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Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

BACKGROUND: HIV partner notification services can help people living with HIV (PLHIV) to identify, locate, and inform their sexual and injecting partners who are exposed to HIV and refer them for proper and timely counseling and testing. To what extent these services were used by PLHIV and what are the related barriers and facilitators in southeast Iran are not known. So, this study aimed to explore HIV notification and its barriers and facilitators among PLHIV in Iran. METHODS: In this qualitative study, the number of 23 participants were recruited from November 2022 to February 2023 including PLHIV (N = 12), sexual partners of PLHIV (N = 5), and staff members (N = 6) of a Voluntary Counseling and Testing (VCT) center in Kerman located in the southeast of Iran. Our data collection included purposive sampling to increase variation. The content analysis was conducted using the Graneheim and Lundman approach. The analysis yielded 221 (out of 322) related codes related to HIV notification, its barriers, and its facilitators. These codes were further categorized into one main category with three categories and nine sub-categories. RESULTS: The main category was HIV notification approaches, HIV notification barriers, and facilitators. HIV notification approaches were notification through clear, and direct conversation, notification through gradual preparation and reassurance, notification due to being with PLHIV, notification through suspicious talking of the physician, and notification due to the behavior of others. Also, the barriers were classified into individual, social, and environmental, and healthcare system barriers and the facilitators were at PLHIV, healthcare staff, and community levels. Stigma was a barrier mentioned by most participants. Also, the main facilitator of HIV notification was social support, especially from the family side. CONCLUSIONS: The findings highlighted the multidimensionality of HIV notification emphasizing the importance of tailored support and education to enhance the notification process for PLHIV and their networks. Also, our results show that despite all the efforts to reduce stigma and discrimination in recent years, stigma still exists as a main obstacle to disclosing HIV status and other barriers are the product of stigma. It seems that all programs should be directed towards destigmatization.

BACKGROUND: Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. RESULTS: We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). CONCLUSIONS: Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

Small non-coding RNAs can be secreted through a variety of mechanisms, including exosomal sorting, in small extracellular vesicles, and within lipoprotein complexes. However, the mechanisms that govern their sorting and secretion are not well understood. Here, we present ExoGRU, a machine learning model that predicts small RNA secretion probabilities from primary RNA sequences. We experimentally validated the performance of this model through ExoGRU-guided mutagenesis and synthetic RNA sequence analysis. Additionally, we used ExoGRU to reveal cis and trans factors that underlie small RNA secretion, including known and novel RNA-binding proteins (RBPs), e.g., YBX1, HNRNPA2B1, and RBM24. We also developed a novel technique called exoCLIP, which reveals the RNA interactome of RBPs within the cell-free space. Together, our results demonstrate the power of machine learning in revealing novel biological mechanisms. In addition to providing deeper insight into small RNA secretion, this knowledge can be leveraged in therapeutic and synthetic biology applications.

Facioscapulohumeral dystrophy (FSHD) is linked to contraction of D4Z4 repeats on chromosome 4q with SMCHD1 mutations acting as a disease modifier. D4Z4 heterochromatin disruption and abnormal upregulation of the transcription factor DUX4, encoded in the D4Z4 repeat, are the hallmarks of FSHD. However, defining the precise effect of D4Z4 contraction has been difficult because D4Z4 repeats are primate-specific and DUX4 expression is very rare in highly heterogeneous patient myocytes. We generated isogenic mutant cell lines harboring D4Z4 and/or SMCHD1 mutations in a healthy human skeletal myoblast line. We found that the mutations affect D4Z4 heterochromatin differently, and that SMCHD1 mutation or disruption of DNA methylation stabilizes otherwise variegated DUX4 target activation in D4Z4 contraction mutant cells, demonstrating the critical role of modifiers. Our study revealed amplification of the DUX4 signal through downstream targets, H3.X/Y and LEUTX. Our results provide important insights into how rare DUX4 expression leads to FSHD pathogenesis.

Abstract Background Identifying the causes and consequences of work interruptions in nursing is crucial, as they play a vital role in improving workflow, nurse well-being, and enhancing patient safety. Therefore, by considering these factors, healthcare institutions can implement effective interventions and strategies to improve the nursing work environment while simultaneously enhancing the quality of patient care. Aim This study aims to culturally adapt and psychometrically evaluate the Persian version of the Nursing Work Interruption Scale. Methods This methodological cross-sectional study involved a sample of 506 nurses selected through convenience sampling. The translation and cultural adaptation of the Nursing Work Interruption Scale were conducted using the Polit and Yang model. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and assessments of internal consistency were conducted to evaluate the validity and reliability of the instrument. SPSS version 27 and LISREL version 8 software were used in this study. Results The results of the EFA and CFA confirmed the tool with two factors and 12 items. The CFA results indicated a well-fitting model (CFI = 0.91, NNFI = 0.92, GFI = 0.91, RMSEA = 0.057, SRMR = 0.045). Pearson’s correlation coefficient confirmed a significant relationship between items, subscales, and the main scale. Additionally, Cronbach’s alpha coefficient (0.896) and McDonald’s Omega (0.892) confirmed the scale’s reliability. Conclusion The Persian version of the Nursing Work Interruption Scale is a valid and reliable tool, consisting of 12 items and two factors. This scale provides a valuable tool for measuring the extent of work interruptions experienced by nurses. Additionally, it can be utilized to develop and evaluate the efficacy of strategies designed to reduce these interruptions. Clinical trial number Not applicable.

