The Association between Type of Insurance Plan, Out-of-Pocket Cost, and Adherence to Antihypertensive Medications in Medicare Supplement Insurance Enrollees.

BACKGROUND: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare Supplement plans. METHODS: We conducted a retrospective analysis of the MerativeTM MarketScan® Medicare Supplement Database (2017-2019) in Medigap enrollees (≥ 65 years) with hypertension. Proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥ 0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics. RESULTS: Among 27,407 patients with hypertension, the average PDC was 0.68 ± 0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs was associated with a 0.06 (95% Confidence intervals [CI]: -0.09 - -0.03) lower probability of adequate adherence, or a 5% (95% C.I.: 4% - 7%) decrease in PDC. Compared to comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (O.R.: 0.69, 95%C.I.: 0.62 - 0.77), but higher among those with preferred provider organization (PPO) plans (O.R.: 1.08, 95%C.I.: 1.01 - 1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees. CONCLUSIONS: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.

The Machine Learning Model for Predicting Inadequate Bowel Preparation before Colonoscopy: a Multicenter Prospective Study.

BACKGROUND AND AIMS: Colonoscopy is a critical diagnostic tool for colorectal diseases; however, its effectiveness depends on adequate bowel preparation (BP). This study aimed to develop a machine learning predictive model based on Chinese adults for inadequate BP . METHODS: A multicenter, prospective study was conducted on adult outpatients undergoing colonoscopy from January 2021 to May 2023. Data on patient characteristics, comorbidities, medication use, and BP quality were collected. Logistic regression and four machine learning models (support vector machines, decision trees, extreme gradient boosting, and bidirectional projection network) were used to identify risk factors and predict inadequate BP. RESULTS: Of 3217 patients, 21.14% had inadequate BP. The decision trees model demonstrated the best predictive capacity with an area under the receiver operating characteristic curve of 0.80 in the validation cohort. The risk factors at the nodes included body mass index, education grade, use of simethicone, diabetes, age, history of inadequate BP, and longer interval. CONCLUSION: The decision trees model we created and the identified risk factors can be used to identify patients at higher risk for inadequate BP before colonoscopy, for whom more PEG or auxiliary medication should be used.

Biochar and zero-valent iron alleviated sulfamethoxazole and tetracycline co-stress on the long-term system performance of bioretention cells: Insights into microbial community, antibiotic resistance genes and functional genes.

Antibiotics and antibiotic resistance genes (ARGs), known as emerging contaminants, have raised widespread concern due to their potential environmental and human health risks. In this study, a conventional bioretention cell (C-BRC) and three modified bioretention cells with biochar (BC-BRC), microbial fuel cell coupled/biochar (EBC-BRC) and zero-valent iron/biochar (Fe/BC-BRC) were established and two antibiotics, namely sulfamethoxazole (SMX) and tetracycline (TC), were introduced into the systems in order to thoroughly investigate the co-stress associated with the long-term removal of pollutants, dynamics of microbial community, ARGs and functional genes in wastewater treatment. The results demonstrated that the SMX and TC co-stress significantly inhibited the removal of total nitrogen (TN) (C-BRC: 37.46%; BC-BRC: 41.64%; EBC-BRC: 55.60%) and total phosphorous (TP) (C-BRC: 53.11%; BC-BRC: 55.36%; EBC-BRC: 62.87%) in C-BRC, BC-BRC and EBC-BRC, respectively, while Fe/BC-BRC exhibited profoundly stable and high removal efficiencies (TN: 89.33%; TP: 98.36%). Remarkably, greater than 99% removals of SMX and TC were achieved in three modified BRCs compared with C-BRC (SMX: 30.86 %; TC: 59.29%). The decreasing absolute abundances of denitrifying bacteria and the low denitrification functional genes (nirK: 2.80 × 105-5.97 × 105 copies/g; nirS: 7.22 × 105-1.69 × 106 copies/g) were responsible for the lower TN removals in C-BRC, BC-BRC and EBC-BRC. The amendment of Fe/BC successfully detoxified SMX and TC to functional bacteria. Furthermore, the co-stress of antibiotics stimulated the propagation of ARGs (sulI, sulII, tetA and tetC) in substrates of all BRCs and only Fe/BC-BRC effectively reduced all the ARGs in effluent by an order of magnitude. The findings contribute to developing robust ecological wastewater treatment technologies to simultaneously remove nutrients and multiple antibiotics.

