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Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular (CV) outcomes in patients with or without Type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a pilot systematic review and meta-analysis to synthesise the available evidence regarding the effectiveness of SGLT2 inhibitors in MI., Methods: A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library and Embase databases to identify randomised controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4 and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes., Results: Five RCTs reporting data for 11,211 patients were included in our study. The mean follow-up duration was 43.8 weeks. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalisations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88, p = 0.001) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41, p = 0.76), CV mortality (RR = 1.04, 95% CI = 0.84-1.29, p = 0.73) and all-cause hospitalisations (RR = 1.06, 95% CI: 0.96-1.17, p = 0.25) remained comparable across the two groups., Conclusion: SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality and all-cause hospitalisations. However, further evidence is required to reach a definitive conclusion., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or μCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (μCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia., (© 2024. The Author(s).)

A 51-year-old female with menorrhagia was found to have a cervical polyp. Polypectomy and endometrial curettage showed an atypical lymphoid infiltrate. Hysterectomy was performed, showing extensive myometrial infiltration by small, cytologically bland CD3-positive αβ T cells with a non-activated cytotoxic phenotype and a low proliferative rate. PCR showed clonal TCR-β gene rearrangement. Lymph nodes were uninvolved. PET-CT was negative. A diagnosis of CD8-positive T-cell lymphoproliferative disorder (T-LPD) was made. At 6 months, the patient was asymptomatic with a negative repeat PET-CT. A critical recent advance in the classification of lymphoid neoplasms is the recognition of indolent extranodal T-LPDs, including those of the gastrointestinal tract (T-cell and NK-cell types) and skin (small/medium CD4-positive and acral CD8-positive). However, T-LPDs of the uterus are rare. Two indolent T-LPDs of the uterus have been reported, both showing a CD8-positive, nonactivated cytotoxic phenotype, low proliferative rate, and clonal TCR rearrangement. Neither developed systemic disease nor recurrence. The etiology of indolent T-LPDs and their relationship to overt T-cell lymphomas remain poorly understood. T-LPDs of the uterus may arise from effector memory T-cells that establish long-term, tissueresident immunologic memory following exposure to fetal extravillous trophoblastic cell alloantigens during a previous pregnancy. Neither our patient nor the 2 previously reported had a current pregnancy or a known recent infection or toxic exposure, and the event(s) triggering evolution into T-LPD are unknown. Indolent T-LPDs can be encountered at new and unusual extranodal sites; knowledge of their clinicopathological features will help avoid unnecessary cytotoxic chemotherapy and improve understanding of this group of disorders., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biomolecules can be sequestered into membrane-less compartments, referred to as biomolecular condensates. Experimental and computational methods have helped define the physical-chemical properties of condensates. Less is known about how the high macromolecule concentrations in condensed phases contribute "solvent" interactions that can remodel the free-energy landscape of other condensate-resident proteins, altering thermally accessible conformations and, in turn, modulating function. Here, we use solution NMR spectroscopy to obtain atomic resolution insights into the interactions between the immature form of superoxide dismutase 1 (SOD1), which can mislocalize and aggregate in stress granules, and the RNA-binding protein CAPRIN1, a component of stress granules. NMR studies of CAPRIN1:SOD1 interactions, focused on both unfolded and folded SOD1 states in mixed phase and demixed CAPRIN1-based condensates, establish that CAPRIN1 shifts the SOD1 folding equilibrium toward the unfolded state through preferential interactions with the unfolded ensemble, with little change to the structure of the folded conformation. Key contacts between CAPRIN1 and the H80-H120 region of unfolded SOD1 are identified, as well as SOD1 interaction sites near both the arginine-rich and aromatic-rich regions of CAPRIN1. Unfolding of immature SOD1 in the CAPRIN1 condensed phase is shown to be coupled to aggregation, while a more stable zinc-bound, dimeric form of SOD1 is less susceptible to unfolding when solvated by CAPRIN1. Our work underscores the impact of the condensate solvent environment on the conformational states of resident proteins and supports the hypothesis that ALS mutations that decrease metal binding or dimerization function as drivers of aggregation in condensates., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Antiplatelet therapy plays an important role in reducing the risk of stroke recurrence in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA). However, data regarding the effectiveness and safety of using aspirin plus clopidogrel in dual antiplatelet therapy (DAPT) compared to aspirin alone in mild ischemic stroke is limited. Methods: PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT to aspirin alone started within 72 hours in mild ischemic stroke or high-risk TIA. We used a random effects model to pool risk ratios (RRs) along with 95% CIs for clinical outcomes. Results: Four RCTs with 16,547 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 26% (RR: 0.74; 95% CI: 0.67-0.83; p < 0.00001), ischemic stroke by 28% (RR: 0.72; 95% CI: 0.65-0.80; p < 0.00001), and major adverse cardiovascular events (MACE) by 24% (RR: 0.76; 95% CI: 0.68-0.84; p < 0.00001) compared to aspirin monotherapy. However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 1.88; 95% CI: 1.10-3.23; p = 0.02) compared to aspirin alone. No significant differences were observed for hemorrhagic stroke (RR: 1.77; 95% CI: 0.96-3.29; p = 0.07), all-cause mortality (RR: 1.25; 95% CI: 0.87-1.80; p = 0.23), cardiovascular mortality (RR: 1.38; 95% CI: 0.81-2.33; p = 0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p = 0.20). Conclusion: DAPT involving aspirin plus clopidogrel reduces stroke recurrence and MACE but can lead to an increased risk of moderate or severe bleeding compared to aspirin monotherapy. (PROSPERO ID: CRD42024499310) ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Dual targeting by a single molecule has emerged as a promising strategy for fighting cancer. In this study, a new set of 2-thioquinazolin-4(3 H )-ones as potential anti-cancer surrogates endowed with dual EGFR/VEGFR-2 kinases inhibitory activities were synthesized. The anti-tumor potency of the newly synthesized candidates 4-27 was evaluated against a panel of four cancer cell lines. The prepared candidates 4-27 showed comparable activity to that of the standard drug sorafenib. For instance, compound 4 (IC 50 = 1.50-5.86 μM) and compound 20 (IC 50 = 4.42-6.39 μM) displayed superior potencies against all cell lines compared to sorafenib (IC 50 = 5.47-7.26 μM). Dual EGFR/VEGFR-2 inhibitory activities of the most active analogues (4, 11, and 20) were investigated. Compound 4 showed comparable EGFR/VEGFR-2 inhibitory activity to the used control drugs. Flow cytometric analysis indicates that the most potent analogue 4 stopped the cell cycle at the G1 phase and induced 46.53% total apoptosis in HCT-116 cells that was much more powerful than the untreated cells with 2.15% apoptosis. Molecular docking and dynamic simulations of 4, 11, and 20 with EGFR and VEGFR-2 were performed to examine the binding mode and interaction within the enzyme binding pockets., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Purpose: Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs)., Methods: We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25 ng/mL and the patient was on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs., Results: There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group, at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001)., Conclusion: The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study aimed to investigate the effect of mitochondria-targeted antioxidants (Mitoquinone, MitoQ) on the quality of frozen-thawed stallion semen. Semen samples collected from three fertile stallions aged 10 - 13 years, were filtered, centrifuged in a skimmed milk-based extender, and diluted to a final concentration of 50 × 106 sperm/mL in freezing medium. Diluted semen was divided into five experimental groups supplemented with MitoQ at concentrations of 0 (control), 25, 50, 100, and 200 nM and then subjected to freezing after cooling and equilibration. After thawing, semen was evaluated for motility and kinetics at different time points. Sperm viability, plasma membrane, acrosome, DNA integrity, mitochondrial membrane potential, apoptosis, and intracellular reactive oxygen species (ROS) concentrations were evaluated. The results revealed that MitoQ at concentrations of 25, 50, and 100 nM improved (P< 0.01) the total sperm motility after 30 minutes of incubation. In addition, 25 nM MitoQ improved the sperm amplitude of lateral head displacement values (P< 0.01) after 30 minutes of incubation. Conversely, negative effects on sperm motility, kinetics, and viability were observed with the highest tested concentration of MitoQ (200 nM). The various concentrations of MitoQ did not affect the plasma membrane, acrosome, and DNA integrity, or the mitochondrial membrane potential and intracellular ROS concentrations. In conclusion, supplementation of MitoQ during cryopreservation, had a mild positive effect on sperm motility and kinetics especially at a concentration of 25 nM, while the highest concentration (200nM) has a detrimental effect on motility and viability parameters of frozen-thawed stallion sperm., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: It was proposed that camels are more effective than other livestock species in selecting plants for their nutritional value. They may self-regulate their voluntary feed intake to satisfy their nutritional needs. This study was designed to investigate camels' feeding selectivity and ability to cover nutritional requirements when grazing alfalfa (high in protein) and/ or barley (high in energy) in a desert climate., Methods: Eighteen lactating camels were equally divided into three feeding treatments. They grazed daily on alfalfa, barley, or a mixed pasture of both, for two periods of one month each. The concentrate supplement was individually administered at 40 g/kg BW 0.75 , divided into two equal parts, in the morning and in afternoon. Total energy expenditure (EE) was estimated by heart rate (HR) monitors for 48 h after being calibrated by oxygen consumption using an upgraded face mask open-circuit respiratory system., Results: During the first period, camels had a greater forage intake and digestibility when they grazed barley rather than alfalfa, while those grazing mixed pasture performed intermediately. In the second period, camels had a similar forage intake and digestibility among treatments due to a decline in barley intake and digestibility compared to the first period, which was expected since the preferred plant part gradually shifted from barley grains to predominantly straw as a function of time. Similar HR and EE were found across periods and treatments. As a result of greater gross and digestible energy intake in period 1, a better energy balance in period 1 was observed compared to period 2. Camels better utilize barley than alfalfa. Grazing on barley had a higher energy balance than grazing alfalfa alone or in combination with barley. However, camels grazing barley produced lower milk yield and energy than those grazing alfalfa alone or in combination with barley, with no interaction detected between period and treatment., Conclusions: Lactating camels are able to self-regulate their voluntary intake to cover their energy requirements when they are grazing barley and/or alfalfa supplemented with a concentrate supplement at 40 g/kg BW 0.75 . Grazing barley is better utilized by camels than alfalfa. The chemical and physical properties of plant species play an important role in the selectivity of foraging camels. It also impacts their intake and digestibility, which is negatively associated with the proportion of cell wall content consumed., (© 2024. The Author(s).)

