Browse Articles
Discover research articles across all indexed journals
In vitro and in silico analyses of amino acid substitution effects at the conserved N-linked glycosylation site in hepatitis B virus surface protein on antigenicity, immunogenicity, HBV replication and secretion
The "a" determinant, a highly conformational region within the hepatitis B virus large surface protein (LHBs), is crucial for antibody neutralization and diagnostic assays. Mutations in this area can lead to conformational changes, resulting in vaccination failure, diagnostic evasion, and disease progression. The "a" determinant of LHBs contains a conserved N-linked glycosylation site at N320, but the mechanisms of glycosylation in LHBs remain unclear. This study aimed to investigate the impact of amino acid substitutions at N320 on antigenicity, three-dimensional (3D) structures of LHBs, immunogenic epitopes, and HBV DNA levels. LHBs were mutated by substituting asparagine 320 with proline, cysteine, lysine, and glutamine. The reactivity of the mutants with antibodies was evaluated by western blotting and immunofluorescence staining. Results showed increased binding affinity in N320C, N320Q, and particularly N320P mutants compared to the wild type, likely attributed to conformational changes predicted by the I-TASSER server and further refined by the GalaxyRefine server. Analysis conducted using the IEDB server indicated that the N320P mutation increased the antigenic index, whereas the N320C mutation significantly decreased it. Conversely, the N320K and N320Q mutations exhibited minor effects on antigenicity. Our observations also identified N320P as a potential B-cell epitope and a binding epitope for MHC-I (T-cell epitope). Furthermore, mutating the conserved N-linked glycosylation site at position N320 to proline significantly increased the secretion of HBV DNA in virions. This study enhances our understanding of the impact of a single amino acid mutation at N320 on antibody interaction, LHBs conformation, immunogenicity, and HBV DNA replication. These insights hold promise for advancements in HBsAg detection and the development of vaccines against hepatitis B virus.
LBNP: Learning features between neighboring points for point cloud classification
Inspired by classical works, when constructing local relationships in point clouds, there is always a geometric description of the central point and its neighboring points. However, the basic geometric representation of the central point and its neighborhood is insufficient. Drawing inspiration from local binary pattern algorithms used in image processing, we propose a novel method for representing point cloud neighborhoods, which we call Point Cloud Local Auxiliary Block (PLAB). This module explores useful neighborhood features by learning the relationships between neighboring points, thereby enhancing the learning capability of the model. In addition, we propose a pure Transformer structure that takes into account both local and global features, called Dual Attention Layer (DAL), which enables the network to learn valuable global features as well as local features in the aggregated feature space. Experimental results show that our method performs well on both coarse- and fine-grained point cloud datasets. We will publish the code and all experimental training logs on GitHub.
An E-Delphi study to facilitate animal welfare assessment in Italian zoos and aquaria
Ensuring animal welfare is a key aspect of animal management in zoological facilities and aquaria, representing a pivotal facet of their mission. Italy currently lacks a comprehensive and valuable assessment methodology for evaluating the welfare of captive animals. To address this gap, the present study aimed to identify the most important criteria that should be considered in the welfare management and assessment of animals housed in Italian zoos and aquaria. To pinpoint this issue, we engaged experts with diverse backgrounds, structuring their communication throughout an iterative process, by applying the Delphi methodology. A pilot and three Delphi rounds were administered online to 74 experts, asking them to a) validate relevant topics derived from current legislation and guidelines divided into three clusters: Care, Wellbeing, and Regulation; b) assess the relevance of these topics across taxonomic groups; c) propose and confirm indicators for each identified topic; d) suggest and refine a list of questions for animal welfare assessment. The results were three lists of questions, one for each cluster, with a total of 80 topics, 174 indicators, and 272 questions identified by the experts. The aspects included in these lists offer valuable insights into the main aspects experts consider relevant for captive animal welfare. Despite the complexity of animal welfare and the huge amount of species hosted in zoos limiting the possibility to cover this aspect with a single expert consultation, this project actively addresses the urgent need for standardization in animal welfare assessment, contributing to the ongoing development of zoological regulations in Italy. This is especially important given the current limited legislative framework, underscoring the link between animal welfare and successful ex-situ species conservation. These questions can be the basis of fine-tuned protocols to be tested in future projects aiming at animal welfare self-assessment, thus supporting authority inspection processes.
