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• Using one of the largest heart failure pragmatic trials (CONNECT-HF; (Care Optimization Through Patient and Hospital Engagement For HF), we assessed the completeness and validity of remote follow-up, integrating participant-reported via a centralized call center and site-reported approaches. • Both participant-reported via centralized call center- and site-reported approaches substantially missed hospitalization events. In contrast, both approaches demonstrated high and comparable adjudication rates for hospitalizations among the reported hospitalization events. • Our study highlighted that integrating both approaches remains essential to capture and validate effective clinical outcomes in the context of current pragmatic trials. Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials. Both approaches (centralized call center and site reports) substantially missed hospitalization events. However, both approaches demonstrated high and comparably adjudicated hospitalization rates among the reported potential hospitalization events. Integrating both approaches remains essential to capture and validate clinical outcomes effectively.   [ABSTRACT FROM AUTHOR]

This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques. Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury. A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared with both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%; adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.65-2.06; P <.001) and CEA (2.9% vs 1.3%; aOR, 2.21; 95% CI, 2.01-2.43; P <.001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%; aOR, 0.83; 95% CI, 0.76-0.91; P <.001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%; aOR, 0.00; 95% CI, 0.00-0.00; P <.001) and CEA (0.0% vs 2.3%; aOR, 0.00; 95% CI, 0.0-0.0; P <.001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%; aOR, 0.67; 95% CI, 0.54-0.84; P <.001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%; aOR, 1.31; 95% CI, 1.13-1.54; P <.001) and cranial nerve injury (2.3% vs 0.3%; aOR, 9.42; 95% CI, 7.78-11.4; P <.001). Although tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it is important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis. [ABSTRACT FROM AUTHOR]

Road traffic accidents (RTAs) are critical global issue, resulting in over 1.3 million deaths annually, with the burden disproportionately affecting low and middle income countries like Nigeria. Thus, the objective of this paper is to develop a predictive model for Road Traffic Accident Involvement in Southwest Nigeria: A Case Study of Ekiti, Osun, and Oyo States using appropriate standard methods after collecting accident data from relevant agencies for a period of ten years (2014-2023). The results indicate a strong correlation between accident cases and the number of people involved, with fatal and minor accidents having the most significant effects. The model explains 75.5% of the variance in accident outcomes, offering insights into predictive trends that can inform road safety interventions. The study highlights the importance of data-driven approaches in mitigating RTAs and improving road safety management in the study region. Recommendations include stricter traffic law enforcement, enhanced road maintenance, and safety education initiatives to reduce the frequency and severity of accidents in the region. [ABSTRACT FROM AUTHOR]

The objective of this paper was to evaluate water, sanitation and hygiene (WASH) facilities in Ekilisiyar Yan'uwa A Nigeria (EYN) internally displaced persons (IDP) camp in Maiduguri, Borno State, Nigeria using appropriate standard methods by selecting 332 respondents out of 1952 IDPs. Data obtained reveals that IDPs have access to latrines and bathrooms in the camp and most (98.3%) of them have demarcation between male and female compartments. The study also revealed that 37.6% of the IDPs dispose their household waste using collective bin and have access to health care centre. The study found that the main source of drinking water among the IDPs is from borehole which also serves as the source of water for daily and domestic use. The study concluded that in order to improve the WASH facilities in EYN IDP camp, various humanitarian organizations should work hand in hand with government officials in providing sanitation, hygiene and health care facilities to the EYN Internally Displace Persons in Camp Maiduguri, Borno State. Nigeria. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the optimal timing of thromboprophylaxis (TPX) initiation after hepatic angioembolization in trauma patients. Background: TPX after hepatic trauma is complicated by the risk of bleeding, but the relative risk after hepatic angioembolization is unknown. Methods: Patients who underwent hepatic angioembolization within 24 hours were retrospectively identified from the 2017 to 2019 American College of Surgeons Trauma Quality Improvement Project data sets. Cases with <24-hour length of stay and other serious injuries were excluded. Venous thromboembolism (VTE) included deep venous thrombosis and PE. Bleeding complications included hepatic surgery, additional angioembolization, or blood transfusion after TPX initiation. Differences were tested with univariate and multivariate analyses. Results: Of 1550 patients, 1370 had initial angioembolization. Bleeding complications were higher in those with TPX initiation within 24 hours (20.0% vs 8.9%, P<0.001) and 48 hours (13.2% vs 8.4%, P=0.013). However, VTE was higher in those with TPX initiation after 48 hours (6.3% vs 3.3%, P= 0.025). In the 180 patients with hepatic surgery before angioembolization, bleeding complications were higher in those with TPX initiation within 24 hours (72% vs 20%, P <0.001), 48 hours (50% vs 17%, P<0.001), and 72 hours (37% vs 14%, P=0.001). Moreover, deep venous thrombosis was higher in those with TPX initiation after 96 hours (14.3% vs 3.1%, P = 0.023). Conclusions: This is the first study to address the timing of TPX after hepatic angioembolization in a national sample of trauma patients. For these patients, initiation of TPX at 48 to 72 hours achieves the safest balance in minimizing bleeding while reducing the risk of VTE. [ABSTRACT FROM AUTHOR]

