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Background: Congenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models., Method: Gas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results., Results: We identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice., Conclusion: Our findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition., 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 Inc. All rights reserved.)

Background: In recent years, the application of AI technologies like ChatGPT has gained traction in the field of plastic surgery. AI models can analyze pre- and post-treatment images to offer insights into the effectiveness of cosmetic procedures. This technological advancement enables rapid, objective evaluations that can complement traditional assessment methods, providing a more comprehensive understanding of treatment outcomes., Objective: The study aimed to comprehensively assess the effectiveness of custom ChatGPT model, "Face Rating and Review AI," in facial feature evaluation in minimally invasive aesthetic procedures, particularly before and after Botox treatments., Method: An analysis was conducted on the Web of Science (WoS) database, identifying 79 articles published between 2023 and 2024 on ChatGPT in the field of plastic surgery from various countries. A dataset of 23 patients from Kaggle, including pre- and post-Botox images, was used. The custom ChatGPT model, "Face Rating & Review AI," was used to assess facial features based on objective parameters such as the golden ratio, symmetry, proportion, side angles, skin condition, and overall harmony, as well as subjective parameters like personality, temperament, and social attraction., Result: The WoS search found 79 articles on ChatGPT in plastic surgery from 27 countries, with most publications originating from the USA, Australia, and Italy. The objective and subjective parameters were analyzed using a paired t-test, and all facial features showed low p-values (<0.05). Higher mean scores on features such as the golden ratio (mean = 5.86, SD = 0.69), skin condition (mean = 3.78, SD = 0.73), and personality (mean = 5.0, SD = 0.79) indicate positive shifts after the treatment., Conclusion: The custom ChatGPT model "Face Rating and Review AI" is a valuable tool for assessing facial features in Botox treatments. It effectively evaluates objective and subjective attributes, aiding clinical decision-making. However, ethical considerations highlight the need for diverse datasets in future research to improve accuracy and inclusivity., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., Competing Interests: Declarations. Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this manuscript. Human and Animal Rights: This article does not contain any studies with human participants or animals performed by any of the authors. Informed Consent: For this type of study, informed consent is not required., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The development of dual-emission ratiometric fluorescent probes with aggregation-induced emission enhancement (AIEE) overcomes the limitations of gold nanocluster (Au NC)-based probes, particularly their weak intrinsic fluorescence, in real-world applications. These AIEE probes also exhibit superior detection limits and enhanced sensitivity. A novel combination for the reliable fluorometric detection of glutathione (GSH) was proposed, utilizing aggregation-induced emission enhancement (AIEE) facilitated by electrostatic interaction and spatial confinement. The probe consists of a ratiometric combination of negatively charged α-lipoic acid-modified Au NCs (LA@Au NCs) and positively charged silicon nanoparticles (SiNPs). The addition of SiNPs causes aggregation of LA@Au NCs, enhancing the fluorescence of LA@Au NCs through the AIE effect under electrostatic interaction and spatial confinement. The addition of Cu 2+ quenched the emission of LA@Au NCs as a result of charge transfer. The fluorescence emissions of LA@Au NCs were restored upon the addition of GSH due to the interaction between GSH and Cu 2+ . Simultaneously, the emission signal of SiNPs remains unchanged, serving as an internal reference signal during GSH measurement. It was found that the fluorescence ratio ( F 680 / F 465 ) is directly proportional to the concentration of GSH in the range of 0.05-100 μM, with a detection limit of 1.7 nM (S/N = 3). The proposed system was applied to detect GSH in real samples, including dietary supplements, human serum, and saliva samples. This work opens new avenues for constructing novel sensors based on AIEE for detecting biomolecules.

Early childhood growth is associated with cognitive function. However, the independent associations of fat mass (FM) and fat-free mass (FFM) with cognitive function are not well understood. We investigated associations of FM and FFM at birth and 0-5 years accretion with cognitive function at 10 years. Healthy term newborns were enrolled in this cohort. FM and FFM were measured at birth, 1.5, 2.5, 3.5, 4.5, 6 months, 4 and 5 years. Cognitive function was assessed using Peabody Picture Vocabulary Test (PPVT) at 10 years. FM and FFM accretion were computed using statistically independent conditional accretion from 0-3 months, 3-6 months, 6 months-4 years, and 4-5 years. Multiple linear regression was used to assess associations. At the 10-year follow-up, we assessed 318 children with mean (SD) age of 9.8 (1.0) years. A 1 SD higher birth FFM was associated with a 0.14 SD (95% CI: 0.01, 0.28) higher PPVT at 10 years . FFM accretion from 0-3 and 3-6 months was associated with PPVT at 10 year, β = 0.5 SD (95% CI: 0.08, 0.93 ) and β = -0.48 SD (95% CI: -0.90, -0.07 , respectively . FFM accretion after 6 months showed no association with PPVT. Neither FM at birth nor 0-5 years accretion showed association with PPVT. Overall, b irth FFM, but not FM was associated with cognitive function at 10 years, while t he association of FFM accretion and cognitive function varied across distinct developmental stages in infancy . The mechanisms underlying this varying association between body composition and cognitive function need further investigation.

Background: Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease, which is diagnosed by a combination of clinical symptoms and magnetic resonance imaging and measurement of an increased intrathecal antibody synthesis. Genetic as well as environmental factors influence onset of the disease, where especially Epstein-Barr virus (EBV) infection is directly involved in MS development. In this open retrospective study, we aimed to elaborate whether various serum and cerebrospinal fluid (CSF)-based EBV antibody indices may aid in the diagnosis of MS., Methods: Epstein-Barr nuclear antigen (EBNA)1 IgG concentrations in serum and CSF of relapsing-remitting (RR)MS patients (n=61) (M:F 28:33, average 40 years), optic neuritis patients (n=26) (M:F 9:17, average 47 years) and healthy controls (HCs) (n=15) (M:F 8:7, average 43 years) were determined by enzyme-linked immunosorbent assay. The obtained EBNA1 IgG levels were compared to factors such as total IgG, albumin concentrations, specific antibody index, and various serum- and CSF-based indices., Results: Significantly elevated EBNA1 IgG levels were detected in serum and CSF of RRMS patients compared to HCs. CSF EBNA1 IgG and indices based on specific CSF EBNA1 IgG associated with CSF albumin or serum EBNA1 IgG associated with total serum IgG obtained the highest sensitivities and complemented the IgG index and oligoclonal bands., Conclusion: These findings indicate that aforementioned indices may supplement existing indices and aid in the diagnosis of MS., Competing Interests: Declaration of competing interest The authors declare no financial or other competing interests related to this work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024. Published by Elsevier B.V.)

As rice has no physiological capacity of fixing nitrogen in the soil, its production had always been reliant on the external application of nitrogen (N) to ensure enhanced productivity. In the light of improving nitrogen use efficiency (NUE) in rice, several advanced agronomic strategies have been proposed. However, the soared increase of the prices of N fertilizers and subsequent environmental downfalls caused by the excessive use of N fertilizers, reinforces the prerequisite adaptation of other sustainable, affordable, and globally acceptable strategies. An appropriate alternative approach would be to develop rice cultivars with better NUE. Conventional breeding techniques, however, have had only sporadic success in improving NUE, and hence, this paper proposes a new schema that employs the wholesome benefits of the recent advancements in omics technologies. The suggested approach promotes multidisciplinary research, since such cooperation enables the synthesis of many viewpoints, approaches, and data that result in a comprehensive understanding of NUE in rice. Such collaboration also encourages innovation that leads to developing rice varieties that use nitrogen more effectively, facilitate smart technology transfer, and promotes the adoption of NUE practices by farmers and stakeholders to minimize ecological impact and contribute to a sustainable agricultural future., 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.)