Designing of an mRNA vaccine against high-risk human papillomavirus targeting the E6 and E7 oncoproteins exploiting immunoinformatics and dynamic simulation
Human papillomavirus 16 and human papillomavirus 18 have been associated with different life-threatening cancers, including cervical, lung, penal, vulval, vaginal, anal, and oropharyngeal cancers, while cervical cancer is the most prominent one. Several research studies have suggested that the oncoproteins E6 and E7 are the leading cause of cancers associated with the human papillomavirus infection. Therefore, we developed two mRNA vaccines (V1 and V2) targeting these oncoproteins. We used several bioinformatics tools to predict helper T lymphocyte, cytotoxic T lymphocyte, and B-cell epitopes derived from the proteins and assessed their antigenicity, allergenicity, and toxicity. Both vaccines were constructed using selected epitopes, linkers, and adjuvants. After that, the vaccines were applied for physicochemical properties, secondary and tertiary structure predictions, and subsequent docking and simulation analyses. Accordingly, vaccine 1 (V1) and vaccine 2 (V2) showed better hydrophilicity with the grand average hydropathicity score of -0.811 and -0.648, respectively. The secondary and tertiary structures of the vaccines were also deemed satisfactory, with high stability indicated by the Ramachandran plot (V1:94.5% and V2:87.1%) and Z scores (V1: -5.15 and V2: -4.1). Docking analysis revealed substantial affinity of the vaccines towards the toll-like receptor-2 (V1: -1159.3, V2: -1246.3) and toll-like receptor-4 (V1: -1109.3, V2: -1244.8) receptors. Molecular dynamic simulation validated structural integrity and indicated varying stability throughout the simulation. Codon optimization showed significant expression of the vaccines (V1:51.88% and V2:51.63%) in E. coli vectors. Furthermore, regarding immune stimulation, the vaccines elicited significant B-cell and T-cell responses, including sustained adaptive and innate immune responses. Finally, thermodynamic predictions indicated stable mRNA structures of the vaccines (V1: -502.60 kcal/mol and V2: -450.90 kcal/mol). The proposed vaccines designed effectively targeting human papillomavirus oncoproteins have demonstrated promising results via robust immune responses, suggesting their suitability for further clinical advancement, including in vitro and in vivo experiments.
Cross-sectional study of lung cancer patients as a potential high-risk factor for abdominal aortic aneurysm
Background Abdominal aortic aneurysm (AAA) is more common in Non-small cell lung cancer (NSCLC) patients. Considering that ruptured AAA is potentially fatal, timely management of AAA would result in long-term survival benefits. We assess the prevalence and characteristics of AAA in resectable NSCLC patients who would benefit from AAA surveillance. Methods 1,019 resectable NSCLC patients in Severance and Kangbuk Samsung Hospitals were reviewed from January 2019 to November 2020. The control group comprised 2,899 cancer-free people who had a health check-up CT scan in Severance between January 2018 and December 2019. Results Among resectable primary NSCLC patients, 39/1,019 (3.8%; odds ratio [OR], 19.19; 95% confidence interval [CI], 8.10–46.46) had AAA compared with 6/2,899 (0.2%) in the control (P<0.001). In multivariable regression analysis, male (OR, 13.24; 95% CI, 1.50–117.48; P = 0.020), aging (OR, 1.10; 95% CI, 1.04–1.15; P<0.001), current smoker (OR, 4.20; 95% CI, 1.20–14.62; P = 0.024), and coronary artery disease (OR, 3.13; 95% CI, 1.48–6.62; P = 0.003) were independent risk factors for AAA in NSCLC. Conclusion The present study found that the incidence of AAA in resectable early-stage lung cancer patients was significantly higher than in the cancer-free control group. Therefore, we suggest that early-stage NSCLC patients, especially smokers older than 60 years, undergo regular AAA surveillance as part of their lung cancer monitoring.
