Detection of Germline Mosaicism for Robertsonian Translocation 14;14: A Case Report.

Background: Chromosomal structural rearrangements can lead to fertility problems and recurrent miscarriages. The intricate interplay of genetics during human development can lead to subtle anomalies that may affect reproduction. Case Presentation: A 33-year-old woman sought fertility treatment after experiencing six miscarriages. Products of conception from the final pregnancy loss had been karyotyped, revealing a Robertsonian translocation (RT), involving chromosome 14. Fertility investigations showed low anti-Mullerian hormone (AMH) levels but otherwise normal female characteristics with normal sperm parameters of her husband were observed and both partners having a normal karyotype. Two embryos were transferred in an IVF cycle but neither resulted in a successful pregnancy. Subsequently, preimplantation genetic testing for aneuploidy (PGT-A) was applied to trophectoderm biopsy specimens from 4 embryos, which revealed abnormalities involving chromosome 14. Sperm aneuploidy testing failed to detect any increase in the incidence of aneuploidy affecting chromosome 14. Further embryos genetic testing indicated that all identified chromosome 14 abnormalities in the embryos had a maternal (oocyte) origin. Conclusion: This case underscores challenges in diagnosing and managing germline mosaicism in fertility. A maternal 14;14 Robertsonian translocation, undetected in the patient's blood but impacting oocytes, likely explains recurrent miscarriage and observed embryo aneuploidies. Genetic mosaicism in reproductive medicine highlights the necessity for advanced testing and personalized treatments. Data integration from various genetic analyses could enhance managing treatment expectations and improving fertility experiences.

Paternal Preconception Hepatitis B Virus Infection and Risk of Congenital Heart Disease in Offspring.

Importance: Previous evidence suggests that maternal hepatitis B virus (HBV) infection during prepregnancy or pregnancy is associated with congenital heart diseases (CHDs) in offspring. However, the association of paternal HBV infection with CHDs is not well examined. Objective: To explore the association of paternal preconception HBV infection with CHDs in offspring. Design, Setting, and Participants: This retrospective cohort study used propensity score matching of data from the Chinese National Free Preconception Checkup Project (NFPCP) from January 1, 2010, to December 31, 2018. Male participants whose wives were aged 20 to 49 years, were uninfected with HBV, and successfully conceived within 1 year after prepregnancy examination were enrolled. Data were analyzed from March 2023 to February 2024. Exposures: The primary exposure was paternal preconception HBV infection status, including uninfected, previous infection (both serum hepatitis B surface antigen and hepatitis B envelope antigen negative), and new infection (serum hepatitis B surface antigen positive). Maternal HBV immune status was further classified as immune or susceptible. Main Outcomes and Measures: The main outcome was CHDs, which were collected from the birth defect registration card of the NFPCP. Logistic regression with robust error variances was used to estimate the association between paternal preconception HBV infection and CHDs in offspring. Results: A total of 6 675 540 couples participated in the NFPCP service. After matching husbands with and without preconception HBV infection in a 1:4 ratio, 3 047 924 couples (median age of husbands, 27 years [IQR, 25-30 years]) were included in this study. Of these couples, 0.025% had offspring with CHDs. Previous paternal HBV infection was independently associated with CHDs in offspring (adjusted relative risk [ARR], 1.40; 95% CI, 1.11-1.76) compared with no infection. Similar results were obtained in subgroup analyses according to maternal HBV immune status. Compared with couples with uninfected husbands and susceptible wives, the risk of CHDs in offspring among couples with previously HBV-infected husbands was similar in couples with wives with susceptible immune status (ARR, 1.49; 95% CI, 1.10-2.03) and in those with wives with immunity (ARR, 1.49; 95%CI, 1.07-2.09). A significantly higher CHD risk in offspring was found among couples with newly infected husbands and immune wives (ARR, 1.38; 95% CI, 1.05-1.82), but there was no difference in risk among those with newly infected husbands and susceptible wives (ARR, 0.99; 95% CI, 0.72-1.36). No interactions were found between maternal immune status and paternal HBV infection. Conclusions and Relevance: In this cohort study using propensity score matching, previous paternal preconception HBV infection was associated with CHD risk in offspring. The findings suggest that personalized reproductive guidance regarding HBV screening and staying free of HBV infection should be provided for both wives and husbands.

Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial.

BACKGROUND: In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. METHODS: Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. RESULTS: A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. CONCLUSION: Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.

Production and biological activity of ß-1,3-xylo-oligosaccharides using xylanase from Caulerpa lentillifera.

In this study, ß-1,3-xylanase (Xyl3088) was designed and prepared by constructing the expression vector plasmid and expressing and purifying the fusion protein. ß-1,3-xylo-oligosaccharides were obtained through the specific enzymatic degradation of ß-1, 3-xylan from Caulerpa lentillifera. The enzymolysis conditions were established and optimized as follows: Tris-HCl solution 0.05 mol/L, temperature of 37 °C, enzyme amount of 250 µL, and enzymolysis time of 24 h. The oligosaccharides' compositions and structural characterization were identified by thin-layer chromatography (TLC), ion chromatography (IC) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS). The IC50 values for scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethyl-benzothiazoline-p-sulfonic acid (ABTS+), and superoxide anion radical (•O2-) were 13.108, 1.258, and 65.926 mg/mL for ß-1,3-xylo-oligosaccharides, respectively, and 27.588, 373.048, and 269.12 mg/mL for ß-1,4-xylo-oligosaccharides, respectively. Compared with ß-1,4-xylo-oligosaccharides, ß-1,3-xylo-oligosaccharides had substantial antioxidant activity and their antioxidant effects were concentration dependent. ß-1,3-xylo-oligosaccharides also possessed a stronger anti-inflammatory effect on RAW 264.7 cells stimulated by lipopolysaccharide (LPS) than ß-1,4-xylo-oligosaccharides. At a working concentration of 100 µg/mL, ß-1,3-xylo-oligosaccharides inhibited the release of NO and affected the expression of IL-1ß, TNF-α, and other proteins secreted by cells, effectively promoting the release of pro-inflammatory mediators by immune cells in response to external stimuli and achieving anti-inflammatory effects. Therefore, ß-1,3-xylo-oligosaccharides are valuable products in food and pharmaceutical industries.

An ensemble model for accurate prediction of key water quality parameters in river based on deep learning methods.

Deep learning models provide a more powerful method for accurate and stable prediction of water quality in rivers, which is crucial for the intelligent management and control of the water environment. To increase the accuracy of predicting the water quality parameters and learn more about the impact of complex spatial information based on deep learning models, this study proposes two ensemble models TNX (with temporal attention) and STNX (with spatio-temporal attention) based on seasonal and trend decomposition (STL) method to predict water quality using geo-sensory time series data. Dissolved oxygen, total phosphorus, and ammonia nitrogen were predicted in short-step (1 h, and 2 h) and long-step (12 h, and 24 h) with seven water quality monitoring sites in a river. The ensemble model TNX improved the performance by 2.1%-6.1% and 4.3%-22.0% relative to the best baseline deep learning model for the short-step and long-step water quality prediction, and it can capture the variation pattern of water quality parameters by only predicting the trend component of raw data after STL decomposition. The STNX model, with spatio-temporal attention, obtained 0.5%-2.4% and 2.3%-5.7% higher performance compared to the TNX model for the short-step and long-step water quality prediction, and such improvement was more effective in mitigating the prediction shift patterns of long-step prediction. Moreover, the model interpretation results consistently demonstrated positive relationship patterns across all monitoring sites. However, the significance of seven specific monitoring sites diminished as the distance between the predicted and input monitoring sites increased. This study provides an ensemble modeling approach based on STL decomposition for improving short-step and long-step prediction of river water quality parameter, and understands the impact of complex spatial information on deep learning model.

Protective Effects of Laminaria japonica Polysaccharide Composite Microcapsules on the Survival of Lactobacillus plantarum during Simulated Gastrointestinal Digestion and Heat Treatment.

To improve probiotics' survivability during gastrointestinal digestion and heat treatment, Lactobacillus plantarum was microencapsulated by spray-drying using Laminaria japonica polysaccharide/sodium caseinate/gelatin (LJP/SC/GE) composites. Thermogravimetry and differential scanning calorimetry results revealed that the denaturation of LJP/SC/GE microcapsules requires higher thermal energy than that of SC/GE microcapsules, and the addition of LJP may improve thermal stability. Zeta potential measurements indicated that, at low pH of the gastric fluid, the negatively charged LJP attracted the positively charged SC/GE, helping to maintain an intact microstructure without disintegration. The encapsulation efficiency of L. plantarum-loaded LJP/SC/GE microcapsules reached about 93.4%, and the survival rate was 46.9% in simulated gastric fluid (SGF) for 2 h and 96.0% in simulated intestinal fluid (SIF) for 2 h. In vitro release experiments showed that the LJP/SC/GE microcapsules could protect the viability of L. plantarum in SGF and release probiotics slowly in SIF. The cell survival of LJP/SC/GE microcapsules was significantly improved during the heat treatment compared to SC/GE microcapsules and free cells. LJP/SC/GE microcapsules can increase the survival of L. plantarum by maintaining the lactate dehydrogenase and Na+-K+-ATPase activity. Overall, this study demonstrates the great potential of LJP/SC/GE microcapsules to protect and deliver probiotics in food and pharmaceutical systems.

Comparative analysis of machine learning methods for prediction of chlorophyll-a in a river with different hydrology characteristics: A case study in Fuchun River, China.

Eutrophication is a serious threat to water quality and human health, and chlorophyll-a (Chla) is a key indicator to represent eutrophication in rivers or lakes. Understanding the spatial-temporal distribution of Chla and its accurate prediction are significant for water system management. In this study, spatial-temporal analysis and correlation analysis were applied to reveal Chla concentration pattern in the Fuchun River, China. Then four exogenous variables (wind speed, water temperature, dissolved oxygen and turbidity) were used for predicting Chla concentrations by six models (3 traditional machine learning models and 3 deep learning models) and compare the performance in a river with different hydrology characteristics. Statistical analysis shown that the Chla concentration in the reservoir river segment was higher than in the natural river segment during August and September, while the dominant algae gradually changed from Cyanophyta to Cryptophyta. Moreover, air temperature, water temperature and dissolved oxygen had high correlations with Chla concentrations among environment factors. The results of the prediction models demonstrate that extreme gradient boosting (XGBoost) and long short-term memory neural network (LSTM) were the best performance model in the reservoir river segment (NSE = 0.93; RMSE = 4.67) and natural river segment (NSE = 0.94; RMSE = 1.84), respectively. This study provides a reference for further understanding eutrophication and early warning of algal blooms in different type of rivers.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Targeting ferroptosis regulators by natural products in colorectal cancer.

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most diagnosed cancer and the second leading cause of cancer-related deaths. Despite advancements in treatment, challenges such as delayed diagnosis, multidrug resistance, and limited therapeutic effectiveness persist, emphasizing the need for innovative approaches. This review explores the potential of natural products, nutraceuticals, and phytochemicals for targeting ferroptosis-related regulators as a novel strategy in CRC. Ferroptosis, a form of regulated cell death characterized by iron-dependent lethal lipid peroxide accumulation, holds substantial importance in CRC progression and therapy resistance. Natural products, known for their diverse bioactive effects and favorable safety profiles, emerge as promising candidates to induce ferroptosis in CRC cells. Exploring amino acid, iron, lipid metabolism regulators, and oxidative stress regulators reveals promising avenues for inducing cell death in CRC. This comprehensive review provides insights into the multifaceted effects of natural products on proteins integral to ferroptosis regulation, including GPX4, SLC7A11, ACSL4, NCOA4, and HO-1. By elucidating the intricate mechanisms through which natural products modulate these proteins, this review lays the foundation for a promising therapeutic strategy in CRC.

Research on nowcasting prediction technology for flooding scenarios based on data-driven and real-time monitoring.

