Global daily mask use estimation in the pandemic and its post environmental health risks: Analysis based on a validated dynamic mathematical model.

The outbreak of the COVID-19 pandemic led to a sharp increase in disposable surgical mask usage. Discarded masks can release microplastic and cause environmental pollution. Since masks have become a daily necessity for protection against virus infections, it is necessary to review the usage and disposal of masks during the pandemic for future management. In this study, we constructed a dynamic model by introducing related parameters to estimate daily mask usage in 214 countries from January 22, 2020 to July 31, 2022. And we validated the accuracy of our model by establishing a dataset based on published survey data. Our results show that the cumulative mask usage has reached 800 billion worldwide, and the microplastics released from discarded masks due to mismanagement account for 3.27% of global marine microplastic emissions in this period. Furthermore, we illustrated the response relationship between mask usage and the infection rates. We found a marginally significant negative correlation existing between the mean daily per capita mask usage and the rate of cumulative confirmed cases within the range of 25% to 50%. This indicates that if the rate reaches the specified threshold, the preventive effect of masks may become evident.

Genome­wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan.

Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome­wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)­R software and chi­square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome­wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5x10­8, located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA­A*02:07 and HLA­C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta­analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

GCTNet: a graph convolutional transformer network for major depressive disorder detection based on EEG signals.

OBJECTIVE: Identifying major depressive disorder (MDD) using objective physiological signals has become a pressing challenge. APPROACH: Hence, this paper proposes a graph convolutional transformer network (GCTNet) for accurate and reliable MDD detection using electroencephalogram (EEG) signals. The developed framework integrates a residual graph convolutional network (ResGCN) block to capture spatial information and a Transformer block to extract global temporal dynamics. Additionally, we introduce the contrastive cross-entropy (CCE) loss that combines contrastive learning to enhance the stability and discriminability of the extracted features, thereby improving classification performance. MAIN RESULTS: The effectiveness of the GCTNet model and CCE loss was assessed using EEG data from 41 MDD patients and 44 normal controls (NC), in addition to a publicly available dataset. Utilizing a subject-independent data partitioning method and 10-fold cross-validation, the proposed method demonstrated significant performance, achieving an average Area Under the Curve (AUC) of 0.7693 and 0.9755 across both datasets, respectively. Comparative analyses demonstrated the superiority of the GCTNet framework with CCE loss over state-of-the-art algorithms in MDD detection tasks. SIGNIFICANCE: The proposed method offers an objective and effective approach to MDD detection, providing valuable support for clinical-assisted diagnosis.

Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics.

BACKGROUND: Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. METHODS: We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. RESULTS: In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. CONCLUSIONS: We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.

Early Therapeutic Drug Monitoring Optimizes Teicoplanin Use in Febrile Neutropenic Patients with Hematological Malignancies.

INTRODUCTION: A target trough concentration (Cmin) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. METHODS: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. RESULTS: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018). CONCLUSIONS: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.

Exploring the flavor changes in mung bean flour through Lactobacillus fermentation: insights from volatile compounds and non-targeted metabolomics analysis.

BACKGROUND: Mung beans are highly nutritious but their leguminous flavor limits their development. Lactic acid bacteria (LAB) fermentation can decrease unwanted bean flavors in legumes and enhance their flavor. This study examined the influence of Lactobacillus fermentation on the flavor characteristics of mung bean flour (MBF) using volatile compounds and non-targeted metabolomics. RESULTS: Lactobacillus plantarum LP90, Lactobacillus casei LC89, and Lactobacillus acidophilus LA85 eliminated 61.37%, 48.29%, and 43.73%, respectively, of the primary bean odor aldehydes from MBF. The relative odor activity value (ROAV) results showed that fermented mung bean flour (FMBF) included volatile chemicals that contributed to fruity, flowery, and milky aromas. These compounds included ethyl acetate, hexyl formate, 3-hydroxy-2-butanone, and 2,3-butanedione. The levels of amino acids with a fresh sweet flavor increased significantly by 93.89, 49.40, and 35.27% in LP90, LC89, and LA85, respectively. A total of 49 up-regulated and 13 down-regulated significantly differential metabolites were annotated, and ten metabolic pathways were screened for contributing to the flavor. The correlation between important volatile compounds and non-volatile substances relies on two primary metabolic pathways: the citric acid cycle pathway and the amino acid metabolic system. CONCLUSION: The flavor of MBF was enhanced strongly by the process of Lactobacillus fermentation, with LP90 having the most notable impact. These results serve as a reference for identifying the flavor of FMBF. © 2024 Society of Chemical Industry.

