Correction: Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0257895.].

Ultra-fast UPLC-MS/MS approach for estimating X-376 in human liver microsomes: Evaluation of metabolic stability via in silico software and in vitro analysis.

X-376 is a novel anaplastic lymphoma kinase (ALK) inhibitor that is capable of penetrating the blood brain barrier. This makes it suitable for use in patients with ALK-positive non-small cell lung cancer (NSCLC) who have metastases in the central nervous system. This study developed a highly sensitive, fast, eco-friendly, and reliable UPLC-MS/MS approach to quantify X-376 in human liver microsomes (HLMs). This approach was used to evaluate X-376's metabolic stability in HLMs in vitro. The UPLC-MS/MS analytical technique validation followed US-FDA bio-analytical method validation guidelines. StarDrop software, containing P450 metabolic and DEREK modules, was utilized to scan X-376's chemical structure for metabolic lability and hazardous warnings. X-376 and Encorafenib (ENF as internal standard) were resoluted on the Eclipse Plus C18 column utilizing an isocratic mobile phase method. The X-376 calibration curve was linear from 1 to 3000 ng/mL. The precision and accuracy of this study's UPLC-MS/MS approach were tested for intra- and inter-day measurements. Inter-day accuracy was -1.32% to 9.36% while intra-day accuracy was -1.5% to 10.00%. The intrinsic clearance (Clint) and in vitro half-life (t1/2) of X-376 were 59.77 mL/min/kg and 13.56 min. The high extraction ratio of X-376 supports the 50 mg twice-daily dose for ALK-positive NSCLC and CNS metastases patients. In silico software suggests that simple structural changes to the piperazine ring or group substitution in drug design may improve metabolic stability and safety compared to X-376.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF ß-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/ß-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data.. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.

Design of a novel multi-epitope vaccine against Marburg virus using immunoinformatics studies.

Marburg virus (MARV) is a highly contagious and virulent agent belonging to Filoviridae family. MARV causes severe hemorrhagic fever in humans and non-human primates. Owing to its highly virulent nature, preventive approaches are promising for its control. There is currently no approved drug or vaccine against MARV, and management mainly involves supportive care to treat symptoms and prevent complications. Our aim was to design a novel multi-epitope vaccine (MEV) against MARV using immunoinformatics studies. In this study, various proteins (VP35, VP40 and glycoprotein precursor) were used and potential epitopes were selected. CTL and HTL epitopes covered 79.44% and 70.55% of the global population, respectively. The designed MEV construct was stable and expressed in Escherichia coli (E. coli) host. The physicochemical properties were also acceptable. MARV MEV candidate could predict comprehensive immune responses such as those of humoral and cellular in silico. Additionally, efficient interaction to toll-like receptor 3 (TLR3) and its agonist (ß-defensin) was predicted. There is a need for validation of these results using further in vitro and in vivo studies.

Biomechanical Comparison of Corticopedicular Spine Fixation versus Pedicle Screw Fixation in a Lumbar Degenerative Spondylolisthesis Finite Element Analysis Model.

OBJECTIVE: To compare the stability of a corticopedicular posterior fixation (CPPF) device to traditional pedicle screws for decompression and fusion in adult degenerative lumbar spondylolisthesis. METHODS: Finite element analysis (FEA) was used in a validated model of grade 1 L4-L5 spondylolisthesis to compare segmental stability following laminectomy alone, laminectomy with pedicle screw fixation, or laminectomy with CPPF device fixation. A 500N follower load was applied to the model and different functional movements were simulated by applying a 7.5Nm force in different directions. Outcomes included degrees of motion, tensile forces experienced in the CPPF device, and stresses in surrounding cortical bone. RESULTS: At maximum loading, laminectomy alone demonstrated an 1° increase in flexion range of motion from 6.35° to 7.39°. Laminectomy with pedicle screw fixation and CPPF device fixation both reduced spinal segmental motion to ≤1° at maximum loading in all ranges of motion, including flexion (0.94° and 1.09°), extension (-0.85°and -1.08°), lateral bending (-0.56° and -0.96°), and torsion (0.63°and 0.91°), respectively. There was no significant difference in segmental stability between pedicle screw fixation and CPPF device fixation during maximum loading with a difference of ≤0.4° in any range of motion. Tensile forces in the CPPF device remained ≤51% the ultimate load to failure (487N) and stress in surrounding cortical bone remained ≤84% the ultimate stress of cortical bone (125.4 MPa) during maximum loading. CONCLUSION: CPFF fixation demonstrated similar segmental stability to traditional pedicle screw fixation while tensile forces and stress in surrounding cortical bone remained below the load to failure.

