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Chronotherapy with Cinacalcet has a striking effect on inhibition of parathyroid gland proliferation in rats with secondary hyperparathyroidism
Secondary hyperparathyroidism (sHPT) is a significant clinical complication of CKD leading to bone abnormalities and cardiovascular disease. Current treatment based on activating the parathyroid calcium-sensing receptor (CaSR) using calcimimetics such as Cinacalcet, aims to decrease plasma PTH levels and inhibit the progression of parathyroid hyperplasia. In the present study, we found significant diurnal rhythmicity of Casr, encoding the Cinacalcet drug target in hyperplastic parathyroid glands (p = 0.006). In rats with sHPT, Cinacalcet treatment timed prior to the acrophase of Casr expression (chronotherapy: Cina1) was compared with the usual timing of treatment early in the active phase (conventional: Cina2). Without Cinacalcet treatment, induction of sHPT resulted in a significant increase in parathyroid proliferation in terms of Ki-67+ cells compared to that of control rats (p = 0.001). Conventional Cinacalcet treatment (Cina2) did not significantly reduce Ki-67 index compared to untreated rats with sHPT (p = 0.09). In contrast, chronotherapy treatment (Cina1) resulted in a marked inhibition of parathyroid proliferation by Ki-67+ cells compared to untreated rats with sHPT (p = 0.0001). We found significantly reduced parathyroid Ki-67 index using chronotherapy compared to conventional timing of Cinacalcet (Cina1 vs. Cina2: 0.92±0.14% vs. 2.46±0.37%, p = 0.006). Transcriptomic analysis showed that the reduced proliferation of Cina1 was associated with downregulation of genes involved in mitotic activity, together with an increased adaptive response of energy metabolism, as evident from upregulated pathways of Oxidative phosphorylation and TCA cycle compared to the untreated uremic group. Conclusively, it is shown that the inhibitory effect of Cinacalcet on parathyroid cell proliferation is markedly impacted by the timing of administration, suggesting a possible benefit of using chronotherapy in Cinacalcet treatment of sHPT.
Impact of CaNa2EDTA fortification on growth, antioxidant activity and stress-related gene expression in tilapia (Oreochromis niloticus) at different stocking densities paradigms
Increasing aquaculture production requires high-density farming, which induces stress, necessitating supplements to mitigate its effects and ensure fish health. The aim of this study was to examine how CaNa2EDTA (EDTA) affects the growth, immune response and antioxidant activity in Nile tilapia (Oreochromis niloticus). The fish were raised at three different stocking densities: low (LD = 2.00 kg/m3), medium (MD = 3.50 kg/m3), and high (HD = 5.00 kg/m3). Each density group was fed with one of four levels of EDTA supplementation (E0 = 0 g/kg, E1 = 5 g/kg, E2 = 10 g/kg, and E3 = 15 g/kg) for 60 days. Each diet was tested in triplicate (n = 66 fish per replicate in LD, 116 per replicate in MD, and 166 per replicate in HD). After 60 days, the results of this study declared that LD group showed better growth than the MD and HD groups, and among all groups, those fed the E1 diet grew better than those on other diets. The study found significant changes in the chemical composition of the fish and the activity of digestive enzymes across all treatments. Antioxidant enzyme levels and cortisol were higher in the HD group compared to the LD and MD groups. However, fish in the HD group fed the E1 diet had the lowest levels of antioxidant enzymes and cortisol. Malondialdehyde levels were higher in the HD group compared to the LD and MD groups, with the lowest levels seen in fish on the E1 diet in the HD group. The expression of Somatostatin-1 did not increase in the MD group compared to the LD and HD groups. The gene expression levels of pro-opiomelanocortin-α and Interleukin 1-β were not significantly affected by either stocking density or EDTA supplementation. In conclusion, EDTA supplementation improved growth and antioxidant response in tilapia, with the best results seen at a dose of 5 g/kg in the high-density group, suggesting that this approach could be beneficial in intensive tilapia farming.
Data transmission delay compensation algorithm for interactive communication network of offshore oil field operation scene in bad weather
A data transmission delay compensation algorithm for an interactive communication network of an offshore oil field operation scene in severe weather is proposed. To solve the problem of unstable microwave signals and a large amount of noise in the communication network caused by bad weather, the communication network signal denoising method based on Lagrange multiplier symplectic singular value mode decomposition is adopted, and the communication network data denoising process is realized through five steps; phase space reconstruction, symplectic geometric similarity transformation, grouping, diagonal averaging, and adaptive reconstruction. Simultaneously, the weak communication signal is compensated after being captured, that is, the characteristics of the weak signal are enhanced. On this basis, the communication network signals are collected to obtain delay information, and the data transmission delay of the communication network is predicted using the neural network algorithm based on long-term and short-term memory; Based on the prediction result of transmission delay, the PID controller is used to calculate the transmission delay compensation amount of the communication network, and the calculation result of the compensation amount is input into the delay compensator to realize transmission delay compensation. The experimental results show that the algorithm can effectively improve the quality of data transmission in the communication network and has a good delay compensation effect to ensure real-time communication.
