Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

The social cost of investor distraction: Evidence from institutional cross-blockholding.

Institutional investors routinely hold blocks of stocks in multiple firms within an industry. While such cross-blockholding boosts a portfolio firm's financial performance, could it distract investors from attending to firm activities in a nonfinancial domain, hurting its performance in that domain? The authors answer this question in the context of corporate social responsibility (CSR). They first document that cross-held firms perform worse on social responsibility than non-cross-held firms do. A quasi-natural experiment based on mergers between institutional blockholders helps establish causality. Next and as their primary contribution, the authors demonstrate investor distraction as the mechanism. Using two proxies of distraction-EDGAR search volume and shareholder proposals on socially responsible investment-they show that the negative impact of institutional cross-blockholding on CSR mainly comes from investor distraction when investors hold multiple blocks simultaneously. By highlighting the social cost of institutional cross-blockholding, this article finds a distraction effect of institutional cross-ownership, which extends our understanding of this unique ownership structure.

Novel RNA genosensor based on highly stable gold nanoparticles decorated phosphorene nanohybrid with graphene for highly sensitive and low-cost electrochemical detection of coconut cadang-cadang viroid.

Coconut cadang-cadang viroid (CCCVd) is an infectious single-stranded RNA (ssRNA) pathogen, which leads directly to the death of a large number of coconut palm trees and heavy economic loss to coconut farmers. Herein, a novel electrochemical impedance RNA genosensor is presented based on highly stable gold nanoparticles (AuNPs) decorated phosphorene (BP) nanohybrid with graphene (Gr) for highly sensitive, low-cost, and label-free detection of CCCVd. BP-AuNPs are environmentally friendly prepared by ultrasonic-assisted liquid-phase exfoliation of black phosphorus, accompanying direct reduction of chloroauric acid. Gr/BP-AuNPs are facilely prepared by the in situ growth of AuNPs onto the BP surface and its nanohybrid with Gr to improve environmental stability of BP. Gr/BP-AuNP-based RNA genosensor is fabricated by immobilizing the thiol-functionalized single-stranded DNA (ssDNA) oligonucleotide probe onto the surface of Gr/BP-AuNP-modified glassy carbon electrode via gold-thiol interactions, which served as an electrochemical genosensing platform for the label-free impedance detection of CCCVd by hybridization between the functionalized ssDNA probe and the complementary CCCVd ssRNA sequence in a wide linear range from 1.0 × 10-11 to 1.0 × 10-7 M with a low limit of detection of 2.8 × 10-12 M. This work supplies an experimental support and theoretical direction for the fabrication of RNA biosensors based on graphene-like materials and potential application for a specific diagnosis of plant RNA viral disease in Arecaceae planting industry.

Disease burden of COPD in the Chinese population: a systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease. OBJECTIVES: This systematic review aimed to evaluate the disease burden of COPD in the Chinese population and to determine the factors influencing the economic burden of the disease. DESIGN: This is a systematic review study. DATA SOURCES AND METHODS: We searched PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, WANGFANG Data, and VIP databases for studies regarding the disease burden of COPD in mainland China published before 31 December 2022. The Agency for Healthcare Research and Quality's recommendation rating tool assessed the cross-sectional studies' risk of bias. RESULTS: A total of 45 studies were included. The disability-adjusted life years (DALYs) for COPD have generally decreased in the Chinese population over the past 30 years. The total number of DALYs due to COPD in China decreased from 26.12 million person-years to 19.92 million person-years, with an annual decline rate of 0.9%. Subjects aged 40 years and older make up the majority of those with COPD in the Chinese population, and the condition is more prevalent among males than females, in rural areas than urban places, and in the West than the East. The median direct medical cost of COPD ranges from 150 to 2014 USD per capita per year. Among 23 influencing factors, age, hospitalization days, hospital type, gender, and career were the most significant variables that had an impact on the economic burden of COPD patients. CONCLUSION: The overall burden of COPD in China has been decreasing over the past 30 years. But there is a lack of standardized indicators for the economic burden of COPD patients in China, and it is recommended to establish a unified standard. REGISTRATION: The systematic review protocol was prospectively registered with PROSPERO (No. CRD42023393429).

