A novel ESIPT fluorescent probe for early detection and assessment of ferroptosis-mediated acute kidney injury via peroxynitrite fluctuation.

BACKGROUND: Acute kidney injury (AKI) poses a severe risk to public health, mostly manifested by damage and death of renal tubular epithelial cells. However, routine blood examination, a conventional approach for clinical detection of AKI, is not available for identifying early-stage AKI. Plenty of reported methods were lack of early biomarkers and real time evaluation tools, which resulted in a vital challenge for early diagnosis of AKI. Therefore, developing novel probes for early detection and assessment of AKI is exceedingly crucial. RESULTS: Based on ESIPT mechanism, a new fluorescent probe (MEO-NO) with 2-(2'-hydroxyphenyl) benzothiazole (HBT) derivatives as fluorophore has been synthesized for dynamic imaging peroxynitrite (ONOO-) levels in ferroptosis-mediated AKI. Upon the addition of ONOO-, MEO-NO exhibited obvious fluorescence changes, a significant Stokes shift (130 nm) and rapid response (approximately 45 s), and featured exceptional sensitivity (LOD = 7.28 nM) as well as high selectivity from the competitive species at physiological pH. In addition, MEO-NO was conducive to the biological depth imaging ONOO- in cells, zebrafish, and mice. Importantly, MEO-NO could monitor ONOO- levels during sorafenib-induced ferroptosis and CP-induced AKI. With the assistance of MEO-NO, we successfully visualized and tracked ONOO- variations for early detection and assessment of ferroptosis-mediated AKI in cells, zebrafish and mice models. SIGNIFICANCE AND NOVELTY: Benefiting from the superior performance of MEO-NO, experimental results further demonstrated that the levels of ONOO- was overexpressed during ferroptosis-mediated AKI in cells, zebrafish, and mice models. The developed novel probe MEO-NO provided a strong visualization tool for imagining ONOO-, which might be a potential method for the prevention, diagnosis, and treatment of ferroptosis-mediated AKI.

Establishing and Validating an Innovative Focal Adhesion-Linked Gene Signature for Enhanced Prognostic Assessment in Endometrial Cancer.

Studies have highlighted the significant role of focal adhesion signaling in cancer. Nevertheless, its specific involvement in the pathogenesis of endometrial cancer and its clinical significance remains uncertain. We analyzed TCGA-UCEC and GSE119041 datasets with corresponding clinical data to investigate focal adhesion-related gene expression and their clinical significance. A signature, "FA-riskScore," was developed using LASSO regression in the TCGA cohort and validated in the GSE dataset. The FA-riskScore was compared with four existing models in terms of their prediction performance. We employed univariate and multivariate Cox regression analyses towards FA-riskScore to assess its independent prognostic value. A prognostic evaluation nomogram based on our model and clinical indexes was established subsequently. Biological and immune differences between high- and low-risk groups were explored through functional enrichment, PPI network analysis, mutation mining, TME evaluation, and single-cell analysis. Sensitivity tests on commonly targeted drugs were performed on both groups, and Connectivity MAP identified potentially effective molecules for high-risk patients. qRT-PCR validated the expressions of FA-riskScore genes. FA-riskScore, based on FN1, RELN, PARVG, and PTEN, indicated a poorer prognosis for high-risk patients. Compared with published models, FA-riskScore achieved better and more stable performance. High-risk groups exhibited a more challenging TME and suppressive immune status. qRT-PCR showed differential expression in FN1, RELN, and PTEN. Connectivity MAP analysis suggested that BU-239, potassium-canrenoate, and tubocurarine are effective for high-risk patients. This study introduces a novel prognostic model for endometrial cancer and offers insights into focal adhesion's role in cancer pathogenesis.

Cross-cultural adaptation and validation of the Chinese version of the intensive care oral care frequency and assessment scale.

