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Abstract Background Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging. Methods PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors. Results Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel. Conclusions Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors.

Abstract The survival of animals is impacted by landscapes of spatially varying mortality factors including habitat type, predation risk or harvest risk, among others. Characterization of these spatial mortality processes is important for managing animal populations and their habitats, yet this information has proved challenging to capture. Advances in telemetry now make it possible to monitor tagged individuals' locations through time for a wide range of taxa, providing opportunity to assess movement and mortality simultaneously through spatial time‐to‐event data. Existing time‐to‐event modelling frameworks have largely ignored spatially varying mortality processes or have treated an animal's location as fixed at a regional level. Here we present a general spatial survival model for analysing time‐to‐event data arising from animal telemetry. Our model has a flexible Cox regression form and can estimate the effects of conventional non‐spatial risk factors (size, seasonality, etc.), spatial covariates (e.g. habitat type) and spatial variation in risk not explained by covariates on mortality. We show how to fit our model using Bayesian methods and demonstrate applications of our model with several simulated examples and two animal telemetry case studies. Our model produced consistent and unbiased parameter estimates throughout simulations with a variety of spatial and non‐spatial hazards. In the first case study, data from 147 tagged caribou in British Columbia, Canada, revealed a spatially heterogeneous mortality landscape with caribou survival varying by elevation, likely in response to space use by predators. Our second case study involved a dataset of 390 acoustically tagged Atlantic cod in a southern Norwegian fjord where a marine protected area (MPA) was established during the study. We found that the MPA led to a shift from mostly fishing mortality to mostly natural mortality within the fjord and that these risks had markedly different spatial hazard patterns. Our spatial time‐to‐event model can make use of data from a variety of widely used telemetry technologies to characterize landscapes of mortality risks for different taxa. Our work provides new opportunities to inform the spatial ecology and management of fish and wildlife populations.

Background: Rhinosinusitis is defined as a multifactorial disorder with persistence of symptoms caused by inflammation of the sinonasal mucosa for 12 or more weeks with confirmation by diagnostic nasal endoscopy and computed tomography. The main aim of this study is to analyze the neutrophilic or eosinophilic predominance among CRS patients with histopathological examination for appropriate management, and to understand the association between the endotypes of CRS and blood parameters. Materials and methods: A prospective cohort study was conducted on 137 patients over a period of two years at a tertiary centre. Diagnostic nasal endoscopy (DNE), computed tomography of the nose and paranasal sinus (CT PNS), complete haemogram (CBC), absolute eosinophil count (AEC), erythrocyte sedimentation rate (ESR), immunoglobulin E(IgE) was done. Patients were planned for functional endoscopic sinus surgery (FESS) and specimen was sent for histopathological examination. Results: The comparison between DNE and AEC groups showed statistical significance and so did the comparison between CT and IgE. When we compared the groups of CRS with and without polyps with DNE and CT, there was no statistical significance. Also 64.2% of patients had an eosinophilic predominance. Conclusion: It has also been reported that CRS are highly eosinophilic, also have substantial levels of neutrophils. Importantly, tissue neutrophilia has been associated with a poor response to corticosteroid therapy in patients with CRS with nasal polyps.

Abstract Advances in tagging technologies are expanding opportunities to estimate survival of fish and wildlife populations. Yet, capture and handling effects could impact survival outcomes and bias inference about natural mortality processes. We developed a multistage time-to-event model that can partition the survival process into sequential phases that reflect the tagged animal experience, including handling and release mortality, post-release recovery mortality, and subsequently, natural mortality. We demonstrate performance of multistage survival models through simulation testing and through fish and bird telemetry case studies. Models are implemented in a Bayesian framework and can accommodate left, right, and interval censorship events. Our results indicate that accurate survival estimates can be achieved with reasonable sample sizes ( $$n\approx 100+)$$ n ≈ 100 + ) and that multimodel inference can inform hypotheses about the configuration and length of survival stages needed to adequately describe mortality processes for tracked specimens. While we focus on survival estimation for tagged fish and wildlife populations, multistage time-to-event models could be used to understand other phenomena of interest such as migration, reproduction, or disease events across a range of taxa including plants and insects.

