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.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Assessment of the safety and gut microbiota modulation ability of an infant formula containing Bifidobacterium animalis ssp. lactis CP-9 or Lactobacillus salivarius AP-32 and the effects of the formula on infant growth outcomes: insights from a four-month clinical study in infants under two months old.

Background: Breast milk is a natural treasure for infants, and its microbiota contains a rich array of bacterial species. When breastfeeding is not possible, infant formula with probiotics can be used as a sole source or as a breast milk supplement. The main aim of this study was to evaluate the growth outcomes and tolerance of infants consuming an infant formula containing Bifidobacterium animalis ssp.

Using a two sample Mendelian randomization approach to explore the causal relationship between erectile dysfunction and lung function.

Background: Recently, some observational studies have suggested potential associations between erectile dysfunction (ED) and respiratory function. However, the underlying biological mechanisms and causal relationships between ED and lung function require further investigation. This study aimed to explore the causalities between ED and lung function traits.

Glucose Testing Methods: A Systematic Review and Meta-Analysis of Diagnostic Accuracy of Point-of-Care Devices for Neonatal Hypoglycemia.

Objective: To evaluate the accuracy of various point-of-care device methodologies for measuring blood glucose concentrations in babies at risk of neonatal hypoglycemia.

Study Design: This systematic review and meta-analysis included studies from Ovid MEDLINE, Ovid Embase, and Web of Science up to May 20, 2024. Studies comparing point-of-care testing methods for neonatal blood glucose to a standard laboratory method were included, excluding those on continuous glucose monitoring or conducted before 1990.

Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.

Cholangiocarcinoma (CCA) is a highly fatal malignancy with an increasing prevalence, a high mortality rate, poor overall survival, and limited responsiveness to conventional chemoradiotherapy. Targeted therapies addressing specific gene mutations have expanded treatment options for some patient populations. The introduction of chimeric antigen receptor-modified T-cell (CAR-T) immunotherapy and personalized vaccines have opened up a new avenue for managing various cancers.

Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes.

Objective: To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) benefits women of advanced reproductive age (≥38 years old) with a diminished ovarian reserve (not more than three retrieved oocytes).

Design: A retrospective analysis comparing two groups: (a) PGT-A group: women who chose PGT-A and subsequent single re-warmed embryo transfers and (b) non-PGT-A group: women who chose not to genetically test their embryos and underwent subsequent fresh or re-warmed embryo transfers of one to two embryos on days 3 or 5.

Subjects: Two hundred thirty patients underwent PGT-A therapy, with 49 of these individuals undergoing more than one PGT-A cycle.

Fungal symbiont transmitted by free-living mice promotes type 2 immunity.

The gut mycobiota is crucial for intestinal homeostasis and immune function. Yet its variability and inconsistent fungal colonization of laboratory mice hinders the study of the evolutionary and immune processes that underpin commensalism. Here, we show that Kazachstania pintolopesii is a fungal commensal in wild urban and rural mice, with an exceptional ability to colonize the mouse gastrointestinal tract and dominate the gut mycobiome.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.

Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes.

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation.

Tuft cells act as regenerative stem cells in the human intestine.

In mice, intestinal tuft cells have been described as a long-lived, postmitotic cell type. Two distinct subsets have been identified: tuft-1 and tuft-2 (ref. ).

Development and Validation of a Contrast-Enhanced US VI-RADS for Evaluating Muscle Invasion in Bladder Cancer.

Background Contrast-enhanced US (CEUS) can be used preoperatively for evaluating muscle invasion in bladder cancer, which is important for determining appropriate treatment. However, diagnostic criteria for assessing this at CEUS have not been standardized. Purpose To develop and validate a CEUS Vesical Imaging Reporting and Data System (VI-RADS) for evaluating muscle invasion in bladder cancer.

Targeting Dual Immune Checkpoints PD-L1 and HLA-G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer.

Immunotherapy targeting immune checkpoints (ICPs), such as programmed death-ligand-1 (PD-L1), is used as a treatment option for advanced or metastatic non-small cell lung cancer (NSCLC). However, overall response rate to anti-PD-L1 treatment is limited due to antigen heterogeneity and the immune-suppressive tumor microenvironment. Human leukocyte antigen-G (HLA-G), an ICP as well as a neoexpressed tumor-associated antigen, is previously demonstrated to be a beneficial target in combination with anti-PD-L1.

Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals.

Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated the effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding the greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate mapping, in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting.

Cataract Surgery and Incidence of Retinal Vascular Occlusion: Population-Based Cohort Study Using a Target Trial Emulation Framework.

Background: Previous studies suggested an association between cataract surgery and retinal vascular occlusion. However, the association may be attributable to detection bias because postoperative monitoring may be more frequent for those who receive cataract surgery than for those who do not.

Design: Population-based cohort study using target trial emulation framework.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.

A joint model of longitudinal pharmacokinetic and time-to-event data to study exposure-response relationships: a proof-of-concept study with alectinib.

Purpose: In exposure-response analyses of oral targeted anticancer agents, longitudinal plasma trough concentrations are often aggregated into a single value even though plasma trough concentrations can vary over time due to dose adaptations, for example. The aim of this study was to compare joint models to conventional exposure-response analyses methods with the application of alectinib as proof-of-concept.

Methods: Joint models combine longitudinal pharmacokinetic data and progression-free survival data to infer the dependency and association between the two datatypes.

Deposition of Gadolinium in the Central and Peripheral Nervous Systems and Its Effects on Sensory, Cognitive, and Athletic Implications after Multiple Injections of Gadolinium-Based Contrast Agents in Rats.

Background And Purpose: After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications.

Materials And Methods: Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.