Objectives: The objective of this study was to translate the Intensive Care Oral Care Frequency and Assessment Scale into Chinese and to evaluate its reliability and validity in Chinese ICU patients. Methods: This study was conducted using a cross-sectional survey design in ICUs of three tertiary hospitals in Huai'an and Taizhou from October 2022 to April 2023. The Chinese version of the Intensive Care Oral Care Frequency and Assessment Scale (C-ICOCFAS) was developed by expert consultation and cultural adaptation according to the two-person verbatim translation-back translation criteria described in the Brislin model. Item analysis was conducted using correlation analysis, and validity analysis included content validity, construct validity, and criterion validity. Reliability analyses included Cronbach's alpha coefficient, Guttman split-half reliability, and interrater reliability. Results: The Chinese version of the scale consisted of one dimension and nine items, consistent with the original version. Exploratory factor analysis showed KMO = 0.891, and the cumulative variance contribution reached 65.534 %. The confirmatory factor analysis indicated a good fit, χ2/df = 2.124, NFI = 0.950, GFI = 0.942, IFI = 0.973, CFI = 0.973, SRMR = 0.037, and RMSEA = 0.073. The content validity of the scale was 0.97, and the content validity of the items ranged from 0.83 to 1.00; the criterion validity was 0.969; the Cronbach's alpha coefficient was 0.919; the total item correlation coefficient was 0.725-0.831; the Guttman split-half reliability was 0.919; and the interrater reliability was 0.885. Conclusion: The C-ICOCFAS has good reliability and validity and can effectively guide nurses in the frequency of oral care for ICU patients. Implications for clinical practice: This tool can significantly improve the level of oral care among ICU patients and further promote the health and safety of patients. These findings can help clinical nursing experts to better understand and master the use of scales and standards to improve nursing.

Impact of an integrated medication management model on the collaborative working relationship among healthcare professionals in a hospital: an explanatory mixed methods study.

An integrated medication management (IMM) model was implemented in a medical center ward to improve the delivery of clinical pharmaceutical services (CPSs). This model incorporated a ward-based clinical pharmacist who performed medication reconciliation and medication reviews. It was perceived to promote interprofessional collaboration between pharmacists and non-pharmacist healthcare professionals (NPHPs, including attending physicians, nurse practitioners, and registered nurses). This study aimed to evaluate the effects of the IMM on NPHPs' intentions to collaborate with pharmacists and understand the mechanism of the impact of the IMM on interprofessional collaboration. A sequential explanatory mixed methods design was employed in the study. Initially, a questionnaire was administered to assess the effects of the IMM on NPHPs' intentions to collaborate with pharmacists. The NPHPs' experiences with the IMM were then documented using semi-structured interviews with inductive thematic analysis. Fifty-eight NPHPs completed the questionnaire, and NPHPs from the intervention ward reported a higher intention to discuss patient-related medication issues with pharmacists, indicating collaboration. Eleven NPHPs were interviewed, and they stated having better working relationships with pharmacists, experiencing more effective CPSs, and noting improved communication with pharmacists. The integration of quantitative and qualitative findings demonstrates that the critical mechanism of the IMM in promoting collaborative relationships is to integrate pharmacists into medical practice, which familiarizes NPHPs with pharmacists' roles, improves communication, and enables pharmacists to identify NPHPs' needs. To summarize, allowing ward-based pharmacists to engage in medical teams on a regular basis appears vital for improving interprofessional teamwork. Furthermore, stakeholders aiming to promote CPS in their institutions should consider the needs and communication channels among NPHPs.

Assessment of left atrioventricular coupling and left atrial function impairment in diabetes with and without hypertension using CMR feature tracking.

