AutoGVP: a dockerized workflow integrating ClinVar and InterVar germline sequence variant classification.

SUMMARY: With the increasing rates of exome and whole genome sequencing, the ability to classify large sets of germline sequencing variants using up-to-date American College of Medical Genetics-Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates germline variant pathogenicity annotations from ClinVar and sequence variant classifications from a modified version of InterVar (PVS1 strength adjustments, removal of PP5/BP6). This tool facilitates large-scale, clinically focused classification of germline sequence variants in a research setting. AVAILABILITY AND IMPLEMENTATION: AutoGVP is an open source dockerized workflow implemented in R and freely available on GitHub at https://github.com/diskin-lab-chop/AutoGVP.

Anterior Chest Wall Reconstruction After Separation of Thoraco-Omphalopagus Conjoined Twins With Cadaveric Rib Grafts and Omental Flap.

BACKGROUND: Anterior chest wall defects have a wide range of etiologies in the pediatric population, ranging from infection, tumor, and trauma to congenital diseases. The reconstructive goals include restoring skeletal stability, obliterating dead space, preserving cardiopulmonary mechanics, and protecting vital underlying mediastinal organs. Although various reconstructive methods have been described in the literature, selecting the optimal method is challenging for the growing pediatric skeleton. Here, we report a case of previously thoraco-omphalopagus twins who underwent successful separation and reconstruction and presented for definitive anterior chest wall reconstruction. METHODS: A pair of previously thoraco-omphalopagus conjoined twins underwent definitive anterior chest wall defect reconstruction using cadaveric ribs and omental flap. Twin A received 2 cadaveric ribs, whereas twin B had a much larger sternal defect that required 3 cadaveric ribs combined with an omental flap for soft tissue chest coverage. Both twins were followed up for 8 months. RESULTS: Twin A's postoperative course was uneventful, and she was discharged on postoperative day 6. Twin B's course was complicated, and she was discharged on supported ventilation on postoperative day 10. At 8 months postoperatively, both twins healed well, and chest radiographs confirmed the stability of the chest reconstructions. The rib grafts in the twin with a tracheostomy were not mobile, and the patient had a solid sternum with adequate pulmonary expansion. The construct initially did not facilitate pulmonary functioning, but after a healing process, it eventually allowed for the twin with the tracheostomy who required pulmonary assistance to no longer need this device. CONCLUSIONS: Cryopreserved cadaveric ribs and omental flaps offer safe and reliable reconstructive methods to successfully reconstruct congenital anterior chest wall skeletal defects in the growing pediatric population. The involvement of multidisciplinary team care is key to optimizing the outcomes.

A transcriptome-based classifier to determine molecular subtypes in medulloblastoma.

Medulloblastoma is a highly heterogeneous pediatric brain tumor with five molecular subtypes, Sonic Hedgehog TP53-mutant, Sonic Hedgehog TP53-wildtype, WNT, Group 3, and Group 4, defined by the World Health Organization. The current mechanism for classification into these molecular subtypes is through the use of immunostaining, methylation, and/or genetics. We surveyed the literature and identified a number of RNA-Seq and microarray datasets in order to develop, train, test, and validate a robust classifier to identify medulloblastoma molecular subtypes through the use of transcriptomic profiling data. We have developed a GPL-3 licensed R package and a Shiny Application to enable users to quickly and robustly classify medulloblastoma samples using transcriptomic data. The classifier utilizes a large composite microarray dataset (15 individual datasets), an individual microarray study, and an RNA-Seq dataset, using gene ratios instead of gene expression measures as features for the model. Discriminating features were identified using the limma R package and samples were classified using an unweighted mean of normalized scores. We utilized two training datasets and applied the classifier in 15 separate datasets. We observed a minimum accuracy of 85.71% in the smallest dataset and a maximum of 100% accuracy in four datasets with an overall median accuracy of 97.8% across the 15 datasets, with the majority of misclassification occurring between the heterogeneous Group 3 and Group 4 subtypes. We anticipate this medulloblastoma transcriptomic subtype classifier will be broadly applicable to the cancer research and clinical communities.

annoFuse: an R Package to annotate, prioritize, and interactively explore putative oncogenic RNA fusions.

