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For close to 2 years, we have witnessed the impacts of the SARS-CoV-2 pandemic on research at several different levels. Among the list, limited access to laboratory-based training for undergraduate students prevented this cohort from gaining exposure to the realities of a research laboratory at a critical time in training when they may have found motivation in this area as a career. COVID exposed a weakness in our training pipeline; an extreme dependency on face-to-face training that threatened to create a void in the research talent needed to replenish the scientific community every year. In the classroom, we witnessed a revolution of e-learning based approaches that could be rapidly implemented based on existing footprints. Out of necessity, our laboratory developed and implemented an e-learning model of an undergraduate peer mentor network that provides a knowledge and experience exchange platform between students with different levels of research experience. Implementation of the platform was to aid students with gaining knowledge in multiple aspects of scientific research and hands-on work in a research laboratory. The collaboration between the students of the network was aimed at not only advancing the theoretical and practical research experience, but also at developing feedback implementation and practicing "soft skills" critical for teamwork and leadership. Herein, we present an overview of the model along with survey responses of the students participating in the peer mentor network. We have found that peer delivery of practical benchwork both via scientific presentations and visualized experiments, reduced the time of training and the amount of staff assistance needed when students returned to the bench. Furthermore, this model accelerated student independence in laboratory work and increased research interest overall. In summary, the model of a peer mentor network has the potential to serve as a training platform and as a customized tool, supplementing research laboratory training at the undergraduate level beyond the pandemic.

Introduction Infant immunization programs using pneumococcal conjugate vaccines (PCVs) have reduced the rates of pneumococcal disease through direct vaccine-induced protection in vaccinated children and through indirect protection in non-vaccinated children and adults.Areas covered This review summarizes current evidence on the indirect protection of adults conferred by pediatric pneumococcal vaccination, including the impact on invasive pneumococcal disease (IPD) incidence and mortality, pneumonia admissions, and nasopharyngeal carriage prevalence. Factors affecting indirect protection against IPD are also discussed.Expert opinion Pediatric immunization with PCVs has substantially decreased vaccine-serotype IPD and pneumonia through indirect protection in both older (≥65 years of age) and younger adults, including those with underlying medical conditions. However, serotype replacement by non-vaccine serotypes, the persistence of some vaccine serotypes, and divergence of serotypes between children and adults have limited the impact of pediatric PCV programs on adult populations. Designing complementary vaccines that leverage indirect protection from pediatric immunization and target the most prevalent adult serotypes may be a preferred strategy to maximize the public health impact of pneumococcal vaccination.

ObjectiveThis study examines the national prevalence of mental health disorders and their associated factors in Lebanon, specifically in the aftermath of the 2020 events, including the catastrophic events of Beirut blast and the concurrent financial meltdown amid the global pandemic.MethodsConducted between July and September 2022, the study interviewed a nationally representative sample of 1,000 Lebanese via telephone, using the Computer Assisted Telephone Interview (CATI) system. Gender-specific bivariate and multivariate models were generated for probable posttraumatic stress disorder (PTSD), depression, and anxiety.ResultsHigh rates of mental health disorders emerged — 47.8% screened positive for probable depression, 45.3% for probable anxiety, and 43.5% met the probable diagnosis for PTSD. Multivariate gender-specific analyses revealed no significant associations with governorate, employment status, or marital status, while the financial composite score consistently influenced all disorders.ConclusionLebanon faces a severe mental health crisis, evidenced by elevated rates of probable depression, anxiety, and PTSD. The universal impact of multiple traumas transcends typical determinants, emphasizing the need for nuanced interventions and targeted policy considerations.