Insights into the progressive impact of high-fat-diet induced insulin resistance on skeletal muscle and myocardium: A comprehensive study on C57BL6 mice
This study aims to provide a theoretical foundation for the future management of diabetes at various stages induced by a high-fat diet. Specifically, it seeks to determine the appropriate pharmacological interventions for each phase of diabetes development and the targeted therapeutic directions at different stages of diabetes progression. This investigation employed C57BL6 mice as experimental subjects, successfully establishing an insulin resistance model through a 12-week high-fat diet. Clinical manifestations, weight, body composition, and overall health of each mouse group were observed on the first day of the 6th, 8th, 10th, and 12th week of high-fat feeding to analyze insulin resistance. Subsequently, open-field test of each mouse group, and histopathological changes in the skeletal muscle and myocardium of each mouse group, along with the detection of protein-level expression of relevant genes, were performed to assess alterations in mitochondrial energy metabolism during insulin resistance. This endeavor aims to contribute insights for future in-depth veterinary research. The outcomes demonstrated that a continuous 12-week high-fat diet successfully induced stable insulin resistance in C57BL6 mice. Following insulin resistance, the motor activity of mice decreased, gradual pathological damage and functional decline were observed in the skeletal muscle and myocardium. The insulin signaling pathway was inhibited, resulting in reduced glucose transport and increased gluconeogenesis. Additionally, mitochondrial dysfunction manifested as diminished ATP synthesis capacity, weakened mitochondrial biogenesis, reduced mitochondrial fusion, increased division, and diminished autophagy. Notably, during insulin resistance progression, skeletal muscles and myocardium in C57BL6 mice predominantly relied on glycolytic pathways for energy supply. In the early stages of insulin resistance, the glycogen synthesis pathway in C57BL6 mouse skeletal muscles was inhibited. Our findings underscore a distinct mechanism in skeletal muscle and myocardium that ensures the utilization of anaerobic fermentation to meet energy demands in instances of inadequate aerobic respiration (Fig 1).
Cost-effectiveness of the SMILE intervention compared with usual care for people with severe mental illness: A randomized clinical trial
Objectives Only studying effectiveness of lifestyle interventions for people with severe mental illness (SMI) is insufficient for policy making. As budgets for healthcare are limited, policy makers face the problem of allocating scarce healthcare resources. Cost-effectiveness studies are needed, but currently cost-effectiveness studies of lifestyle interventions for people with SMI delivered in ambulatory care are limited. The aim of this current study was to evaluate the cost-effectiveness of a lifestyle intervention for people with SMI living in the Dutch community in comparison with usual care. Methods and findings An economic evaluation was performed using a societal perspective alongside the Severe Mental Illness Lifestyle Evaluation (SMILE) pragmatic cluster randomized controlled trial. The SMILE lifestyle intervention is a one-year, group-based intervention delivered by trained mental healthcare workers. Costs, body weight change and quality of life were assessed at baseline, 6 and 12 months. Mixed models were used to estimate incremental costs and effects between the treatment group and the usual care group. Overall, the SMILE intervention resulted in lower total costs compared to the usual care group (-€719, 95% CI -7133; 3897). The effect difference between the intervention and usual care groups was -3.76 (95% CI -6.30; -1.23) kilograms for body weight and -0.037 (95% CI -0.083; 0.010) for QALYs. Conclusions Overall, the SMILE intervention resulted in lower total costs compared to the usual care group and was cost-effective for body weight change. However, the SMILE intervention does not seem cost-effective with regards to QALYs. More cost-effectiveness studies in other countries and other settings are needed to gain further insight into the cost-effectiveness of lifestyle interventions for people with SMI.
