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Background: Emerging research indicates that gut microbiota (GM) are pivotal in the regulation of immune-mediated bone diseases. Nonunion, a bone metabolic disorder, has an unclear causal relationship with GM and immune cells. This study aims to elucidate the causal relationship between GM and nonunion using Mendelian Randomization (MR) and to explore the mediating role of immune cells. Methods: Using a two-step, two-sample Mendelian randomization approach, this study explores the causal link between GM and nonunion, as well as the mediating role of immune cells in this relationship. Data were sourced from multiple cohorts and consortiums, including the MiBioGen consortium. GM data were derived from a recently published dataset of 473 gut microbiota, and nonunion data were obtained from genome-wide association studies (GWAS). Results: MR analysis identified 12 bacterial genera with protective effects against nonunion and seven bacterial genera associated with a higher risk of nonunion, including Agathobacter sp000434275, Aureimonas, Clostridium M, Lachnospirales, Megamonas funiformis, and Peptoccia. Reverse MR analysis indicated that nonunion does not influence GM. Additionally, MR analysis identified 12 immune cell types positively associated with nonunion and 14 immune cell types negatively associated with nonunion. Building on these findings, we conducted mediation MR analysis to identify 24 crucial GM and immune cell-mediated relationships affecting nonunion. Notably, Campylobacter D, Megamonas funiformis, Agathobacter sp000434275, Lachnospirales, Clostridium E sporosphaeroides, and Clostridium M significantly regulated nonunion through multiple immune cell characteristics. Conclusions: To our knowledge, our research results are the first to emphasize a causal relationship between the gut microbiome and nonunion, potentially mediated by immune cells. The correlations and mediation effects identified in our study provide valuable insights into potential therapeutic strategies targeting the gut microbiome, informing global action plans. [ABSTRACT FROM AUTHOR]

The study of the senile osteoporosis in men still lags significantly behind that in women. The changes of protein molecule levels and their relationships with bone loss remain poorly understood. In the present study, we used C57BL/6J male mice at ages from 3 to 24 mo to delineate the mechanisms of aging effects on bone loss. We used the microcomputed tomography, mechanical testing, histomorphometry assays, and detection of serum levels of undercarboxylated osteocalcin (ucOcn) and carboxylated osteocalcin (cOcn) to assess bone mass changes and their relationships with the ratios of ucOcn-to-cOcn in mice from different age groups. The results showed that mouse trabecular bone mass reduced gradually with age, whereas cortical bone loss and mechanical property changes mostly occurred in advanced age. Our findings further demonstrated that the increase in osteoclast activity and the decrease in osteoblast function were significantly corelated with blood levels of ucOcn and cOcn, respectively. The dynamic metabolic changes of ucOcn to cOcn ratio were correlated with age-dependent bone loss in mice. In summary, metabolic shifts in the ratio of ucOcn to cOcn toward bone resorption from young adult to elderly mice contribute to the pathogenesis of age-related bone loss. Simultaneously monitoring blood ratios of ucOcn-to-cOcn may be useful to predict the status of bone mass in vivo. NEW & NOTEWORTHY: To our knowledge, our finding in this study shows for the first time that metabolic shifts in ratio of ucOcn to cOcn toward bone resorption are markedly correlated with age-dependent bone loss in male mice. These findings for the effects of aging on bone loss will assist in studying the pathogenesis of human type II osteoporosis. [ABSTRACT FROM AUTHOR]

Although genetic testing is recommended for all children diagnosed with autism spectrum disorder (ASD) in the United States, it remains unclear how many parents have received and followed these recommendations. This study aimed to assess parental experiences and perspectives of healthcare providers' genetic testing recommendations. A total of 1043 parents of children with ASD from Simons Foundation Powering Autism Research for Knowledge completed an online survey. Only about one‐third of the parents (34.2%) reported that their children's providers had recommended genetic testing. Factors associated with whether parents received these recommendations included the type of healthcare providers diagnosing ASD, parents' knowledge of genetic testing, the age of their children's diagnosis, and the presence of certain co‐occurring medical conditions in their children. Our study also revealed that most parents (76.9%) who received recommendations had pursued genetic testing for their children. Adherence to the recommendations was associated with the characteristics of the parents (i.e., age and employment status) and children (i.e., gender), and their trust in the information from providers. The findings highlight the critical role of healthcare providers in facilitating genetic testing among families of children with ASD. Healthcare providers are recommended to increase their competencies and practice in providing genetic testing recommendations for ASD, assist parents in navigating testing challenges, and support parents through the testing process. Lay Summary: This study examined what parents of autistic children think about doctors' recommendations for genetic testing. Among 1043 surveyed parents, only 34.2% said that their doctors recommended genetic testing, with factors such as the type of diagnosing doctors, timing of the diagnosis, parents' knowledge about genetic testing, and certain medical conditions in the autistic children influencing whether parents received the testing recommendations. Notably, 76.9% of parents who received testing recommendations had pursued genetic testing for their autistic children, emphasizing the need for doctors to enhance their genetic testing recommendation practices and support for parents. [ABSTRACT FROM AUTHOR]

Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health. We studied the database of the National Health and Nutrition Examination Survey, 2005–2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8–1.0, 1.0–1.2, and >1.2 g/kg/day). Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8–1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062–1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057–1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015–1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051–1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098–1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8–1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group. In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis. A low-protein diet should be encouraged in patients with CKD, but protein is essential for bone health. In this study, we showed that a low-protein diet did not affect lumbar bone density. Therefore, in the care of CKD, a low-protein diet is beneficial for renal function and without harm to lumbar bone health. [ABSTRACT FROM AUTHOR]

