Osteopontin as a Biomarker for Coronary Artery Disease.

Osteopontin (OPN) is a sialylated phosphoprotein highly expressed in atherosclerosis and upregulated in settings of both acute and chronic inflammation. It is hypothesised that plasma levels of OPN may correlate with the presence of coronary artery disease, "CAD". This offers potential as a point-of-care testing biomarker for early diagnosis, disease monitoring, and prognosis.

Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

Differential Impact of Risk Factors for Cognitive Decline in Heterosexual and Sexual Minority Older Adults in England.

Background/objectives: Sexual minority older adults (SMOAs) report greater subjective cognitive decline (SCD) than heterosexual older adults (HOAs). This study aimed to compare the impact of multiple psycho-social risk factors on objective and subjective cognitive decline in HOAs and SMOAs.

Methods: Two samples of self-identified HOAs and SMOAs were selected from the English Longitudinal Study of Ageing.

Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis.

Background: Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation and the infiltration of immune cells into the brain contribute to this process. However, no study has investigated the role of peripheral blood immune cells in ALS pathophysiology using single-cell RNA sequencing (scRNAseq).

Methods: We aimed to characterize immune cells from blood and identify ALS-related immune alterations at single-cell resolution.

Co-design of a novel rehabilitation intervention for patients after ankle fracture surgery: establishing healthcare professional consensus.

Post-surgical rehabilitation advice after ankle fracture surgery, particularly regarding weight-bearing, varies significantly, leading to patient frustration and inconsistent recovery outcomes. This study aimed to establish a consensus for ankle fracture rehabilitation advice and identify content and implementation options for future interventions through consultation with healthcare professionals (HCPs). This study was part of the weight-bearing in ankle fractures (WAX) trial, a multicentre, randomised controlled trial.

Impact of a Long-Term Home-Based Rehabilitation Program on Quality of Life, Balance, and Autonomy in Adults with Disabilities.

Background: Rehabilitation is a critical process for enhancing functionality, independence, and quality of life in individuals with disabilities. Grounded in the biopsychosocial model, it addresses physical, emotional, and social dimensions through personalized, evidence-based interventions. By integrating standardized assessments and continuous evaluation, rehabilitation has the potential to promote recovery and support active participation in society.

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Evaluation of a Machine Learning-Guided Strategy for Elevated Lipoprotein(a) Screening in Health Systems.

Background: While universal screening for Lp(a; lipoprotein[a]) is increasingly recommended, <0.5% of patients undergo Lp(a) testing. Here, we assessed the feasibility of deploying Algorithmic Risk Inspection for Screening Elevated Lp(a; ARISE), a validated machine learning tool, to health system electronic health records to increase the yield of Lp(a) testing.

Quasi-static and dynamic compression behavior of stacked pyramidal lattice structures with I-beam struts.

This study investigates the quasi-static and dynamic compression performance of a newly designed stacked pyramidal lattice (SPL) structure composed of struts that resemble I-beams. These novel lattice structures are 3D-printed considering three different stacking sequences, and their stiffness, strength, and energy absorption properties are experimentally assessed through low-velocity impact (1.54 m/s) and quasi-static compression tests.

Empowering African Expertise: Enhancing Safety Data Integration and Signal Detection for COVID-19 Vaccines Through the African Union Smart Safety Surveillance Joint Signal Management Group.

Introduction: The COVID-19 pandemic accelerated new vaccine development. Limited safety data necessitated robust global safety surveillance to accurately identify and promptly communicate potential safety issues. The African Union Smart Safety Surveillance (AU-3S) program established the Joint Signal Management (JSM) group to support identification of potential vaccine safety concerns in five pilot countries (Ethiopia, Ghana, Kenya, Nigeria, South Africa), accounting for approximately 35% of the African population.

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.

Nature and prevalence of long-term conditions in people with intellectual disability: retrospective longitudinal population-based study.

Objective: Explore the nature and prevalence of long-term conditions in individuals with intellectual disability.

Design: Retrospective longitudinal population-based study.

Setting: Primary and secondary care data across the population of Wales with the Secure Anonymised Information Linkage (SAIL) Databank.

REVEAL-CP: Selective Screening of Pediatric Patients for Aromatic L-Amino Acid Decarboxylase Deficiency with a Guthrie Card and Structural Modeling of One Index Case.

The main objective of this prospective, multicenter study (REVEAL-CP) was to test children with cerebral palsy-like signs and symptoms for raised 3--methyldopa (3-OMD) blood levels, a biomarker for aromatic L-amino acid decarboxylase deficiency (AADCd). A secondary objective was to characterize the molecular basis for the defective aromatic L-amino acid decarboxylase (AADC) gene product. Patients were identified in pediatric secondary and tertiary care hospitals through database searches and personal communication.

Item-Level Analysis of Category Fluency Test Performance: A Systematic Review and Meta-Analysis of Studies of Normal and Neurologically Abnormal Ageing.

While Category Fluency (CF) is widely used to help profile semantic memory, item-level scoring (ILS) approaches to this test have been proposed to obtain indices that are less influenced by non-semantic supportive functions. We systematically reviewed the literature to test the hypotheses that (1) compared with healthy adults, individuals with a clinical diagnosis suggestive of neurodegeneration generate words of lower semantic complexity; (2) compared with young adults, older adults generate words of higher semantic complexity. We searched six databases (date of search: 8 December 2023) for studies that relied on CF and ILS methods, in normal ageing and in age-associated neurodegeneration.

Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein-based materials.

The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment.

Machine Learning-Based Prediction of Binge Drinking among Adults in the United State: Analysis of the 2022 Health Information National Trends Survey.

Little is known about the association of social media and belief in alcohol and cancer with binge drinking. This study aimed to perform feature selection and develop machine learning (ML) tools to predict occurrence of binge drinking among adults in the United State. A total of 5,886 adults including 1,252 who ever experienced with binge drinking were selected from the 2022 Health Information National Trends Survey (HINTS 6).

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

Mycodiversity in a micro-habitat: twelve species, including four new taxa, isolated from uredinia of coffee leaf rust, .

During surveys in the centres of origin of the coffee leaf rust (CLR), in Africa, as well as in its exotic range in Brazil, 23 isolates of the genus were obtained from uredinial pustules. Using a phylogenetic analysis of all isolates involving a combination of partial sequences of the internal transcribed spacer region of rDNA (ITS) and two gene regions: actin ( and translation elongation factor-1α (), 12 species were delimited; including four new species - , , and . GCPSR criteria were employed for species recognition, supported by morphological and cultural characters.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.

Population pharmacokinetics and exposure-response analysis of durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer.

Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.

Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.

Postprandial glycaemic response and pain sensitivity in breast cancer survivors suffering from chronic pain: a double-blind, randomised controlled cross-over pilot experiment.

Introduction: The study's primary goal is to investigate differences in postprandial glycaemic response (PPGR) to beverages with varying glycaemic index (i.e. low and medium) between breast cancer survivors (BCS) with chronic pain and healthy pain-free controls (HC).

Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.

Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.

The (in)dependence of single-cell data inferences on model constructs.

Recent developments in single-cell analysis have revolutionized basic research and have garnered the attention of the forensic domain. Though single-cell analysis is not new to forensics, the ways in which these data can be generated and interpreted are. Modern interpretation strategies report likelihood ratios that rely on a model of the world that is a simplification of it.

Lipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.

Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS.