Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures.

Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally available, safe-in-man pleconaril, AG7404, and mindeudesivir, that at non-toxic concentrations effectively inhibited enterovirus replication in human cell and organoid cultures.

Mechanisms of change in an online acceptance and commitment therapy intervention for insomnia.

Insomnia, i.e., difficulty falling asleep or staying asleep, is a common condition that is connected to many psychological and physical problems.

Preterm birth and risk of bone fractures during childhood and early adulthood.

People born preterm have reduced bone mineral density, subnormal peak bone mass, and an increased risk of osteoporosis. Whether this translates to increased risk of bone fractures is uncertain. We assessed fracture risk from childhood to early adulthood in relation to gestational age and sex by conducting a nationwide register-linkage cohort study comprising all 223 615 liveborn (1/1987- 9/1990) singletons (9161, 4.

Investigating the interactions between a poloxamer and TEMPO-oxidised cellulose nanocrystals.

Cellulose nanocrystals (CNCs) have emerged as promising, sustainable materials, with applications in sensors, coatings, pharmaceuticals, and composites. Their modification with block copolymers such as PEO-PPO-PEO triblock copolymers of the Pluronic family has been attempted many times in the literature, with claims that such modification would happen by an anchor(PEO)-buoy(PPO)-anchor(PEO) mechanism. However, there is much disagreement in the literature on this.

Retrospective cross-sectional study on bronchiectasis in adult Aboriginal Australians: disease characteristics and comparison with ethnically diverse global bronchiectasis registry cohorts.

Background: Globally, adult Indigenous people, including Aboriginal Australians, have a high burden of chronic respiratory disorders, and bronchiectasis is no exception. However, literature detailing bronchiectasis disease characteristics among adult Indigenous people is sparse. This study assessed the clinical profile of bronchiectasis among adult Aboriginal Australians and compared against previously published international bronchiectasis registry reports.

Behavioral interventions targeting treatment adherence in chronic kidney disease: A systematic review and meta-analysis.

Adherence to dialysis, medication regimens and dietary and fluid intake recommendations can improve quality of life and survival in chronic kidney disease, but non-adherence is prevalent. This review and meta-analysis investigated the effects of behavioral interventions on treatment adherence in chronic kidney disease and examined intervention characteristics (Behavior Change Techniques and delivery methods) associated with direct and indirect measures of adherence. Literature searches in five databases identified 149 eligible studies (255 study arms; 15878 patients).

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.

Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort study.

Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes.

Methods: Quantification of apolipoproteins was performed on maternal plasma samples (N = 243 trios) collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study.

HBM4EU E-waste study - An untargeted metabolomics approach to characterize metabolic changes during E-waste recycling.

E-waste contains hazardous chemicals that may be a direct health risk for workers involved in recycling. We conducted an untargeted metabolomics analysis of urine samples collected from male e-waste processing workers to explore metabolic changes associated with chemical exposures in e-waste recycling in Belgium, Finland, Latvia, Luxembourg, the Netherlands, Poland, and Portugal. Questionnaire data and urine samples were obtained from workers involved in the processing of e-waste (sorting, dismantling, shredding, pre-processing, metal, and non-metal processing), as well as from controls with no known occupational exposure.

Ferritin Outperforms Other Biomarkers in Predicting Bone Marrow Iron Stores in Hematological Patients.

Although iron deficiency anemia is common, interpreting iron laboratory test results can be challenging in patients with comorbidities. We aimed to study the accuracy of common iron biomarkers compared with bone marrow iron staining in a large retrospective dataset of hematological patients. We collected from 6610 patients (median age 66 years) results of iron staining, with their concurrent ferritin, transferrin saturation, soluble transferrin receptor, transferrin, hemoglobin, and mean red blood cell volume results from Helsinki University Hospital electronic health records.

Impact of Ligand Structure on Biological Activity and Photophysical Properties of NHC-Protected Au Nanoclusters.

N-heterocyclic carbene (NHC)-protected gold nanoclusters display high stability and high photoluminescence, making them well-suited for fluorescence imaging and photodynamic therapeutic applications. We report herein the synthesis of two bisNHC-protected Au nanoclusters with π-extended aromatic systems. Depending on the position of the π-extended aromatic system, changes to the structure of the ligand shell in the cluster are observed, with the ability to correlate increases in rigidity with increases in fluorescence quantum yield.

Beyond , Pharmaceutical Molecule Production in Cell-Free Systems and the Use of Noncanonical Amino Acids Therein.

Throughout history, we have looked to nature to discover and copy pharmaceutical solutions to prevent and heal diseases. Due to the advances in metabolic engineering and the production of pharmaceutical proteins in different host cells, we have moved from mimicking nature to the delicate engineering of cells and proteins. We can now produce novel drug molecules, which are fusions of small chemical drugs and proteins.

Mitochondria complex III-generated superoxide is essential for IL-10 secretion in macrophages.

Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mitochondria ETC complex III (CIII)-deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow-derived macrophages (BMDMs) isolated from these mitochondria CIII-deficient mice released less IL-10 than controls following TLR3 or TLR4 stimulation.