Objective: Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE., Methods: We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls., Results: HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions., Interpretation: Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Clinical phenotypic presentations associated with LAMA2 deficiency have shown a variety of manifestations. LAMA2 mutations are mainly linked to congenital muscular dystrophy, but there is also mounting evidence suggesting their presence in inflammatory breast cancer, laryngopharyngeal squamous cell carcinoma, and ventricular tachycardia related to coronary artery disease and cardiomyopathy. This study examined the structural and functional impacts of 144 non-synonymous single nucleotide polymorphisms (nsSNPs) within the LAMA2 gene. Through multi-tiered sequence and structure-based methods, 11 deleterious and destabilizing mutations were identified (A1362T, E1308Q, E1360G, I1276S, L1195P, M1359T, P1232H, P1238A, P1272L, Y1234H, Y1338C). Further, four mutations (L1195P, Y1234H, P1238A, A1362T), which aligned with conserved positions, were subjected to 500 ns molecular dynamics (MD) simulations. RMSD calculated from MD trajectories highlighted structural disparities between wild-type and mutant forms, with the latter showing greater flexibility. Radius of gyration analysis indicated reduced compactness, solvent accessibility changes suggested unfolding, and hydrogen bond (HB) analysis demonstrated disrupted integrity. The HB analysis revealed disruptions in structural integrity due to diminished hydrogen bonds in mutants. Secondary structure analysis revealed significant alterations in secondary structural content. Principal Component Analysis unveiled increased dynamic behavior in mutants. Gibbs free energy landscape analysis reflected distinct energy minima regions in mutants, indicating structural destabilization. Overall, this study revealed the functional and structural ramifications of nsSNPs in the LAMA2 gene, providing valuable insights into potential disease-causing mutations and warranting future research on understanding LAMA2 associated diseases and disorders.

Carboxylesterase 2 (CES2) is expressed mainly in liver and intestine, but most abundantly in intestine. It hydrolyzes carboxylester, thioester, and amide bonds in many exogenous and endogenous compounds, including lipids. CES2 therefore not only plays an important role in the metabolism of many (pro-)drugs, toxins and pesticides, directly influencing pharmacology and toxicology in humans, but it is also involved in energy homeostasis, affecting lipid and glucose metabolism. In this study we investigated the pharmacological and physiological functions of CES2. We constructed Ces2 cluster knockout mice lacking all eight Ces2 genes (Ces2 -/- strain) as well as humanized hepatic or intestinal CES2 transgenic strains in this Ces2 -/- background. We showed that oral availability and tissue disposition of capecitabine were drastically increased in Ces2 -/- mice, and tissue-specifically decreased by intestinal and hepatic human CES2 (hCES2) activity. The metabolism of the chemotherapeutic agent vinorelbine was strongly reduced in Ces2 -/- mice, but only marginally rescued by hCES2 expression. On the other hand, Ces2 -/- mice exhibited fatty liver, adipositis, hypercholesterolemia and diminished glucose tolerance and insulin sensitivity, but without body mass changes. Paradoxically, hepatic hCES2 expression rescued these metabolic phenotypes but increased liver size, adipose tissue mass and overall body weight, suggesting a "healthy" obesity phenotype. In contrast, intestinal hCES2 expression efficiently rescued all phenotypes, and even improved some parameters, including body weight, relative to the wild-type baseline values. Our results suggest that the induction of intestinal hCES2 may combat most, if not all, of the adverse effects of metabolic syndrome. These CES2 mouse models will provide powerful preclinical tools to enhance drug development, increase physiological insights, and explore potential solutions for metabolic syndrome-associated disorders., (© 2024. The Author(s).)

Due to its diverse topography, Pakistan faces different types of floods each year, which cause substantial physical, environmental, and socioeconomic damage. However, the susceptibility of specific regions to different flood types remains unexplored. To the best of our knowledge for the first time, this study employed an integrated approach by leveraging a GIS-based Analytical Hierarchy Process (AHP), remote sensing, and machine learning (ML) algorithms, to assess susceptibility to three different types of flooding in Peshawar, Pakistan. The study first evaluated the degree of susceptibility to riverine, urban, and flash floods using the GIS-based AHP technique, and then employed ML models, (i.e., specifically Random Forest [RF] and Extreme Gradient Boosting [XG-Boost] to analyze multi-type flood susceptibility in the study region. The performance of the ML models was also evaluated, and the XG-Boost model outperforms RF, demonstrating a higher correlation coefficient (R 2  = 0.561-0.922) and lower mean absolute error (MAE = 0.042-0.354), and root-mean-square error (RMSE = 0.119-0.415) for both training and testing datasets. The superior performance of the XG-Boost was further confirmed by the higher value of the area under the curve (AUC) values, which is relatively higher (0.87) than that of the AHP (0.70) and RF (0.86) models. Based on the relative best performance, the XG-Boost model was chosen for further susceptibility assessment of different types of floods, and the generated flood susceptibility maps revealed that 20.9% of the total area is susceptible to riverine flooding, while 30.27% and 48.68% of the total area is susceptible to urban and flash flooding, respectively. The study's findings are significant, offering valuable insights for relevant stakeholders in guiding future flood risk management and sustainable land use plans in the study area., 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 Ltd. All rights reserved.)

An electrochemical sensing approach was developed for the detection of the agricultural antibiotic drug kasugamycin. The method involves the construction of an electrochemical sensor comprising molecularly imprinted polymers (MIPs) embedded within a carbon paste (CP) matrix. The MIPs are designed to have imprinted sites that match the size and geometry of the Cu(II)-kasugamycin coordinated complex. Upon removal of kasugamycin, cavities suitable for the drug's entrance are formed within the MIPs. The presence of Cu(II) facilitates the detection of the drug by generating a redox signal of Cu(II)-Cu(I), which can be easily detected using differential pulse voltammetry (DPV). The signal response of Cu(II)-Cu(I) increases in the presence of the drug, promoting the accumulation of Cu(II) ions within the imprinted cavities. Under optimized conditions, the anodic peak ( I pa ) signal of Cu(II)-Cu(I) exhibits an increase proportional to the concentration of kasugamycin within the range of 0.15-140 μM. The detection limit (LOD, S/N = 3) achieved is 0.046 μM. The proposed sensor demonstrates several characteristic features including good stability, reliable performance, a low detection limit, and excellent selectivity. The Cu(II)-MIP@CP sensor proved effective in detecting kasugamycin within complex samples like meat, milk, and cucumber, yielding recovery% ranging from 96.0 to 103.8%. Additionally, the relative standard deviation % (RSD%) fell within the range of 2.2% to 4.0%, indicating good precision and reliability.

Aims: Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture. Secondary aims were to assess the variation in the provision of chemical prophylaxis and risk factors for VTE., Methods: This was a multicentre, prospective national collaborative audit with data collection over nine months for all patients undergoing foot and ankle surgery in an operating theatre or TA rupture treatment, within participating UK hospitals. The association between VTE and thromboprophylaxis was assessed with a univariable logistic regression model. A multivariable logistic regression model was used to identify key predictors for the risk of VTE., Results: A total of 13,569 patients were included from 68 sites. Overall, 11,363 patients were available for analysis: 44.79% were elective (n = 5,090), 42.16% were trauma excluding TA ruptures (n = 4,791), 3.50% were acute diabetic procedures (n = 398), 2.44% were TA ruptures undergoing surgery (n = 277), and 7.10% were TA ruptures treated nonoperatively (n = 807). In total, 11 chemical anticoagulants were recorded, with the most common agent being low-molecular-weight heparin (n = 6,303; 56.79%). A total of 32.71% received no chemical prophylaxis. There were 99 cases of VTE (incidence 0.87% (95% CI 0.71 to 1.06)). VTE-related mortality was 0.03% (95% CI 0.005 to 0.080). Univariable analysis showed that increased age and American Society of Anesthesiologists (ASA) grade had higher odds of VTE, as did having previous cancer, stroke, or history of VTE. On multivariable analysis, the strongest predictors for VTE were the type of foot and ankle procedure and ASA grade., Conclusion: The 90-day incidence of symptomatic VTE and mortality related to VTE is low in foot and ankle surgery and TA management. There was notable variability in the chemical prophylaxis used. The significant risk factors associated with 90-day symptomatic VTE were TA rupture and high ASA grade., Competing Interests: J. Mangwani reports support from the Leicester Hospitals Charity, related to this study. J. Mangwani reports payment or honoraria for lectures, presentations, educational events from Orthosolutions, and royalties from Meshworks, unrelated to this study. K. Malhotra reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from NewClip Technics, unrelated to this study. L. W. Mason reports royalties or licenses, consulting fees, and patents planned, issued or pending from Orthosolutions, unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Background: Double-kissing (DK) crush and DK culotte are the recommended 2-stent strategies in true coronary bifurcation lesions. However, it is a matter of curiosity about which of the DK crush and DK culotte stenting techniques will have superior results. We aimed to compare the clinical outcomes of DK crush and DK culotte stenting in nonleft main coronary artery bifurcation., Methods: Consecutive patients who received DK crush or DK culotte technique for de novo true nonleft main coronary artery bifurcation lesion were categorized according to which treatment they received. The primary end point of the study was target lesion failure as a composite end point of target lesion revascularization, target vessel myocardial infarction, and cardiac death. Secondary end points were all-cause death and definite stent thrombosis., Results: A total of 202 patients were categorized as DK crush (101 patients) or DK culotte (101 patients) techniques. The target lesion failure had occurred frequently in the DK crush (10.9%) compared with the DK culotte (3.0%; P =0.028) that was mainly driven by increased target lesion revascularization (9.9% in the DK crush versus 3.0% in the DK culotte; P =0.045). The number of patients with target vessel myocardial infarction (3.0% in the DK crush versus 2.0% in the DK culotte; P =0.651) and cardiac death (1.0% in the DK crush versus 0.0% in the DK culotte; P =0.315) was higher in the DK crush. There were no differences in terms of definite stent thrombosis and all-cause death between groups., Conclusions: In the present analysis, DK culotte was associated with lower 1-year target lesion failure rates compared with DK crush in true nonleft main coronary artery bifurcations., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789161., Competing Interests: None.

Neurodegenerative diseases are a leading cause of death and disability and pose a looming global public health crisis. Despite progress in understanding biological and molecular factors associated with these disorders and their progression, effective disease modifying treatments are presently limited. Focused ultrasound (FUS) is an emerging therapeutic strategy for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these contexts, applications of FUS include neuroablation, neuromodulation, and/or blood-brain barrier opening with and without facilitated intracerebral drug delivery. Here, the authors review preclinical evidence and current and emerging applications of FUS for neurodegenerative diseases and summarize future directions in the field., Competing Interests: Disclosure The authors have no relevant disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The wettability of subsurface minerals is a critical factor influencing the pore-scale displacement of fluids in underground reservoirs. As such, it plays a key role in hydrocarbon production and greenhouse gas geo-sequestration. We present a comprehensive and critical review of the current state of knowledge on the intermolecular forces governing wettability of rock minerals most relevant to subsurface fluid storage and recovery. In this review we first provide a detailed summary of the available data, both experimental and theoretical, from the perspective of the fundamental intermolecular and surface forces, specifically considering the roles played by the surface chemistry, fluid properties, as well as other significant factors. We subsequently offer an analysis of the effects of chemical additives such as surfactants and nanoparticles that have emerged as viable means for manipulating wettability. In each example, we highlight the practical implications for hydrocarbon production and CO 2 geo-storage as two of the most important current applications. As the physico-chemical mechanisms governing the wetting phenomena are the main focus, special emphasis is placed on nano-scale experimental approaches along with atomic-scale modeling that specifically probe the underlying intermolecular and surface forces. Lastly, we discuss the gaps in the current state of knowledge and outline future research directions to further our fundamental understanding of the interactions and their impact on the wetting characteristics of Earth's minerals., 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.)

Anticancer chemotherapies damage normal tissues, and various drug carriers are under consideration to address this issue. Metal-organic frameworks (MOFs) are promising due to their drug-carrying capacity and tunable properties. Target-inspired surface functionalization may further magnify their potential. In this study, we aim to investigate the anticancer activity of reduced iron-based MOFs (RMOFs) functionalized with ferritin and folic acid and loaded with doxorubicin. Successful synthesis and functionalization are confirmed by electron microscopes, Fourier transform infrared spectroscopy and X-ray diffraction. Anticancer activity is evaluated in different tumor cell lines at various doses. Results indicate that the folic acid functionalized and Dox loaded MOF (FADMOF) showed maximum anticancer potential, leaving only 6 % of 4 T1 cells alive at the highest dose. Ferritin and combo MOFs followed closely, while the plain RMOF lagged behind. Furthermore, in HeLa cells, the RMOF showed the best cytotoxicity, reducing cell viability to a mere 30 % at the highest dose. Similarly, in MCF7 cells, theRMOF) showed the best cytotoxicity, reducing cell viability in a dose-dependent manner and to a mere 25 % at the highest dose. Taken together, this study shows that functionalized MOFs have promising anticancer potential across various cancer cell lines. However, loading with doxorubicin reduces their cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Muhammad Imran Khan, Fenfen Li, Yi Hu and Bensheng Qiu has a patent pending to University of Science and Technology of China. If there are other authors, they 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.)

Objective: To identify evidence syntheses of health interventions addressing racial health equity reporting the use of equity-focused frameworks and logic models., Study Design and Setting: The search strategy included three sources; a search of three bibliographic databases to identify systematic reviews assessing interventions to improve racial health equity, semi-structured interviews with diverse group and a targeted organization website searches (e.g. NIH, USPSTF) to identify relevant logic models and frameworks. The searches were conducted between January 1, 2020, and January 25, 2023. We used a qualitative approach to identify and describe key characteristics of equity-focused logic models and frameworks used in evidence syntheses., Results: Of the 153 racial health equity-focused evidence syntheses identified, 2 explicitly used logic models to describe the intervention mechanism. We identified seven existing health equity frameworks from semi-structured interviews and electronic search of key websites that were categorized by stated purpose as providing guidance for 1) research, 2) health policy, 3) digital healthcare solutions, and 4) clinical preventive services. Two out of 7 frameworks included guidance on integrating frameworks or logic models in evidence synthesis while the majority provided contextual information on how to define or consider race or racism as a structural determinant of health., Conclusion: There is limited use of logic models and frameworks in evidence syntheses addressing racial health equity. There is a need for more applied frameworks providing guidance for framing, conducting and interpreting findings of evidence syntheses addressing racial health equity., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Systematic reviews hold immense promise as tools to highlight evidence-based practices that can reduce or aim to eliminate racial health disparities. Currently, consensus on centering racial health equity in systematic reviews and other evidence synthesis products is lacking. Centering racial health equity implies concentrating or focusing attention on health equity in ways that bring attention to the perspectives or needs of groups that are typically marginalized., Study Design and Setting: This Cochrane US Network team and colleagues, with the guidance of a steering committee, sought to understand the views of varied interest holders through semistructured interviews and conducted evidence syntheses addressing (1) definitions of racial health equity, (2) logic models and frameworks to centering racial health equity, (3) interventions to reduce racial health inequities, and (4) interest holder engagement in evidence syntheses. Our methods and teams include a primarily American and Canadian lens; however, findings and insights derived from this work are applicable to any region in which racial or ethnic discrimination and disparities in care due to structural causes exist., Results: In this series, we explain why centering racial health equity matters and what gaps exist and may need to be prioritized. The interviews and systematic reviews identified numerous gaps to address racial health equity that require changes not merely to evidence synthesis practices but also to the underlying evidence ecosystem. These changes include increasing representation, establishing foundational guidance (on definitions and causal mechanisms and models, building a substantive evidence base on racial health equity, strengthening methods guidance, disseminating and implementing results, and sustaining new practices)., Conclusion: Centering racial health equity requires consensus on the part of key interest holders. As part of the next steps in building consensus, the manifold gaps identified by this series of papers need to be prioritized. Given the resource constraints, changes in norms around systematic reviews are most likely to occur when evidence-based standards for success are clearly established and the benefits of centering racial health equity are apparent., Plain Language Summary: Racial categories are not based on biology, but racism has negative biological effects. People from racial or ethnic minority groups have often been left out of research and ignored in systematic reviews. Systematic reviews often help clinicians and policymakers with evidence-based decisions. Centering racial health equity in systematic reviews will help clinicians and policymakers to improve outcomes for people from racial or ethnic minority groups. We conducted interviews and a series of four systematic reviews on definitions, logic models and frameworks, methods, interventions, and interest-holder engagement in syntheses. We found that much work remains to be done in centering racial health equity in systematic reviews. Specifically, systematic reviewers need to change who is represented on their teams, establish foundational guidance (on definitions and causal mechanisms and models, identify what interventions work to address racial health equity, strengthen method guidance, disseminate and implement results, and sustain new practices)., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Animals will experience energy deprivation processes such as moulting, clutching, migration and long-distance transportation under natural survival conditions and in production practices, and the body will trigger a series of adaptive metabolic changes during these processes. Fasting and refeeding after fasting can induce remodeling of nutrients and energy metabolism. This study aims to investigate the mechanisms by which the gut microbiota and liver of poultry respond to energy deprivation under specific conditions., Methods: Ninety 252-day-old laying hens were randomly divided into 3 groups: (1) fed ad libitum (control group); (2) fasted from day 13 to day 17 (fasting group); (3) fasted from day 1 to day 5, then refed on a specific feeding way (refeeding group). After that, the serum, liver, jejunum tissues, and cecum contents were sampled and sent for metabolome, transcriptome, morphology, and 16S rDNA sequencing analyses, respectively., Results: Results showed that food deprivation not only observably decreased the body weight, liver index, and the villus height and villus/crypt ratio of jejunum, but also significantly changed the gut microbiota compositions, serum metabolic profiles, and the hepatic gene expression patterns of laying hens, whereas these changes were effectively reversed by the following refeeding operation. At the same time, metabolome combined transcriptome analysis revealed that both serum differential metabolites and hepatic differential expressed genes (DEGs) were consistently enriched in the lipid and amino metabolism pathways, and strong correlations were synchronously found between the differential metabolites and both of the differential gut microbial genera and DEGs, suggesting the crosstalks among gut, liver and their resulting serum metabolic products., Conclusion: The results suggested that the organism might coordinate to maintain metabolic homeostasis under energy deprivation through a combination of changes in gut microbial composition and hepatic gene expression.

Purpose: To evaluate how the implementation of superior hypogastric nerve block (SHNB) during uterine artery embolization (UAE) for uterine fibroids impacts same-day discharge and healthcare encounters (HE) within 30 days., Materials and Methods: 240 patients who underwent successful UAE for fibroids between January 2018 and December 2022 were retrospectively reviewed. HE within 30 days, including emergency department (ED) and urgent care visits, admissions, and readmissions, were categorized as early (0-7 days of discharge) and late (8-30 days of discharge), and related or unrelated to interventional radiology (IR) care. Factors associated with same-day discharge and HE were identified with univariate analyses. Rates of HE based on SHNB status were compared using chi-square tests., Results: Mean age was 46 ± 5 years; 125 patients received UAE with SHNB. Patients who underwent SHNB were significantly more likely to undergo same-day discharge (113/125, 90%) compared to those without SHNB (55/115, 48%) (p<0.001). There were no factors associated with rates of all-cause 30-day HE, including SHNB status (SHNB 17% (21/125) vs no SHNB 10% (12/115), p=0.20). A majority of HE were due to an IR-related cause (26/33, 79%), including abdominal or pelvic pain (22/33, 67%), nausea, vomiting, or poor oral intake (18/33, 55%), and vaginal bleeding (4/33, 12%). Comparing SHNB to no SHNB patients, there was no difference in the proportion of IR-related HE (17/21 (81%) vs 9/12 (75%), p=0.69)., Conclusions: UAE with SHNB is associated with significantly higher rates of same-day discharge but similar rates of 30-day healthcare encounters, compared to UAE alone., (Copyright © 2024. Published by Elsevier Inc.)

Nash equilibrium is a key concept in game theory fundamental for elucidating the equilibrium state of strategic interactions, with applications in diverse fields such as economics, political science, and biology. However, the Nash equilibrium may not always align with desired outcomes within the broader system. This article introduces a novel game engineering framework that tweaks strategic payoffs within a game to achieve a pre-defined desired Nash equilibrium while averting undesired ones. Leveraging mixed-integer linear programming, this framework identifies intricate combinations of players and strategies and optimal perturbations to their payoffs that enable the shift from undesirable Nash equilibria to more favorable ones. We demonstrate the effectiveness and scalability of our approach on games of varying complexity, ranging from simple prototype games such as the Prisoner's Dilemma and Snowdrift games with two or more players to complex game configurations with up to 10 6 entries in the payoff matrix. These studies showcase the capability of this framework in efficiently identifying the alternative ways of reshaping strategic payoffs to secure desired Nash equilibria and preclude undesired equilibrium states. Our game engineering framework offers a versatile toolkit for precision strategic decision-making with far-reaching implications across diverse domains., (© 2024. The Author(s).)

Most of published research on magnetic hyperthermia focused on iron oxides, ferrites, and binary alloy nanostructures, while the ternary alloys attracted much limited interest. Herein, we prepared NiCuCo ternary alloy nanocomposites with variable compositions by mechanical alloying. Physical properties were fully characterized by XRD, Rietveld analysis, XPS, SEM/EDX, TEM, ZFC/FC and H-M loops. DFT calculations were used to confirm the experimental results in terms of structure and magnetism. The results showed that the fabricated nanoalloys are face centered cubic (FCC) with average core sizes of 9-40 nm and behave as superparamagnetic with saturation in the range 4.67-42.63 emu/g. Langevin fitting corroborated the superparamagnetic behavior, while law of approach to saturation (LAS) was used to calculate the magnetic anisotropy constants. Heating effciencies were performed under an alternating magnetic field (AMF, H 0  = 170 Oe and f = 332.5 kHz), and specific absorption rate (SAR) values were determined. The highest magnetic saturation (M s ), heating potentials, and SAR values were attained for Ni 35 Cu 30 Co 35 containing the lowest Cu but highest Ni and Co percentages, and the least for Ni 15 Cu 70 Co 15 . Importantly, the nanoalloys reached the required temperatures for magnetic hyperthermia (42 °C) in relatively short times. We also showed that heat dissipiation can be simply tuned by changing many parameters such as concentration, field amplitude, and frequency. Finally, cytotoxicity viability assays against two different breast cancer cell lines treated with Ni 25 Cu 50 Co 25 nanoalloy in the presence and absence of AMF were investigated. No significant decrease in cancer cell viability was observed in the absence of AMF. When tested against tumorigenic KAIMRC2 breast cancer cells under AMF, the NiCuCo nanoalloy was found to be highly potent to the cells (~ 2-fold enhancement), killing almost all the cells in short times (20 min) and clinically-safe AC magnetic fields. These findings strongly suggest that the as-prepared ternary NiCuCo nanoalloys hold great promise for potential magnetically-triggered cancer hyperthermia., (© 2024. The Author(s).)