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Radiological assessments of metatarsal biometrics have been documented in few studies and often lack direct clinical significance. The narrower diameter of female metatarsals could be an impediment for intramedullary implant suitability. This investigation examines the radiological morphometry of female metatarsals to assess the diameter fitness of intramedullary implants used for midfoot Charcot fusion. Methods: Foot roentgenograms of 143 female patients in the standing position were collected for radiological assessment. Initially, basic biometric parameters were determined at the level of the metatarsal neck. Cortical thickness was derived by subtracting the inner width from the outer width measurements. Following a hypothetical reaming, mean values of inner width, outer width, and cortical thickness were assessed for fitness estimation. Implant fitness was considered satisfactory if either a) the inner width was below the threshold of 6mm, and/or b) the cortical thickness was below the threshold of 2mm (1 mm on each side of the cortex). Additional examination was performed using the lower quartile values for further analysis. Results: The findings revealed that: a) the mean inner width of M5 was significantly greater compared to M2, M3 and M4 (p ˂ 0.00001), while no significant difference was observed among the median metatarsals, and b) M2 exhibited a significantly higher outer width than M3 and M4 (p ˂ 0.00001), with no difference observed with M5. According to the predefined threshold values, the estimated width fitness values (after hypothetical reaming) for accepting implant diameter were deemed inadequate for M2, M3 and M4, and the estimated cortical thickness values deemed inadequate for M3, M4 and M5. Conclusion: Our study indicates, for the first time, a discrepancy in the inner width of the lateral metatarsals at the neck level concerning commercially available Charcot-specific intramedullary implants for female patients. This mismatch suggests an increased vulnerability to cortex fractures at the metatarsal neck and potential implant migration. If a critical width is identified, utilizing smaller implant diameters or opting for a proximal insertion at the base of the metatarsals might present more suitable alternatives.

Background: Surgery is often needed for resistant plantar diabetic foot ulcers (DFUs) of the big toe. For noninfected ulcers, 2 types of surgery are available: the Keller and the hallux interphalangeal joint arthroplasty (HIPJ-A) procedures. Yet, no evidence synthesis on the outcomes of these procedures has been conducted; thus, this systematic review is an attempt to fill this gap. Methods: Only studies reporting the results of Keller (or its variants) and HIPJ-A (or its variants) procedures for noncomplicated ulcers (Texas 1A/2A, or Wagner I/II) were included. Ulcers located beneath the metatarsal head were excluded. Ultimately, 11 studies were selected for inclusion and were analyzed. The primary outcome was defined as the ulcer healing frequency. The secondary outcomes were mean healing time, ulcer recurrence frequency, ulcer transfer frequency, postoperative infection rate, and revision surgery rate. Results: The overall (combined techniques) weighted healing rate was 94% with a mean healing time of 3.1 ± 0.4 weeks. The ulcer recurrence frequency was 6%, the ulcer transfer frequency 4.5%, the postoperative infection rate 18%, and the revision surgery rate 3.8%. No significant differences were found between both techniques. When compared to standard of care, the odds ratio of ulcer healing frequency was 27.1 (95% CI 1.442-508.174, P = .01) in favor of the Keller arthroplasty with a faster healing time ( P = .02). Conclusion: Both surgical offloading procedures are highly effective in treating chronic noncomplicated DFU of the plantar aspect of the hallux along with low complication frequencies. There is a need to fine-tune the indication in relation to the location of the plantar wound with future comparative controlled research studies with far more patients than we could include in this meta-analysis.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase mainly found in the focal adhesion regions of the plasma membrane and it has a crucial role in migration and the remodeling of cellular morphology. FAK is also linked to several aspects of cancer biology, from cytokine production to angiogenesis, drug resistance, invasion, and metastasis, as well as epithelial-to-mesenchymal transition. The gene locus of FAK is frequently amplified in several human tumors, thus causing FAK overexpression in several cancers. Furthermore, FAK can influence extracellular matrix production and exosome secretion through cancer-associated fibroblasts, thus it has an important role in tumor microenvironment regulation. Although the role of FAK in solid tumors is well known, its importance in onco-hematological diseases remains poorly explored. This review collects studies related to FAK significance in onco-hematological diseases and their microenvironments. Overall, the importance of FAK in blood tumors is increasingly evident, but further research is required to confirm it as a new therapeutic target in hematological contexts.