IntroductionRenal cell carcinoma (RCC) represents cancer originating from the renal epithelium and accounts for > 90% of cancers in the kidney. Prostate-specific membrane antigen (PSMA) is overexpressed in tumor-associated neovascular endothelial cells of many solid tumors, including metastatic RCC. Although studied in several small clinical studies, PSMA-based imaging and therapy have not been pursued rigorously in preclinical RCC. This study aimed to evaluate the preclinical performance of PSMA-based radiotheranostic agents in a relevant murine model.MethodsA PSMA-overexpressing murine cell line, PSMA+ RENCA, was developed by lentiviral transduction. PSMA-based theranostic agents, 68Ga-L1/177Lu-L1/225Ac-L1, were synthesized in high radiochemical yield and purity following our reported methods. Immunocompetent BALB/c mice were used for flank and orthotopic tumor inoculation. 68Ga-L1 was evaluated in small animal PET/CT imaging in flank and PET/MR imaging in orthotopic models. Cell viability studies were conducted for 177Lu-L1 and 225Ac-L1. Proof-of-concept treatment studies were performed using 225Ac-L1 (0, 37 kBq, 2 kBq × 37 kBq, 1 week apart) using PSMA+ RENCA in the flank model.ResultsCellular uptake of 68Ga-L1, 177Lu-L1, and 225Ac-L1 confirmed the specificity of the agents to PSMA+ RENCA cells rather than to RENCA (wt) cells, which are low in PSMA expression. The uptake in PSMA+ RENCA cells at 1 h for 68Ga-L1 (49.0% incubated dose [ID] ± 3.6%ID/million cells), 177Lu-L1 (22.1%ID ± 0.5%ID)/million cells), and 225Ac-L1 (4.1% ± 0.2% ID)/million cells), respectively, were higher than the RENCA (wt) cells (~ 1%ID–2%ID/million cells). PET/CT images displayed > 7-fold higher accumulation of 68Ga-L1 in PSMA+ RENCA compared to RENCA (wt) in flank implantation at 1 h. A twofold higher accumulation of 68Ga-L1 was observed in orthotopic tumors than in normal kidneys during 1–3 h postinjection. High lung uptake was observed with 68Ga-L1 PET/MR imaging 3 weeks after orthotopic implantation of PSMA+ RENCA due to spontaneous lung metastases. The imaging data were further confirmed by immunohistochemical characterization. 225Ac-L1 (0-37 kBq) displayed a dose-dependent reduction of cell proliferation in the PSMA+ RENCA cells after 48 h incubation; ~ 40% reduction in the cells with treated 37 kBq compared to vehicle (p < 0.001); however, no effect was observed with 177Lu-L1 (0–3700 kBq) up to 144 h postinoculation, suggesting lower efficacy of β-particle-emitting radiations in cellular studies compared to α-particle-emitting 225Ac-L1. Animals treated with 225Ac-L1 at 1 week posttumor inoculation in flank models displayed significant tumor growth delay (p < 0.03) and longer median survival of 21 days and 24 days for the treatment groups 37 kBq and 2 kBq × 37 kBq, respectively, compared to the vehicle group (12 days).ConclusionThe results suggest that a theranostic strategy targeting PSMA, employing PET and α-emitting radiopharmaceuticals, enabled tumor growth control and enhanced survival in a relevant immunocompetent murine model of RCC. These studies provide the rationale for clinical studies of PSMA-targeted theranostic agents in patients with RCC.

Abstract Terrestrial ecosystems evolved substantially through the Palaeozoic, especially the Permian, gaining much new complexity, especially among predators. Key among these predators were non-mammalian synapsids. Predator ecomorphology reflect interactions with prey and competitors, which are key controls on carnivore diversity and ecology. Therefore, carnivorous synapsids may offer insight on wider ecological evolution as the first complex, tetrapod-dominated, terrestrial ecosystems formed through the late Palaeozoic. Using morphometric and phylogenetic comparative methods, we chart carnivorous synapsid trophic morphology from the latest Carboniferous to the earliest Triassic (307-251.2 Ma). We find a major morphofunctional shift in synapsid carnivory between the early and middle Permian, via the addition of new feeding modes increasingly specialised for greater biting power or speed that captures the growing antagonism and dynamism of terrestrial tetrapod predator-prey interactions. The further evolution of new hypo- and hypercarnivorous synapsids highlight the nascent intrinsic pressures and complexification of terrestrial ecosystems across the mid-late Permian.

Abstract Background Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition. Aim This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis. Methods In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken. Results Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p

Microstrip antennas usually suffer from high losses, gain, and efficiency degradation. It is a challenging task to miniaturize the patch antenna without degrading the performance parameters. To mitigate the above problems, a microstrip patch antenna loaded with stubs and printed on the ground plane loaded with dumbbell meta-atom is presented in this paper. The proposed double dumbbell meta-atom consists of two complementary split ring resonator (CSRR) cells loaded with rectangular rings. This exhibits the Double Negative (DNG) characteristic at 2.45 GHz. The devised meta-atom possesses dimensions of 0.05λ x 0.03λ at lower giga-hertz range. The meta-atom is further analyzed in CST-Microwave Studio and the corresponding S-parameters are extracted in MATLAB using the Nicolson Ross Weir (NRW) method. The electrical model of the meta-atom is also analyzed using Agilent ADS simulator. Further, two models of the proposed antenna with FR-4 and RT/Duroid-5880 are designed and compared. The proposed patch antenna resonates at three different frequency bands i.e. 2.445 GHz with a 3-dB bandwidth of 110 MHz (2.4 GHz–2.51 GHz), at 5.85 GHz with a 3-dB bandwidth of 730 MHz (5.13 GHz–5.86 GHz), and at 8.83 GHz with a 3-dB bandwidth of 1.83 GHz (7.7 GHz–9.53 GHz). This exhibit peak gains of 2.75dBi, 3.53dBc and 4.36dBi with low cross polarization levels at the said frequencies of operation. Further, the antenna possesses circular polarization in the frequency band (5.15 GHz–5.63 GHz). This antenna is used for Wi-Fi, ISM and X-band communications. The designed prototype is fabricated and tested and bears resemblance to the simulated results.

