Introduction: Virtual reality training (VRT) is an advanced technology that creates virtual games by a computer through specific software. It is a type of rehabilitation training commonly used in balance problems to treat musculoskeletal conditions. Objective: To determine and compare the effects of virtual reality games with those of core stabilization training on physical efficiency in soccer players with chronic low back pain. Methods: A randomized, double-blinded, controlled study was conducted on 60 LBP participants at a university hospital. The first group (n=20) received virtual reality (VR) training; the second group (n=20) received core stabilization (CS) training; and the third group (n=20) received conventional training exercises for four weeks. Scores of clinical and sports performance were measured at baseline, and after 4 weeks, 8 weeks and 6 months. Results: The baseline demographic and clinical characters did not show any significant differences (p>0.05) in the statistical analysis, which shows a homogenous population. Four weeks following the training, the VR training group showed more significant changes in clinical scores than the CS training and control groups (p≤0.001). The scores for sports performance also showed more significant improvement in the VR training group than in the other two groups (p≤0.001). The same improved clinical and sports performance changes were seen at 8 weeks and 6 months of follow-up in the VR training group, when compared to the other two groups (p≤0.001). Conclusion: This study suggests that training through virtual reality games results in long-term improvement in clinical and sports performance compared to other forms of training in soccer players with chronic low back pain.Level of evidence I b; Therapeutic studies – Investigation of treatment results.

Hemophilia A (HA) is associated with FVIII coagulation insufficiency or inactivity leading to excessive bleeding. Elevated FVIII, on the contrary, is associated with thrombophilia, thrombosis, myocardial infarctions, and stroke. Active FVIII (aFVIII) uses its C2 domain to bind to blood cells’ membranes, consequently carrying out its coagulative function. We developed a reliable flow cytometry (FC) method for FVIII detection that can be utilized for assessing surface-bound FVIII on leukocytes in different coagulation/clinical states; we analyzed 49 pediatric subjects, encompassing patients with HA, other coagulopathies, venous thrombosis, and normal coagulation. Interestingly, the total leukocyte surface FVIII showed a declining trend across thrombosis, normal, and hypo-coagulation states. As expected, the leukocytes of HA patients displayed significantly lower levels of cellular-surface FVIII in comparison to patients with thrombosis. However, no significant correlation was observed between circulating levels of FVIII in plasma and the levels of FVIII bound to leukocytes, indicating that the differences in FVIII surface binding are not directly proportional to the availability of FVIII in the circulation and suggesting a specific binding mechanism governing the interaction between FVIII and leukocytes. Intriguingly, when analyzing the distinct blood subpopulations, we observed that surface FVIII levels were significantly elevated in classical monocytes of thrombosis patients compared to HA patients, healthy controls, and patients with other coagulopathies. Our study highlights the reliability of our FC platform in assessing FVIII abundance on leukocytes’ membranes across coagulation states. Monocytes, particularly in cases of thrombosis, exhibit active binding of FVIII on their surface, suggesting a potential role in the pathophysiology of thrombosis that requires further investigation.

Pediatric cancers pose significant treatment challenges due to their biological heterogeneity and variable responses to chemotherapy. SLFN11, a DNA/RNA helicase-like protein known to sensitize adult tumors to DNA-damaging agents, remains underexplored in pediatric malignancies. Here, we investigate the role of SLFN11 across pediatric Wilms tumor, osteosarcoma, and medulloblastoma using integrated bioinformatics, epigenetic profiling, and functional assays. In silico analysis of TARGET and ICGC datasets revealed distinct correlations between SLFN11 expression and patient survival, with positive, negative, or neutral predictive value depending on tumor type. Baseline expression and promoter methylation analysis in pediatric cancer cell lines demonstrated epigenetic regulation of SLFN11, similar to adult cancers. Using CRISPR-dCas9-mediated activation, we successfully upregulated SLFN11, which significantly enhanced sensitivity to cisplatin and the PARP inhibitor talazoparib across all tested cell lines. Transcriptomic profiling under cisplatin treatment indicated that SLFN11 modulates DNA damage response and MAPK signaling pathways, potentially contributing to chemotherapy sensitivity. These findings establish SLFN11 as a context-dependent predictive biomarker and a potential therapeutic target to overcome chemoresistance in pediatric solid cancers.

Background Familial Hemophagocytic Lymphohistiocytosis (FHLH) is an inherited life-threatening disease. Five types are identified with the addition of congenital immunodeficiency syndromes in which HLH is a typical manifestation. The literature on this disease is very scarce in the Middle East, with only a few scattered reports. Methods: We report detailed demographic, clinical, and genomic data from 28 patients diagnosed with FHLH and Griscelli syndrome type 2 over the last decade in Qatar. Evaluation of allele frequencies of deleterious variants from 12 FHLH causative genes was performed on the Qatar Genome Programme (QGP) cohort of 14,669 Qatari individuals. Results The genetic diagnosis was obtained in 15 patients and 4 novel mutations in PRF1, UNC13D, LYST and RAB27A genes were identified. We identified 22,945 low/high/moderate impact variants significantly enriched in the QGP in those 12 genes. The variants rs1271079313 in PRF1 and rs753966933 in RAB27A found in our patients’ cohort were significantly more prevalent in QGP compared to the gnomAD database, with a high carrier frequency in the Qatari population. Conclusions We established the first FHLH Registry in the Gulf Region and identified novel pathogenic variants present at higher frequency in the Qatari population, which could be used for screening purposes. Raising awareness about FHLH and implementing screening activities in the Qatari highly inbred population could stem into more comprehensive pre-marital and prenatal evaluations and faster diagnosis.

Background: Graft versus host disease (GVHD) and the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) result from complex interactions between the donor immune system and the recipient environment. High-temporal longitudinal monitoring might be necessary to identify triggering events of GVHD and GVT and to intercept these events before their occurrence. But it would require an overall considerable amount of blood by venipuncture, which is unfeasible in such a fragile population. Methods: In this study, we implemented a targeted multiplex microfluidics q-PCR-based transcriptional fingerprint assay (TFA) on 50 µL of blood collected by a simple fingerstick to evaluate post-allo-HCT systemic immune perturbations associated with the development of GVHD. Fluctuations of a panel of 264 genes were measured in 31 allo-HCT patients by frequent (weekly or biweekly) analysis of 50 µL serial blood samples. Cross-sectional and longitudinal analyses correlated with detailed clinical annotations were performed. Results: Signatures of neutrophil activation and interferon (IFN) characterized the onset of acute GVHD, while an ongoing cytotoxic response was modulated in chronic mild GVHD and protein-synthesis and B-cell-related signatures characterized late acute/overlap GVHD. An unexpected erythroid signature distinguished patients with acute and mild chronic GVHD. Conclusions: Our micro-invasive approach unveiled the molecular heterogeneity of GVHD and identified hierarchically important biological processes conducive to different forms of GVHD. These findings increase our understanding of GVHD and reveal potentially targetable alterations. This approach might be implemented clinically to intercept GVHD before its occurrence and to modulate therapeutic interventions accordingly.