Transcriptomic analysis of the hypoxia-inducible factor 1α impact on the gene expression profile of chicken fibroblasts under hypoxia.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional regulator that mediates cellular adaptive responses to hypoxia. Hypoxia-inducible factor 1α (HIF-1α) is involved in the development of ascites syndrome (AS) in broiler chickens. Therefore, studying the effect of HIF-1α on the cellular transcriptome under hypoxic conditions will help to better understand the mechanism of HIF-1α in the development of AS in broilers. In this study, we analyzed the gene expression profile of the chicken fibroblast cell line (DF-1) under hypoxic conditions by RNA-seq. Additionally, we constructed the HIF-1α knockdown DF-1 cell line by using the RNAi method and analyzed the gene expression profile under hypoxic conditions. The results showed that exposure to hypoxia for 48 h had a significant impact on the expression of genes in the DF-1 cell line, which related to cell proliferation, stress response, and apoptosis. In addition, after HIF-1α knockdown more differential expression genes appeared than in wild-type cells, and the expression of most hypoxia-related genes was either down-regulated or remained unchanged. Pathway analysis results showed that differentially expressed genes were mainly enriched in pathways related to cell proliferation, apoptosis, and oxidative phosphorylation. Our study obtained transcriptomic data from chicken fibroblasts at different hypoxic times and identified the potential regulatory network associated with HIF-1α. This data provides valuable support for understanding the transcriptional regulatory mechanism of HIF-1α in the development of AS in broilers.

Climate and Environmental Variables Drive Stream Biofilm Bacterial and Fungal Diversity on Tropical Mountainsides.

High mountain freshwater systems are particularly sensitive to the impacts of global warming and relevant environmental changes. Microorganisms contribute substantially to biogeochemical processes, yet their distribution patterns and driving mechanism in alpine streams remain understudied. Here, we examined the bacterial and fungal community compositions in stream biofilm along the elevational gradient of 745-1874 m on Mt. Kilimanjaro and explored their alpha and beta diversity patterns and the underlying environmental drivers. We found that the species richness and evenness monotonically increased towards higher elevations for bacteria, while were non-significant for fungi. However, both bacterial and fungal communities showed consistent elevational distance-decay relationships, i.e., the dissimilarity of assemblage composition increased with greater elevational differences. Bacterial alpha diversity patterns were mainly affected by chemical variables such as total nitrogen and phosphorus, while fungi were affected by physical variables such as riparian shading and stream width. Notably, climatic variables such as mean annual temperature strongly affected the elevational succession of bacterial and fungal community compositions. Our study is the first exploration of microbial biodiversity and their underlying driving mechanisms for stream ecosystems in tropical alpine regions. Our findings provide insights on the response patterns of tropical aquatic microbial community composition and diversity under climate change.

Risk of papillary thyroid carcinoma and nodular goiter associated with exposure to semi-volatile organic compounds: A multi-pollutant assessment based on machine learning algorithms.