Background: The umbilical cord (UC) provides life support to the fetus.The length of UC is of great clinical relevance and is associated with a wide range of unfavorable obstetric outcomes. Objectives: Evaluating the feasibility of sonographic measurement of the UC length index in predicting any adverse feto-maternal outcomes of an uncomplicated full-term pregnancy Patients and Methods: This prospective cohort study was done on 369 pregnant women with a singleton pregnancy and ≥ 37 weeks of gestation. The UC length index was calculated by ultrasonography by counting UC rings in each amniotic fluid quadrant. Results: Both groups of women, based on the occurrence of UC problems, had insignificant differences as regards the different characteristics of the studied women, UC length, and UC index. Meanwhile, the frequency of neck loops was significantly higher among women with UC problems (44.2% vs. 25.5%; p = 0.01). There were insignificant differences between different umbilical cord problems regarding UC length (p = 0.42) and UC index (p = 0.28). Conclusion: The UC length index was not a statistically significant predictor of umbilical cord abnormalities.

Background: Diabetic foot ulcers (DFUs) are serious complications that induce a high risk of lower extremity amputations and mortality. Compared with the standard of care, few reports analyzed the outcome of surgical treatment mainly for diabetic toe deformities and ulcers. The aim of this study is to collate evidence on the outcomes of interphalangeal resection arthroplasty (IP-RA) in preventing and treating diabetic toe ulcers distal to the metatarsophalangeal joint. Methods: A search strategy has been developed including electronic databases from inception. Only ulcers distal to the metatarsophalangeal joints were included. Noninfected and infected ulcers were also included at any toe location (dorsal/side/plantar). Outcomes were defined as healing rate, time to heal, ulcer recurrence, ulcer transfer, postintervention infection, wound dehiscence, and additional surgeries including amputation. Proportional meta-analysis was conducted for frequency outcomes. Results: Six observational studies comprising 217 patients with 244 IP-RA procedures were included. The mean follow-up period was 23.4 ± 8.2 months. Weighted frequencies were as follows: healing rate (93.6%), ulcer recurrence frequency (4.3%), ulcer transfer frequency (15.4%), postoperative infection (10.5%), wound dehiscence (17.8%), revision surgery (5%), and amputation rate (3.4%). The mean healing time was 4.3 ± 1.8 weeks. Conclusion: This review suggests that IP-RA is effective in preventing and treating diabetic toe deformities and ulcers with a modest rate of complications for this specific and often challenging clinical presentation.

الخلفية: يعد خثار وريد الباب من الحالات الهامة الغير مدروسة بشكل واسع ذات التطور السريري غير المحدد بدقة. ازدادت حالات تشخيص خثار وريد الباب في السنوات الأخيرة نظراً لتوافر تقنيات التصوير الحديثة. يهدف هذا البحث بشكل رئيسي الى تحديد عوامل الخطورة والأعراض والعلامات السريرية لحالات خثار وريد الباب. الطرائق: شملت الدراسة 30 مريض شخّص له خثار وريد الباب بالإيكو دوبلر أو عبر الطبقي المحوري من المرضى مراجعي مستشفى تشرين الجامعي في الفترة الممتدة بين كانون الثاني 2023م حتى كانون الثاني 2024م. النتائج: وجد عامل خطر وحيد لخثار وريد الباب عند 70% من المرضى واشترك عاملان عند 10% وكانت نسبة الخثار مجهول السبب 20%. كانت الخباثات البطنية هي عامل الخطورة الأشيع بنسبة 36.6%، والألم البطني هو التظاهر الأكثر شيوعاً بنسبة 53.3% . كانت نسبة الخثار الحاد 63.3% والخثار المزمن 36.7% . الضخامة الطحالية والنزف الهضمي ودوالي المري والمعدة كانت موجودات أكثر شيوعاً بفارق هام احصائياً عند مرضى الخثار المزمن. كان الحبن أكثر شيوعاً عند مرضى التشمع أو السرطان بفارق هام احصائياً مقارنةً بالمرضى بدون تشمع وسرطان. حدثت الوفاة عند 9 مرضى منهم 7 مرضى سرطان. الخلاصة: خثار وريد الباب من الحالات الهامة التي أصبحت تعتبر كيان سريري مستقل، يجب البحث عن الأسباب وعوامل الخطورة ومعالجتها إن أمكن ذلك لأن إنذار المرض متعلق بشكل أساسي بالسبب أكثر مما هو بالخثار واختلاطاته.