PURPOSE: The study was designed to assess the effect of co-occurrence of diabetes mellitus (DM) and hypertension on the deterioration of left atrioventricular coupling index (LACI) and left atrial (LA) function in comparison to individuals suffering from DM only. METHODS: From December 2015 to June 2022, we consecutively recruited patients with clinically diagnosed DM who underwent cardiac magnetic resonance (CMR) at our hospital. The study comprised a total of 176 patients with DM, who were divided into two groups based on their blood pressure status: 103 with hypertension (DM + HP) and 73 without hypertension (DM-HP). LA reservoir function (reservoir strain (εs), total LA ejection fraction (LAEF)), conduit function (conduit strain (εe), passive LAEF), booster-pump function (booster strain (εa) and active LAEF), LA volume index (LAVI), LV global longitudinal strain (LVGLS), and LACI were evaluated and compared between the two groups. RESULTS: After adjusting for age, sex, body surface area (BSA), and history of current smoking, total LAEF (61.16 ± 14.04 vs. 56.05 ± 12.72, p = 0.013) and active LAEF (43.98 ± 14.33 vs. 38.72 ± 13.51, p = 0.017) were lower, while passive LAEF (33.22 ± 14.11 vs. 31.28 ± 15.01, p = 0.807) remained unchanged in the DM + HP group compared to the DM-HP group. The DM + HP group had decreased εs (41.27 ± 18.89 vs. 33.41 ± 13.94, p = 0.006), εe (23.69 ± 12.96 vs. 18.90 ± 9.90, p = 0.037), εa (17.83 ± 8.09 vs. 14.93 ± 6.63, p = 0.019), and increased LACI (17.40±10.28 vs. 22.72±15.01, p = 0.049) when compared to the DM-HP group. In patients with DM, multivariate analysis revealed significant independent associations between LV GLS and εs (ß=-1.286, p < 0.001), εe (ß=-0.919, p < 0.001), and εa (ß=-0.324, p = 0.036). However, there was no significant association observed between LV GLS and LACI (ß=-0.003, p = 0.075). Additionally, hypertension was found to independently contribute to decreased εa (ß=-2.508, p = 0.027) and increased LACI in individuals with DM (ß = 0.05, p = 0.011). CONCLUSIONS: In DM patients, LV GLS showed a significant association with LA phasic strain. Hypertension was found to exacerbate the decline in LA booster strain and increase LACI in DM patients, indicating potential atrioventricular coupling index alterations.

Comparison of robotic versus laparoscopic versus open distal gastrectomy for locally advanced gastric cancer: a prospective trial-based economic evaluation.

IMPORTANCE: It is largely unclear whether robotic distal gastrectomy (RDG) is cost-effective for locally advanced gastric cancer (LAGC). OBJECTIVE: To evaluate the cost-effectiveness of RDG, laparoscopic distal gastrectomy (LDG), and open distal gastrectomy (ODG) for patients with LAGC. DESIGN, SETTING, AND PARTICIPANTS: Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. A decision-analytic model was constructed to evaluate the cost-effectiveness of RDG, LDG, and ODG. EXPOSURES: RDG, LDG, and ODG. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio (ICER) and quality-adjusted life year (QALY). RESULTS: This pooled analysis of two randomized controlled trials included 449 patients: 117, 254, and 78 patients in the RDG, LDG, and ODG groups, respectively. After IPTW, RDG demonstrated its priority in terms of less blood loss, postoperative length, and complication rate (all P < 0.05). RDG also showed higher QOL with more cost, representing an ICER of $85,739.73 per QALY and $42,189.53 per QALY compared to LDG and ODG, respectively. In probabilistic sensitivity analysis, RDG achieved the best cost-effectiveness for patients with LAGC only when the willingness-to-pay threshold was > $85,739.73 per QALY, which significantly exceeded 3 times Chinese per capita GDP. Furthermore, one of the most important factors was the indirect costs of robotic surgery in terms of the cost-effectiveness of RDG compared to that of LDG or ODG. CONCLUSIONS AND RELEVANCE: Although improved short-term outcomes and QOL were seen in patients underwent RDG, the economic burden should be considered in the clinical decision-making regarding robotic surgery use for patients with LAGC. Our findings may vary in different health care settings and affordability. Trial registration CLASS-01 trial (ClinicalTrials.gov, CT01609309) and FUGES-011 trial (ClinicalTrials.gov, NCT03313700).