Natural products received much attention as an environmentally beneficial solution for pest management. Therefore, the extracts of invasive silverleaf nightshade (Solanum elaeagnifolium Cav.) weeds using their berries parts (seeds, peels and mucilage) supported by bioassay-guided fractionation were tested against both the greater wax moth (Galleria mellonella) and Erwinia carotovora pv. carotovora causes of the blackleg of potatoes. The seeds and peels of S. elaeagnifolium were successively extracted by maceration using dichloromethane (DCM), ethyl acetate (EtOAc), and ethanol (EtOH), respectively. While, its mucilage was extracted using EtOAc. The successive EtOH extract of the plant seeds had promising inhibition efficacy and the best minimal inhibition concentration (MIC) of 50 µg/ml against E. Carotovora amongst other extracts (DCM and EtOAc of the plant berries parts). Depending on dose response activity, EtOH extract had G. mellonella larval mortality and pupal duration rates (LC 50 ; 198.30 and LC 95 ; 1294.73 µg/ml), respectively. Additionally, this EtOH extract of seeds was fractionated using preparative TLC to three characteristic bands. The insecticidal and bacterial activities of these isolated bands (SEA, SEB, and SEC) were evaluated at a dose of 100 µg/ml, causing mortality by 48.48, 62.63 and 92.93% (G. mellonella larvae) and inhibition by 15.22, 0.00 and 31.66 mm (E. carotovora), respectively. Moreover, the separated major three bands were tentatively identified using LC-ESI-MS analysis revealing the presence of two phenolic acids; chlorogenic acid (SEA) and dicaffeoyl quinic acid (SEB) in addition to one steroidal saponin (SEC) annotated as borassoside E or yamoscin. Finally, the plant seeds' successive EtOH extract as well as its active constituents, exhibited potential broad-spectrum activity and the ability to participate in future pest management initiatives. A field study is also recommended to validate its bio-efficacy against selected pests and to develop its formulations., (© 2024. The Author(s).)

Introduction: Benign prostatic hyperplasia (BPH) is a prevalent urologic condition leading to lower urinary tract symptoms (LUTS). Transurethral prostatectomy has been a cornerstone for surgical management of LUTS due to BPH. A growing interest has recently emerged to develop a surgical approach that can decrease the effect on sexual and ejaculatory functions while maintaining its efficacy in treating LUTS., Objective: The aim of this meta-analysis is to assess patient-reported outcomes of ejaculatory-sparing transurethral prostatectomy in management of BPH., Methods: Cochrane Library, Scopus, PubMed, and Web of Science databases were searched systematically until July 6, 2024. Randomized controlled trials reporting data on ejaculatory-sparing techniques during transurethral prostatectomy were included. The Cochrane risk-of-bias tool for randomized trials was used for quality assessment. The meta-analysis was conducted with Review Manager software. Numerical data were analyzed by standardized mean difference (SMD), while the risk ratio was used for analysis of categorical data. Fixed or random effects models were used according to heterogeneity., Results: Five randomized controlled trials were included with 274 patients. No statistically significant differences were found between groups for International Prostate Symptom Score (SMD, 0.07; 95% CI, -0.45 to 0.59; P = .79), Qmax (SMD, -0.53; 95% CI, -1.11 to 0.06; P = .08), and International Index of Erectile Function (SMD, 0.89; 95% CI, -0.07 to 1.84; P = .07). Ejaculation was better preserved in ejaculatory-sparing techniques (risk ratio, 0.19; 95% CI, 0.12-0.30; P < .00001)., Conclusions: Ejaculatory-sparing transurethral prostatectomy techniques are feasible to preserve ejaculation while improving outcomes without compromising functional voiding outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.)

Early detection of cancer is vital for increasing patient survivability chances. The three major techniques used to diagnose cancers are instrumental examination, tissue biopsy, and tumor biomarker detection. Circulating tumor DNA (ctDNA) has gained much attention in recent years due to advantages over traditional technology, such as high sensitivity, high specificity, and noninvasive nature. Through the mechanism of apoptosis, necrosis, and circulating exosome release in tumor cells, ctDNA can spread throughout the circulatory system and carry modifications such as methylations, mutations, gene rearrangements, and microsatellite instability. Traditional gene-detection technology struggles to achieve real-time, low-cost, and portable ctDNA measurement, whereas electrochemical biosensors offer low cost, high specificity alongside sensitivity, and portability for the detection of ctDNA. Therefore, this review focuses on describing the recent advancements in ctDNA biomarkers for various cancer types and biosensor developments for real-time, noninvasive, and rapid ctDNA detection. Further in the review, ctDNA sensors are also discussed in regards to their selections of probes for receptors based on the electrode surface recognition elements.

The frequent occurrence of antibiotics in the aquatic environment has engendered negative impacts on non-target organisms. The effects of the veterinary antibiotic florfenicol (FLO) during the embryo-larval development of the sea urchin, Paracentrotus lividus was assessed using four increasing concentrations (1, 2, 5 and 10 mg/L). Furthermore, FLO toxicity to adults was investigated through the analysis of oxidative damage, histopathological alterations, lipid metabolism and acetylcholinesterase activity following an exposure period of 96 h. FLO induced embryotoxicity with estimated EC50 values of 5.75, 7.56 and 3.29 mg/L after 12 h, 24 h and 48 h, respectively. It generated oxidative stress assessed as lipid peroxidation in gonads despite the increased antioxidant activity of catalase (CAT). Neurotoxicity was also evident since the AChE activity significantly decreased. Moreover, FLO affected the lipid metabolism by increasing saturated fatty acid (SFA) and monounsaturated fatty acid proportions (MUFA), except in the group exposed to 5 mg/L. The increase in polyunsaturated fatty acid (PUFA) levels and docosahexaenoic acid (DHA, C22:6n-3) proportions were noted with all FLO concentrations. Eicosapentaenoic acid (EPA, C20:5n-3) decreased, while arachidonic acid (ARA, C20:4n-6) increased in sea urchins exposed to 5 and 10 mg/L FLO. Histopathological alterations of gonadal tissues represent an additional confirmation about the toxicity of this antibiotic that might decrease the reproductive performance of this species. Nevertheless, even if reproduction of sea urchins would be partially successful, the embryotoxicity would compromise the normal development of the embryos with consequences on the population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Hypothesis: Clinical trials have demonstrated positive cardiovascular and kidney outcomes of sodium-glucose-co-transporter-2 (SGLT2) inhibitors in adult patients with diabetic and other chronic kidney diseases (CKD). Whether benefits extend to children, teenagers, and young adults with early-stage CKD is unknown. For this reason, the DOUBLE PRO-TECT Alport trial (NCT05944016) will study the progression of albuminuria in young patients with Alport syndrome (AS), the most common hereditary CKD, to assess the safety and efficacy of the SGLT2-inhibitor dapagliflozin. Patients living with AS and chronically elevated albuminuria have a high risk of kidney failure before the age of 50 years., Methods and Rationale: DOUBLE PRO-TECT Alport is a multicenter, randomized, double-blind, placebo-controlled trial (RCT). Participants (aged 10 to 39 years) must have a diagnosis of AS by genetic testing or kidney biopsy, be on a stable (> 3 months) maximum tolerated dose of a renin-angiotensin-system-inhibitor (RASi) and must have a Urinary Albumin to Creatinine Ratio (UACR) of >300 mg/g (pediatric) or >500 mg/g (adult).Eligible participants will be randomly assigned at a 2:1 ratio to 48 weeks of treatment with dapaglifozin 10 mg/day -to- matched placebo. Most participants are expected to be children with a normal glomerular filtration rate (eGFR). In addition to safety, the primary (change in UACR from baseline to Week 48) and key secondary (eGFR change from baseline to Week 52) efficacy outcomes will be analyzed with a mixed model repeated measures approach. Efficacy analyses will be performed primarily in the full analysis set according to the intention-to-treat principle. A sensitivity analysis will be performed using reference-based multiple imputation., Conclusion: DOUBLE PRO-TECT Alport will assess whether SGLT2-inhibitors can safely reduce change from baseline in UACR as a marker for progression of CKD in young patients living with AS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Sound speed estimation can potentially correct the focusing errors in medical ultrasound. Maximizing the echo spatial coherence as a function of beamforming sound speed is a known technique to estimate the average sound speed. However, beamformation with changing sound speed causes a spatial shift of the echo signals resulting in noise and registration errors in the average sound speed estimates. We show that the spatial shift can be predicted and corrected, leading to superior sound speed estimates. Methods are presented for axial and two-dimensional location correction. Methods were evaluated using simulations and experimental phantom data. The location correction strategies improved the variance of sound speed estimates and reduced artifacts in the presence of strong backscatter variations. Limitations of the proposed methods and potential improvement strategies were evaluated.