Summary: Ribonucleoside monophosphates (rNMPs) are abundantly found within genomic DNA of cells. The embedded rNMPs alter DNA properties and impact genome stability. Mutations in ribonuclease (RNase) H2, a key enzyme for rNMP removal, are associated with the Aicardi-Goutières syndrome (AGS), a severe neurological disorder. Here, we engineered orthologs of the human RNASEH2A-G37S and RNASEH2C-R69W AGS mutations in yeast Saccharomyces cerevisiae: rnh201-G42S and rnh203-K46W. Using the ribose-seq technique and the Ribose-Map bioinformatics toolkit, we unveiled rNMP abundance, composition, hotspots, and sequence context in these AGS-ortholog mutants. We found a high rNMP presence in the nuclear genome of rnh201-G42S-mutant cells, and an elevated rCMP content in both mutants, reflecting preferential cleavage of RNase H2 at rGMP. We discovered unique rNMP patterns in each mutant, showing differential activity of the AGS mutants on the leading or lagging replication strands. This study guides future research on rNMP characteristics in human genomes with AGS mutations.

IntroductionIn classical Hodgkin lymphoma (cHL), the survival of neoplastic cells is mediated by the activation of NF-κB, JAK/STAT and PI3K/Akt signaling pathways. CK2 is a highly conserved serine/threonine kinase, consisting of two catalytic (α) and two regulatory (β) subunits, which is involved in several cellular processes and both subunits were found overexpressed in solid tumors and hematologic malignancies.Methods and resultsBiochemical analyses and in vitro assays showed an impaired expression of CK2 subunits in cHL, with CK2α being overexpressed and a decreased expression of CK2β compared to normal B lymphocytes. Mechanistically, CK2β was found to be ubiquitinated in all HL cell lines and consequently degraded by the proteasome pathway. Furthermore, at basal condition STAT3, NF-kB and AKT are phosphorylated in CK2-related targets, resulting in constitutive pathways activation. The inhibition of CK2 with CX-4945/silmitasertib triggered the de-phosphorylation of NF-κB-S529, STAT3-S727, AKT-S129 and -S473, leading to cHL cell lines apoptosis. Moreover, CX-4945/silmitasertib was able to decrease the expression of the immuno-checkpoint CD274/PD-L1 but not of CD30, and to synergize with monomethyl auristatin E (MMAE), the microtubule inhibitor of brentuximab vedotin.ConclusionsOur data point out a pivotal role of CK2 in the survival and the activation of key signaling pathways in cHL. The skewed expression between CK2α and CK2β has never been reported in other lymphomas and might be specific for cHL. The effects of CK2 inhibition on PD-L1 expression and the synergistic combination of CX-4945/silmitasertib with MMAE pinpoints CK2 as a high-impact target for the development of new therapies for cHL

Biconcave (B2) glenoids, characterized by significant posterior glenoid bone loss and a biconcave wear pattern, are a challenging pathology in shoulder surgery. Significant bone defects present in B2 glenoids increases the risk of complications and rates of failure for operative patients with glenohumeral osteoarthritis. Diagnosing this entity is of pivotal importance, and can be accomplished with imaging and a comprehensive clinical investigation. There are no clear-cut guidelines for management, but options include hemiarthroplasty, anatomic total shoulder arthroplasty, and reverse shoulder arthroplasty. In recent years, modern techniques such as corrective reaming, bone grafts, and the use of augmented components have improved patient outcomes. Educating prospective patients is essential for reaching a shared management decision, setting appropriate expectations, and optimizing prognostic outcomes.

