Diverse pathways to permanent childlessness in Singapore: A latent class analysis.

The proportions of adults reaching midlife without having children have been rising rapidly across the globe, particularly in Asia. However, little is known about the pathways to permanent childlessness within the region's childless population. This study utilized latent class analysis (LCA) to typologize pathways to childlessness based on dynamic characteristics of multiple life domains (i.e., partnership, education, and occupation) among 489 childless Singaporeans aged 50 and above from a 2022 nationwide survey. Additionally, we utilized multinomial logistic regressions to examine the sociodemographic correlates of pathway profiles and Shannon's entropy index to assess the heterogeneity in pathways to childlessness among successive cohorts. Results revealed five distinct profiles of pathways to childlessness: the Never-Married Semi-Professionals, the Low-Flex Blue-Collars, the Highly Educated Professionals, the Ever-Married Semi-Professionals, and the Flexible Blue-Collars. These pathway profiles were significantly associated with sociodemographic characteristics such as gender and family background. Women's pathways to childlessness were more standardized and heavily influenced by partnership characteristics, compared to those of men. The childless from privileged family background were less likely to follow pathways characterized by disadvantageous education and occupational status. There were also rising trends of voluntary childlessness among married childless individuals and increasing heterogeneity in pathways to childlessness across successive birth cohorts. In sum, our findings are consistent with some of the predictions of the Second Demographic Transition theory, suggesting that Singapore may be experiencing a demographic transition characterized by rising childlessness, decoupling of marriage and childbearing, and de-standardization of the life course.

Acoustic assessment in mandarin-speaking Parkinson's disease patients and disease progression monitoring and brain impairment within the speech subsystem.

Approximately 90% of Parkinson's patients (PD) suffer from dysarthria. However, there is currently a lack of research on acoustic measurements and speech impairment patterns among Mandarin-speaking individuals with PD. This study aims to assess the diagnosis and disease monitoring possibility in Mandarin-speaking PD patients through the recommended speech paradigm for non-tonal languages, and to explore the anatomical and functional substrates. We examined total of 160 native Mandarin-speaking Chinese participants consisting of 80 PD patients, 40 healthy controls (HC), and 40 MRI controls. We screened the optimal acoustic metric combination for PD diagnosis. Finally, we used the objective metrics to predict the patient's motor status using the Naïve Bayes model and analyzed the correlations between cortical thickness, subcortical volumes, functional connectivity, and network properties. Comprehensive acoustic screening based on prosodic, articulation, and phonation abnormalities allows differentiation between HC and PD with an area under the curve of 0.931. Patients with slowed reading exhibited atrophy of the fusiform gyrus (FDR p = 0.010, R = 0.391), reduced functional connectivity between the fusiform gyrus and motor cortex, and increased nodal local efficiency (NLE) and nodal efficiency (NE) in bilateral pallidum. Patients with prolonged pauses demonstrated atrophy in the left hippocampus, along with decreased NLE and NE. The acoustic assessment in Mandarin proves effective in diagnosis and disease monitoring for Mandarin-speaking PD patients, generalizing standardized acoustic guidelines beyond non-tonal languages. The speech impairment in Mandarin-speaking PD patients not only involves motor aspects of speech but also encompasses the cognitive processes underlying language generation.

ATST-Net: A method to identify early symptoms in the upper and lower extremities of PD.

Bradykinesia, a core symptom of motor disorders in Parkinson's disease (PD), is a major criterion for screening early PD patients in clinical practice. Currently, many studies have proposed automatic assessment schemes for bradykinesia in PD. However, existing schemes suffer from problems such as dependence on professional equipment, single evaluation tasks, difficulty in obtaining samples and low accuracy. This paper proposes a manual feature extraction- and neural network-based method to evaluate bradykinesia, effectively solving the problem of a small sample size. This method can automatically assess finger tapping (FT), hand movement (HM), toe tapping (TT) and bilateral foot sensitivity tasks (LA) through a unified model. Data were obtained from 120 individuals, including 93 patients with Parkinson's disease and 27 age- and sex-matched normal controls (NCs). Manual feature extraction and Attention Time Series Two-stream Networks (ATST-Net) were used for classification. Accuracy rates of 0.844, 0.819, 0.728, and 0.768 were achieved for FT, HM, TT, and LA, respectively. To our knowledge, this study is the first to simultaneously evaluate the upper and lower limbs using a unified model that has significant advantages in both model training and transfer learning.

