Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and Mortality of Venous Leg Diseases of the Deep Veins: An Observational Cohort Study Based on German Health Claims Data

This study estimates the prevalence and mortality of diseases of the deep veins of the legs such as deep vein thrombosis (DVT), postthrombotic syndrome (PTS), and venous leg ulceration (VLU). We used a random sample of 250 000 patients at age 50+ years of the register of the Allgemeine Ortskrankenkasse from 2004 to 2015. Selected manifestations of venous diseases assumed as risk factors for mortality were analyzed using Cox models while adjusting for various basic demographic and health characteristics. The prevalence in 2004 was 0.05% for DVT of the femoral veins, 0.50% for DVT of any deep veins, 0.86% for PTS, and 0.91% for VLU. The mortality rate in 2004 to 2015 was 20.40 deaths/100 person-years for DVT of the femoral veins, 10.69 for DVT of any deep veins, 4.34 for PTS, and 7.02 for VLU. The model revealed a 35% higher risk (p < .001) in patients with any DVT, an 88% higher mortality (p < .001) for femoral DVT, a 23% higher risk (p < .001) for VLU, and no health disadvantage in persons with PTS. Our study revealed an increased mortality for patients with VLU and DVT. Even after adjustment for embolic events and infections of the venous ulcers mortality remained significantly higher.
A smart approach to enable preclinical studies in pharmaceutical industry: PLGA-based extended release formulation platform for subcutaneous applications

Abstract Objective: Validation of a prospective new therapeutic concept in a proof of concept study is costly and time-consuming. In particular, pharmacologically active tool compounds often lack suitable pharmacokinetic (PK) properties for subsequent studies. The current work describes a PLGA-based formulation platform, encapsulating different preclinical research compounds into extended release microparticles, to optimize their PK properties after subcutaneous administration. Significance: Developing a PLGA-based formulation platform offers the advantage of enabling early proof of concept studies in pharmaceutical research for a variety of preclinical compounds by providing a tailor-made PK profile. Methods: Different model compounds were encapsulated into PLGA microparticles, utilizing emulsification solvent evaporation or spray drying techniques. Formulations aiming different release rates were manufactured and characterized. Optimized formulations were assessed in in vivo studies to determine their PK properties, with the mean residence time (MRT) as one key PK parameter. Results: Utilizing both manufacturing methods, tested tool compounds were encapsulated successfully, with a drug load between 5% and 40% w/w, and an extended release time up to 250 h. In the following PK studies, the MRT was extended by a factor of 90, resulting in prolonged coverage of the required target through level. This approach was confirmed to be equally successful for additional internal compounds, verifying a general applicability of the platform. Conclusion: For different active pharmaceutical ingredients (API), an optimized, tailor-made PK profile was obtained utilizing the described formulation platform. This approach is applicable for a variety of pharmacologically active tool compounds, reducing timelines and costs in preclinical research.
An Assessment of Knowledge on Type 2 Diabetes, the Means of Preventing It, and Attitudes Towards Preventing Type 2 Diabetes Mellitus in Middle-Aged Nigerian Women

ii Abstract Nigerian women commonly develop type 2 diabetes at about the age of onset of menopause. Metabolic syndrome is also common in menopausal Nigerian women The purpose of this study is to assess the level of knowledge of type 2 diabetes, the means of preventing it, and the attitude towards preventing type 2 diabetes in middle-aged Nigerian women. This study used questionnaires to assess these criteria in middle-aged Nigerian women between ages 45 and 55, who attended the medical outpatient clinics at Ibeju-Logistic regression was used to perform the statistical analysis on the data collected from the survey. The findings showed there is a poor level of knowledge of type 2 diabetes mellitus and the means to prevent it, and a poor attitude towards preventing type 2 diabetes mellitus amongst middle-aged Nigerian women. It is hoped; however, that participation in this study increased the participants' knowledge of type 2 diabetes and the means of preventing it, and improved their attitude towards preventing type 2 diabetes mellitus. 45
The Application of Internet-Based Sources for Public Health Surveillance (Infoveillance): Systematic Review