Background: The prevalence of obesity in the Eastern Mediterranean is increasing significantly up to 20.8% in 2016. Therefore, a higher percentage of colorectal cancer (CRC) patients are expected to be obese. Laparoscopic colorectal cancer surgery (LCRCS) is regarded as a safe and feasible procedure as laparoscopic approach is becoming the gold standard in CRC surgery, especially in the early stages of disease. However, LCRCS is correlated with a higher risk of short-term post-operative complications in obese patients (body mass index [BMI] ≥30 Kg/m2) than in patients with BMI

Due to the scarcity of low-grade appendiceal mucinous neoplasm (LAMN), there is an absence of systematized guidelines concerning its management, especially after incidental finding on an appendiceal specimen. In this study, we evaluate the active surveillance (AS) strategy adopted for a series of patients diagnosed with LAMN on resection specimens who were considered to have a low risk of pseudomyxoma progression.

Abstract Background The revised Opioid Risk Tool (ORT-OUD) is a brief, self-report scale designed to provide clinicians with a simple, validated method to screen for the risk of developing an Opioid Use Disorder (OUD) in patients without a prior history of substance abuse. This study aimed to translate and validate the Arabic version of ORT-OUD in the Lebanese population and assess its clinical validity in a sample of patients with OUD. Methods This cross-sectional study in the Lebanese population used several validated scales to assess the risk of OUD, including the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Other tools evaluated chronotype and sleep and mood disturbances. Principal component analysis with Varimax rotation was applied to assess ORT-OUD construct validity. Convergent validity with the Arabic version of ASSIST was evaluated. The ORT-OUD criterion validity was then assessed in a clinical sample of patients with OUD. Results This study included 581 participants. The prevalence of the OUD risk in the Lebanese population using the ORT-OUD scale and the ASSIST-opioids scale was estimated at 14.5% and 6.54%, respectively. No items of the ORT-OUD were removed; all items converged over a solution of four factors with an eigenvalue > 1, explaining a total of 68.2% of the variance (Cronbach’s alpha = 0.648). The correlation coefficients between the ORT-OUD total score and ASSIST subscales were as follows: ASSIST-opioids (r = 0.174; p =

Abstract Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.

Glioblastoma multiforme (GBM) is a highly aggressive and fatal primary brain tumor. The resistance of GBM to conventional treatments is attributed to factors such as the blood–brain barrier, tumor heterogeneity, and treatment-resistant stem cells. Current therapeutic efforts show limited survival benefits, emphasizing the urgent need for novel treatments. In this context, natural anti-cancer extracts and especially animal venoms have garnered attention for their potential therapeutic benefits. Bee venom in general and that of the Middle Eastern bee, Apis mellifera syriaca in particular, has been shown to have cytotoxic effects on various cancer cell types, but not glioblastoma. Therefore, this study aimed to explore the potential of A. mellifera syriaca venom as a selective anti-cancer agent for glioblastoma through in vitro and in vivo studies. Our results revealed a strong cytotoxic effect of A. mellifera syriaca venom on U87 glioblastoma cells, with an IC50 of 14.32 µg/mL using the MTT test and an IC50 of 7.49 µg/mL using the LDH test. Cells treated with the bee venom became permeable to propidium iodide without showing any signs of early apoptosis, suggesting compromised membrane integrity but not early apoptosis. In these cells, poly (ADP-ribose) polymerase (PARP) underwent proteolytic cleavage similar to that seen in necrosis. Subsequent in vivo investigations demonstrated a significant reduction in the number of U87 cells in mice following bee venom injection, accompanied by a significant increase in cells expressing caspase-3, suggesting the occurrence of cellular apoptosis. These findings highlight the potential of A. mellifera syriaca venom as a therapeutically useful tool in the search for new drug candidates against glioblastoma and give insights into the molecular mechanism through which the venom acts on cancer cells.