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.

A Novel Preclinical Murine Model of Systemic Lupus Erythematosus-Like Cardiovascular Disease.

Objective: Systemic lupus erythematosus (SLE) affects nine women to every man worldwide, and these patients are at greater risk for cardiovascular disease (CVD) morbidity and mortality. Clinical studies have demonstrated that patients with SLE are more likely to develop CVD, including cardiac and vascular dysfunction. Although many preclinical models of SLE are available, including treatment with Toll-like receptor (TLR) 7/8 agonists, a consistent preclinical model of SLE-like CVD with systemic, cardiac, renal, and cerebral endothelial activation and cardiac dysfunction has yet to be described.

PHONETIC UNDERPINNINGS OF SOUND SYMBOLISM ACROSS MULTIPLE DOMAINS OF MEANING.

Sound symbolism occurs when the sound of a word alone can convey its meaning, e.g. 'balloon' and 'spike' sound rounded and pointed, respectively.

Biofilm mitigation in hybrid chemical-biological upcycling of waste polymers.

Accumulation of plastic waste in the environment is a serious global issue. To deal with this, there is a need for improved and more efficient methods for plastic waste recycling. One approach is to depolymerize plastic using pyrolysis or chemical deconstruction followed by microbial-upcycling of the monomers into more valuable products.

Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort.

Background: Pollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied.

Objective: We described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators.

Geministatins: new depside antibiotics from the fungus Austroacremonium gemini.

Two new depside antibiotics, geministatins A (1) and B (2), were isolated from the fungus Austroacremonium gemini MST-FP2131 (Sordariomycetes, Ascomycota), which was recovered from rotting wood in the wet tropics of northern Australia. The structures of the geministatins were elucidated by detailed spectroscopic analysis, chemical degradation and comparison with literature values. Chemical degradation of 1 and 2 yielded three new analogues, geministatins C-E (3-5), as well as a previously reported compound dehydromerulinic acid A (6).

The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade.

Construction of residential histories to estimate long-term environmental exposures in the California Teachers Study cohort.

Environmental epidemiologic studies using geospatial data often estimate exposure at a participant's residence upon enrollment, but mobility during the exposure period can lead to misclassification. We aimed to mitigate this issue by constructing residential histories for participants in the California Teachers Study through follow-up (1995-2018). Address records have been collected from the US Postal Service, LexisNexis, Experian, and California Cancer Registry.

The multilevel correlates, contributions, and consequences of leader humility in humanitarian aid work.

Objective: Leader humility has been linked to many positive outcomes but not examined in humanitarian aid work. Three studies examined the multilevel correlates, contributions, and consequences of leader humility in Medair-a large, multinational, faith-based aid organization. Study 1 examined correlates of leader humility in a sample of 308 workers and 167 leaders.

Talcarpones A and B: bisnaphthazarin-derived metabolites from the Australian fungus Talaromyces johnpittii sp. nov. MST-FP2594.

Talcarpones A (1) and B (2) are rare bisnaphthazarin derivatives produced by Talaromyces johnpittii (ex-type strain MST-FP2594), a newly discovered Australian fungus, which is formally described and named herein. The talcarpones were isolated along with the previously reported monomeric naphthoquinone, aureoquinone (3), suggesting a biosynthetic link between these metabolites. Talcarpone A is a lower homologue of hybocarpone (4), which was first isolated from a mycobiont of the lichen Lecanora hybocarpa.

Persistence of SARS-CoV-2 antibodies over 18 months following infection: UK Biobank COVID-19 Serology Study.

Background: Little is known about the persistence of antibodies after the first year following SARS-CoV-2 infection. We aimed to determine the proportion of individuals that maintain detectable levels of SARS-CoV-2 antibodies over an 18-month period following infection.

Methods: Population-based prospective study of 20 000 UK Biobank participants and their adult relatives recruited in May 2020.

Central Adiposity Increases Risk of Kidney Stone Disease through Effects on Serum Calcium Concentrations.

Significance Statement: Kidney stone disease is a common disorder with poorly understood pathophysiology. Observational and genetic studies indicate that adiposity is associated with an increased risk of kidney stone disease. However, the relative contribution of general and central adipose depots and the mechanisms by which effects of adiposity on kidney stone disease are mediated have not been defined.

Social determinants of ethnic disparities in SARS-CoV-2 infection: UK Biobank SARS-CoV-2 Serology Study.

Background: The social determinants of ethnic disparities in risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK remain unclear.

Methods: In May 2020, a total of 20 195 adults were recruited from the general population into the UK Biobank SARS-CoV-2 Serology Study. Between mid-May and mid-November 2020, participants provided monthly blood samples.

Neural basis of sound-symbolic pseudoword-shape correspondences.

Non-arbitrary mapping between the sound of a word and its meaning, termed sound symbolism, is commonly studied through crossmodal correspondences between sounds and visual shapes, e.g., auditory pseudowords, like 'mohloh' and 'kehteh', are matched to rounded and pointed visual shapes, respectively.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

Neural Basis Of Sound-Symbolic Pseudoword-Shape Correspondences.

Unlabelled: Non-arbitrary mapping between the sound of a word and its meaning, termed sound symbolism, is commonly studied through crossmodal correspondences between sounds and visual shapes, e.g., auditory pseudowords, like 'mohloh' and 'kehteh', are matched to rounded and pointed visual shapes, respectively.

Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells.

Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR.

LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis.

The leishmaniases are neglected tropical diseases caused by various parasite species transmitted by sand flies. They comprise a number of systemic and cutaneous syndromes including kala-azar (visceral leishmaniasis, VL), cutaneous leishmaniasis (CL), and post-kala-azar dermal leishmaniasis (PKDL). The leishmaniases cause significant mortality (estimated 20 - 50,000 deaths annually), morbidity, psychological sequelae, and healthcare and societal costs.

Building resilience and reversing frailty: a randomised controlled trial of a primary care intervention for older adults.

Background: There is a need for effective primary care interventions that help older people combat frailty and build resilience.

Objective: To study the effectiveness of an optimised exercise and dietary protein intervention.

Design: Multicentre, randomised-controlled, parallel-arm trial.

Improved Strength Recovery and Reduced Fatigue with Suppressed Plasma Myostatin Following Supplementation of a Hydrolysate, in a Healthy Male Population.

Delayed onset muscle soreness (DOMS) due to intense physical exertion can negatively impact contractility and performance. Previously, NPN_1 (PeptiStrong™), a hydrolysate derived from a protein concentrate discovered through artificial intelligence (AI), was preclinically shown to help maintain muscle health, indicating the potential to mediate the effect of DOMS and alter molecular markers of muscle damage to improve recovery and performance. A randomised double-blind placebo-controlled trial was conducted on 30 healthy male (30-45 years old) volunteers (NCT05159375).

Balancing the safeguarding of privacy and data sharing: perceptions of genomic professionals on patient genomic data ownership in Australia.

There are inherent complexities and tensions in achieving a responsible balance between safeguarding patients' privacy and sharing genomic data for advancing health and medical science. A growing body of literature suggests establishing patient genomic data ownership, enabled by blockchain technology, as one approach for managing these priorities. We conducted an online survey, applying a mixed methods approach to collect quantitative (using scale questions) and qualitative data (using open-ended questions).