The existence of intrinsic capacity (IC) subtypes and their distinct impacts on age-related outcomes remain unexplored. This study sought to investigate IC impairment trajectories across domains and their associations with the risk of age-related outcomes, including falls, functional limitations, reduced quality of life (QoL) and mortality at 4- and 8-year follow-ups. The study sample comprised 1,782 older adults residing in the community from the Taiwan Longitudinal Study on Ageing (TLSA). Utilizing group-based multitrajectory modeling, distinct subtypes of IC decline trajectories across various domains were identified. Cox proportional hazard models and multivariable logistic regression analyses were employed to assess the associations between the identified subtypes and age-related outcomes. We identified four subtypes of IC decline: robust with mild decline (n=902), hearing loss with cognitive decline (n=197), physio-cognitive decline (PCD) with depression (n=373), and severe IC decline (n=310). Over the 4-year study period, compared to the robust with mild decline group, hearing loss with cognitive decline group exhibited a significantly higher risk of diminished QoL (OR=2.53 [1.66-3.86], p<0.01), whereas those in the PCD with depression group experienced an elevated risk of falls (OR=1.62 [1.18-2.23], p<0.01), as well as functional limitation (OR=2.61 [1.81-3.75], p<.01). Individuals in the severe IC decline group faced a substantially increased risk of all outcomes of interest. Distinct subtypes of IC decline across different domains have varying impacts on age-related outcomes, highlighting the need for a personalized approach to promote healthy ageing at the population level, while further investigation into specific pathophysiological mechanisms is warranted as well. [ABSTRACT FROM AUTHOR]

Simple Summary: 3-Monochloropropanediol esters (3-MCPDEs) are process contaminants generated during food processing. Although there is no clinical evidence directly linking them to adverse health effects, concerns have been raised regarding their potential to cause renal damage and cancer. To investigate this, we analyzed the concentrations of 3-MCPDEs in kidney tissues from 68 individuals, categorized into two groups: those with kidney cancer and those without. The levels of 3-MCPDEs were quantified using a validated analytical method, with the analyst blinded to the sample origins to ensure objectivity. The results indicated that 3-MCPDE concentrations were significantly higher in the kidneys of patients with kidney cancer compared to those without cancer. However, no significant correlation was found between 3-MCPDE levels and tumor size or stage. These findings suggest that 3-MCPDEs can accumulate in human kidneys and that their levels are elevated in cancerous tissues. Background: 3-Monochloro-propanediol esters (3-MCPDEs), commonly found in refined edible oils and related products, have generated concerns due to their nephrotoxicity and carcinogenicity, yet clinical evidence remains limited. Objectives: In this study, we aimed to assess, for the first time, the accumulation of 3-MCPDEs in human kidney tissues, focusing on 68 participants, some with and others without renal cell carcinoma (RCC). Methods: An analytical method for 3-MCPDE determination in kidney tissues underwent partial validation to ensure its suitability for sample analysis. The analyst was blind to the sample groups. Results: Results revealed significantly higher 3-MCPDE levels in RCC patients compared to non-RCC counterparts (0.22 vs. 0.01 µg/g) (p < 0.01). Moreover, no significant correlation was found between 3-MCPDE levels and tumor stage or size in the RCC group. Conclusions: Accumulation of 3-MCPDEs in humans, with significantly higher levels was observed in kidney tumor specimens compared to non-patients. These findings suggest minimizing the intake of 3-MCPD and its esters in diets in order to reduce potential negative health impacts. [ABSTRACT FROM AUTHOR]

Background Evaluation of the impact of a hepatitis B virus (HBV) prevention program that incorporates maternal antiviral prophylaxis on mother-to-child transmission (MTCT) is limited using real-world data. Methods We analyzed data on maternal HBV screening, neonatal immunization, and post-vaccination serologic testing (PVST) for hepatitis B surface antigen (HBsAg) among at-risk infants born to HBV carrier mothers from the National Immunization Information System during 2008–2022. Through linkage with the National Health Insurance Database, information on maternal antiviral therapy was obtained. Multivariate logistic regression was performed to explore MTCT risk in relation to infant–mother characteristics and prevention strategies. Results In total, 2 460 218 deliveries with maternal HBV status were screened. Between 2008 and 2022, the annual HBsAg and hepatitis B e antigen (HBeAg) seropositivity rates among native pregnant women decreased from 12.2% to 2.6% and from 2.7% to 0.4%, respectively (P for both trends <.0001). Among the 22 859 at-risk infants who underwent PVST, the MTCT rates differed between infants born to HBsAg-positive/HBeAg-negative and HBeAg-positive mothers (0.75% and 6.33%, respectively; P <.001). MTCT risk increased with maternal HBeAg positivity (odds ratio [OR], 9.29; 95% confidence interval [CI], 6.79–12.73) and decreased with maternal antiviral prophylaxis (OR, 0.28; 95% CI,.16–.49). For infants with maternal HBeAg positivity, MTCT risk was associated with mothers born in the immunization era (OR, 1.40; 95% CI, 1.17–1.67). Conclusions MTCT was related to maternal HBeAg positivity and effectively prevented by maternal prophylaxis in the immunized population. At-risk infants born to maternal vaccinated cohorts might possibly pose further risk. [ABSTRACT FROM AUTHOR]

The face of corporate governance is changing as new technologies in the scope of artificial intelligence and data analytics are used to make better future-oriented decisions on performance management. This study attempts to provide empirical results to analyze when the impact of diversity on the board of directors is most evident through the multi-breaks model and artificial neural networks. The input data for the simulation includes 853 electronic companies listed on the Taiwan Stock Exchange from 2000 to 2021. The empirical results show that the higher the percentage of female board members, the more influential the company's performance is, which is only evident when the company is in good business condition. By integrating ANNs with multi-breakpoint regression, this study introduces a novel approach to management research, providing a detailed perspective on how board diversity impacts firm performance across different conditions. The ANN results show that using the number of business board members for predicting Return on Assets yields the highest accuracy, with female board members following closely in predictive effectiveness. The presence of women on the board contributes positively to ROA, particularly when the company is experiencing favorable business conditions and high profitability. Our analysis also reveals that a higher percentage of male board members improves company performance, but this benefit is observed only in highly favorable and unfavorable business conditions. Conversely, a higher percentage of business members tends to affect performance during periods of high profitability negatively. The power of the board of directors and significant shareholders is positively correlated with performance, whereas CEO power positively impacts performance only when it is not extremely low. Independent board members generally do not have a significant effect on profits. Additionally, the company's asset value positively influences performance primarily when the return on assets is high, and increased financial leverage is associated with reduced profitability. [ABSTRACT FROM AUTHOR]

This study established a model system to evaluate the effectiveness of sesame lignans and their derivatives in enhancing oxidative stability. Sesame triacylglycerols (STAGs) were prepared by purifying sesame oil through silica gel column chromatography to remove polar components. Oxidative stability, determined by the induction period using the Rancimat method, significantly decreased after converting sesame oil into STAGs. The efficacy of examined compounds in retarding STAGs oxidation, in descending order, was tertbutyl-hydroquinone (TBHQ), propyl gallate, butylated hydroxytoluene, butylated hydroxyanisole, sesamol, sesaminol, and γ-tocopherol. Induction period of STAGs fortified with TBHQ, comparable to sesame oil, was approximately three times longer than those fortified with sesamol or sesaminol. Dominant sesame lignans, sesamin and sesamolin, and sesamolin derivatives, 7R,7’S-samin and 7R,7’R-samin, showed negligible antioxidant effects at 200 mg/kg. Dose-dependent pro-oxidant behavior was observed in samin isomers at concentrations of 400 to 1,000 mg/kg. Chemical structures of lignans and derivatives played a crucial role in determining their in situ antioxidant effects on STAGs. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a widespread health problem with limited treatment options and poor survival rates. Metformin, a common medication for managing diabetes, has recently shown promise as a potential treatment for various cancers, including OSCC. This review examines the potential benefits of repurposing metformin to treat oral cancer. Studies have shown that metformin can reduce the growth of cancer cells, induce cancer cell death, and improve the effectiveness of existing treatments. It works by affecting several pathways involved in cancer development, such as those related to cell energy and inflammation. However, using metformin for cancer treatment comes with challenges, including possible side effects and interactions with other medications. More research and clinical trials are needed to understand how metformin can be effectively used in cancer treatment and to ensure its safety. If proven effective, metformin could provide a new, cost-effective option for treating oral cancer, potentially improving outcomes and quality of life for patients. Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Rapid mapping is a transcranial magnetic stimulation (TMS) mapping method which can significantly reduce data collection time compared to traditional approaches. However, its validity and reliability has only been established for upper-limb muscles during resting-state activity. Here, we determined the validity and reliability of rapid mapping for non-upper limb muscles that require active contraction during TMS: the masseter and quadriceps muscles. Eleven healthy participants attended two sessions, spaced two hours apart, each involving rapid and 'traditional' mapping of the masseter muscle and three quadriceps muscles (rectus femoris, vastus medialis, vastus lateralis). Map parameters included map volume, map area and centre of gravity (CoG) in the medial-lateral and anterior-posterior directions. Low to moderate measurement errors (%SEMeas = 10–32) were observed across muscles. Relative reliability varied from good-to-excellent (ICC = 0.63–0.99) for map volume, poor-to-excellent (ICC = 0.11–0.86) for map area, and fair-to-excellent for CoG (ICC = 0.25–0.8) across muscles. There was Bayesian evidence of equivalence (BF's > 3) in most map outcomes between rapid and traditional maps across all muscles, supporting the validity of the rapid mapping method. Overall, rapid TMS mapping produced similar estimates of map parameters to the traditional method, however the reliability results were mixed. As mapping of non-upper limb muscles is relatively challenging, rapid mapping is a promising substitute for traditional mapping, however further work is required to refine this method. Highlights: We assessed the validity and reliability of rapid mapping for muscles that require active contraction during TMS: masseter and quadriceps. Rapid TMS mapping showed equivalence in map parameters with the "gold standard", however relative reliability was mixed. Rapid TMS mapping is a promising substitute for traditional TMS mapping, but reliability of some parameters remains questionable. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. Methods: A total of 4717 individuals aged 1–60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti‐HBs), and hepatitis B core antibody (anti‐HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. Results: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti‐HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti‐HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. Conclusion: The 35‐year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV. [ABSTRACT FROM AUTHOR]

Peak alpha frequency (PAF), the dominant oscillatory frequency within the alpha range (8–12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions, potentially providing new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non‐invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre‐ and post‐NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk‐of‐bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta‐analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk‐of‐bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta‐analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = −0.12, 95% CI = −0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. However, it is crucial to note that small sample sizes were used, there was substantial variation in stimulation protocols, and most studies did not specifically target PAF alteration. Further studies are needed to determine NIBS's potential for modulating PAF. [ABSTRACT FROM AUTHOR]

