Insular operculum disconnection and herniation into the parapharyngeal space due to a fetal Galassi Type III arachnoid cyst: a case report.

Arachnoid cysts (ACs) are frequently encountered as incidental findings in the brain, with most cases being asymptomatic and not requiring intervention. However, severe brain malformations caused by ACs are rare. In this study, we describe the case of an 8-day-old female infant with a left mandibular mass that was diagnosed as an insular operculum, which has become disconnected and herniated into the parapharyngeal space through an incompletely ossified greater wing of the sphenoid, caused by a fetal Galassi Type III AC. The newborn also exhibited left hearing impairment, which did not improve at the 6-month follow-up after the cyst peritoneal shunt. This report highlights that ACs that manifest during the early fetal period may protrude from the cranial cavity through an unossified skull, potentially affecting the development of brain tissues.

Effect of High-Voltage Electrostatic Precipitator Dust Collection Plate Structure on Collection Efficiency.

To investigate the effect of changes in the dust collector structure on the flow field and electric field distribution resulting from the secondary flow generated by the corona discharge in the collector coupled with the main flow and to improve the dust collection efficiency of the ESP, a folding plate design has been adopted. A multiphysics-coupled corona discharge and flow field numerical model was analyzed to analyze the internal flow and electric field characteristics of linear flat plates and folded plates with three different pole configurations. The study indicates that the dust collecting plate's structure significantly affects the dust collector's internal flow field and electric field distribution within the dust collector. The near-plate electric field and flow field inside the folded plate type are superior to those of the linear flat electrostatic precipitator. With the augmentation of the inlet velocity, the ionic wind disturbance on the flow field inside the electrostatic precipitator channel gradually decreases. Additionally, the folding plate has a certain inhibitory effect on the influence of the ionic wind. At an inlet velocity of 0.5 m/s, the speed near the folding plate is approximately 20% lower than that of the traditional linear flat plate. The folding plate can effectively reduce the flow velocity near the dust collection plate, thereby reducing the occurrence of particle re-entrainment and improving dust removal efficiency. By comparing the speed at the center line of the plate and near the plate, it is obvious that the speed of model B decreases significantly, and as the number of discharge electrodes increases, the speed decreases more obviously. At the same time, when the dust collection efficiency of the two models was compared, it was found that the working efficiency of the B model has been significantly improved, among which the B3 model has the best dust collection effect.

Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and cerebrovascular diseases: a meta-analysis of controlled clinical trials.

Objective: Evaluate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiovascular and cerebrovascular diseases. Methods: Articles of SGLT2i on cardiovascular and cerebrovascular diseases were searched. Two authors independently screened the literature, extracted the data, assessed the quality of the study and performed statistical analyses using Review Manager 5.4. Results: Random-effect model was used to merge the OR values, and the pooled effect showed that SGLT2i had significant preventive effects on cardiovascular death (OR=0.76, 95%CI 0.64 to 0.89), myocardial infarction (OR=0.90, 95%CI 0.84 to 0.96), heart failure (OR=0.69, 95%CI 0.64 to 0.74) and all-cause mortality (OR=0.65, 95%CI 0.58 to 0.73). Empagliflozin, dapagliflozin and canagliflozin all reduced the incidence of heart failure (OR=0.72, 95%CI 0.64 to 0.82; OR=0.56, 95%CI 0.39 to 0.80; OR=0.62, 95%CI 0.53 to 0.73), but only dapagliflozin displayed a favorable effect on inhibiting stroke (OR=0.78, 95%CI 0.63 to 0.98). SGLT2i could prevent stroke (OR=0.86, 95%CI 0.75 to 0.99), heart failure (OR=0.63, 95%CI 0.56 to 0.70) and all-cause mortality (OR=0.64, 95%CI 0.57 to 0.72) compared to DPP-4i. Furthermore, SGLT2i could reduce the incidence of heart failure (OR=0.72, 95%CI 0.67 to 0.77) and cardiovascular death (OR=0.72, 95%CI 0.54 to 0.95) in patients with high-risk factors. Conclusions: SGLT2i affects cardiovascular death, myocardial infarction, heart failure and all-cause mortality. Only dapagliflozin displayed a favorable effect on inhibiting stroke. SGLT2i could prevent stroke, heart failure and all-cause mortality compared to DPP-4i. In addition, SGLT2i significantly reduced the development of heart failure and cardiovascular death in patients with high-risk factors. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024532783.

Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.

In vitro models of the human blood-brain barrier (BBB) are increasingly used to develop therapeutics that can cross the BBB for treating diseases of the central nervous system. Here we report a meta-analysis of the make-up and properties of transwell and microfluidic models of the healthy BBB and of BBBs in glioblastoma, Alzheimer's disease, Parkinson's disease and inflammatory diseases. We found that the type of model, the culture method (static or dynamic), the cell types and cell ratios, and the biomaterials employed as extracellular matrix are all crucial to recapitulate the low permeability and high expression of tight-junction proteins of the BBB, and to obtain high trans-endothelial electrical resistance. Specifically, for models of the healthy BBB, the inclusion of endothelial cells and pericytes as well as physiological shear stresses (~10-20 dyne cm-2) are necessary, and when astrocytes are added, astrocytes or pericytes should outnumber endothelial cells. We expect this meta-analysis to facilitate the design of increasingly physiological models of the BBB.

The effects of dipeptidyl peptidase-4 inhibitors on cardiac structure and function using cardiac magnetic resonance: a meta-analysis of clinical studies.

Objective: The aim of the study was to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP4i) on cardiac structure and function by cardiac magnetic resonance (CMR). Research Methods & Procedures: Database including PubMed, Cochrane library, Embase and SinoMed for clinical studies of DPP4i on cardiac structure and function by CMR were searched. Two authors extracted the data and evaluated study quality independently. Mean difference (MD) or standardized MD and 95% confidence intervals (CI) were used for continuous variables. Review Manager 5.3 was used to performed the analysis. Results: Ten references (nine studies) were included in this meta-analysis. Most of the studies were assessed as well quality by the assessment of methodological quality. For clinical control studies, the merged MD values of △LVEF by fixed-effect model and the pooled effect size in favor of DPP4i was 1.55 (95% CI 0.35 to 2.74, P=0.01). Compared with positive control drugs, DPP4i can significantly improve the LVEF (MD=4.69, 95%CI=2.70 to 6.69), but no such change compared to placebo (MD=-0.20, 95%CI=-1.69 to 1.29). For single-arm studies and partial clinical control studies that reported LVEF values before and after DPP4i treatment, random-effect model was used to combine effect size due to a large heterogeneity (Chi2 = 11.26, P=0.02, I2 = 64%), and the pooled effect size in favor of DPP4i was 2.31 (95% CI 0.01 to 4.62, P=0.05). DPP4i significantly increased the Peak filling rate (PFR) without heterogeneity when the effect sizes of two single-arm studies were combined (MD=31.98, 95% CI 13.69 to 50.27, P=0.0006; heterogeneity test: Chi2 = 0.56, P=0.46, I2 = 0%). Conclusions: In summary, a possible benefit of DPP4i in cardiac function (as measured by CMR) was found, both including ventricular systolic function and diastolic function.

Transfer RNA acetylation regulates in vivo mammalian stress signaling.

Transfer RNA (tRNA) modifications are crucial for protein synthesis, but their position-specific physiological roles remain poorly understood. Here we investigate the impact of N4-acetylcytidine (ac4C), a highly conserved tRNA modification, using a Thumpd1 knockout mouse model. We find that loss of Thumpd1-dependent tRNA acetylation leads to reduced levels of tRNALeu, increased ribosome stalling, and activation of eIF2α phosphorylation. Thumpd1 knockout mice exhibit growth defects and sterility. Remarkably, concurrent knockout of Thumpd1 and the stress-sensing kinase Gcn2 causes penetrant postnatal lethality, indicating a critical genetic interaction. Our findings demonstrate that a modification restricted to a single position within type II cytosolic tRNAs can regulate ribosome-mediated stress signaling in mammalian organisms, with implications for our understanding of translation control as well as therapeutic interventions.