Background Public health surveillance is based on the continuous and systematic collection, analysis, and interpretation of data. This informs the development of early warning systems to monitor epidemics and documents the impact of intervention measures. The introduction of digital data sources, and specifically sources available on the internet, has impacted the field of public health surveillance. New opportunities enabled by the underlying availability and scale of internet-based sources (IBSs) have paved the way for novel approaches for disease surveillance, exploration of health communities, and the study of epidemic dynamics. This field and approach is also known as infodemiology or infoveillance. Objective This review aimed to assess research findings regarding the application of IBSs for public health surveillance (infodemiology or infoveillance). To achieve this, we have presented a comprehensive systematic literature review with a focus on these sources and their limitations, the diseases targeted, and commonly applied methods. Methods A systematic literature review was conducted targeting publications between 2012 and 2018 that leveraged IBSs for public health surveillance, outbreak forecasting, disease characterization, diagnosis prediction, content analysis, and health-topic identification. The search results were filtered according to previously defined inclusion and exclusion criteria. Results Spanning a total of 162 publications, we determined infectious diseases to be the preferred case study (108/162, 66.7%). Of the eight categories of IBSs (search queries, social media, news, discussion forums, websites, web encyclopedia, and online obituaries), search queries and social media were applied in 95.1% (154/162) of the reviewed publications. We also identified limitations in representativeness and biased user age groups, as well as high susceptibility to media events by search queries, social media, and web encyclopedias. Conclusions IBSs are a valuable proxy to study illnesses affecting the general population; however, it is important to characterize which diseases are best suited for the available sources; the literature shows that the level of engagement among online platforms can be a potential indicator. There is a necessity to understand the population’s online behavior; in addition, the exploration of health information dissemination and its content is significantly unexplored. With this information, we can understand how the population communicates about illnesses online and, in the process, benefit public health.
Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils.

BACKGROUND Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of ɣ-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-ɣ-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively. OBJECTIVES The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleotide polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA, and ARA. METHODS Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Merr. ; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention. RESULTS SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03, 2.85) in TT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA. CONCLUSIONS The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils. This trial was registered at clinicaltrials.gov as NCT02337231.
Association Between Continuous Glucose Monitoring-Derived Time in Range, Other Core Metrics, and Albuminuria in Type 2 Diabetes.

BACKGROUND As the use of continuous glucose monitoring (CGM) has increased, time in range (TIR) and other core CGM metrics are now emerging as the core metrics for clinical targets and assessing diabetic complications, beyond HbA1c. This study investigated the association between the CGM-derived TIR, hyperglycemia, hypoglycemia metrics, and albuminuria. METHODS A total of 866 subjects with type 2 diabetes who underwent three or six days of CGM and had urinary albumin-to-creatinine ratio (ACR) measurements were retrospectively reviewed. CGM metrics were defined according to the most recent international consensus. Albuminuria was defined as one or more of the ACR measurements being greater than 30 mg/g. RESULTS The overall prevalence of albuminuria was 36.6%. The prevalence of albuminuria was lower in subjects who achieved the target of TIR 70-180 mg/dL, time above range (TAR) > 180 mg/dL, and TAR > 250 mg/dL, as recommended by international consensus (p-value < 0.001). Multiple logistic regression analysis revealed that the odds ratio of having albuminuria was 0.94 (95% CI: 0.88-0.99, p for trend = 0.04) per 10% increase in TIR of 70-180 mg/dL, after adjusting for multiple factors including glycemic variability. The results were similar for hyperglycemia metrics (TAR> 250 mg/dL and TAR> 180 mg/dL). CONCLUSIONS TIR 70-180 mg/dL and hyperglycemia metrics are strongly associated with albuminuria in type 2 diabetes.
"It is much more real when it comes from them": The role of experts by experience in the integration of mental health nursing theory and practice.

PURPOSE To examine nursing students' perceptions of Experts by Experience impact on theoretical and practical learning. DESIGN AND METHODS Qualitative exploratory study involving focus groups with undergraduate nursing students from five European countries and Australia. Data were analyzed thematically. FINDINGS Participants described positive impacts as: bridging the theory and practice gap through first-hand experience, including sub-themes: bringing theory to life; can't be taught any other way, and innovative teaching methods fueling curiosity. RELEVANCE TO CLINICAL PRACTICE Integrating theory and practice is key for quality mental health nursing practice. Experts by experience can potentially contribute to reducing this enduring gap.
Engineering an enhanced voltage-sensing phosphatase

Voltage-sensing phosphatases (VSPs) can be used to experimentally manipulate cellular phosphoinositide levels. Kawanabe et al. describe an enhanced VSP based on the zebrafish orthologue Dr-VSP and developed by the introduction of a mutation into a membrane-interacting site and fusion with the N-terminal cytoplasmic region of sea squirt VSP.
Utility of isocitrate dehydrogenase 1 as a serum protein biomarker for the early detection of non‐small‐cell lung cancer: A multicenter in vitro diagnostic clinical trial