Fine particulate matter exposure and systemic inflammation: A potential mediating role of bioactive lipids.

Inflammation is a key mechanism underlying the adverse health effects of exposure to fine particulate matter (PM2.5). Bioactive lipids in the arachidonic acid (ARA) pathway are important in the regulation of inflammation and are reportedly altered by PM2.5 exposure. Ceramide-1-phosphate (C1P), a class of sphingolipids, is required to initiate ARA metabolism. We examined the role of C1P in the alteration of ARA metabolism after PM2.5 exposure and explored whether changes in the ARA pathway promoted systemic inflammation based on a panel study involving 112 older adults in Beijing, China. Ambient PM2.5 levels were continuously monitored at a fixed station from 2013 to 2015. Serum cytokine levels were measured to assess systemic inflammation. Multiple bioactive lipids in the ARA pathway and three subtypes of C1P were quantified in blood samples. Mediation analyses were performed to test the hypotheses. We observed that PM2.5 exposure was positively associated with inflammatory cytokines and the three subtypes of C1P. Mediation analyses showed that C1P significantly mediated the associations of ARA and 5, 6-dihydroxyeicosatrienoic acid (5, 6-DHET), an ARA metabolite, with PM2.5 exposure. ARA, 5, 6-DHET, and leukotriene B4 mediated systemic inflammatory response to PM2.5 exposure. For example, C1P C16:0 (a subtype of C1P) mediated a 12.9 % (95 % confidence interval: 3.7 %, 32.5 %) increase in ARA associated with 3-day moving average PM2.5 exposure, and ARA mediated a 27.1 % (7.8 %, 61.2 %) change in interleukin-8 associated with 7-day moving average PM2.5 exposure. Our study indicates that bioactive lipids in the ARA and sphingolipid metabolic pathways may mediate systemic inflammation after PM2.5 exposure.

Genome-wide prediction and functional analysis of WOX genes in blueberry.

BACKGROUND: WOX genes are a class of plant-specific transcription factors. The WUSCHEL-related homeobox (WOX) family is a member of the homeobox transcription factor superfamily. Previous studies have shown that WOX members play important roles in plant growth and development. However, studies of the WOX gene family in blueberry plants have not been reported. RESULTS: In order to understand the biological function of the WOX gene family in blueberries, bioinformatics were used methods to identify WOX gene family members in the blueberry genome, and analyzed the basic physical and chemical properties, gene structure, gene motifs, promoter cis-acting elements, chromosome location, evolutionary relationships, expression pattern of these family members and predicted their functions. Finally, 12 genes containing the WOX domain were identified and found to be distributed on eight chromosomes. Phylogenetic tree analysis showed that the blueberry WOX gene family had three major branches: ancient branch, middle branch, and WUS branch. Blueberry WOX gene family protein sequences differ in amino acid number, molecular weight, isoelectric point and hydrophobicity. Predictive analysis of promoter cis-acting elements showed that the promoters of the VdWOX genes contained abundant light response, hormone, and stress response elements. The VdWOX genes were induced to express in both stems and leaves in response to salt and drought stress. CONCLUSIONS: Our results provided comprehensive characteristics of the WOX gene family and important clues for further exploration of its role in the growth, development and resistance to various stress in blueberry plants.

Associations between chronic obstructive pulmonary disease and ten common cancers: novel insights from Mendelian randomization analyses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. METHODS: We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. RESULTS: The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15-1.77, FDR = 6.37 × 10-3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03-2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7-26.1%), 36.1% (24.9-33.2%), 35.9% (25.7-34.9%), and 35.5% (26.2-34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. CONCLUSIONS: COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression.

lncRNA ZNF593 antisense (ZNF593-AS) transcripts have been implicated in heart failure through the regulation of myocardial contractility. The decreased transcriptional activity of ZNF593-AS has also been detected in cardiac hypertrophy. However, the function of ZNF593-AS in cardiac hypertrophy remains unclear. Herein, we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine (PE). In vivo, ZNF593-AS aggravated pressure overload-induced cardiac hypertrophy in knockout mice. By contrast, cardiomyocyte-specific transgenic mice (ZNF593-AS MHC-Tg) exhibited attenuated TAC-induced cardiac hypertrophy. In vitro, vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy, whereas GapmeR-induced inhibition aggravated hypertrophic phenotypes. By using RNA-seq and gene set enrichment analyses, we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2 (Mfn2) is a direct target of ZNF593-AS. ZNF593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial function. Therefore, it represents a promising therapeutic target for combating pathological cardiac remodeling.