Disease burden of COPD in the Chinese populationChronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease. This systematic review aimed to evaluate the disease burden of COPD in the Chinese population and to determine the factors influencing the economic burden of the disease. We searched PubMed, Web of Science, Embase, CNKI, WANGFANG Data, and VIP databases for studies regarding the disease burden of COPD in mainland China published before December 31, 2022. The Agency for Healthcare Research and Quality's (AHRQ) recommendation rating tool assessed the cross-sectional studies' risk of bias. The overall burden of COPD in China has been decreasing over the past 30 years. But there is a lack of standardized indicators for the economic burden of COPD patients in China, and it is recommended to establish a unified standard.

Tumor response assessment by measuring the single largest lesion per organ in advanced non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitor.

Background: For Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), measuring up to two target lesions per organ is an arbitrary criterion. Objectives: We sought to compare response assessment using RECIST1.1 and modified RECIST1.1 (mRECIST1.1, measuring the single largest lesion per organ) in advanced non-small cell lung cancer (aNSCLC) patients undergoing anti-PD-1/PD-L1 monotherapy. Methods: Concordance of radiologic response categorization between RECIST1.1 and mRECIST1.1 was compared using the Kappa statistics. C-index was calculated to evaluate prognostic accuracy of radiologic response by the two criteria. The Kaplan-Meier method and Cox regression analysis were conducted for progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients who had at least two target lesions in any organ per the RECIST1.1 were eligible for comparison analysis. Tumor response showed excellent concordance when measured using the RECIST1.1 and mRECIST1.1 (Kappa = 0.961). C-index by these two criteria was similar for PFS (0.784 versus 0.785) and OS (0.649 versus 0.652). Responders had significantly longer PFS and OS versus non-responders (p < 0.05), whichever criterion adopted. Radiologic response remained a significant predictor of PFS and OS in multivariate analysis (p < 0.05). Conclusion: The mRECIST1.1 was comparable to RECIST1.1 in response assessment among aNSCLC patients who received single-agent PD-1/PD-L1 inhibitor. The mRECIST1.1, with reduced number of lesions to be measured, may be sufficient and more convenient to assess antitumor activity in clinical practice.

Quantifying the mental health and economic impacts of prospective Universal Basic Income schemes among young people in the UK: a microsimulation modelling study.

OBJECTIVE: Universal Basic Income (UBI)-a largely unconditional, regular payment to all adults to support basic needs-has been proposed as a policy to increase the size and security of household incomes and promote mental health. We aimed to quantify its long-term impact on mental health among young people in England. METHODS: We produced a discrete-time dynamic stochastic microsimulation that models a close-to-reality open cohort of synthetic individuals (2010-2030) based on data from Office for National Statistics and Understanding Society. Three UBI scheme scenarios were simulated: Scheme 1-Starter (per week): £41 per child; £63 per adult over 18 and under 65; £190 per adult aged 65+; Scheme 2-Intermediate (per week): £63 per child; £145 per adult under 65; £190 per adult aged 65+; Scheme 3-Minimum Income Standard level (per week): £95 per child; £230 per adult under 65; £230 per adult aged 65+. We reported cases of anxiety and depression prevented or postponed and cost savings. Estimates are rounded to the second significant digit. RESULTS: Scheme 1 could prevent or postpone 200 000 (95% uncertainty interval: 180 000 to 210 000) cases of anxiety and depression from 2010 to 2030. This would increase to 420 000(400 000 to 440 000) for Scheme 2 and 550 000(520 000 to 570 000) for Scheme 3. Assuming that 50% of the cases are diagnosed and treated, Scheme 1 could save £330 million (£280 million to £390 million) to National Health Service (NHS) and personal social services (PSS), over the same period, with Scheme 2 (£710 million (£640 million to £790 million)) or Scheme 3 (£930 million (£850 million to £1000 million)) producing more considerable savings. Overall, total cost savings (including NHS, PSS and patients' related costs) would range from £1.5 billion (£1.2 billion to £1.8 billion) for Scheme 1 to £4.2 billion (£3.7 billion to £4.6 billion) for Scheme 3. CONCLUSION: Our modelling suggests that UBI could substantially benefit young people's mental health, producing substantial health-related cost savings.

A microfluidic platform integrating dynamic cell culture and dielectrophoretic manipulation for in situ assessment of endothelial cell mechanics.