BACKGROUND: Exposure to semi-volatile organic compounds (SVOCs) may link to thyroid nodule risk, but studies of mixed-SVOCs exposure effects are lacking. Traditional analytical methods are inadequate for dealing with mixed exposures, while machine learning (ML) seems to be a good way to fill the gaps in the field of environmental epidemiology research. OBJECTIVES: Different ML algorithms were used to explore the relationship between mixed-SVOCs exposure and thyroid nodule. METHODS: A 1:1:1 age- and gender-matched case-control study was conducted in which 96 serum SVOCs were measured in 50 papillary thyroid carcinoma (PTC), 50 nodular goiters (NG), and 50 controls. Different ML techniques such as Random Forest, AdaBoost were selected based on their predictive power, and variables were selected based on their weights in the models. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to assess the mixed effects of the SVOCs exposure on thyroid nodule. RESULTS: Forty-three of 96 SVOCs with detection rate >80 % were included in the analysis. ML algorithms showed a consistent selection of SVOCs associated with thyroid nodule. Fluazifop-butyl and fenpropathrin are positively associated with PTC and NG in single compound models (all P < 0.05). WQS model shows that exposure to mixed-SVOCs was associated with an increased risk of PTC and NG, with the mixture dominated by fenpropathrin, followed by fluazifop-butyl and propham. In the BKMR model, mixtures showed a significant positive association with thyroid nodule risk at high exposure levels, and fluazifop-butyl showed positive effects associated with PTC and NG. CONCLUSION: This study confirms the feasibility of ML methods for variable selection in high-dimensional complex data and showed that mixed exposure to SVOCs was associated with increased risk of PTC and NG. The observed association was primarily driven by fluazifop-butyl and fenpropathrin. The findings warranted further investigation.

Lycium barbarum polysaccharide alleviates DSS-induced chronic ulcerative colitis by restoring intestinal barrier function and modulating gut microbiota.

PURPOSE: This study examined the protective effects and mechanism of Lycium barbarum polysaccharides (LBP) in the context of intestinal barrier function and intestinal microbiota in mice with dextran sulfate sodium (DSS)-induced chronic ulcerative colitis (UC). METHODS: C57BL/6J male mice were assigned to a standard normal diet without DSS (control group), a normal diet with DSS (DSS group, 2% DSS given discontinuously for 3 weeks) or a normal diet supplemented with LBP (1% dry feed weight, LBP group, 2% DSS given discontinuously for 3 weeks) for a total of 8 weeks, at which point colonic tissues and caecal contents were collected. RESULTS: LBP exerted a significant effect against colitis by increasing body weight, colon length, DAI and histopathological scores. LBP inhibited proinflammatory cytokines (IL-1ß, IL-6, iNOS and TNF-α) expression, improved anti-inflammatory cytokine (IL-10) expression, promoted the expression of tight junction proteins (Occludin and ZO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2) activation and decreased Claudin-2 expression to maintain the intestinal mucosal barrier. In addition, the abundances of some probiotics (Ruminococcaceae, Lactobacillus, Butyricicoccus, and Akkermansia) were decreased with DSS treatment but increased obviously with LBP treatment. And LBP reduced the abundance of conditional pathogens associated with UC (Mucispirillum and Sutterella). Furthermore, LBP improved the production of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid and isobutyric acid. CONCLUSION: LBP can alleviate DSS-induced UC by regulating inflammatory cytokines and tight junction proteins. Moreover, LBP promotes probiotics, suppresses conditional pathogens and increases SCFAs production, showing a strong prebiotic effect.

Electrocatalytic Lignin Valorization into Aromatic Products via Oxidative Cleavage of Cα-Cß Bonds.

Lignin is the most promising candidate for producing aromatic compounds from biomass. However, the challenge lies in the cleavage of C-C bonds between lignin monomers under mild conditions, as these bonds have high dissociation energy. Electrochemical oxidation, which allows for mild cleavage of C-C bonds, is considered an attractive solution. To achieve low-energy consumption in the valorization of lignin, the use of highly efficient electrocatalysts is essential. In this study, a meticulously designed catalyst consisting of cobalt-doped nickel (oxy)hydroxide on molybdenum disulfide heterojunction was developed. The presence of molybdenum in a high valence state promoted the adsorption of tert-butyl hydroperoxide, leading to the formation of critical radical intermediates. In addition, the incorporation of cobalt doping regulated the electronic structure of nickel, resulting in a lower energy barrier. As a result, the heterojunction catalyst demonstrated a selectivity of 85.36% for cleaving the Cα-Cß bond in lignin model compound, achieving a substrate conversion of 93.69% under ambient conditions. In addition, the electrocatalyst depolymerized 49.82 wt% of soluble fractions from organosolv lignin (OL), resulting in a yield of up to 13 wt% of aromatic monomers. Significantly, the effectiveness of the prepared electrocatalyst was also demonstrated using industrial Kraft lignin (KL). Therefore, this research offers a practical approach for implementing electrocatalytic oxidation in lignin refining.

