Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence, time-trends and clinical characteristics of hypertension in young adults: nationwide cross-sectional study of 1.7 million Swedish 18-year-olds, 1969–2010

Objective: The prevalence of hypertension in young adulthood, as well as the clinical characteristics associated with different hypertension subtypes, have been inconsistently described. Our aim was to assess the prevalence, time-trends and characteristics associated with isolated systolic hypertension (ISH), isolated diastolic hypertension and combined systodiastolic hypertension. Methods: Serial cross-sectional analysis, using data from the Swedish conscription registry, including 1701 314 (99.2% male) individuals from 1969 to 2010. Risk factor associations were assessed through multivariable logistic regression. Results: The prevalence of hypertension increased progressively during the study period, from 20.4% in 1969 to 29.3% in 2010, with ISH being the most common subtype (94.3%). ISH was associated with elevated resting heart rate (odds ratio 1.85, 95% confidence interval 1.84–1.86, per SD), increased exercise capacity (1.37, 1.36–1.39) and increased BMI (1.30, 1.29–1.31). Isolated diastolic hypertension and combined hypertension were also associated with elevated resting heart rate (1.37, 1.32–1.41 and 2.05, 1.99–2.11, respectively) and more strongly associated with increased BMI (1.36, 1.33–1.40 and 1.54, 1.51 – 1.58), but inversely associated with exercise capacity (0.79, 0.75–0.83 and 0.90, 0.86–0.95). Conclusion: The prevalence of hypertension in young adulthood has increased substantially over time, predominantly due to an increase in ISH. Risk factor patterns differed between ISH and other forms of hypertension, suggesting potentially different underlying mechanisms.
Effect of station format on the psychometric properties of Multiple Mini Interviews

Given the widespread use of Multiple Mini Interviews (MMIs), their impact on the selection of candidates and the considerable resources invested in preparing and administering them, it is essential to ensure their quality. Given the variety of station formats used and the degree to which that factor resides in the control of training programmes that we know so little about, format's effect on MMI quality is a considerable oversight. This study assessed the effect of two popular station formats (interview vs. role‐play) on the psychometric properties of MMIs.
The plant host environment influences competitive interactions between bacterial pathogens

Abstract Bacteria compete for resources in diverse environments using an array of antagonistic strategies, including the production of narrow‐spectrum protein antibacterials termed bacteriocins. Although significant research has focused on bacteriocin‐mediated dynamics in culture environments, little research has explored bacteriocin‐mediated dynamics within a host context, particularly in plant environments. Here, we show that a bacterial plant pathogen, Pseudomonas syringae pv. syringae (Psy), expresses a bacteriocin both in culture and in leaf apoplast when co‐inoculated with a bacteriocin‐sensitive competitor, P. syringae pv. phaseolicola (Pph). Although there is an observable negative effect of the bacteriocin on the Pph population at most time points both in culture and in the leaf apoplast, a bacteriocin‐mediated benefit to Psy was only observed when the producing strain was co‐infiltrated at a low population frequency (1:9) into the leaf apoplast. At 6 days post‐infiltration, Psy achieved an eightfold population increase compared to a bacteriocin‐deficient mutant in the apoplast. No bacteriocin‐mediated benefit for Psy was observed under the culture conditions tested. Additionally, we found that the bacteriocin‐mediated benefit for Psy was dependent on the Type III Secretion System. Taken together, our results demonstrate that the fitness benefit of bacteriocin‐mediated antagonism is influenced by interactions within the host plant.
Advancements in Three Dimensional In‐Vitro Cell Culture Models

The scientific field is observing a gradual shift from monolayer cultures to three‐dimensional (3D) models, as they give a more relevant data in pre‐clinical stages. This review summarizes the major techniques and materials used to develop 3D platforms, especially for cancer. It also discusses the challenges and some unresolved issues of the field and highlights some techniques that have made it to the market.
Therapeutic Drug Monitoring of Paliperidone in Patients With Schizophrenia in Taiwan