BACKGROUND: Gene fusion events are significant sources of somatic variation across adult and pediatric cancers and are some of the most clinically-effective therapeutic targets, yet low consensus of RNA-Seq fusion prediction algorithms makes therapeutic prioritization difficult. In addition, events such as polymerase read-throughs, mis-mapping due to gene homology, and fusions occurring in healthy normal tissue require informed filtering, making it difficult for researchers and clinicians to rapidly discern gene fusions that might be true underlying oncogenic drivers of a tumor and in some cases, appropriate targets for therapy. RESULTS: We developed annoFuse, an R package, and shinyFuse, a companion web application, to annotate, prioritize, and explore biologically-relevant expressed gene fusions, downstream of fusion calling. We validated annoFuse using a random cohort of TCGA RNA-Seq samples (N = 160) and achieved a 96% sensitivity for retention of high-confidence fusions (N = 603). annoFuse uses FusionAnnotator annotations to filter non-oncogenic and/or artifactual fusions. Then, fusions are prioritized if previously reported in TCGA and/or fusions containing gene partners that are known oncogenes, tumor suppressor genes, COSMIC genes, and/or transcription factors. We applied annoFuse to fusion calls from pediatric brain tumor RNA-Seq samples (N = 1028) provided as part of the Open Pediatric Brain Tumor Atlas (OpenPBTA) Project to determine recurrent fusions and recurrently-fused genes within different brain tumor histologies. annoFuse annotates protein domains using the PFAM database, assesses reciprocality, and annotates gene partners for kinase domain retention. As a standard function, reportFuse enables generation of a reproducible R Markdown report to summarize filtered fusions, visualize breakpoints and protein domains by transcript, and plot recurrent fusions within cohorts. Finally, we created shinyFuse for algorithm-agnostic interactive exploration and plotting of gene fusions. CONCLUSIONS: annoFuse provides standardized filtering and annotation for gene fusion calls from STAR-Fusion and Arriba by merging, filtering, and prioritizing putative oncogenic fusions across large cancer datasets, as demonstrated here with data from the OpenPBTA project. We are expanding the package to be widely-applicable to other fusion algorithms and expect annoFuse to provide researchers a method for rapidly evaluating, prioritizing, and translating fusion findings in patient tumors.

Aberrant splicing in B-cell acute lymphoblastic leukemia.

Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing these samples to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ∼100 SFs, e.g. hnRNPA1. HNRNPA1 3'UTR was most pervasively mis-spliced, yielding the transcript subject to nonsense-mediated decay. To mimic this event, we knocked it down in B-lymphoblastoid cells and identified 213 hnRNPA1-regulated exon usage events comprising the hnRNPA1 splicing signature in pediatric leukemia. Some of its elements were LSVs in DICER1 and NT5C2, known cancer drivers. We searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 additional genes. Seventy-seven LSVs out of 81 were confirmed using two large independent B-ALL RNA-seq datasets, and the twenty most common B-ALL drivers, including NT5C2, showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contributes to disease pathogenesis.

Assessment of patient safety challenges and electronic occurrence variance reporting (e-OVR) barriers facing physicians and nurses in the emergency department: a cross sectional study.

BACKGROUND: The purpose of patient safety is to prevent harm occurring in the healthcare system. Patient safety is improved by the use of a reporting system in which healthcare workers can document and learn from incidents, and thus prevent potential medical errors. The present study aimed to determine patient safety challenges facing clinicians (physicians and nurses) in emergency medicine and to assess barriers to using e-OVR (electronic occurrence variance reporting). METHODS: This cross-sectional study involved physicians and nurses in the emergency department (ED) at King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. Using convenience sampling, a self-administered questionnaire was distributed to 294 clinicians working in the ED. The questionnaire consisted of items pertaining to patient safety and e-OVR usability. Data were analyzed using frequencies, means, and percentages, and the chi-square test was used for comparison. RESULTS: A total of 197 participants completed the questionnaire (67% response rate) of which 48 were physicians (24%) and 149 nurses (76%). Only 39% of participants thought that there was enough staff to handle work in the ED. Roughly half (48%) of participants spoke up when something negatively affected patient safety, and 61% admitted that they sometimes missed important patient care information during shift changes. Two-thirds (66%) of the participants reported experiencing violence. Regarding e-OVR, 31% of participants found reporting to be time consuming. Most (85%) participants agreed that e-OVR training regarding knowledge and skills was sufficient. Physicians reported lower knowledge levels regarding how to access (46%) and how to use (44%) e-OVR compared to nurses (98 and 95%, respectively; p < 0.01). Less than a quarter of the staff did not receive timely feedback after reporting. Regarding overall satisfaction with e-OVR, only 25% of physicians were generally satisfied compared to nearly half (52%) of nurses. CONCLUSION: Although patient safety is well emphasized in clinical practice, especially in the ED, many factors hinder patient safety. More awareness is needed to eliminate violence and to emphasize the needs of additional staff in the ED. Electronic reporting and documentation of incidents should be well supported by continuous staff training, help, and feedback.