Association between Ambient Volatile Organic Compounds Exposome and Emergency Hospital Admissions for Cardiovascular Disease.

The limited research on volatile organic compounds (VOCs) has not taken into account the interactions between constituents. We used the weighted quantile sum (WQS) model and generalized linear model (GLM) to quantify the joint effects of ambient VOCs exposome and identify the substances that play key roles. For a 0 day lag, a quartile increase of WQS index for n-alkanes, iso/anti-alkanes, aromatic, halogenated aromatic hydrocarbons, halogenated saturated chain hydrocarbons, and halogenated unsaturated chain hydrocarbons were associated with 1.09% (95% CI: 0.13, 2.06%), 0.98% (95% CI: 0.22, 1.74%), 0.92% (95% CI: 0.14, 1.69%), 1.03% (95% CI: 0.14, 1.93%), 1.69% (95% CI: 0.48, 2.91%), and 1.85% (95% CI: 0.93, 2.79%) increase in cardiovascular disease (CVD) emergency hospital admissions, respectively. Independent effects of key substances on CVD-related emergency hospital admissions were also reported. In particular, an interquartile range increase in 1,1,1-trichloroethane, methylene chloride, styrene, and methylcyclohexane is associated with a greater risk of CVD-associated emergency hospital admissions [3.30% (95% CI: 1.93, 4.69%), 3.84% (95% CI: 1.21, 6.53%), 5.62% (95% CI: 1.35, 10.06%), 8.68% (95% CI: 3.74, 13.86%), respectively]. We found that even if ambient VOCs are present at a considerably low concentration, they can cause cardiovascular damage. This should prompt governments to establish and improve concentration standards for VOCs and their sources. At the same time, policies should be introduced to limit VOCs emission to protect public health.

Earthquake supercycles and fault interaction over the past 32 ka in the Lake Ebinur area, Xinjiang, China.

Earthquake prediction and disaster assessment in tectonically active regions require a continuous and complete regional seismic archive, which is commonly difficult to obtain, especially for prehistoric records. Here, high-resolution analysis of the sedimentary sequence from Lake Ebinur in Xinjiang revealed a detailed history of environment evolution since 32 ka ago. Both the Cl content and ultrafine proportion revealed the changing climate: the climate was relatively dry with low lake-water volumes from 32 to 12 ka, while the climate became warmer and wetter since 12 ka. In addition, eight earthquakes were identified by comprehensive analysis of grain size and geochemical element proxies, showing more than two seismic supercycles, with gaps of ∼10.4 ka; these gaps are much larger than those inferred previously (∼4-7 ka). Notably, these seismic events exhibited a pattern of mutual transmittance between the BoA and Jinghenan faults. Such fault interaction can occur in the Lake Ebinur area because it is dominated by weak lithosphere in which strain is easily accumulated and released; the interaction can also be attributed to the unique spatial distribution and immature nature of both faults. Combined with trenching investigations, our high-resolution analysis of lacustrine sediments can reveal a complete history of tectonic activity, which can efficiently serve regional earthquake prediction and disaster assessment.

Intricate synergistic effects between air pollution and carbon emission: An emerging evidence from China.

