 1 (GBE1), which played a crucial role in glycogen branching. GSD IV occurs once in approximately 1 in every 760,000 to 960,000 live births and is inherited in an autosomal recessive pattern. Early diagnosis of GSD IV is challenging due to non-specific symptoms, such as liver and spleen enlargement, which can overlap with other hematologic and hepatobiliary disorders.

Geographic origin and evolution of dengue virus serotypes 1 and 3 circulating in Africa.

Despite the increasing burden of dengue in Kenya and Africa, the introduction and expansion of the virus in the region remain poorly understood. The objective of this study is to examine the genetic diversity and evolutionary histories of dengue virus (DENV) serotypes 1 and 3 in Kenya and contextualize their circulation within circulation dynamics in the broader African region. Viral RNA was extracted from samples collected from a cohort of febrile patients recruited at clinical sites in Kenya from 2013 to 2022.

Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease.

Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.