Effect of astrocyte GPER on the optic nerve inflammatory response following optic nerve injury in mice.

Activated astrocytes are a primary source of inflammatory factors following traumatic optic neuropathy (TON). Accumulation of inflammatory factors in this context leads to increased axonal damage and loss of retinal ganglion cells (RGCs). Therefore, in the present study, we explored the role of the astrocyte G protein-coupled estrogen receptor (GPER) in regulating inflammatory factors following optic nerve crush (ONC), and analyzed its potential regulatory mechanisms. Overall, our results showed that GPER was abundantly expressed in the optic nerve, and co-localized with glial fibrillary acidic proteins (GFAP). Exogenous administration of G-1 led to a significant reduction in astrocyte activation and expression of inflammation-related factors (including IL-1ß, TNF-α, NFκB, and p-NFκB). Additionally, it dramatically increased the survival of RGCs. In contrast, astrocytes were activated to a greater extent by exogenous G15 administration; however, RGCs survival was significantly reduced. In vitro, GPER activation significantly reduced astrocyte activation and the release of inflammation-related factors. In conclusion, activation of astrocyte GPER significantly reduced ONC inflammation levels, and should be explored as a potential target pathway for protecting the optic nerve and RGCs after TON.

Surface Crystallization Enhancement and Defect Passivation for Efficiency and Stability Enhancement of Inverted Wide-Bandgap Perovskite Solar Cells.

Wide-bandgap (WBG) inverted perovskite solar cells (PSCs) are used as the top cell for tandem solar cells, which is an effective way to outperform the Shockley-Queisser limit. However, the low efficiency and poor phase stability still seriously restrict the application of WBG inverted PSCs. Here, the surface of the WBG perovskite film was passivated by the synthesized 1,2,4-tris(3-thienyl)benzene (THB). The THB size well matches with the halogen ion vacancy on the perovskite surface, and the S atom in THB can strongly interact with Pb2+ on the surface of the WBG perovskite film to the greatest extent, which effectively passivates surface defects and suppresses the recombination of carriers caused by these defects. At the same time, the S atom in THB occupied the migration site of the halogen ions, which inhibits the migration of halogen ions. Due to the strong conjugation effect and stability of THB, it can be locked on the surface of perovskite to increase the lattice strength and inhibit the segregation of photoinduced halide, thus improving the performance and operational stability of PSCs. The THB-modified WBG (Eg = 1.71 eV) PSC achieves a maximum power conversion efficiency of 20.75%, and its 99.0% is retained after 1512 h at a relative humidity of 10-25%. Under the irradiation of 1000 lx LED light, the indoor power conversion efficiency of the THB-modified WBG PSC reaches 34.15%.

A web-based dynamic predictive model for postoperative nausea and vomiting in patient receiving gynecological laparoscopic surgery.

OBJECTIVE: The aim of this study was to develop a web-based dynamic prediction model for postoperative nausea and vomiting (PONV) in patients undergoing gynecologic laparoscopic surgery. METHODS: The patients (N = 647) undergoing gynecologic laparoscopic surgery were included in this observational study. The candidate risk-factors related to PONV were included through literature search. Lasso regression was utilized to screen candidate risk-factors, and the variables with statistical significance were selected in multivariable logistic model building. The web-based dynamic Nomogram was used for model exhibition. Accuracy and validity of the experimental model (EM) were evaluated by generating receiver operating characteristic (ROC) curves and calibration curves. Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model. Decision curve analysis (DCA) was used to evaluate the clinical practicability of the risk prediction model. RESULTS: Ultimately, a total of five predictors including patient-controlled analgesia (odds ratio [OR], 4.78; 95% confidence interval [CI], 1.98-12.44), motion sickness (OR, 4.80; 95% CI, 2.71-8.65), variation of blood pressure (OR, 4.30; 95% CI, 2.41-7.91), pregnancy vomiting history (OR, 2.21; 95% CI, 1.44-3.43), and pain response (OR, 1.64; 95% CI, 1.48-1.83) were selected in model building. Assessment of the model indicates the discriminating power of EM was adequate (ROC-areas under the curve, 93.0%; 95% CI, 90.7%-95.3%). EM showed better accuracy and goodness of fit based on the results of the calibration curve. The DCA curve of EM showed favorable clinical benefits. CONCLUSIONS: This dynamic prediction model can determine the PONV risk in patients undergoing gynecologic laparoscopic surgery.