Synergistic driving effects of risk factors on human brucellosis in Datong City, China: A dynamic perspective from spatial heterogeneity.

Brucellosis is a highly contagious zoonotic and systemic infectious disease caused by Brucella, which seriously affects public health and socioeconomic development worldwide. Particularly, in China accumulating eco-environmental changes and agricultural intensification have increased the expansion of human brucellosis (HB) infection. As a traditional animal husbandry area adjacent to Inner Mongolia, Datong City in northwestern China is characterized by a high HB incidence, demonstrating obvious variations in the risk pattern of HB infection in recent years. In this study, we built Bayesian spatiotemporal models to detect the transfer of high-risk clusters of HB occurrence in Datong from 2005 to 2020. Geographically and Temporally Weighted Regression and GeoDetector were employed to investigate the synergistic driving effects of multiple potential risk factors. Results confirmed an evident dynamic expansion of HB from the east to the west and south in Datong. The distribution of HB showed a negative correlation with urbanization level, economic development, population density, temperature, precipitation, and wind speed, while a positive correlation with the normalized difference vegetation index, and grassland/cropland cover areas. Especially, the local animal husbandry and related industries imposed a large influence on the spatiotemporal distribution of HB. This work strengthens the understanding of how HB spatial heterogeneity is driven by environmental factors, through which helpful insights can be provided for decision-makers to formulate and implement disease control strategies and policies for preventing the further spread of HB.

Acetolysis of waste polyethylene terephthalate for upcycling and life-cycle assessment study.

To reduce environmental pollution and reliance on fossil resources, polyethylene terephthalate as the most consumed synthetic polyester needs to be recycled effectively. However, the existing recycling methods cannot process colored or blended polyethylene terephthalate materials for upcycling. Here we report a new efficient method for acetolysis of waste polyethylene terephthalate into terephthalic acid and ethylene glycol diacetate in acetic acid. Since acetic acid can dissolve or decompose other components such as dyes, additives, blends, etc., Terephthalic acid can be crystallized out in a high-purity form. In addition, Ethylene glycol diacetate can be hydrolyzed to ethylene glycol or directly polymerized with terephthalic acid to form polyethylene terephthalate, completing the closed-loop recycling. Life cycle assessment shows that, compared with the existing commercialized chemical recycling methods, acetolysis offers a low-carbon pathway to achieve the full upcycling of waste polyethylene terephthalate.

Effectiveness assessment of using water environmental microHI to predict the health status of wild fish.

Aquatic wildlife health assessment is critically important for aquatic wildlife conservation. However, the health assessment of aquatic wildlife (especially aquatic wild animals) is difficult and often accompanied by invasive survey activities and delayed observability. As there is growing evidence that aquatic environmental microbiota could impact the health status of aquatic animals by influencing their symbiotic microbiota, we propose a non-invasive method to monitor the health status of wild aquatic animals using the environmental microbiota health index (microHI). However, it is unknown whether this method is effective for different ecotype groups of aquatic wild animals. To answer this question, we took a case study in the middle Yangtze River and studied the water environmental microbiota and fish gut microbiota at the fish community level, population level, and ecotype level. The results showed that the gut microHI of the healthy group was higher than that of the unhealthy group at the community and population levels, and the overall gut microHI was positively correlated with the water environmental microHI, whereas the baseline gut microHI was species-specific. Integrating these variations in four ecotype groups (filter-feeding, scraper-feeding, omnivorous, and carnivorous), only the gut microHI of the carnivorous group positively correlated with water environmental microHI. Alcaligenaceae, Enterobacteriaceae, and Achromobacter were the most abundant groups with health-negative-impacting phenotypes, had high positive correlations between gut sample group and environment sample group, and had significantly higher abundance in unhealthy groups than in healthy groups of carnivorous, filter-feeding, and scraper-feeding ecotypes. Therefore, using water environmental microHI to indicate the health status of wild fish is effective at the community level, is effective just for carnivorous fish at the ecotype level. In the middle Yangtze River, Alcaligenaceae, Enterobacteriaceae (family level), and Achromobacter (genus level) were the key water environmental microbial groups that potentially impacted wild fish health status. Of course, more data and research that test the current hypothesis and conclusion are encouraged.