Abstract Emerging research suggests a connection between dietary habits and metabolic dysfunction associated steatotic liver disease (MASLD). We aimed to assess the relationship between the Dietary Inflammatory Index (DII) and the severity of MASLD. This cross-sectional study involved 125 participants aged 7–18 with MASLD. Dietary intakes were assessed using a validated 147-item food frequency questionnaire. The DII was applied to measure diet-induced inflammation, categorizing diets into anti-inflammatory (DII < -1) and inflammatory diets (DII > + 1). To evaluate hepatic steatosis and fibrosis, transabdominal ultrasonography and the fibrosis-4 (FIB-4) index were utilized. After adjusting for potential confounding factors, individuals on inflammatory diets exhibited a significantly higher odds ratio (OR) for experiencing more severe steatosis (OR: 4.11; 95% CI: 1.08–15.71) compared to those on anti-inflammatory diets. Furthermore, each unit increase in DII scores was linked to a 2.6-fold increase in the odds of more severe steatosis (OR: 2.61; 95% CI: 1.28–5.32) and a 0.006 increase in FIB-4 scores (β: 0.006; 95% CI: 0.003–0.011). In conclusion, modifying dietary intakes to lower DII scores may be a beneficial approach to improving clinical outcomes in pediatric MASLD, as anti-inflammatory diets are associated with reduced severity of hepatic steatosis and fibrosis.

Abstract Background Social capital has long been recognized as a determinant of various health outcomes. However, the existence and magnitude of these associations may vary across different health conditions, different communities, and periods. This study aimed to investigate the association between social capital and major depressive disorder (MDD) among participants of the Persian Youth Cohort (PYC) study. Methods The PYC study enrolled 11,592 participants aged 15–34 years, from four cities in Iran representing a range of geographic areas. Baseline assessments included measuring lifetime MDD using the Persian version of the Composite International Diagnostic Interview (CIDI-2.1) and a 27-item social capital questionnaire to evaluate voluntary participation, trust, and sense of cohesion. We analyzed the baseline data using logistic regression to identify potential associations. Results The prevalence of lifetime MDD was 18.3%. The mean social capital-total score was 73.93 (SD = 13.93). A higher social capital-total score was inversely associated with the likelihood of MDD (AOR: 0.70, 95% CI: 0.66–0.74). Moreover, participants with higher scores in voluntary participation (AOR: 0.88, 95% CI: 0.83–0.92), trust (AOR: 0.65, 95% CI: 0.62–0.68), and sense of cohesion (AOR: 0.72, 95% CI: 0.68–0.75) were less probable to suffer from MDD. Conclusion Our study corroborates the existing evidence of the association between MDD and the three dimensions of social capital- participation, trust, and sense of cohesion- highlighting the consistency of these findings across diverse settings including young adults in Iran. The use of a valid diagnostic tool for assessing MDD adds robustness to our results, offering valuable insights for regions with similar social and cultural contexts. These findings suggest that interventions fostering social capital, particularly trust and cohesion, may help reduce the burden of MDD in youth.

Abstract: The antiapoptotic protein, myeloid cell leukemia-1 (Mcl-1), contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models. This dose escalation study evaluated voruciclib in patients with previously treated hematologic malignancies. Initially, voruciclib was administered daily, continuously, on a 28-day cycle (group 1). After 2 patients with prior allogeneic stem cell transplantation had a dose-limiting toxicity (DLT) of interstitial pneumonitis at 100 mg, voruciclib administration was changed to days 1 to 14 of a 28-day cycle (group 2). Forty patients, 21 with AML and 19 with B-cell malignancies, were enrolled. Patients had a median of 3 prior lines of therapy (range, 1-8). Dose escalation in group 2 was stopped at 200 mg, a dose that achieved plasma concentrations sufficient for target inhibition, without DLTs observed. The most common adverse events were diarrhea (30%), nausea (25%), anemia (22%), fatigue (22%), constipation (17%), dizziness (15%), and dyspnea (15%). In AML, 1 patient achieved a morphologic leukemia-free state, and 2 had stable disease. Voruciclib treatment led to a decrease in MCL1 messenger RNA expression, downregulation of myelocytomatosis (MYC) and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase 2. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax for patients with previously treated AML. This trial was registered at www.clinicaltrials.gov as #NCT03547115.