Cytokine-induced killer cells-mediated chlorin e6-loaded gold nanostars for targeted NIR imaging and immuno-photodynamic combination therapy for lung cancer.

Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activityin vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.

Alcohol consumption may be a risk factor for cerebrovascular stenosis in acute ischemic stroke and transient ischemic attack.

BACKGROUND: Atherosclerosis are well established risk factors for ischemic stroke, however the association between alcohol consumption and atherosclerosis is controversial. This study aims to explore the potential correlation between alcohol consumption and cerebral stenosis in patients with acute ischemic stroke and transient ischemic attack (TIA). METHODS: Nine hundreds and eighty-eight patients with first acute ischemic stroke attack or TIA were recruited retrospectively. Alcohol consumption was classified into five consumption categories (non-drinkers, occasional drinkers, < 140 g per week [mild drinkers], 140-279 g per week [moderate drinkers], ≥ 280 g per week [heavy drinkers]). Computed tomography angiography (CTA) and digital subtraction angiography (DSA) were utilized to assess the carotid and cerebral artery in all patients. Five-step scale for degree of stenosis was applied: normal (0, 0 points), mild (< 50%, 1 point), moderate (50-69%, 2 points), severe (70-99%, 3 points), and occlusion (100%, 4 points). RESULTS: The carotid and cerebral artery stenosis scores were positively correlated with moderate alcohol consumption (B = 1.695, P < 0.001). Compared with nondrinkers, moderate alcohol consumption had significant increasing risk of moderate carotid and cerebral artery stenosis (OR = 4.28, 95% CI: 1.47-12.49, P = 0.008) and severe stenosis (OR = 4.24, 95% CI: 1.55-11.64, P = 0.005) and occlusion (OR = 3.87, 95% CI: 1.65-9.06, P = 0.002). Compared with nondrinkers, heavy alcohol consumption patients had significant higher risk of carotid and cerebral artery occlusion (OR = 2.71, 95% CI: 1.36-5.41, P = 0.005). CONCLUSIONS: Higher alcohol consumption may associate with higher risk and more severity of carotid and cerebrovascular stenosis.

Analysis of factors affecting intraoperative hemorrhage during percutaneous nephrolithotomy and establishment of nomogram model.

Intraoperative hemorrhage is an important factor affecting intraoperative safety and postoperative patient recovery in percutaneous nephrolithotomy (PCNL). This study aimed to identify the factors that influence intraoperative hemorrhage during PCNL and develop a predictive nomogram model based on these factors.A total of 118 patients who underwent PCNL at the Department of Urology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2021 to September 2023 was included in this study. The patients were divided into a hemorrhage group (58 cases) and a control group (60 cases) based on the decrease in hemoglobin levels after surgery. The clinical data of all patients were collected, and both univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for intraoperative hemorrhage during PCNL. The independent risk factors were used to construct a nomogram model using R software. Additionally, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were utilized to evaluate the model.Multivariate logistic regression analysis revealed that diabetes, long operation time and low psoas muscle mass index (PMI) were independent risk factors for intraoperative hemorrhage during PCNL (P < 0.05). A nomogram model was developed incorporating these factors, and the areas under the ROC curve (AUCs) in the training set and validation set were 0.740 (95% CI: 0.637-0.843) and 0.742 (95% CI: 0.554-0.931), respectively. The calibration curve and Hosmer-Lemeshow test (P = 0.719) of the model proved that the model was well fitted and calibrated. The results of the DCA showed that the model had high value for clinical application.Diabetes, long operation time and low PMI were found to be independent risk factors for intraoperative hemorrhage during PCNL. The nomogram model based on these factors can be used to predict the risk of intraoperative hemorrhage, which is beneficial for perioperative intervention in high-risk groups to improve the safety of surgery and reduce the incidence of postoperative complications.

Magnetically modified bacteriophage-triggered ATP release activated EXPAR-CRISPR/Cas14a system for visual detection of Burkholderia pseudomallei.

