Methods: Patients diagnosed with cervical degenerative spondylolisthesis were identified from a hospital’s medical records. Demographic and surgical characteristics were collected through a structured query language search and manual chart review. Radiographic measurements were made on preoperative MRIs for all vertebral levels diagnosed with spondylolisthesis and adjacent undiagnosed levels between C3 and C6. The facet fluid index was calculated by dividing the facet fluid measurement by the width of the facet. Bivariate analysis was conducted to compare facet characteristics based on radiographic spondylolisthesis and spondylolisthesis stability. Results: We included 154 patients, for whom 149 levels were classified as having spondylolisthesis and 206 levels did not. The average facet fluid index was significantly higher in patients with spondylolisthesis (0.26±0.07 vs. 0.23±0.08, p <0.001). In addition, both fluid width and facet width were significantly larger in patients with spondylolisthesis (p <0.001 each). Cervical levels in the fusion construct demonstrated a greater facet fluid index and were more likely to have unstable spondylolisthesis than stable spondylolisthesis (p <0.001 each). Conclusions Facet fluid index is associated with cervical spondylolisthesis and an increased facet size and fluid width are associated with unstable spondylolisthesis. While cervical spondylolisthesis continues to be an inconclusive finding, vertebral levels with spondylolisthesis, especially the unstable ones, were more likely to be included in the fusion procedure than those without spondylolisthesis.

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

INTRODUCTION: The impact of sex and diabetes mellitus (DM) on patients with heart failure with mildly reduced ejection fraction (HFmrEF) is not well elucidated. This study aims to evaluate sex differences in the clinical profile and outcomes in Asian HFmrEF patients with and without DM. METHODS: Patients admitted nationally for HFmrEF (ejection fraction 40-49%) between 2008 and 2014 were included and followed up until December 2016. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular (CV) death and/or heart failure (HF) rehospitalisations. RESULTS: A total of 2,272 HFmrEF patients (56% male) were included. More women had DM than men (60% versus 55%, P=0.013). Regardless of DM status, HFmrEF females were older, less likely to smoke, had less coronary artery disease, narrower QRS and lower haemoglobin compared to men. The odds of having DM decreases in smokers who are women as opposed to men (P_interaction =0.017). In multivariate analysis, DM reached statistical analysis for all-cause mortality and combined CV mortality or HF rehospitalisation in both men and women. However, the results suggest that there may be sex differences in terms of outcomes. DM (vs non-DM) was less strongly associated with increased all-cause mortality (adjusted hazards ratio [adj HR] 1.234 vs adj HR 1.290, P_interaction <0.001] but more strongly associated with the combined CV death/HF rehospitalisation (adj HR 1.429 vs adj HR 1.317, P_interaction =0.027) in women (vs men). CONCLUSION Asian women with HFmrEF had a higher prevalence of DM, with differences in clinical characteristics, compared to men. While diabetes conferred poor outcomes regardless of sex, there were distinct sex differences. These highlight the need for sex-specific management strategies.
Diabetes Mellitus/epidemiology* ; Female ; Heart Failure ; Humans ; Male ; Prognosis ; Stroke Volume ; Ventricular Dysfunction, Left/epidemiology* ; Ventricular Function, Left