Management of esophageal atresia and early predictive factors of mortality and morbidity in a developing country.

The aim of this study is to investigate management and outcome in esophageal atresia (EA) and to identify early predictive factors of morbidity and mortality in a developing country. Charts of neonates with repaired EA from 2007 to 2016 were reviewed. Patients' characteristics, operative details, and postoperative outcomes were collected. Statistical analyses were performed to identify predictors of complicated evolution. Forty-two cases were collected. There were 14 girls and 28 boys. Only one patient had antenatal diagnosis (2.3%). The mean gestational age was 38 weeks. Nine patients (21.4%) weighed less than 2.5 kg. Seventeen (40.4%) patients had associated malformations most commonly cardiac (9/17). Thirteen patients had delayed diagnosis (30.9%). Thirty-nine (92.8%) patients underwent primary esophageal anastomosis. Overall survival was 76.2%. Nineteen patients (57% of survivals) had complicated evolution before the age of one year and 15 patients (46.8% of survivals) developed complications after the age of one year. Perinatal variables associated with mortality were prematurity (p = 0.004, OR = 5.4, IC95% = [1.13-25.80]), low birth weight (p = 0.023, OR = 7, IC95% = [1.38-35.47]), cardiac malformations (p = 0.006, OR = 10.5, IC95% = [2.03-54.27]) and delayed diagnosis (p = 0.005, OR = 10.11, IC95% = [2.005-50.980]). Variables associated with short-term and middle-term complications were duration of intubation (p = 0.019, OR = 0.118, IC95% = [0.019-0.713]) and the presence of short-term complications (p = 0.016, OR = 7.33, IC95% = [1.467-36.664]) respectively. These factors may be used to identify patients who will benefit from more intensive follow-up program.

Hybrid laparoendoscopic single-site (LESS) pyeloplasty: Initial experience in children.

BACKGROUND AND OBJECTIVE: Mini-invasive surgery is still evolving to get better surgical conditions for patients with ureteropelvic junction obstruction. We used technical modifications (hybrid pyeloplasty) that simplify surgical steps of laparoendoscopic single-site pyeloplasty in children. Our aim was to compare hybrid pyeloplasty to laparoendoscopic single-site pyeloplasty and to open pyeloplasty. PATIENTS AND METHODS: We retrospectively reviewed records of patients with ureteropelvic junction obstruction aged<14years undergoing pyeloplasty at our institute from January 2011 to December 2015. Demographic data, laterality, operative time, length of hospital stay, drainage tubes, and postoperative complications were recorded. Surgical outcomes were evaluated based on renal sonography and Lasix diuretic renography. RESULTS: Among 38 patients, 17 underwent open pyeloplasty (group I), 10 had laparoendoscopic single-site pyeloplasty (group II) and 11 had hybrid pyeloplasty (group III). The mean age at the time of operation was 55 months. The operative time in group III was significantly shorter than that in group I and group II (P<0.001). The shortest median hospital stay was noted in the group III. The mean follow-up period was 26 months (range: 6-52 months). CONCLUSION: The hybrid pyeloplasty using LESS combine the successful outcomes of open surgery and advantages of minimally invasive surgery. It offers small incision surgery, good working space, short operation time, secure anastomosis and good cosmetic results. LEVEL OF EVIDENCE: 5.

Community point distribution of insecticide-treated bed nets and community health worker hang-up visits in rural Zambia: a decision-focused evaluation.