Age-related variations in physical activity, happiness, and psychological well-being: Evidence from Iran
Background Physical activity (PA) is associated with higher levels of PWB and happiness. The high prevalence of physical inactivity among the Iranian population is concerning. Moreover, according to the Happiness Report 2024, Iran is ranked 100th out of 143 countries. Thus, this research aimed to study the PWB, happiness, and PA in Iranian age groups. Methods The study sampled 1,050 participants, equally divided into young, middle-aged, and elderly groups, using randomized cluster sampling from urban areas across five geographic regions in Iran. The study utilized four questionnaires: a Demographic Information Questionnaire, the International Physical Activity Questionnaire (IPAQ), Ryff’s Scales of PWB (18-item form), and the Oxford Happiness Questionnaire (OHQ). Descriptive statistics were used for summarizing data, and inferential analyses included Pearson’s correlation coefficient, one-way ANOVA, the Bonferroni test, and multivariate regression, all with a significance level set at P<0.05. Results Middle-aged individuals had the highest PA (1015.69±730.63 MET-minutes per week) and reported the highest happiness (111.97±24.08) and PWB (63.75±11.17) levels. The elderly had the lowest levels of PA (677.78±592.50 MET-minutes per week), happiness (107.63±24.01), and PWB (60.05±10.02). Statistical tests showed significant differences in PA, happiness, and PWB between the age groups (P<0.05), with no significant difference between young and elderly in PA (P>0.05). Physical activity positively correlated with happiness and PWB, especially in the elderly. Multivariate regression revealed that PA significantly predicts happiness (F = 30.993, t = 6.96, B = 0.211) and PWB (F = 86.85, t = 9.32, B = 0.004), explaining 4.4% and 8.0% of their variances, respectively. Conclusions The study concludes that increasing PA enhances happiness and PWB. Practical applications include promoting PA to improve mental health and PWB. Future research should investigate the effects of specific types of PA and explore longitudinal impacts on PWB to provide a deeper understanding of these relationships.
Research on quantitative evaluation of medical insurance fraud supervision policy based on ‘Antecedents-Process-Outcomes’ framework
Fraud in medical insurance is a serious problem that threatens the safety and sustainability of medical insurance funds. The process of reducing or even eliminating the impact of fraud is related to maintaining the balance of payments for medical insurance funds and reforming the payment system based on total amount control. As a result of reviewing the policy background of medical insurance fraud in China, combined with the policy evaluation model in the area of public management, this paper develops a conceptual framework of ’Antecedents-Process-Outcomes’ that emphasizes the fraud and governance of medical insurance funds. This paper uses grounded theory to look at 180 cases of medical insurance fraud and then uses the PMC index model to rate 18 policies. It then looks at the joint progressive analysis framework of medical insurance fraud and fraud supervision. In this paper, we analyze the policy similarities and differences of medical insurance fraud supervision in China from three perspectives: policy attributes, policy contents, and policy effects. The average PMC index of the 18 policies is 4.98, which is generally acceptable; however, there are some deficiencies in the policy field, policy supervision chain, policy orientation, and policy tools. Then, it puts forward suggestions for improving the four policy shortcomings in order to provide theoretical and practical enlightenment for the high-quality development of the medical security system and realize the new medical security in the process of Chinese-style modernization.
Expanding first-line options for depression: Protocol of a pragmatic comparative effectiveness trial of yoga vs. behavioral activation (the COMPARE study)
Depression is a prevalent mental health condition in the United States and a significant cause of morbidity and mortality. The treatment guidelines for depression recommends either psychotherapy, such as behavioral activation (BA), or a second-generation antidepressant as a first-line treatment for adult patients with depression. However, many individuals with depression do not experience improvement from first-line treatments or choose not to engage in them due to stigma, cost, difficulty with access, and/or side effects. As such we need new treatments for depression and yoga is especially promising given recent data on its efficacy for depression. This study seeks to compare a first-line treatment for depression, or BA, versus yoga to examine whether yoga does as well as BA at improving depressive symptoms and secondary outcomes. We will also examine improvements in depressive symptoms, and secondary outcomes, by specific sub-populations to determine who might do better in which treatment (i.e., BA or yoga). Given that this is the first non-inferior, comparative effectiveness study of yoga, this paper explains the study design, the rationale for the study design, as well as lessons learned in conducting the study.
GPT, ontology, and CAABAC: A tripartite personalized access control model anchored by compliance, context and attribute
As digital healthcare evolves, the security of electronic health records (EHR) becomes increasingly crucial. This study presents the GPT-Onto-CAABAC framework, integrating Generative Pretrained Transformer (GPT), medical-legal ontologies and Context-Aware Attribute-Based Access Control (CAABAC) to enhance EHR access security. Unlike traditional models, GPT-Onto-CAABAC dynamically interprets policies and adapts to changing healthcare and legal environments, offering customized access control solutions. Through empirical evaluation, this framework is shown to be effective in improving EHR security by accurately aligning access decisions with complex regulatory and situational requirements. The findings suggest its broader applicability in sectors where access control must meet stringent compliance and adaptability standards.