Due to global climate change and intensifying anthropogenic pollution, China confronts the dual challenge of controlling particulate matter 2.5 µm (PM2.5) pollution and reducing carbon emissions. Quantifying the characteristics of PM2.5 concentrations and CO2 emissions, as well as identifying the driving factors and synergistic effects of PM2.5 reduction and CO2 mitigation, are crucial steps in promoting sustainable urban development and achieving the Sustainable Development Goals (SDGs) in China. In this study, we selected 168 cities as our case-study, and quantified spatial characteristics of PM2.5 concentrations and CO2 emissions from 2015 to 2020 in China. Then we analyzed driving factors affecting the spatial heterogeneity of PM2.5 reduction and CO2 mitigation applying Multi-scale Geographically Weighted Regression (MGWR) model. By employing coupling coordination degree (CCD) model, we further detected the spatiotemporal evolution patterns of the synergistic effects between PM2.5 reduction and CO2 mitigation in key Chinese cities. The result showed that: (a) From 2015 to 2020, PM2.5 concentrations experienced a significant reduction from 59.78 µg/m3 to 49.83 µg/m3, while CO2 emissions increased from 44.88 × 106 t in 2015 to 45.77 × 106 t in 2020; (b) Green economy efficiency (gee), government attention (gover), and environmental regulation (envir) demonstrate the most pronounced synergistic effect on pollution reduction and carbon mitigation, with the drivers exhibiting obvious spatial heterogeneity; (c) The overall coupling coordination level of PM2.5 pollution and CO2 emissions in China dropped from 0.49 in 2015 to 0.46 in 2020, and the coupling coordination grade in northern cities was notably higher than that in southern cities. The result enhances our understanding of spatiotemporal patterns of synergistic effects between PM2.5 reduction and CO2 mitigation, and provides the theoretical basis for policy decision-making to realize pollution decrease and carbon neutral and regional environment governance.

Individual Structural Covariance Network Predicts Long-Term Motor Improvement in Parkinson Disease with Subthalamic Nucleus Deep Brain Stimulation.

BACKGROUND AND PURPOSE: The efficacy of long-term chronic subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson disease (PD) exhibits substantial variability among individuals. The preoperative identification of suitable deep brain stimulation (DBS) candidates through predictive means becomes crucial. Our study aims to investigate the predictive value of characterizing individualized structural covariance networks for long-term efficacy of DBS, offering patients a precise and cost-effective preoperative screening tool. MATERIALS AND METHODS: We included 138 patients with PD and 40 healthy controls. We developed individualized structural covariance networks from T1-weighted images utilizing network template perturbation, and computed the networks' topological characteristics. Patients were categorized according to their long-term motor improvement following STN-DBS. Intergroup analyses were conducted on individual network edges and topological indices, alongside correlation analyses with long-term outcomes for the entire patient cohort. Finally, machine learning algorithms were employed for regression and classification to predict post-DBS motor improvement. RESULTS: Among the patients with PD, 6 edges (left middle frontal and left caudate nucleus, right olfactory and right insula, left superior medial frontal gyrus and right insula, right middle frontal and left paracentral lobule, right middle frontal and cerebellum, left lobule VIIb of the cerebellum and the vermis of the cerebellum) exhibited significant results in intergroup comparisons and correlation analyses. Increased degree centrality and local efficiency of the cerebellum, parahippocampal gyrus, and postcentral gyrus were associated with DBS improvement. A regression model constructed from these 6 edges revealed a significant correlation between predicted and observed changes in the unified PD rating scale (R = 0.671, P < .001) and receiver operating characteristic analysis demonstrated an area under the curve of 0.802, effectively distinguishing between patients with good and moderate improvement post-DBS. CONCLUSIONS: Our findings reveal the link between individual structural covariance network fingerprints in patients with PD and long-term motor outcome following STN-DBS. Additionally, binary and continuous cerebellum-basal ganglia-frontal structural covariance network edges have emerged as potential predictive biomarkers for DBS motor outcome.

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette's syndrome: Experience and evidence.

OBJECTIVES: To evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette's syndrome (TS). METHODS: This retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. RESULTS: In total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28-74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67-25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26-23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90-15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68-52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5-87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. CONCLUSIONS: Combined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

Correlation of T2DM and Anthropometric Measures with Total Small Bowel Length and Its Effects on Diabetes Remission After Bariatric Surgery.