Impact of integrated medication management program on medication errors in a medical center: an interrupted time series study.

BACKGROUND: Medication errors (MEs) are harmful to patients during hospitalization, especially elderly patients. To reduce MEs, an integrated medication management (IMM) model was developed in a 2500-bed medical center, allowing a clinical pharmacist to participate in the daily ward round and perform medication reconciliation and medication reviews. This study aimed to evaluate the impact of the IMM model on MEs and medication utilization using a quasi-experimental design. METHODS: We conducted an interrupted time-series study using the aggregated data of monthly admissions from two wards of a medical center, where one ward served as the intervention and the other served as the external control. The pre- and post-intervention phases comprised of 40 and 12 monthly observational units, respectively. The primary outcome was the mean number of ME reports, which were further investigated for different ME types. The mean number of daily inpatient prescriptions, mean number of daily self-prepared medications, and median daily medication costs were measured. All outcomes were measured per admission episode. Segmented regression was used to evaluate the level and slope changes in the outcomes after IMM model implementation, and subgroup analyses were performed to examine the effects on different groups. RESULTS: After IMM model implementation, the mean number of ME reports increased (level change: 1.02, 95% confidence interval [CI]: 0.68 to 1.35, P < 0.001). The number of reports has shown a dramatic increase in omissions or medication discrepancies, inappropriate drug choices, and inappropriate routes or formulations. Furthermore, the mean number of daily inpatient prescriptions was reduced for patients aged ≥75 years (level change: -1.78, 95% CI: -3.06 to -0.50, P = 0.009). No significant level or slope change was observed in the control ward during the post-intervention phase. CONCLUSIONS: The IMM model improved patient safety and optimized medication utilization by increasing the reporting of MEs and decreasing the number of medications used.

The influence of multidisciplinary team clinic on the prognosis of patients with chronic kidney disease.

Chronic kidney disease (CKD) seriously affects the quality of life and survival time of patients, and even affects social and national economic development. In China, how to effectively control the disease process of CKD outpatients has not been determined. A retrospective analysis was made to 100 patients with CKD. Fifty patients treated with traditional clinical treatment were in the control group, and the other fifty patients treated with multidisciplinary team (MDT) clinical treatment were in the MDT group. The prognosis of the two groups after treatment was compared, including glomerular filtration rate (GFR), number of renal replacement treatments, and mortality, to evaluate the actual effect of MDT clinic. CKD patients in the MDT group received the MDT clinic for 24 months. There was no significant difference between GFR and serum creatinine level before treatment, and the quality of life was significantly higher than before. In the control group, the GFR declined more dramatically, the serum creatinine level was higher, and the quality of life was lower than before (P < 0.05). The frequency of renal replacement therapy and mortality in the MDT group were significantly lower than those in the control group (P < 0.05). MDT clinic can effectively improve the prognosis of patients with CKD, delay kidney disease progression, and reduce mortality.

Impact of the Requirement of Bone Mineral Density Evidence on Utilization of Anti-osteoporosis Medications, Clinical Outcome and Medical Expenditures of Patient With Hip Fracture in Taiwan.

BACKGROUND: Since 2011, Taiwan's National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. METHODS: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. RESULTS: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old. CONCLUSION: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.

Comparative cradle-to-grave life cycle assessment of bio-based and petrochemical PET bottles.