Background: To evaluate the Retinal Nerve Fiber Layer and Ganglion Cell Complex thickness using Spectral Domain Optical Coherence Tomography with and without positive family history of Primary Open Angle Glaucoma and its relation to visual field. Methods: Total 120 eyes with each subjects with positive family history of Primary Open Angle Glaucoma (Group I, n=30) and healthy subjects without positive family history of Primary Open Angle Glaucoma (Group II, n=30) undergone complete ophthalmic evaluation with Retinal Nerve Fiber Layer, Ganglion Cell Complex and VF obtained from Spectral Domain Optical Coherence Tomography RTVue-100 and Humphrey visual field respectively .The measurements were analyzed and compared among two groups using independent-t test by using SPSS version 23.The relationship of Retinal Nerve Fiber Layer with visual field were evaluated with correlation analysis. Results: The Intra Ocular Pressure and vertical Cup Disc Ratio were significantly higher in Group I with mean difference of 2.48±0.43 (p

Abstract Estimates of juvenile survival are critical for informing population dynamics and the ecology of fish, yet these demographic parameters are difficult to measure. Here, we demonstrate that advances in animal tracking technology provide opportunities to evaluate survival of juvenile tagged fish. We implemented a whole-lake telemetry array in conjunction with small acoustic tags (including tags

Abstract Selecting regions of interest (ROI) is a common step in medical image analysis across all imaging modalities. An ROI is a subset of an image appropriate for the intended analysis and identified manually by experts. In modern pathology, the analysis involves processing multidimensional and high resolution whole slide image (WSI) tiles automatically with an overwhelming quantity of structural and functional information. Despite recent improvements in computing capacity, analyzing such a plethora of data is challenging but vital to accurate analysis. Automatic ROI detection can significantly reduce the number of pixels to be processed, speed the analysis, improve accuracy and reduce dependency on pathologists. In this paper, we present an ROI detection method for WSI and demonstrated it for human epidermal growth factor receptor 2 (HER2) grading for breast cancer patients. Existing HER2 grading relies on manual ROI selection, which is tedious, time-consuming and suffers from inter-observer and intra-observer variability. This study found that the HER2 grade changes with ROI selection. We proposed an ROI detection method using Vision Transformer and investigated the role of image magnification for ROI detection. This method yielded an accuracy of 99% using 20 × WSI and 97% using 10 × WSI for the ROI detection. In the demonstration, the proposed method increased the diagnostic agreement to 99.3% with the clinical scores and reduced the time to 15 seconds for automated HER2 grading.

Wind energy conversion systems (WECS) have gained increasing attention in recent years as promising renewable energy sources. Despite their potential, a clear research gap exists: the majority of WECS underperform in low wind speed conditions, limiting their applicability in many regions. To address this problem, this study proposes a novel approach by developing a 100 W micro wind turbine using Polylactic Acid (PLA) to generate efficient power in low wind speed conditions. The proposed wind turbine design employs Blade Element Momentum Theory (BEMT), which is commonly used for modeling wind turbine performance. Geometric design, mechanical analysis, and aerodynamic analysis are the fundamental considerations for designing any machine. In this work, the CREO 3.0 three-dimensional modeling software is used to create the geometric design of the proposed work. The airfoil SD7080 is selected due to its superior aerodynamic performance, and mechanical properties such as Young's modulus, density, and Poisson's ratio are attained to evaluate the wind blade's performance. Additionally, ANSYS 15.0 is used to conduct a detailed analysis of the proposed wind turbine, evaluating properties such as equivalent stress, deformation, and equivalent strain. Both simulation (ANSYS 15.0) and experimental setups are used to investigate the proposed wind turbine's performance, and the corresponding results are presented and discussed in this manuscript. The results indicate a significant performance improvement of the proposed wind blade when compared to conventional and ABS wind blades, demonstrating its potential as a more efficient solution for WECS. This proposed wind turbine design overcomes the problems like underprformance in low wind speed conditions and the wind turbine efficiency in all regions.

Background/objectives Surgical populations and particularly injury survivors often present with complex trauma that elevates their risk for prolonged opioid use and misuse. Changes in opioid prescribing guidelines during the past several years have yielded mixed results for pain management after trauma, with a limiting factor being the heterogeneity of clinical populations and treatment needs in individuals receiving opioids. The present analysis illuminates this gap between clinical guidelines and clinical practice through qualitative feedback from hospital trauma providers and unit staff members regarding current opioid prescribing guidelines and practices in the setting of traumatic injury.Methods The parent study aimed to implement a pilot screening tool for opioid misuse in four level I and II trauma hospitals throughout Wisconsin. As part of the parent study, focus groups were conducted at each study site to explore the facilitators and barriers of implementing a novel screening tool, as well as to examine the current opioid prescribing guidelines, trainings, and resources available for trauma and acute care providers. Focus group transcripts were independently coded and analyzed using a modified grounded theory approach to identify themes related to the facilitators and barriers of opioid prescribing guidelines in trauma and acute care.Results Three major themes were identified as impactful to opioid-related prescribing and care provided in the setting of traumatic injury; these include (1) acute treatment strategies; (2) patient interactions surrounding pain management; and (3) the multifactorial nature of trauma on pain management approaches.Conclusion Providers and staff at four Wisconsin trauma centers called for trauma-specific opioid prescribing guidelines in the setting of trauma and acute care. The ubiquitous prescription of opioids and challenges in long-term pain management in these settings necessitate additional community-integrated research to inform development of federal guidelines.Level of evidence Therapeutic/care management, level V.