Objective: In high-risk agricultural environments, tasks, weather, and work conditions vary throughout the year. Also, injuries peak during certain periods. The primary objective of this study was to examine operator- and farm-level characteristics as risk factors for injuries within each of the four seasons. The secondary objective was to examine seasonal differences in the incident location and primary cause of these injuries., Method: We analyzed data from the 2018 and 2020 Farm and Ranch Health and Safety Surveys (FRHSS), conducted in seven U.S. states by the Central States Center for Agricultural Safety and Health (CS-CASH), which were collected using a stratified random sampling approach to ensure representativeness. The survey data were merged with operation-level data from the Farm Market iD database. We employed Generalized Estimating Equations (GEE) to examine the association of seasonal injuries with individual and operation-level characteristics. The chi-square test of independence was used to assess the association between injury incident location and season, as well as injury cause and season. Pairwise Z-tests of proportions were conducted to evaluate the differences in the proportions of injuries due to specific combinations of injury location and cause across each pair of seasons., Results: Surveys conducted in 2018 and 2020 yielded a combined response rate of 15.9%, with 5,428 responses and 7,915 unique operators. Of these, 903 operators reported at least one injury during the past 12 months. Seasonally, most injuries occurred in spring (34.2%), followed by summer (24.7%). Male operators had higher injury odds in the spring (adjusted OR = 1.42) and summer (aOR = 2.41). Those managing both a farm and a ranch reported increased injury risks in winter (aOR = 1.73) and spring (aOR = 1.48). Operators in cow-calf operations faced higher springtime injury risks (aOR = 1.45). High stress and exhaustion were consistent risk factors across all seasons. The highest proportion of injury incidents occurred in the farmyard (43.6%), and livestock were the most common cause of injury (24.9%)., Conclusion: Results highlight the need for season-specific prevention and intervention strategies, considering farmers' and ranchers' risk characteristics, injury locations, and causes. These findings can inform targeted measures for high-risk populations at optimal times and locations.

Using the gas chromatography mass spectrometry method, the chemical components of essential oil from flowers of Lantana camara growing in Egypt are analyzed. Through this investigation, 22 chemicals from floral oil were identified. Most of the oil is made up of sesquiterpene caryophyllene (15.51%) and monoterpene sabinene (14.90%). When the oil's composition was compared to oils extracted from the same plant on several continents, we observed that the essential components were largely the same with some difference in proportions and some compounds due to geographical differences. A molecular docking study of essential oil components was conducted with human superoxide dismutase 1, a target involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). Isospathulenol showed a comparable docking score to the reference ligand bound to the dismutase enzyme. Isospathulenol showed a reasonable drug score with some safety concerns. In addition, isospathulenol is predicted to have high GI absorption, good permeability through the blood-brain barrier and reasonable bioavailability score with ease access to synthetic modifications. In addition, the same compound is devoid from any violation to Lipinski rules or any PAINS alerts. This may establish the promising characteristics of such a compound to be optimized into potential drug candidates for treatment of ALS., Competing Interests: The Authors declare that there is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing the severity of the disease and deaths, the decline in vaccine-induced immunity over time and the continuing emergence of new viral variants or mutations underscore the need for an alternative strategy for developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature of severe COVID-19 is dysregulated innate immune signaling, culminating in a high expression of numerous pro-inflammatory cytokines and chemokines and a lack of antiviral interferons (IFNs), particularly type I (alpha and beta) and type III (lambda). As a natural host defense, the myeloid differentiation primary response protein, MyD88, plays pivotal roles in innate and acquired immune responses via the signal transduction pathways of Toll-like receptors (TLRs), a type of pathogen recognition receptors (PRRs). However, recent studies have highlighted that infection with viruses upregulates MyD88 expression and impairs the host antiviral response by negatively regulating type I IFN. Galectin-3 (Gal3), another key player in viral infections, has been shown to modulate the host immune response by regulating viral entry and activating TLRs, the NLRP3 inflammasome, and NF-κB, resulting in the release of pro-inflammatory cytokines and contributing to the overall inflammatory response, the so-called "cytokine storm". These studies suggest that the specific inhibition of MyD88 and Gal3 could be a promising therapy for COVID-19. This review presents future directions for MyD88- and Gal3-targeted antiviral drug discovery, highlighting the potential to restore host immunity in SARS-CoV-2 infections.

Accurate segmentation of chronic stroke lesions from mono-spectral magnetic resonance imaging scans (e.g., T1-weighted images) is a difficult task due to the arbitrary shape, complex texture, variable size and intensities, and varied locations of the lesions. Due to this inherent spatial heterogeneity, existing machine learning methods have shown moderate performance for chronic lesion delineation. In this study, we introduced: (1) a method that integrates transformers' deformable feature attention mechanism with convolutional deep learning architecture to improve the accuracy and generalizability of stroke lesion segmentation, and (2) an ecological data augmentation technique based on inserting real lesions into intact brain regions. Our combination of these two approaches resulted in a significant increase in segmentation performance, with a Dice index of 0.82 (±0.39), outperforming the existing methods trained and tested on the same Anatomical Tracings of Lesions After Stroke (ATLAS) 2022 dataset. Our method performed relatively well even for cases with small stroke lesions. We validated the robustness of our method through an ablation study and by testing it on new unseen brain scans from the Ischemic Stroke Lesion Segmentation (ISLES) 2015 dataset. Overall, our proposed approach of transformers with ecological data augmentation offers a robust way to delineate chronic stroke lesions with clinically relevant accuracy. Our method can be extended to other challenging tasks that require automated detection and segmentation of diverse brain abnormalities from clinical scans., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

This study aims to examine how the climate affects the behaviour of the stock market. To achieve this, we have drawn on daily data from Jan 2005 to Jan 31, 2023 and several environmental factors (e.g., temperature, humidity, cloud cover and visibility) to account for extreme weather conditions using the 21-day moving average and its standard deviation. The empirical analysis has revealed three key findings regarding the impact of weather on the stock market's behaviour. First, various forms of extreme weather conditions consistently lead to influence stock behaviour. Second, results provide valuable insights into market behaviour and help investors to make more informed investment decisions. Third, the weather conditions have new information about the climate risk and investors should react to it swiftly in light of our findings. The saliency theory can help reconcile the theoretical conflicts between the real options and risk-shifting theories when it comes to investing in uncertain and extreme climate conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Worker trust in employer-provided occupational health services has not been explored in essential industries, such as meatpacking. The purpose of this study was to describe workplace health culture and trust in the occupational health office and highlight meatpacking workers' experiences with the occupational health office., Methods: Meatpacking workers were surveyed between February 2021 and October 2022. Descriptive statistics and nonparametric tests were used to explore trust across demographic variables, including workplace health culture. Thematic analysis was used to examine the short-answer qualitative data., Results: Among workers who completed surveys (n = 731), health culture was rated low (M = 1.3 (0.73); possible range 0-3). Trust in the occupational health office was also rated low (M = 8.2 (5.06); possible range 0-20). Workers' descriptions of interactions with the occupational health office were mostly unfavorable (287 negative opinion units; 97 positive opinion units) and primarily focused on quality of care, communication, the supervisor as gatekeeper to health services, and the prioritization of company interests., Conclusion: Meatpacking worker health may be improved by building worker trust in the occupational health office. Suggested strategies include enhanced communication, protection of confidentiality, prioritization of worker well-being, and promotion of a stronger health culture in plants and throughout the industry. Supporting workers without a regular healthcare provider to establish a relationship with a primary care provider of their choice is also recommended., (© 2024 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Introduction: The pandemic-driven surge in global distance simulation (DS) adoption highlighted the need for effective educator training. A literature search identified the gap regarding human factors (HF) considerations for the professional development of DS practitioners. This study addresses this gap by applying HF principles to guide educators in developing and delivering evidence-based DS., Methods: This was a consensus-gathering, three-phase study using the nominal group technique (NGT) in the first phase, qualitative thematic analysis with member checking in the second phase and external expert opinion in the third. A dichotomised approach was used to divide the post-consensus discussion survey results into an agreement and non-agreement for quantitative analysis., Results: The results of the quantitative analysis identified the following needs: developing a conceptual framework for DS, tailoring the technical aspect to the educational objectives, investigating learner engagement, training faculty at an earlier stage and identifying at-risk students. Qualitative results identified primary themes of technology, people and outcome measurements. Key aspects of technology were identified as system- and programme-fit and resource considerations. Outcome measurement highlights the need for increased measurement and research at all levels of DS., Discussion: Specific HF focal points include human-technology interaction and learning outcome assessment within the DS context. Incorporating HF principles throughout the DS process, from inception to outcome evaluation, promises substantial benefits for both learners and educators. This approach empowers both learners and educators, fostering a dynamic and enriched educational environment and improved learning experiences., (© 2024 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