This article presents a life cycle assessment of bio-based polyethylene terephthalate (PET) bottles with a cradle to grave scope and provides a comparison with petrochemical PET bottles for 13 environmental impact categories. Besides the baseline bio-based PET bottles, which are produced from Brazilian sugarcane reflecting status-quo, two alternative hypothetical bio-based product systems were considered: European wheat straw and European crops market mix composed of maize, wheat and sugar beet. The land-use change (LUC) impacts were assessed based on a deterministic model. The end-of-life impact was assessed using the EASETECH model. Baseline bio-based PET bottles performed overall worse than conventional petrochemical PET bottles, offering only better performance (about 10%) in abiotic depletion (fossil fuels). Comparable performance is observed for climate change (2% difference without the LUC, and 7% with LUC impacts). Using European crops for ethanol production (alternative 1) instead of Brazilian sugarcane resulted in a worse environmental performance, due to lower yields attained compared to Brazilian sugarcane. When wheat straw was considered as biomass feedstock for ethanol production (alternative 2), similar environmental performance with petrochemical PET bottles was seen.

High nitrogen stainless steel drug-eluting stent - Assessment of pharmacokinetics and preclinical safety in vivo.

Pharmacokinetic analyses were performed using 20 pigs for 120-days implantation, while one sirolimus-eluting stent was implanted into one of their coronary artery. At different time points, the residual sirolimus on the stent, delivered locally (to artery wall), regionally (to adjacent and downstream muscle) and systemically (to plasma and visceral organs), was detected throughout 120 days. Preclinical safety evaluation was performed using 32 pigs for 180-days implantation to study the safety of metal platform material and the effectiveness of sirolimus eluting coating on the HNS stent. The neointima area, restenosis rate and inflammatory grade for HNS and control group stents were detected and analyzed. Approximately 80% sirolimus was eluted from the sirolimus-eluting stents after 30-days implantation in vivo. Additionally, there was sustained sirolimus in the artery wall, cardiac muscle and heart throughout 120-days implantation, and sirolimus accumulated to the peak at 90-days implantation. It was inferred that the sirolimus eluting stent in this study was covered by neointima before 90-days implantation, indicating that the sirolimus eluting coating on the HNS stent was safe and effective. Very little sirolimus was distributed in visceral organs after 14-days implantation. HNS sirolimus-eluting stent exhibited lower restenosis rate and lower inflammatory grade than control group, which verified that the sirolimus-eluting coating design in this study was reasonable and practical. In addition, there were no significant difference in restenosis rate and inflammatory score between HNS bare-metal stent and drug-eluting stents, illustrating that HNS has good bio-compatibility and is suitable to use as coronary artery stent material.

Evaluation of Combined Artificial Intelligence and Radiologist Assessment to Interpret Screening Mammograms.

Importance: Mammography screening currently relies on subjective human interpretation. Artificial intelligence (AI) advances could be used to increase mammography screening accuracy by reducing missed cancers and false positives. Objective: To evaluate whether AI can overcome human mammography interpretation limitations with a rigorous, unbiased evaluation of machine learning algorithms. Design, Setting, and Participants: In this diagnostic accuracy study conducted between September 2016 and November 2017, an international, crowdsourced challenge was hosted to foster AI algorithm development focused on interpreting screening mammography. More than 1100 participants comprising 126 teams from 44 countries participated. Analysis began November 18, 2016. Main Outcomes and Measurements: Algorithms used images alone (challenge 1) or combined images, previous examinations (if available), and clinical and demographic risk factor data (challenge 2) and output a score that translated to cancer yes/no within 12 months. Algorithm accuracy for breast cancer detection was evaluated using area under the curve and algorithm specificity compared with radiologists' specificity with radiologists' sensitivity set at 85.9% (United States) and 83.9% (Sweden). An ensemble method aggregating top-performing AI algorithms and radiologists' recall assessment was developed and evaluated. Results: Overall, 144 231 screening mammograms from 85 580 US women (952 cancer positive ≤12 months from screening) were used for algorithm training and validation. A second independent validation cohort included 166 578 examinations from 68 008 Swedish women (780 cancer positive). The top-performing algorithm achieved an area under the curve of 0.858 (United States) and 0.903 (Sweden) and 66.2% (United States) and 81.2% (Sweden) specificity at the radiologists' sensitivity, lower than community-practice radiologists' specificity of 90.5% (United States) and 98.5% (Sweden). Combining top-performing algorithms and US radiologist assessments resulted in a higher area under the curve of 0.942 and achieved a significantly improved specificity (92.0%) at the same sensitivity. Conclusions and Relevance: While no single AI algorithm outperformed radiologists, an ensemble of AI algorithms combined with radiologist assessment in a single-reader screening environment improved overall accuracy. This study underscores the potential of using machine learning methods for enhancing mammography screening interpretation.