The Triassic was a time of ecological upheaval as life recovered from the Permian-Triassic mass extinction. Archosauromorphs were a key component of the recovery, diversifying substantially during the Triassic and encompassing the origins of dinosaurs, pterosaurs and crocodylomorphs. Here, we explore the evolution of locomotion in Archosauromorpha to test whether dinosaurs show any distinctive locomotory features that might explain their success. We implement geometric morphometrics on limb bone shapes and use limb ratios to calculate bipedality and cursoriality metrics. We find that the Avemetatarsalia (dinosaurs, pterosaurs and relatives) exhibit more variable limb form and limb ratios than any other group, indicating a wider range of locomotory modes. The earliest avemetatarsalians were bipedal and cursorial, and their range of form increased through the Triassic with notable diversification shifts following extinction events. This is especially true of dinosaurs, even though these changes cannot be discriminated from a stochastic process. By contrast, the Pseudosuchia (crocodilians and relatives) were more restricted in limb form and locomotor mode with disparity decreasing through time, suggesting more limited locomotor adaptation and vulnerability to extinction. Perhaps the greater locomotor plasticity of dinosaurs gave them a competitive advantage in the changing climates of the Late Triassic.

ObjectiveThe purpose of this study is to examine the efficacy of BETTER (Brain Injury, Education, Training, and Therapy to Enhance Recovery) vs. usual transitional care management among diverse adults with traumatic brain injury (TBI) discharged home from acute hospital care and families.MethodsThis will be a single-site, two-arm, randomized controlled trial (N = 436 people, 218 patient/family dyads, 109 dyads per arm) of BETTER, a culturally- and linguistically-tailored, patient- and family-centered, TBI transitional care intervention for adult patients with TBI and families. Skilled clinical interventionists will follow a manualized protocol to address patient/family needs. The interventionists will co-establish goals with participants; coordinate post-hospital care, services, and resources; and provide patient/family education and training on self- and family-management and coping skills for 16 weeks following hospital discharge. English- and Spanish-speaking adult patients with mild-to-severe TBI who are discharged directly home from the hospital without inpatient rehabilitation or transfer to other settings (community discharge) and associated family caregivers are eligible and will be randomized to treatment or usual transitional care management. We will use intention-to-treat analysis to determine if patients receiving BETTER have a higher quality of life (primary outcome, SF-36) at 16-weeks post-hospital discharge than those receiving usual transitional care management. We will conduct a descriptive, qualitative study with 45 dyads randomized to BETTER, using semi-structured interviews, to capture perspectives on barriers and facilitators to participation. Data will be analyzed using conventional content analysis. Finally, we will conduct a cost/budget impact analysis, evaluating differences in intervention costs and healthcare costs by arm.DiscussionFindings will guide our team in designing a future, multi-site trial to disseminate and implement BETTER into clinical practice to enhance the standard of care for adults with TBI and families. The new knowledge generated will drive advancements in health equity among diverse adults with TBI and families.Trial registrationNCT05929833.

Pancreatic cancer is a highly aggressive disease with a poor prognosis. Its tumor microenvironment is characterized by severe nutrient deprivation and hypoxia, leading to the activation of adaptive pathways that allow cancer cells to survive and thrive under these harsh conditions. This makes conventional therapies less effective, highlighting the urgent need for novel treatment strategies. Naphthoquinones have recently emerged as promising anti-austerity agents, demonstrating preferential cytotoxicity against pancreatic cancer cells in nutrient-deprived medium (NDM). To further explore their potential, we investigated the structure–activity relationships and mechanism of action of a library of 28 natural and synthetic naphthoquinones. Our results reveal a significant influence of functional groups at positions C-2, C-3, C-5, and C-6 on anticancer activity. Strong electron-donating substituents at C-3 decreased the activity, while electron-withdrawing groups at C-3 and H-bond acceptors at C-6 (without H-bond donor activity) increased the potency. The naphthoate esters 4 and 5 exhibited the strongest activity against PANC-1 cells, with PC50 values of 0.87 and 0.42 μM, respectively. These compounds significantly altered cancer cell morphology, induced apoptosis, and inhibited colony formation. Further investigation revealed that compound 5 downregulated the expression of Akt and p-Akt(S473) proteins, suggesting that its anti-austerity activity might involve suppression of the Akt signaling pathway. These findings demonstrate the immense potential of naphthoquinones as novel anticancer agents targeting the austerity-adapted pancreatic cancer cells. Further development of these promising compounds holds significant potential for treating this devastating disease.