In this study, gold nanoparticles (AuNPs) were bioreduced from Ajuga bracteosa, a medicinal herb known for its therapeutic properties against various diseases. Different fractions of the plant extract were used, including the methanolic fraction (ABMF), the n-hexane fraction (ABHF), the chloroform fraction (ABCF), and the aqueous extract for AuNPs synthesis. The characterization of AuNPs was performed using UV-Vis spectrophotometry, FT-IR, XRD, EDX, and TEM. UV-Vis spectroscopy confirmed the formation of AuNPs, with peaks observed at 555 nm. FT-IR analysis indicated strong capping of phytochemicals on the surface of AuNPs, which was supported by higher total phenolic contents (TPC) and total flavonoid contents (TFC) in AuNPs. XRD results showed high crystallinity and a smaller size distribution of AuNPs. TEM analysis revealed the spherical shape of AuNPs, with an average size of 29 ± 10 nm. The biologically synthesized AuNPs exhibited superior antibacterial, antioxidant, and cytotoxic activities compared to the plant extract fractions. The presence of active biomolecules in A. bracteosa, such as neoclerodan flavonol glycosides, diterpenoids, phytoecdysone, and iridoid glycosides, contributed to the enhanced biological activities of AuNPs. Overall, this research highlights the potential of A. bracteosa-derived AuNPs for various biomedical applications due to their remarkable therapeutic properties and effective capping by phytochemicals. RESEARCH HIGHLIGHTS: This research underscores the growing significance of herbal medicine in contemporary healthcare by exploring the therapeutic potential of Ajuga bracteosa and gold nanoparticles (AuNPs). The study highlights the notable efficacy of A. bracteosa leaf extracts and AuNPs in treating bacterial infections, demonstrating their bactericidal effects on a range of strains. The anti-inflammatory properties of plant extracts and nanoparticles are evidenced through paw edema method suggesting their applicability in managing inflammatory conditions. These findings position A. bracteosa and AuNPs as potential candidates for alternative and effective approaches to modern medication., (© 2024 Wiley Periodicals LLC.)

Purpose: This study investigates the associations between women empowerment and the prevalence of mental health symptoms and care-seeking behavior among ever-married Nepalese women aged 15-49 years., Methods: We utilized 2022 Nepal Demographic and Health Survey data to measure women empowerment, employing the Survey-Based Women's Empowerment (SWPER) index. The index focuses on the domains of social independence, decision-making, and attitudes towards violence. Symptoms of anxiety and depression were measured using the Generalized Anxiety Disorder-7 scale (GAD-7) and the Patient Health Questionnaire (PHQ-9), respectively. Multiple logistic regression was performed to estimate adjusted odds ratio (aOR) for associations of women empowerment domains and mental health problems and care-seeking behavior., Results: Among 5556 women, the prevalence of symptoms of anxiety and depression was 23.1% and 6.1%, respectively. Among those with any symptoms of anxiety or depression, 18.3% sought care. Compared to women with low level of empowerment in the "social independence" domain, those with high level of empowerment were less likely to suffer from symptoms of anxiety (aOR = 0.68; 95%CI, 0.57-0.82) and depression (aOR = 0.69; 95%CI, 0.50-0.94). However, high empowerment in "decision-making" domain was associated with higher likelihood of anxiety (aOR = 1.67; 95%CI, 1.33-2.10) and depression (aOR = 1.80; 95%CI, 1.26-2.58). There was evidence of positive association between high empowerment in "decision-making" and care-seeking (aOR = 1.28; 95%CI, 0.96-1.71)., Conclusions: This study underscores important roles of women empowerment on mental health symptoms and care-seeking behavior, suggesting the need to integrate empowerment initiatives into strategies to promote mental health among women in Nepal and similar low- and middle-income settings., (© 2024. The Author(s).)

Aims: The postvoid residual (PVR) volume of urine in the bladder is widely used in clinical practice as a guide to initiate treatment, including clean-intermittent self-catheterization (CISC). It is often believed that an elevated PVR causes complications such as recurrent urinary tract infections (UTI) and renal failure. However, evidence for this is limited and identifying alternative measures to guide treatment decisions may optimize patient care. At the International Consultation on Incontinence Research Society (ICI-RS) meeting in 2023 a Think Tank addressed the question of whether we can define the optimal PVR at which CISC should be recommended, and whether there are other measures that could guide a CISC protocol., Methods: The Think Tank conducted a literature review and expert consensus meeting focusing on current limitations in defining and measuring PVR, and highlighting other measures that may optimize selection for, and persistence with, CISC., Results: There is no consensus on the threshold value of PVR that is considered "elevated" or "significant." There is a lack of standardization on terminology, and the normal range of PVR in different populations of different ages remains to be well-studied. The measurement of PVR is influenced by several factors, including intraindividual variation, timing and method of measurement. Furthermore, the evidence linking an elevated PVR with complications such as UTI and renal failure is mixed. Other measures, such as bladder voiding efficiency or urodynamic parameters, may be better at predicting such complications, and therefore may be more relevant at guiding a CISC protocol., Conclusions: There is a lack of high quality evidence to support PVR as a predictor for complications of UTI or renal failure. Threshold values for normal PVR in different populations are unknow, and so threshold values for "elevated" or "significant" PVR cannot be determined. Other factors, such as urodynamic findings, may be better at predicting complications and therefore guiding management decisions, and this remains to be studied. Areas for further research are proposed., (© 2023 Wiley Periodicals LLC.)

Aims: This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted., Methods: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS., Results: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended., Conclusions: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing., (© 2024 Wiley Periodicals LLC.)

Background: Bladder diaries represent a fundamental component in the assessment of patients presenting with lower urinary tract symptoms. Nevertheless, their importance often remains underappreciated and undervalued within clinical practice. This paper aims to conduct a comprehensive review of the existing literature concerning the utility of bladder diaries, underscore the criticality of their precision, elucidate the factors contributing to noncompliance with bladder diary completion, and investigate potential strategies for enhancing patient compliance., Materials and Methods: A review of the English-language scientific literature available in the domains of Medline, Embase, Emcare, Midirs, and Cinahl was conducted. This was supplemented by discussion at the International Consultation on Incontinence Research Society Proposal session to define knowledge and identify gaps in knowledge surrounding the utility of bladder diaries. The existing evidence and outcome of the relevant discussion held in the meeting are presented., Results: Bladder diaries (BD) serve to characterize the nature and severity of storage lower urinary tract symptoms (LUTS) and provide an objective record of an individual's urination patterns. They aid in the refinement and customization of treatment strategies based on the clinical responses documented in the diary, optimizing treatment outcomes. Notably, both BD and urodynamic studies (UDS) play complementary yet distinct roles in LUTS evaluation. BD offers a more comprehensive and accessible approach to assessing specific storage LUTS, particularly due to their affordability and widespread availability, especially in resource-limited settings. Nevertheless, the absence of a standardized BD format across global healthcare systems presents a significant challenge. Despite being recognized as reliable, noninvasive, validated, and cost-effective tools for evaluating patients with LUTS, the implementation and completion of BD have proven to be complex. The introduction of automated bladder diaries heralds an era of precise, real-time data collection, potentially enhancing the patient-clinician relationship. Completion of bladder diaries depends on an array of individual, social, and healthcare-specific factors. Compliance with bladder diary completion could be enhanced with clear instructions, patient education, regular follow-ups and positive re-enforcement. This study has identified four critical areas for future research: Addressing healthcare disparities between affluent and developing nations, enhancing the current functionality and effectiveness of bladder diaries, exploring the feasibility of incorporating bladder diaries into the treatment and education process and improving the quality and functionality of existing bladder diaries., Conclusion: Bladder diaries play a pivotal role in the evaluation and management of patients with LUTS, providing a holistic perspective. When their complete potential is harnessed, they have the capacity to revolutionize the paradigm of LUTS management, ushering in a patient-centered era of care., (© 2023 Wiley Periodicals LLC.)