The adulteration of cold‐pressed avocado oil (AVO), a high‐value commodity, poses significant economic and health concerns. This study aimed to develop a method for identifying adulteration of cold‐pressed AVO with refined oil and its utilization to evaluate commercial AVO (cAVO) samples. Avocados from the United States and New Zealand at different stages of maturity were subjected to oven‐drying and microwave‐drying to produce authentic in‐house AVOs. Various parameters, including glycidyl ester (GE) and 3‐monochloropropanediol ester (3‐MCPDE) contents, fatty acid composition, phytosterol content, acid value, and pigment contents, were measured. In‐house AVOs exhibited trace amounts of 3‐MCPDE formation, and a threshold of 0.25 mg kg–1 for GEs and 3‐MCPDEs was established to differentiate samples adulterated with refined oil. However, no clear correlation between 3‐MCPDE concentrations and adulteration ratios was observed. Determination of chlorophyll and carotenoid contents enabled the identification of partial or complete adulteration. The acid value and phytosterol content did not provide sufficient distinctions for detecting adulteration. GE and 3‐MCPDE contents could effectively be used to discriminate cold‐pressed AVO blended with refined oil, providing a reliable method for detecting misrepresentation of cAVO products. Practical Applications: Measuring GEs and 3‐MCPDEs is crucial for identifying refined oil adulteration of cold‐pressed oils. The systematic discrimination methods and criteria developed in this study can be applied to different types of high‐value pressed oils in the future. Addressing this issue is essential for maintaining the authenticity and quality of cold‐pressed oils in the industry. [ABSTRACT FROM AUTHOR]

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future. [ABSTRACT FROM AUTHOR]

Tough conductive carbon black/nylon66 (CCB/PA66) antistatic composites modified by maleic anhydridegrafted ethylene-vinyl acetate copolymer (EVA-g-MAH) were prepared by twin-screw extrusion and injection molding. The mechanical, melt flow, and antistatic properties of the composites were tested, and the fracture surface morphologies and crystallization behavior of the composites were observed and studied by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC), respectively. The results showed that EVA-g-MAH has good compatibility with PA66. The antistatic properties of PA66 increased with the addition of CCB, however the toughness and processing ability of the composites decreased significantly. The addition of 10% EVA-g-MAH in the 8% CCB/PA66 blend resulted in a 75.4% and 45.1% increase in impact strength and elongation at break, respectively, while maintaining relatively higher tensile strength (50.5 MPa). When the mass fraction of EVA-g-MAH was 20%, the volume resistivity and surface resistance and of 8% CCB/PA66 decreased by 2 to 3 orders of magnitude to 4.3 x 107 Ω · cm and 6.5 x 106 Ω, respectively, due to the selective location of CCB particles in 8% CCB/EVA-g-MAH/PA66. 10% EVA-g-MAH enhanced the crystal formation of PA66 in the 8% CCB/EVA-g-MAH/PA6 composites, however 20% EVA-g-MAH inhibited the crystal formation of PA66. [ABSTRACT FROM AUTHOR]

The article explores the relationship between corporate social responsibility (CSR) activities, data breach disclosures, and firm stock performance. It investigates whether companies benefit from CSR activities during adverse events like data breaches and how environmental, social, and corporate governance (ESG) scores impact stock market reactions to data breach announcements. The study uses empirical analysis to show that firms with higher ESG scores experience lower negative market reactions to data breaches, suggesting that CSR engagement is value-enhancing. Additionally, it examines how different types of data breaches, industries, and firms influence market reactions and post-breach operations. [Extracted from the article]

The steel plate reinforcement method is widely used for strengthening damaged linings. Nevertheless, low durability is one of the disadvantages of the steel plate reinforcement method, which uses epoxy resin as the interface binder. To enhance the load-bearing performance and strengthening effect of steel-plate-reinforced structures, this study introduced ultra-high performance concrete (UHPC) as the reinforcing bonding layer and proposed a novel method for steel plate–UHPC reinforcement of cracked linings. A mechanical performance model test was conducted on a 1/5 scale lining model using a loading test device to evaluate the load-bearing performance and stress deformation of both conventional steel plate and steel plate–UHPC reinforced cracked linings. The characteristics, mechanisms of failure, and impacts of strengthening of the steel plate reinforcement method and steel plate–UHPC reinforcement method for cracked linings were compared. A numerical simulation model was developed to investigate the reinforcement effect of cracked linings using steel plate–UHPC reinforcement. The analysis included examining the influence of steel plate thickness, UHPC bonding layer thickness, and reinforcement timing. Model test results show that the overall damage mode of the steel plate–UHPC-reinforced structure had good elastic–plastic behaviour, and the deformation and damage process under the vertical concentrated load can be divided into four typical phases. Compared with the traditional steel plate reinforcement, the ultimate load-carrying capacity and ductility of the steel plate–UHPC-reinforced structure were increased by 53% and 366%, respectively, showing significantly better load-carrying capacity and deformation performance. Numerical simulation results show that the reinforced structure's load-carrying capacity and stiffness enhancement rate increased non-linearly with the increase in UHPC layer thickness and steel plate thickness. However, reasonable reinforcement timing exists for steel plate-UHPC reinforcement, and too late reinforcement timing leads to a decrease in structural load-carrying capacity and stiffness enhancement rate. [ABSTRACT FROM AUTHOR]

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling. [ABSTRACT FROM AUTHOR]

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes. [ABSTRACT FROM AUTHOR]