Risk of Tendon Injury in Patients Treated With Fluoroquinolone (FQ) Versus Non-Fluoroquinolone Antibiotics for Community-Acquired Pneumonia (CAP).

BACKGROUND: Fluoroquinolones (FQs) are associated with increased risk of tendon injury but comparative risk versus other antibiotic options for the same indication has yet to be evaluated. OBJECTIVE: Describe the incidence (relative risk) of any tendon injury in patients receiving FQ compared with other (non-FQs) antibiotics for treatment of community-acquired pneumonia (CAP). METHODS: A retrospective propensity score weighted cohort study was performed to evaluate the association between FQ antibiotics and tendon injury risk at 2 time points (within 1 month and within 6 months of use) compared with non-FQ regimens for treatment of CAP. The evaluation was performed using the CCAE (MarketScan Commercial Claims and Encounters) and COB (Medicare Supplemental and Coordination of Benefits) databases from 2014 to 2020. Patients with ICD (International Classification of Diseases) 9/10 coding for outpatient pneumonia who were >18 years and without history of tendon injury were included. Patients with history of tendon injury, who received multiple antibiotic therapies for recurrent pneumonia, or who received both FQ and non-FQ regimens during the study period were excluded. Propensity score weighting was used to adjust for selection bias due to contributing risk factors, including demographics (age, sex), comorbidities (diabetes mellitus, chronic kidney disease), and concurrent medications (corticosteroids). RESULTS: At 1 month, the odds of tendon injury were estimated to be significantly higher (41.9%) in patients receiving FQs compared with those receiving a non-FQ-based regimen (odds ratio [OR] = 1.419, 95% confidence interval [CI] = [1.188-1.698]). The odds of tendon injury were also estimated to be higher (OR = 1.067, 95% CI = [0.975-1.173]) in the FQ population within 180 days, but this effect was not statistically significant. The most frequent sites of tendon injuries were rotator cuff, shoulder, and patellar tendon. CONCLUSIONS AND RELEVANCE: Prescribers should recognize the risk of tendon injury within 1 month of FQ use when considering treatment regimens for CAP and use alternative options with lower risk whenever possible.

The Juvenile-Hormone-Responsive Factor AmKr-h1 Regulates Caste Differentiation in Honey Bees.

Honey bees are typical model organisms for the study of caste differentiation, and the juvenile hormone (JH) is a crucial link in the regulatory network of caste differentiation in honey bees. To investigate the mechanism of JH-mediated caste differentiation, we analyzed the effect of the JH response gene AmKr-h1 on this process. We observed that AmKr-h1 expression levels were significantly higher in queen larvae than in worker larvae at the 48 h, 84 h, and 120 h larval stages, and were regulated by JH. Inhibiting AmKr-h1 expression in honey bee larvae using RNAi could lead to the development of larvae toward workers. We also analyzed the transcriptome changes in honey bee larvae after AmKr-h1 RNAi and identified 191 differentially expressed genes (DEGs) and 682 differentially expressed alternative splicing events (DEASEs); of these, many were related to honey bee caste differentiation. Our results indicate that AmKr-h1 regulates caste differentiation in honey bees by acting as a JH-responsive gene.

Characterization of the immune cell function landscape in head and neck squamous carcinoma to assist in prognosis prediction and immunotherapy.