Objectives: In the context of profound and persistent racial health inequities, we sought to understand how to define racial health equity in the context of systematic reviews and how to staff, conduct, disseminate, sustain, and evaluate systematic reviews that address racial health equity., Study Design and Setting: The study consisted of virtual, semistructured interviews followed by structured coding and qualitative analyses using NVivo., Results: Twenty-nine individuals, primarily United States-based, including patients, community representatives, systematic reviewers, clinicians, guideline developers, primary researchers, and funders, participated in this study. These interest holders brought up systems of power, injustice, social determinants of health, and intersectionality when conceptualizing racial health equity. They also emphasized including community members with lived experience in review teams. They suggested making changes to systematic review scope, methods, and eligible evidence (such as adapting review methods to include racial health equity considerations in prioritizing topics for reviews, formulating key questions and searches, and specifying outcomes) and broadening evidence to include designs that address implementation and access. Interest holders noted that sustained efforts to center racial health equity in systematic reviews require resources, time, training, and demonstrating value to funders., Conclusion: Interest holders identified changes to the funding, staffing, conduct, dissemination, and implementation of systematic reviews to center racial health equity. Action on these steps requires clear standards for success, an evidence base to support transformative changes, and consensus among interest holders on the way forward., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Extracellular vesicles, including exosomes, are small extracellular vesicles that range in size from 30 nm to 10 μm in diameter and have specific membrane markers. They are naturally secreted and are present in various bodily fluids, including blood, urine, and saliva, and through the variety of their internal cargo, they contribute to both normal physiological and pathological processes. These processes include immune modulation, neuronal synapse formation, cell differentiation, cancer metastasis, angiogenesis, lymphangiogenesis, progression of infectious disease, and neurodegenerative disorders like Alzheimer's and Parkinson's disease. In recent years, interest has grown in the use of exosomes as a potential drug delivery system for various diseases and injuries. Importantly, exosomes originating from a patient's own cells exhibit minimal immunogenicity and possess remarkable stability along with inherent and adjustable targeting capabilities. This review explores the roles of exosomes in angiogenesis, lymphangiogenesis, and nerve repair with a specific emphasis on these processes within the cornea. Furthermore, it examines exosomes derived from specific cell types, discusses the advantages of exosome-based therapies in modulating these processes, and presents some of the most established methods for exosome isolation. Exosome-based treatments are emerging as potential minimally invasive and non-immunogenic therapies that modulate corneal angiogenesis and lymphangiogenesis, as well as enhance and accelerate endogenous corneal nerve repair., (Copyright © 2024. Published by Elsevier Inc.)

Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients of BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving from anteromedial to posterolateral BF, we observe reduced tethering between structural and functional connectivity gradients, with the lowest tethering in the nucleus basalis of Meynert. In the neocortex, this gradient is expressed by progressively reduced tethering from unimodal sensory to transmodal cortex, with the lowest tethering in the midcingulo-insular network, and is also spatially correlated with the molecular concentration of VAChT, measured by [ 18 F]fluoroethoxy-benzovesamicol (FEOBV) PET. In mice, viral tracing of BF cholinergic projections and [ 18 F]FEOBV PET confirm a gradient of axonal arborization. Altogether, our findings reveal that BF cholinergic neurons vary in their branch complexity, with certain subpopulations exhibiting greater modularity and others greater diffusivity in the functional integration with their cortical targets., (© 2024. The Author(s).)

Hepatic insulin resistance (IR) is often said to be "pathway-selective" with preserved insulin stimulation of de novo lipogenesis (DNL) despite attenuated insulin signaling toward glucose metabolism. However, DNL has not been assessed in models of liver-specific IR. We studied mice with differential tissue-specific lipid-induced IR achieved by different durations of high-fat diet (HFD) feeding. Mice with isolated hepatic IR demonstrated markedly reduced DNL, with a rebound seen in mice with whole-body IR. Insr T1150A mice (protected against diacylglycerol-PKCε-induced hepatic IR) maintained normal DNL with HFD feeding. During hyperinsulinemic clamps, hepatic IR reduced DNL, but hyperglycemia augmented DNL in both resistant and sensitive animals. Regulation through SREBP1c did not consistently correlate with changes in DNL. These results demonstrate that hepatic IR is not pathway-selective, highlighting the primacy of lipogenic substrate in stimulation of DNL. Future therapeutics to reduce lipogenesis should target substrate drivers of DNL rather than targeting plasma insulin levels., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Millions globally suffer from visual impairment, complicating the management of eye diseases due to various ocular barriers. The eye's complex structure and the limitations of existing treatments have spurred interest in tissue engineering (TE) as a solution. This approach offers new functionalities and improves therapeutic outcomes over traditional drug delivery methods, creating opportunities for treating various eye disorders, from corneal injuries to retinal degeneration. In our review of recent articles concerning the use of scaffolds for eye repair, we categorized scaffolds employed in eye TE from recent studies into four types based on tissue characteristics: natural, synthetic, biohybrid, and decellularized tissue. Additionally, we gathered data on the cell types and animal models associated with each scaffold. This allowed us to gather valuable insights into the benefits and drawbacks of each material. Our research elucidates that, in comparison to conventional treatment modalities, scaffolds in TE emulate the extracellular matrix (ECM) of the eye and facilitate cell proliferation and tissue regeneration. These scaffolds can be precisely tailored to incorporate growth factors that augment the healing process while also providing considerable advantages such as bacterial inhibition, biocompatibility, and enhanced durability. However, they also have drawbacks, such as potential immune responses, poor tissue integration, complex and costly manufacturing, and inconsistent degradation rates that can affect their effectiveness. In this review, we provide an overview of the present condition of eye regenerative treatments, assess notable preclinical and clinical research endeavors, contemplate the obstacles encountered, and speculate on potential advancements in the upcoming decade., 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.)

Background and Purpose: Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ)., Method: Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes' stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ's efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time-kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM., Results: The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%)., Conclusions: The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN.

Melamine, often used as an adulterant in infants' formula due to its high protein content, can be harmful when ingested in large amounts, leading to the formation of cyanurate-melamine co-crystals in infants and potentially causing kidney damage. In this study, we introduce a fluorescent method for the selective and reliable detection of melamine in milk and infants' formula. The fluorescent probe comprises copper nanoclusters (Cu NCs) functionalized with thiosalicylic acid (TSA) and polyvinylpyrrolidone (PVP) as double-protecting ligands. Upon the addition of Hg 2+ , the fluorescence emission of TSA-PVP@Cu NCs is diminished due to static quenching. Subsequently, the fluorescence emission of the TSA-PVP@Cu NCs + Hg 2+ probe is restored upon the introduction of melamine, facilitated by the coordination interaction between melamine and Hg 2+ and the formation of a stable chelate between them. Under optimized conditions, the fluorescence emission was recorded initially for the TSA-PVP@Cu NCs + Hg 2+ probe (F°) and after melamine addition (F). The (F/F°) ratio increased with rising melamine concentrations within the range of 0.025-65 µM. The detection limit, calculated using a signal-to-noise ratio of 3, was determined to be 8.0 nM. The TSA-PVP@Cu NCs + Hg 2+ probe was successfully employed to detect melamine in milk and infants' formula, yielding acceptable recovery percentages and relative standard deviations. These results underscore the reliability and efficacy of the proposed probe for the fluorometric detection of melamine in real-world samples., 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.)

Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare and complex clinical condition in which allergic reactions are triggered by specific foods combined with physical activity, even though the food allergen and exercise are tolerated individually. Wheat is the most common culprit food leading to wheat dependent exercise induced anaphylaxis (WDEIA). Management of FDEIA is challenging due to the unpredictability of attacks and the lack of approved prophylactic medications. This report presents a case of successful symptom control in a young woman with WDEIA through the addition of omalizumab to the treatment regimen. To our knowledge, this is the first reported case of food-dependent exercise-induced anaphylaxis (FDEIA) treated with omalizumab as the primary indication. We also summarize the pathophysiology, diagnosis and treatment of FDEIA. The need for heightened awareness and innovative therapeutic approaches is crucial for those affected by FDEIA., 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., (© 2024 Mohamed, Thalappil and Mohammed Ali.)

Objectives: We propose and validate a domain knowledge-driven classification model for diagnosing post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID, using Electronic Health Records (EHRs) data., Materials and Methods: We developed a robust model that incorporates features strongly indicative of PASC or associated with the severity of COVID-19 symptoms as identified in our literature review. The XGBoost tree-based architecture was chosen for its ability to handle class-imbalanced data and its potential for high interpretability. Using the training data provided by the Long COVID Computation Challenge (L3C), which was a sample of the National COVID Cohort Collaborative (N3C), our models were fine-tuned and calibrated to optimize Area Under the Receiver Operating characteristic curve (AUROC) and the F1 score, following best practices for the class-imbalanced N3C data., Results: Our age-stratified classification model demonstrated strong performance with an average 5-fold cross-validated AUROC of 0.844 and F1 score of 0.539 across the young adult, mid-aged, and older-aged populations in the training data. In an independent testing dataset, which was made available after the challenge was over, we achieved an overall AUROC score of 0.814 and F1 score of 0.545., Discussion: The results demonstrated the utility of knowledge-driven feature engineering in a sparse EHR data and demographic stratification in model development to diagnose a complex and heterogeneously presenting condition like PASC. The model's architecture, mirroring natural clinician decision-making processes, contributed to its robustness and interpretability, which are crucial for clinical translatability. Further, the model's generalizability was evaluated over a new cross-sectional data as provided in the later stages of the L3C challenge., Conclusion: The study proposed and validated the effectiveness of age-stratified, tree-based classification models to diagnose PASC. Our approach highlights the potential of machine learning in addressing the diagnostic challenges posed by the heterogeneity of Long-COVID symptoms., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Reduced functional connectivity of physiological systems is associated with poor prognosis in critically ill patients. However, physiological network analysis is not commonly used in clinical practice and awaits quantitative evidence. Acute liver failure (ALF) is associated with multiorgan failure and mortality. Prognostication in ALF is highly important for clinical management but is currently dependent on models that do not consider the interaction between organ systems. This study aims to examine whether physiological network analysis can predict survival in patients with ALF. Data from 640 adult patients admitted to the ICU for paracetamol-induced ALF were extracted from the MIMIC-III database. Parenclitic network analysis was performed on the routine biomarkers using 28-day survivors as reference population and network clusters were identified for survivors and non-survivors using k-clique percolation method. Network analysis showed that liver function biomarkers were more clustered in survivors than in non-survivors. Arterial pH was also found to cluster with serum creatinine and bicarbonate in survivors compared with non-survivors, where it clustered with respiratory nodes indicating physiologically distinctive compensatory mechanism. Deviation along the pH-bicarbonate and pH-creatinine axes significantly predicts mortality independent of current prognostic indicators. These results demonstrate that network analysis can provide pathophysiologic insight and predict survival in critically ill patients with ALF., (© 2024. The Author(s).)

The role of efficient fuel mixing and a stable flame holder is crucial in enhancing the performance and capabilities of scramjet engines for high-speed flight. The present research paper has tried to disclose the fuel mixing efficiency of 3-lobe annular nozzle on the mixing mechanism of the fuel jet behind the strut. In addition, using internal air jet flow for increasing the circulation strength and fuel mixing behind the strut is also examined in this study. Numerical simulation of the flow and fuel jet behind the strut is done to reveal the main physics related to the mechanism of fuel mixing inside the combustor with the proposed injection system. The results of our simulation show that using annular 3-lobe fuel jet improve the fuel mixing via production of the multiple vortex pairs within the combustor behind the strut. The use of internal air jet also enhances the fuel mixing efficiency up to 90% in combustor of scramjet engine., (© 2024. The Author(s).)

Streptococcus pneumoniae is a major cause of meningitis in under developed countries with low vaccination rates and high antibiotic resistance. This study aimed to analyze 83 suspected meningitis patients in Karachi for the detection of S. pneumoniae followed by its whole genome sequencing and Pan Genome analysis. Out of the 83 samples collected, 33 samples with altered physical (turbidity), cytological (white blood cell count) and biochemical (total protein and total glucose concentrations) parameters indicated potential meningitis cases, while these parameters were within normal healthy ranges in remaining 50 samples. Latex particle agglutination (LPA) was performed on the 33 samples, revealing 20 positive cases of bacterial meningitis. The PCR and culturing methods revealed 5 S. pneumoniae isolates. Antibiotic susceptibility tests showed that one S. pneumoniae strain was resistant to erythromycin, levofloxacin, and tetracycline. Whole-genome sequencing of this resistant strain was performed and S. pneumoniae was confirmed with MLST analysis, while it had > 2.3 Mb genome and a single repUS43 plasmid. In CARD analysis, the strain had tet(M), ermB, RlmA(II), patB, pmrA, and patA ARGs, which could provide resistance against tetracycline, macrolide, fluoroquinolone, and glycopeptide antibiotics. Phylogenetic analysis revealed that the isolate was closely related to strains from Hungary and the USA. Pan-genome analysis with 144 genome assemblies from NCBI database showed that 1101 non-redundant core genes were shared between all strains. This study gives valuable understanding into the prevalence and characterization of meningitis-causing bacteria in Karachi, Pakistan  with prime focus on multi-drug resistant S. pneumoniae., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that originates from the mesothelial cells lining the parietal peritoneum or visceral peritoneum and extensively spreads within the abdominal cavity. It is a rare malignancy characterized by an insidious onset and poor prognosis. We present the case of a 79-year-old Caucasian male who experienced escalating abdominal pain for six weeks and acute abdominal distension. His medical history was significant for hypertension, gastroesophageal reflux disease (GERD), hypercholesterolemia, and prior coronary artery bypass grafting (CABG). The patient had a 30-pack-year smoking history and worked as a plumber and roofer until retirement. We also confirmed with the patient that he has never been diagnosed with asbestosis. He reported no family history of mesothelioma or related conditions. A computed tomography (CT) scan revealed a prior sternotomy, mild pleural calcifications, mild hepatic steatosis, diffuse peritoneal ascites, diffuse omental edema, and pelvic phleboliths. MPM was confirmed through histopathological examination, which revealed atypical mesothelial cells with high nucleus-to-cytoplasm ratios, prominent nucleoli, and irregular nuclear membranes. It also revealed tumor cells positive for p53, calretinin, WT1, and podoplanin (D2-40). This case highlights the importance of considering MPM in the differential diagnosis for patients with ascites and possible asbestos exposure, particularly with respect to occupational hazards, as it is a rare manifestation of the disease., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Lief et al.)