Miniaturized spectral sensing with a tunable optoelectronic interface.

Reconstructive optoelectronic spectroscopy has generated substantial interest in the miniaturization of traditional spectroscopic tools, such as spectrometers. However, most state-of-the-art demonstrations face fundamental limits of rank deficiency in the photoresponse matrix. In this work, we demonstrate a miniaturized spectral sensing system using an electrically tunable compact optoelectronic interface, which generates distinguishable photoresponses from various input spectra, enabling accurate spectral identification with a device footprint of 5 micrometers by 5 micrometers.

What emotions does music express? Structure of affect terms in music using iterative crowdsourcing paradigm.

Music is assumed to express a wide range of emotions. The vocabulary and structure of affects are typically explored without the context of music in which music is experienced, leading to abstract notions about what affects music may express. In a series of three experiments utilising three separate and iterative association tasks including a contextualisation with typical activities associated with specific music and affect terms, we identified the plausible affect terms and structures to capture the wide range of emotions expressed by music.

Diving into Unknown Waters: Water-Soluble Clickable Au Nanoclusters Protected with N-Heterocyclic Carbenes for Bio-Medical Applications.

The use of gold nanoclusters in biomedical applications has been steadily increasing in recent years. However, water solubility is a key factor for these applications, and water-soluble gold nanoclusters are often difficult to isolate and susceptible to exchange or oxidation in vivo. Herein, we report the isolation of N-heterocyclic carbene (NHC)-protected atomically precise gold nanoclusters functionalized with triethylene glycol monomethyl ether groups.

Early precursor-derived pituitary gland tissue-resident macrophages play a pivotal role in modulating hormonal balance.

The pituitary gland is the central endocrine regulatory organ producing and releasing hormones that coordinate major body functions. The physical location of the pituitary gland at the base of the brain, though outside the protective blood-brain barrier, leads to an unexplored special immune environment. Using single-cell transcriptomics, fate mapping, and imaging, we characterize pituitary-resident macrophages (pitMØs), revealing their heterogeneity and spatial specialization.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Tuberculosis vaccines and therapeutic drug: challenges and future directions.

Tuberculosis (TB) remains a prominent global health challenge, with the World Health Organization documenting over 1 million annual fatalities. Despite the deployment of the Bacille Calmette-Guérin (BCG) vaccine and available therapeutic agents, the escalation of drug-resistant Mycobacterium tuberculosis strains underscores the pressing need for more efficacious vaccines and treatments. This review meticulously maps out the contemporary landscape of TB vaccine development, with a focus on antigen identification, clinical trial progress, and the obstacles and future trajectories in vaccine research.

A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer.

Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells.

CpG island methylator phenotype classification improves risk assessment in pediatric T-cell Acute Lymphoblastic Leukemia.

Current intensive treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has substantial side-effects, highlighting a need for novel biomarkers to improve risk stratification. Canonical biomarkers such as genetics and immunophenotype are largely not used in pediatric T-ALL stratification. This study aimed to validate the prognostic relevance of DNA methylation CpG island methylator phenotype (CIMP) risk stratification in two pediatric T-ALL patient cohorts: the Nordic NOPHO ALL2008 T-ALL study cohort (n=192) and the Dutch DCOG ALL-10/ALL-11 validation cohorts (n=156).

Synthesis of a Transient Cationic Phosphaborene and its Trapping by Facile Aliphatic C-H Bond Activation.

The synthesis of a transient cationic phosphaborene [(Mes*)P=B(CAAC)]+ (Mes* = 2,4,6,-trit-tert-butylphenyl, CAAC = cyclic alkylamino carbene) by halide abstraction from the B-brominated analogue is reported. This species was found to undergo rapid and selective intramolecular aliphatic C-H bond activation to yield a phosphinoborenium cation, which undergoes facile deprotonation to give a cyclic base-stabilized phosphaborene. Computational investigation of the mechanism of C-H activation indicates a boron-centred activation route with an exceptionally low barrier of 8 kJ mol-1, followed by a nearly barrierless hydride migration from boron to phosphorus.

Molecular cytogenetic study of the fetal genome in idiopathic recurrent pregnancy loss.

Objective: Despite numerous studies on the causes of recurrent pregnancy loss (RPL), nearly half of cases remain unidentified, which determines the research relevance. This study aims to investigate microchromosomal variations in the fetal genome associated with the development of idiopathic RPL.

Methods: The research was supported by the Centre for Molecular Medicine and the Research Institute of Obstetrics, Gynecology and Perinatology and conducted over a period of 2 years.

Ascending aortic replacement versus aortic root replacement in patients with type A aortic dissection involving the aortic root.

Background: Extensive surgical resection of the thoracic aorta in patients with type A aortic dissection (TAAD) is thought to reduce the risk of late aortic wall degeneration and the need for repeat aortic operations.

Objectives: We evaluated the early and late outcomes after aortic root replacement and supracoronary ascending aortic replacement in patients with TAAD involving the aortic root.

Design: Retrospective, multicenter cohort study.