Background: Isolated cardiac sarcoidosis (iCS) is a poorly understood and under-recognised entity. Previous research has postulated that those with iCS have worsened outcomes compared to those with other manifestations of the disease, however, there have been studies which both support and refute this hypothesis., Purpose of Review: This review will summarise the literature which focuses on differences in the epidemiology, imaging findings and patient outcome of those with isolated cardiac sarcoidosis (iCS) versus 'systemic' cardiac sarcoidosis (sCS) which is not isolated to the heart., Summary: Variations in study design make accurate comparison between current papers challenging, and that the factors which indicate poor prognosis in patients with iCS is not yet fully understood. Current literature suggests those with iCS are more likely to be male, have higher numbers of abnormal uptake patterns on cardiac imaging, and may have poorer prognosis than sCS patients. Multi-centre, prospective studies analysing isolated cardiac sarcoidosis across geographical regions are needed to improve our understanding of this phenomenon and ultimately improve patient outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: While the exact pathogenesis of peripartum cardiomyopathy, a potentially life-threatening condition, is still unknown, its incidence is rising globally. We sought to understand the differences in outcomes and complications based on age., Methods: Records from the 2016-2020 National Inpatient Sample were used for our study. The sample consisted of females diagnosed with peripartum cardiomyopathy that required hospitalization care. They were divided into two age-based cohorts: 15-29 years and 30-40 years. We evaluated differences in in-hospital complications between the two groups using multivariable regression., Results: The analysis consisted of 20520 females diagnosed with peripartum cardiomyopathy, of whom 57.3 % were in the 30-40 years cohort and 42.7 % in the 15-29 years group. The prevalence of cardiovascular risk factors such as smoking, obesity, hypertension, diabetes and lipid disorder was higher among women aged 30-40 years (p < 0.01). These patients also demonstrated higher odds of reporting acute ischemic stroke (aOR 1.354, 95 % CI 1.038-1.767, p = 0.026) while having a reduced risk of cardiogenic shock (aOR 0.787, 95 % CI 0.688-0.901, p < 0.01) as compared to those aged 15-29 years during their hospitalisation with PPCM. No statistically significant differences were noted for events of acute kidney injury (aOR 1.074, 95 % CI 0.976-1.182, p = 0.143), acute pulmonary oedema (aOR 1.147, 95 % CI 0.988-1.332, p = 0.071) or in-hospital mortality (aOR 0.978, 95 % CI 0.742-1.290, p = 0.877)., Conclusion: Peripartum cardiomyopathy is a serious condition that requires appropriate care and management. Our study linked cases of ages 30-40 years with increased odds of acute ischemic stroke but lower odds of cardiogenic shock., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups., Methods: The US Nationwide Readmission Database was queried from 2010 to 2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, 9th and 10th Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed., Results: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs 1.4%, P < .0001), ventricular tachycardia (6.5% vs 1.3%, P < .0001), ventricular fibrillation (0.4% vs 0.1%, P < .0001) and atrial fibrillation (22.1% vs 7.5%, P < .0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, P < .0001), had higher length of hospital stay (5 vs 4 days, P < .0001), adjusted healthcare-associated costs ($9,667.0 vs $9,087.1, P < .0001) and mortality rates on readmission (5.1% vs 3.8%, P < .0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI, and liver disease., Conclusion: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Tricuspid valve regurgitation, or TR, is a difficult-to-manage condition. In addition to EVOQUE, percutaneous annuloplasty, and surgical repair, the TriClip G4 system has been added to the interventional therapeutic choices for TR. Recently, the Food and Drug Administration (FDA) approved the use of the TriClip G4 device to treat patients with symptomatic, severe TR who have received optimal medication therapy but are at intermediate or higher risk of surgery. This review attempts to offer a thorough examination of the procedural features, learning curves, results of the device and compares the TriClip G4 system to other interventional therapies for TR. TriClip G4 has shown to have promising results in pivotal clinical trials, be cost-effective, and improve the quality of life of patients. Furthermore, it has its unique advantages against other conventional techniques and devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Clinical practice recommendations guide healthcare decisions. This study aims to evaluate the strength and quality of evidence supporting the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracerebral hemorrhage (ICH)., Methods: We reviewed the current AHA/ASA guidelines for aSAH and spontaneous ICH and compared with previous guidelines. Guidelines were classified based on the Class of recommendation (COR) and Level of evidence (LOE). COR signifies recommendation strength (COR 1: Strong; COR 2a: Moderate; COR 2b: Weak; COR 3: No Benefit/Harm), while LOE denotes evidence quality (LOE A: High-Quality; LOE B-NR: Moderate-Quality, Not Randomized; LOE B-R: Moderate-Quality, Randomized; LOE C-EO: Expert Opinion; LOE C-LD: Limited Data)., Results: For aSAH, we identified 84 recommendations across 15 guideline categories. Of these, 31% were classified as COR I, 30% as COR 2a, 17% as COR 2b, and 18% as COR 3. In terms of LOE, 7% were based on LOE A, 10% on LOE B-R, 65% on LOE B-NR, 14% on LOE C-LD, and 5% on LOE C-EO. Compared to previous guidelines, there was a 46% decrease in LOE A, a 45% increase in LOE B, and an 11% decrease in LOE C. For spontaneous ICH, 124 guidelines were identified across 31 guideline categories. Of these, 28% were COR I, 32% COR 2b, and 9% COR 3. For LOE, 4% were based on LOE A, 35% on LOE B-NR, and 42% on LOE C-LD. Compared to previous guidelines, there was a 78% decrease in LOE A, an 82% increase in LOE B, and a 14% increase in LOE C. This analysis highlights that less than a third of AHA/ASA guidelines are classified as the highest class of recommendation, with less than 10% based on the highest LOE., Conclusion: Less than a third of AHA/ASA guidelines on aSAH and spontaneous ICH are classified as the highest class of recommendation with less than 10% based on highest LOE. There appears to be a decrease in proportion of guidelines based on highest LOE in most recent guidelines., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

During chronic infection, virus-specific CD8 + cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Pdcd1 alleles dissociate from transcriptionally repressive chromatin domains (lamin B) in virus-specific exhausted CTLs but not in naive or effector CTLs. Relative to naive CTLs, nuclear positioning and Pdcd1-lamina dissociation in exhausted CTLs reflect loss of Pdcd1 promoter methylation and greater PD-1 upregulation, although a direct correlation is not observed in effector cells, 8 days post-infection. Genetic deletion of B lymphocyte-induced maturation protein 1 (Blimp-1) enhances Pdcd1-lamina dissociation in effector CTLs, suggesting that Blimp-1 contributes to maintaining Pdcd1 localization to repressive lamina. Our results identify mechanisms governing Pdcd1 subnuclear localization and the broader role of chromatin dynamics in T cell exhaustion., Competing Interests: Declaration of interests Catarina Sacristán is an employee of Cell Press, Elsevier, but was uninformed of manuscript handling. Peer review was fully independent of said author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Stroke-associated pneumonia (SAP) considerably burden healthcare systems. This study aimed to identify predictors of developing SAP in acute ischemic stroke patients admitted to the Stroke Unit at Manial Specialized Hospital factors with microbiological causality and impact on 30-day mortality., Methods: This was a retrospective cohort study. All patients with acute ischemic stroke admitted to the Stroke Unit at Manial Specialized Hospital (from February 2021 to August 2023) were divided into the SAP and non-SAP groups. Detailed clinical characteristics and microbiological results were recorded., Results: Five hundred twenty-two patients diagnosed with acute ischemic stroke (mean age of 55 ± 10) were included. One hundred sixty-nine (32.4%) of stroke patients developed SAP; Klebsiella pneumoniae was the most commonly detected pathogen (40.2%), followed by Pseudomonas aeruginosa (20.7%). Bacteremia was identified in nine cases (5.3%). The number of deaths was 11, all of whom were diagnosed with SAP, whereas none from the non-SAP group died (P < 0.001). The binary logistic regression model identified three independent predictors of the occurrence of SAP: previous history of TIA/stroke (OR = 3.014, 95%CI = 1.281-7.092), mechanical ventilation (OR = 4.883, 95%CI = 1.544-15.436), and bulbar dysfunction (OR = 200.460, 95%CI = 80.831-497.143)., Conclusions: Stroke-associated pneumonia was reported in one-third of patients with acute ischemic stroke, adversely affecting mortality outcomes. Findings showed that the main predictors of SAP were bulbar dysfunction, the use of mechanical ventilation and previous history of TIA/stroke. More attention to these vulnerable patients is necessary to reduce mortality., (© 2024. The Author(s).)

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH 2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies., (© 2024 Wiley Periodicals LLC.)

