Cytokine Dynamics in Action: A Mechanistic Approach to Assess Interleukin 6 Related Therapeutic Protein-Drug-Disease Interactions.

Understanding cytokine-related therapeutic protein-drug interactions (TP-DI) is crucial for effective medication management in conditions characterized by elevated inflammatory responses. Recent FDA and ICH guidelines highlight a systematic, risk-based approach for evaluating these interactions, emphasizing the need for a thorough mechanistic understanding of TP-DIs. This study integrates the physiologically based pharmacokinetic (PBPK) model for TP (specifically interleukin-6, IL-6) with small-molecule drug PBPK models to elucidate cytokine-related TP-DI mechanistically.

Tenascin-X deficiency causing classical-like Ehlers Danlos syndrome type 1 in humans is a significant risk factor for GI and tracheal ruptures.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.

The burden of Alagille syndrome: uncovering the potential of emerging therapeutics - a comprehensive systematic literature review.

Alagille syndrome (ALGS) is a rare, cholestatic multiorgan disease associated with bile duct paucity, leading to cholestasis. Clinical symptoms of cholestasis include debilitating pruritus, xanthomas, fat-soluble vitamin deficiencies, growth failure, renal disease and impaired health-related quality of life (HRQoL). The main objective was to review the current literature on the epidemiological, clinical, psychosocial and economic burden of ALGS in view of the development of ileal bile acid transporter (IBAT) inhibitors.

The cognitive and evolutionary science of behavioural modernity goes beyond material chronology.

Stibbard-Hawkes' taphonomic findings are valuable, and his call for caution warranted, but the hazards he raises are being mitigated by a multi-pronged approach; current research on behavioural/cognitive modernity is not based solely on material chronology. Theories synthesize data from archaeology, anthropology, psychology, neuroscience, and genetics, and predictions arising from these theories are tested with mathematical and agent-based models.

Not just symbolism: Technologies may also have a less than direct connection with cognition.

I expand Stibbard-Hawkes' exploration of symbolism and cognition to suggest that we also ought to reconsider the strength of connections between cognition and technological complexity. Using early weaponry as a case study I suggest that complexity may be "hidden" in early tools, and further highlight that assessments of technologies as linear and progressive have roots in Western colonial thought.

Material culture both reflects and causes human cognitive evolution.

Our commentary suggests that different materialities (fragile, enduring, and mixed) may influence cognitive evolution. Building on Stibbard-Hawkes, we propose that predictive brains minimise errors and seek information, actively structuring environments for epistemic benefits. This perspective complements Stibbard-Hawkes' view.

Hominin cognition: The null hypothesis.

The target article explores material culture datasets from three African forager groups. After demonstrating that these modern, contemporary human populations would leave scant evidence of symbolic behaviour or material complexity, it cautioned against using material culture as a barometer for human cognition in the deep past. Twenty-one commentaries broadly support or expand these conclusions.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

An evaluation of a community dementia screening program in rural Kenya: DEM-SKY.

Introduction: This study describes the implementation outcomes and evaluation of DEM-SKY, a community-based dementia screening program developed in rural Kenya with the support of community health care workers (CHWs).

Methods: DEM-SKY was delivered to 3546 older adults in Makueni County, Kenya, over a 6-month period. Using a mixed-methods design, we explored implementation outcomes with stakeholders through surveys and interviews.

Non-native species have higher consumption rates than their native counterparts.

Non-native species can be major drivers of ecosystem alteration, especially through changes in trophic interactions. Successful non-native species have been predicted to have greater resource use efficiency relative to trophically analogous native species (the Resource Consumption Hypothesis), but rigorous evidence remains equivocal. Here, we tested this proposition quantitatively in a global meta-analysis of comparative functional response studies.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.

A non-interpenetrated mesoporous hydrogen-bonded organic framework constructed with 1,3,5-tri(4-carboxyphenyl)benzene.

The discovery of porous molecular solids has been constantly hindered by phase transformation and interpenetration. Here, we crystallize two molecules with three substituted carboxylic groups. A mesoporous, non-interpenetrated HOF that is constructed from 1,3,5-tri(4-carboxyphenyl)benzene (TCPB) is discovered and reported for the first time.

HIF1α Plays a Crucial Role in the Development of TFE3-Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis.

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α.

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome.

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic).