Background: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. Methods: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to “very-long-PFAS”, “long-PFAS”, and “short-PFAS”, respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. Results: Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (β range 1.22–1.41 mL/SD, all P

The effects of Mesua ferrea Linn flower (MFE) extract on the pathogenic cascade of Alzheimer’s disease (AD) were determined by an in vitro and cell culture model in the search for a potential candidate for the treatment of AD. The 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay exhibited that the MFE extract had antioxidant activities. According to the Ellman and the thioflavin T method’s result, the extracts could inhibit acetylcholinesterase and β-amyloid (Aβ) aggregation. Studies on neuroprotection in cell culture found that the MFE extract could reduce the death of human neuroblastoma cells (SH-SY5Y) caused by H2O2 and Aβ. Western blot analysis exhibited that the MFE extract alleviated H2O2-induced neuronal cell damage by downregulating the pro-apoptotic proteins, including cleaved caspase-3, Bax, and by enhancing the expression of anti-apoptotic markers including MCl1, BClxl, and survivin. Moreover, MFE extract inhibited the expression of APP, presenilin 1, and BACE, and increased the expression of neprilysin. In addition, the MFE extract could enhance scopolamine-induced memory deficit in mice. Overall, results showed that the MFE extract had several modes of action related to the AD pathogenesis cascade, including antioxidants, anti-acetylcholinesterase, anti-Aβ aggregation, and neuroprotection against oxidative stress and Aβ. Therefore, the M. ferrea L. flower might be a possibility for further development as a medication for AD.

Abstract The introduction of hippos into the wild in Colombia has been marked by their rapid population growth and widespread dispersal on the landscape, high financial costs of management, and conflicting social perspectives on their management and fate. Here we use population projection models to investigate the effectiveness and cost of management options under consideration for controlling introduced hippos. We estimate there are 91 hippos in the middle Magdalena River basin, Colombia, and the hippo population is growing at an estimated rate of 9.6% per year. At this rate, there will be 230 hippos by 2032 and over 1,000 by 2050. Applying the population control methods currently under consideration will cost at least 1–2 million USD to sufficiently decrease hippo population growth to achieve long-term removal, and depending on the management strategy selected, there may still be hippos on the landscape for 50–100 years. Delaying management actions for a single decade will increase minimum costs by a factor of 2.5, and some methods may become infeasible. Our approach illustrates the trade-offs inherent between cost and effort in managing introduced species, as well as the importance of acting quickly, especially when dealing with species with rapid population growth rates and potential for significant ecological and social impacts.

With additive manufacturing (AM) processes such as Wire Arc Additive Manufacturing (WAAM), components with complex shapes or with functional properties can be produced, with advantages in the areas of resource conservation, lightweight construction, and load-optimized production. However, proving component quality is a challenge because it is not possible to produce 100% defect-free components. In addition to this, statistically determined fluctuations in the wire quality, gas flow, and their interaction with process parameters result in a quality of the components that is not 100% reproducible. Complex testing procedures are therefore required to demonstrate the quality of the components, which are not cost-effective and lead to less efficiency. As part of the project “3DPrintFEM”, a sound emission analysis is used to evaluate the quality of AM components. Within the scope of the project, an approach was being developed to determine the quality of an AM part dependent not necessarily on its geometry. Samples were produced from WAAM, which were later cut and milled to precision. To determine the frequencies, the samples were put through a resonant frequency test (RFM). The unwanted modes were then removed from the spectrum produced by the experiments by comparing it with FEM simulations. Later, defects were introduced in experimental samples in compliance with the ISO 5817 guidelines. In order to create a database of frequencies related to the degree of the sample defect, they were subjected to RFM. The database was further augmented through frequencies from simulations performed on samples with similar geometries, and, hence, a training set was generated for an algorithm. A machine-learning algorithm based on regression modelling was trained based on the database to sort samples according to the degree of flaws in them. The algorithm’s detectability was evaluated using samples that had a known level of flaws which forms the test dataset. Based on the outcome, the algorithm will be integrated into an equipment developed in-house to monitor the quality of samples produced, thereby having an in-house quality assessment routine. The equipment shall be less expensive than conventional acoustic equipment, thus helping the industry cut costs when validating the quality of their components.

Background: The doctor-patient relationship is a fundamental and essential component of healthcare that plays a critical role in patient outcomes, trust, and overall quality of care. Internet-based health information has been found to have both positive and negative effects on patients. Objectives: To assess the internet health-seeking behaviour among patients, and its effect on the doctor-patient relationship Methodology: In this facility-based cross-sectional study, 110 patients were assessed regarding their internet health-seeking behaviour and its effect on the doctor-patient relationship. Patient-Doctor Depth-of-Relationship Scale and Patient Satisfaction Questionnaire – Short form (PSQ-18) was used to assess the relationship. A comparison of patient satisfaction scores and doctor-patient relationship scores among those who use the internet for seeking health-related information with those who do not was done by independent t-test and P < 0.05 will be considered to be a statistically significant difference. Results: Sixty-seven-point three per cent use the internet for health-related information. Most of the patients felt satisfied with their medical care but there was still some scope of improvement in the domains of communication and the time devoted by the doctor to the patient. The overall level of patient satisfaction was above average. Our study also showed that 77.2% of the study participants had a good relationship with their doctor. Conclusion: In our study, we found that the internet using study participants were found to have an above average satisfaction with their doctors.