Hypoxic microenvironment-induced exosomes confer temozolomide resistance in glioma through transfer of pyruvate kinase M2.

OBJECTIVE: Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ. METHODS: Sensitive and TMZ-resistant glioma cells were subjected to either a normoxic or hypoxic environment, and the growth patterns and enzymatic activity of glycolysis enzymes were subsequently measured. From these cells, exosomal PKM2 was isolated and the subsequent effect on TMZ resistance was examined and characterized, with a particular focus on understanding the relevant mechanisms. Furthermore, the intercellular communication between hypoxic resistant cells and tumor-associated macrophages (TAMs) via exosomal PKM2 was also assessed. RESULTS: The adverse impact of hypoxic microenvironments on TMZ resistance in glioma cells was identified and characterized. Among the three glycolysis enzymes that were examined, PKM2 was found to be a critical mediator in hypoxia-triggered TMZ resistance. Upregulation of PKM2 was found to exacerbate the hypoxia-mediated TMZ resistance. Exosomal PKM2 were identified and isolated from hypoxic TMZ-resistant glioma cells, and were found to be responsible for transmitting TMZ resistance to sensitive glioma cells. The exosomal PKM2 also contributed towards mitigating TMZ-induced apoptosis in sensitive glioma cells, while also causing intracellular ROS accumulation. Additionally, hypoxic resistant cells also released exosomal PKM2, which facilitated TMZ resistance in tumor-associated macrophages. CONCLUSION: In the hypoxic microenvironment, glioma cells become resistant to TMZ due to the delivery of PKM2 by exosomes. Targeted modulation of exosomal PKM2 may be a promising strategy for overcoming TMZ resistance in glioma.

Relationship between syncopal symptoms and head-up tilt test modes.

OBJECTIVE: Head-up tilt test (HUTT) is an important tool in the diagnosis of pediatric vasovagal syncope. This research will explore the relationship between syncopal symptoms and HUTT modes in pediatric vasovagal syncope. METHODS: A retrospective analysis was performed on the clinical data of 2513 children aged 3-18 years, who were diagnosed with vasovagal syncope, from Jan. 2001 to Dec. 2021 due to unexplained syncope or pre-syncope. The average age was 11.76 ± 2.83 years, including 1124 males and 1389 females. The patients were divided into the basic head-up tilt test (BHUT) group (596 patients) and the sublingual nitroglycerine head-up tilt test (SNHUT) group (1917 patients) according to the mode of positive HUTT at the time of confirmed pediatric vasovagal syncope. RESULTS: (1) Baseline characteristics: Age, height, weight, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and composition ratio of syncope at baseline status were higher in the BHUT group than in the SNHUT group (all P < 0.05). (2) Univariate analysis: Age, height, weight, HR, SBP, DBP, and syncope were potential risk factors for BHUT positive (all P < 0.05). (3) Multivariate analysis: syncope was an independent risk factor for BHUT positive, with a probability increase of 121% compared to pre-syncope (P<0.001). CONCLUSION: The probability of BHUT positivity was significantly higher than SNHUT in pediatric vasovagal syncope with previous syncopal episodes.

Musculoskeletal Organs-on-Chips: An Emerging Platform for Studying the Nanotechnology-Biology Interface.

Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology-biology interactions. This review first covers recent advances and applications of MSK OoCs and their ability to mimic the biophysical and biochemical stimuli encountered by MSK tissues. Next, by integrating nanotechnology into MSK OoCs, cellular responses and tissue behaviors may be investigated by precisely controlling and manipulating the nanoscale environment. Analysis of MSK disease mechanisms, particularly bone, joint, and muscle tissue degeneration, and drug screening and development of personalized medicine may be greatly facilitated using MSK OoCs. Finally, future challenges and directions are outlined for the field, including advanced sensing technologies, integration of immune-active components, and enhancement of biomimetic functionality. By highlighting the emerging applications of MSK OoCs, this review aims to advance the understanding of the intricate nanotechnology-MSK biology interface and its significance in MSK disease management, and the development of innovative and personalized therapeutic and interventional strategies.

Direct aqueous photochemistry of methylglyoxal and its effect on sulfate formation.