Objective: To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades. Background: The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. Methods: A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era. Results: All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were > 35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year deathcensored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. Conclusions: Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss. [ABSTRACT FROM AUTHOR]

Characterization of visible abnormalities in patients with Barrett's esophagus (BE) can be challenging, especially for inexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CADx) systems may assist endoscopists. We aimed to develop, validate, and benchmark a CADx system for BE neoplasia. The CADx system received pretraining with ImageNet and then consecutive domain-specific pretraining with GastroNet, which includes 5 million endoscopic images. It was subsequently trained and internally validated using 1758 narrow-band imaging (NBI) images of early BE neoplasia (352 patients) and 1838 NBI images of nondysplastic BE (173 patients) from 8 international centers. CADx was tested prospectively on corresponding image and video test sets with 30 cases (20 patients) of BE neoplasia and 60 cases (31 patients) of nondysplastic BE. The test set was benchmarked by 44 general endoscopists in 2 phases (phase 1, no CADx assistance; phase 2, with CADx assistance). Ten international BE experts provided additional benchmark performance. Stand-alone sensitivity and specificity of the CADx system were 100% and 98% for images and 93% and 96% for videos, respectively. CADx outperformed general endoscopists without CADx assistance in terms of sensitivity (P =.04). Sensitivity and specificity of general endoscopists increased from 84% to 96% and 90% to 98% with CAD assistance (P <.001). CADx assistance increased endoscopists' confidence in characterization (P <.001). CADx performance was similar to that of the BE experts. CADx assistance significantly increased characterization performance of BE neoplasia by general endoscopists to the level of expert endoscopists. The use of this CADx system may thereby improve daily Barrett surveillance. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited. METHODS: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US‐representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross‐sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression. RESULTS: In weighted models, greater loneliness was associated with microinfarcts, lower episodic and working memory in the absence of AD pathology, lower working memory in the absence of infarcts, a stronger association of infarcts with lower episodic memory, and a stronger association of microinfarcts with lower working and semantic memory. DISCUSSION: Loneliness may relate to AD through multiple pathways involving cerebrovascular pathology and cognitive reserve. Highlights: Loneliness was associated with worse cognition in five domains.Loneliness was associated with the presence of microinfarcts.Loneliness moderated cognition–neuropathology associations.Transportability methods can provide insight into selection bias. [ABSTRACT FROM AUTHOR]

Background. People living with HIV continue to face laws, policies, and practices that impact their potential for travel and migration. These laws include: mandatory HIV testing and involuntary disclosure of HIV; lack of access to affordable HIV-related health care, treatment and counselling during the migration process; deportation of foreign nationals living with HIV; and restrictions on the length of stays. Methods. HIV migration laws were the topic of a half-day community forum held as part of the 12th International AIDS Society Conference on HIV Science held in Brisbane, Australia, in July 2023. Over 150 delegates attended and, after a series of presentations, delegates were invited to participate in structured, facilitated conversations about issues related to policy, health and law concerning migration of people living with HIV. In this paper, we report on key themes from those discussions and identify areas for ongoing investigation. Results. Advocates recommended the removal of unfair and unjust migration laws and policies that contribute to HIV stigma and discrimination; updated migration policies that reflect the current context and cost of biomedical approaches to HIV management and prevention; expanded and equitable access to HIV-related care regardless of migration or residency status; and the development of advocacy networks to promote changes to migration policies. Conclusions. Laws limiting the migration of people living with HIV actively discourage individuals from seeking HIV testing, treatment and care. Ultimately, restrictive migration laws and policies undermine global efforts to end AIDS as a public health concern and to virtually eliminate HIV transmission by 2030. [ABSTRACT FROM AUTHOR]

Animals interact with their worlds using sensory information (sounds, smells, sights) that is perceived differently by each species. This sensory information and how it is interpreted underpins most behaviours, but especially foraging decisions. Creating sensory misinformation, that is uninformative or unrewarding cues, is a new approach with applications for managing wildlife and conserving threatened species across a range of global contexts. Here we discuss recent research that demonstrates the power of strategically deploying olfactory misinformation to reduce predation on birds by predators, consumption of vulnerable seedlings by herbivores, and seeds by rodents as well as how multimodal misinformation may work. Single and multimodal sensory tactics can alter foraging decisions by both herbivores and predators, with profound consequences for the survival of prey and plants. There remains much to understand regarding sensory perception and learning but results to date suggest there are enormous opportunities to harness innovative sensory tactics in the future to improve many conservation and wildlife management scenarios. [ABSTRACT FROM AUTHOR]

