Thyroid Autoimmunity: The Treatment of Hashimoto's Disease, or the Presence of Antithyroid Antibodies Alone, in Pregnancy.

Problem: Hashimoto's disease is the commonest autoimmune disease of pregnancy. The presence of Anti-Thyroid antibodies (ATAs) alone [subclinical hypothyroidism] has also been shown to have adverse pregnancy effects. These can result in failure to conceive, recurrent miscarriages, anemia, preeclampsia, and abruption.

Tailoring Kidney Transplant Strategies: Unraveling the Impact of Acute Kidney Injury and Preservation Methods Across Different Strata of Kidney Risk.

Background: The use of donor kidneys with acute kidney injury (AKI) aims to expand the organ pool, but uncertainty remains regarding their outcomes across different Kidney Donor Profile Index (KDPI) groups and preservation methods.

Methods: We retrospectively analyzed 108 160 deceased donor kidney transplants from the OPTN database, focusing on adult recipients of kidneys from donors with or without AKI between December 2014 and December 2022. Propensity matching was used for each KDPI group (1-20, 21-59, 60-84, and 85-100), comparing donors with AKIN stages 0-1 to AKIN stages 2-3.

Development of novel patient-reported outcome instruments to assess atopic dermatitis-associated dyspigmentation and xerosis in patients with skin of colour.

Background: The prevalence and burden of atopic dermatitis (AD) are disproportionately high in individuals with skin of colour (SOC). Previous research shows that risk for xerosis and/or dyspigmentation is heightened in this population and may be more bothersome. However, there are no patient-reported instruments developed specifically for these disease sequelae in patients with SOC.

A regulatory network involving calmodulin controls phytosulfokine peptide processing during drought-induced flower abscission.

Drought stress substantially decreases crop yields by causing flowers and fruits to detach prematurely. However, the molecular mechanisms modulating organ abscission under drought stress remain unclear. Here, we show that expression of CALMODULIN2 (CaM2) is specifically and sharply increased in the pedicel abscission zone (AZ) in response to drought and plays a positive role in drought-induced flower drop in tomato (Solanum lycopersicum).

Protocol for applying Tumor Treating Fields in mouse models of cancer using the inovivo system.

Tumor Treating Fields (TTFields) are electric fields clinically approved for cancer treatment, delivered via arrays attached to the patient's skin. Here, we present a protocol for applying TTFields to torso orthotopic and subcutaneous mouse tumor models using the inovivo system. We guide users on proper system component connections, study protocol design, mouse fur depilation, array application, and treatment condition adjustment and monitoring.

Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class.

The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.

ERK activation dynamics in maturing oocyte controls embryonic nuclear divisions in Caenorhabditis elegans.

ERK activity oscillates between sustained activation during oocyte formation and transient inactivation during oocyte maturation, fertilization, and early embryogenesis. Consequences of ectopic ERK activity upon oocyte maturation and in early embryogenesis are unknown. We show, in Caenorhabditis elegans, that ectopic ERK activity upon oocyte maturation (metaphase I oocytes) results in embryos with abnormalities in nuclear divisions leading to embryonic death.

TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.

IL-21 shapes the B cell response in a context-dependent manner.

The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1 B cells.

Transcriptional determinants of goal-directed learning and representational drift in the parahippocampal cortex.

Task learning involves learning associations between stimuli and outcomes and storing these relationships in memory. While this information can be reliably decoded from population activity, individual neurons encoding this representation can drift over time. The circuit or molecular mechanisms underlying this drift and its role in learning are unclear.

Previous short-term disuse dictates muscle gene expression and physiological adaptations to subsequent resistance exercise.

Short-term unloading experienced following injury or hospitalisation induces muscle atrophy and weakness. The effects of exercise following unloading have been scarcely investigated. We investigated the functional and molecular adaptations to a resistance training (RT) programme following short-term unloading.

Probing the Neurodynamic Mechanisms of Cognitive Flexibility in Depressed Individuals with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by deficits in social behavior and executive function (EF), particularly in cognitive flexibility. Whether transcranial magnetic stimulation (TMS) can improve cognitive outcomes in patients with ASD remains an open question. We examined the acute effects of prefrontal TMS on cortical excitability and fluid cognition in individuals with ASD who underwent TMS for refractory major depression.

Discovery of Diverse CRISPR Leader Motifs, Putative Functions, and Applications for Enhanced CRISPR Detection and Subtype Annotation.