In recent years, among many oxidation pathways studied for atmospheric sulfate formation, the aqueous phase oxidation pathways of H2O2 and organic hydroperoxides (ROOHs) have attracted great scientific attention. Higher concentrations of H2O2 and ubiquitous ROOHs have been observed in atmospheric aqueous phase environments (cloud water, fog droplets, etc.). However, there are still some gaps in the study of their aqueous phase generation and their influences on sulfate formation. In this study, the aqueous phase photochemical reaction of methylglyoxal, a ubiquitous organic substance in the atmospheric aqueous phase, was studied under UV irradiation, and the generation of H2O2 and ROOHs in this system was investigated. It is found for the first time that the aqueous phase photolysis of methylglyoxal not only produces H2O2 but also produces ROOHs, and UV light and O2 are necessary for the formation of H2O2 and ROOHs. Based on the experimental results, the possible mechanism of aqueous phase photochemistry of methylglyoxal and the generation of H2O2 and ROOHs were proposed. The effect of aqueous phase photolysis of methylglyoxal on sulfate formation under different conditions was also investigated. The results show that the aqueous phase photolysis of methylglyoxal significantly promoted SO2 oxidation and sulfate formation, in which SO2 oxidation was realized by the generated H2O2, ROOHs and •OH radicals, and the importance of the formed ROOHs cannot be ignored. These results fill some gaps in the field of aqueous phase H2O2 and ROOHs production, and to a certain extent confirm the important roles of the aqueous phase photolysis of methylglyoxal and the formed H2O2 and ROOHs in the production of sulfate. The study reveals the new sources of H2O2 and ROOHs, and provides a new insight into the heterogeneous aqueous phase oxidation pathways and mechanisms of SO2 in cloud and fog droplets and haze particles.

Boryl Ancillary Ligands: Influencing Stability and Reactivity of Amidinato-Silanone and Germanone Systems in Ammonia Activation.

While the nucleophilic addition of ammonia to ketones is an archetypal reaction in classical organic chemistry, the reactivity of heavier group 14 carbonyl analogues (R2E=O; E=Si, Ge, Sn, or Pb) with NH3 remains sparsely investigated, primarily due to the synthetic difficulties in accessing heavier ketone congeners. Herein, we present a room-temperature stable boryl-substituted amidinato-silanone {(HCDippN)2B}{PhC(tBuN)2}Si=O (Dipp=2,6-iPr2C6H3) (together with its germanone analogue), formed from the corresponding silylene under a N2O atmosphere. This system reacts cleanly with ammonia in 1,2-fashion to give an isolable sila-hemiaminal complex {(HCDippN)2B}{PhC(tBuN)2}Si(OH)(NH2). Quantum chemical calculations reveal that the formation of this sila-hemiaminal is crucially dependent on the nature of the ancillary ligand scaffold. It is facilitated thermodynamically by the hemi-lability of the amidinate ligand (which allows for the formation of an energetically critical intramolecular N⋅⋅⋅HO hydrogen bond within the product) and is enabled mech-anistically by a process in which the silanone initially acts in umpolung fashion as a base (rather than an acid), due to the strongly electron-releasing and sterically bulky nature of the ancillary boryl ligand.

Genetic susceptibility to prostate cancer in Taiwan: A genome-wide association study.

We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × 10-8 ). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36-1.76, p = 5.30 × 10-11 ; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31-1.51), p = 8.77 × 10-21 ; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16-1.35), p = 2.14 × 10-8 . We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10-43 , and rs1456315 (inside PRNCR1), p = 4.33 × 10-42 . We confirmed 35 out of 49 GWAS-identified East Asian PCa susceptibility SNPs. In addition, we identified two SNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver-operating characteristic curve for the GRS to predict PCa was 0.67 (95% CI, 0.63-0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence.

Optimization of stereotactic radiotherapy (SRT) planning for brain metastases from lung cancer by Cyberknife system: reducing dose distribution inner ear.

Objective: Through retrospective statistical analysis of radiation distribution in inner ear avoidance for brain metastases from lung cancer by the CyberKnife (CK) system, it can provide a reference for stereotactic radiotherapy (SRT) planning and treatment optimization. Methods: Computed tomography/magnetic resonance imaging data of 44 patients with one brain metastases lesion from lung cancer were used to re-plan and analyze, who had been treated by CK system from April 2021 to April 2022. The prescribed doses of 14-30 Gy in 1-3 fractions was simultaneously delivered to the metastatic lesions. The SRT plans for the same patients were replaned under with and without inner ear avoidance setting. The plan parameters and dose distribution differences were compared between plans. Results: All plans met the dose restrictions. There were no significant differences in the coverage (Coverage), conformity index (CI), mean dose (Dmean), the maximum dose (Dmax) and minimum dose (Dmin) of planning target volume (PTV). With inner ear avoidance setting, the Dmax and Dmean of inner ear area decreased by 13.76% and 12.15% (p<0.01), respectively. The total number of machine nodes and monitor units (MU) increased by 4.63% and 1.06%. Conclusions: During the SRT plan designing for brain metastases from lung cancer, the dose distribution in inner ear area could be reduced by avoidance setting, and the patient's hearing would be well protected.