Burkholderia pseudomallei, widely distributed in tropical and subtropical ecosystems, is capable of causing the fatal zoonotic disease melioidosis and exhibiting a global trend of dissemination. Rapid and sensitive detection of B. pseudomallei is essential for environmental monitoring as well as infection control. Here, we developed an innovative biosensor for quantitatively detecting B. pseudomallei relies on ATP released triggered by bacteriophage-induced bacteria lysis. The lytic bacteriophage vB_BpP_HN01, with high specificity, is employed alongside magnetic nanoparticles assembly to create a biological receptor, facilitating the capture and enrichment of viable target bacteria. Following a brief extraction and incubation process, the captured target undergoes rapid lysis to release contents including ATP. The EXPAR-CRISPR cascade reaction provides an efficient signal transduction and dual amplification module that allowing the generated ATP to guide the signal output as an activator, ultimately converting the target bacterial amount into a detectable fluorescence signal. The proposed bacteriophage affinity strategy exhibited superior performance for B. pseudomallei detection with a dynamic range from 10^2 to 10^7 CFU mL-1, and a LOD of 45 CFU mL-1 within 80 min. Moreover, with the output signal compatible across various monitoring methods, this work offers a robust assurance for rapid diagnosis and on-site environmental monitoring of B. pseudomallei.

Flexible scaffold-based cheminformatics approach for polypharmacological drug design.

Effective treatments for complex central nervous system (CNS) disorders require drugs with polypharmacology and multifunctionality, yet designing such drugs remains a challenge. Here, we present a flexible scaffold-based cheminformatics approach (FSCA) for the rational design of polypharmacological drugs. FSCA involves fitting a flexible scaffold to different receptors using different binding poses, as exemplified by IHCH-7179, which adopted a "bending-down" binding pose at 5-HT2AR to act as an antagonist and a "stretching-up" binding pose at 5-HT1AR to function as an agonist. IHCH-7179 demonstrated promising results in alleviating cognitive deficits and psychoactive symptoms in mice by blocking 5-HT2AR for psychoactive symptoms and activating 5-HT1AR to alleviate cognitive deficits. By analyzing aminergic receptor structures, we identified two featured motifs, the "agonist filter" and "conformation shaper," which determine ligand binding pose and predict activity at aminergic receptors. With these motifs, FSCA can be applied to the design of polypharmacological ligands at other receptors.

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis.

Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.

A POLR3B-variant reveals a Pol III transcriptome response dependent on La protein/SSB.

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B:c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B. Genome-edited POLR3B1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E. La protein was increased relative to its abundant pre-tRNA ligands which bind via their U(n)U-3'-termini. Assays for cellular transcription revealed greater deficiencies for tRNA genes bearing terminators comprised of 4Ts than of ≥5Ts. La-knockdown decreased Pol III ncRNA expression unlinked to RNA stability. Consistent with these effects, small-RNAseq showed that POLR3B1625A>G and patient fibroblasts express more tRNA fragments (tRFs) derived from pre-tRNA 3'-trailers (tRF-1) than from mature-tRFs, and higher levels of multiple miRNAs, relative to control cells. The data indicate that decreased levels of Pol III transcripts can lead to functional excess of La protein which reshapes small ncRNA profiles revealing new depth in the Pol III system. Finally, patient cell RNA analysis uncovered a strategy for tRF-1/tRF-3 as POLR3-deficiency biomarkers.

A Transcription Factor ZNF384, Regulated by LINC00265, Activates the Expression of IFI30 to Stimulate Malignant Progression in Glioma.

Glioma remains one of the most challenging primary brain malignancies to treat. Long noncoding RNAs (lncRNAs) and mRNAs (mRNAs) are implicated in regulating the malignant phenotypes of cancers including glioma. This study aimed to elucidate the functions and mechanisms of lncRNA LINC00265 and mRNA IFI30 in the pathogenesis of glioma. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis revealed the upregulated expression of LINC00265 and IFI30 in glioma cells compared to normal human astrocytes. Western blot (WB) quantified the associated proteins. Glioma stemness and epithelial-to-mesenchymal transition (EMT) were assessed by aldehyde dehydrogenase 1 (ALDH1) activity, sphere formation, and WB. Mechanistic and rescue assays evaluated the LINC00265/miR-let-7d-5p/IFI30/ZNF384/IGF2BP2 axis. The results demonstrated that LINC00265 and IFI30 were highly expressed in glioma cells, promoting stemness and EMT. ZNF384 was identified as a transcription factor that upregulates IFI30. Moreover, LINC00265 elevated ZNF384 by sponging miR-let-7d-5p and recruiting IGF2BP2. In conclusion, LINC00265 and IFI30 act as oncogenes in glioma by driving stemness and EMT, underscoring their potential as therapeutic targets.