The function of vascular endothelial cells (ECs) within the complex vascular microenvironment is typically modulated by biochemical cues, cell-cell interactions, and fluid shear stress. These regulatory factors play a crucial role in determining cell mechanical properties, such as elastic and shear moduli, which are important parameters for assessing cell status. However, most studies on the measurement of cell mechanical properties have been conducted in vitro, which is labor-intensive and time-consuming. Notably, many physiological factors are lacking in Petri dish culture compared with in vivo conditions, leading to inaccurate results and poor clinical relevance. Herein, we developed a multi-layer microfluidic chip that integrates dynamic cell culture, manipulation and dielectrophoretic in situ measurement of mechanical properties. Furthermore, we numerically and experimentally simulated the vascular microenvironment to investigate the effects of flow rate and tumor necrosis factor-alpha (TNF-α) on the Young's modulus of human umbilical vein endothelial cells (HUVECs). Results showed that greater fluid shear stress results in increased Young's modulus of HUVECs, suggesting the importance of hemodynamics in modulating the biomechanics of ECs. In contrast, TNF-α, an inflammation inducer, dramatically decreased HUVEC stiffness, demonstrating an adverse impact on the vascular endothelium. Blebbistatin, a cytoskeleton disruptor, significantly reduced the Young's modulus of HUVECs. In summary, the proposed vascular-mimetic dynamic culture and monitoring approach enables the physiological development of ECs in organ-on-a-chip microsystems for accurately and efficiently studying hemodynamics and pharmacological mechanisms underlying cardiovascular diseases.

Evaluating the global, regional, and national impact of syphilis: results from the global burden of disease study 2019.

Syphilis is a global public health concern. This study aimed to assess the global and regional burden of syphilis from 1990 to 2019. Disease burden was evaluated using disability-adjusted life-years (DALYs) and prevalence. Data were extracted from the 2019 global burden of disease Study, an open database available for download. Age-standardized rates (ASR) and estimated annual percentage changes (EAPC) were calculated to evaluate the syphilis burden over time. In 2019, the total number of prevalent cases of syphilis was 49.71 million worldwide. The ASR of prevalence was stable from 1990 to 2019 with an EAPC of 0.00 (95% CI - 0.10-0.11). The number of DALYs caused by syphilis was 7.36 million in 2019, reflecting a reduction of 16.38% compared with that in 1990 (8.80 million). The ASR of DALYs exhibited a decreasing trend from 1990 to 2019 (EAPC = - 1.01; 95% CI - 1.19 to - 0.84), with the highest rates observed in the younger age group (< 14 years old). In 2019, the highest ASR of DALYs was found in low sociodemographic index (SDI) regions (239.21/100,000), and the lowest in high SDI regions (3.14/100,000). Generally, the ASR of DALYs decreased as the SDI increased. The top three countries with the highest ASR of DALYs for syphilis were the Solomon Islands, Equatorial Guinea, and Liberia. While the global prevalence of syphilis remained persistently high from 1990 to 2019, there has been a recent decrease in the ASR of DALYs. Increased attention should be dedicated to younger populations and regions characterized by low SDIs.

The tigecycline resistance gene tetX has an expensive fitness cost based on increased outer membrane permeability and metabolic burden in Escherichia coli.

Livestock-derived tetX-positive Escherichia coli with tigecycline resistance poses a serious risk to public health. Fitness costs, antibiotic residues, and other tetracycline resistance genes (TRGs) are fundamental in determining the spread of tetX in the environment, but there is a lack of relevant studies. The results of this study showed that both tetO and tetX resulted in reduction in growth and an increased in the metabolic burden of E. coli, but the presence of doxycycline reversed this phenomenon. Moreover, the protection of E. coli growth and metabolism by tetO was superior to that of tetX in the presence of doxycycline, resulting in a much lower competitiveness of tetX-carrying E. coli than tetO-carrying E. coli. The results of RNA-seq showed that the increase in outer membrane proteins (ompC, ompF and ompT) of tetX-carrying E. coli resulted in increased membrane permeability and biofilm formation, which is an important reason for fitness costs. Overall, the increased membrane permeability and metabolic burden of E. coli is the mechanistic basis for the high fitness cost of tetX, and the spread of tetO may limit the spread of tetX. This study provides new insights into the rational use of tetracycline antibiotics to control the spread of tetX.