Transgenerational hormesis in healthy aging and antiaging medicine from bench to clinics: Role of food components.

Neurodegenerative diseases have multifactorial pathogenesis, mainly involving neuroinflammatory processes. Finding drugs able to treat these diseases, expecially because for most of these diseases there are no effective drugs, and the current drugs cause undesired side effects, represent a crucial point. Most in vivo and in vitro studies have been concentrated on various aspects related to neurons (e.g. neuroprotection), however, there has not been focus on the prevention of early stages involving glial cell activation and neuroinflammation. Recently, it has been demonstrated that nutritional phytochemicals including polyphenols, the main active constituents of the Mediterranean diet, maintain redox balance and neuroprotection through the activation of hormetic vitagene pathway. Recent lipidomics data from our laboratory indicate mushrooms as strong nutritional neuronutrients with strongly activity against neuroinflammation in Meniere' diseaseas, a model of cochleovestibular neural degeneration, as well as in animal model of traumatic brain injury, or rotenone induced parkinson's disease. Moreover, Hidrox®, an aqueous extract of olive containing hydroxytyrosol, and Boswellia, acting as Nrf2 activators, promote resilience by enhancing the redox potential, and thus, regulate through hormetic mechanisms, cellular stress response mechanisms., Thus, modulation of cellular stress pathways, in particular vitagenes system, may be an innovative approach for therapeutic intervention in neurodegenerative disorders.

Prenatal stress impacts foetal neurodevelopment: Temporal windows of gestational vulnerability.

Prenatal maternal stressors ranging in severity from everyday occurrences/hassles to the experience of traumatic events negatively impact neurodevelopment, increasing the risk for the onset of psychopathology in the offspring. Notably, the timing of prenatal stress exposure plays a critical role in determining the nature and severity of subsequent neurodevelopmental outcomes. In this review, we evaluate the empirical evidence regarding temporal windows of heightened vulnerability to prenatal stress with respect to motor, cognitive, language, and behavioural development in both human and animal studies. We also explore potential temporal windows whereby several mechanisms may mediate prenatal stress-induced neurodevelopmental effects, namely, excessive hypothalamic-pituitary-adrenal axis activity, altered serotonin signalling and sympathetic-adrenal-medullary system, changes in placental function, immune system dysregulation, and alterations of the gut microbiota. While broadly defined developmental windows are apparent for specific psychopathological outcomes, inconsistencies arise when more complex cognitive and behavioural outcomes are considered. Novel approaches to track molecular markers reflective of the underlying aetiologies throughout gestation to identify tractable biomolecular signatures corresponding to critical vulnerability periods are urgently required.

Efficiency of Fine-Needle Aspiration (FNA) in Relation to Tru-Cut Biopsy of Lateral Neck Swellings.

Background Lateral neck masses have always been difficult to diagnose without proposing a differential diagnosis. Fine-needle aspiration (FNA) was proposed to be a cost-effective method and less invasive than a tru-cut biopsy and may provide a provisional diagnosis in relation to cytopathology. FNA has also been shown to improve the diagnosis of neck masses such as cervical lymphadenopathy, neck cysts, and parotid masses, whether malignant or benign. This study aims to evaluate the accuracy of FNA cytopathology versus a tru-cut biopsy histopathological examination. Materials and methods This study was conducted retrospectively in King Hussein Medical Hospital, Royal Medical Services, Hashemite Kingdom of Jordan, from January 2019 to January 2024. Ethical approval was taken to conduct this study with reference number 06/2024. All patients included in this study have given verbal and written consent to perform FNA and surgical tru-cut biopsy. The inclusion of patients was based on any person above the age of 16 who underwent an FNA followed by a surgical biopsy to correlate with the primary diagnosis. Exclusion criteria involved any patient who missed one of the above criteria. Statistical analysis was performed using IBM SPSS v29 (IBM Corp., Armonk, NY, US) with significant results considered with a p-value <0.05. Results A total of 107 patients were included in this study. A correlation between FNA results and final histopathological biopsy was done with an accuracy of 90.6%, specificity of 94.3, predictive positive value of 73.6%, and negative predictive value of 94.3%. There was a statistical significance between FNA and tru-cut biopsy with a p-value of <0.001. Conclusion FNA is a great tool to consider when diagnosing lateral neck swellings. Since it was statistically significant, FNA should be considered for any lateral neck swelling before any surgical tru-cut biopsy for a definitive diagnosis.