With the impact of global climate change and the urbanization process, the risk of urban flooding has increased rapidly, especially in developing countries. Real-time monitoring and prediction of flooding extent and drainage system are the foundation of effective urban flood emergency management. Therefore, this paper presents a rapid nowcasting prediction method of urban flooding based on data-driven and real-time monitoring. The proposed method firstly adopts a small number of monitoring points to deduce the urban global real-time water level based on a machine learning algorithm. Then, a data-driven method is developed to achieve dynamic urban flooding nowcasting prediction with real-time monitoring data and high-accuracy precipitation prediction. The results show that the average MAE and RMSE of the urban flooding and conduit system in the deduction method for water level are 0.101 and 0.144, 0.124 and 0.162, respectively, while the flooding depth deduction is more stable compared to the conduit system by probabilistic statistical analysis. Moreover, the urban flooding nowcasting method can accurately predict the flooding depth, and the R2 are as high as 0.973 and 0.962 of testing. The urban flooding nowcasting prediction method provides technical support for emergency flood risk management.

Interpregnancy Interval After Healthy Live Birth and Subsequent Spontaneous Abortion.

Importance: Many studies have reported that the interpregnancy interval (IPI) is a potential modifiable risk factor for adverse perinatal outcomes. However, the association between IPI after live birth and subsequent spontaneous abortion (SA) is unclear. Objective: To investigate the association of IPI after a healthy live birth and subsequent SA. Design, Setting, and Participants: This prospective cohort study used data from 180 921 women aged 20 to 49 years who had a single healthy live birth and planned for another pregnancy and who participated in the Chinese National Free Prepregnancy Checkups Project from January 1, 2010, to December 31, 2020. Statistical analysis was conducted from June 20 to October 5, 2023. Exposure: Interpregnancy interval, defined as the interval between the delivery date and conception of the subsequent pregnancy, was categorized as follows: less than 18 months, 18 to 23 months, 24 to 35 months, 36 to 59 months, and 60 months or longer. Main Outcomes and Measures: The main outcome was SA. Multivariable-adjusted odds ratios (ORs) were calculated by logistic regression models to examine the association between IPI and the risk of SA. Dose-response associations were evaluated by restricted cubic splines. Results: The analyses included 180 921 multiparous women (mean [SD] age at current pregnancy, 26.3 [2.8] years); 4380 SA events (2.4% of all participants) were recorded. A J-shaped association between IPI levels and SA was identified. In the fully adjusted model, compared with IPIs of 18 to 23 months, both short (<18 months) and long (≥36 months) IPIs showed an increased risk of SA (IPIs of <18 months: OR, 1.15 [95% CI, 1.04-1.27]; IPIs of 36-59 months: OR, 1.28 [95% CI, 1.15-1.43]; IPIs of ≥60 months: OR, 2.13 [95% CI, 1.78-2.56]). Results of the subgroup analysis by mode of previous delivery were consistent with the main analysis. Conclusions and Relevance: This cohort study of multiparous women suggests that an IPI of shorter than 18 months or an IPI of 36 months or longer after a healthy live birth was associated with an increased risk of subsequent SA. The findings are valuable to make a rational prepregnancy plan and may facilitate the prevention of SA and improvement in neonatal outcomes.

Association of psychological stress with wives' hypertension across over 10 million Chinese married female population aged 20-49 years.

BACKGROUND: Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women. METHODS: Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension. RESULTS: Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives' hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. CONCLUSION: Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.

Garsorasib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 2 trial.

BACKGROUND: Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRASG12C inhibitor, has shown promising antitumour activity in patients with KRASG12C-mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRASG12C-mutated NSCLC. METHODS: This open-label, multicentre, single-arm, phase 2 trial enrolled adult patients with KRASG12C-mutated NSCLC who had previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors from 43 hospitals in China. Participants received 600 mg garsorasib orally twice per day. Tumour assessments were performed at baseline, at the end of every two cycles (of 21 days) for the first eight cycles, and at the end of every three cycles thereafter. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC) following the guidelines in Response Evaluation Criteria in Solid Tumours, version 1.1. Efficacy and safety were assessed in all patients who received at least one dose of garsorasib. This trial is registered at ClinicalTrials.gov, NCT05383898, and is active but no longer recruiting. FINDINGS: From June 17, 2022, to May 17, 2023, of 225 patients screened for eligibility, 123 patients were enrolled and treated with garsorasib. Of these 123 participants, the median age was 64 years (IQR 59-68), 108 (88%) were male and 15 (12%) were female. At data cutoff (Nov 17, 2023), the median follow-up duration was 7·9 months (IQR 6·3-10·4), and 82 (67%) of 123 patients had discontinued treatment. The IRC-confirmed ORR was 50% (61 of 123 patients; 95% CI 41-59). 117 (95%) of 123 patients reported treatment-related adverse events, with 61 (50%) experiencing grade 3 or higher events. The most common types of adverse events of grade 3 or higher associated with garsorasib were hepatic and gastrointestinal events, including increased liver enzymes, such as aspartate aminotransferase (21 [17%] of 123 participants), alanine aminotransferase (19 [15%] of 123 participants), and gamma-glutamyltransferase (28 [23%] of 123 participants); nausea (2 [2%] of 123 participants); and vomiting (2 [2%] of 123 participants). No new safety signals were identified, and most of the adverse events were well managed. INTERPRETATION: The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRASG12C-mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population. FUNDING: InventisBio.

