Search Results (181)

Background: BK polyomavirus (BKPyV) reactivation is a common complication after kidney transplantation and may result in nephropathy and graft loss. As there is no effective antiviral therapy, management focuses on early detection and reduction of immunosuppression, which increases the risk of rejection. Identifying patients at higher risk remains challenging. Monitoring BKPyV-specific T-cell responses could aid in predicting reactivation. This study evaluated the usefulness of ELISpot to monitor BKPyV-specific cellular immunity before and after kidney transplantation. Methods: A prospective multicenter study was conducted between October 2020 and March 2022. ELISpot assays were performed prior to transplantation and two months afterward. Results: Seventy-two patients were included, with a median age of 56 years; 61% were men, and 24% had undergone previous transplantation. Nine patients developed presumptive BKPyV-nephropathy. No significant differences were found in donor type, induction therapy, or rejection rates between patients with or without nephropathy (p = 0.38). Based on ELISpot results, patients were classified into three groups according to their risk of BKPyV-nephropathy. The high-risk group included those who changed from positive to negative at 2 months post-transplant, representing 40% of presumptive BKPyV-nephropathy cases. Patients who remained negative at 2 months were classified as moderate risk (14.5%), while those with a positive ELISpot at 2 months comprised the low-risk group (0%). In the logistic regression analysis, both the ELISpot risk category [OR 19 (CI 1.7–2.08)] and the use of mTOR inhibitors from the start of transplantation [OR 0.02 (CI 0.01–0.46)] were significantly associated with BKPyV-nephropathy. Conclusions: Monitoring BKPyV-specific T cells with ELISpot before and after kidney transplantation may help stratify patients by risk of reactivation. Loss of BKPyV immunity at two months is associated with nephropathy, while mTOR-based immunosuppression appears protective. This strategy could guide personalized immunosuppression and surveillance. Full article

Addressing privacy concerns is one of the key challenges facing the development of Internet of Things (IoT)-based systems (IoTSs). As IoT devices often collect and process personal and sensitive information, strict privacy policies must be defined and enforced to keep data secure and safe, ensuring security and regulatory compliance. Any data breach could compromise the security of the system, leading to various types of threats and attacks, some of which could even endanger human life. Therefore, it is crucial to design and build a comprehensive and general privacy framework for the development of IoTSs. This framework should not be limited to specific IoTS domains but should be general enough to support and cover most IoTS domains. In this paper, we present a framework that assists developers by (i) enabling them to build IoTSs that comply with privacy standards, such as the General Data Protection Regulation (GDPR), and (ii) providing a simplified and practical approach to identifying and addressing privacy concerns. In addition, the framework enables developers to implement effective countermeasures. Full article

Obesity represents a serious and growing disease worldwide. The pathophysiological changes secondary to chronic inflammation lead to the development of diseases that increase the morbidity and mortality of individuals. Chronic kidney disease (CKD) is a condition with deleterious effects that acts bidirectionally with obesity. From approximately 20% to 30% of individuals share phenotypes of CKD and obesity, increasing their cardiovascular risk and the risk of other complications. Obesity and CKD form a vicious cycle in which inflammation is the central axis of multiorgan damage. Despite increasing the risk of cardiac and renal mortality, CKD progresses in relation to body mass index and albuminuria. Nowadays, the implementation of the new medications aimed at mitigating the peak of inflammation is becoming a cornerstone of treatments for obesity, diabetes, cardiovascular diseases, and renal disease. Full article

Tonsils are secondary lymphoid organs that play a crucial role in the immunological response, with B cells being a major component involved in both innate and adaptive immunity. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and obstructive sleep apnea syndrome (OSAS) are both common pediatric conditions involving tonsillar pathology. In both syndromes, the molecular pathways dysregulated in tonsillar B cells are still to be understood. The study aimed to unravel and compare the proteomic profiles of tonsillar CD19+ B cells isolated from pediatric patients with PFAPA (n = 6) and OSAS (n = 6) to identify disease-specific molecular signatures. B cells were isolated from the tonsillar tissue using magnetic microbeads (with a purity of 93.50%). Proteomic analysis was performed by nanoLC-MS/MS with both data-dependent (DDA) and data-independent acquisition (DIA) methods, followed by comprehensive bioinformatic analysis. By merging DDA and DIA datasets, a total of 18.078 unique proteins were identified. Differential expression analysis revealed 83 proteins increased and 49 proteins decreased in OSAS B cells compared to PFAPA B cells (fold change ≥ 1.5 or ≤0.6, p < 0.05). Distinct pathway enrichments were highlighted, including alterations in the regulation of PTEN gene transcription, circadian gene expression, inflammasome pathways (IPAF and AIM2), and the metabolism of angiotensinogen to angiotensin. Specific proteins such as p53, Hdac3, RPTOR, MED1, Caspase-1, Cathepsin D, Chymase, and TLR2 (validated by WB) were shown to be differentially expressed. These findings reveal distinct proteomic signatures in tonsillar B cells from patients with PFAPA and OSAS, offering novel insights into the pathophysiology and potential avenues for biomarker discovery. Full article