Outcomes of biological therapy in patients with severe asthma with chronic rhinosinusitis in Saudi Arabia: patients with nasal polyps versus those without nasal polyps.

BACKGROUND: This study's purposes were to evaluate the impact of biological therapies on outcomes in patients with severe asthma (SA) and chronic rhinosinusitis (CRS) and to compare these effects among those with NP (CRSwNP) versus those without NP (CRSsNP) in the "real-world" setting in Saudi Arabian patients. METHODS: From March to September 2022, a retrospective observational cohort study was undertaken at the severe asthma clinics of the Armed Forces Hospital-Southern Region (AFHSR) and King Khalid University Hospital, Abha, Saudi Arabia, to delineate the effects of dupilumab therapy. Outcomes were assessed, including clinical outcomes, FEV1, and laboratory findings before and one year after dupilumab. Post-therapy effects were compared between CRSwNP and CRSsNP. RESULTS: Fifty subjects were enrolled, with a mean age of 46.56. There were 27 (54%) females and 23(46%) males. Significant improvements in clinical parameters (frequency of asthma exacerbations and hospitalizations, the use of OCs, anosmia, SNOTT-22, and the ACT), FEV1, and laboratory ones (serum IgE and eosinophilic count) were observed 6 and 12 months after using dupilumab (p < 0.001), respectively. However, after 12 months of dupilumab therapy, there were no significant differences between those with and without NP with regards to clinical (anosmia, ACT, and OCs use), laboratory (eosinophilic count, serum IgE level) parameters, and FEV1%. CONCLUSIONS: Patients with CRS experienced significant improvements in clinical, FEV1, and laboratory outcomes after dupilumab therapy. However, these improvements were not maintained when comparing CRSwNP with CRSsNP. There were no significant differences between those with and without NP regarding ACT and OCs use or laboratory (eosinophilic count, serum IgE level) parameters. Further prospective multicenter studies are warranted.

Ultrasound-guided vs. Standard Coronary Access in Coronary Angiography: A Systematic Review and Meta-analysis.

Objectives: Coronary angiography is a procedure performed during cardiac catheterization to define the coronary anatomy and determine the extent of coronary artery disease (CAD). The use of a cheap, relatively available tool like an ultrasound machine to assist in vascular access might reduce the risks associated with blind access. This study aimed to explore the efficacy and associated complications of ultrasound-guided coronary artery catheterization. Methods: This systematic review of randomized controlled trials (RCTs) was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in PROSPERO (CRD42022365518). A systematic search was performed for all published studies without language or country restrictions and all study variables were extracted into prefilled sheets by two independent reviewers. Results: This meta-analysis identified 10 RCTs. The results confirmed statistically significantly reductions of total complications (RR = 0.53, 95% CI 0.39-0.72, P < .001), and hematoma >5 cm formation (RR = 0.43, 95% CI 0.25-0.75, P = 0.003) in patients who underwent ultrasound-guided coronary artery catheterization. Conclusion: Ultrasound with catheterization, as opposed to landmark-based catheterization, significantly improved the peri-catheterization operative outcomes, providing evidence for further research to be conducted and consideration for its implementation within the medical setting.

Posaconazole-hemp seed oil loaded nanomicelles for invasive fungal disease.

Invasive fungal infections (IFI) pose a significant health burden, leading to high morbidity, mortality, and treatment costs. This study aims to develop and characterize nanomicelles for the codelivery of posaconazole and hemp seed oil for IFI via the oral route. The nanomicelles were prepared using a nanoprecipitation method and optimized through the Box Behnken design. The optimized nanomicelles resulted in satisfactory results for zeta potential, size, PDI, entrapment efficiency, TEM, and stability studies. FTIR and DSC results confirm the compatibility and amorphous state of the prepared nanomicelles. Confocal laser scanning microscopy showed that the optimized nanomicelles penetrated the tissue more deeply (44.9µm) than the suspension (25µm). The drug-loaded nanomicelles exhibited sustained cumulative drug release of 95.48 ± 3.27% for 24 h. The nanomicelles showed significant inhibition against Aspergillus niger and Candida albicans (22.4 ± 0.21 and 32.2 ± 0.46 mm, respectively). The pharmacokinetic study on Wistar rats exhibited a 1.8-fold increase in relative bioavailability for the nanomicelles compared to the suspension. These results confirm their therapeutic efficacy and lay the groundwork for future research and clinical applications, providing a promising synergistic antifungal nanomicelles approach for treating IFIs.

Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy.

INTRODUCTION: Hereditary vitamin D resistant rickets (HVDRR) is a rare autosomal recessive disorder marked by end-organ resistance of 1,25-dihydroxyvitamin D secondary to various mutations in the vitamin D receptor gene. The currently accepted treatment modality involves bypassing the affected receptors in the gut with high-dose intravenous calcium. In a few limited case reports, cinacalcet, a calcimimetic, has been used as an adjunctive therapy. MATERIAL AND METHODS: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation. RESULTS: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels. CONCLUSIONS: This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.

Utilizing AI for extracting insights on post WHO's COVID-19 vaccination declaration from X (Twitter) social network.

This study explores the use of artificial intelligence (AI) to analyze information from X (previously Twitter) feeds related to COVID-19, specifically focusing on the time following the World Health Organization's (WHO) vaccination announcement. This aspect of the pandemic has not been studied by other researchers focusing on vaccination news. By utilizing advanced AI algorithms, the research aims to examine a wealth of data, sentiments, and trends to enhance crisis management strategies effectively. Our methods involved collecting a dataset of tweets from December 2020 to July 2021. By using specific keywords strategically, we gathered a substantial 15.5 million tweets, focusing on important hashtags like #vaccine and #coronavirus while filtering out irrelevant replies and retweets. The assessment of three different machine learning models-BiLSTM, FFNN, and CNN - highlights the exceptional performance of BiLSTM, achieving an impressive F1-score of 0.84 on the test set, with Precision and Recall metrics at 0.85 and 0.83, respectively. The study provides a detailed visualization of global sentiments on COVID-19 topics, with a main goal of extracting insights to manage public health crises effectively. Sentiment labels were predicted using various classification models and categorized as positive, negative, and neutral for each country after adjusting for population differences. An important finding from the analysis is the variation in sentiments across regions, for instance, with Eastern European countries showing positive views on post-vaccination economic recovery, while China and the United States express negative opinions on the same topic.

A Novel Technique for Improving Cyclic Behavior of Steel Connections Equipped with Smart Memory Alloys.

Residual drifts are an important measure of post-earthquake functionality in bridges and buildings, and can determine whether the structure remains fit for its intended purpose or not. This study aims at investigating numerically, through finite element (FE) analysis in ABAQUS, the cyclic response of exterior steel I beam-hollow column connection using welded shape memory alloys (SMA) bolts and seat angles. This is followed by validating the numerical model using an accredited experimental data available in the literature through different techniques, (1) SMA bolts, (2) SMA angles, (3) SMA bolts and angles. The parameters investigated included: SMA type, SMA angle thickness, SMA bolt diameter, SMA angle stiffener and SMA angle direction. The cyclic performance of the steel connection was enhanced further by varying the bolt diameter, plate thickness, angle type and direction. The results revealed that the connections equipped with a combination of SMA plates and SMA angles reduced the residual drift by up to 94%, and doubled the self-centering capability compared to conventional steel connections. Moreover, the parametric analysis showed that Fe-based SMA members could be a good alternative to NiTi based SMA members for improving the self-centering capability and reducing the residual drifts of conventional steel connections.

Self-Recording of Eye Movements in Amyotrophic Lateral Sclerosis Patients Using a Smartphone Eye-Tracking App.

Introduction: Amyotrophic lateral sclerosis (ALS) can affect various eye movements, making eye tracking a potential means for disease monitoring. In this study, we evaluated the feasibility of ALS patients self-recording their eye movements using the "EyePhone," a smartphone eye-tracking application. Methods: We prospectively enrolled ten participants and provided them with an iPhone equipped with the EyePhone app and a PowerPoint presentation with step-by-step recording instructions. The goal was for the participants to record their eye movements (saccades and smooth pursuit) without the help of the study team. Afterward, a trained physician administered the same tests using video-oculography (VOG) goggles and asked the participants to complete a questionnaire regarding their self-recording experience. Results: All participants successfully completed the self-recording process without assistance from the study team. Questionnaire data indicated that participants viewed self-recording with EyePhone favorably, considering it easy and comfortable. Moreover, 70% indicated that they prefer self-recording to being recorded by VOG goggles. Conclusion: With proper instruction, ALS patients can effectively use the EyePhone to record their eye movements, potentially even in a home environment. These results demonstrate the potential for smartphone eye-tracking technology as a viable and self-administered tool for monitoring disease progression in ALS, reducing the need for frequent clinic visits.