While enabling students to refer to and build on peer-produced work (termed 'citing' herein) during content creation appears pedagogically promising, its associated learning effects remain under-studied. This research aimed at examining the effects of online citing of peer-generated assessment items during student test-construction on promoting learning and task performance. Additionally, any negative effects this approach may have on inducing cognitive and emotional burdens were examined. A pretest-posttest quasi-experimental research design was adopted, where two treatment groups were devised (i.e. the citing and no-citing groups). A group of fifth-graders from six classes participated in an 11-week study. Based on the results of the analysis of covariance, it was found that students in the citing group scored significantly higher than those in the no-citing group on academic achievement and question-generation performance. In addition, citing did not induce significantly higher cognitive load or learning anxiety as compared to the no-citing situation. [ABSTRACT FROM AUTHOR]

Glycidyl esters (GEs) and 3-monochloropropanediol esters (3-MCPDEs) are process contaminants commonly found in refined edible oils which are often added to infant formulas. The Taiwan Food and Drug Administration (TFDA) launched regulations for GEs in infant formulas that went into effect on 1 July 2021. To investigate levels of GEs and 3-MCPDEs in infant formula powder, 45 products were sampled and analysed during 2020–2021. The contents of GEs and 3-MCPDEs in formulas of different brands significantly varied, but their concentrations in all of the formulas complied with European Union (EU) regulations. Infant formulas containing palm oil had significantly higher 3-MCPDE levels in both extracted oils and milk powder than those without palm oil. Concentrations of GEs and 3-MCPDEs in infant formula powder and extracted oils were significantly lower in products from Europe than those from Australia and New Zealand. Infants aged 0–1 years in Taiwan who consumed only infant formula showed a margin of exposure (MoE) exceeding 25,000. Mean consumer exposures to 3-MCPDEs stayed below the tolerable daily intake (TDI), while high exposures at the 95th percentile (P95) exceeded the TDI by 1.7-fold. Herein, we present the changing trends in the risk assessment results of infant formula across various countries in the decade. Implementation of regulations and mitigation strategy effectively reduced the risk of infants being exposed to GEs and 3-MCPDEs through infant formula. [ABSTRACT FROM AUTHOR]

Introduction: Postmenopausal osteoporosis (PMOP) is a common chronic disease, and the loss of bone density and bone strength after menopause are its main symptoms. Effective treatments for PMOP are still uncertain, but Chinese medicine has some advantages in slowing down bone loss. Shengu granules are often used clinically to treat PMOP. It has been shown to be an effective prescription for the treatment of PMOP, and there is evidence that gut flora may play an important role. However, whether Shengu granules attenuate PMOP by modulating gut flora and related mechanisms remains unclear. Methods: In this study, we mainly examined the bone strength of the femur, the structure of the intestinal microbiota, SCFAs in the feces and the level of FOXP3 cells in the colon. To further learn about the inflammation response, the condition of the mucosa and the level of cytokines in the serum also included in the testing. In addition, to get the information of the protein expression, the protein expression of OPG and RANKL in the femur and the protein expression of ZO-1 and Occludin in the colon were taken into account. Results: The osteoporosis was significantly improved in the SG group compared with the OVX group, and the diversity of intestinal flora, the secretion level of SCFAs and the expression level of FOXP3 were significantly increased compared with the OVX group. In terms of inflammatory indicators, the intestinal inflammation scores of the SG group was significantly lower than those in the OVX group. Additionally, the serum expression levels of IL-10 and TGF-ß in the SG group were significantly increased compared with the OVX group, and the expression levels of IL-17 and TNF-a were significantly decreased compared with the OVX group. In terms of protein expression, the expression levels of ZO-1, Occluding and OPG were significantly increased in the SG group compared with the OVX group, and the expression level of RANKL was significantly decreased compared with the OVX group. Discussion: Shengu granules treatment can improve the imbalance of intestinal flora, increase the secretion of SCFAs and the expression of FOXP3, which reduces the inflammatory response and repairs the intestinal barrier, as well as regulates the expression of OPG/RANKL signaling axis. Overall, Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis. [ABSTRACT FROM AUTHOR]

During the early months of life, infant formula plays a crucial role as a primary source of both food and essential nutrients for infants, serving as a replacement for or supplement to breast milk. However, nonessential metals in infant formulas are a concern because infants are highly vulnerable to chemical exposure. The aim of this study was to investigate infant exposure to nonessential metals in infant formula products in Taiwan and assess the associated health risks. In this study, concentrations of arsenic (As), barium (Ba), cadmium (Cd), manganese (Mn), lead (Pb), and vanadium (V) in 45 formula products for 0–1‐year‐old infants were determined by inductively coupled plasma mass spectrometry. The mean As, Ba, Cd, Mn, Pb, and V concentrations were 6.42, 280, 3.72, 1425, 20.4, and 21.9 µg/kg, respectively. According to our probabilistic simulation of the estimated daily intake of metals, the proportion of hazard quotients exceeding one was 7.69% for As and 3.29% for Mn, and that of hazard index (HI) values exceeding 1 was >17% for metals. Arsenic had the largest HI contribution (46.9%), followed by Mn (22.3%) and Pb (12.7%). The nonessential metals content in infant formula raises potential noncarcinogenic health concerns for infants in Taiwan. Therefore, regulations for nonessential metals must be imposed on related food products in Taiwan, with a particular focus on As and Mn. [ABSTRACT FROM AUTHOR]