Specifications of the ACMG/AMP Variant Classification Guidelines for Germline DICER1 Variant Curation.

Germline pathogenic variants in DICER1 predispose individuals to develop a variety of benign and malignant tumors. Accurate variant curation and classification is essential for reliable diagnosis of DICER1-related tumor predisposition and identification of individuals who may benefit from surveillance. Since 2015, most labs have followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) sequence variant classification guidelines for DICER1 germline variant curation. However, these general guidelines lack gene-specific nuances and leave room for subjectivity. Consequently, a group of DICER1 experts joined ClinGen to form the DICER1 and miRNA-Processing Genes Variant Curation Expert Panel (VCEP), to create DICER1- specific ACMG/AMP guidelines for germline variant curation. The VCEP followed the FDA-approved ClinGen protocol for adapting and piloting these guidelines. A diverse set of 40 DICER1 variants were selected for piloting, including 14 known Pathogenic/Likely Pathogenic (P/LP) variants, 12 known Benign/Likely Benign (B/LB) variants, and 14 variants classified as variants of uncertain significance (VUS) or with conflicting interpretations in ClinVar. Clinically meaningful classifications (i.e., P, LP, LB, or B) were achieved for 82.5% (33/40) of the pilot variants, with 100% concordance among the known P/LP and known B/LB variants. Half of the VUS or conflicting variants were resolved with four variants classified as LB and three as LP. These results demonstrate that the DICER1-specific guidelines for germline variant curation effectively classify known pathogenic and benign variants while reducing the frequency of uncertain classifications. Individuals and labs curating DICER1 variants should consider adopting this classification framework to encourage consistency and improve objectivity.

Frameless robot-assisted stereoelectroencephalography-guided radiofrequency: methodology, results, complications and stereotactic application accuracy in pediatric hypothalamic hamartomas.

Objective: We aimed to investigate the methodology, results, complications and stereotactic application accuracy of electrode implantation and its explanatory variables in stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) for pediatric hypothalamic hamartoma. Methods: Children with hypothalamic hamartoma who underwent robot-assisted SEEG-RFTC between December 2017 and November 2021 were retrospectively analyzed. The methodology, seizure outcome, complications, in vivo accuracy of electrode implantation and its explanatory variables were analyzed. Results: A total of 161 electrodes were implanted in 28 patients with 30 surgeries. Nine electrodes not following the planned trajectories due to intraoperative replanning were excluded, and the entry point and target point errors of 152 electrodes were statistically analyzed. The median entry point error was 0.87 mm (interquartile range, 0.50-1.41 mm), and the median target point error was 2.74 mm (interquartile range, 2.01-3.63 mm). Multifactor analysis showed that whether the electrode was bent (b = 2.16, p < 0.001), the length of the intracranial electrode (b = 0.02, p = 0.049), and the entry point error (b = 0.337, p = 0.017) had statistically significant effects on the target error. During follow-up (mean duration 31 months), 27 of 30 (90%) procedures were seizure-free. The implantation-related complication rate was 2.6% (4/152), and the major complication rate in all procedures was 6.7% (2/30). Conclusion: Robot-assisted SEEG-RFTC is a safe, effective and accurate procedure for pediatric hypothalamic hamartoma. Explanatory variables significantly associated with the target point localization error at multivariate analysis include whether the intracranial electrode is bent, the intracranial electrode length and the entry point error.

Synchronous detection of Burkholderia pseudomallei and its ceftazidime resistance mutation based on RNase-HII hydrolysis combined with lateral flow strip assay.