Abstract Background The blood level of antipsychotics affects clinical responses to the drug; it can be influenced by race and several individual factors. This study analyzed the therapeutic plasma concentrations (Cps) of paliperidone for both oral and long-acting injectable (LAI) formulations in clinical samples from Taiwanese patients. Methods Patients diagnosed with schizophrenia and treated with either oral paliperidone for at least 4 weeks or LAI paliperidone for at least 6 months were enrolled. Blood samples were taken before the morning dose of oral paliperidone or the injection of LAI paliperidone to obtain the trough Cps. Results Among the patients in this study, 51 were taking oral paliperidone, and 26 were receiving LAI paliperidone. In the oral group, the mean Cps were 40.2 ± 19.8 ng/mL in patients taking 9 mg/d and 44.2 ± 15.9 ng/mL in those taking 12 mg/d. In the LAI group, the mean Cps were 32.9 ± 12.7 ng/mL in patients receiving 100 mg per 28 days and 49.9 ± 25.9 ng/mL in those receiving 150 mg per 28 days. The mean Cps per daily dose (Cps/DD) were 4.11 ± 1.99 ng/mL/mg in the oral group and 9.24 ± 3.78 ng/mL/mg in the LAI group. Conclusions Under the suggested DD for oral and LAI paliperidone treatment, most Taiwanese patients with schizophrenia can reach the suggested therapeutic Cps range. Wide interindividual differences were observed in the Cps/DD for both the oral (7-fold) and LAI paliperidone (4-fold) groups. Compared with Western reports, no difference was observed in the body weight–adjusted Cps/DD.
CPOPT : optimization for fitting CANDECOMP/PARAFAC models.

Tensor decompositions (e.g., higher-order analogues of matrix decompositions) are powerful tools for data analysis. In particular, the CANDECOMP/PARAFAC (CP) model has proved useful in many applications such chemometrics, signal processing, and web analysis; see for details. The problem of computing the CP decomposition is typically solved using an alternating least squares (ALS) approach. We discuss the use of optimization-based algorithms for CP, including how to efficiently compute the derivatives necessary for the optimization methods. Numerical studies highlight the positive features of our CPOPT algorithms, as compared with ALS and Gauss-Newton approaches.
Multitask Learning With Recurrent Neural Networks for Acute Respiratory Distress Syndrome Prediction Using Only Electronic Health Record Data: Model Development and Validation Study

Background Acute respiratory distress syndrome (ARDS) is a condition that is often considered to have broad and subjective diagnostic criteria and is associated with significant mortality and morbidity. Early and accurate prediction of ARDS and related conditions such as hypoxemia and sepsis could allow timely administration of therapies, leading to improved patient outcomes. Objective The aim of this study is to perform an exploration of how multilabel classification in the clinical setting can take advantage of the underlying dependencies between ARDS and related conditions to improve early prediction of ARDS in patients. Methods The electronic health record data set included 40,703 patient encounters from 7 hospitals from April 20, 2018, to March 17, 2021. A recurrent neural network (RNN) was trained using data from 5 hospitals, and external validation was conducted on data from 2 hospitals. In addition to ARDS, 12 target labels for related conditions such as sepsis, hypoxemia, and COVID-19 were used to train the model to classify a total of 13 outputs. As a comparator, XGBoost models were developed for each of the 13 target labels. Model performance was assessed using the area under the receiver operating characteristic curve. Heat maps to visualize attention scores were generated to provide interpretability to the neural networks. Finally, cluster analysis was performed to identify potential phenotypic subgroups of patients with ARDS. Results The single RNN model trained to classify 13 outputs outperformed the individual XGBoost models for ARDS prediction, achieving an area under the receiver operating characteristic curve of 0.842 on the external test sets. Models trained on an increasing number of tasks resulted in improved performance. Earlier prediction of ARDS nearly doubled the rate of in-hospital survival. Cluster analysis revealed distinct ARDS subgroups, some of which had similar mortality rates but different clinical presentations. Conclusions The RNN model presented in this paper can be used as an early warning system to stratify patients who are at risk of developing one of the multiple risk outcomes, hence providing practitioners with the means to take early action.
Pro-Oxidant and Cytotoxic Effects of Tucum-Do-Cerrado (Bactris setosa Mart.) Extracts in Colorectal Adenocarcinoma Caco-2 Cells