Association between fine particulate matter and fecundability in Henan, China: A prospective cohort study.

OBJECTIVE: To investigate the relationship between ambient fine particulate matter (PM2.5) exposure and fecundability. METHODS: This study included 751,270 female residents from Henan Province who participated in the National Free Pre-conception Check-up Projects during 2015-2017. Ambient cycle-specific PM2.5 exposure was assessed at the county level for each participant using satellite-based PM2.5 concentration data at 1-km resolution. Cox proportional hazards models with time-varying exposure were used to estimate the association between fecundability and PM2.5 exposure, adjusted for potential individual risk factors. RESULTS: During the study period, 568,713 participants were pregnant, monthly mean PM2.5 concentrations varied from 25.5 to 114.0 µg/m3 across study areas. For each 10 µg/m3 increase in cycle-specific PM2.5, the hazard ratio for fecundability was 0.951 (95 % confidence interval: 0.950-0.953). The association was more pronounced in women who were older, with urban household registration, history of pregnancy, higher body mass index (BMI), hypertension, without exposure to tobacco, or whose male partners were older, with higher BMI, or hypertension. CONCLUSION: In this population-based prospective cohort, ambient cycle-specific PM2.5 exposure was associated with reduced fecundability. These findings may support the adverse implications of severe air pollution on reproductive health.

IMpower210: A phase III study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer.

Objective: IMpower210 (NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs. docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC) in East Asian patients. Methods: Key eligibility criteria for this phase III, open-label, randomized study included age ≥18 years; histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system (7th edition); Eastern Cooperative Oncology Group performance status of 0 or 1; and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab (1,200 mg) or docetaxel (75 mg/m2). The primary study endpoint was overall survival (OS) in the intention-to-treat (ITT) population with wild-type epidermal growth factor receptor expression (ITT EGFR-WT) and in the overall ITT population. Results: Median OS in the ITT EGFR-WT population (n=467) was 12.3 [95% confidence interval (95% CI), 10.3-13.8] months in the atezolizumab arm (n=312) and 9.9 (95% CI, 7.8-13.9) months in the docetaxel arm [n=155; stratified hazard ratio (HR), 0.82; 95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5 (95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1 (95% CI, 8.4-14.2) months (n=377) with docetaxel treatment (n=188; stratified HR, 0.87; 95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm. Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade 3/4 TRAEs.

Long-Term Exposure to Fine Particulate Matter and Fasting Blood Glucose and Diabetes in 20 Million Chinese Women of Reproductive Age.

OBJECTIVE: Evidence of the associations between fine particulate matter (PM2.5) and diabetes risk from women of reproductive age, in whom diabetes may have adverse long-term health effects for both themselves and future generations, remains scarce. We therefore examined the associations of long-term PM2.5 exposure with fasting blood glucose (FBG) level and diabetes risk in women of reproductive age in China. RESEARCH DESIGN AND METHODS: This study included 20,076,032 women age 20-49 years participating in the National Free Preconception Health Examination Project in China between 2010 and 2015. PM2.5 was estimated using a satellite-based model. Multivariate linear and logistic regression models were used to examine the associations of PM2.5 exposure with FBG level and diabetes risk, respectively. Diabetes burden attributable to PM2.5 was estimated using attributable fraction (AF) and attributable number. RESULTS: PM2.5 showed monotonic relationships with elevated FBG level and diabetes risk. Each interquartile range (27 µg/m3) increase in 3-year average PM2.5 concentration was associated with a 0.078 mmol/L (95% CI 0.077, 0.079) increase in FBG and 18% (95% CI 16%, 19%) higher risk of diabetes. The AF attributed to PM2.5 exposure exceeding 5 µg/m3 was 29.0% (95% CI 27.5%, 30.5%), corresponding to an additional 78.6 thousand (95% CI 74.5, 82.6) diabetes cases. Subgroup analyses showed more pronounced diabetes risks in those who were overweight or obese, age >35 years, less educated, of minority ethnicity, registered as a rural household, and residing in western China. CONCLUSIONS: We found long-term PM2.5 exposure was associated with higher diabetes risk in women of reproductive age in China.