The MIR-NAT MAPT-AS1 does not regulate Tau expression in human neurons
The MAPT gene encodes Tau protein, a member of the large family of microtubule-associated proteins. Tau forms large insoluble aggregates that are toxic to neurons in several neurological disorders, and neurofibrillary Tau tangles represent a key pathological hallmark of Alzheimer’s disease (AD) and other tauopathies. Lowering Tau expression levels constitutes a potential treatment for AD but the mechanisms that regulate Tau expression at the transcriptional or translational level are not well understood. Natural antisense transcripts (NATs) are a particular class of long non-coding RNAs (lncRNAs) that can regulate expression of their overlapping protein-coding genes at the epigenetic, transcriptional, or translational level. We and others identified a long non-coding RNA associated with the MAPT gene, named MAPT antisense 1 (MAPT-AS1). We confirmed that MAPT-AS1 is expressed in neurons in human post mortem brain tissue. To study the role of MAPT-AS1 on MAPT expression regulation, we modulated the expression of this lncRNA in human neuroblastoma cell lines and in human induced pluripotent stem cell (iPSC) derived neurons. In contrast to previous reports, we observed no changes on MAPT mRNA or Tau protein levels upon modulation of MAPT-AS1 levels in these cellular models. Our data suggest that MAPT-AS1 does not regulate Tau expression levels in human neurons in vitro. Thus, MAPT-AS1 does not represent a valuable therapeutic target to lower Tau expression in patients affected by tauopathies including AD.
Mortality and predictors among HIV-TB co-infected patients in Ethiopia: A systematic review and meta-analysis
Background HIV-TB co-infection poses a significant public health threat, notably in sub-Saharan Africa including Ethiopia. Despite this public health problem, studies in Ethiopia regarding the mortality of HIV-TB co-infection patients have been inconsistent, and the overall estimate of mortality was not determined. Accordingly, this meta-analysis aims to assess the magnitude of mortality and predictors among HIV-TB co-infected patients in Ethiopia. Methods A search of the literature was conducted from three databases (PubMed, Global Index Medicus, and CINHAL), and other sources (Google Scholar, Google, Worldwide Science). All observational studies that reported the mortality of HIV-TB co-infected patients in Ethiopia were included. Joanna Briggs Institute’s (JBI) quality appraisal checklist was used to assess the quality of studies. Effect sizes were pooled using the random effects model. Heterogeneity was assessed using Cochrane Q and I2 test statistics, and the prediction interval was determined. Subgroup analysis was conducted by region. To examine the presence of an influential study, a sensitivity analysis was done. Egger’s test was used to check publication bias. A non-parametric trim and fill analysis was carried out. Results A total of 886 studies were identified, using database searches and keywords. Of these, 37 met the criteria for inclusion. The pooled proportion of mortality among HIV-TB co-infected patients was found to be 18.42% (95% CI:14.27–22.57). In the subgroup analysis, the highest mortality was observed in the Tigray region at 31.86% (95% CI: 7.69–56.03), and the lowest mortality was reported in two general studies in Ethiopia 11.95 (95% CI: 4.19–19.00). From the examined 20 predictors, only four predictors such as Anaemia (HR = 2.25, 95% CI: 1.65–3.07), Poor adherence to ART (HR = 2.42, 95% CI: 1.39–4.21), not taking co-trimoxazole preventive therapy (HR = 1.87, 95% CI: 1.28–2.73), and extrapulmonary tuberculosis (HR = 1.23, 95% CI: 1.01–1.51) were significant predictors. Conclusions In Ethiopia, 18.42% of HIV-TB co-infected patients died. Anaemia, poor adherence, not taking CPT, and extrapulmonary tuberculosis were found to be significant predictors. Hence, the concerned stakeholders need to expand and strengthen the HIV-TB collaborative services and attention should be given to patients presented with the aforementioned predictors. Trial registration This meta-analysis has been registered in PROSPERO with registration number CRD42023466558.
