Trametinib alters contractility of paediatric Noonan syndrome-associated hypertrophic myocardial tissue slices.

Aims: No curative treatment is available for RASopathy-associated childhood-onset hypertrophic cardiomyopathy (RAS-CM). Preclinical data and individual reports suggest a beneficial effect of small molecules targeting the RAS-mitogen-activated protein (MAP) kinase (MAPK) pathway in severely affected RAS-CM patients. The aim of this study was to evaluate the biophysical effects of trametinib, rapamycin and dasatinib on cultivated myocardial tissue slices of a paediatric RAS-CM patient using biomimetic cultivation chambers (BMCCs) and to correlate the findings with clinical data.

State-level disparities in cervical cancer prevention and outcomes in the U.S.: a modeling study.

Background: Despite HPV vaccines' availability for over a decade, coverage across the US varies. While some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model.

Risk Factors for Developing Adenovirus-Associated Post-Infectious Bronchiolitis Obliterans.

Background: Risk factors for progression of adenovirus (AdV)-associated bronchiolitis (AdV-B) to post-infectious bronchiolitis obliterans (PIBO) are poorly defined. We aimed to investigate this in a multicenter cohort.

Methods: A multicenter hospital-based analysis included children admitted with AdV-B in Jerusalem during 2016-2022.

Postoperative Opioid Reduction Using a Multimodal Pain Protocol for Outpatient Orthopaedic Sports Medicine Surgery.

Background: Orthopaedic surgery regularly employs opioids for postoperative pain management. Multimodal pain protocols have been shown to reduce opioid prescriptions in orthopaedic surgery.

Purpose: To analyze the impact of a division-level multimodal pain protocol for orthopaedic sports medicine surgery on opioid prescription reduction and pain level postoperatively.

Dopamine D1 and NMDA Receptor Co-Regulation of Protein Translation in Cultured Nucleus Accumbens Neurons.

Protein translation is essential for some forms of synaptic plasticity. Here we used fluorescent noncanonical amino acid tagging (FUNCAT) to examine whether dopamine modulates protein translation in cultured nucleus accumbens (NAc) medium spiny neurons (MSN). These neurons were co-cultured with cortical neurons to restore excitatory synapses.

Assessing the spatial scale of synchrony in forest tree population dynamics.

Populations of forest trees exhibit large temporal fluctuations, but little is known about the synchrony of these fluctuations across space, including their sign, magnitude, causes and characteristic scales. These have important implications for metapopulation persistence and theoretical community ecology. Using data from permanent forest plots spanning local, regional and global spatial scales, we measured spatial synchrony in tree population growth rates over sub-decadal and decadal timescales and explored the relationship of synchrony to geographical distance.

Cardiorespiratory Fitness From Cardiopulmonary Exercise Testing Is a Comprehensive Risk-stratifying Tool in Liver Transplant Candidates.

Background: Cardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates.

Hormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple Negative Breast Cancers.

Purpose: The MammaPrint prognostic assay categorizes breast cancers into high- and low-risk subgroups, and the high-risk group can be further subdivided into high 1 (MP-H1), and very high-risk high-2 (MP/H-2). The aim of this analysis was to assess clinical and molecular differences between the hormone receptor positive/HER2-negative (HR+) MP-H1, -H2, and triple negative (TN) MP-H1 and -H2 cancers.

Experimental Design: Pre-treatment gene expression data from 742 HER2 negative breast cancers enrolled in the I-SPY2 neoadjuvant trial was used.

Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial.

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination.

Sex differences in ectopic lipid deposits and cardiac function across a wide range of glycemic control: a secondary analysis.

Objective: The objective of this study was to identify sex differences in ntrahepatocellular (HCL) and intramyocardial lipids (MYCL) and cardiac function in participants with different grades of glucometabolic impairment and different BMI strata.

Methods: Data from 503 individuals from 17 clinical experimental studies were analyzed. HCL and MYCL were assessed with 3T and 7T scanners by magnetic resonance spectroscopy.

Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts.

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components.

The codevelopment of early social and cognitive skills in Ghana.

Children's early skills are strong predictors of later learning outcomes. Research aiming to disentangle the causal effects of early skills from unmeasured, stable characteristics related to learning throughout development demonstrates that unmeasured confounders explain a large portion of the effects of early skills previously identified. To date, such research has been conducted exclusively in high-income Western countries, where education systems are better funded and overall learning outcomes are much higher than in low- and middle-income countries.

Social Anxiety Reduces Visual Attention to the Eyes of Emotional Faces in Autistic Youth.