Assessment of bone density using the 1.5 T or 3.0 T MRI-based vertebral bone quality score in older patients undergoing spine surgery: does field strength matter?

BACKGROUND CONTEXT: Recently published studies have revealed a correlation between MRI-based vertebral bone quality (VBQ) score and bone mineral density (BMD) measured using dual X-ray absorptiometry (DXA) or quantitative computed tomography (QCT). However, no studies have determined if differences in field strength (1.5 vs 3.0 T) could affect the comparability of the VBQ score among different individuals. PURPOSE: To compare the VBQ score obtained from 1.5 T and 3.0 T MRI (VBQ1.5T vs VBQ3.0T) in patients undergoing spine surgery and assess the predictive performance of VBQ for osteoporosis and osteoporotic vertebral fracture (VCF). DESIGN: A nested case‒control study based on an ongoing prospective cohort study of patients undergoing spine surgery. PATIENT SAMPLE: All older patients (men aged >60 years and postmenopausal women) with available DXA, QCT and MR images within 1 month were included. OUTCOME MEASURES: VBQ score, DXA T-score, and QCT derived vBMD. METHODS: The osteoporotic classifications recommended by the World Health Organization and American College of Radiology were used to categorize the DXA T-score and QCT-derived BMD, respectively. For each patient, the VBQ score was calculated using T1-weighted MR images. Correlation analysis between VBQ and DXA/QCT was performed. Receiver operating characteristic (ROC) curve analysis, including determination of the area under the curve (AUC), was performed to assess the predictive performance of VBQ for osteoporosis. RESULTS: A total of 452 patients (98 men aged >60 years and 354 postmenopausal women) were included in the analysis. Across different BMD categories, the correlation coefficients between the VBQ score and BMD ranged from -0.211 to -0.511, and the VBQ1.5T score and QCT BMD demonstrated the strongest correlation. The VBQ score was a significant classifier of osteoporosis detected by either DXA or QCT, with VBQ1.5T showing the highest discriminative power for QCT-osteoporosis (AUC=0.744, 95% CI=0.685-0.803). In ROC analysis, the VBQ1.5T threshold values ranged from 3.705 to 3.835 with a sensitivity between 48% and 55.6% and a specificity between 70.8% and 74.8%, while the VBQ3.0T threshold values ranged from 2.59 to 2.605 with a sensitivity between 57.6% and 67.1% and a specificity between 67.8% and 69.7%. CONCLUSIONS: VBQ1.5T exhibited better discriminability between patients with and without osteoporosis than VBQ3.0T. Considering the non-negligible difference in osteoporosis diagnosis threshold values between the VBQ1.5T and VBQ3.0T scores, it is essential to clearly distinguish the magnetic field strength when assessing the VBQ score.

[Osteoporosis Screening Values of Osteoporosis Self-Assessment Tool for Asians Index and Body Mass Index in Middle-Aged and Elderly Tibetan Population in Tibet].

Objective: To analyze the screening value of osteoporosis self-screening tool for Asia (OSTA) and body mass index (BMI) for osteoporosis (OP) in middle-aged and elderly Tibetan population in the Tibetan region. Methods: Data on demographic information, bone mineral density (BMD), and other information of 627 middle-aged and elderly people were collected. Analysis of the correlation between OSTA index, BMI and BMD, and receiver operating characteristic (ROC) curve was performed to evaluate the OP screening effects. Results: OSTA index and BMI were correlated with BMD in both female and male populations ( P<0.05). In both male and female populations, OSTA index screening results for OP yielded higher area under the curve ( AUC) than BMI did, with the AUC for female OSTA index being 0.886 and that for female BMI being 0.785, while that for male OSTA index being 0.957 and that for male BMI being 0.834. When comparing the different age groups, the AUC of OSTA index and BMI of the middle-age group was higher than those of the quasi-elderly group and the elderly group, with the AUC of OSTA index and BMI of the middle-age being 0.939 and 0.858, those of the quasi-elderly group being 0.860 and 0.813, and those of the elderly group being 0.750 and 0.650, respectively. When the optimal cut-off value of diagnosis with OSTA index was －2.20, the sensitivity and specificity were both 100%. When the optimal cut-off value for diagnosis with BMI was 17.512 kg/m2, the sensitivity and specificity were both 100%. Conclusion: OSTA index and BMI have different OP screening effects in different middle-aged and elderly Tibetan populations, and OSTA index shows better effects for OP screening than BMI does.