Objective: To analyze the prevalence of hypomineralized second primary molar (HSPM) and its association with socioeconomic characteristics and dental caries in a Brazilian population of preschoolers. Material and methods: 603 preschoolers, enrolled in public preschools in Itajaí (state of Santa Catarina, Brazil), took part in the study. To assess the participants' socio-economic characteristics, an original questionnaire was formulated and sent to the children's parents. The clinical evaluation was carried out by a calibrated examiner using the deft/DMFT index for dental caries and Ghanim et al. (Ghanim et al., Eur Arch Paediatr Dent, 2015) criteria for HSPM. The data were analyzed through Poisson regression, using STATA statistical software, and the association analyses were presented by prevalence ratios (PR). Results: The prevalence of at least one HSPM-affected second molar was 24.5%. The prevalence of HSPM was associated to the city's geographical regions of the Educational hubs (p < 0.001). A significant association was found between dental caries and HSPM (p = 0.003; PR: 1.31; 95% CI 1.09–1.56). Children with HSPM were 31% more likely to experience dental caries than children without HSPM. Geographical regions of educational hubs were also significantly associated with HSPM (p < 0.001). None of the socioeconomic characteristics was associated with HSPM (p > 0.05). Conclusion: HSPM is a common developmental defect of enamel in children in our study. The HSPM distribution was associated with the city's geographic regions. Children with HSPM are more likely to experience dental caries. Socioeconomic characteristics were not associated with HSPM. [ABSTRACT FROM AUTHOR]

Social determinants of health (SDOH) have been insufficiently addressed by payers and providers despite increased prioritization at the national level. This led to the development of a separate, for-profit "SDOH industry" found to have a valuation of $18.5 billion (all dollar amounts in U.S. dollars) with $2.4 billion in funding as of July 2021. The purpose of this article is to determine the growth of the industry from 2021 to 2023 and provide a multifaceted explanation for this development. The authors conducted an analysis of 57 SDOH industry companies using a third-party market research platform. Over the previous two-year period, 10 out of 57 (18%) companies were acquired, and the industry gained an additional $1.1 billion (46% increase) in funding and $13.7 billion (74% increase) in valuation. The authors propose four contributing factors to explain the nature of this industry's evolution. They include developments in national health care policy favoring SDOH, standardization of SDOH information as actionable claims data, multi-source investment in SDOH, and improved methods of industry intervention measurement. These trends appear likely to continue, requiring additional scrutiny by all relevant stakeholders to ensure maximum improvement of rampant SDOH disparities that impact millions of individuals daily. [ABSTRACT FROM AUTHOR]

To assess the construct validity and responsiveness of 3 performance-based tests in individuals with knee osteoarthritis (KOA). This study has a prospective cohort design. Assessments were administered at the Federal University of São Carlos (Brazil) by 3 different raters. A total of 107 participants with KOA were aged ≥40 years (N=107). Not applicable. This study assessed the construct validity and responsiveness of 3 performance-based tests: 40-meter fast-paced walk test (40-m FPWT), 11-step stair climb test (11-step SCT), and 30-second chair stand test (30-s CST). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), sedentary behavior (activPAL), and numeric pain rating scale (NPRS) were used as comparator instruments. Measurements were obtained at baseline and after 6 months. The construct validity and responsiveness were calculated using Spearman correlation coefficient within predefined hypotheses based on a panel comprising 5 experts in the field of outcome measurement in KOA. The three performance-based tests showed excellent (ICC>0.9) reliability (intra and inter); however, only the 40-m FPWT and 11-step SCT were considered valid and responsive because both confirmed >75% of the priori hypotheses. The 30-s CST was not considered valid or responsive because it has not confirmed ≥75% of the priori hypotheses. The 3 performance-based tests are reliable for intra and inter assessments. The 40-m FPWT and 11-step SCT are both valid and responsive for measuring physical function in patients with KOA. The 30-s CST was not considered valid or responsive. Therefore, 40-m FPWT and 11-step SCT can detect changes over time and are indicated for functional assessment in clinical practice. [ABSTRACT FROM AUTHOR]