Application of Rice Straw Inhibits Clubroot Disease by Regulating the Microbial Community in Soil.

Straw return is an effective agricultural management practice for alleviating soil sickness, but only a few studies have focused on the incorporation of straw with deep plowing and rotary tillage practices in vegetable production. To determine the effects of rice straw return on Chinese cabbage clubroot, a field experiment for three consecutive years in the same area was performed. Soil microbial high-throughput sequencing, quantitative real-time polymerase chain reaction (PCR) and other methods were used to detect Chinese cabbage plant growth, clubroot occurrence, soil chemical properties and soil microbial diversity and abundance. The results showed that straw addition could significantly reduce the clubroot disease incidence. Through Illumina Miseq sequencing, the diversity of the fungi decreased obviously. The relative abundance of the phyla Proteobacteria and Firmicutes was strikingly reduced, while that of Chloroflexi was significantly increased. Redundancy analysis suggests that soil properties may also affect the soil microbial composition; changes in the microbial structure of bacteria and fungi were associated with the available phosphorus. In conclusion, the continuous addition of rice straw can promote the growth and control the occurrence of clubroot, which is closely related to the microbial composition, and the inhibition effect is proportional to the age of addition.

An Effective Method to Prepare Curcumin-Loaded Soy Protein Isolate Nanoparticles Co-Stabilized by Carrageenan and Fucoidan.

In this study, a novel and simple strategy is proposed based on 3D network formed by easily blending polysaccharide carrageenan (Car) and fucoidan (Fuc) without a crosslinker. The Fuc/Car dual coating effectively assists the self-assembly of soy protein-isolated (SPI)/curcumin (Cur, C) composite microcapsules (SPI/C) and achieves an excellent curcumin encapsulation efficiency (EE) up to 95.28% with a 4.16% loading capacity (LC) under optimal conditions. The resulting nanocomposites achieved a satisfying redispersibility in aqueous solution and enhanced the water solubility with a lower size dispersity index (PDI) of 0.12 and a larger zeta potential of -29.67 mV. The Fuc/Car double-layer network not only dramatically improved its thermal stability and photostability, but also provided controlled release and enhanced antioxidant activity in in vitro conditions. The underlying mechanism of the self-assembly of the curcumin-loaded nanoparticles was also addressed. The results proved the feasibility of the encapsulation of unstable hydrophobic bioactive substances (curcumin) with the dual anionic polysaccharide Fuc/Car co-stabilized SPI nanoparticles. This study paves the way for an alternative way of developing novel curcumin delivery systems and will have broad prospects in the pharmaceutical industries.

A document-level information extraction pipeline for layered cathode materials for sodium-ion batteries.

Natural language processing techniques enable extraction of valuable information from large amounts of published literature for the application of data science and technology, i.e. machine learning in the field of materials science. Nevertheless, the automated extraction of data from full-text documents remains a complex task. We propose a document-level natural language processing pipeline for literature extraction of comprehensive information on layered cathode materials for sodium-ion batteries. The pipeline enhances entity recognition with contextual supplementary information while capturing the article structure. Finally, a heuristic multi-level relationship extraction algorithm is employed in relation extraction to extract experimental parameters and complex performance relationships respectively. We successfully extracted a comprehensive dataset containing 5265 records from 1747 documents, encompassing essential information such as chemical composition, synthesis parameters, and electrochemical properties. By implementing our pipeline, we have made significant progress in overcoming the challenges associated with data scarcity in battery informatics. The extracted datasets provide a valuable resource for further research and development in the field of layered cathode materials.