Monoexponential, biexponential, stretched-exponential and kurtosis models of diffusion-weighted imaging in kidney assessment: comparison between patients with primary aldosteronism and healthy controls.

PURPOSE: This study used various diffusion-weighted imaging (DWI) models (including monoexponential, biexponential, stretched-exponential and kurtosis models) in renal magnetic resonance imaging (MRI) to compare whether there were differences in each diffusion parameter between patients with primary aldosteronism (PA) and healthy volunteers. MATERIALS AND METHODS: Twenty-two (female:male, 14:8; age, 48 ± 10 years) patients with PA and 22 age- and sex-matched healthy controls (HCs) underwent MRI examinations of the kidneys. The independent-sample t test or the Mann‒Whitney U test was used to detect differences in the diffusion metrics of the kidneys between the two groups. Univariable and multivariable linear regression were applied to analyze the correlations between diffusion parameters and the clinical indicators. RESULTS: The mean diffusivity (MD, p < 0.001) and radial diffusivity (Dr, p < 0.001) values in the medulla were lower in the PA group than in the HC group. The medullary fractional anisotropy (FA, p < 0.001) was higher than that of HCs. The FA (p < 0.001) and axial diffusivity (Da, p < 0.001) values in the cortex were lower in the PA group. The cortical α (anomalous exponent term, p = 0.016) was higher in the PA patients than in the HCs. Linear regression analysis showed that log(plasma aldosterone concentration) and the estimated glomerular filtration rate (eGFR) were correlated with medullary FA. CONCLUSION: The stretched-exponential model (cortical α) and the kurtosis model (FA, MD and Dr in the medulla and FA and Da in the cortex) showed significant differences between PA patients and healthy volunteers and may have potential for noninvasive renal assessment in PA patients.

A win ratio approach for comparing crossing survival curves in clinical trials.

Many clinical trials include time-to-event or survival data as an outcome. To compare two survival distributions, the log-rank test is often used to produce a P-value for a statistical test of the null hypothesis that the two survival curves are identical. However, such a P-value does not provide the magnitude of the difference between the curves regarding the treatment effect. As a result, the P-value is often accompanied by an estimate of the hazard ratio from the proportional hazards model or Cox model as a measurement of treatment difference. However, one of the most important assumptions for Cox model is that the hazard functions for the two treatment groups are proportional. When the hazard curves cross, the Cox model could lead to misleading results and the log-rank test could also perform poorly. To address the problem of crossing curves in survival analysis, we propose the use of the win ratio method put forward by Pocock et al. as an estimand for analysing such data. The subjects in the test and control treatment groups are formed into all possible pairs. For each pair, the test treatment subject is labelled a winner or a loser if it is known who had the event of interest such as death. The win ratio is the total number of winners divided by the total number of losers and its standard error can be estimated using Bebu and Lachin method. Using real trial datasets and Monte Carlo simulations, this study investigates the power and type I error and compares the win ratio method with the log-rank test and Cox model under various scenarios of crossing survival curves with different censoring rates and distribution parameters. The results show that the win ratio method has similar power as the log-rank test and Cox model to detect the treatment difference when the assumption of proportional hazards holds true, and that the win ratio method outperforms log-rank test and Cox model in terms of power to detect the treatment difference when the survival curves cross.

Deciphering key genomic regions controlling flag leaf size in wheat via integration of meta-QTL and in silico transcriptome assessment.