Comparison and optimization of SAR-PAGE tests for erythropoietins in doping analysis.

Erythropoietins (EPOs) are substances listed in S2 of the World Anti-Doping Agency (WADA) Prohibited List and are used commonly by athletes to increase endurance performance. According to the current WADA Technical Documents, sarcosyl-polyacrylamide gel electrophoresis (SAR-PAGE) followed by western blotting to differentiate erythropoietins based on their molecular weights is the only method that can be used for both screening and confirmation of all types of erythropoietins. The efficiency of immunopurification and protein transfer is crucial for ensuring the selectivity and sensitivity of erythropoietin detection. Several comparisons and optimization of the SAR-PAGE tests were conducted in this study. We optimized the first blotting conditions and then compared different immunopurification methods based on their selectivity, repeatability, and sensitivity for both urine and blood analysis. Additionally, rapid procedures for both urine and blood analysis were established and compared. The two-step procedure at 1.0 mA/cm2 for 60 min followed by 1.56 mA/cm2 for 20 min increased the blotting efficiency compared with the commonly used constant current approach. Comparison of immunopurification revealed no significant difference in selectivity and sensitivity between the different methods. For other factors, such as operation complexity, time and cost, a StemCell® purification kit followed by single blotting and magnetic beads followed by double blotting are recommended for urine screening and confirmation, respectively. While magnetic beads and a MAIIA® kit followed by double blotting are recommended for both screening and confirmation of blood samples, respectively. To ensure high sensitivity and selectivity, double blotting is recommended for a rapid procedure for both urine and blood analysis.

Sex-Related Differences in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: To describe characteristics and outcomes in women and men with heart failure with preserved ejection fraction. METHODS: Baseline characteristics (including biomarkers and quality of life) and outcomes (primary outcome: composite of first heart failure hospitalization or cardiovascular death) were compared in 4458 women and 4010 men enrolled in CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) (EF≥45%), I-Preserve (Irbesartan in heart failure with Preserved ejection fraction), and TOPCAT-Americas (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial). RESULTS: Women were older and more often obese and hypertensive but less likely to have coronary artery disease or atrial fibrillation. Women had more symptoms and signs of congestion and worse quality of life. Despite this, the risk of the primary outcome was lower in women (hazard ratio, 0.80 [95% CI, 0.73-0.88]), as was the risk of cardiovascular death (hazard ratio, 0.70 [95% CI, 0.62-0.80]), but there was no difference in the rate for first hospitalization for heart failure (hazard ratio, 0.92 [95% CI, 0.82-1.02]). The lower risk of cardiovascular death in women, compared with men, was in part explained by a substantially lower risk of sudden death (hazard ratio, 0.53 [0.43-0.65]; P<0.001). E/A ratio was lower in women (1.1 versus 1.2). CONCLUSIONS: There are significant differences between women and men with heart failure with preserved ejection fraction. Despite worse symptoms, more congestion, and lower quality of life, women had similar rates of hospitalization and better survival than men. Their risk of sudden death was half that of men. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00853658, NCT01035255.