Health equity is defined as the sixth domain of healthcare quality. Understanding health disparities in acute care surgery (defined as trauma surgery, emergency general surgery and surgical critical care) is key to identifying targets that will improve outcomes and ensure delivery of high-quality care within healthcare organizations. Implementing a health equity framework within institutions such that local acute care surgeons can ensure equity is a component of quality is imperative. Recognizing this need, the AAST (American Association for the Surgery of Trauma) Diversity, Equity and Inclusion Committee convened an expert panel entitled ‘Quality Care is Equitable Care’ at the 81st annual meeting in September 2022 (Chicago, Illinois). Recommendations for introducing health equity metrics within health systems include: (1) capturing patient outcome data including patient experience data by race, ethnicity, language, sexual orientation, and gender identity; (2) ensuring cultural competency (eg, availability of language services; identifying sources of bias or inequities); (3) prioritizing health literacy; and (4) measuring disease-specific disparities such that targeted interventions are developed and implemented. A stepwise approach is outlined to include health equity as an organizational quality indicator.

Diacetylcurcumin manganese complex (DiAc-Cp-Mn) is a diacetylcurcumin (DiAc-Cp) derivative synthesized with Mn (II) to mimic superoxide dismutase (SOD). It exhibited superior reactive oxygen species (ROS) scavenging efficacy, particularly for the superoxide radical. The present study investigated the ROS scavenging activity, neuroprotective effects, and underlying mechanism of action of DiAc-Cp-Mn in a cellular model of Parkinson’s disease. This study utilized rotenone-induced neurotoxicity in SH-SY5Y cells to assess the activities of DiAc-Cp-Mn by measuring cell viability, intracellular ROS, mitochondrial membrane potential (MMP), SOD, and catalase (CAT) activities. The mRNA expression of the nuclear factor erythroid 2 p45-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), inducible nitric oxide synthase (iNOS), and Interleukin 1β (IL-1β), which are oxidative and inflammatory genes, were also evaluated to clarify the molecular mechanism. The results of the in vitro assays showed that DiAc-Cp-Mn exhibited greater scavenging activity against superoxide radicals, hydrogen peroxide, and hydroxyl radicals compared to DiAc-Cp. In cell-based assays, DiAc-Cp-Mn demonstrated greater neuroprotective effects against rotenone-induced neurotoxicity when compared to its parent compound, DiAc-Cp. DiAc-Cp-Mn maintained MMP levels, reduced intracellular ROS levels, and increased the activities of SOD and CAT by activating the Nrf2-Keap1 signaling pathway. In addition, DiAc-Cp-Mn exerted its anti-inflammatory impact by down-regulating the mRNA expression of iNOS and IL-1β that provoked neuro-inflammation. The current study indicates that DiAc-Cp-Mn protects against rotenone-induced neuronal damage by reducing oxidative stress and inflammation.

The current work focuses on using rectangular inserts with water as the working fluid to investigate heat transfer experimentally and numerically in a horizontal circular tube [10]. The study considers variations in the number of rectangular slots within the same strip. The tube has dimensions of 0.0266 m diameter. Twisted tapes, featuring rectangular cuts, are constructed from a 3 mm thick Stainless-steel strip with a length of 1035 mm. For experimentation, two different types of rectangular inserts were considered: one with nine cuts and the other with eighteen cuts. The dimensions of the cuts were as follows: length of 1000 mm, width of 13 mm, depth of cut 8 mm, and thickness 3 mm. The heat flux applied to the horizontal tube was steady and uniform. The range of the Reynolds number was 9,000–19,000. A plain tube without an insert was used to compare the results. The horizontal tube along with rectangular insert was modelled in Ansys Fluent software with fine meshing and analysed. Initially, CFD analysis was done for plain tube with and without insert, and results have been verified by comparison with experimental values. A comprehensive comparison is established, evaluating different heat transfer parameters, including convective heat transfer coefficient (h), heat transfer rate (q), and Nusselt number (Nu).

The transition to sustainable urban mobility solutions is imperative in the face of escalating environmental and health challenges. This paper reviews the work in the areas of decarbonizing power systems, urban mobility and transportation modes, and the integration of renewable energy in smart cities. The integration of renewable energy sources, such as wind and solar power, into power systems is pivotal for decarbonization. However, their intermittent nature poses challenges for high-level integration. Energy storage emerges as a crucial solution, with technologies like fuel cell vehicles, water electrolysis, and flow batteries playing significant roles. Urban mobility, dominated by internal combustion engines, has led to environmental degradation and health issues. Transitioning to cleaner transportation modes, integrating electric vehicle stations with renewable energy, and ensuring uninterrupted power supply are essential steps forward. Furthermore, the potential of smart cities harnessing non-dispatchable photovoltaic and wind power is vast. Yet, the challenge of large-scale energy storage remains. The concept of using renewable energy to produce hydrogen, which can then stabilize the grid, offers a promising avenue. This review underscores the importance of integrating hydrogen energy storage to revolutionize urban mobility solutions.