Genomic data from millions of individuals have been generated worldwide to drive discovery and clinical impact in precision medicine. Lowering the barriers to using these data collectively is needed to equitably realize the benefits of the diversity and scale of population data. We examine the current landscape of global genomic data sharing, including the evolution of data sharing models from data aggregation through to data visiting, and for certain use cases, cross-cohort analysis using federated approaches across multiple environments. We highlight emerging examples of best practice relating to participant, patient and community engagement; evolution of technical standards, tools and infrastructure; and impact of research and health-care policy. We outline 12 actions we can all take together to scale up efforts to enable safe global data sharing and move beyond projects demonstrating feasibility to routinely cross-analysing research and clinical data sets, optimizing benefit., (© 2024. Springer Nature Limited.)

Introduction: The costs of providing medication-assisted treatment for opioid dependence can determine its scale of provision. To provide estimates of the costs of extended-release buprenorphine (BUP-XR), we performed a bottom-up costing analysis of provider operational treatment costs., Methods: Data were collected in a single-arm open label trial of BUP-XR injections conducted in specialist public drug treatment services and primary care private practices in three Australian states (the CoLAB study). The unit costs of resources used for each activity were combined with quantities used at each participating facility to arrive at the average annual cost per client., Results: One hundred participants across the six health facility sites received monthly subcutaneous BUP-XR injections administered by a health-care practitioner. The average cost of providing 1 year of treatment per participant was $6656 ($6026-$8326). Screening cost (initial assessment and medical history) was $282 while monthly follow-up appointments cost $531 per client. The main cost driver was the monthly treatment costs accounting for 79% of the average annual client cost, with medication costs comprising 95% of this cost., Discussion and Conclusion: With medication costs making up the largest proportion of treatment costs, treatment using BUP-XR has the potential to free up other health system resources, for example, staff time. The costs reported in this study can be used in an economic evaluation to estimate the net benefit or cost-effectiveness of BUP-XR especially when compared to other opioid agonist treatments., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Due to the increase in demand for donor organs and tissues during the past 20 years, new approaches have been created. These methods include, for example, tissue engineering in vitro and the production of regenerative biomaterials for transplantation. Applying the natural extracellular matrix (ECM) as a bioactive biomaterial for clinical applications is a unique approach known as decellularization technology. Decellularization is the process of eliminating cells from an extracellular matrix while preserving its natural components including its structural and functional proteins and glycosaminoglycan. This can be achieved by physical, chemical, or biological processes. A naturally formed three-dimensional structure with a biocompatible and regenerative structure is the result of the decellularization process. Decreasing the biological factors and antigens at the transplant site reduces the risk of adverse effects including inflammatory responses and immunological rejection. Regenerative medicine and tissue engineering applications can benefit from the use of decellularization, a promising approach that provides a biomaterial that preserves its extracellular matrix., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To assess the efficacy of Toxfin and Novasil as aflatoxin-binding agents in broilers exposed to aflatoxin B 1 (AFB 1 ) from 11 to 30 days, 288 mixed-sex Ross 308 broiler chickens were randomly allocated to four dietary groups: control feed, control feed + 0.25 mg/kg AFB 1 , AFB 1 feed + 0.3% Toxfin, and AFB 1 feed + 0.3% Novasil. The evaluation encompassed growth performance for the grower (11-20 days), finisher (21-30 days), and overall (11-30 days) phases, carcass characteristics, serum biochemical components, liver function enzymes, hepatic antioxidant capacity, AFB 1 residue in the liver and kidney, and ileal morphology at 30 days, and apparent nutrient digestibility during 29-30 days. Exposure to AFB 1 significantly resulted in reduced growth efficiency, lowered carcass yields, liver hypertrophy, impaired metabolic and hepatic functions, liver oxidative stress, disrupted ileum architecture, diminished nutrient digestibility, and accumulated AFB 1 in the liver and kidney. Conversely, supplementation of Toxfin or Novasil significantly augmented body weight gain (BWG) and reduced feed conversion ratio (FCR) during the finisher and overall phases, elevated BWG in the grower phase, heightened levels of glucose, hepatic protein, and glutathione peroxidase, declined malondialdehyde content, improved apparent metabolizable energy, and lowered AFB 1 residues in the liver and kidney. Furthermore, Toxfin inclusion significantly reduced FCR during the grower phase, enhanced European production efficiency factor during the grower and overall phases, augmented dressing percentage, declined proportional liver weight, elevated concentrations of total protein, albumin, and total antioxidant capacity, heightened villus surface area, and boosted crude protein digestibility. To conclude, incorporating 0.3% Toxfin into broilers' feeds confers a more effectual safeguard than Novasil against the deleterious consequences of AFB 1 exposure., (© 2024. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

Echinococcus species (spp.) are regarded as neglected cestodes causing several potential zoonoses of global public health. This systematic review critically appraises the worldwide distribution of Echinococcus spp. and genotypes (Echinococcus spp.: recognized species in the genus; genotypes: variants identified within E. granulosus sensu lato.) in definitive hosts. We analyzed 82 studies from major databases, comprising 24 individual host species, including canids, felids, and a hyenid species. Canids, particularly dogs, were the most studied group among the host species, with E. granulosus sensu stricto (G1-G3) being the most frequently reported. E. granulosus s.s. was distributed across five major continents, while other Echinococcus spp. and genotypes exhibited an uneven continental distribution. The highest overlap of species existed among Asia, Europe, and Africa. Among the reported host species, 4.2 % were endangered (e.g. Lycaon pictus), 12.5 % species were vulnerable (e.g. Panthera leo, Panthera pardus, and Acinonyx jubatus), and 4.2 % were near threatened (e.g. Speothos venaticus). Overall, our review highlights the significance of canids, particularly dogs, as the core focus of scientific investigations, with E. granulosus s.s. being the most widely distributed species across five major continents, emphasizing the urgent need for continued research and public health efforts., 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.)