Abstract Colorectal cancer is one of the most common types of cancer. Bioactive natural compounds can act in cancer chemoprevention as tumor growth inhibitors. Tucum-do-cerrado (Bactris setosa Mart.) is a Brazilian fruit that contains several phenolic compounds. This study investigated the effect of tucum aqueous extract in Caco-2 cells in comparison to primary human intestinal organoids and fibroblasts. Cells were exposed to 0.5 and 1 mg/ml of tucum aqueous extract for 24 h. ROS production, mRNA levels for SOD1 and SOD2, CAT, GPX1, NFE2L2, HIF1A and NOS2 were evaluated in Caco-2 cells exposed to tucum extract. Cell viability of Caco-2 cells was decreased upon tucum extract exposure. Mitochondrial ROS levels increased in Caco-2 cells exposed to tucum extract. The mRNA levels of SOD1, SOD2, CAT, GPX, NFE2L2 and HIF1A were downregulated in Caco-2 cells exposed to tucum extract, while NOS2 mRNA levels remained unchanged. Protein levels of SOD2, CAT and NRF2 remained unchanged in Caco-2 cells treated with tucum extract, indicating that catalase and SOD2 cellular functions may be unaffected by the tucum extract at 24 h, of exposure. Aqueous extract of tucum-do-cerrado may induce cellular toxicity in a cancer cell-specific manner, possibly through increased mitochondrial ROS production and gene expression regulation.
Up-regulation of LINC00665 contributes to the progression of glioma and correlates with its MRI characteristics.

BACKGROUND LncRNA LINC00665 partakes in controlling the malignant phenotype of cancer cells, but its role in glioma and the related regulatory mechanism remain uncertain. METHODS RT-PCR was exploited to examine LINC00665 expression. The relationships among the LINC00665 expression, the clinicopathologic values and magnetic resonance imaging (MRI) characteristics of glioma were analyzed. The multiplication, movement, and aggressiveness of glioma cell lines were evaluated by CCK-8, EdU, and Transwell experiments after constructing LINC00665 overexpression and LINC00665 knockdown cell models. A dual-luciferase reporter gene experiment and RIP experiment were executed to validate the interactions between LINC00665 and miR-129-5p, and between miR-129-5p and HMGB1. Western blot and RT-PCR were conducted to find the impact of LINC00665 and miR-129-5p on HMGB1 expression. Nude mouse model was also constructed to examine the impact of LINC00665 on multiplication and aggressiveness of glioma cells in vivo. RESULTS LINC00665 expression was markedly increased in glioma. High LINC00665 expression in glioma was closely linked to larger tumor diameter, higher pathologic grade, heterogeneous MRI signal of the tumor, increased peritumoral edema, and stronger MRI enhancement characteristics. LINC00665 overexpression facilitated the malignant behavior of glioma cells, while LINC00665 knockdown played the reverse role. Mechanistically, LINC00665 could decoy miR-129-5p, and indirectly increased HMGB1 expression. CONCLUSION LINC00665 functions as an oncogenic lncRNA in glioma, to accelerate glioma progression by modulating miR-129-5p and increasing HMGB1 expression.
Revisiting the relationship between (Pro)Renin receptor and the intrarenal RAS: focus on the soluble receptor

Purpose of review The (pro)renin receptor (PRR), also termed as ATPase H+ transporting accessory protein 2 (ATP6AP2), was originally cloned as a specific receptor for prorenin and renin [together called (pro)renin]. Given the wide tissue distribution of PRR, PRR was further postulated to act as a regulator of tissue renin. However, assigning a physiological role of PRR within the renin-angiotensin system (RAS) has been challenging largely due to its pleotropic functions in regulation of embryogenesis, autophagy, and H+ transport. The current review will summarize recent advances in understanding the roles of sPPR within the intrarenal RAS as well as those outside this local system. Recent findings Site-1 protease (S1P) is a predominant source of sPPR at least in the kidney. So far most of the known physiological functions of PRR including renal handling of electrolytes and fluid and blood pressure are mediated by sPRR. In particular, sPRR serves as a positive regulator of collecting duct renin to activate the intrarenal RAS during water deprivation or angiotensin-II (AngII) infusion. However, PRR/sPRR can act in renin-independent manner under other circumstances. Summary S1P-derived sPRR has emerged as a key regulator of kidney function and blood pressure and its relationship with the intrarenal RAS depends on the physiological context.
An empirical study of factors influencing e-health services adoption among public in Saudi Arabia