BACKGROUND: In 2013, the Zambian Ministry of Health through its National Malaria Control Programme distributed over two million insecticide-treated bed nets (ITNs) in four provinces using a door-to-door distribution strategy, and more than 6 million ITNs were allocated to be distributed in 2014. This study was commissioned to measure attendance rates at a community point distribution and to examine the impact of follow-up community health worker (CHW) hang-up visits on short and medium-term ITN retention and usage with a view of informing optimal ITN distribution strategy in Zambia. METHODS: Households received ITNs at community point distributions conducted in three rural communities in Rufunsa District, Zambia. Households were then randomly allocated into five groups to receive CHW visits to hang any unhung ITNs at different intervals: 1-3, 5-7, 10-12, 15-17 days, and no hang-up visit. Follow-up surveys were conducted among all households at 7-11 weeks after distribution and at 5-6 months after distribution to measure short- and medium-term household retention and usage of ITNs. RESULTS: Of the 560 pre-registered households, 540 (96.4 %) attended the community point distribution. Self-installation of ITNs by households increased over the first 10 days after the community point distribution. Retention levels remained high over time with 90.2 % of distributed ITNs still in the household at 7-11 weeks and 85.7 % at 5-6 months. Retention did not differ between households that received a CHW visit and those that did not. At 7-11 weeks, households had an average of 73.8 % of sleeping spaces covered compared to 80.3 % at 5-6 months. On average, 65.6 % of distributed ITNs were hanging at 7-11 weeks compared to 63.1 % at 5-6 months. While a CHW hang-up visit was associated with increased usage at 7-11 weeks, this difference was no longer apparent at 5-6 months. CONCLUSIONS: This evaluation revealed that (1) the community point distributions achieved high attendance rates followed by acceptable rates of short-term and medium-term ITN retention and usage, as compared to reported rates achieved by door-to-door distributions in the recent past, (2) CHW hang-up visits had a modest short-term impact on ITN usage but no medium-term effect, and (3) community point distributions can yield sizeable time savings compared to door-to-door distributions.

The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double-blind, controlled study.

Ketamine and pregabalin each provide postoperative analgesia, although the combination has yet to be evaluated. One hundred and forty-two patients undergoing total hip arthroplasty were randomly assigned to receive ketamine alone, pregabalin alone, ketamine and pregabalin combined, or placebo. Pain scores at rest and on movement, morphine consumption, side-effects, pressure pain thresholds and secondary hyperalgesia were evaluated. Mean (SD) total 48-h morphine use was reduced in patients given ketamine alone (52 (22) mg) and pregabalin alone (44 (20) mg) compared with placebo (77 (36) mg) p < 0.001. Morphine use was further reduced in patients given both ketamine and pregabalin (38 (19) mg) with an interaction between ketamine and pregabalin (ANOVA factorial; p = 0.028). Secondary hyperalgesia was reduced by ketamine. There were no differences between groups in pain scores after surgery, pressure pain thresholds or side-effects. The combination of pregabalin and ketamine has a small, beneficial clinical effect.

Congenital Syphilis: A Case Report Presenting a Rare Clinical Manifestation in Two-Month-Old Newborn in Bahrain.

Congenital syphilis, caused by the Gram-negative obligate bacterium Treponema pallidum, can manifest as early- or late-onset infection, typically exhibiting classic symptoms such as a maculopapular rash, failure to thrive, and hepatosplenomegaly. This case report presents rare clinical manifestations of congenital syphilis not typically observed during early onset infection in a newborn in Bahrain. Additionally, it details the physical findings and investigations conducted to diagnose the disease.

Effectiveness of high-frequency vibration, cotton rolls and elastomeric wafers in alleviating debonding pain of orthodontic metal brackets: a randomized clinical trial.

This study aimed to evaluate the effectiveness of different pain mitigation methods during orthodontic debonding and to evaluate pain sensitivity across various regions of the dentition. A total of 144 participants (50 males and 94 females) with metal brackets were randomly assigned to one of four groups: High-Frequency Vibration (V), Cotton Roll (CR), Elastomeric Wafer (EW), and Open Mouth group (OM). Pain levels were measured using the Visual Analog Scale (VAS) across different sextants of the dentition. The Kruskal-Wallis test and post hoc analyses were conducted to compare VAS scores between groups. The Mann-Whitney test was used to analyse sex-based differences. The V group, utilizing high-frequency vibration, had the lowest total VAS score, indicating superior pain relief compared to CR, EW, and OM groups. No significant difference was observed between the CR and EW groups. Median VAS scores were highest in the lower front sextant, followed by the upper front sextants, and lowest in the posterior regions, indicating greater pain sensitivity in the anterior regions during debonding. High-frequency vibration was the most effective method for reducing pain during orthodontic debonding, particularly in the anterior dental regions. Both CR and EW methods were also effective but to a lesser extent. These findings suggest that high-frequency vibration could significantly improve patient comfort during orthodontic procedures. Utilizing high-frequency vibration for orthodontic debonding can enhance patient comfort, especially in the more sensitive anterior dental regions, thereby potentially improving treatment compliance and experience.Trial registration: NCT05904587.