The present study explores the diversity and ecology of freshwater diatom in the Kanyakumari district, Tamilnadu. Six freshwater ponds namely, Thuckalay pond, Eraniel pond, Pampanvilai pond, Villukuri pond, Erachakulam and Thottiyodu pond were selected from Kalkulam Taluk in Kanyakumari district. A total of 27 taxa of 17 genera were recorded from these freshwater ponds. Among the freshwater diatom species, Gomphonema montanum was found to be the predominant species in all stations except St- 2. The correlation analysis between diatom density and physico-chemical parameters revealed a significant positive correlation of diatoms (Nitzschia sp., Navicula sp., Cyclotella meneghiniana and Stauroneis sp) with nitrate, phosphate and lead at sampling statins St- 2 and 6. CCA analysis revealed that the concentration of calcium, chloride, pH, alkalinity, silica, and ammonia were found to favor the occurrence of dominant species such as Cymbella turgiduta, Gomphonema sp., Rhopalodia sp., in St-3 and St-4. Among all ponds, certain parameters like total alkalinity, nitrite, phosphate, sodium, cobalt, potassium perhaps reflect the influence of agricultural waste, sewage waste, or anthropogenic activities. The statistical indices in coherence with the dominance of pollution indicator species such as Nitzschia palea, Melosira granulata and Cyclotella meneghiniana revealed that the stations St-2, 4 and 6 were heavily polluted, whereas St- 1, 3 and 5 were less polluted.

Abstract Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves’ disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12–24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health. Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.

Abstract Marine wastes pose a great threat to the ecosystem leading to severe environmental hazards and health issues particularly the shellfish wastes. The shellfish waste which contains half of the amount of chitin can be efficiently transformed into useful products. Various approaches for the hydrolysis of chitin like physical, chemical, and enzymatic processes are there. Still, the use of enzyme chitinase is well documented as an effective and eco-friendly method. The present study summarizes the isolation of chitinase enzyme producing bacteria from different shrimp waste disposal sites in Parangipettai (India), and the possible use of an enzyme hydrolyzate as an immunostimulant to Asian Seabass (Lates calcarifer). The potential chitinase-producing bacteria were identified by 16S rRNA gene sequencing as Stenotrophomonas maltophilia. After purification, the chitinase specific activity was 5.01 (U/ml) and the protein content was 72 mg and the recovery rate was 48.06%. The optimum pH and temperature for the chitinolytic activity were 6.5 and at 35–50 °C, respectively. The animal experiment trial was done with our feed supplements which included 0.0 (control), 0.5%, 1% and 2% of chitin degraded product. All the supplementary feed had an optimal 42% (w/w) of crude protein. The feed protein level was 41–43% on average and gross energy was 13–17 kcal/g and the feed was observed to exhibit a significantly higher (p

Major depressive disorder (MDD) is one life-threatening disorder that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Currently, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, could have an antidepressive property. An in vitro monoamine oxidase-A (MAO-A) inhibitory assay was used to preliminarily screening for the antidepressant effect of O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks, and the daily administration of OIS extract started from week 4. The mechanisms involved in the antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in the UCMS-induced mouse model via two possible pathways: (i) it normalized the HPA axis function via the restoration of negative feedback (decreased FKBP5 and increased GR expressions) and the reduction in the glucocorticoid-related negative gene (SGK-1), and (ii) it improved neurogenesis via the escalation of BDNF and CREB expressions in the hippocampus and the frontal cortex. In addition, an HPLC analysis of the OIS extract showed the presence of baicalin, baicalein, and chrysin as major constituents. All of the results obtained from this study emphasize the potential of OIS extract containing baicalin and baicalein as an effective and novel alternative treatment for MDD.

Mathematical modeling and analysis of biologically inspired systems has been a fascinating research topic in recent years. In this work, we present the results obtained from the simulation of an elastic rod (that mimics a flagellum axoneme) rotational motion in a viscous fluid by using the lattice Boltzmann method (LBM) combined with an immersed boundary method (IBM). A finite element model consists of a set of beam and truss elements used to discretize the flagellum axoneme while the fluid flow is solved by the well-known LBM. The hydrodynamic coupling to maintain the no-slip boundary condition between the fluid and the elastic rod is conducted with the IBM. The rod is actuated with a torque applied at its base cross-section that acts as a driving motor of the axoneme. We simulated the rotational dynamics of the rod for three different rotational frequencies (low, medium, and high) of the motor. To compare with previous publication results, we chose the sperm number Sp=L(4πμω)/(EI)1/4 as the validation parameter. We found that at the low rotational frequency, f = 1.5 Hz, the rod performs stable twirling motion after attaining an equilibrium state (the rod undergoes rigid rotation about its axis). At the medium frequency, f = 2.65 Hz, the rod undergoes whirling motion, where the tip of the rod rotates about the central rotational axis of the driving motor. When the frequency increases further, i.e., when it reaches the critical value, fc ≈ 2.7 Hz, the whirling motion becomes over-whirling, where the tip of the filament falls back to the base and performs a steady crank-shafting motion. All three rotational dynamics, twirling, whirling, and over-whirling, and the critical value of rotational frequency are in good agreement with the previously published results. We also observed that our present simulation technique is computationally more efficient than previous works.