Bacteria and archaea acquire resistance to genetic parasites by preferentially integrating short fragments of foreign DNA at one end of a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR). "Leader" DNA upstream of CRISPR loci regulates transcription and foreign DNA integration into the CRISPR. Here, we analyze 37,477 CRISPRs from 39,277 bacterial and 556 archaeal genomes to identify conserved sequence motifs in CRISPR leaders.

Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain andN-Terminal Domain mRNA Vaccine.

Background: mRNA-1283 is an investigational COVID-19 mRNA vaccine encoding the receptor-binding and N-terminal domains of the SARS-CoV-2 spike protein in contrast to the original mRNA-1273, which encodes the full-length spike protein.

Methods: A phase 2a, dose-ranging, observer-blind, randomized study (NCT05137236) conducted in adults (≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.

Self-Perceptions of Aging and Physical Activity in Older Adults with Arthritis: Impact of General Health.

How negative self-perceptions of aging relate to physical activity (PA) in older adults with arthritis is unclear. We examined whether general health mediated the relationship between Awareness of Age-Related change (AARC) losses and PA. We analyzed baseline data from a randomized controlled trial of a PA intervention for adults ≥60 years who self-reported PA, AARC, general health, pain, and social support.

Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in mice.

Exposure to ionizing radiation (IR), both low-LET (e.g., X-rays, γ rays) and high-LET (e.

Amplicon Sequencing Reveals Diversity in Spatially Separated Microbial Communities in the Icelandic Mars Analog Environment Mælifellssandur.

Exploration missions to Mars rely on landers or rovers to perform multiple analyses over geographically small sampling regions, while landing site selection is done using large-scale but low-resolution remote-sensing data. Utilizing Earth analog environments to estimate small-scale spatial and temporal variation in key geochemical signatures and biosignatures will help mission designers ensure future sampling strategies meet mission science goals. Icelandic lava fields can serve as Mars analog sites due to conditions that include low nutrient availability, temperature extremes, desiccation, and isolation from anthropogenic contamination.

Long-Term Safety and Efficacy with Roflumilast Cream 0.15% in Patients Aged ≥6 Years with Atopic Dermatitis: A Phase 3 Open-Label Extension Trial.

Safety and efficacy of roflumilast cream 0.15% for atopic dermatitis (AD) were demonstrated in two 4-week phase 3 trials. Evaluate long-term safety, tolerability, and efficacy of roflumilast cream 0.

Lectin Microarray Analysis of Salivary Gland Glycoproteins from the Arboviral Vector Aedes aegypti and the Malaria Vector Anopheles stephensi.

Background And Objectives: Salivary glands proteins but not glycoconjugates have been previously studied in mosquito vectors of human diseases. Glycoconjugates from salivary gland-derived proteins from human-feeding tick vectors can elicit hypersensitivity reactions which may also occur with mosquito bites. Protein glycoconjugate in salivary glands of the principal arboviral vector Aedes aegypti and the rapidly spreading malaria vector Anopheles stephensi were therefore investigated.

Genome-wide association study of varenicline-aided smoking cessation.

Introduction: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

Methods: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes.

The Association Between Dietary Supplement Use and COVID-19 Symptoms.

The scientific evidence supporting recommendations for dietary supplement use to prevent or treat coronavirus disease 2019 (COVID‑19) is not well‑established. This cohort study investigates the relationship between dietary supplement usage and COVID‑19 symptoms among 27,181 adults tested for COVID‑19. Using data from surveys following COVID‑19 testing, conducted by the University of Arkansas for Medical Sciences, associations between dietary supplement usage, symptomatology, and COVID‑19 status were explored.

Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory diffuse large B-cell lymphoma: A phase III bridging study in Chinese patients.

Background: Patients with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options and poor outcomes.

Methods: This phase III study (NCT04236141) evaluated the efficacy and safety of polatuzumab vedotin plus bendamustine and rituximab (Pola+BR) versus BR in Chinese patients with transplant-ineligible R/R DLBCL to support regulatory submission in China. Patients were randomized 2:1 to receive Pola+BR or placebo+BR.

Tailed molecular beacon probes: an approach for the detection of structured DNA and RNA analytes.

Molecular beacon (MB) probes have been extensively used for nucleic acid analysis. However, MB probes fail to hybridize with folded DNA or RNA. Here, we demonstrate that MB probes equipped with extra sequences complementary to the analyte, named 'tail', can increase the signal-to-background ratio by ∼40-fold and hybridization rates by ∼800-fold compared to conventional MB probes.