BACKGROUND: The malignant characteristics of cancer depend not only on intrinsic properties of cancer cells but also on the functions of infiltrating immune cells. In this study, we aimed to investigate the functional landscape of immune cells in head and neck squamous cell carcinoma (HNSCC). METHODS: We employed single-sample gene set enrichment analysis to examine the immunophenotypes of HNSCC based on 29 immune cell functions (ICFs) in TCGA and GSE65858 datasets. We analyzed the clinical features, immune microenvironment, molecular profiles, and biological processes. Additionally, we developed and validated an ICF-based risk score for personalized prognosis prediction. We confirmed the value of the ICF score in our cohort using qRT-PCR and immunohistochemistry. Molecular docking was used to predict potential compounds for immunotherapy. RESULTS: Three immunophenotypes (Immune-L, Immune-M, and Immune-H) were identified in 769 HNSCC samples. The characteristics of Immune-H were consistent with a "Hot" tumor, Immune-L was similar to a "Cold" tumor, and Immune-M exhibited intermediate features. The ICF risk score was associated with immune checkpoints, infiltrating immune cells, tumor mutation burden, and sensitivities to targeted/chemotherapeutic agents. Gene set variation analysis implicated the involvement of metabolic reprogramming pathways in the high-risk group. The combination of "Tumor Immune Dysfunction and Exclusion" and "Immunophenoscore" algorithms indicated that the low-risk group had a higher likelihood of benefiting from immunotherapy. Finally, we identified Eltrombopag and other compounds that may be beneficial for HNSCC immunotherapy. CONCLUSION: Our study provides a novel perspective on the tumor microenvironment of HNSCC, aiding in the understanding of HNSCC heterogeneity and the development of personalized/precision medicine.

Comparative study on the clinical efficacy of small plate assisted anatomic plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of small plate assisted anatomical plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture. METHODS AND MATERIALS: The data of 68 patients with pilon fracture admitted to Hospital from June 2017 to June 2020 were retrospectively analyzed. Study group and control group were divided according to different operation methods, with 34 cases in each group. There were 28 cases of Rüedi and Allgöwer II type and 40 cases of Rüedi and Allgöwer III type. Perioperative period data, Ankle joint function score, visual analog scale (VAS) scores and the incidence of incision complications were analyzed between these two groups. RESULTS: There were no significant differences in full load time, fracture healing time between these two groups (P > 0.05). The operation time, intraoperative blood loss, length of hospital stay, Ankle joint function score and postoperative incision complication rate in observation group were lower than those in control group (P < 0.05). CONCLUSION: Small plate assisted anatomic plate is comparable to traditional double plate in the treatment of pilon fracture in terms of complete loading time, fracture healing time, but the former can shorten the operation time, reduce intraoperative blood loss and effectively reduce the incidence of postoperative complications.

Racial and ethnic differences in patterns of use and discontinuation of long-acting injectable antipsychotics using Medicaid claims data.

Introduction: In general, racial and ethnic differences exist in antipsychotic prescription practices. However, little is known about such differences between individual long-acting injectable (LAI) antipsychotic formulations, specifically. This study's primary objective was to determine racial and ethnic differences among LAI antipsychotic use. Secondary objectives were to identify if discontinuation rates differed between agents and by race or ethnicity. Methods: International Classification of Diseases, 10th edition (ICD-10) codes were used to identify patients with schizophrenia and related disorders (18-64 years) who received an LAI antipsychotic between 2016 and 2020 using Merative Multi-State Medicaid databases. Using National Drug Code numbers for LAI antipsychotics, pharmacy claims were identified and data analyzed. Cochran-Mantel-Haenszel tests and odds ratio estimators were used to investigate conditional association between race or ethnicity and medication, while controlling for age, sex, health plan, and prescription year. Kaplan-Meier survival curves were examined, and stratified log-rank tests were conducted to compare the time until discontinuation distributions by race or ethnicity. Results: The analysis included 37 712 patients. Blacks received an LAI first-generation antipsychotic more often than Whites (OR: 1.64, 95% CI: [1.56, 1.73], Hispanics (OR: 1.46, 95% CI: [1.21, 1.75]) and others (OR: 1.44, 95% CI: [1.20, 1.73]). Aside from fluphenazine decanoate showing earlier discontinuation rates for Whites over Blacks (P = .02), no significant differences in discontinuation across race or ethnicity were identified. Discussion: Despite no significant differences in second-generation antipsychotic LAI discontinuation rates between Blacks and other racial or ethnic groups, Blacks received second-generation antipsychotic LAIs significantly less often than other groups. Further studies are needed to determine why differences may be occurring.

Advanced nanopesticides: Advantage and action mechanisms.