Until now most of the studies concerning eHealth in Saudi Arabia are about the exploration of the national benefits from eHealth and the technical and infrastructural challenges in implementing eHealth rather than finding the factors influencing the users in adopting eHealth services. Further, the eHealth adoption rate in Saudi Arabia is low despite the scope of potential growth for the eHealth market. In this study, the authors added Trust, Privacy and System Quality factors to Technology Acceptance Model by considering the research context to examine the factors influencing eHealth services adoption. The proposed model was empirically tested based on the data collected, through survey questionnaire from 314 responses in Saudi Arabia. Structural Equation Modelling was followed to analysis and validates the proposed model based on partial least squares method using SmartPLS. Based on the findings, Perceived Usefulness in addition to Privacy significantly affect eHealth adoption. Moreover, Perceived Ease of Use factor has indirect effect on people perception toward eHealth services. Furthermore, the results show that System Quality and Trust are not influencing factors. This study is important for the healthcare policymakers for getting direction for future studies to avail the maximum benefits of eHealth in Saudi Arabia.
Myoinhibitory peptides in the central complex of the locust Schistocerca gregaria and colocalization with locustatachykinin‐related peptides

The central complex in the brain of insects provides a neural network for sensorimotor processing that is essential for spatial navigation and locomotion and plays a role in sleep control. Studies on the neurochemical architecture of the central complex have been performed especially in the fruit fly Drosophila melangoaster and the desert locust, Schistocerca gregaria. In several insect species, myoinhibitory peptides (MIPs) are involved in circadian control and sleep‐wake regulation. To identify neurons that might underlie these functions, we investigated the distribution of MIPs in the central complex of the locust. In silico transcript analysis suggests the presence of eight different MIPs in the desert locust. Through immunolabeling, we identified five systems of central‐complex neurons that express MIP‐like peptides. Two systems constitute columnar neurons of the protocerebral bridge and the lower division of the central body, while the other three systems are columnar neurons (two systems) and tangential neurons (one system) of the upper division of the central body. The innervation pattern and cell count of two systems of columnar neurons revealed the existence of 18 instead of 16 columns of the protocerebral bridge. Immunostaining of preparations containing intracellularly stained single cells allowed us to further specify subtypes of labeled columnar neurons. Double‐label experiments showed that three systems of MIP‐immunostained columnar neurons are also locustatachykinin‐immunoreactive. No colocalization was found with serotonin immunostaining. The data provide novel insights into the architecture of the locust central complex and suggest that MIPs play a prominent role within the central‐complex network.
Polycythemia in dogs with chronic hypoxic pulmonary disease

Abstract Background Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little clinical data are available to support this hypothesis. Objective To study the prevalence and severity of erythrocytosis accompanying chronic hypoxic pulmonary disease in dogs. Animals Forty‐seven dogs with hypoxic chronic pulmonary disease, 27 dogs with nonhypoxic chronic pulmonary disease, and 60 healthy controls. Methods Dogs with chronic pulmonary disease and chronic hypoxemia (partial pressure of arterial oxygen [PaO2] < 80 mm Hg on at least 2 arterial blood gas measurements a minimum of 1 month apart) were identified retrospectively from patient records. Association between arterial oxygen and red blood cell parameters was analyzed using Pearson's correlation coefficients and multivariable linear regression analysis. Results Red blood cell parameters measured at the end of the hypoxemia period were within the laboratory reference range in most dogs. In chronically hypoxemic dogs, hematocrit (Hct) was increased in 4/47 (8.5%; 95% confidence interval [CI], 0‐17) dogs, erythrocyte count (Erytr) was increased in 12/47 (26%; 95%CI, 13‐38) dogs and hemoglobin concentration (Hb) was increased in 3/47 (6.4%; 95%CI, 0‐14) dogs. No marked polycythemia (Hct ≥65%) was noted in any of the dogs. Red blood cell parameters were not associated with the severity of hypoxemia (correlation to PaO2: Erytr, r = −.14; Hb, r = −.21; Hct, r = −.14; P > .05 for all). Conclusions and Clinical Importance Polycythemia is uncommon, and usually mild if present, in dogs with chronic hypoxia caused by pulmonary disease.
VLA Observations of H_2O Masers in the Class 0 Protostar S106FIR