Keeping the teeth in line: Exploring the necessity of bonded retainers in orthodontics: A narrative review.

In most recent studies, long-term retention after orthodontic treatment has been hypothesized that may be necessary to maintain the stability of the dentition and avoid post-treatment changes. The bonded fixed retainer is characterized by its clinical effectiveness, patient acceptance, and lack of patient complaints as compared with a removable retainer. An electronic database (such as PubMed, PubMed Central, Web of Science, Science Direct, Cochrane Library, Scopus, and ResearchGate) has been collected using specific keywords. Of the 152 articles, only randomized clinical trials that investigated different types of fixed retainers or compared fixed with removable retainers were illustrated in tables and included in this review. The present review has gone some way towards enhancing our understanding of the bonded fixed retainer, types, material, bonding methods, and how to improve its the success rate, besides the importance of new technology in fixed orthodontic retention.

Up-converting ß-NaY0.8[Yb0.18Er0.02]F4 nanoparticles coated by superparamagnetic γ-Fe2O3 nanosatellites: elaboration, characterization and in vitro cytotoxicity.

Current biomedical imaging techniques are vital for the diagnosis of various diseases. They are related to the development of multimodal probes encompassing all the functionalities required for comprehensive imaging. In this context, we applied a simple and reproducible wet synthesis route to produce such probes. This method allowed us to prepare about 100 nm sized lanthanide-doped yttrium fluoride nanoparticles ß-NaY0.8[Yb0.18Er0.02]F4, coated with about 10 nm sized iron oxide γ-Fe2O3 nanocrystals. By this way, the built granular hetero-nanostructures combine desirable up-converting photoluminescence (the core) and superparamagnetic properties (the satellites), enabling dual optical and magnetic resonance imaging applications. Through citrate ligand grafting, the designed core-satellite particles formed stable aqueous colloids, which are valuable for biomedical applications. Optical spectroscopy and confocal microscopy revealed their capability for sustained visible light emission (predominantly green) upon near-infrared excitation (980 nm). Additionally, based on XTT assays, when incubated for 24 hours with mammalian healthy or cancer cells, even at doses as high as 0.1 mg mL-1 (milligrams of particles), they did not induce significant cytotoxicity. The measured body temperature magnetization of the engineered nanoconstructs was found to be about 10 emu g-1 (grams of particles) at 1.5 T, which is high enough to use them as positive or negative contrast magnetic resonance agents in the clinic, as confirmed by relaxometry measurements in Milli-Q water. This result underscores their promising biomedical utility as bimodal probes for optical and magnetic imaging.

Rate of glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia at a private tertiary centre.

OBJECTIVES: To investigate the rate of hospitalized neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency presented with indirect hyperbilirubinemia at a private tertiary center in Al-Ahsa, Saudi Arabia, over 4 years and to compare the characteristics of G6PD-deficient and normal neonates admitted for indirect hyperbilirubinemia. METHODS: The retrospective case control study was carried out at Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia. Data were collected from Yassasi Medical System from 2018-2021 and finalized in 2024. The study included 2 groups: G6PD-normal and G6PD-deficient neonates with indirect hyperbilirubinemia not having recognizable triggers of hemolysis. The analysis focused on serum bilirubin levels, direct bilirubin levels, hematocrit levels, hemoglobin levels, reticulocyte percentage, G6PD levels, duration of phototherapy, and the need for exchange transfusion. RESULTS: The study enrolled 3200 neonates with hyperbilirubinemia, of whom 274 met inclusion criteria. A total of 103 (37.6%) neonates were G6PD-deficient, with 77 (74.8%) being male and 26 (25.2%) female. Glucose-6-phosphate dehydrogenase-deficient neonates exhibited significantly higher initial total bilirubin levels and earlier sampling times. There was no significant correlation between G6PD deficiency and hematocrit or hemoglobin levels in hyperbilirubinemic neonates, but 4 neonates required exchange transfusion, demonstrating statistical significance (p=0.009). CONCLUSION: High rate of G6PD deficiency in neonates with indirect hyperbilirubinemia, requiring close monitoring to prevent exchange transfusions, with no significant differences in hematocrit or hemoglobin levels.

Exploring the Landscape of Adult Acute Poisoning in Saudi Arabia: A Comprehensive Narrative Review.