A Bayesian inference formulation is applied to the Resin Transfer Moulding process to estimate bulk permeability and race-tracking effects using measured values of pressure at discrete sensor locations throughout a preform. The algorithm quantifies uncertainty in both the permeability and race-tracking effects, which decreases when more sensors are used or the preform geometry is less complex. We show that this approach becomes less reliable with a smaller resin exit vent. Numerical experiments show that the formulation can accurately predict race-tracking effects with few measurements. A Bayesian A-optimality formulation is used to develop a method for producing optimal sensor locations that reduce the uncertainty in the permeability and race-tracking estimates the most. This method is applied to two numerical examples which show that optimal designs reduce uncertainty by up to an order of magnitude compared to a random design.

Background: Despite advances in hypertension care, developing countries have a high burden of uncontrolled blood pressure (BP). The Government of Tamil Nadu, India, initiated a noncommunicable disease program to improve hypertension management in public facilities. Method: We conducted cross-sectional surveys at baseline and follow-up to evaluate BP control after a multipronged intervention among patients with hypertension visiting public health facilities in Tamil Nadu. The intervention included protocol-based hypertension treatment, lifestyle counseling and monitoring by trained nurses, alongside monthly free drug refills. Descriptive statistics and adjusted odds ratio (AOR) for BP control were analyzed. Results: We surveyed 923 patients at baseline and 941 at follow-up. Most patients were over 60 years of age, with female predominance. Proportion of patients dispensed drugs for 30 days increased at follow-up (84.5%) compared to baseline (11.4%) (P < 0.01). Proportion of patients with BP control was 32.4% at baseline and 40.5% at follow-up (P < 0.001). AOR for BP control at follow-up was 1.4 (95% confidence interval 1.1–1.7, P < 0.05) after adjusting for age, sex, type of facility, and the number of drugs. Conclusion: Focussing on accessibility, availability, and affordability, the program facilitated the provision of free drugs and counseling, resulting in optimal BP control. Encouraging physician adherence to protocols and task sharing with nurses can help streamline sustainable hypertension management.

Abstract Background Life-threatening invasive fungal infections are treated with antifungal drugs such as Amphotericin B (AmB) loaded liposomes. Our goal herein was to show that targeting liposomal AmB to fungal cells with the C-type lectin pathogen recognition receptor DC-SIGN improves antifungal activity. DC-SIGN binds variously crosslinked mannose-rich and fucosylated glycans and lipomannans that are expressed by helminth, protist, fungal, bacterial and viral pathogens including three of the most life-threatening fungi, Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. Ligand recognition by human DC-SIGN is provided by a carbohydrate recognition domain (CRD) linked to the membrane transit and signaling sequences. Different combinations of the eight neck repeats (NR1 to NR8) expressed in different protein isoforms may alter the orientation of the CRD to enhance its binding to different glycans. Results We prepared two recombinant isoforms combining the CRD with NR1 and NR2 in isoform DCS12 and with NR7 and NR8 in isoform DCS78 and coupled them to a lipid carrier. These constructs were inserted into the membrane of pegylated AmB loaded liposomes AmB-LLs to produce DCS12-AmB-LLs and DCS78-AmB-LLs. Relative to AmB-LLs and Bovine Serum Albumin coated BSA-AmB-LLs, DCS12-AmB-LLs and DCS78-AmB-LLs bound more efficiently to the exopolysaccharide matrices produced by A. fumigatus, C. albicans and C. neoformans in vitro, with DCS12-AmB-LLs performing better than DCS78-AmB-LLs. DCS12-AmB-LLs inhibited and/or killed all three species in vitro significantly better than AmB-LLs or BSA-AmB-LLs. In mouse models of invasive candidiasis and pulmonary aspergillosis, one low dose of DCS12-AmB-LLs significantly reduced the fungal burden in the kidneys and lungs, respectively, several-fold relative to AmB-LLs. Conclusions DC-SIGN’s CRD specifically targeted antifungal liposomes to three highly evolutionarily diverse pathogenic fungi and enhanced the antifungal efficacy of liposomal AmB both in vitro and in vivo. Targeting significantly reduced the effective dose of antifungal drug, which may reduce drug toxicity, be effective in overcoming dose dependent drug resistance, and more effectively kill persister cells. In addition to fungi, DC-SIGN targeting of liposomal packaged anti-infectives have the potential to alter treatment paradigms for a wide variety of pathogens from different kingdoms including protozoans, helminths, bacteria, and viruses which express its cognate ligands.

PURPOSEThere are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 (BRCA1/BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features.METHODSThis prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/BRCA2 mutations, and the secondary objective was to correlate BRCA1/BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay.RESULTSBetween March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively.CONCLUSIONThere is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.