Two previously undescribed dihydrochalcones, 4,2′-dihydroxy- [2″, 2″-dimethylpyrano (3″, 4″: 4′, 5′]) dihydrochalcone (1) and 4, 2′, 4′, 2″-tetrahydroxy-5′-(3″-methylbut-3″-enyl) dihydrochalcone (2), along with six known compounds (3 - 8) were isolated from chloroform-methanol (1:1) extract of Baphia Massaiensis twigs. Their chemical structures were determined using NMR analysis, mass spectrometry, electronic circular dichroism (ECD), density functional theory (DFT) calculations, and a thorough comparison with reported data from the literature. All the isolated compounds (1−8) were assessed for their antioxidant activities, α-amylase and α-glucosidase inhibition effects. Dihydrochalcone 1 showed significant antioxidant activity with IC 50 value of 118.8 ± 2.95 µM, and a more potent antioxidant activity was exhibited by compounds 3 and 6 with IC 50 values of 84.3 ± 0.07 µM and 62.1 ± 1.59 µM, respectively, compared to the positive control, gallic acid with IC 50 value of 92.9 µM. Dihydrochalcone 2 showed moderate inhibition against α-amylase and α-glucosidase with IC 50 values of 44.0 ± 4.83 µM and 51.7 ± 9.72 µM compared to the standard acarbose with IC 50 values of 22.9 ± 0.92 µM and 31.5 ± 0.63 µM, respectively. Molecular docking studies of the new dihydrochalcones 1 and 2 , revealed the active binding sites which support the observed α-amylase and α-glucosidase inhibitory effects. [Display omitted] • Two undescribed dihydrochalcones were isolated from Baphia massaiensis. • The structures were confirmed by extensive spectroscopic analyses. • Compounds 1 and 2 showed significant inhibitory activities against α-amylase and α-glucosidase. • Compounds 1 , 3 and 6 also showed potent antioxidant activities. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) platforms such as Chat Generative Pre-Trained Transformer (ChatGPT) (Open AI, San Francisco, California, USA) have the capacity to answer health-related questions. It remains unknown whether AI can be a patient-friendly and accurate resource regarding third molar extraction. The purpose was to determine the accuracy and readability of AI responses to common patient questions regarding third molar extraction. This is a cross sectional in-silico assessment of readability and soundness of a computer-generated report. Not applicable. Accuracy, or the ability to provide clinically correct and relevant information, was determined subjectively by 2 reviewers using a 5-point Likert scale, and objectively by comparing responses to American Association of Oral and Maxillofacial Surgeons (AAOMS) clinical consensus papers. Readability, or how easy a piece of text is to read, was assessed using the Flesch Kincaid Reading Ease (FKRE) and Flesch Kincaid Grade Level (FKGL). Both assess readability based on mean number of syllables per word, and words per sentence. To be deemed readable, FKRE should be >60 and FKGL should be <8. Not applicable. Descriptive statistics were used to analyze the findings of this study. AI-generated responses above the recommended level for the average patient (FKRE: 52; FKGL: 10). The average Likert score was 4.36, suggesting that most responses were accurate with minor inaccuracies or missing information. AI correctly deferred to the provider in instances where no definitive answer exists. Of the responses that addressed content in AAOMS consensus papers, 18/19 responses closely aligned with them. All prompts did not provide citations or references. AI was able to provide mostly accurate responses, and content was closely aligned with AAOMS guidelines. However, responses were too complex for the average third molar extraction patient, and were deficient in citations and references. It is important for providers to educate patients on the utility of AI, and to decide whether to recommend using it for information. Ultimately, the best resource for answers is from the practitioners themselves because the AI platform lacks clinical experience. [ABSTRACT FROM AUTHOR]

Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB). This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU). PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee. Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures. This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB. [ABSTRACT FROM AUTHOR]