Using deep learning to shorten the acquisition time of brain MRI in acute ischemic stroke: Synthetic T2W images generated from b0 images
Objective This study aimed to assess the feasibility of the deep learning in generating T2 weighted (T2W) images from diffusion-weighted imaging b0 images. Materials and methods This retrospective study included 53 patients who underwent head magnetic resonance imaging between September 1 and September 4, 2023. Each b0 image was matched with a corresponding T2-weighted image. A total of 954 pairs of images were divided into a training set with 763 pairs and a test set with 191 pairs. The Hybrid-Fusion Network (Hi-Net) and pix2pix algorithms were employed to synthesize T2W (sT2W) images from b0 images. The quality of the sT2W images was evaluated using three quantitative indicators: Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Normalized Mean Squared Error (NMSE). Subsequently, two radiologists were required to determine the authenticity of (s)T2W images and further scored the visual quality of sT2W images in the test set using a five-point Likert scale. The overall quality score, anatomical sharpness, tissue contrast and homogeneity were used to reflect the quality of the images at the level of overall and focal parts. Results The indicators of pix2pix algorithm in test set were as follows: PSNR, 20.549±1.916; SSIM, 0.702±0.0864; NMSE, 0.239±0.150. The indicators of Hi-Net algorithm were as follows: PSNR, 20.646 ± 2.194; SSIM, 0.722 ± 0.0955; NMSE, 0.469 ± 0.124. Hi-Net performs better than pix2pix, so the sT2W images obtained by Hi-Net were used for radiologist assessment. The two readers accurately identified the nature of the images at rates of 69.90% and 71.20%, respectively. The synthetic images were falsely identified as real at rates of 57.6% and 57.1%, respectively. The overall quality score, sharpness, tissue contrast, and image homogeneity of the sT2Ws images ranged between 1.63 ± 0.79 and 4.45 ± 0.88. Specifically, the quality of the brain parenchyma, skull and scalp, and middle ear region was superior, while the quality of the orbit and paranasal sinus region was not good enough. Conclusion The Hi-Net is able to generate sT2WIs from low-resolution b0 images, with a better performance than pix2pix. It can therefore help identify incidental lesion through providing additional information, and demonstrates the potential to shorten the acquisition time of brain MRI during acute ischemic stroke imaging.
High glucose couples DJ-1 with PTEN to activate PDGFRβ for renal proximal tubular cell injury
High glucose milieu in diabetes induces proximal tubular epithelial cells in the kidney to undergo hypertrophy and matrix protein expansion via Akt/mTORC1 signaling, leading to renal fibrosis. The familial Parkinson’s disease protein DJ-1 acts as a driver of Ras-dependent tumorigenesis and protects dopaminergic neurons from apoptosis. But its function and mechanistic basis to regulate renal fibrosis is not clear. Here, we identify DJ-1 as a high glucose-promoted protein in renal proximal tubular epithelial cells. Mechanistic interrogation revealed that DJ-1 formed complex with the lipid phosphatase PTEN in high glucose-stimulated cells, resulting in phosphorylation/activation of Akt and mTORC1. siRNAs against DJ-1 decreased high glucose-stimulated Akt/mTORC1 activation. In contrast, overexpression of DJ-1 mimicked all effects of high glucose. Interestingly, inhibition of DJ-1 blocked high glucose-induced hypertrophy of proximal tubular epithelial cells and, matrix proteins fibronectin and collagen I (α2) expression while overexpression of DJ-1 mimicked the high glucose effects on these phenomena. Previously, we reported a role of PDGFRβ in proximal tubular cell injury. In exploring the mechanism of DJ-1 function, we found that siDJ-1 inhibited high glucose-induced activating and PI 3 kinase docking site tyrosine phosphorylation of PDGF receptor-β (PDGFRβ) to block phosphorylation of PI 3 kinase. Interestingly, overexpression of PTEN mimicked these effects of siDJ-1. Together, our results reveal an important role of DJ-1-PTEN nodal point for PDGFRβ activation during high glucose-induced proximal tubular epithelial cell injury.