We measured relative positions of the 22 GHz H2O maser components toward the class 0 protostar S106FIR with the VLA. Two clusters of H2O masers were found. The separation between these clusters is approximately 50 AU at position angle = 73° and each cluster is spread over about 10-20 AU The size of the S106FIR maser clusters is unusually compact compared with other known H2O masers associated with outflows of forming stars. The maser emission appears to originate from MHD driven outflow very close to the star.
Ethical Considerations in Surgical Decompression for Stroke

Stroke is a major cause of morbidity and mortality. Neurosurgical decompression is often considered for the treatment of malignant infarcts and intraparenchymal hemorrhages, but this treatment can be frought with ethical dilemmas. In this article, the authors outline the primary principles of bioethics and their application to stroke care, provide an overview of key ethical issues and special situations in the neurosurgical management of stroke, and highlight methods to improve ethical decision-making for patients with stroke. Understanding these ethical principles is essential for stroke care teams to deliver appropriate, timely, and ethical care to patients with stroke.
Exploring Reticular Pseudodrusen Extent and Impact on Mesopic Visual Sensitivity in Intermediate Age-Related Macular Degeneration

Purpose To explore the impact of the extent of reticular pseudodrusen (RPD) on mesopic visual sensitivity in individuals with intermediate age-related macular degeneration (AMD). Methods In total, 570 eyes from 285 participants with bilateral large drusen underwent microperimetry testing to assess the visual sensitivity of the central 3.6-mm region and multimodal imaging to determine the extent of RPD in the central 20° × 20° region (at the eye level). Mean visual sensitivity within five sectors in the central 3.6-mm region sampled on microperimetry and the extent of RPD in these sectors were derived. Linear mixed models were used to examine the association between the extent of RPD on overall mean visual sensitivity and sector-based mean sensitivity. Results An increasing extent of RPD at the eye level and within sectors was associated with a significant reduction in overall and sector-based mean sensitivity, respectively (P < 0.001 for both). However, when both RPD parameters were considered together in a multivariable model, only an increasing extent of RPD at the eye level (P < 0.001) and not within each sector (P = 0.178) was independently associated with reduced sector-based mean sensitivity. Conclusions Mesopic visual sensitivity is generally reduced in eyes with large drusen and coexistent RPD compared to eyes without RPD, with greater reductions with an increasing extent of RPD. However, reduced sector-based visual sensitivities are explained by the overall extent of RPD present, rather than their extent within the sector itself. These findings suggest that there are generalized pathogenic changes in eyes with RPD accounting for the observed mesopic visual dysfunction.
Distinct stromal and immune cell interactions shape the pathogenesis of rheumatoid and psoriatic arthritis

Objectives Immune and stromal cell communication is central in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), however, the nature of these interactions in the synovial pathology of the two pathotypes can differ. Identifying immune-stromal cell crosstalk at the site of inflammation in RA and PsA is challenging. This study creates the first global transcriptomic analysis of the RA and PsA inflamed joint and investigates immune-stromal cell interactions in the pathogenesis of synovial inflammation. Methods Single cell transcriptomic profiling of 178 000 synovial tissue cells from five patients with PsA and four patients with RA, importantly, without prior sorting of immune and stromal cells. This approach enabled the transcriptomic analysis of the intact synovial tissue and identification of immune and stromal cell interactions. State of the art data integration and annotation techniques identified and characterised 18 stromal and 14 immune cell clusters. Results Global transcriptomic analysis of synovial cell subsets identifies actively proliferating synovial T cells and indicates that due to differential λ and κ immunoglobulin light chain usage, synovial plasma cells are potentially not derived from the local memory B cell pool. Importantly, we report distinct fibroblast and endothelial cell transcriptomes indicating abundant subpopulations in RA and PsA characterised by differential transcription factor usage. Using receptor–ligand interactions and downstream target characterisation, we identify RA-specific synovial T cell-derived transforming growth factor (TGF)-β and macrophage interleukin (IL)-1β synergy in driving the transcriptional profile of FAPα+THY1+ invasive synovial fibroblasts, expanded in RA compared with PsA. In vitro characterisation of patient with RA synovial fibroblasts showed metabolic switch to glycolysis, increased adhesion intercellular adhesion molecules 1 expression and IL-6 secretion in response to combined TGF-β and IL-1β treatment. Disrupting specific immune and stromal cell interactions offers novel opportunities for targeted therapeutic intervention in RA and PsA.