BACKGROUND: The outcome of weight loss surgery is related to several factors, and for super-obese patients, the rate of weight loss failure and weight recovery after Roux-en-Y gastric bypass (RYGB) is high. Relevant studies have shown that the weight loss effect also correlates with total small bowel length (TSBL) and biliopancreatic (BP) and Roux limbs. However, there are few studies on the relationship between TSBL and anthropometric parameters, the BP limb, the Roux limb, and weight loss effect, and no relevant reports have been reported in China. OBJECTIVES: The objective was to study the relationship between the total length of the small intestine and anthropometric parameters in the Chinese population. The effect of the Roux limb/biliopancreatic limb (RL/BPL) ratio on weight loss and diabetes remission in RYGB patients 1 year after surgery was evaluated to find the appropriate ratio relationship. METHODS: In this prospective study, 148 patients between the ages of 19 and 68 years who underwent laparoscopic Roux-en-Y gastric bypass were enrolled. Height, weight, BMI, the BP limb, the Roux limb, fasting blood glucose (FBG), etc., were noted. To explore the correlation between the total length of the small intestine and these values. Subsequently, the 148 patients were followed up for 1 year after surgery. The patients diagnosed with T2DM before surgery were screened out, and 56 patients were finally identified according to the postoperative follow-up, in which BPL = 50 cm and RL = 150 cm, 175 cm, and 200 cm, respectively. RL/BPL was divided into 3, 3.5, and 4 groups according to the proportional relationship to explore the relationship between RL/BPL and diabetes remission and weight loss. RESULTS: (1) The study included 148 patients (61 women and 87 men). The mean age was 35.68 ± 10.46 years, weight = 127.46 ± 34.51 kg, height = 167.83 ± 9.16 cm, BMI = 44.94 ± 10.58 kg/m2. The average TSBL value was 714.41 ± 101.08 cm. Linear regression analysis showed that TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. (2) Fifty-six patients with T2DM who were followed up 1 year after surgery were divided into three groups. Group 1: BPL = 50 cm, RL = 150 cm (n = 20); group 2: BPL = 50 cm, RL = 175 cm (n = 26); group 3: BPL = 50 cm, RL = 200 cm (n = 10); RL/BPL = 3 was associated with higher weight loss than the other groups. The remission rate of diabetes did not differ between the three groups. CONCLUSIONS: TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. The TSBL of males was significantly higher than that of females. Among patients with T2DM who participated in the follow-up 1 year after surgery, RL/BPL = 3 (n = 20) had greater weight loss than the other groups.

Quantitative Assessment of Hemodynamics Associated With Embolization Degree in Brain Arteriovenous Malformations.

BACKGROUND AND OBJECTIVES: Grading systems, including the novel brain arteriovenous malformation endovascular grading scale (NBAVMES) and arteriovenous malformation embocure score (AVMES), predict embolization outcomes based on arteriovenous malformation (AVM) morphological features. The influence of hemodynamics on embolization outcomes remains unexplored. In this study, we investigated the relationship between hemodynamics and embolization outcomes. METHODS: We conducted a retrospective study of 99 consecutive patients who underwent transarterial embolization at our institution between 2012 and 2018. Hemodynamic features of AVMs were derived from pre-embolization digital subtraction angiography sequences using quantitative digital subtraction angiography. Multivariate logistic regression analysis was performed to determine the significant factors associated with embolization outcomes. RESULTS: Complete embolization (CE) was achieved in 17 (17.2%) patients, and near-complete embolization was achieved in 18 (18.2%) patients. A slower transnidal relative velocity (TRV, odds ratio [OR] = 0.71, P = .002) was significantly associated with CE. Moreover, higher stasis index of the drainage vein (OR = 16.53, P = .023), shorter transnidal time (OR = 0.15, P = .013), and slower TRV (OR = 0.9, P = .049) were significantly associated with complete or near-complete embolization (C/nCE). The area under the receiver operating characteristic curve for predicting CE was 0.87 for TRV, 0.72 for NBAVMES scores (ρ = 0.287, P = .004), and 0.76 for AVMES scores. The area under the receiver operating characteristic curve for predicting C/nCE was 0.77 for TRV, 0.61 for NBAVMES scores, and 0.75 for AVMES scores. Significant Spearman correlation was observed between TRV and NBAVMES scores and AVMES scores (ρ = 0.512, P < .001). CONCLUSION: Preoperative hemodynamic factors have the potential to predict the outcomes of AVM embolization. A higher stasis index of the drainage vein, slower TRV, and shorter transnidal time may indicate a moderate blood flow status or favorable AVM characteristics that can potentially facilitate embolization.

Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.

Diagnosis of intracranial aneurysms by computed tomography angiography using deep learning-based detection and segmentation.