Our objective was to determine the number of major cardiovascular events (MACE, nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and deaths from any cause that could be prevented across varying nationwide uptake of semaglutide 2.4 mg SC weekly for the secondary prevention of cardiovascular disease. Using a nationally representative cross-sectional study of participants in the 2017-2018 and 2019-March 2020 cycles of the National Health and Nutrition Examination Survey in the U.S. (NHANES), we estimated the number of MACE and deaths from any cause potentially prevented over a four-year period among participants meeting SELECT trial inclusion criteria. In a sample of n = 216 individuals (corresponding to 4,473,681 adults in the U.S. population) potentially eligible for this therapy, a total of 356,329 MACE and 232,808 all-cause mortality events were expected without semaglutide over 4 years and 35,633 MACE and 22,117 all-cause mortality events would be prevented with 50% uptake of semaglutide. Approximately 4.5 million adults in the U.S. are forecasted to be eligible for semaglutide 2.4mg SC weekly therapy, with substantial impact on CVD and mortality if accessible and broadly used. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ferroptosis of neurons is a significant cause of brain injury following intracerebral hemorrhage (ICH). As an iron-containing compound in hemoglobin, heme contributes to nerve injury post-ICH. Melatonin has been shown to mitigate the effects of ICH, yet its specific functions remain largely elusive. In this study, we aimed to explore the roles and mechanisms of melatonin in heme-induced ferroptosis subsequent to ICH. MATERIALS AND METHODS: C57BL/6 mice were intracranially injected with heme and then treated with melatonin. Behavior tests [modified neurological severity score (mNSS), forelimb placing, and corner turn tests], H&E staining, Nissl staining, and Prussian blue staining were used to evaluate mouse brain tissue injury. In vitro, HT-22 cells were stimulated with heme and cell viability was determined by crystal violet staining. The iron contents were determined in heme-treated brains and cells, and the levels of 4-hydroxynonenal (4-HNE) and malonaldehyde (MDA) were assessed by ELISA. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to investigate the mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Immunoblotting was used to analyze the protein expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Finally, small interfering RNA (siRNA) was used to knock down Nrf2 in HT-22 cells. RESULTS: Melatonin treatment alleviated heme-induced injuries to neural function, as indicated by improved behavior in the mice. Moreover, melatonin decreased cell death and iron concentrations, increased MDA and 4-HNE levels, and reversed the decreases in GPX4, SLC7A11, Nrf2, and HO-1 induced by heme in vitro and in vivo. These results indicated that melatonin could improve the ferroptosis induced by heme. In addition, we found that Nrf2 knockdown attenuated the therapeutic effect of melatonin on neuronal ferroptosis induced by heme. CONCLUSIONS: In general, melatonin alleviates heme-induced ferroptosis by activating the Nrf2/HO-1 pathway, which implies that melatonin is a promising treatment for ferroptosis in ICH. [ABSTRACT FROM AUTHOR]

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain. METHODS: VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. RESULTS: At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (P=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (P=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (P=0.62 and P=0.56, respectively). CONCLUSIONS: In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function. [ABSTRACT FROM AUTHOR]

Breast cancer is still a dangerous and common disease that affects women all over the world, which highlights how crucial early identification is to better patient outcomes. In recent years, utilizing machine learning (ML) algorithms has improved accuracy and efficiency dramatically in a variety of applications, showing promising outcomes. This article provides a novel machine-learning approach to increase the accuracy of breast cancer detection. To improve diagnostic efficiency and accuracy, our suggested methodology combines sophisticated feature selection strategies, reliable classification algorithms, and enhanced model training methodologies. We investigated several ML classifiers, and after thorough hyperparameter tuning, the models were. Random forest and gradient boosting have achieved the highest performance with an accuracy of 97.90% and an ROC score of 0.99. This research highlights the effectiveness of ML, particularly the random forest algorithm, in breast cancer diagnosis and prognosis. Future work may explore deep learning techniques for determining the disorder's severity. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii infections are common in a range of mammalian and avian species, but clinical disease has been reported only rarely in domestic rabbits. Two cases of toxoplasmosis in domestic rabbits from the same premises were submitted to a diagnostic pathology facility in Athens, GA, USA. Both rabbits died after exhibiting clinical signs of gastrointestinal stasis. The gross findings observed in both rabbits comprised miliary, random, white-to-tan, necrotic foci throughout the spleen, liver, and lungs. Histologically, tachyzoites were observed within necrotizing inflammatory foci in the spleens of both rabbits, and in various other organs (tracheobronchial lymph node, lung, heart, and cecal appendix) of one rabbit. In both cases, the tachyzoites were immunoreactive with anti– Toxoplasma gondii antibodies. In addition, T. gondii DNA was detected via PCR and sequencing from a fresh lung sample from one rabbit and formalin-fixed, paraffin-embedded spleen, liver, femoral bone marrow, and haired skin from the second rabbit. Given that T. gondii can cause disease in domestic rabbits and is also a concern for other potential intermediate hosts (e.g., humans, other domestic animals), this parasite warrants consideration in the diagnostic evaluation of lagomorph tissues with compatible lesions. [ABSTRACT FROM AUTHOR]