Introduction: In patients with cardiac sarcoidosis (CS), implantable cardioverter-defibrillators (ICDs) are important for preventing sudden cardiac death. This study aimed to investigate sex disparities in CS patients undergoing ICD implantation., Methods: The 2016-2020 National Inpatient Sample (NIS) database compared the characteristics and outcomes of males and females with CS receiving ICDs., Results: Among 760 CS patients who underwent inpatient ICD implantation, 66.4% were male. Males were younger (55.0 vs. 56.9 years, p < .01), had higher rates of diabetes (31.7% vs. 21.6%, p < .01) and chronic kidney disease (CKD) (16.8% vs. 7.8%, p < .01) but lower prevalence of atrial fibrillation (AF) (11.9% vs. 23.5%, p < .01), sick sinus syndrome (4.0% vs. 7.8%, p = .024), ventricular fibrillation (VF) (9.9% vs. 15.7%, p = .02), and black ancestry (31.9% vs. 58.0%, p < .01). Unadjusted major adverse cardiovascular events (MACE), defined as a composite of in-hospital death, myocardial infarction (MI), and ischemic stroke, was higher in females (11.8% vs. 6.9%, p = .024), but when adjusted for age and tCharlson Comorbidity Index (CCI), females demonstrated significantly lower odds of experiencing MACE (aOR: 0.048, 95% CI: 0.006-0.395, p = .005). Incidence of acute kidney injury (AKI) post-ICD was significantly lower in females (15.7% vs. 23.8%, p = .01) as was the adjusted odds (aOR: 0.282, 95% CI: 0.146-0.546, p < .01). There was comparable mean length of stay and hospital charges., Conclusion: ICD utilization in CS patients is more common among males, who have a higher prevalence of diabetes and CKD but a lower prevalence of AF, sick sinus syndrome, and VF. Adjusted MACE and AKI were significantly lower in females., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Introduction: Alzheimer pathology (AD) is characterized by the deposition of amyloid beta (Aβ) and chronic neuroinflammation, with the NLRP3 inflammasome playing a significant role. This study demonstrated that the OCD drug fluvoxamine maleate (FXN) can potently ameliorate AD pathology in 5XFAD mice by promoting autophagy-mediated clearance of Aβ and inhibiting the NLRP3 inflammasome., Methods: We used mice primary astrocytes to establish the mechanism of action of FXN against NLRP3 inflammasome by using various techniques like ELISA, Western blotting, confocal microscopy, Immunofluorescence, etc. The anti-AD activity of FXN was validated in transgenic 5XFAD mice following two months of treatment. This was followed by behavior analysis, examination of inflammatory and autophagy proteins and immunohistochemistry analysis for Aβ load in the hippocampi., Results: Our data showed that FXN, at a low concentration of 78 nM, induces autophagy to inhibit NF-κB and the NLRP3 inflammasome, apart from directly inhibiting NLRP3 inflammasome in primary astrocytes. FXN activated the PRKAA2 pathway through CAMKK2 signaling, leading to autophagy induction. It inhibited the ATP-mediated NLRP3 inflammasome activation by promoting the autophagic degradation of NF-κB, resulting in the downregulation of pro-IL-1β and NLRP3. The anti-NLRP3 inflammasome effect of FXN was reversed when autophagy was inhibited by either genetic knockdown of the PRKAA2 pathway or pharmacological inhibition with bafilomycin A1. Furthermore, FXN treatment led to improved AD pathology in 5XFAD mice, resulting in significant improvements in various behavioral parameters such as working memory and neuromuscular coordination, making their behavior more similar to that of wild-type animals. FXN improved behavior in 5XFAD mice by clearing the Aβ deposits from the hippocampi and significantly reducing multiple inflammatory proteins, including NF-κB, GFAP, IBA1, IL-1β, TNF-α, and IL-6, which are associated with NF-κB and NLRP3 inflammasome in the brain. Moreover, these changes were accompanied by increased expression of autophagic proteins., Discussion: Our data suggest that FXN ameliorates AD pathology, by simultaneously targeting two key pathological features: Aβ deposits and neuroinflammation. As an already approved drug, FXN holds potential as a candidate for human studies against AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kaur, Sharma, Sharma, Sandha, Ali, Ahmed, Ramajayan, Singh, Ahmed and Kumar.)

Post inflammatory hyperpigmentation (PIH) affects all skin types with a heightened predilection for darker skin tones. Its course is chronic once developed and treatment is often difficult. This systematic review aims to summarize the treatment outcomes for PIH with a focus on skin of colour (SOC) individuals. A literature search was conducted using MEDLINE (from 1946), Embase (from 1974), PubMed, and Cochrane in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. Results from 48 studies summarized 1356 SOC individuals. The mean age was 29 years (n = 1036) and 78% were female (n = 786). The ethnic prevalence was 70% Black, 27% Asian, and 3% Latin. Overall, 20% were Fitzpatrick skin type (FST) III, 40% FST IV, 34% FST V, and 6% FST VI. Most cases were precipitated by inflammatory conditions (89%) and localized to the face (83%). The most frequently reported interventions were topical retinoids (22%) and laser therapy (17%). Partial improvement was seen in 85% and 66% of participants, respectively. Laser was the only intervention that offered complete resolution in a subgroup of patients (26%); however, there were reported cases of PIH exacerbation following treatment. Chemical peels (9%) and hydroquinone (7%) were among other treatments with less effective outcomes. PIH and its persistence is a prevalent issue, significantly affecting many affected individuals with darker skin tones. Our results show a lack of robust efficacy across all treatment modalities. There is considerable room for improvement in interventions for at-risk populations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sepsis affects 25 million children per year globally, leading to 2.9 million deaths and substantial disability in survivors. Extensive characterization of interactions between the host and bacteria in children is required to design novel preventive and therapeutic strategies tailored to this age group. Vγ9Vδ2 T cells are the first T cells generated in humans. These cells are defined by the expression of Vγ9Vδ2 T-cell receptors (TCRs, using the TRGV9 and TRDV2 gene segments), which react strongly against the prototypical bacterial phosphoantigen HMBPP. We investigated this reactivity by analyzing the TCR δ (TRD) repertoire in the blood of 76 children (0-16 years) with blood culture-proven bacterial sepsis caused by HMBPP-positive Escherichia coli or by HMBPP-negative Staphylococcus aureus or by HMBPP-negative Streptococcus pneumoniae. Strikingly, we found that S. aureus, and to a lesser extent E. coli but not S. pneumoniae, shaped the TRDV2 repertoire in young children (<2 years) but not in older children or adults. This dichotomy was due to the selective expansion of a fetal TRDV2 repertoire. Thus, young children possess fetal-derived Vγ9Vδ2 T cells that are highly responsive toward specific bacterial pathogens., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Introduction: Collagen is extensively utilised in regenerative medicine due to its highly desirable properties. However, collagen is typically derived from mammalian sources, which poses several limitations, including high cost, potential risk of immunogenicity and transmission of infectious diseases, and ethical and religious constraints. Jellyfish-sourced type 0 collagen represents a safer and more environmentally sustainable alternative collagen source., Methods: Thus, we investigated the potential of jellyfish collagen-based hydrogels, obtained from Rhizostoma pulmo (R. pulmo) jellyfish, to be utilised in regenerative medicine. A variety of R. pulmo collagen hydrogels (RpCol hydrogels) were formed by adding a range of chemical crosslinking agents and their physicochemical and biological properties were characterised to assess their suitability for regenerative medicine applications., Results and Discussion: The characteristic chemical composition of RpCol was confirmed by Fourier-transform infrared spectroscopy (FTIR), and the degradation kinetics, morphological, and rheological properties of RpCol hydrogels were shown to be adaptable through the addition of specific chemical crosslinking agents. The endotoxin levels of RpCol were below the Food and Drug Administration (FDA) limit for medical devices, thus allowing the potential use of RpCol in vivo . 8-arm polyethylene glycol succinimidyl carboxyl methyl ester (PEG-SCM)-crosslinked RpCol hydrogels preserved the viability and induced a significant increase in the metabolic activity of immortalised human mesenchymal stem/stromal cells (TERT-hMSCs), therefore demonstrating their potential to be utilised in a wide range of regenerative medicine applications., Competing Interests: Authors RA and AM-S were employed by Jellagen Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Salthouse, Goulding, Reay, Jackson, Xu, Ahmed, Mearns-Spragg, Novakovic, Hilkens and Ferreira.)

Biomolecular condensates can influence cellular function in a number of ways, including by changing the structural dynamics and conformational equilibria of the molecules partitioned within them. Here we use methyl transverse relaxation optimized spectroscopy (methyl-TROSY) NMR in conjunction with 2'- O -methyl labeling of RNA to characterize the thermodynamics and kinetics of RNA-RNA base pairing in condensates formed by the C-terminal intrinsically disordered region of CAPRIN1, an RNA-binding protein involved in RNA transport, translation, and stability. CAPRIN1 condensates destabilize RNA-RNA base pairing, resulting from a ∼270-fold decrease and a concomitant ∼15-fold increase in the on- and off-rates for duplex formation, respectively. The ∼30-fold slower diffusion of RNA single strands within the condensed phase partially accounts for the reduced on-rate, but the further ∼9-fold reduction likely reflects shedding of CAPRIN1 chains that are interacting with the RNA prior to hybridization. Our study emphasizes the important role of protein solvation in modulating nucleic acid recognition processes inside condensates.