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by ¹H-MR spectroscopy. Full article

Background/Objectives: We previously demonstrated that nilotinib can sufficiently enter the brain to pharmacologically inhibit discoidin domain receptors (DDR)-1 in patients with Parkinson’s and Alzheimer’s disease. We primarily hypothesized that nilotinib is safe, and may alter disease-related biomarkers to improve, motor, cognitive and/or behavioral features in dementia with Lewy bodies (DLB). Methods: Forty-three participants were randomized 1:1 into nilotinib, 200 mg, or matching placebo in a single-center, phase 2, randomized, double-blind study. Study drug was taken orally once daily for 6 months followed by one-month wash-out. Results: Of 43 individuals enrolled, 14 were women (33%); age (mean ± SD) was 73 ± 8.5 years. Nilotinib was safe and well-tolerated, and more adverse events were noted in the placebo (74) vs. nilotinib (37) groups (p = 0.054). The number of falls were reduced in the nilotinib (six) compared to placebo (21) group (p = 0.006). Cerebrospinal fluid homovanillic acid, a biomarker of dopamine levels, was increased (p = 0.004), while the ratio of pTau181/Aβ42 was reduced (p = 0.034). The Alzheimer’s Disease Assessment Scale—cognition 14 improved by 2.8 pts (p = 0.037), and no differences were observed in Movement Disorders Society–Unified Parkinson’s Disease Rating Scale parts II and III. However, part I (cognition) improved (p = 0.044) in nilotinib compared to placebo. Conclusions: Nilotinib demonstrates favorable safety, biomarkers, and efficacy outcomes in patients with DLB supporting further trials in DLB or advanced Parkinson’s disease with dementia. Full article

Introduction: The indication for a free flap in acute burn reconstruction is very specific. It should avoid several complications that are more common in the burned patient population. We propose an anterolateral thigh (ALT) flap as a first option for primary burn reconstruction in microvascular free flap reconstruction in burned patients. Patients and Methods: A retrospective review of all acutely burned patients treated with microvascular ALT free flap reconstruction between the years 2005 and 2022 in the Vall d’Hebron Barcelona Hospital Campus Burn Centre was conducted. Results: We performed 30 ALT flaps for primary burn reconstruction. The majority of patients were male (87.5%), with a mean age of 36.7 years, and 37% of patients were smokers. High-voltage electrical burns were the most common etiology. The mean time between burn injury and microsurgery was 22 days. The main recipient site was the lower limb. The flap survival rate was 96.6%. One patient required a meshed skin graft to cover a defect in the proximal third due to peripheral flap necrosis. One flap experienced mild congestion, which resolved spontaneously. Another flap had a local infection, which resolved with antibiotic therapy and surgical debridement. Conclusions: An ALT flap offers several advantages to a burned patient, provided that the surgical technique and postoperative management described in this study are followed. We propose it as the first option for primary burn reconstruction using free flaps in a burned patient. Full article

Background: The growth patterns of children and adolescents are influenced by multiple factors. This study employed structural equation modeling (SEM) to determine the primary factors influencing the growth of Palestinian children and adolescents in the West Bank (WB). Methods: A cross-sectional survey conducted in 2022 in the WB collected data from 1400 households, of which 500 with children aged 5–17 years and were selected for analysis. The survey assessed household food insecurity, socioeconomic status (SES), parental health history, nutritional awareness, food consumption patterns, and nutrient intake. The latent construct “Child Growth” was measured using Body Mass Index-for-age Z-score (BAZ), height-for-age Z-score (HAZ), and Mean Adequacy Ratio (MAR). SEM was employed to examine the interrelations among latent variables and their observed indicators. Results: Mineral intake showed the strongest direct effect on child growth (β = 0.812, p < 0.001), followed by food availability (β = 0.492), vitamin intake (β = 0.481), SES (β = 0.439), and macronutrient intake (β = 0.383). MAR exhibited the highest factor loading as a growth indicator, while HAZ had limited significance, suggesting its chronic nature. SES influenced growth both directly and indirectly through its effects on food availability and dietary intake pathways. Strong correlations between nutritional knowledge and nutrient classes reflect the interrelationship between behavioral and biological determinants. Conclusions: Both structural and immediate nutritional factors influence child growth. In Palestinian youth, mineral intake, food security, and SES have the greatest influence. These findings offer a framework for understanding the growth determinants of Palestinian youth in the WB and support the development of targeted interventions to improve dietary quality and overall nutritional status. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by amyloid-beta (Aβ) accumulation and neuroinflammation. A previous multicenter, phase 2, double-blind, placebo-controlled trial randomized 179 participants into placebo or resveratrol over 52 weeks. Sub-analysis of CSF biomarkers of neuronal damage, inflammation, and microglial activity was performed in a subset of patients treated with a placebo (n = 21) versus resveratrol (n = 30). Markers of neuronal damage, including neuron-specific enolase and hyperphosphorylated neurofilaments, were reduced. Microglial activation was measured via a triggering receptor expressed on myeloid cells (TREM)-2 at baseline and after resveratrol treatment. Resveratrol significantly reduced CSF TREM2 levels and decreased inflammation and tissue damage, including matrix metalloprotease (MMP)-9. Cathepsin D, a lysosomal marker of autophagy, was reduced in the resveratrol group compared with placebo, while angiogenin, a marker of vascular angiogenesis, was increased. These data suggest that resveratrol may exert anti-inflammatory and neuroprotective effects in AD by reducing CSF TREM2 and other markers of neuronal damage. Further research is needed to assess the significance of these biomarker changes on clinical outcomes in patients with neurodegenerative diseases. Full article