A retrospective comparative study of the clinical and radiological outcomes of intertrochanteric fractures treated with proximal femoral nail antirotation (PFN-A) and INTERTAN nail
Background This study aimed to analyze the files of patients treated using PFN-A or INTERTAN intramedullary nails to reveal additional superiorities or disadvantageous factors for selecting the better intramedullary fixation method in patients presenting with intertrochanteric femur fractures. Methods In this retrospective study, the files of the patients who were operated on for intertrochanteric femur fractures using intramedullary fixation methods between September 2010 and June 2015 in the Orthopedics and Traumatology Clinic, Çukurova University Faculty of Medicine, were reviewed. The data including age, gender, chronic diseases, causes of fractures, fracture classification based on Arbeitsgemeinschaft für Osteosynthesefragen (AO), the nail type (long or short), the interval between trauma and surgery, duration of anesthesia and surgery, hospitalization duration, amount of blood transfusion, the Tip-Apex Distance (TAD) in postoperative radiographs, functional outcomes according to Harris Hip Score (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), postoperative complications, need for revision, and mortality was noted. The data of the follow-up visits included physical examination findings in addition to the radiological assessment findings obtained using X-ray imaging involving the evaluation of the union in terms of the presence of infection, loss of reduction, implant failure, avascular necrosis, additional signs related to poor union formation, and the position data of the lag screw placement point according to Cleveland and Bosworth Quadrants. Results The records showed that 194 files were available for analysis. The mean age of the patients included in the study was 70.9±16.4 years; 100 patients (51.5%) were male, and 94 (48.5%) were female. There were 76 patients (39%) in the PFN-A group and 118 patients (61%) in the INTERTAN group. Analysis of the mean Harris Hip Scores in both nail groups showed that only the mean scores at the 1st follow-up were statistically significantly different (P = 0.025). Conclusion In conclusion, comparing the two nail types in terms of complication rates and clinical data, neither nail has proven superior to the other. Moreover, the temporary difference in the first follow-up HHS scores should not be considered an indicator of the overall functional outcome because long-term follow-up HHS scores did not differ.
Unveiling endothelial cell border heterogeneity: VE-cadherin adherens junction stratification by deep convolutional neural networks
Background Systemic diseases are often associated with endothelial cell (EC) dysfunction. A key function of ECs is to maintain the barrier between the blood and the interstitial space. The integrity of the endothelial cell barrier is maintained by VE-Cadherin homophilic interactions between adjacent cells. The morphology of these borders is highly dynamic and can be actively remodeled by numerous drivers in a (patho)physiologic context specific fashion. Objectives High-content screening of the impact of circulatory factors on the morphology of VE-Cadherin borders in endothelial monolayers in vitro will enable the assessment of the progression of systemic vascular disease. We therefore aimed to create an image analysis pipeline, capable of automatically analyzing images from large scale screenings, both capturing all VE-cadherin phenotypes present in a sample while preserving the higher-level 2D structure. Our pipeline is aimed at creating 1D tensor representations of the VE-cadherin adherence junction structure and negate the need for normalization. Method An image analysis pipeline, with at the center a convolution neural network was developed. The deep neural network was trained using examples of distinct VE-Cadherin morphologies from many experiments. The generalizability of the model was extensively tested in independent experiments, before further validation using ECs exposed ex vivo to plasma from patients with liver cirrhosis and proven vascular complications. Results Our workflow was able to detect and stratify many of the different VE-Cadherin morphologies present within the datasets and produced similar results within independent experiments, proving the generality of the model. Finally, by EC-cell border morphology profiling, our pipeline enabled the stratification of liver cirrhosis patients and associated patient-specific morphological cell border changes to responses elicited by known inflammatory factors. Conclusion We developed an image analysis pipeline, capable of intuitively and robustly stratifying all VE-Cadherin morphologies within a sample. Subsequent VE-Cadherin morphological profiles can be used to compare between stimuli, small molecule screenings, or assess disease progression.