This paper presents a mathematical optimization framework for the strategic placement of quasi-dynamic wireless charging (QWC) stations within road networks to address the charging needs of battery electric buses (BEBs). This study evaluates two scenarios for powering the buses. In the first scenario, a grid-connected system is considered. The optimization aims to minimize annual costs related to capital, operation, and energy losses of the electric bus fleet. This involves determining the optimal locations for QWC stations, the length of power transmitters, and the corresponding battery capacities for the BEBs. Using MATLAB-based optimization tools Casadi and Yalmip, with solvers Bonmin and Fmincon, the optimal configuration includes a 13 kWh battery capacity and a 300 m power transmitter distributed across five bus stop areas. The second scenario employs a chance-constrained optimization approach for an isolated solar photovoltaic (PV) and battery energy storage system (BESS). This system is designed to reliably meet the BEBs' energy requirements throughout the day, considering different seasonal data (winter, summer, all seasons/year-round). The optimization results for the PV and BESS capacities vary with the seasons: 394.247 kW and 2012.6 kWh using summer data, 1762.1 kW and 2738.2 kWh using winter data, and 1610.8 kW and 2741.9 kWh using year-round data. Additionally, the paper examines the impact of varying bus fleet sizes on the optimal battery size and power transmitter combination using a real-world example of the bus route between Khalifa City and Abu Dhabi Downtown in the UAE. The findings suggest that larger batteries with fewer or no charging stations are more economical for smaller fleets. Conversely, as the fleet size increases, a combination of smaller battery sizes and a greater number (and length) of QWC (power transmitters) becomes more cost-effective. This research offers significant insights into the efficient deployment of QWC stations and the integration of renewable energy and energy storage for sustainable urban electric bus networks. The proposed optimization models provide a systematic approach to designing and operating charging infrastructure, contributing to sustainable urban transportation systems. Moreover, the study highlights the influence of seasonal data on PV system sizing and costs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Early detection of suspicious pigmented skin lesions is crucial for improving the outcomes and survival rates of skin cancers. However, the accuracy of clinical diagnosis by primary care physicians (PCPs) is suboptimal, leading to unnecessary referrals and biopsies. In recent years, deep learning (DL) algorithms have shown promising results in the automated detection and classification of skin lesions. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of DL algorithms for the detection of suspicious pigmented skin lesions in primary care settings. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, IEEE Xplore, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Data from eligible studies were extracted, including study characteristics, sample size, algorithm type, sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and receiver operating characteristic curve analysis. Three studies were included. The results showed that DL algorithms had a high sensitivity (90%, 95% CI: 90-91%) and specificity (85%, 95% CI: 84-86%) for detecting suspicious pigmented skin lesions in primary care settings. Significant heterogeneity was observed in both sensitivity (p = 0.0062, I 2 = 80.3%) and specificity (p < 0.001, I 2 = 98.8%). The analysis of DOR and PLR further demonstrated the strong diagnostic performance of DL algorithms. The DOR was 26.39, indicating a strong overall diagnostic performance of DL algorithms. The PLR was 4.30, highlighting the ability of these algorithms to influence diagnostic outcomes positively. The NLR was 0.16, indicating that a negative test result decreased the odds of misdiagnosis. The area under the curve of DL algorithms was 0.95, indicating excellent discriminative ability in distinguishing between benign and malignant pigmented skin lesions. DL algorithms have the potential to significantly improve the detection of suspicious pigmented skin lesions in primary care settings. Our analysis showed that DL exhibited promising performance in the early detection of suspicious pigmented skin lesions. However, further studies are needed., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abdalla et al.)