This narrative review meticulously examines the intricate landscape of poisoning incidents within Saudi Arabia, delineating the prevalence and characteristics across three main categories: pharmaceutical, illicit, and chemical substances. Pharmaceutical agents, particularly analgesics and antipsychotics, are identified as leading causes of acute adult poisoning, highlighting the paramount role of their widespread accessibility and the potential risks associated with over-the-counter availability. The review underscores the alarming prevalence of over-the-counter analgesics, such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), as the most frequent culprits in poisoning cases, with a significant correlation observed between analgesic poisoning and gender, notably affecting the female population. Additionally, the study delves into the burgeoning issue of illicit drug use, with opioids and amphetamines emerging as substantial contributors to the poisoning landscape, reflecting a broader global trend of increasing substance misuse and its associated health risks. Chemical poisoning, encompassing a range of substances from household cleaners to industrial chemicals, presents another critical area of concern, with specific emphasis on the dangers posed by antiseptics, detergents, and organophosphates. The review identifies a pressing need for targeted public health interventions and policy reforms aimed at mitigating the risks associated with these diverse types of poisoning. By offering a comprehensive overview of the poisoning epidemiology in Saudi Arabia, the study contributes valuable insights into the multifaceted nature of this public health challenge, advocating for enhanced regulatory measures, public awareness campaigns, and improved access to mental health services to address the underlying factors contributing to poisoning incidents.

Banded Versus Non-banded Sleeve Gastrectomy: A Systematic Review and Meta-Analysis.

Standard bariatric surgeries include biliopancreatic diversion (BPD), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and adjustable gastric banding (AGB). Laparoscopic sleeve gastrectomy (LSG) is currently favored due to safety, efficacy, and shorter operation time. However, previous literature shows 75.6% weight regain post LSG. Introducing Laparoscopic band sleeve gastrectomy (LBSG) to maintain pouch size is proposed to improve outcomes and reduce weight regain. This study aims to compare the safety and efficacy of LSG vs. LBSG in obese patients. A comprehensive search strategy was executed to identify pertinent literature comparing LBSG and LSG in obese patients. Eligible studies underwent independent screening, and pertinent data were systematically extracted. The analysis employed pooled risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous variables, each accompanied by their respective 95% confidence intervals (CI). Our systematic review and meta-analysis included 15 studies encompassing 3929 patients. Regarding body mass index (BMI), at six, 12, and 24 months, no substantial differences were found between LBSG and LSG groups (p < 0.05). Still, at 36 months, LBSG exhibited significantly lower BMI than LSG (MD = -2.07 [-3.84, -0.29], p = 0.02). Excess Weight Loss (EWL) favored LBSG at 12, 24, and 36 months with MD of 3.30 [0.42, 6.18], 4.13 [1.44, 6.81], and 18.43 [9.44, 27.42], p = 0.02, 0.003, < 0.00001, respectively). Operative time did not significantly differ between the procedures (MD = 2.95, 95%CI [-0.06, 5.95], p = 0.05). Resolution of comorbidities, overall complications, post-operative bleeding, reflux, and early complications did not significantly differ between LBSG and LSG. However, LBSG showed higher post-operative regurgitation than LSG (RR = 2.38, 95%CI [1.25, 4.54], p = 0.008). LBSG showed a substantial decrease in BMI at three-year follow-up and higher EWL at one, two, and three years. However, LBSG procedures exhibited a higher incidence of post-operative regurgitation symptoms than LSG. No substantial differences were noted in BMI at six, 12, or 24 months, EWL at six months, operative time, bleeding, reflux, or overall complications.

Characterization of aberrant splicing in pediatric central nervous system tumors reveals CLK1 as a candidate oncogenic dependency.

Pediatric brain cancer is the leading cause of disease-related mortality in children, and many aggressive tumors still lack effective treatment strategies. We characterized aberrant alternative splicing across pediatric brain tumors, identifying pediatric high-grade gliomas (HGGs) among the most heterogeneous. Annotating these events with UniProt, we identified 11,940 splice events in 5,368 genes leading to potential protein function changes. We discovered CDC-like kinase 1 (CLK1) is aberrantly spliced to include exon 4, resulting in a gain of two phosphorylation sites and subsequent activation. Inhibition of CLK1 with Cirtuvivint significantly decreased both cell viability and proliferation in the pediatric HGG KNS-42 cell line. Morpholino-mediated depletion of CLK1 exon 4 splicing reduced RNA expression, protein abundance, and cell viability with concurrent differential expression of 78 cancer genes and differential splicing at functional sites in 193 cancer genes. Our findings highlight a dependency of pediatric HGGs on CLK1 and represent a promising therapeutic strategy.