We aimed to verify the expression status and diagnostic significance of isocitrate dehydrogenase 1 (IDH1) in non‐small‐cell lung cancer (NSCLC), especially during early stages. Serum IDH1 levels were measured by ELISA. A total of 1223 participants (660 patients with NSCLC, 276 healthy controls [HCs], 95 patients with benign pulmonary conditions [BPCs], 135 patients with other cancers [OCs], and 57 samples with interfering factors) were divided into a training cohort and a validation cohort according to 3 testing centers. The IDH1 concentrations in the NSCLC group were obviously higher than those in the control groups (P < .001). Area under the receiver operating characteristic curves (AUCs) for discriminating NSCLC patients from controls (HC, BPC, and OC) were 0.870 and 0.745 (sensitivity, 63.3% and 55.0%; specificity, 86.8% and 86.3%) in the training cohort and validation cohort, respectively. The AUCs for discriminating stage 0‐IA lung cancer patients from HCs were 0.907 and 0.788 (sensitivity, 58.6% and 59.1%; specificity, 92.9% and 89.3%) in 2 cohorts, respectively. Isocitrate dehydrogenase 1 showed specificity for NSCLC and had no diagnostic value for other common cancers. Furthermore, IDH1 was significantly reduced in postoperative serum. Isocitrate dehydrogenase 1 shows clinical utility as a serum protein biomarker for the early diagnosis of NSCLC.
Mapping Mourning Among Muslims of Kashmir: Analysis of Religious Principles and Current Practices

From the instance a person passes away, the funeral, mourning, and memorial ceremonies follow sets of religious principles and procedures in every society. However, at the same time, these ceremonies and practices are influenced by the cultural patterns that people endorse. Mourning practices among Muslims of Kashmir also derive from such a religious-cultural amalgamation. This study aims to highlight mourning practices from two standpoints: (a) the prerequisites of the Islamic tradition and (b) the way mourning is actually practiced in Kashmir. To compare the general mourning practices with the actual Kashmiri Muslim mourning practices, different secondary sources were used and in-depth interviews were conducted with 11 participants (6 women, 4 men, and 1 Islamic scholar). The study revealed that mourning practices followed by Muslims of Kashmir are influenced by traditions outside the religion of Islam.
Validity of a Smartphone Application and Chest Strap for Recording RR Intervals at Rest in Athletes.

OBJECTIVE To evaluate the accuracy of the smartphone application (app) HRV Expert (CardioMood) and a chest strap (H10 Polar) for recording R-R intervals compared with electrocardiogram (ECG). METHODS A total of 31 male recreational runners (age 36.1 [6.3] y) volunteered for this study. R-R intervals were recorded simultaneously by the smartphone app and ECG for 5 minutes to analyze heart-rate variability in both the supine and sitting positions. Time-domain indexes (heart rate, mean R-R, SD of RR intervals, count of successive normal R-R intervals differing by more than 50 ms, percentage of successive normal R-R intervals differing by more than 50 ms, and root mean square of successive differences between normal R-R intervals), frequency-domain indexes (low frequency, normalized low frequency, high frequency, normalized high frequency, low-frequency to high-frequency ratio, and very low frequency), and nonlinear indexes (SD of instantaneous beat-to-beat variability and long-term SD of continuous R-R intervals) were compared by unpaired t test, Pearson correlation, simple linear regression, and Bland-Altman plot to evaluate the agreement between the devices. RESULTS High similarity with P value varying between . 97 and 1.0 in both positions was found. The correlation coefficient of the heart-rate-variability indexes was perfect (r = 1.0; P = .00) for all variables. The constant error, standard error of estimation, and limits of agreement between ECG and the smartphone app were considered small. CONCLUSION The smartphone app and chest strap provide excellent ECG compliance for all variables in the time domain, frequency domain, and nonlinear indexes, regardless of the assessed position. Therefore, the smartphone app replaces ECG for any heart-rate-variability analysis in runners.
Oral corticosteroid prescription patterns for asthma in France, Germany, Italy and the UK

