Preclinical safety and effectiveness of a long-acting somatostatin analogue [Ac]Ac-EBTATE against small cell lung cancer and pancreatic neuroendocrine tumors.

Purpose: We report the preclinical evaluation of potent long-acting [Ac]Ac-EBTATE against SSTR2-positive small cell lung cancer (SCLC) and pancreatic neuroendocrine tumors (pan-NETs).

Methods: The pharmacokinetic, biodistribution, and safety studies were evaluated in healthy female and/or male BALB/c mice after intravenous injections of [Ac]Ac-EBTATE. Further biodistribution and radioligand therapy were investigated in female athymic BALB/c nude mice bearing high or low SSTR2-expressing subcutaneous SCLC models NCI-H524 or NCI-H727, respectively, and in a pan-NET model QGP1.

Decoding Adenine DNA Methylation Effects in Streptococcus Mutans: Insights Into Self-DNA Protection and Autoaggregation.

Streptococcus mutans, a key player in dental caries, faces multiple environmental challenges within the oral cavity, including oxidative stress, nutrient scarcity, and acidic pH. To survive and thrive, S. mutans has evolved intricate mechanisms, including the CSP-ComDE quorum sensing system, which coordinates responses to environmental cues.

Prediction of the upright articulated spine shape in the operating room using conditioned neural kernel fields.

Anterior vertebral tethering (AVT) is a non-invasive spine surgery technique, treating severe spine deformations and preserving lower back mobility. However, patient positioning and surgical strategies greatly influences postoperative results. Predicting the upright geometry from pediatric spines is needed to optimize patient positioning in the operating room (OR) and improve surgical outcomes, but remains a complex task due to immature bone properties.

Proteostasis restoration: a new metric for tau immunotherapy efficacy.

This scientific commentary refers to ‘Proteostasis as a fundamental principle of Tau immunotherapy’ by Cruz (https://doi.org/10.1093/brain/awae254).

Ultrastructural features of psychological stress resilience in the brain: a microglial perspective.

Psychological stress is the major risk factor for major depressive disorder. Sustained stress causes changes in behaviour, brain connectivity and in its cells and organelles. Resilience to stress is understood as the ability to recover from stress in a positive way or the resistance to the negative effects of psychological stress.

Bulk mRNA-sequencing data of the estrogen and androgen responses in the human prostate cancer cell line VCaP.

Prostate cancer is a hormone-dependent disease that relies on the androgen signaling, as well as on the estrogen signaling, for growth and survival. To identify the genes regulated by these sex-steroid hormones in the human prostate cancer cell line VCaP, these cells were treated for 24 h with either androgens and/or estrogens. Then, the RNA of each sample was purified for sequencing to generate bulk mRNA-seq data.

Haralick texture feature analysis for Monte Carlo dose distributions of permanent implant prostate brachytherapy.

Purpose: Demonstrate quantitative characterization of 3D patient-specific absorbed dose distributions using Haralick texture analysis, and interpret measures in terms of underlying physics and radiation dosimetry.

Methods: Retrospective analysis is performed for 137 patients who underwent permanent implant prostate brachytherapy using two simulation conditions: "TG186" (realistic tissues including 0-3.8% intraprostatic calcifications; interseed attenuation) and "TG43" (water-model; no interseed attenuation).

Exploring Magnetic and Electrical Brain Stimulation in Parkinsonian Dyskinetic Monkeys.

Background: Parkinson's disease (PD) chronic L-Dopa treatment often triggers motor complications, such as L-Dopa-induced dyskinesias (LID). LID are reported to be associated with abnormal glutamatergic activity between the striatum and primary motor cortex (M1), resulting in M1 hyperactivation. Beneficial noninvasive brain stimulation (NIBS) paradigms were reported to normalize glutamatergic activity.

Population-level impact of switching to 1-dose human papillomavirus vaccination in high-income countries: examining uncertainties using mathematical modeling.

Background: A concern in high-income countries is that switching to 1-dose human papillomavirus (HPV) vaccination could cause a rebound in HPV infection and cervical cancer if 1-dose efficacy or duration were inferior to 2 doses. Using mathematical modeling and up-to-date trial-based data, we projected the population-level effectiveness of switching from 2-dose to 1-dose vaccination under different vaccine efficacy and duration assumptions in high-income countries.

