Time-Resolved Hierarchical Modeling Highlights Metabolites Influencing Productivity and Cell Death in Chinese Hamster Ovary Cells.

Biopharmaceuticals are medical compounds derived from biological sources and are often manufactured by living cells, primarily Chinese hamster ovary (CHO) cells. CHO cells display variation among cell clones, leading to growth and productivity differences that influence the product's quantity and quality. The biological and environmental factors behind these differences are not fully understood.

Vestibular modulation by stimulant derivatives in a pentameric ligand-gated ion channel.

Background And Purpose: Allosteric modulation of pentameric ligand-gated ion channels (pLGICs) are critical for the action of neurotransmitters and many psychoactive drugs. However, details of their modulatory mechanisms remain unclear, especially beyond the orthosteric neurotransmitter-binding sites. The recently reported prokaryotic symbiont of Tevnia jerichonana ligand-gated ion channel (sTeLIC), a pH-gated homologue of eukaryotic receptors in the pLGIC family, is thought to be modulated by aromatic compounds via a relatively uncharacterised modulatory site in the extracellular vestibule.

Genetic origins of the Kiritimati population from central-eastern Micronesia.

The migration of Austronesian-speaking populations through Oceania has intrigued researchers for decades. The Kiribati islands, situated along the boundaries of Micronesia and Polynesia, provide a crucial link in this migration. We analyzed the genome-wide data of the Kiritimati population of Kiribati to uncover their genetic origins and connections with other Oceanian groups.

The Expansion of Colonial State Healthcare in Twentieth-Century British Africa.

We chart and assess the scope and utilisation of state-supplied hospital infrastructure in British Africa, c. 1900-60. Using archival sources, we examine the heterogeneity in colonial administrations' investment into curative healthcare provision across various regions of British Africa.

Substantial Reduction of Systemic Corticosteroid Use After Primary Ileocaecal Resection in Swedish Patients With Crohn's Disease: A Population-Based Cohort Study.

Background: The corticosteroid-sparing effects of ileocaecal resection have not been thoroughly investigated in a population-based cohort.

Aim: To investigate systemic corticosteroid use before and after primary ileocaecal resection in patients with Crohn's disease.

Methods: Through nationwide registries, we identified 1565 patients with Crohn's disease undergoing primary ileocaecal resection in Sweden 2006-2019.

Optimizing calibration designs with uncertainty in abilities.

Before items can be implemented in a test, the item characteristics need to be calibrated through pretesting. To achieve high-quality tests, it's crucial to maximize the precision of estimates obtained during item calibration. Higher precision can be attained if calibration items are allocated to examinees based on their individual abilities.

Predicting adherence and clinical response of cognitive behavioral therapy among individuals with chronic low back pain plus depressive symptoms: A secondary analysis of a randomized controlled trial.

Background: Identifying predictors for adherence and clinical response to psychological therapies is essential for improving individual treatment outcomes.

Objective: To explore predictors of adherence and clinical response among individuals with co-occurring chronic low back pain (CLBP) and depression receiving cognitive behavioral therapy (CBT).

Methods: This study employs a secondary analysis of data from a randomized controlled trial (NCT04140838), including 156 individuals with CLBP plus depressive symptoms who received CBT.

Individualized PEEP can improve both pulmonary hemodynamics and lung function in acute lung injury.

Rationale: There are several approaches to select the optimal positive end-expiratory pressure (PEEP), resulting in different PEEP levels. The impact of different PEEP settings may extend beyond respiratory mechanics, affecting pulmonary hemodynamics.

Objectives: To compare PEEP levels obtained with three titration strategies-(i) highest respiratory system compliance (C), (ii) electrical impedance tomography (EIT) crossing point; (iii) positive end-expiratory transpulmonary pressure (P)-in terms of regional respiratory mechanics and pulmonary hemodynamics.

Association between conflict intensity and health outcomes in contemporary conflicts, while accounting for the vulnerability and functioning of healthcare services.