The use of various chemical substances to control pests, diseases, and weeds in the field is a necessary part of the agricultural development process in every country. While the application of pesticides can improve the quality and yield of crops, plant resistance and the harm caused by pesticide residues to the environment and humans have led to the search for greener and safer pesticide formulations to improve the current situation. In recent years, nanopesticides (NPts) have shown great potential in agriculture due to their high efficiency, low toxicity, targeting, resistance, and controlled slow release demonstrated in the experimental stage. Commonly used approaches to prepare NPts include the use of nanoscale metal materials as active ingredients (AI) (ingredients that can play a role in insecticide, sterilization and weeding) or the construction of carriers based on commonly used pesticides to make them stable in nano-sized form. This paper systematically summarizes the advantages and effects of NPts over conventional pesticides, analyzes the formation and functions of NPts in terms of structure, AI, and additives, and describes the mechanism of action of NPts. Despite the feasibility of NPts use, there is not enough comprehensive research on NPts, which must be supplemented by more experiments in terms of biotoxicology and ecological effects to provide strong support for NPts application.

Prevalence and factors associated with pentavalent vaccination: a cross-sectional study in Southern China.

BACKGROUND: Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives. A complex immunization schedule, however, may be burdensome to parents and lead to reduced vaccine compliance and completion. Thus, it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule. This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis and Haemophilus influenzae type B conjugate (DTaP-IPV/Hib) vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations. METHODS: A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023. The study employed a stratified multistage cluster random sampling method. Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire. Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations. RESULTS: Of the 4818 valid responses, 95.3% of children were aged 3-4 years, and 2856 (59.3%) held rural hukou. Coverage rates of the DTaP-IPV/Hib vaccine, from 1 to 4 doses, were 24.4%, 20.7%, 18.5%, and 16.0%, respectively. Caregivers who are concerned about vaccine efficacy [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI): 1.30-1.79], the manufacturer (aOR = 2.05, 95% CI: 1.69-2.49), and a simple immunization schedule (aOR = 1.26, 95% CI: 1.04-1.54) are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib. In addition, caregivers in urban areas showed more concern about the vaccine price (P = 0.010) and immunization schedule (P = 0.022) in regard to vaccinating children. CONCLUSIONS: The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low. Factors such as lower socioeconomic status, cultural beliefs, concerns about vaccine safety, and cost may hinder caregivers from vaccinating their children. Further measures, such as health education campaigns to raise knowledge and awareness, and encouragement of domestic vaccine innovation, which would reduce out-of-pocket costs, could be implemented to improve the coverage of DTap-IPV/Hib vaccination.

Impact of progesterone concentration on human chorionic gonadotropin trigger day on clinical outcomes with one top-quality cleavage-stage embryo or blastocyst transfer in fresh in vitro fertilization cycles.

Objective: To investigate the impact of the progesterone concentration on the human chorionic gonadotropin (hCG) trigger day on clinical outcomes with an antagonist protocol. Methods: The retrospective cohort study included a total of 1,550 fresh autologous ART cycles with one top-quality embryo transfer. Multivariate regression analysis, curve fitting, and threshold effect analysis were performed. Results: A significant association was found between the progesterone concentration and clinical pregnancy rate (adjusted OR, 0.77; 95% CI, 0.62-0.97; P = 0.0234), especially in blastocyst transfer (adjusted OR, 0.56; 95% CI, 0.39-0.78; P = 0.0008). The association between the progesterone concentration and the ongoing pregnancy rate was insignificant. The clinical pregnancy rate showed a linear relationship with an increased progesterone concentration in cleavage-stage embryo transfer. In blastocyst transfer, as the progesterone concentration increased, the clinical and ongoing pregnancy rates showed a parabolic reverse-U curve; the curve initially increased before declining at high progesterone concentrations. The clinical pregnancy rate increased with a progesterone concentration up to 0.80 ng/mL rather than tended to be stable. The clinical pregnancy rate significantly decreased when the progesterone concentration was ≥0.80 ng/mL. Conclusion: The progesterone concentration on the hCG trigger day exhibits a curvilinear relationship with pregnancy outcomes in blastocyst transfer cycles, and the optimal threshold of the progesterone concentration is 0.80 ng/mL.