Background: Minimizing the risk of heavy metal pollution is of utmost importance to ensure consumer safety. In this research, we utilized inductively coupled plasma‐mass spectrometry to determine the presence of 12 heavy metals in Taiwanese commercial edible oils, both refined and unrefined. Results: Our analytical findings revealed significantly lower levels of heavy metals in refined oils compared with unrefined oils. Through principal component analysis and cluster analysis of 19 types of edible oils, we identified Cd, Ba, Fe, Pb, and Co as the primary variables influencing heavy metal levels in edible oils. Notably, the heavy metal contents in the edible oils did not surpass international standards. Risk assessment results indicated that unrefined oils carried higher risk levels than refined oils. The incremental lifetime cancer risk values calculated for unrefined oils exceeded 10−6 in all age groups except for the 19 ~ 65 years category, while the noncarcinogenic risks remained well below 1, regardless of refined or unrefined oils. Conclusions: Our study sheds light on the distribution characteristics of heavy metal contents in edible oils, highlighting higher levels of heavy metals and associated risks in non‐refined oils compared with refined oils. Ultimately, the presence of heavy metals in edible oils poses low health risks to the human body. [ABSTRACT FROM AUTHOR]

The article introduces Diff-POI, a diffusion-based model for Point-of-Interest (POI) recommendation in location-based services. It addresses limitations of existing methods by incorporating sequential information into user spatial preference and avoiding a focus solely on aggregated previous positions. It is further reported that the proposed diffusion-based sampling strategy effectively addresses limitations of existing methods.

Semi-supervised node classification is a crucial challenge in relational data mining and has attracted increasing interest in research on graph neural networks (GNNs). However, previous approaches merely utilize labeled nodes to supervise the overall optimization, but fail to sufficiently explore the information of their underlying label distribution. Even worse, they often overlook the robustness of models, which may cause instability of network outputs to random perturbations. To address the aforementioned shortcomings, we develop a novel framework termed Hybrid Curriculum Pseudo-Labeling (HCPL) for efficient semi-supervised node classification. Technically, HCPL iteratively annotates unlabeled nodes by training a GNN model on the labeled samples and any previously pseudo-labeled samples, and repeatedly conducts this process. To improve the model robustness, we introduce a hybrid pseudo-labeling strategy that incorporates both prediction confidence and uncertainty under random perturbations, therefore mitigating the influence of erroneous pseudo-labels. Finally, we leverage the idea of curriculum learning to start from annotating easy samples, and gradually explore hard samples as the iteration grows. Extensive experiments on a number of benchmarks demonstrate that our HCPL beats various state-of-the-art baselines in diverse settings. [ABSTRACT FROM AUTHOR]

Summary: Most studies investigating the association between physical activity and osteoporosis prevention only focused on specific types of physical activity. This study's evidence regarding the combined effects or interaction of sleep duration and physical activity. The findings emphasize the role of sleep duration and physical activity in association with osteoporosis. Purpose: The associations between physical activity, sleep duration, and prevalent osteoporosis in Taiwanese adults were studied in this cross-sectional study. Methods: The Taiwan Biobank enrolled a community-based cohort of ~ 120,000 volunteers (as of April 30, 2020) between 30 and 76 years of age with no history of cancer. Amongst, bone mineral density (BMD) measures by dual-energy X-ray absorptiometry (DXA) were available in 22,402 participants. After excluding individuals who had no complete data of BMI (n = 23), MET score (n = 207), T-score (n = 8,826), and sleep duration (n = 16), 13,330 subjects were included as the primary cohort. Univariate and multivariable regression analyses were performed to determine the associations between the presence of osteoporosis, physical activity level, sleep duration, and other variables. Results: The results showed that after adjustment, subjects with physical activity < 20 METs/week and ≥ 20 METs/week (aOR = 1.017 and 0.767, respectively) were associated with risk of osteoporosis than those with zero MET. The odds of osteoporosis were not significantly lower in subjects who slept for ≥ 8 h/day (aOR = 0.934,p=0.266). In addition, compared to short sleepers with no physical activity, adults with increased physical activity ≥ 20 METs/week and sleep ≥ 8 h/day had a significantly lowest likelihood of osteoporosis (aOR = 0.702). Those with medium physical activity (< 20 METs/week) plus average sleep duration (6.5–8 h/day) did not have significant higher odds of osteoporosis (aOR = 1.129,p=0.151). Conclusion: The findings emphasize the joint role of sleep duration and physical activity in association with osteoporosis. Adults with high physical activity plus high sleep hours have the highest BMD and lowest risk of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Frailty is a common geriatric syndrome related to multiple adverse outcomes. Sex differences in its prevalence and impact on mortality remain incompletely understood. Methods: This study was conducted with data from the I-Lan Longitudinal Aging Study, in which community-dwelling subjects aged > 50 years without coronary artery disease or diabetes were enrolled. Sex disparities in phenotypically defined frailty and sex–morality predictor interactions were evaluated. Sex- and frailty-stratified analyses of mortality were performed. Results: The sample comprised 1371 subjects (51.4% women, median age 61 years). The median follow-up period was 6.3 (interquartile range, 5.8–7.0) years. The frailty prevalence did not differ between men (5.3%) and women (5.8%). Frail individuals were older and less educated and had poorer renal function than did non-frail individuals. Body composition trends differed between sexes, regardless of frailty. Relative to non-frail men, frail men had significantly lower body mass indices (BMIs; 24.5 vs. 23.4 kg/m2, p = 0.04) and relative appendicular skeletal muscle masses (7.87 vs. 7.05 kg/m2, p < 0.001). Frail women had significantly higher BMIs (25.2 vs. 23.9 kg/m2, p = 0.02) and waist circumferences (88 vs. 80 cm, p < 0.001) than did non-frail women. Frailty was an independent mortality predictor for men only [hazard ratio (95% confidence interval) = 3.395 (1.809–6.371), psex–frailty interaction = 0.03]. Conclusion: Frailty reflected poorer health in men than in women in the present cohort. This study revealed sex disparities in the impact of frailty on mortality among relatively healthy community-dwelling older adults. [ABSTRACT FROM AUTHOR]