BACKGROUND: Grain yield is a complex and polygenic trait influenced by the photosynthetic source-sink relationship in wheat. The top three leaves, especially the flag leaf, are considered the major sources of photo-assimilates accumulated in the grain. Determination of significant genomic regions and candidate genes affecting flag leaf size can be used in breeding for grain yield improvement. RESULTS: With the final purpose of understanding key genomic regions for flag leaf size, a meta-analysis of 521 initial quantitative trait loci (QTLs) from 31 independent QTL mapping studies over the past decades was performed, where 333 loci eventually were refined into 64 meta-QTLs (MQTLs). The average confidence interval (CI) of these MQTLs was 5.28 times less than that of the initial QTLs. Thirty-three MQTLs overlapped the marker trait associations (MTAs) previously reported in genome-wide association studies (GWAS) for flag leaf traits in wheat. A total of 2262 candidate genes for flag leaf size, which were involved in the peroxisome, basal transcription factor, and tyrosine metabolism pathways were identified in MQTL regions by the in silico transcriptome assessment. Of these, the expression analysis of the available genes revealed that 134 genes with > 2 transcripts per million (TPM) were highly and specifically expressed in the leaf. These candidate genes could be critical to affect flag leaf size in wheat. CONCLUSIONS: The findings will make further insight into the genetic determinants of flag leaf size and provide some reliable MQTLs and putative candidate genes for the genetic improvement of flag leaf size in wheat.

Meta-QTL analysis and in-silico transcriptome assessment for controlling chlorophyll traits in common wheat.

Chlorophyll is an important plant molecule for absorbing light and transferring electrons to produce energy for photosynthesis, which has a significant impact on crop yield. To identify quantitative trait loci (QTL) controlling chlorophyll traits in wheat (Triticum aestivum L.), a comprehensive meta-analysis of 411 original QTLs for six chlorophyll traits was performed, including the evolution of soil plant analysis development (SPAD), chlorophyll content index (CCI), chlorophyll a content (Chla), chlorophyll b content (Chlb), chlorophyll content (Chl), and ratio of chlorophyll a to b (Chla/b), derived from 41 independent experiments conducted over the past two decades. Fifty-six consensus meta-QTLs (MQTLs) were detected, unevenly distributed on chromosomes 1A, 1B, 2A, 2B, 2D, 3B, 3D, 4B, 4D, 5A, 5D, 6A, 6D, 7B, and 7D. The confidence interval (CI) of the identified MQTLs was 0.18 to 15.07 cM, with an average of 5.74 cM, and 3.17-times narrower than that of the original QTLs. A total of 30 MQTLs were aligned with marker-trait associations (MTAs) reported in genome-wide association studies (GWAS) for chlorophyll traits in wheat. Based on MQTL-flanking marker information and homology analyses combined with RNA-seq data, 136 putative candidate genes were identified in MQTL regions, involved in porphyrin metabolism, photosynthesis, terpene biosynthesis, glyoxylate and dicarboxylate metabolism, and secondary metabolites. The results of this study contribute to the understanding of the genetic basis for controlling chlorophyll traits and can be used in breeding wheat with high photosynthetic efficiency.

Aging and reactivity assessment of nanoscale zerovalent iron in groundwater systems.

In this study, changes in the reactivity of nanoscale zerovalent iron (NZVI) in five different groundwater (GW) systems under anoxic and oxic conditions were examined over a wide range of aging time (0 - 60 d). p-nitrophenol (p-NP) was used as a redox-sensitive probe, whereas nalidixic acid (NA), a typical antibiotic found in the natural environment, was used as a sorbing compound. Investigation of the p-NP reduction in pure water systems showed that NZVI lost 41% and 98% of its reductive activity under anoxic and oxic conditions after 60 d, while enhancement of its reactivity was observed after short-term aging in GW (1 - 5 d), followed by a further decline. This behavior has been ascribed to the formation of secondary Fe(II)-bearing phases, including magnetite and green rust, resulting from NZVI aging in GW. Adsorption experiments revealed that GW-anoxic-aged NZVI samples exhibited a good affinity toward NA, and a greater NA adsorption (∼27 µmol g - 1) than that of pristine NZVI (∼2 µmol g - 1) at alkaline pH values. Surface complexation modeling showed that the enhanced adsorption of NA onto secondary minerals can be attributed to the Fe(II)-NA surface complexation. This considerable change in the reductive ability and the adsorption capacity of NZVI arising from groundwater corrosion calls for greater attention to be paid in assessment studies, where NZVI is injected for long-term remediation in groundwater.

Risk assessment and microbial community structure in agricultural soils contaminated by vanadium from stone coal mining.