BACKGROUND: Detecting and segmenting intracranial aneurysms (IAs) from angiographic images is a laborious task. OBJECTIVE: To evaluates a novel deep-learning algorithm, named vessel attention (VA)-Unet, for the efficient detection and segmentation of IAs. METHODS: This retrospective study was conducted using head CT angiography (CTA) examinations depicting IAs from two hospitals in China between 2010 and 2021. Training included cases with subarachnoid hemorrhage (SAH) and arterial stenosis, common accompanying vascular abnormalities. Testing was performed in cohorts with reference-standard digital subtraction angiography (cohort 1), with SAH (cohort 2), acquired outside the time interval of training data (cohort 3), and an external dataset (cohort 4). The algorithm's performance was evaluated using sensitivity, recall, false positives per case (FPs/case), and Dice coefficient, with manual segmentation as the reference standard. RESULTS: The study included 3190 CTA scans with 4124 IAs. Sensitivity, recall, and FPs/case for detection of IAs were, respectively, 98.58%, 96.17%, and 2.08 in cohort 1; 95.00%, 88.8%, and 3.62 in cohort 2; 96.00%, 93.77%, and 2.60 in cohort 3; and, 96.17%, 94.05%, and 3.60 in external cohort 4. The segmentation accuracy, as measured by the Dice coefficient, was 0.78, 0.71, 0.71, and 0.66 for cohorts 1-4, respectively. VA-Unet detection recall and FPs/case and segmentation accuracy were affected by several clinical factors, including aneurysm size, bifurcation aneurysms, and the presence of arterial stenosis and SAH. CONCLUSIONS: VA-Unet accurately detected and segmented IAs in head CTA comparably to expert interpretation. The proposed algorithm has significant potential to assist radiologists in efficiently detecting and segmenting IAs from CTA images.

EB1C forms dimer and interacts with protein phosphatase 2A (PP2A) to regulate fiber elongation in upland cotton (Gossypium hirsutum).

Cotton is the most economically important natural fiber crop grown in more than sixty-five countries of the world. Fiber length is the main factor affecting fiber quality, but the existing main varieties are short in length and cannot suit the higher demands of the textile industry. It is necessary to discover functional genes that enable fiber length improvement in cotton through molecular breeding. In this study, overexpression of GhEB1C in Arabidopsis thaliana significantly promotes trichomes, tap roots, and root hairs elongation. The molecular regulation of GhEB1C involves its interactions with itself and GhB'ETA, and the function of GhEB1C regulation mainly depends on the two cysteine residues located at the C-terminal. In particular, the function activity of GhEB1C protein triggered with the regulation of protein phosphatase 2A, while silencing of GhEB1C in cotton significantly influenced the fiber protrusions and elongation mechanisms., Further, influenced the expression of MYB-bHLH-WD40 complex, brassinosteroids, and jasmonic acid-related genes, which showed that transcriptional regulation of GhEB1C is indispensable for cotton fiber formation and elongation processes. Our study analyzed the brief molecular mechanism of GhEB1C regulation. Further elucidated that GhEB1C can be a potential target gene to improve cotton fiber length through transgenic breeding.

Plastic additive components of PM2.5 increase corrected QT interval: Screening for exposure markers based on airborne exposome.

The impact of industrial chemical components of ambient fine particles (e.g. PM2.5) on cardiovascular health has been poorly explored. Our study reports for the first time the associations between human exposure to complex plastic additive (PA) components of PM2.5 and prolongation of heart rate-corrected QT (QTC) interval by employing a screening-to-validation strategy based on a cohort of 373 participants (136 in the screening set and 237 in the validation set) recruited from 7 communities across China. The high-throughput airborne exposome framework revealed ubiquitous occurrences of 95 of 224 target PAs in PM2.5, totaling from 66.3 to 555 ng m-3 across the study locations. Joint effects were identified for 9 of the 13 groups of PAs with positive associations with QTC interval. Independent effect analysis also identified and validated tris(2-chloroisopropyl) phosphate, di-n-butyl/diisobutyl adipate, and 3,5-di-tert-butyl-4-hydroxybenzaldehyde as the key exposure markers for QTC interval prolongation and changes of selected cardiovascular biomarkers. Our findings highlight the important contributions of airborne industrial chemicals to the risks of cardiovascular diseases and underline the critical need for further research on the underlying mechanisms, toxic modes of action, and human exposure risks.