Methods: We used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), a transmission-dynamic model of HPV infection and cervical cancer, varying key model assumptions to identify those with the greatest impact on projections of HPV-16 and cervical cancer incidence over time: 1) 1-dose vaccine efficacy and vaccine duration, 2) mechanisms of vaccine efficacy and duration over time, 3) midadult (>30 years of age) sexual behavior, 4) progression to cervical cancer among midadults, and 5) vaccination coverage and programs.

School Readiness and Early Childhood Education and Care Services Among Dual Language Learners.

Importance: Dual language learners (DLL) (ie, children learning 2 or more languages) present lower school readiness than non-DLL children, putting DLL children at risk of later school difficulties and adverse outcomes. However, it is unclear whether participation in early childhood education and care (ECEC) services may reduce this gap.

Objective: To assess whether ECEC exposure may reduce the school readiness gap between DLL and non-DLL children in a population-based sample.

External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high-flux intermittent haemodialysis.

Aims: Patients undergoing haemodialysis (HD) are at greater risk of methicillin-resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model-informed dosing is commonly used.

Synthesis and Evaluation of Fluorinated Piperazine-Hydroxyethylamine Analogues as Potential Antiplasmodial Candidates.

In this manuscript, twenty-one novel fluorinated piperazine-hydroxyethylamine analogues were synthesized and tested against Plasmodium falciparum (Pf). Among tested compounds, two 13 g and 14 g exhibited promising inhibitory activity on Pf3D7 with IC values of 0.28 and 0.

Identification of Mood Disorders in Self-Reported Versus Health Administrative Data.

Background: Producing relevant knowledge on the prevalence of mood disorders (MDs) requires a clear identification of people living with the condition. Analyzing this multifaceted disease from the perspective of health administrative data and population-based surveys could contribute to document inconsistencies between these data sources and highlight the strengths and limitations of each methodological approaches.

Objectives: The aim of this study was to estimate the prevalence of MD disease, assess concordance of MD patterns in population-based surveys versus health administrative data, and investigate statistical differences in characteristics between individuals presenting the disease in each data sources.

Empiric antibiotic prescribing practices for gram-positive coverage of late-onset sepsis in neonatal intensive care units in North America.

Late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) causes significant morbidity and mortality, yet guidance on empiric management is limited. We surveyed NICUs across Canada and the United States regarding their empiric antimicrobial regimens for LOS, thereby identifying large practice variations and high rates of empiric vancomycin use.

Lower uterine segment thickness to predict uterine rupture: a secondary analysis of PRISMA cluster randomized trial.

Background: Third-trimester lower uterine segment thickness (LUST) is associated with uterine rupture during trial of labor after cesarean (TOLAC) but threshold values vary according to the approach used (lower values with vaginal ultrasound, higher values with abdominal ultrasound).

Objective: To estimate the optimal LUST cut-off value combining vaginal and abdominal ultrasound to predict uterine rupture during TOLAC.

Study Design: We performed a secondary analysis of PRISMA cluster randomized trial including women with a single previous cesarean who underwent ultrasound LUST measurement at 34-38 weeks using the thinnest measurement obtained by combining transvaginal and transabdominal measurements.

Adiposity and Muscle Strength in Men With Prostate Cancer and Cardiovascular Outcomes.

Background: There are limited data on the physical effects of androgen deprivation therapy (ADT) for prostate cancer (PC), and on the relationships of such measures of adiposity and strength to cardiovascular outcomes.

Objectives: The primary objective of this study was to evaluate the relationships of measures of adiposity and strength to cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, heart failure, arterial revascularization, peripheral arterial disease, and venous thromboembolism) in patients with PC. A secondary objective was to characterize the relationships between ADT use and 12-month changes in these physical measures.

Comparative small molecule screening of primary human acute leukemias, engineered human leukemia and leukemia cell lines.

Targeted therapeutics for high-risk cancers remain an unmet medical need. Here we report the results of a large-scale screen of over 11,000 molecules for their ability to inhibit the survival and growth in vitro of human leukemic cells from multiple sources including patient samples, de novo generated human leukemia models, and established human leukemic cell lines. The responses of cells from de novo models were most similar to those of patient samples, both of which showed striking differences from the cell-line responses.