Tele-Instruction Tool for Multiple Lay Responders Providing Cardiopulmonary Resuscitation in Telehealth Emergency Dispatch Services: Mixed Methods Study.

BACKGROUND: Telephone-assisted cardiopulmonary resuscitation (T-CPR) has proven to be a crucial intervention in enhancing the ability of lay responders to perform cardiopulmonary resuscitation (CPR) during telehealth emergency services. While the majority of established T-CPR protocols primarily focus on guiding individual rescuers, there is a lack of emphasis on instructing and coordinating multiple lay responders to perform resuscitation collaboratively. OBJECTIVE: This study aimed to develop an innovative team-based tele-instruction tool to efficiently organize and instruct multiple lay responders on the CPR process and to evaluate the effectiveness and feasibility of the tool. METHODS: We used a mixed methods design in this study. We conducted a randomized controlled simulation trial to conduct the quantitative analysis. The intervention groups used the team-based tele-instruction tool for team resuscitation, while the control groups did not have access to the tool. Baseline resuscitation was performed during the initial phase (phase I test). Subsequently, all teams watched a team-based CPR education training video and finished a 3-person practice session with teaching followed by a posttraining test (phase II test). In the qualitative analysis, we randomly selected an individual from each team and 4 experts in emergency medical services to conduct semistructured interviews. The purpose of these interviews was to evaluate the effectiveness and feasibility of this tool. RESULTS: The team-based tele-instruction tool significantly improved the quality of chest compression in both phase I and phase II tests. The average compression rates were more appropriate in the intervention groups compared to the control groups (median 104.5, IQR 98.8-111.8 min-1 vs median 112, IQR 106-120.8 min-1; P=.04 in phase I and median 117.5, IQR 112.3-125 min-1 vs median 111, IQR 105.3-119 min-1; P=.03 in phase II). In the intervention group, there was a delay in the emergency response time compared to that in the control group (time to first chest compression: median 20, IQR 15-24.8 seconds vs median 25, IQR 20.5-40.3 seconds; P=.03; time to open the airway: median 48, IQR 36.3-62 seconds vs median 73.5, IQR 54.5-227.8 seconds; P=.01). However, this delay was partially mitigated after the phase II test. The qualitative results confirmed the compatibility and generalizability of the team-based tele-instruction tool, demonstrating its ability to effectively guide multiple lay responders through teamwork and effective communication with telecommunicators. CONCLUSIONS: The use of the team-based tele-instruction tool offers an effective solution to enhance the quality of chest compression among multiple lay responders. This tool facilitated the organization of resuscitation teams by dispatchers and enabled efficient cooperation. Further assessment of the widespread adoption and practical application of the team-based tele-instruction tools in real-life rescue scenarios within the telehealth emergency services system is warranted.

Curcumin supplementation increases longevity and antioxidant capacity in Caenorhabditis elegans.

Curcumin is well known as a potent antioxidant and free radical scavenger and has great potential for anti-aging applications. In this study, we investigate the molecular mechanism of curcumin in prolonging the lifespan of C. elegans. Four concentrations of curcumin (10, 25, 50, and 100 µM) were administered, and the optimal treatment concentration was determined by analyzing the nematode lifespan, physiology, and biochemistry. Additionally, RNA-seq and qRT-PCR were performed to explore the antioxidant effect of curcumin and its underlying mechanism. Results revealed that curcumin could significantly improve the survival capacity of C. elegans without influencing its growth. Curcumin was observed to significantly decrease the levels of reactive oxygen species (ROS) under extreme conditions such as heat stress and paraquat stress. In addition, curcumin increased the amount of nematode mitochondrial DNA (mtDNA) replication. RNA-seq results revealed that the underlying mechanism of curcumin in C. elegans is related to the mitogen-activated protein kinase (MAPK) pathway. qRT-PCR results confirmed that the expression of oxidative stress-related genes (sod-1, sod-2, sod-3, gst-4) was increased, and the expression of MAPK signaling pathway-related genes (sek-1, pmk-1, nsy-1) was significantly downregulated. Furthermore, the administration of curcumin extended the lifespan of nematodes, potentially through the enhancement of oxidative stress resistance and the downregulation of the MAPK signaling pathway. These findings improve our understanding of both lifespan extension and the potential mechanism of curcumin in C. elegans.