Autism and social anxiety (SA) share behavioral features like reduced eye contact, variable social attention, and differences in social interactions. However, the impact of the co-occurrence of these conditions (e.g.

A Novel Machine Learning Model to Predict Revision ACL Reconstruction Failure in the MARS Cohort.

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights.

Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure.

Study Design: Cohort study; Level of evidence, 3.

Breast tumor microbiome regulates anti-tumor immunity and T cell-associated metabolites.

Background: Breast cancer, the most common cancer type among women, was recently found to contain a specific tumor microbiome, but its impact on host biology remains unclear. CD8 tumor-infiltrating lymphocytes (TILs) are pivotal effectors of anti-tumor immunity that influence cancer prognosis and response to therapy. This study aims to elucidate interactions between CD8 TILs and the breast tumor microbiome and metabolites, as well as how the breast tumor microbiome may affect the tumor metabolome.

A scheduling perspective on modular educational systems in Europe.

In modular educational systems, students are allowed to choose a part of their curriculum themselves. The rationale behind letting students choose their courses themselves is to enhance self-responsibility, improve student motivation, and allow for focus on specific areas of interest. A central instrument for bringing these systems to fruition is the timetable.

Siglec15/TGF-β bispecific antibody mediates synergistic anti-tumor response against 4T1 triple negative breast cancer in mice.

An ideal tumor-specific immunomodulatory therapy should both preferentially target the tumor, while simultaneously reduce the immunosuppressive environment within the tumor. This guiding principle led us to explore engineering Siglec-15 (S15) targeted bispecific antibody (bsAb) to enhance therapy against triple negative breast cancer (TNBC). S15 appears to be exclusively expressed on macrophages and diverse tumor cells, including human and mouse 4T1 TNBC.

Obesity-related maternal complications during the COVID-19 pandemic.

Objectives: To compare gestational weight gain (GWG) during pregnancy and obesity-related maternal morbidity between three months of the first year of the COVID-19 pandemic and three months of the previous year.

Methods: A retrospective comparative study was conducted in a tertiary university-affiliated hospital. GWG, obesity rates and pregnancy complications were compared between the time periods.

Ultrasound Assessment of Pleural Effusions After Orthotopic Pig-to-Baboon Cardiac Xenotransplantation.

Background: Pleural effusions develop frequently after cardiac surgery in humans. Lung ultrasound is an essential non-invasive tool in the diagnosis and treatment of these effusions. Pleural effusions also develop regularly after preclinical cardiac xenotransplantation experiments.

Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation.

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes.

Creative music therapy in preterm infants effects cerebrovascular oxygenation and perfusion.

Creative music therapy (CMT) has been shown to promote the development of brain function and structure in preterm infants. We aimed to investigate the effect of CMT on cerebral oxygenation and perfusion to examine how the brain reacts to CMT. Absolute levels of cerebrovascular oxygen saturation (StO) were measured in clinically stable preterm-born neonates (n = 20, gestational age: ≥30 weeks and < 37 weeks) using two near-infrared spectroscopy (NIRS)-based tissue oximeters over the right prefrontal cortex and left auditory cortex.

Spatial transcriptomics reveals molecular cues underlying the site specificity of the adult mouse oral mucosa and its stem cell niches.

The oral cavity is a multifunctional organ composed of structurally heterogeneous mucosal tissues that remain poorly characterized. Oral mucosal tissues are highly stratified and segmented along an epithelial-lamina propria axis. Here, we performed spatial transcriptomics (tomo-seq) on the tongue, cheeks, and palate of the adult mouse to understand the cues that maintain the oral mucosal sites.

Autodetachment of Diatomic Carbon Anions from Long-Lived High-Rotation Quartet States.

We show that strong molecular rotation drastically modifies the autodetachment of C_{2}^{-} ions in the lowest quartet electronic state a^{4}Σ_{u}^{+}. In the strong-rotation regime, levels of this state only decay by a process termed "rotationally assisted" autodetachment, whose theoretical description is worked out based on the nonlocal resonance model. For autodetachment linked with the exchange of six rotational quanta, the results reproduce a prominent, hitherto unexplained electron emission signal with a mean decay time near 3 ms, observed on stored C_{2}^{-} ions from a hot ion source.

Variations in the management of pediatric cerebral vasospasm.

Objective: Pediatric cerebral vasospasm (PCV) is associated with aneurysmal subarachnoid hemorrhage (aSAH), but aSAH is uncommon in children. No universal guidelines exist for PCV management. The authors sought to assess variations in practice patterns in pediatric aSAH and PCV management.