Purpose: Clinical diagnosis of dry eye disease is based on a subjective Ocular Surface Disease Index questionnaire or various objective tests, however, these diagnostic methods have several limitations., Methods: We conducted a comprehensive review of articles discussing various applications of artificial intelligence (AI) models in the diagnosis of the dry eye disease by searching PubMed, Web of Science, Scopus, and Google Scholar databases up to December 2022. We initially extracted 2838 articles, and after removing duplicates and applying inclusion and exclusion criteria based on title and abstract, we selected 47 eligible full-text articles. We ultimately selected 17 articles for the meta-analysis after applying inclusion and exclusion criteria on the full-text articles. We used the Standards for Reporting of Diagnostic Accuracy Studies to evaluate the quality of the methodologies used in the included studies. The performance criteria for measuring the effectiveness of AI models included area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy. We calculated the pooled estimate of accuracy using the random-effects model., Results: The meta-analysis showed that pooled estimate of accuracy was 91.91% (95% confidence interval: 87.46-95.49) for all studies. The mean (±SD) of area under the receiver operating characteristic curve, sensitivity, and specificity were 94.1 (±5.14), 89.58 (±6.13), and 92.62 (±6.61), respectively., Conclusions: This study revealed that AI models are more accurate in diagnosing dry eye disease based on some imaging modalities and suggested that AI models are promising in augmenting dry eye clinics to assist physicians in diagnosis of this ocular surface condition., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The current study devises an optimized ethanolic extraction for efficient recovery of high-value components from Pakistani olives (cv. Arbequina) using response surface methodology (RSM) and artificial neural networking (ANN). Four factors such as time, temperature, solvent concentration, and solute weight (g/100 mL) were evaluated as independent variables for determining the response (% yield). The results obtained under optimum extraction conditions such as duration (25 min), temperature (45 °C), solvent concentration (65 %; ethanol: water v/v), and solute (7.50 g/100 mL) offered bioactives extract yield of 40.96 % from Arbiquina olives. The analysis of variance (ANOVA) for the RSM model showed significant p-values and a correlation coefficient (R 2 ) of 0.9960, confirming model's reliability. The results of ANN, which employed the multilayer perceptron design, were fairly in line with the findings of the experiments. The antioxidant characteristics and GC-MS metabolite profile of the obtained extracts were examined. Arbequina olive extract (AOE) demonstrated very good antioxidant ability in terms of total phenolic, total flavonoid contents, and DPPH radical scavenging. The GC-MS analysis of AOE confirmed the presence of several bioactives, including oleic acid (36.22 %), hydroxytyrosol (3.95 %), tyrosol (3.32 %), β-sitosterol (2.10 %), squalene (1.10 %), sinapic acid (0.67 %), α-tocopherol (0.66 %), vanillic acid (0.56 %), 3,5-di-tert-butylcatechol (0.31 %), and quercetin (0.21 %). The suggested optimized extraction method can be employed to efficiently extract a wide variety of high-value components from olives with potential for nutraceutical applications., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

As the indications for endoscopic skull base approaches have increased, so has the need for more versatile vascularized flaps for skull base reconstruction. Here, we describe a novel lateral based nasopharyngeal flap (LNPF). Two cadaver heads were dissected to elucidate flap anatomy, dimensions, and technique. A retrospective review was performed on two cases where LNPF was used to repair CSF leaks in the nasopharyngeal area, and outcomes reported. The LNPF is an ascending pharyngeal artery myomucosal flap that includes the nasopharyngeal mucosa and the superior pharyngeal constrictor muscle. The flap was 1.2 × 2.2 cm in greatest dimensions. The LNPF was used for salvage CSF leak repair in two cases: one clival and one tubal. Both patients had resolution of leak at 7 months follow-up. The LNPF is a novel flap with reconstruction potential for the nasopharynx, including the lower clivus and the eustachian tube., (© 2024 Wiley Periodicals LLC.)

Diclofenac sodium (DIC) is a widely used non-steroidal anti-inflammatory drug. Unfortunately, its prolonged use is associated with nephrotoxicity due to oxidative stress, inflammation, and fibrosis. We aimed to investigate the nephroprotective effects of vitamin B complex (B1, B6, B12) against DIC-induced nephrotoxicity and its impact on NOX4/RhoA/ROCK, a pathway that plays a vital role in renal pathophysiology. Thirty-two Wistar rats were divided into four groups: (1) normal control; (2) vitamin B complex (16 mg/kg B1, 16 mg/kg B6, 0.16 mg/kg B12, intraperitoneal); (3) DIC (10 mg/kg, intramuscular); and (4) DIC plus vitamin B complex group. After 14 days, the following were assayed: serum renal biomarkers (creatinine, blood urea nitrogen, kidney injury molecule-1), oxidative stress, inflammatory (tumor necrosis factor-α, interleukin-6), and fibrotic (transforming growth factor-β) markers as well as the protein levels of NOX4, RhoA, and ROCK. Structural changes, inflammatory cell infiltration, and fibrosis were detected using hematoxylin and eosin and Masson trichrome stains. Compared to DIC, vitamin B complex significantly decreased the renal function biomarkers, markers of oxidative stress and inflammation, and fibrotic cytokines. Glomerular and tubular damage, inflammatory infiltration, and excessive collagen accumulation were also reduced. Protein levels of NOX4, RhoA, and ROCK were significantly elevated by DIC, and this elevation was ameliorated by vitamin B complex. In conclusion, vitamin B complex administration could be a renoprotective approach during treatment with DIC via, at least in part, suppressing the NOX4/RhoA/ROCK pathway., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the frequency and clinical features of intraocular paraneoplastic sarcoid-like reaction (SLR) in patients with chronic lymphocytic leukemia (CLL)., Methods: Retrospective review of patients with CLL from January 1, 1980, to December 31, 2020. Eye examinations were searched for 22 keywords suggestive of SLR, and charts were manually reviewed., Results: Of 4209 unique patients with CLL, 1021 (24%) had at least 1 eye examination on record, and 324 (8%) had 1 or more keyword eye examination findings. After manual review, 12 patients (<1%) were identified as having probable SLR with characteristic features (n = 7), possible but not classic (n = 1), or suspect but less likely (n = 4). All patients (n = 8) with probable or possible SLR were White, and half (n = 4) were male. Intraocular SLR was diagnosed a mean of 49.7 months after the CLL diagnosis (n = 7) or preceded the CLL diagnosis by 1 month (n = 1). Involvement was bilateral in 5 patients, with 13 total affected eyes and mean presenting Snellen visual acuity of 20/50. Common characteristic features on initial examination included vitreous cell (n = 13), anterior-chamber cell (n = 10), keratic precipitates (n = 9), posterior synechiae (n = 6), chorioretinal lesions (n = 5), and vitreous haze (n = 5). Treatment included topical corticosteroids alone (n = 5), with sub-Tenon corticosteroids (n = 1), or with steroid-sparing immunosuppressive agents (n = 1) or oral corticosteroids alone (n = 1). After a mean follow-up of 19.8 months, final mean visual acuity was 20/30., Conclusion: Intraocular SLRs affect fewer than 1% of patients with CLL. SLR should be on the differential diagnosis list for any CLL patient with ocular complaints, and most patients can be managed successfully with corticosteroids., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe ocular involvement in subjects with Whipple's disease (WD)., Methods: Retrospective review of documented WD cases seen at Mayo Clinic between 1980 and 2021 with ocular involvement., Results: Of 217 patients with WD, 30 had eye exams and four (two female, median age 58.5 years) had ocular involvement. Findings included anterior/intermediate uveitis ( n  = 2), intermediate uveitis and phlebitis ( n  = 1), and chorioretinitis with vitritis ( n  = 1). The diagnosis was confirmed by vitreous biopsy in three of four cases. In two cases, WD diagnosis was unconfirmed prior to the ocular diagnosis. Systemic manifestations included gastrointestinal symptoms in all patients, synovitis ( n  = 3), weight loss ( n  = 2), and pericarditis ( n  = 1). Mean time from onset of ocular symptoms to ocular diagnosis was 11 months (range 2-28 months). Prior systemic symptoms were present as long as 3 years., Conclusions: WD is uncommon and ocular involvement is even more rare. However, WD should be considered in the differential for all patients with chronic recalcitrant uveitis, especially in the setting of polyarthralgias and/or gastrointestinal symptoms. Vitreous biopsy is a reliable method to diagnose ocular WD. Abbreviations and Acronyms: Whipple's disease (WD), intestinal lipodystrophy (IL), polymerase-chain reaction (PCR), periodic acid-Schiff (PAS), trimethoprim/sulfamethoxazole (TMP/SMX).