Hypoxia-induced reprogramming of glucose-dependent metabolic pathways maintains the stemness of human bone marrow-derived endothelial progenitor cells.

The benefits of hypoxia for maintaining the stemness of cultured human bone marrow-derived endothelial progenitor cells (BM EPCs) have previously been demonstrated but the mechanisms responsible remain unclear. Growing evidences suggest that cellular metabolism plays an important role in regulating stem cell fate and self-renewal. Here we aimed to detect the changes of glucose metabolism and to explore its role on maintaining the stemness of BM EPCs under hypoxia. We identified the metabolic status of BM EPCs by using extracellular flux analysis, LC-MS/MS, and 13C tracing HPLC-QE-MS, and found that hypoxia induced glucose metabolic reprogramming, which manifested as increased glycolysis and pentose phosphate pathway (PPP), decreased tricarboxylic acid (TCA) and mitochondrial respiration. We further pharmacologically altered the metabolic status of cells by employing various of inhibitors of key enzymes of glycolysis, PPP, TCA cycle and mitochondria electron transport chain (ETC). We found that inhibiting glycolysis or PPP impaired cell proliferation either under normoxia or hypoxia. On the contrary, inhibiting pyruvate oxidation, TCA or ETC promoted cell proliferation under normoxia mimicking hypoxic conditions. Moreover, promoting pyruvate oxidation reverses the maintenance effect of hypoxia on cell stemness. Taken together, our data suggest that hypoxia induced glucose metabolic reprogramming maintains the stemness of BM EPCs, and artificial manipulation of cell metabolism can be an effective way for regulating the stemness of BM EPCs, thereby improving the efficiency of cell expansion in vitro.

Novel Aggregation-Induced Emission Fluorescent Molecule for Platinum(IV) Ion-Selective Recognition and Imaging of Controlled Release in Cells.

The loading, delivery, and release of Pt(IV) precursors in living organisms are important aspects of exploring the development of platinum drugs. In recent years, the biological application of the fluorescent sensors to platinum drugs has been insufficient to meet the study of Pt(IV) precursors. It is urgent to design and develop a biocompatible, multifunctional fluorescent sensor for the study of loading, transport, and release of Pt(IV) ions. Herein, we report a fluorescent molecule (E)-6-(diethylamino)-N'-(4-(diphenylamino) benzylidene)-2-oxo-2H-chromene-3 carbohydrazide (CHTPA). CHTPA has good sensitivity and selectivity to Pt(IV) when the water content is 5%, and significant increase of the fluorescence emission intensity of CHTPA is observed with Pt(IV) concentration. The sensing mechanism is attributed to photo-induced electron transfer, which is verified by X-ray absorption near edge spectroscopy spectra, UV-vis absorption spectroscopy, 1H NMR spectra, and Fourier transform infrared spectra. Furthermore, the CHTPA-Pt(IV) complex is able to release Pt(IV) in aqueous solution, and the green fluorescence of CHTPA based on the aggregation-induced emission effect can be observed. Inspired by these, the amphiphilic block copolymer poly(ethyloxide)-block-polystyrene (PEO-b-PS) is used to prepare the nonconjugated polymer dots (Pdots). The experimental results show that Pdots can effectively slow down the release speed of Pt(IV) in aqueous solution and it has a great monodispersity in aqueous solution. Meanwhile, Pdots show low cytotoxicity, and this is favorable for intracellular applications. The investigation of cellular imaging indicates that these Pdots can act as a carrier to deliver Pt(IV) into MCF-7 cells for visualized delivery and sustained release of platinum(IV) ions. Therefore, this study provides a new avenue to design and develop a biocompatible multifunctional fluorescent sensor for studying the loading, delivery, and release of Pt(IV) in cells.