The orthodontic research trends in Arab League Nations from 2002 to 2021: A bibliometric appraisal.

The evaluation of publication growth is a vital indicator to assess any branch of knowledge. The present study aimed to investigate the Scopus-indexed publications on orthodontics produced by the Arab League Nations in the last two decades (2002-2021). Quantitative research method based on bibliometric analysis has been used and the meta-data for the study was retrieved from Elsevier's Scopus database on November 14, 2022. The bibliographic description of all types of literature published on orthodontics from 2002 to 2021 by the authors affiliated with the Arab countries has been downloaded. The selected bibliometric indicators of the data were analyzed by using Microsoft Excel, VOSviewer and SPSS software. The Arab League Nations contributed 5.02 % to global orthodontic research. This segment has demonstrated an amazing escalation of documents from a global perspective between 2002 and 2021 from 1.24 % to 10.94 %. Slightly more than 60 % of documents were published during the last five years of study (2017-2021). The highest number of documents (41 %) was produced by Saudi Arabia, whereas documents contributed by Jordan gained the maximum citation impact. The majority of collaboration was done with the United States, but documents produced in collaboration with Turkey gained the highest citation impact. The paper highlighted that the share of Arab League Nations in orthodontic research has been growing, and Saudi Arabia emerged as the most productive country. The constructive evolution of orthodontic literature with international collaboration display an ambitious approach by Arab countries.

Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.

Surgical Stone Trends from 2013 to 2021 in the US Medicare Population: Before and after the COVID-19 Pandemic.

Introduction and Objective: In early 2020, as the SARS-Cov-2 (COVID-19) pandemic progressed, many institutions limited nonurgent surgical care. This coincided with a decade-long trend of increasing percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS) and decreasing shock wave lithotripsy (SWL) for surgical management of urolithiasis. Herein, we evaluate temporal stone surgery rates and surgeon volumes in the Medicare population and suggest how COVID-19 contributed to them. Methods: Retrospective analysis was conducted using the "Medicare Physician & Other Practitioners" database containing data from January 2013 to December 2021. Adult patients who underwent stone surgery were included. We evaluated surgeon characteristics and changes in case volumes over time adjusted for population. Results: In 2013, urologists performed 68,910 stone surgeries: SWL 42,903 (62%); URS 25,321 (37%); PCNL 686 (1%). Over the next 8 years, there was an average annual increase in URS (+13%) and PCNL (+13%) and decrease in SWL (-2%). In 2020, there was a 14% reduction in all stone cases: SWL (-25%); URS (-6%); PCNL (-8%). By 2021, case volumes recovered to pre-2020 levels, though SWL remained low: SWL 33,974 (34%); URS 64,541 (64%); PCNL 1764 (2%). From 2013 to 2021, the number of urologists performing SWL decreased (1718 to 1361) while URS and PCNL providers doubled (1,347 to 2,914 and 28 to 76, respectively). Conclusions: From 2013 to 2021, there was an increase in URS and PCNL and a decrease in SWL in the US Medicare population. The COVID-19 pandemic was associated with a decline in stone surgeries, particularly SWL. By 2021, PCNL and URS case numbers increased significantly with a smaller increase in SWL.

Frankincense: A neuronutrient to approach Parkinson's disease treatment.

Parkinson's disease (PD), characterized by tremor, slowness of movement, stiffness, and poor balance, is due to a significant loss of dopaminergic neurons in the substantia nigra pars compacta and dopaminergic nerve terminals in the striatum with deficit of dopamine. To date the mechanisms sustaining PD pathogenesis are under investigation; however, a solid body of experimental evidence involves neuroinflammation, mitochondrial dysfunction, oxidative stress, and apoptotic cell death as the crucial factors operating in the pathogenesis of PD. Nutrition is known to modulate neuroinflammatory processes implicated in the pathogenesis and progression of this neurodegenerative disorder. Consistent with this notion, the Burseraceae family, which includes the genera Boswellia and Commiphora, are attracting emerging interest in the treatment of a wide range of pathological conditions, including neuroinflammation and cognitive decline. Bioactive components present in these species have been shown to improve cognitive function and to protect neurons from degeneration in in vitro, animal, as well as clinical research. These effects are mediated through the anti-inflammatory, antiamyloidogenic, anti-apoptotic, and antioxidative properties of bioactive components. Although many studies have exploited possible therapeutic approaches, data from human studies are lacking and their neuroprotective potential makes them a promising option for preventing and treating major neurodegenerative disorders.