Background: Armed conflict can be described as human development in reverse. In addition to the direct consequences of violence, there are numerous ways in which armed conflict may have indirect effects on people's health and well-being. Studies give varying results, and health impacts seem to differ from context to context.

Beekeepers as guardians of apitherapeutic knowledge in Estonia, SW Ukraine, and NE Italy.

Background: Bees have been important to people in Europe in many ways. Honey was the only sweetener available for a long time. The introduction of frame hives allowed for the collection of various hive products and better production of honey and wax.

Ginseng exosomes modulate M1/M2 polarisation by activating autophagy and target IKK/IкB/NF-кB to alleviate inflammatory bowel disease.

Background: Exosomes are involved in intercellular communication and regulation of the inflammatory microenvironment. In a previous study, we demonstrated that fresh ginseng exosomes (GEs) alleviated inflammatory bowel disease. However, the precise mechanism by which GEs activate the immune system and subsequently inhibit the formation of intestinal inflammatory microenvironment remains unknown.

Development of a community-based peer-support intervention to improve contraceptive agency and diffuse self-injectable contraception in Uganda: Application of the human-centered design approach.

Background: The low use of self-injectable contraception, coupled with the recognition that many individuals need support beyond training to use self-care technologies successfully, suggests the need for innovative programming. We describe the participatory human-centered design process we used in two districts of Uganda to develop a community-based peer support intervention to improve women's agency to make and act on contraceptive decisions and help diffuse self-injectable contraception.

Methods: The design team included multi-disciplinary researchers from Uganda and the United States, representatives of local community-based organizations and village health teams, and local women of reproductive age.

Mitogenomic phylogeny and divergence time estimation of Artemia Leach, 1819 (Branchiopoda: Anostraca) with emphasis on parthenogenetic lineages.

The brine shrimp Artemia, a crustacean adapted to the extreme conditions of hypersaline environments, comprises nine regionally distributed sexual species scattered (island-like) over heterogeneous environments and asexual (parthenogenetic) lineages with different ploidies. Such sexual and asexual interaction within the genus raises questions regarding the origin and time of divergence of both sexual species and asexual lineages, including the persistence of the latter over time, a problem not yet clarified using single mitochondrial and nuclear markers. Based on the complete mitochondrial genome of all species and parthenogenetic lineages, this article first describes the mitogenomic characteristics (nucleotide compositions, genome mapping, codon usage, and tRNA secondary structure) of sexual species and asexual types and, secondly, it provides a comprehensive updated phylogenetic analysis.

An enhanced framework for local genetic correlation analysis.

Genetic correlation is a key parameter in the joint genetic model of complex traits, but it is usually estimated on a global genomic scale. Understanding local genetic correlations provides more detailed insight into the shared genetic architecture of complex traits. However, a state-of-the-art tool for local genetic correlation analysis, LAVA, is prone to false inference.

EMD missense variant causes X-linked isolated dilated cardiomyopathy with myocardial emerin deficiency.

Pathogenic variants in the EMD gene cause X-linked Emery-Dreifuss muscular dystrophy type 1 (EDMD1), typically presenting with joint contractures and skeletal muscle atrophy, followed by atrial arrhythmias, cardiac conduction defects, and atrial dilatation. Although an association with isolated dilated cardiomyopathy (DCM) has been suggested, evidence is currently insufficient to verify the gene-disease association. We investigated the causality of a missense variant, c.

Observation of an Associative State in Aqueous Hydroxide.

The dynamics of chemical reactions in solution are of paramount importance in fields ranging from biology to materials science. Because the hydrogen-bond network and proton dynamics govern the behavior of aqueous solutions, they have been the subject of numerous studies over the years. Here, we report the observation of a previously unknown associative state in the hydroxide ion that forms when a proton from a neighboring water molecule approaches the hydroxide ion, utilizing resonant inelastic soft X-ray scattering (RIXS) and quantum dynamical simulations.

Early Pregnancy Waist Circumference for Prediction of Fetal Macrosomia.

Fetal macrosomia is associated with adverse short- and long-term outcomes for the mother and the child. Present models to predict fetal macrosomia cannot be used in all settings, and their precision could be improved. We assessed if waist circumference could replace or outperform weight for early pregnancy prediction of macrosomia.