Innate immune responsive inflammation in development of progressive myopia.

PURPOSE: Inflammation has been implicated for development of myopia. It is not clear when inflammation is kicked in during the course of myopia, and what characteristics of the inflammation. In this study, we tested for cytokines from aqueous humour of eyes with wide spectrum of refractive status for profiling the inflammation. METHODS: Aqueous humour of 142 patient eyes were tested for soluble intercellular adhesion molecule 1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta 2 (TGF-ß2) using an enzyme-linked immunosorbent assay (ELISA). Eye globe axial length of these patients ranged from emmetropia to high myopia. RESULTS: Of 142 patients, an average axial length is 25.51 ± 3.31 mm, with a range of 21.56-34.37 mm. There are 36 cases in lower 25 percentile, 37 cases in upper 25 percentile, and 69 case in the middle 50 percentile. sICAM-1 and MCP-1 were significantly higher in the eyes with staphyloma (407.48 pg/mL, 312.31 pg/mL, n = 33) or macular schisis (445.86 pg/mL,345.33 pg/mL, n = 19) than that in the eyes without these changes (206.44 pg/mL, 244.76 pg/mL, n = 107). All three cytokines level was significantly associated with eye globe axial in a positive mode while adjusting for the age and sex. Strength of the association was the greatest for sICAM-1 and the weakest for TGF- ß2. MCP-1 was in between. CONCLUSION: sICAM-1 and MCP-1 in ocular fluid may be indicative biomarkers for progressive high myopia and the underneath autoimmune inflammation. sICAM-1 may be used as a monitoring biomarker for development of pathologic myopia.

The association between patent foramen ovale and unexplained syncope in pediatric patients.

BACKGROUND: Patent foramen ovale (PFO) is associated with transient ischemia attack (TIA) or stroke, paradoxical embolism, and migraines. PFO closure decreases the recurrent incidence of cerebral ischemic events and reduces the incidence of syncope in adults. However, whether PFO is associated with syncope in pediatric patients has not been investigated. METHODS: 1001 pediatric patients (aged 4 to 17 years, mean age 10.31 ± 2.61 years, 519 males) who complained of unexplained syncope, palpitation, headache, dizziness and chest pain and were hospitalized in the Syncope Ward, The Second Xiangya Hospital, Central South University between January 2013 and April 2022 were recruited. Children with definite etiology of syncope, neurological, cardiogenic, psychological and other system diseases were excluded. PFO was measured by transthoracic echocardiography and right-heart contrast echocardiography was performed to identify the presence of right-to-left shunting. The demographic data and medical records were retrospectively reviewed and analyzed. RESULTS: 276 cases were included in the simple syncope group, 379 cases in the headache/dizziness group, 265 cases in the chest pain group, and 81 cases in the palpitation group. The incidence of PFO between the four groups was insignificant (4.71%, 4.74%, 4.15%, 6.17%, respectively, P = 0.903). Multivariate Logistic regression demonstrated that PFO is not associated with the increased risk of syncope (P = 0.081). CONCLUSION: PFO may not increase the risk of syncope in pediatric patients. Further study may include a large and multicenter sample to investigate the association between PFO and unexplained syncope.

The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases.

Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA1*03:02 - HLA-DQB1*03:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10-14), corresponding to HLA-DQA1 Asp160 and HLA-DQB1 Leu87 amino acid residues. The genetic correlation showed significance between IgE and allergic diseases including asthma, atopic dermatitis, and pollinosis. IgE PRS was significantly correlated with total IgE levels. Furthermore, the top decile IgE polygenic risk score (PRS) group had the highest risk of asthma for the Taiwan Biobank and Biobank Japan cohorts. IgE PRS may be used to aid in predicting the occurrence of allergic reactions before symptoms occur and biomarkers are detectable. Our study provided a more comprehensive understanding of the impact of genomic variants, including complex HLA alleles, on serum IgE levels.