The recently developed unsupervised graph representation learning approaches apply contrastive learning into graph-structured data and achieve promising performance. However, these methods mainly focus on graph augmentation for positive samples, while the negative mining strategies for graph contrastive learning are less explored, leading to sub-optimal performance. To tackle this issue, we propose a Graph Adversarial Contrastive Learning (GraphACL) scheme that learns a bank of negative samples for effective self-supervised whole-graph representation learning. Our GraphACL consists of (i) a graph encoding branch that generates the representations of positive samples and (ii) an adversarial generation branch that produces a bank of negative samples. To generate more powerful hard negative samples, our method minimizes the contrastive loss during encoding updating while maximizing the contrastive loss adversarially over the negative samples for providing the challenging contrastive task. Moreover, the quality of representations produced by the adversarial generation branch is enhanced through the regularization of carefully designed bank divergence loss and bank orthogonality loss. We optimize the parameters of the graph encoding branch and adversarial generation branch alternately. Extensive experiments on 14 real-world benchmarks on both graph classification and transfer learning tasks demonstrate the effectiveness of the proposed approach over existing graph self-supervised representation learning methods. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) imposes a substantial burden, and patient prognosis remains grim. The impact of AST-120 (AST-120) on the survival of CKD patients lacks a consensus. This study aims to investigate the effects of AST-120 usage on the survival of CKD patients and explore the utility of artificial intelligence models for decision-making. We conducted a retrospective analysis of CKD patients receiving care in the pre-end-stage renal disease (ESRD) program at Taichung Veterans General Hospital from 2000 to 2019. We employed Cox regression models to evaluate the relationship between AST-120 use and patient survival, both before and after propensity score matching. Subsequently, we employed Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost) models to assess their performance in predicting AST-120's impact on patient survival. Among the 2584 patients in our cohort, 2199 did not use AST-120, while 385 patients received AST-120. AST-120 users exhibited significantly lower mortality rates compared to non-AST-120 users (13.51% vs. 37.88%, p < 0.0001) and a reduced prevalence of ESRD (44.16% vs. 53.17%, p = 0.0005). Propensity score matching at 1:1 and 1:2 revealed no significant differences, except for dialysis and all-cause mortality, where AST-120 users exhibited significantly lower all-cause mortality (p < 0.0001), with a hazard ratio (HR) of 0.395 (95% CI = 0.295–0.522). This difference remained statistically significant even after propensity matching. In terms of model performance, the XGBoost model demonstrated the highest accuracy (0.72), specificity (0.90), and positive predictive value (0.48), while the logistic regression model showed the highest sensitivity (0.63) and negative predictive value (0.84). The area under the curve (AUC) values for logistic regression, DNN, and XGBoost were 0.73, 0.73, and 0.69, respectively, indicating similar predictive capabilities for mortality. In this cohort of CKD patients, the use of AST-120 is significantly associated with reduced mortality. However, the performance of artificial intelligence models in predicting the impact of AST-120 is not superior to statistical analysis using the current architecture and algorithm. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) imposes a substantial burden, and patient prognosis remains grim. The impact of AST-120 (AST-120) on the survival of CKD patients lacks a consensus. This study aims to investigate the effects of AST-120 usage on the survival of CKD patients and explore the utility of artificial intelligence models for decision-making. We conducted a retrospective analysis of CKD patients receiving care in the pre-end-stage renal disease (ESRD) program at Taichung Veterans General Hospital from 2000 to 2019. We employed Cox regression models to evaluate the relationship between AST-120 use and patient survival, both before and after propensity score matching. Subsequently, we employed Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost) models to assess their performance in predicting AST-120's impact on patient survival. Among the 2584 patients in our cohort, 2199 did not use AST-120, while 385 patients received AST-120. AST-120 users exhibited significantly lower mortality rates compared to non-AST-120 users (13.51% vs. 37.88%, p < 0.0001) and a reduced prevalence of ESRD (44.16% vs. 53.17%, p = 0.0005). Propensity score matching at 1:1 and 1:2 revealed no significant differences, except for dialysis and all-cause mortality, where AST-120 users exhibited significantly lower all-cause mortality (p < 0.0001), with a hazard ratio (HR) of 0.395 (95% CI = 0.295–0.522). This difference remained statistically significant even after propensity matching. In terms of model performance, the XGBoost model demonstrated the highest accuracy (0.72), specificity (0.90), and positive predictive value (0.48), while the logistic regression model showed the highest sensitivity (0.63) and negative predictive value (0.84). The area under the curve (AUC) values for logistic regression, DNN, and XGBoost were 0.73, 0.73, and 0.69, respectively, indicating similar predictive capabilities for mortality. In this cohort of CKD patients, the use of AST-120 is significantly associated with reduced mortality. However, the performance of artificial intelligence models in predicting the impact of AST-120 is not superior to statistical analysis using the current architecture and algorithm. [ABSTRACT FROM AUTHOR]

Context Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. Objective We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. Methods This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. Results A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). Conclusion Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation. [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2alt mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation. [ABSTRACT FROM AUTHOR]