The increasing computational demand for real-time mobile applications has led to the development of mobile edge computing (MEC), with support from unmanned aerial vehicles (UAVs), as a promising paradigm for constructing high-throughput line-of-sight links for ground users and pushing computational resources to network edges. Users can reduce processing latency and the load on their local computers by delegating tasks to the UAV in its role as an edge server. The coverage capacity of a single UAV is, however, very limited. Moreover, it will be easy to intercept the data that is transferred to the unmanned aerial vehicle. Thus, for UAV-assisted mobile edge computing, we proposed a transmission technique based on multi-agent deep reinforcement learning in this study. The recommended approach to maximize UAV deployment first applies the particle swarm optimization algorithm. Then, deep reinforcement learning is utilized to optimize the secure offloading to maximize the system utility and minimize the quantity of information eavesdropping, taking into consideration different user task types with diverse preferences for processing time and residual energy of computing equipment. The results of the simulation demonstrate that, in comparison to the single-agent strategy and the benchmark, the multi-agent approach can optimize offloading more successfully and produce higher system utility. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis results from alveolar injury, leading to extracellular matrix remodelling and impaired lung function. This study aimed to classify patients with pulmonary fibrosis according to blood biomarkers to differentiate distinct disease patterns, known as endotypes. In this cluster analysis, we first classified patients from the PROFILE study, a multicentre, prospective, observational cohort of individuals with incident idiopathic pulmonary fibrosis or non-specific interstitial pneumonia in the UK (Nottingham University Hospitals, Nottingham; and Royal Brompton Hospital, London). 13 blood biomarkers representing extracellular matrix remodelling, epithelial stress, and thrombosis were measured by ELISA in the PROFILE study. We classified patients by unsupervised consensus clustering. To evaluate generalisability, a machine learning classifier trained on biomarker signatures derived from consensus clustering was applied to a replication dataset from the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR). Biomarker associations with mortality and change in percentage of predicted forced vital capacity (FVC%) were assessed, adjusting for age, gender, baseline FVC%, and antifibrotic treatment and steroid treatment before and after baseline. Mortality risk associated with the clusters in the PROFILE cohort was evaluated with Cox proportional hazards models, and mixed-effects models were used to analyse how clustering was associated with longitudinal FVC% in the PROFILE and AIPFR cohorts. 455 of 580 participants from the PROFILE study (348 [76%] men and 107 [24%] women; mean age 72·4 years [SD 8·3]) were included in the analysis. Within this group, three clusters were identified based on blood biomarkers. A basement membrane collagen (BM) cluster (n=248 [55%]) showed high concentrations of PRO-C4, PRO-C28, C3M, and C6M, whereas an epithelial injury (EI) cluster (n=109 [24%]) showed high concentrations of MMP-7, SP-D, CYFRA211, CA19-9, and CA-125. The third cluster (crosslinked fibrin [XF] cluster; n=98 [22%]) had high concentrations of X-FIB. In the replication dataset (117 of 833 patients from AIPFR; 87 [74%] men and 30 [26%] women; mean age 72·9 years [SD 7·9]), we identified the same three clusters (BM cluster, n=93 [79%]; EI cluster, n=8 [7%]; XF cluster, n=16 [14%]). These clusters showed similarities with clusters in the PROFILE dataset regarding blood biomarkers and phenotypic signatures. In the PROFILE dataset, the EI and XF clusters were associated with increased mortality risk compared with the BM cluster (EI vs BM: adjusted hazard ratio [HR] 1·88 [95% CI 1·42–2·49], p<0·0001; XF vs BM: adjusted HR 1·53 [1·13–2·06], p=0·0058). The EI cluster showed the greatest annual FVC% decline, followed by the BM and XF clusters. A similar FVC% decline pattern was observed in these clusters in the AIPFR replication dataset. Blood biomarker clustering in pulmonary fibrosis identified three distinct blood biomarker signatures associated with lung function and prognosis, suggesting unique pulmonary fibrosis biomarker patterns. These findings support the presence of pulmonary fibrosis endotypes with the potential to guide targeted therapy development. None. [ABSTRACT FROM AUTHOR]

Objectives: This trial examines the impact of the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum on surgical residents' knowledge, cross-cultural care, skills, and beliefs. Background: Cross-cultural training of providers may reduce health care outcome disparities, but its effectiveness in surgical trainees is unknown. Methods: PACTS focuses on developing skills needed for building trust, working with patients with limited English proficiency, optimizing informed consent, and managing pain. The PACTS trial was a randomized crossover trial of 8 academic general surgery programs in the United States: The Early group ("Early") received PACTS between periods 1 and 2, while the Delayed group ("Delayed") received PACTS between periods 2 and 3. Residents were assessed preintervention and postintervention on Knowledge, Cross-Cultural Care, Self-Assessed Skills, and Beliefs. χ² and Fisher exact tests were conducted to evaluate within-intervention and between-intervention group differences. Results: Of 406 residents enrolled, 315 were exposed to the complete PACTS curriculum. Early residents' Cross-Cultural Care (79.6%-88.2%, P< 0.0001), Self-Assessed Skills (74.5%--85.0%, P<0.0001), and Beliefs (89.6%-92.4%, P=0.0028) improved after PACTS; knowledge scores (71.3%-74.3%, P=0.0661) were unchanged. Delayed resident scores pre-PACTS to post-PACTS showed minimal improvements in all domains. When comparing the 2 groups in period 2, Early residents had modest improvement in all 4 assessment areas, with a statistically significant increase in Beliefs (92.4% vs 89.9%, P=0.0199). Conclusions: The PACTS curriculum is a comprehensive tool that improved surgical residents' knowledge, preparedness, skills, and beliefs, which will help with caring for diverse patient populations. [ABSTRACT FROM AUTHOR]