Bifurcation analysis of an influenza A (H1N1) model with treatment and vaccination
This research uses numerical simulations and mathematical theories to simulate and analyze the spread of the influenza virus. The existence, uniqueness, positivity, and boundedness of the solution are established. We investigate the fundamental reproduction number guaranteeing the asymptotic stability of equilibrium points that are endemic and disease-free. We also examine the qualitative behavior of the models. Using the Lyapunov method, Routh-Hurwitz, and other criteria, we explore the local and global stability of these states and present our findings graphically. Our research assesses control policies and proposes alternatives, performing bifurcation analyses to establish prevention strategies. We investigate transcritical, Hopf, and backward bifurcations analytically and numerically to demonstrate disease transmission dynamics, which is novel to our study. Contour plots, box plots, and phase portraits highlight key characteristics for controlling epidemics. The disease’s persistence depends on its fundamental reproduction quantity. To validate our outcomes, we fit the model to clinical data from influenza cases in Mexico and Colombia (October 1, 2020, to March 31, 2023), aiming to analyze trends, identify critical factors, and forecast influenza trajectories at national levels. Additionally, we assess the efficacy of implemented control policies.
Barriers and missed opportunities in PrEP uptake, use and care among men who have sex with men with recent HIV infection in the Netherlands
Introduction Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis. We aimed to identify barriers and missed opportunities in PrEP uptake, care and use among MSM with HIV and previous PrEP experience. Methods Between March 2022-March 2023, we conducted semi-structured in-depth interviews on PrEP among MSM diagnosed with HIV from 2019 onwards with previous PrEP experience. Interviewees were recruited through their HIV treatment centers and social media. Results Of the 11 included MSM, most reported significant PrEP-uptake delay because of the limited NPP capacity and high threshold of accessing PrEP from GPs (e.g. stigma, lack of sexual health expertise). Additional uptake or use barriers included anticipated/experienced side-effects, burden of daily pill-taking or event-driven regimen complexity, the latter leading to PrEP discontinuation. Missed opportunities in counseling on adherence and safer sex alternatives after discontinuation were reported. Most interviewees considered informal PrEP unsuitable. Conclusion PrEP uptake delay played a crucial role in context of HIV infection among MSM with HIV and previous PrEP experience. HIV diagnoses at or shortly after PrEP initiation emphasize the importance of ensuring rapid and timely PrEP access. Uptake barriers at GPs, stigma on sexuality, lack of expertise, and missed care opportunities need to be addressed. Early detection of PrEP protocol/user-mismatch and counseling on safer sex alternatives after discontinuation are pivotal for sustainable HIV prevention.
Metabolite changes during developmental transitions in Adonis amurensis Regel et Radde flowers: Insights from HPLC-MS analysis
Adonis amurensis Regel et Radde is a remarkable and important spring ephemeral plant and gained considerable attention because of its remarkable medicinal properties. Extensive research has been conducted on its therapeutic applications, physical characteristics, flowering patterns, reproductive, cultural and molecular biology. However, there is a lack of comprehensive understanding regarding the metabolic changes associated with flower developmental stages. This study was designed to investigate the changes in metabolites and their interrelationships at five distinct developmental stages of A . amurensis flower: Flower Primordium (FP), Sepal Stage (SE), Perianth Primordium (PE), Stamens Stage (SE), and Pistil Stage (PI). High-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) was utilized to investigate and characterize the metabolites associated with specific flower developmental stages. The various stages of flower development exerted a substantial influence on both the quantity and composition of metabolites present, signifying significant changes in the types and quantities of metabolites throughout the developmental progression of the flower. Metabolite Set Enrichment Analysis (MSEA) and annotation via the KEGG database highlighted enriched pathways such as flavonoid biosynthesis and plant hormone signal transduction, which are crucial for flower maturation. The highest number of differentially expressed metabolites was identified between the SE and PI stages, emphasizing a marked appreciation in metabolite expression linked to the development of reproductive organs. Key pathways such as flavonoid biosynthesis and plant hormone signal transduction were markedly enriched, underscoring their roles in flower maturation and potential pharmacological applications. Our research not only helps us in understanding the metabolomic dynamics during the flower development of A . amurensis but also emphasizes the potential pharmacological implication of stage-specific metabolites. Identifying these metabolites can help targeted bioprospecting and optimization of extraction methods to tackle the plant’s full therapeutic potential, particularly in the development of treatments for cardiac insufficiency, edema, and possibly cancer.