The Zigong area in southern Sichuan Basin is one of the key shale gas production areas in China, and the Longmaxi and Wufeng Formations within it are currently the key exploration and development layers. The present-day in-situ stress field has a significant impact on well trajectory deployment, horizontal well construction, hydraulic fracturing and other aspects. However, it has not been finely quantified in shale gas reservoirs of Zigong area, making it difficult to effectively guide development practice. Therefore, this study constructed a geomechanical model of the target layer in the Zigong area, quantitatively characterized the distribution of present-day in-situ stress, and explored its shale gas development effects. The results show that: (1) Based on the analysis of drilling induced fractures obtained from rock acoustic emission experiments and imaging logging interpretation, the dominant orientation of the maximum horizontal principal stress in the target layer is mainly NW-SE-trending; (2) The horizontal principal stress difference in the Layer S1l1-1-1 and Wufeng Formation is 5-30 MPa (the majority is 6-15 MPa) and 5-35 MPa (the majority is 6-18 MPa), respectively. Low stress difference values are mainly concentrated in the southeastern and northern parts. The overall prediction accuracy is high, with an error rate of less than 8% for the Layer S1l1-1-1 and less than 10% for the Wufeng Formation; (3) Based on rock acoustic emission experiments and finite element model simulation results, the study area is mainly under strike-slip stress faulting mechanism; (4) Due to the influence of the strike-slip faulting stress mechanism, when deploying horizontal wells in the area, priority should be given to selecting areas with low stress mechanism factor (Af) and low stress differences, to achieve better fracturing and transformation effects and reduce the risk of casing deformation and wellbore instability. [ABSTRACT FROM AUTHOR]

Background: Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health. Methods: We studied the database of the National Health and Nutrition Examination Survey, 2005–2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8–1.0, 1.0–1.2, and >1.2 g/kg/day). Results: Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8–1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062–1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057–1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015–1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051–1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098–1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8–1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group. Conclusions: In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis. KEY LEARNING POINTS: A low-protein diet should be encouraged in patients with CKD, but protein is essential for bone health. In this study, we showed that a low-protein diet did not affect lumbar bone density. Therefore, in the care of CKD, a low-protein diet is beneficial for renal function and without harm to lumbar bone health. [ABSTRACT FROM AUTHOR]

This paper proposes wide-range and fast locking all-digital delay-locked loop (WRADDLL) circuit with one cycle dynamic synchronizing. The WRADDLL not only synchronizes the input and output clocks in 5 clock cycles but maintains one cycle dynamic locking. The WRADDLL reduces the clock skew between the input and output clocks with three innovative techniques. First, by improving the mirror control circuit, the WRADDLL operates correctly with a flexible duty cycle clock signal. Second, the WRADDLL works precisely and ignores the effect of output load changes by moving the measurement delay line beyond the output driver. Besides, it can achieve one-cycle dynamic locking. Finally, the WRADDLL utilizes the band selector to achieve wide-range operation. After fine tuning, the maximum static phase error is less than 3% of clock cycle. The chip is fabricated by 90 nm standard CMOS process. Its operating frequency range is from 200 MHz to 2 GHz. The power consumption and RMS jitter are 3.24 mW and 1.49 ps at 2 GHz, respectively. The active area of this chip is 0.011 mm2. [ABSTRACT FROM AUTHOR]

The American College of Medical Genetics and Genomics (ACMG) recommends carrier screening for all pregnant women regardless of race or ethnicity. In recent years, the ACMG broadened the guidelines to include expanded carrier screening (ECS) which can screen for 112 conditions. This study seeks to explore the perceptions of pregnant Latina women about the benefits and concerns related to ECS use. Partnering with prenatal clinics in Texas, we conducted semi-structured qualitative interviews with 32 pregnant Latina women in their second or third trimester of pregnancy. NVivo 8 was used to conduct content analysis and emergent coding of the data. Participants reported the benefits of ECS as helping them prepare for the baby's arrival, informing them of the baby's risk for genetic conditions, ensuring the health of their baby, and preventing diseases before birth. The ECS-related concerns expressed by the participants included worries surrounding potential positive ECS results, insufficient knowledge about the genetic diseases screened for by ECS, the accuracy of the ECS, the potential harm ECS may cause the baby, and the affordability of ECS. After weighing both their perceived benefits and concerns, nearly all the participants believed that ECS should be offered to all pregnant women. This study contributes to an understudied research area in the genetic/genomic field. Our findings can help increase the awareness of obstetricians, genetic professionals, and other healthcare providers regarding pregnant Latina women's views on ECS and inform the design of culturally appropriate care as ECS is adopted into routine clinical practice. [ABSTRACT FROM AUTHOR]

Development of single-component organic phosphor attracts increasing interest due to its wide applications in optoelectronic technologies. Theoretically, activating efficient intersystem crossing (ISC) via 1(p, p*) to 3(p, p*) transitions, rather than 1(n, p*) - 3(p, p*) transitions, is an alternative access to purely organic phosphors but remains challenging. Herein, we designed and successfully synthesized the sila-8-membered ring fused biaryl benzoskeleton by transition metal catalysis, which served as a new organic phosphor with efficient 1(p, p*) to 3(p, p*) ISC. We first found that such a compound exhibits a record-long phosphorescence lifetime of 6.5 s at low temperature for single-component organic systems. Then, we developed two strategies to tune their decay channels to evolve such nonemissive molecules into bright phosphors with elongated lifetimes at room temperature: 1) Physic-based design, where quantitative analyses of electron-phonon coupling led us to reveal and hinder the major nonradiative channels, thus lighted up room temperature phosphorescence (RTP) with a lifetime of 480 ms at 298 K; 2) chemical geometry-driven molecular engineering, where a geometry-based descriptor -TT1-S0/TS0 was developed for rational screening RTP candidates and further improved the RTP lifetime to 794 ms. This study clearly shows the power of interdiscipline among synthetic methodology, physics-based rational design, and computational modeling, which represents a paradigm for the development of an organic emitter. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention. [ABSTRACT FROM AUTHOR]