Income Inequality and Outcomes in Heart Failure: A Global Between-Country Analysis.

OBJECTIVES: This study examined the relationship between income inequality and heart failure outcomes. BACKGROUND: The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes. METHODS: This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density. RESULTS: Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: <33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (>41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively. CONCLUSIONS: Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.

Optimization of ultrasound-assisted water extraction of flavonoids from Psidium guajava leaves by response surface analysis.

Psidium guajava leaves are rich in health-promoting flavonoids compounds. For better utilization of the resource, the ultrasound-assisted aqueous extraction was investigated using Box-Behnken design under response surface methodology. A high coefficient of determination (R2 = 97.8%) indicated good agreement between the experimental and predicted values of flavonoids yield. The optimal extraction parameters to obtain the highest total flavonoids yield were ultrasonic power of 407.41 W, extraction time of 35.15 min, and extraction temperature of 72.69 °C. The average extraction rate of flavonoids could reach 5.12% under the optimum conditions. Besides, HPLC analysis and field emission scanning electron microscopy indicated that the ultrasonic treatment did not change the main component of flavonoids during extraction process and the higher flavonoids content was attributed by the disruption of the cell walls of guava particles. Thus, the extraction method could be applied successfully for large-scale extraction of total flavonoids from guava leaves.

A Real-World Anti-Diabetes Medication Cost Comparison Between Premixed Insulin Analogs and Long-Acting Insulin Analogs in Chinese Patients with Type 2 Diabetes: A Retrospective Database Analysis.

INTRODUCTION: To assess and compare per-day anti-diabetic medication costs for Chinese type-2 diabetes mellitus (T2DM) insulin-naïve patients between those who initiated premixed insulin analogs ("premixed group") and those who initiated long-acting insulin analogs ("long-acting group"). METHODS: Data were obtained from an electronic medical record database between 2010.01.01 and 2015.06.30 covering medical encounter records from all general hospitals in a district from Shanghai, China. Insulin-naïve T2DM patients who were aged ≥ 18 years, treated with an oral anti-diabetic drug (OAD) only during the baseline period (3 months prior to insulin initiation), and initiated premixed or long-acting insulin analogs were included. Patients were followed until index insulin discontinuation or 12 months after initiation, whichever came first. The t test and generalized linear models adjusting for propensity score (PS) (including baseline demographics, number of OAD classes, comorbidities, costs, and healthcare resource utilization) were used to examine the differences between the two insulin groups. RESULTS: A total of 570 and 185 patients were identified for the premixed and long-acting groups, with mean (SD) ages of 63.0 (12.8) and 61.1 (11.9) (P = 0.08) and male proportions of 47.4% and 51.4% (P = 0.35), respectively. During the baseline period, 19.3% of the premixed users had T2DM-related hospitalizations, while the rate was 12.4% in the long-acting group (P = 0.03). The mean number of T2DM-related outpatient visits was 0.98 and 1.23 for the premixed and long-acting groups, respectively (P = 0.07). During the follow-up period, the per-day insulin dose averaged 31.7 and 15.3 international units (IU) for the premixed and long-acting groups, respectively. Compared with the patients on premixed insulin, the mean per-day cost for patients on long-acting insulin was 37.3% higher [15.3 vs 11.2 Chinese yuan (RMB); mean difference (MD) (95% CI): 4.2 (3.2, 5.1)] for the overall anti-diabetes medication, 81.3% higher [3.3 vs 1.8 RMB; MD (95% CI): 1.5 (0.8, 2.2)] for OAD, and 28.6% higher [12.0 vs 9.3 RMB; MD (95% CI): 2.7 (2.1, 3.3)] for insulin. The results were consistent after adjusting for the PS. CONCLUSION: Among Chinese T2DM insulin-naïve patients, those who initiated premixed insulin had a lower per-day antidiabetic medication cost than those who initiated long-acting insulin. FUNDING: Lilly Suzhou Pharmaceutical Co. Ltd, China.