A commitment to diversity, equity, inclusion, and belonging in medical education requires addressing both explicit and implicit biases based on sexual orientation, gender identity and expression, and sex characteristics and the intersectionality with other identities. Heterosexism and heteronormative attitudes contribute to health and healthcare disparities for lesbian, gay, bisexual, transgender and queer or questioning, intersex, asexual individuals. Student, trainee, and faculty competencies in medical education curricula regarding the care of lesbian, gay, bisexual, transgender and queer or questioning, intersex, asexual patients and those who are gender nonconforming or born with differences of sex development allow for better understanding and belonging within the clinical learning environment of lesbian, gay, bisexual, transgender and queer/questioning, intersex, asexual learners and educators. The Association of Professors of Gynecology and Obstetrics issued a call to action to achieve a future free from racism and bias through inclusivity in obstetrics and gynecology education and healthcare, which led to the creation of the Association of Professors of Gynecology and Obstetrics Diversity, Equity, and Inclusion Guidelines Task Force. The task force initially addressed racism, racial- and ethnicity-based bias, and discrimination in medical education and additionally identified other groups that are subject to bias and discrimination, including sexual orientation, gender identity and expression, and sex characteristic identities, persons with disabilities, and individuals with various religious and spiritual practices. In this scholarly perspective, the authors expand on previously developed guidelines to address sexual orientation, gender identity and expression, and sex characteristics bias, heterosexism, and heteronormative attitudes in obstetrics and gynecology educational products, materials, and clinical learning environments to improve access and equitable care to vulnerable individuals of the lesbian, gay, bisexual, transgender and queer or questioning, intersex, asexual community. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate gender differences in the association between metacarpal cortical thickness (T cort)—a surrogate for bone density—and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study. Hand radiographs of 3575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate T cort , a measurement of the cortical thickness, for metacarpals 2–4. Average T cort at baseline and change in T cort from baseline to 48 months was determined and stratified by gender and age for 7 5-year age groups. Spearman's rank correlation coefficients were calculated for the association of baseline T cort and 2 measures of baseline HOA severity: the sum of Kellgren-Lawrence (KL) grade and total number of joints with radiographic HOA. Longitudinally, logistic regression was used to assess the relationship of T cort loss to new finger joint radiographic HOA, increase in KL grades, and incident hand pain. Male T cort was higher than females. Significant correlations between T cort and radiographic severity were noted for women but not men, with stronger associations among women >60 years (rho = −0.25; 95% confidence interval (CI) = −0.31 to −0.19). Statistically significant associations were seen between T cort change and radiographic osteoarthritis change among women but not men, with substantial gender differences for T cort change, particularly ages 50 to 70 years (p < 0.01; e.g., T cort change ages 55 to <60: males = −0.182 (0.118), females = −0.219 (0.124)). We found significant HOA-related gender differences in T cort , suggesting the involvement of female bone loss during and after menopause. [ABSTRACT FROM AUTHOR]

Microwave ablation is becoming increasingly common for the treatment of liver tumors. Despite numerous studies aimed at identifying risk factors for local recurrence after microwave ablation, a consensus on modifiable risk factors for failure remains elusive, partly because of the limited statistical power of these studies. This study investigated the incidence of technical failure after microwave ablation, encompassing both incomplete ablation and local recurrence, and aimed to identify modifiable factors that reduce technical failure. This retrospective review included patients who underwent surgical microwave ablation at a high-volume institution between October 2006 and March 2023. Univariate analysis, multivariate analysis, and propensity score matching were performed to identify risk factors for technical failure. A total of 1,613 surgical microwave ablations were performed on 3,035 tumors, with 226 instances (14% per procedure, 7.4% per tumor) of technical failure. Incomplete ablation occurred at a rate of 1.7% per tumor, whereas local recurrence was identified in 6.5% of ablations in per-tumor analysis. Body mass index >25 was significant for failure (odds ratio, 1.50; 95% confidence interval, 1.07–2.11; P <.05), suggesting that more difficult targeting may lead to increased technical failure rates. African American race (odds ratio, 1.62; 95% confidence interval, 1.16–2.27; P <.05), pre–microwave ablation transarterial chemoembolization (odds ratio, 1.54; 95% confidence interval, 1.08–2.21; P <.05), and previous ablation (odds ratio, 1.58; 95% confidence interval, 1.09–2.29; P <.05) were found to be statistically significant. On the basis of the largest microwave ablation database available to date, this study identified novel modifiable and nonmodifiable risk factors of microwave ablation failure. These results can lead to decreasing technical failure rates after microwave ablation. [Display omitted] [ABSTRACT FROM AUTHOR]