IMPORTANCE: This study focused on the development of a reaction system using rhPCR to amplify a specific gene, ORF2, of B. pseudomallei and to identify the P174L mutation associated with increased drug resistance to ceftazidime (CAZ). The system incorporated universal primer probes and a simple temperature cycle reaction. The amplified products were then analyzed using lateral flow strip assay (LFSA) for strain identification and mutation interpretation. The developed system provides a reliable basis for diagnosing melioidosis and selecting appropriate drugs. Its potential impact is particularly significant in resource-limited settings where access to advanced diagnostic techniques is limited. This platform stands out for its simplicity, convenience, sensitivity, specificity, and portability. It shows promise as a point-of-care testing method for detecting single nucleotide polymorphism in genes associated with other diseases. By leveraging the advantages of this platform, researchers and healthcare professionals can potentially expand its use beyond melioidosis and apply it to the rapid detection of genetic variations in other disease-related genes.

Association between SCN1A polymorphism and risk of epilepsy in children: A systematic review and meta-analysis.

Epilepsy is a common neurological disorder in children. Numerous studies have demonstrated the association between SCN1A polymorphisms and risk of epilepsy in adults, but their role in epilepsy in children has just gained traction and results have remained inconsistent. In this work, we performed a systematic review and meta-analysis to assess the association between SCN1A polymorphisms and risk for epilepsy in children. A systematic literature search was performed in PubMed, Scopus, Web of Science, China National Knowledge Internet, Wanfang and VIP databases to identify eligible studies up to June 2023. Quantitative data synthesis was then performed under five genetic models: dominant, recessive, homozygous, heterozygous, and allele. Five studies involving 1380 subjects were included in the meta-analysis. Among many SCN1A polymorphisms reported, only rs2298771 was repeatedly studied in these reports. Pooled analysis demonstrated that there was no significant association between the polymorphism and risk of epilepsy in children (P>0.05). In conclusion, SCN1A rs2298771 polymorphism was not significantly associated with the risk of epilepsy in children.

Mining electronic health records using artificial intelligence: Bibliometric and content analyses for current research status and product conversion.

BACKGROUND: The use of Electronic Health Records is the most important milestone in the digitization and intelligence of the entire medical industry. AI can effectively mine the immense medical information contained in EHRs, potentially assist doctors in reducing many medical errors. OBJECTIVE: This article aims to summarize the research status and trends in using AI to mine medical information from EHRs for the past thirteen years and investigate its information application. METHODS: A systematic search was carried out in 5 databases, including Web of Science Core Collection and PubMed, to identify research using AI to mine medical information from EHRs for the past thirteen years. Furthermore, bibliometric and content analysis were used to explore the research hotspots and trends, and systematically analyze the conversion rate of research resources in this field. RESULTS: A total of 631 articles were included and analyzed. The number of published articles has increased rapidly after 2017, with an average annual growth rate of 55.73%. The US (41.68%) and China (19.65%) publish the most articles, but there is a lack of international cooperation. The extraction of disease lesions is a hot topic at present, and the research topic is gradually shifting from disease risk grading to disease risk prediction. Classification (66%), and regress (15%) are the main implemented AI tasks. For AI algorithms, deep learning (31.70%), decision tree algorithms family (26.47%), and regression algorithms family (17.43%) are used most frequently. The funding rate for publications is 69.26%, and the input-output conversion rate is 21.05%. CONCLUSIONS: Over the past decade, the use of AI to mine medical information from EHRs has been developing rapidly. However, it is necessary to strengthen international cooperation, improve EHRs data availability, focus on interpretable AI algorithms, and improve the resource conversion rate in future research.

Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase.

The dual functions of TMEM16F as Ca2+-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca2+-activated Cl- channel. Here, we report evidence for a lipid scrambling pathway along a groove harboring a lipid trail outside the ion permeation pore. This groove contains the binding pocket for niclosamide and 1PBC. Mutations of two residues in this groove specifically affect lipid scrambling. Whereas mutations of some residues in the binding pocket of niclosamide and 1PBC reduce their inhibition of TMEM16F-mediated Ca2+ influx and PS exposure, other mutations preferentially affect the ability of niclosamide and/or 1PBC to inhibit TMEM16F-mediated PS exposure, providing further support for separate pathways for ion permeation and lipid scrambling.