The relationships of plasma profenofos and ethanol concentrations to clinical outcome in acute profenofos self-poisoning.

Introduction: Many patients acutely self-poisoned with organophosphorus insecticides have co-ingested ethanol. Currently, profenofos 50% emulsifiable concentrate (EC50) is commonly ingested for self-harm in Sri Lanka. Clinical experience suggests that ethanol co-ingestion makes management more difficult.

Biallelic variants in AGRN with recurrent pregnancy losses in a family with a fetal akinesia deformation sequence.

Introduction: Agrin, encoded by AGRN, plays a vital role in the acetylcholine receptor clustering pathway, and any defects in this pathway are known to cause congenital myasthenic syndrome (CMS) 8 in early childhood with variable fatigable muscle weakness. The most severe or lethal form of CMS manifests as a fetal akinesia deformation sequence (FADS). To date, only one family has been reported with an association of null variants in AGRN and a lethal FADS.

Unraveling the transcriptomic landscape of brain vascular cells in dementia: A systematic review.

Introduction: Cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia and related neurodegenerative disorders. Recent omics-driven research has revealed associations between vascular abnormalities and transcriptomic alterations in brain vascular cells, particularly endothelial cells (ECs) and pericytes (PCs). However, the impact of these molecular changes on dementia remains unclear.

Exposure Contrasts of Women Aged 40-79 Years during the Household Air Pollution Intervention Network Randomized Controlled Trial.

Exposure to household air pollution has been linked to adverse health outcomes among women aged 40-79. Little is known about how shifting from biomass cooking to a cleaner fuel like liquefied petroleum gas (LPG) could impact exposures for this population. We report 24-h exposures to particulate matter (PM), black carbon (BC), and carbon monoxide (CO) among women aged 40 to <80 years participating in the Household Air Pollution Intervention Network trial.

Accurate Estimation of Diffusion Coefficients and their Uncertainties from Computer Simulation.

Self-diffusion coefficients, *, are routinely estimated from molecular dynamics simulations by fitting a linear model to the observed mean squared displacements (MSDs) of mobile species. MSDs derived from simulations exhibit statistical noise that causes uncertainty in the resulting estimate of *. An optimal scheme for estimating * minimizes this uncertainty, i.

A review on the effects of flavan-3-ols, their metabolites, and their dietary sources on gut barrier integrity.

Impairment of gut barrier integrity is associated with the pathogenesis of gastrointestinal diseases, including inflammatory bowel disease, colorectal cancer, and coeliac disease. While many aspects of diet have been linked to improved barrier function, (poly)phenols, a broad group of bioactive phytochemicals, are of potential interest. The (poly)phenolic sub-class, flavan-3-ols, have been investigated in some detail owing to their abundance in commonly consumed foods, including grapes, tea, apples, cocoa, berries, and nuts.

Exploring public support for novel tobacco and alcohol control policies in Great Britain 2021-2023: A population-based cross-sectional survey.

Objective And Rationale: This study assessed support for novel tobacco compared with alcohol control policies among adults in Great Britain in 2021-2023. Objectives were to assess 1) overall level of support for tobacco compared to alcohol control policies; 2) level of support for tobacco compared to alcohol control policies among people who smoke tobacco or who consume alcohol at increasing and higher risk levels, or who do both; 3) level of support for tobacco compared to alcohol control policies among different sociodemographic groups?

Methods: Data were collected in September/October 2021-2023 in a monthly population-based survey on smoking and drinking behaviour of adults across Great Britain (N = 6311), weighted to match the overall population. Outcome measure was level of support for each seven tobacco and alcohol control policies.

Lower bounds on trees and unicyclic graphs with respect to the misbalance rodeg index.

The Misbalance Rodeg () index stands out among the 148 discrete Adriatic indices demonstrating considerable predictive capabilities in evaluations carried out by the International Academy of Mathematical Chemistry. This index excels particularly in forecasting both the enthalpy and the standard enthalpy of vaporization for octane isomers. Despite its significant chemical applicability, the index has not been extensively explored in the literature.

Cardiovascular health and risks of atrial fibrillation and its prognosis.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia around the world with an increased risk of a broad spectrum of adverse comorbidities and death. Whether cardiovascular health (CVH) is associated with AF development remains unclear.

Methods: 238,420 participants without cardiovascular disease at baseline were selected from the UK Biobank study cohort from 2006 to 2010.