Accurate information about locoregional treatments in breast cancer neoadjuvant systemic therapy (NST) trials is vital to support surgical decision-making and allow meaningful interpretation of long-term oncological outcomes. This systematic review (PROSPERO registration CRD42023470891) aimed to describe the current practice of outcome reporting in NST studies. A systematic search identified primary research studies published 01/01/2018-08/09/2023 reporting outcomes in patients receiving NST for breast cancer followed by locoregional treatment. Included were randomised controlled trials (RCTs) and non-randomised studies (NRS) with >250 participants reporting at least one locoregional treatment outcome. Outcomes were extracted verbatim and categorised using content analysis. Descriptive statistics were used to summarise results. Of the 3111 abstracts screened, 137 studies (22 RCTs and 115 NRS) reporting at least one locoregional outcome in 575,531 patients were included. The 137 studies reported a total of 510 surgical outcomes with a median of 3 (range 1-12) per study. No single outcome was reported in all studies. Type of breast (n = 129, 94.2 %) and axillary (n = 86, 62.8 %) surgery were reported most frequently. Only 34 % (n = 47) studies reported how treatment response was assessed and if/how this informed surgical decision-making. Only a fifth (n = 28) reported outcomes relating to surgical de-escalation. Only 72 studies (52.6 %) reported any radiation therapy (RT)-related outcome, most frequently whether RT had been received (n = 63/72, 87.5 %). Current reporting of locoregional treatment outcomes in NST studies is poor, inconsistent and urgently needs to be improved. A core outcome set and reporting guidelines may improve the quality and value of future research., Competing Interests: Declaration of competing interest SMcI reports speaker honoraria from MSD, Roche, BD and Astra Zeneca; advisory boards for Lilly, Novartis, MSD, Roche and Astra Zeneca; conference travel and support from Roche, Lilly and MSD, and institutional research funding from Novartis. HI reports consulting fees from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer and Gilead; honoraria from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer, Taiho and Kyowa Kirin, and institutional research funding from Chugai, Daiichi Sankyo and Astra Zeneca. H-BL reports being a co-founder and member of the DCGen Co., Ltd board of directors; research funding from Devicor Medical Product, Inc.; consulting fees and honoraria from Alvogen, Boryung, Hologic, Lilly, Need, Novartis, Roche, Takeda, Celltrion, and Shin Poong. PD reports institutional research funding from Cepheid and Roche; consulting fees from Roche, and honoraria from Astra Zeneca and Oncoviews, and conference and travel support from Roche. NZ reports consulting fees from Lilly, Eisai, Astra Zeneca, MSD, Novartis and Gilead; honorarium from Roche, Pfizer, Eisai, Gilead, Novartis, Lilly and Astra Zeneca; and conference travel support from Novartis, Roche, Pfizer and Lilly. The remaining authors have no conflicts or competing of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Endocardial fibroelastosis (EFE) is a rare form of restrictive cardiomyopathy associated with high morbidity and mortality. The literature is sparse on information pertaining to risk stratification. Thus, we sought to highlight the risk factors of acute ischemic stroke (AIS) and mortality in adults with EFE., Methods: The National Inpatient Sample (NIS) database was queried from 2001 to 2020 using the International Classification of Diseases 9th Revision (ICD-9) and 10th Revision (ICD-10) codes for adult patients with EFE. Factors associated with AIS and mortality were identified., Results: In all, 18495 cases of EFE fit the inclusion criteria, of which 2370 (12.82%) had AIS. The mean ages for patients with and without AIS were 62.37 and 54.24, respectively. Multivariate regression suggested greater odds of AIS in patients with hypertension (aOR 2.329, P<0.01), dyslipidemia (aOR: 1.566, P<0.01), peripheral vascular disease (PVD) (aOR: 1.736, P<0.01), alcohol abuse (aOR: 1.817, P<0.01), age >60 y (aOR: 1.646, P<0.01), females (vs. males, aOR: 1.238, P<0.01), and smokers (aOR: 1.697, P<0.01). Patients with cirrhosis (aOR: 0.174, P<0.01), CKD (aOR: 0.369, P<0.01), COPD (aOR: 0.402, P<0.01), atrial fibrillation (aOR: 0.542, P<0.01) had lower odds of AIS. 3.1% of EFE patients with AIS died. Diabetes (aOR: 11.665, P<0.01) and COPD (aOR: 3.201, P=0.017) were associated with the greatest odds of all-cause mortality. Dyslipidemia (aOR: 0.387, P=0.010) and females (vs. males, aOR: 0.432, P=0.012) had reduced odds of all-cause mortality., Conclusion: Several risk factors are associated with AIS in EFE, while diabetes, COPD, and being male are associated with mortality in EFE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer., Patients and Methods: In a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection., Results: Among patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (P = .002)., Conclusions: In a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical., Competing Interests: Disclosure The authors report no conflicts directly relevant to the submitted work. Beyond this submission, the authors report the following disclosures: P.C.M. reports participation in advisory boards for Guardant Health, consulting for Vivace Therapeutics, and honoraria from Amgen. A.C.M. reports advisory board participation with Bayer, BMS, Exact Sciences, Gilead, and Novartis and board of directors of NTRKers. A.M.’s spouse, Dr. Martin Moore, is CSO and co-founder of Meissa Vaccines. J.C.K. reports consulting and advisory board participation for the following companies, all paid to GO2 for Lung Cancer: Amgen, Bristol Myers Squibb, Boehringer Ingelheim, and EQRX. C.R. reports speaker honoraria from AstraZeneca, Roche, and MSD; advisory board honoraria from Inivata, Archer, Boston Pharmaceuticals, MD Serono and Novartis, Bayer, Invitae, Regeneron, and Bostongene; scientific advisory board member for Imagene; institutional research funding from LCRF-Pfizer and NCRF; non-re-numerated research support from Guardant Health and Foundation Medicine; nonrenumerated leadership roles at the International Society of Liquid Biopsy (ISLB), the International Association for Study of Lung Cancer (IASLC), the European School of Oncology (ESO), and Oncology Latin American Association (OLA). J.D.M. reports licensing fees from the NIH and UTSW for distribution of human tumor cell lines. S.B. reports serving in consulting/advisory roles for Takeda, Mirati, and Merus. F.K. reports filed patents through The Icahn School of Medicine at Mount Sinai relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines, influenza virus vaccines, and influenza virus therapeutics, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS- CoV-2, and another company, Castlevax, to develop SARS-CoV-2 vaccines. F.K. is co-founder and scientific advisory board member of Castle-vax. F.K. has consulted for Merck, Curevac, Seqirus, and Pfizer and is currently consulting for third Rock Ventures, GSK, Gritstone, and Avimex. He is also collaborating with Dynavax on influenza vaccine development. A.G.-S. has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avi-mex, Johnson & Johnson, Dynavax, 7Hills Pharma,Pharmamar, ImmunityBio, Accurius, Nanocompo-6, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories, and Merck, outside of the reported work; consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Syn-airgen, Paratus, Pfizer, and Prosetta, outside of the reported work; has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca; and is an inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. K.L.R. has served on advisory boards for Amgen, AstraZeneca, Bluprint, Daiichi Sankyo, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Lilly, Novocure, and Mirati A.A.M. holds a consultant or advisory role at Novartis, Amgen and MorphoSys and has research funding from Amgen and Pfizer. S.S.R. reports research funding (institutional) from AstraZeneca, Amgen, Merck, Bristol Myers Squibb, and Pfizer. F.R.H. reports advisory board participation with Amgen, AstraZeneca, Genentech, Merck, Novo-cure, NextCure, Regeneron, Sanofi, Daiichi, G1 Therapeutics, Novartis, Merus Therapeutics, and ITeos Therapeutics. F.R.H. also reports a patent through University of Colorado on ‘‘EGFR Protein and Gene Copy Number as Predictive Biomarker for EGFR-directed Therapy. D.E.G. reports consulting fees from Catalyst Pharmaceuticals; U.S. patent 11,747,345; pending patents 17/045,482, 63/386,387, 63/382,972, and 63/382,257; participating in advisory boards for Astra-Zeneca, Daiichi-Sankyo, Elevation Oncology, Janssen Scientific Affairs, Jazz Pharmaceuticals, Regeneron Pharmaceuticals, and Sanofi; stock shares in Gilead; and serving as co-founder and Chief Scientific Officer of OncoSeer Diagnostics, Inc. M.S., C.-Y.H., Y.H., J.E.G., A.M.R., J.C., S.C.T., J.M.C., R.B., N.C.R., P.A.B., J.C.F., E.K., M.N., and Y.S. report no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Liraglutide, a glucagon-like peptide 1 receptor agonist, effectively treats type 2 diabetes(T2D) by lowering glucose levels, suppressing glucagon release, and promoting insulin secretion. Liraglutide has been shown to reduce body weight and glycated hemoglobin (HbA1c) levels and improve cardiovascular outcomes. However, evidence regarding the association between liraglutide and diabetic retinopathy in the Middle East is insufficient. Therefore, this study aimed to investigate the characteristics and risk factors of diabetic retinopathy in patients with T2D treated with liraglutide in Saudi Arabia. This retrospective cohort study was conducted on patients (≥14 years) with T2D treated with liraglutide between 2015 and 2021, who had a documented retinopathy assessment at baseline before liraglutide initiation and during follow-up, at King Abdulaziz Medical City (KAMC), Riyadh. Data collection included demographic information, retinopathy status, body mass index (BMI), and HbA1c level at baseline and follow-up after liraglutide use. The study included 181 patients with a mean age of 58.2 (9.8) years. Of these, 72.9% were females. At baseline, the median weight (interquartile range) was 88 (77-100) kg, diabetes duration was 19 (13-23.5) years, and HbA1c level was 9% (8-10%). Total of 69.6% were on insulin, 22.7% were on oral hypoglycemic agents, and 7.7% were on no other medications in addition to liraglutide. After a median of 2 years follow-up, both HbA1c level and weight decreased significantly (P < .001). Seventy-one of the 87 patients (81.6%) without retinopathy at baseline continued to show no retinopathy. Among patients with retinopathy at baseline, 25.5% showed improvement and 44.7% showed no change. In the multivariate binary mixed effect analysis, factors significantly associated with retinopathy were: use of insulin (odds ratio [OR]:2.68; 95% confidence interval [CI]: 1.18-6.09, P = .019), older age (OR:1.03; 95% CI: 1.00-1.06; P = .022), higher HbA1c level (OR:1.17; 95% CI: 1.02-1.34; P = .024), Hypertension (OR:2.56; 95% CI: 1.13-5.76; P=<.0001) and longer diabetes duration (OR:1.04; 95% CI: 1.00-1.08; P = .024). In conclusion, liraglutide use caused significant reductions in the HbA1c level and weight of patients with T2D. Most patients showed no change in retinopathy status after liraglutide use., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The continuum of care for maternal health (COCM) is a critical strategy for addressing preventable causes of maternal and perinatal mortality. Despite notable progress in reducing maternal and infant deaths globally, the problem persists, particularly in low-resource settings. Additionally, significant disparities in the provision of continuous care exist both between continents and within countries on the same continent. This study aimed to assess the pooled prevalence of completion across the maternity care continuum in Africa and investigate the associated factors., Methods: Relevant articles were accessed through the EMBASE, CINAHL, Cochrane Library, PubMed, HINARI, and Google Scholar databases. Funnel plots and Egger's test were employed to assess publication bias, while the I-squared test was used to evaluate study heterogeneity. The inclusion criteria were limited to observational studies conducted exclusively in Africa. The quality of these studies was assessed using the JBI checklist. Data extraction from the included studies was performed using Microsoft Excel and then analysed using Stata 16 software., Results: A total of 23 studies involving 74,880 mothers met the inclusion criteria. The overall prevalence of women who successfully completed the COCM was 20.9% [95% CI: 16.9-25.0]. Our analysis revealed several factors associated with this outcome, including urban residency [OR: 2.3; 95% CI: 1.6-3.2], the highest wealth index level [OR: 2.1; 95% CI: 1.4-3.0], primiparous status [OR: 1.3; 95% CI: 2.2-5.1], planned pregnancy [OR: 3.0; 95% CI: 2.3-3.7], and exposure to mass media [OR: 2.7; 95% CI: 1.9-3.8]., Conclusion: The study revealed that only 20.9% of women fully completed the COCM. It also identified several factors associated with completion of the COCM, such as residing in urban areas, possessing a higher wealth index, being a first-time mother, experiencing a planned pregnancy, and having access to mass media. Based on the study's findings, it is recommended that targeted interventions be implemented in rural areas, financial assistance be provided to women with lower wealth index levels, educational campaigns be conducted through mass media, early antenatal care be promoted, and family planning services be strengthened., Review Registration: PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42020205736)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patient and procedure factors are considered in the decision-making process for surgical repair of hiatal hernias. Recurrence is multi-factorial and has been shown to be related to size, type, BMI and age., Aims: This study examined recurrence rates in a single institution, identified areas for improved surgical technique, and re-assessed recurrence following implantation of a quality improvement initiative., Methods: A retrospective review of patients undergoing hiatal hernia repair surgery between 2018 and 2022 was conducted. Demographics, pre-operative characteristics, intra-operative procedures and recurrence rates were reviewed., Results: Seventy-five patients from 2018 to 2020 and 34 patients from 2021 to 2022 were identified. The recurrence rate was 21% in 2018-2020, with 14% requiring a revisional procedure. Recurrence and re-operation were subsequently reduced to 6% in 2021 and 2022, which was statistically significant (p = 0.043). There was an increase in gastropexy from 21% to 41% following the review (p = 0.032), which was mainly reserved for large and giant hernias. Procedural and literature review, alongside gastropexy, can be attributed to recurrence rate reduction., Conclusions: It is important to educate patients on the likelihood and risk factors of recurrence. A comprehensive review of procedures and a quality improvement program in our facility for hiatal hernia repair is shown to reduce recurrence., (© 2024. The Author(s).)

Recycling gold from electronic waste offers significant benefits for both environmental protection and resource sustainability. However, this process presents considerable challenges due to high costs, prolonged processing times, and interference from coexisting metals. In this study, we synthesized a hybrid mesoporous nanocomposite comprising platelets-like CoNi 2 S 4 incorporated with g-C 3 N 4 nanosheets (CoNi 2 S 4 @g-C 3 N 4 ) for the selective recovery of gold (Au(iii)) ions from spent computer motherboards. Comprehensive characterization of the CoNi 2 S 4 @g-C 3 N 4 nanocomposite was conducted, including its physicochemical properties, textural and structural characteristics, morphology, and elemental composition. The CoNi 2 S 4 @g-C 3 N 4 extractor demonstrated an exceptional adsorption capacity of 200.6 mg g -1 , with high selectivity at pH 2, rapid equilibrium time of 60 minutes, and satisfactory reusability for over ten cycles. Adsorption isotherm and kinetic studies revealed that the CoNi 2 S 4 @g-C 3 N 4 nanocomposite adheres to the Langmuir adsorption model and the pseudo-second-order kinetic model for Au(iii) ion adsorption. Overall, this study introduces a viable adsorbent that shows considerable promise for industrial-scale Au(iii) extraction from e-waste., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)