Background: Conventional modality requires several days observation by Holter monitor to differentiate atrial fibril‑ lation (AF) between Paroxysmal atrial fibrillation (PAF) and Non-paroxysmal atrial fibrillation (Non-PAF). Rapid and practical differentiating approach is needed. Objective: To develop a machine learning model that observes 10-s of standard 12-lead electrocardiograph (ECG) for real-time classification of AF between PAF versus Non-PAF. Methods: In this multicenter, retrospective cohort study, the model training and cross-validation was performed on a dataset consisting of 741 patients enrolled from Severance Hospital, South Korea. For cross-institutional validation, the trained model was applied to an independent data set of 600 patients enrolled from Ewha University Hospital, South Korea. Lasso regression was applied to develop the model. Results: In the primary analysis, the Area Under the Receiver Operating Characteristic Curve (AUC) on the test set for the model that predicted AF subtype only using ECG was 0.72 (95% CI 0.65–0.80). In the secondary analysis, AUC only using baseline characteristics was 0.53 (95% CI 0.45–0.61), while the model that employed both baseline characteris‑ tics and ECG parameters was 0.72 (95% CI 0.65–0.80). Moreover, the model that incorporated baseline characteristics, ECG, and Echocardiographic parameters achieved an AUC of 0.76 (95% CI 0.678–0.855) on the test set. Conclusions Our machine learning model using ECG has potential for automatic differentiation of AF between PAF versus Non-PAF achieving high accuracy. The inclusion of  Echocardiographic parameters further increases model per‑ formance. Further studies are needed to clarify the next steps towards clinical translation of the proposed algorithm.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Background: Occupational hazards in crop farms vary diversely based on different field operations as soil management, harvesting processes, pesticide, or fertilizer application. We aimed at evaluating the immunological status of crop farmers, as limited systematic investigations on immune alteration involved with crop farming have been reported yet. Methods: Immunological parameters including plasma immunoglobulin level, major peripheral immune cells distribution, and level of cytokine production from activated T cell were conducted. Nineteen grape orchard, 48 onion open-field, and 21 rose greenhouse farmers were participated. Results: Significantly low proportion of natural killer (NK) cell, a core cell for innate immunity, was revealed in the grape farmers (19.8 ± 3.3%) in comparison to the onion farmers (26.4 ± 3.1%) and the rose farmers (26.9 ± 2.5%), whereas cytotoxic T lymphocyte proportion was lower in the grape and the onion farmers than the rose farmers. The proportion of NKT cell, an immune cell implicated with allergic response, was significantly higher in the grape (2.3 ± 0.3%) and the onion (1.6 ± 0.8%) farmers compared with the rose farmers (1.0 ± 0.4%). A significantly decreased interferon-gamma:interleukin-13 ratio was observed from ex vivo stimulated peripheral blood mononuclear cells of grape farmers compared with the other two groups. The grape farmers revealed the lowest levels of plasma IgG1 and IgG4, and their plasma IgE level was not significantly different from that of the onion or the rose farmers. Conclusion Our finding suggests the high vulnerability of workplace-mediated allergic immunity in grape orchard farmers followed by open-field onion farmers and then the rose greenhouse farmers.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide

INTRODUCTION: Dengue continues to be a major health concern in the Philippines. This study aimed to establish trends and correlations between the incidence of dengue and rainfall, humidity and temperature, respectively, in the different regions. METHODS: Using 2018 records obtained from DOH and PAGASA, correlations were made between monthly measurements of climatic factors and the incidence of dengue using Pearson’s r, while maps and interpolations were generated using quantum geographical information system software. RESULTS: There was a significant positive but weak correlation between the incidence of dengue and rainfall (r = 0.379, 95% CI 0.255, 0.491; p < 0.001) and humidity (r = 0.215, 95% CI 0.080, 0.342; p = 0.002). There was a significant negative but weak correlation between the incidence of dengue and temperature (r = -0.145, 95% CI -0.277, -0.008; p = 0.039). A strong positive correlation was noted between the incidence of dengue, and rainfall and humidity, respectively, in several regions. Multiple regression indicates that rainfall, humidity and temperature are poor predictors of the incidence of dengue (R2 = 0.1436, 0.0461 and 0.0209, respectively). CONCLUSION This study showed overall a significant but weak correlation between an increased incidence of dengue and heavy rainfalls and high relative humidity, and a weak negative correlation for temperature. A high positive correlation of an increased incidence of dengue and heavy rainfalls and high relative humidity was observed in several regions.
Dengue ; humidity ; temperature

INTRODUCTION: Paediatric patients presenting to the general emergency departments (EDs) differ from those presenting to paediatric EDs. General EDs vary in preparedness to manage paediatric patients, which may affect delivery of emergency care with varying clinical outcomes. We aimed to elucidate the differences in utilisation patterns of paediatric and general EDs by paediatric patients. METHODS: This study was conducted in a public healthcare cluster in Singapore consisting of 4 hospitals. A retrospective review of the medical records of paediatric patients, defined as age younger than 16 years old, who attended the EDs from 1 January 2015 to 31 December 2018, was performed. Data were collected using a standardised form and analysed. RESULTS: Of the 704,582 attendances, 686,546 (97.4%) were seen at the paediatric ED. General EDs saw greater number of paediatric patients in the emergent (P1) category (921 [5.1%] versus 14,829 [2.2%]; CONCLUSION General EDs need to build their capabilities and enhance their preparedness according to the paediatric population they serve so that optimal paediatric emergency care can be delivered, especially for critically ill patients who are most in need of life-saving and timely treatment.