Bladder cancer is the ninth most common cancer globally, with most cases classified as non-muscle-invasive bladder cancer (NMIBC). While transurethral resection of the bladder tumor (TURBT) remains the gold-standard treatment, its complications, high recurrence rates, and economic burden have prompted interest in alternative strategies like active surveillance (AS) for low-grade and low-grade NMBIC recurrences. AS minimizes surgical interventions and patient burden, but lacks standardized protocols for inclusion criteria and follow-up schedules. Most studies suggest intensive monitoring during the first year, with criteria often based on tumor size, number, and grade. Acquisition of evidence: A comprehensive literature search was conducted in December 2024 using Pubmed, Cochrane, and Trip databases to identify studies on AS for low-grade NMBIC recurrences. Only English studies were included, with Boolean operators used to refine the search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Population, Intervention, Comparison and Outcomes (PICO) selection criteria were followed. The Newcastle–Ottawa quality assessment scale was used to analyze the quality of the included studies. Evidence synthesis: This systematic review included 11 studies evaluating AS for NMIBC. Early studies, such demonstrated AS as a feasible alternative to TURBT, with low progression rates. Subsequent research confirmed its safety in selected patients, with tumor growth and positive cytology being the main reasons for intervention. More recent investigations, further supported AS as a viable strategy, highlighting the low risk of stage and grade progression and its potential to reduce surgical interventions. Conclusions: AS may be considered an alternative approach for low-risk NMIBC recurrences. However, there is need for prospective studies and personalized approaches to optimize AS, addressing follow-up strategies, inclusion criteria and progression thresholds. Full article

This study explores the intersection of competitiveness in a circular economy and the role of digital innovations through an integrative literature review. Synthesizing quantitative and qualitative research identifies gaps and offers insights on how these trends shape competitive strategies. The review emphasizes three main areas: technological enablers, operational challenges, and the role of policy and collaboration. It highlights the interrelationship among the circular economy, digital innovations, and competitiveness in promoting sustainable practices. The research suggests that policymakers should support small- and medium-sized enterprises (SMEs) with financial assistance for digital tool adoption and establish regional digital innovation hubs for technology access and training. Standardized data-sharing protocols are crucial for effective circular economy practices and cybersecurity. Ultimately, the review identifies key research opportunities at the nexus of digital innovations and the circular economy, aiming to enhance theoretical knowledge and inform sustainable business model development. Full article

Background/Objectives: Breast cancer (BC) is the most prevalent cancer among Palestinian women and significantly affects their quality of life (QoL). Coping strategies are pivotal in shaping QoL outcomes; however, research examining coping strategies and QoL in the Palestinian context remains scarce. This study aims to evaluate coping strategies among newly diagnosed BC patients and their impact on QoL in the southern West Bank. Methods: A cross-sectional study recruited 147 newly diagnosed BC patients undergoing treatment in governmental hospitals in the Hebron and Bethlehem governorates. Data were collected via face-to-face questionnaires, which included the EORTC QLQ-C30, the Cancer Coping Questionnaire (CCQ), sociodemographic and clinical characteristics, and social support. Results: Participants exhibited moderate QoL scores, with physical functioning scoring highest (67) and emotional functioning lowest (49). Fatigue, insomnia, and pain were the most common symptoms. Coping strategies were moderately utilized, and global QoL was significantly associated with these strategies. Hierarchical regression showed education had a small positive effect on global QoL (R² = 0.052, p = 0.005), while family support was a moderate predictor (R² = 0.080, p = 0.041). The CCQ coping score negatively impacted global QoL (R² = 0.186, p < 0.001), whereas CCQ positive focus (R² = 0.342, p < 0.001) and diversion techniques (R² = 0.406, p < 0.001) had substantial positive effects. Conclusions: Positive coping strategies, education, and family support play a vital role in enhancing QoL for newly diagnosed BC patients. Coping-focused interventions should be integrated into oncology care in Palestine to improve patient outcomes. Full article