ETL: From the German Health Data Lab data formats to the OMOP Common Data Model
Objective The German Health Data Lab is going to provide access to German statutory health insurance claims data ranging from 2009 to the present for research purposes. Due to evolving data formats within the German Health Data Lab, there is a need to standardize this data into a Common Data Model to facilitate collaborative health research and minimize the need for researchers to adapt to multiple data formats. For this purpose we selected transforming the data to the Observational Medical Outcomes Partnership Common Data Model. Methods We developed an Extract, Transform, and Load (ETL) pipeline for two distinct German Health Data Lab data formats: Format 1 (2009-2016) and Format 3 (2019 onwards). Due to the identical format structure of Format 1 and Format 2 (2017 -2018), the ETL pipeline of Format 1 can be applied on Format 2 as well. Our ETL process, supported by Observational Health Data Sciences and Informatics tools, includes specification development, SQL skeleton creation, and concept mapping. We detail the process characteristics and present a quality assessment that includes field coverage and concept mapping accuracy using example data. Results For Format 1, we achieved a field coverage of 92.7%. The Data Quality Dashboard showed 100.0% conformance and 80.6% completeness, although plausibility checks were disabled. The mapping coverage for the Condition domain was low at 18.3% due to invalid codes and missing mappings in the provided example data. For Format 3, the field coverage was 86.2%, with Data Quality Dashboard reporting 99.3% conformance and 75.9% completeness. The Procedure domain had very low mapping coverage (2.2%) due to the use of mocked data and unmapped local concepts The Condition domain results with 99.8% of unique codes mapped. The absence of real data limits the comprehensive assessment of quality. Conclusion The ETL process effectively transforms the data with high field coverage and conformance. It simplifies data utilization for German Health Data Lab users and enhances the use of OHDSI analysis tools. This initiative represents a significant step towards facilitating cross-border research in Europe by providing publicly available, standardized ETL processes (https://github.com/FraunhoferMEVIS/ETLfromHDLtoOMOP) and evaluations of their performance.
Effect of power training on function and body composition in older women with probable sarcopenia. A study protocol for a randomized controlled trial
Background Sarcopenia is a clinical syndrome characterized by the loss of muscle mass and strength. Hormonal changes that occur early in women may influence protein synthesis and promote muscle atrophy, leading to probable sarcopenia, defined as a loss of muscle strength without an obvious decrease in muscle mass. Various types of exercise have already proven effective in treating sarcopenia. Power training (PT), a subtype of resistance training performed at high speed, has not yet been studied in this population group. Methods A randomized controlled trial will be conducted with three parallel groups: a PT group, a multicomponent training (MT) group, and a no-exercise group. The inclusion criteria will be women over 65 years of age who meet the diagnostic criteria for probable sarcopenia (Hand grip test less than 16 kg and Five Times Sit to Stand Test more than 15 s) according to the European Working Group on Sarcopenia in Older People (EWGSOP2). Two assessments will be conducted at the beginning and at the end of the 32 weeks of intervention, in which variables of body composition (muscle, fat and weight) and functionality (strength and physical performance) will be collected. There will be 3 sessions of 50 minutes per week in each intervention group. The masking strategy will be double-blind. The analysis of intergroup differences will be conducted using multivariate and univariate analysis of variance (MANOVA and ANOVA), as well as pairwise comparisons (Bonferroni corrections). Changes in the degree of sarcopenia and how many women eliminate the risk of sarcopenia (no probable sarcopenia) after the different interventions will be tested. Discussion The study aims to investigate the impact of PT in older women at risk of sarcopenia. The expected results are that PT will significantly improve functionality and body composition compared to other forms of exercise (MT) and no physical activity. The results may represent a significant advance in understanding and addressing sarcopenia before it becomes established, providing preventive treatment and new tools whose clinical applicability has been studied. Trial registration The clinical trial was prospectively registered at ClinicalTrials.gov Identifier: NCT05870046.
Sequence and biochemical analysis of vaccinia virus A32 protein: Implications for in vitro stability and coiled-coil motif mediated regulation of the DNA-dependent ATPase activity
Nucleocytoplasmic large DNA viruses (NCLDVs) have massive genome and particle sizes compared to other known viruses. NCLDVs, including poxviruses, encode ATPases of the FtsK/HerA superfamily to facilitate genome encapsidation. However, their biochemical and structural characteristics are yet to be discerned. In this study, we demonstrate that the viral ATPases are significantly shorter than their bacterial homologs, representing the minimal ATPase core of the FtsK/HerA superfamily. We analysed the sequence and secondary structural features of the vaccinia virus A32 protein and determined their roles in the protein’s ATPase activity. We sought to purify A32 by various techniques and noted that recombinant A32 expressed in E. coli is highly insoluble and unstable in solution. N-terminal fusion with the thioredoxin solubility tag could alleviate this issue to some extent, but subsequent tag cleavage results in increased susceptibility to precipitation and degradation. We have also predicted a highly conserved coiled-coil motif (CCM) towards the C-terminus of vaccinia virus A32. ATPase activity of A32 is known to increase in the presence of DNA. Comparative analysis of the wildtype protein versus its CCM mutants suggests that this DNA dependence of A32’s ATPase activity is likely regulated by the CCM. We demonstrate that oligomerization of A32, mediated by the CCM, is required for its DNA-binding but is not dependent on ATP- or DNA-binding. Our findings suggest a key role of the CCM, and thus, higher-order structure formation in the regulated ATPase activity of A32, providing new opportunities for further detailed characterization of the poxvirus genome packaging process.
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.