High health risks of vanadium (V) released by the mining of vanadium titanomagnetite (VTM) have been widely recognized, but little is known about the risks and microbial community responses of V pollution as a consequence of the stone coal mining (SCM), another important resource for V mining. In this study, the topsoils and the profile soils were collected from the agricultural soils around a typical SCM in Hunan Province, China, with the investigation of ecological, health risks and microbial community structures. The results showed that ∼97.6% of sampling sites had levels of total V exceeding the Chinese National standard (i.e., 130 mg/kg), and up to 41.1% of V speciation in the topsoils was pentavalent vanadium (V(V)). Meanwhile, the proportions of HQ > 1 and 0.6-1 in the topsoils were ∼8.3% and ∼31.0% respectively, indicating that V might pose a non-carcinogenic risk to children. In addition, the microbial community varied between the topsoils and the profile soils. Both sulfur-oxidizing bacteria (e.g. Thiobacillus, MND1, Ignavibacterium) and sulfate-reducing bacteria (e.g. Desulfatiglans, GOUTB8, GOUTA6) might have been involved in V(V) reductive detoxification. This study helps better understand the pollution and associated risks of V in the soils of SCM and provides a potential strategy for bioremediation of the V-contaminated environment.

Heavy metal pollution in a black shale post-mining site of southern China: Pollution pattern, source apportionment and health risk assessment.

Source apportionment is critical but remains largely unknown for heavy metals in the soil surrounding black shale mining areas. Herein, the distribution, potential hazards, and sources of heavy metals in the soil around a black shale post-mining site were investigated. The content of Cadmium (Cd) in topsoil samples (0.77-50.29 mg/kg, N = 84) all exceeded the Chinese agricultural soil standard (0.3 mg/kg). The majority of Cd in the soil existed in the mobile fraction posing a high potential risk to the local ecosystem. and Zn and V in soils existed in the residual form. The percentages of HQing > 1 and 0.6-1 for Vanadium (V) in soil were 8.3% and 31.0%, respectively, and the percentages of HQing > 0.5 for Cd in soil were 3.7% showed that V and Cd were the main factors that increased the potential non-cancer risk. Five potential sources were identified using the geostatistical and positive matrix factorization (PMF) model, among which Cd was mainly derived from the short-term weathering process of black shale (81.06%), most Zinc (Zn) was from the long-term weathering of black shale (67.35%), whereas V was contributed by many factors including long-term weathering of black shale (42.99%), traffic emissions (31.12%) and agricultural activities (21.05%). This study reveals the potential risk and identifies the sources of heavy metals, which is helpful to manage the contaminated soil in black shale mining areas.

Automatic assessment of calcified plaque and nodule by optical coherence tomography adopting deep learning model.

Optical coherence tomography (OCT) has become the best imaging tool to assess calcified plaque and nodule. However, every OCT pullback has numerous images, and artificial analysis requires too much time and energy. Thus, it is unsuitable for clinical application. This study aimed to develop and validate an automatic assessment of calcified plaque and nodule by OCT using deep-learning model. The OCT images of calcified plaque and nodule were labeled by two expert readers based on the consensus. A deep-learning model with a MultiScale and MultiTask u-net network (MS-MT u-net) was developed. Then, with the ground truth labeled by expert readers as reference, the diagnostic accuracy and agreement of the model was validated. For the pixelwise evaluation of calcified plaque, the model had a high performance with precision (93.95%), recall (88.95%), and F1 score (91.38%). For the lesion-level evaluation of calcified plaque, the quantitative metrics by the model excellently correlated with the ground truth (calcium score, r = 0.90, p < 0.01; calcified volume, r = 0.99, p < 0.01). For calcified nodules, the model showed excellent diagnostic performance including sensitivity (91.7%), specificity (89.3%), and accuracy (91.0%). We developed a novel deep-learning model to identify the attributes of calcified plaque and nodule. This model provided excellent diagnostic accuracy and agreement with the ground truth, thereby reducing the subjectivity of manual measurements and substantially saving time. These findings can help practitioners efficiently adopt appropriate therapeutic strategies to treat calcified lesions.

Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial.

BACKGROUND: HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis. METHODS: The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed. FINDINGS: The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314-1424) in the AmBisome group and $1237 (1181-1293) in the control group. The incremental cost-effectiveness ratio was $128 (59-257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15-275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda. INTERPRETATION: The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays. FUNDING: European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research. TRANSLATIONS: For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section.