Metabolic dysfunction associated steatotic liver disease (MASLD) has been linked to heart failure with preserved ejection fraction (HFpEF). We sought to understand association between individuals with amounts of liver adiposity greater than would be predicted by their body mass index (BMI) in order to understand whether this disproportionate liver fat (DLF) represents a proxy of metabolic risk shared between liver and heart disease. We studied 2,932 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who received computed tomography (CT) measurements of hepatic attenuation. Quartiles of DLF were compared and multivariable linear regression was performed to evaluate the association of DLF with clinical, echocardiographic, and quality of life metrics. Compared to the lowest quartile of DLF, individuals in the highest quartile of DLF were more likely to be male (52.0% vs 47.1%, P <.001), less likely to be Black or African American (14.8 % vs 38.1% P <.001), have higher rates of dysglycemia (31.9% vs 16.6%, P <.001) and triglycerides (140 [98.0, 199.0] vs 99.0 [72.0, 144.0] mg/dL, P >.001). These individuals had lower global longitudinal strain (−0.13 [−0.25, −0.02], P =.02), stroke volumes (−1.05 [−1.76, −0.33], P <.01), lateral e' velocity (−0.10 [−0.18, −0.02], P =.02), and 6-minute walk distances (−4.25 [−7.62 to −0.88], P =.01). DLF is associated with abnormal metabolic profiles and ventricular functional changes known to be associated with HFpEF and may serve as an early metric to assess for those that may progress to clinical HFpEF. [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND: Vascular risk factors, particularly hypertension, are important contributors to accelerated brain aging. We sought to quantify vascular risk factor risks over adulthood and assess the empirical evidence for risk thresholds. METHODS: We used SBP (systolic blood pressure) and diastolic blood pressure, total cholesterol, fasting blood glucose, and body mass index measurements collected from participants in the CARDIA study (Coronary Artery Risk Development in Young Adults) at 2- to 5-year intervals through year 30. The Montreal Cognitive Assessment and domain-specific cognitive tests were performed at year 30. White matter hyperintensity volume was measured by magnetic resonance imaging. We used a 2-step method to fit longitudinal vascular risk factor exposures to optimized spline functions with mixed-effects models, then used the participant-specific random effects that characterized individual exposures over time in cross-sectional models adjusted for sex, race, age, and education to study effects on midlife brain health. RESULTS: Change in SBP up to 33 years of age was negatively associated with Montreal Cognitive Assessment scores (-0.29 Montreal Cognitive Assessment Z score per mm Hg/y change [95% CI, -0.49 to -0.09]; P=0.005), with similar effects for SBP changes from 33 to 49 years of age (-0.08 [95% CI, -0.16 to 0.01]; P=0.08). We observed comparable, significant associations between SBP exposure during those ages, midlife performance on specific cognitive domains, and volume of white matter hyperintensity (all P<0.05). SBP ≤111 mm Hg was the estimated threshold below which no harmful association with midlife cognitive performance was identified. CONCLUSIONS: SBP in early adulthood is the vascular risk factor most strongly associated with midlife cognitive performance and white matter hyperintensity burden, with SBP 111 mm Hg suggested as a harm threshold. [ABSTRACT FROM AUTHOR]

This study investigated the effect of a mixed obstacle layout on the deflagration mechanism of propane--air premixed gases. Most previous studies focused on a single type of obstacle, changing the shape and number of the obstacles to observe the effect on the flame deflagration characteristics. However, in real explosion accident sites, obstacles are often a mixture of different types. Little literature exists on the deflagration characteristics of hybrid barriers in semiconfined spaces. In this paper, the deflagration characteristics of propane-air premixed gas with a mixed structure of hurdles and square obstacles was studied. First, the effectiveness of numerical simulations was demonstrated by comparing experimental and large eddy simulation (LES) results for the flame dynamics with a single flat plate obstacle. Based on this, the flame behavior for different layouts of square obstacles in a mixed obstacle configuration was further simulated using the large eddy simulation method, focusing on the flame behavior, overpressure characteristics, and flow field structure in the vicinity of the obstacle. The results showed that a mixed obstacle promoted flame evolution more than a single obstacle when the square obstacle was within a critical distance from the ignition source location at the same moment in time. When the flame front crossed the first hurdle-type obstacle, the flame pattern spread in a "cat's paw" pattern to the unburned portion of the tube. In addition, the increased distance of the square obstacle from the ignition source did not allow the peak overpressure and the peak rate of overpressure rise to show a positive feedback mechanism. Finally, the strength of the vorticity in the flow field was positively correlated with the distance of the square obstacle from the ignition source. The results of study provide theoretical for the prevention of explosions. [ABSTRACT FROM AUTHOR]