Who Benefits Most? Personality Traits as Predictors of Identity Intervention Outcomes in Adolescence.

Interventions focused on adolescents' identity development have shown promising results, but questions remain as to which adolescents benefit most from them. This preregistered study examined how personality traits (Big Five domains and higher-order meta-traits) moderate adolescents' responsiveness to the Identity Project, a school-based intervention supporting ethnic-racial identity development. A total of 509 adolescents from 22 classrooms in the southwestern regions of Sweden participated in an intervention and control group design (M = 16.

Identification of Predictive Factors for the Development of In-Transit Metastasis in Patients with Melanoma.

Background: In patients with melanoma, in-transit metastasis (ITM) can develop. This study aimed to identify the risk for a first recurrence of ITM and associated predictive clinical factors in a large international cohort of patients with melanoma.

Methods: Patients with primary cutaneous melanoma who underwent wide local excision (WLE) and sentinel lymph node biopsy (SLNB) were identified from the Sentinel Lymph Node Working Group (SLNWG) database between January 1993 and February 2023.

Mastrevirus Transmission by the Insect Vectors, Leafhoppers.

Mastreviruses are important pathogens on many crops and they are transmitted in a persistent manner by leafhoppers. For experimental studies on mastreviruses, transmission with leafhoppers remains as an important method for virus inoculation. Here, we describe a protocol for setting up a culture of the leafhopper vector Psammotettix alienus and efficient leafhopper-mediated transmission of wheat dwarf virus.

Trabecular-bone mimicking osteoconductive collagen scaffolds: an optimized 3D printing approach using freeform reversible embedding of suspended hydrogels.

Background: Technological constraints limit 3D printing of collagen structures with complex trabecular shapes. However, the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) method may allow for precise 3D printing of porous collagen scaffolds that carry the potential for repairing critical size bone defects.

Methods: Collagen type I scaffolds mimicking trabecular bone were fabricated through FRESH 3D printing and compared either with 2D collagen coatings or with 3D-printed polyethylene glycol diacrylate (PEGDA) scaffolds.

Feasibility of a single-day protocol for SPECT and PET assessment of dopamine transporter availability, cardiac innervation and metabolic patterns in patients with movement disorders.

Purpose: Due to new advances in molecular and imaging biomarkers, a biological classification of Parkinson's disease (PD) called SyNeurGe (Hoglinger et al. Lancet Neurol 2024;23:191-204) has been proposed for research use recently. [I]ioflupane dopamine transporter single-photon-emission-computed tomography (DaT-SPECT) and cardiac [I]meta-iodobenzylguanidine (MIBG) scintigraphy are included in this biological classification scheme together with 2-[F]fluoro-2-deoxy-D-glucose (FDG-PET) as central imaging biomarkers for the assessment of dopaminergic function, cardiac sympathetic denervation, and metabolic patterns in brain.

Rare MTNR1B variants causing diminished MT2 signalling associate with elevated HbA levels but not with type 2 diabetes.

Aims/hypothesis: An intronic variant (rs10830963) in MTNR1B (encoding the melatonin receptor type 2 [MT2]) has been shown to strongly associate with impaired glucose regulation and elevated type 2 diabetes prevalence. However, MTNR1B missense variants have shown conflicting results on type 2 diabetes. Thus, we aimed to gain further insights into the impact of MTNR1B coding variants on type 2 diabetes prevalence and related phenotypes.

Specific targeting of the 5-hydroxytryptamine 2B receptor (5-HTR) demonstrates antifibrotic effects in murine models and ex vivo models of scleroderma skin.

Objectives: Systemic sclerosis (SSc) is a connective tissue disease with fibrotic remodeling of the skin and various internal organs. SSc is associated with the highest case-specific mortality of all rheumatic autoimmune diseases with limited antifibrotic treatment options. Here, we evaluated the therapeutic effects of the highly selective 5-hydroxytryptamine 2B receptor (5-HTR) inhibitor AM1476.