Small and medium-sized enterprises (SMEs) in Palestine face significant challenges in risk management, in which safety culture, risk mitigation, and sustainability practices play a critical role in business performance. However, the ways these variables influence business performance through employee engagement are less explored. This study investigates the impact of safety culture, risk mitigation, and sustainability practices on the business performance of Palestinian SMEs, with a special emphasis on employee engagement’s mediating effect. The quantitative approach was adopted, and data were collected from 450 SME respondents within the main clusters of the West Bank (Ramallah, Hebron, Nablus, and Jericho) based on purposive sampling. The findings indicate that safety culture, risk mitigation, and sustainability practices positively and significantly impact business performance. Furthermore, employee engagement is a potent mediator that enhances these variables’ positive effects on business performance. These results have practical and theoretical implications for building a robust safety culture, possessing effective risk minimization measures, and incorporating sustainability practices to advance business performance in Palestinian SMEs. The study recommends that SME owners and managers prioritize employee engagement in addressing safety and sustainability matters to achieve long-term business growth. Full article

Levodopa is the gold standard symptomatic treatment for Parkinson’s disease. Disease progression due to alpha-synuclein accumulation, brain inflammation, and the loss of dopamine neurons, as well as motor fluctuations, due to variations in levodopa plasma levels, remain a significant problem for Parkinson’s patients. Developing a therapeutic option that can simultaneously reduce the neuropathology associated with alpha-synuclein aggregation, attenuate oxidative stress and inflammation, and overcome variations in levodopa plasma levels is an unmet need to treat Parkinson’s disease. We determined the pharmacokinetics and pharmacodynamics of a small molecule, dubbed Pegasus, that conjugates dopamine with a nonantibiotic doxycycline derivative via a molecular linker. Mice harboring the human A53T mutation of alpha-synuclein or treated with MPTP were injected once daily with 50 mg/kg Pegasus for 2 weeks and assessed for motor, behavioral, and cognitive effects, followed by biochemical and histochemical analysis. Pegasus is a poor brain penetrant but it was metabolized to stable dopamine and tetracycline derivatives, and abundant plasma and brain levels of these metabolites were detected. Pegasus reduced soluble and insoluble alpha-synuclein levels, protected dopamine-producing neurons, and reduced astrocytic activation in A53T mice. Mice treated with Pegasus exhibited motor improvement (6.5 h) and reduction in anxiety-like behavior. Rotarod and grip strength improved in MPTP-treated mice when mice were treated with Pegasus or levodopa. Pegasus may be a multi-modal therapeutic option that can deliver stable dopamine into the CNS and reduce misfolded alpha-synuclein, activate dopamine receptors, and attenuate variations in dopamine levels. Full article

(1) Background: Respiratory viral infections, including those caused by SARS-CoV-2, respiratory syncytial virus (RSV), influenza viruses, rhinovirus, and adenovirus, are major causes of acute respiratory infections (ARIs) in children. Symptom-based predictive models are valuable tools for expediting diagnoses, particularly in primary care settings. This study assessed the effectiveness of machine learning-based models in estimating infection probabilities for these common pediatric respiratory viruses, using symptom data. (2) Methods: Data were collected from 868 children with ARI symptoms evaluated across 14 primary care centers, members of COPEDICAT (Coronavirus Pediatria Catalunya), from October 2021 to October 2023. Random forest and boosting models with 10-fold cross-validation were used, applying SMOTE-NC to address class imbalance. Model performance was evaluated via area under the curve (AUC), sensitivity, specificity, and Shapley additive explanations (SHAP) values for feature importance. (3) Results: The model performed better for RSV (AUC: 0.81, sensitivity: 0.64, specificity: 0.77) and influenza viruses (AUC: 0.71, sensitivity: 0.70, specificity: 0.59) and effectively ruled out SARS-CoV-2 based on symptom absence, such as crackles and wheezing. Predictive performance was lower for non-enveloped viruses like rhinovirus and adenovirus, due to their nonspecific symptom profiles. SHAP analysis identified key symptoms patterns for each virus. (4) Conclusions: The study demonstrated that symptom-based predictive models effectively identify pediatric respiratory infections, with notable accuracy for those caused by RSV, SARS-CoV-2, and influenza viruses. Full article