Oral corticosteroids (OCS) are used to manage asthma exacerbations and severe, uncontrolled asthma, but OCS use is associated with adverse effects. We aimed to describe the patterns of OCS use in the real-world management of patients with asthma in western Europe. We used electronic medical records from databases in France, Germany, Italy and the United Kingdom from July 2011 through February 2018. Patients aged ≥12 years with an asthma diagnosis, at least one non-OCS asthma medication within ±6 months of diagnosis, and available data ≥6 months prior to and ≥90 days after cohort entry were included. High OCS use was defined as OCS ≥450 mg prescribed in a 90-day window during follow-up. Baseline characteristics and OCS use during follow-up were described overall and by OCS use status. Of 702 685 patients with asthma, 14–44% were OCS users and 6–9% were high OCS users at some point during follow-up. Annual prevalence of high OCS use across all countries was ∼3%. High OCS users had a mean of between one and three annual OCS prescriptions, with an average daily OCS dosage of 1.3–2.2 mg. For patients who continued to meet the high-use definition, daily OCS exposure was generally stable at 5.5–7.5 mg for ≥2 years, increasing the risk of adverse effects. Our study demonstrates that OCS use is relatively common across the four studied European countries. Data from this study may provide decisive clinical insights to inform primary care physicians and specialists involved in the management of severe, uncontrolled asthma. This study gives a real-world snapshot of oral corticosteroid (OCS) use in western Europe, by highlighting an opportunity to shift towards corticosteroid-sparing therapies or safer alternatives that mitigate the risk of OCS-associated adverse effects http://bit.ly/3cB8kk8
Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients

Background Coronary artery calcification (CAC) is common in end-stage renal disease (ESRD) patients, and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients. Cartilage oligomeric matrix protein (COMP), as a component of the vascular matrix, has been found to be an inhibitor of arterial calcification in basic studies. However, there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis (MHD) patients. The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients. Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people. MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events (MACEs), which were defined as a combined end point of new onset angina pectoris, nonfatal myocardial infarction, heart failure, coronary artery revascularization, hospitalization due to angina pectoris and all-cause deaths. The CAC score was calculated based on computed tomography scans. Results The serum COMP level in MHD patients was significantly higher than that in the general population [984.23 (248.43–1902.61) ng/mL vs. 219.01 (97.26–821.92) ng/mL, P < 0.01]. Serum COMP levels were positively correlated with CAC (r = 0.313, P = 0.021) and serum parathyroid hormone in MHD patients (r = 0.359, P < 0.01). Linear regression suggested that after adjusting for age, fasting blood glucose (Glu) and glycosylated hemoglobin (HbAlc), CAC score was an independent predictor in the final model for COMP level (β = 0.424, t = 3.130, P < 0.01). The receiver operating characteristic (ROC) curve showed that COMP ≥ 994 mg/mL had 68.0% sensitivity and 72.4% specificity for the prediction of severe CAC [area under the curve (AUC): 0.674, P = 0.030, 95% CI: 0.526–0.882]. After a median follow-up of 16 months (8–24 months), there was no difference in the incidence rate of MACEs between the upper, middle and lower serum COMP groups. Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls. The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients. However, there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.
The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques

Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of HIV as a potential “shock and kill” therapeutic for HIV cure. However, the ability of N-803 to reactivate latent virus and modulate anti-viral immunity in vivo under the cover of ART remains undefined. Here, we show that in ART-suppressed, simian-human immunodeficiency virus (SHIV)SF162P3-infected rhesus macaques, subcutaneous administration of N-803 activates and mobilizes both NK cells and SHIV-specific CD8+ T cells from the peripheral blood to lymph node B cell follicles, a sanctuary site for latent virus that normally excludes such effector cells. We observed minimal activation of memory CD4+ T cells and no increase in viral RNA content in lymph node resident CD4+ T cells post N-803 administration. Accordingly, we found no difference in the number or magnitude of plasma viremia timepoints between treated and untreated animals during the N-803 administration period, and no difference in the size of the viral DNA cell-associated reservoir post N-803 treatment. These results substantiate N-803 as a potent immunotherapeutic candidate capable of activating and directing effector CD8+ T and NK cells to the B cell follicle during full ART suppression, and suggest N-803 must be paired with a bona fide latency reversing agent in vivo to facilitate immune-mediated modulation of the latent viral reservoir.
Diagnosis of renal transplant rejection: Banff classification and beyond

Diagnosis of renal transplant rejection is dependent on interpretation of renal allograft biopsies. The Banff Classification of Allograft Pathology, which was developed as a standardized working classification system in 1991, has contributed to the standardization of definitions for histologic injuries resulting from renal allograft rejections and provided a universal grading system for assessing these injuries. It has also helped to provide insight into the underlying pathogenic mechanisms that contribute to transplant rejection. In addition to histological and immunologic parameters, molecular tools are now being used to facilitate the diagnosis of rejection. In this review, I will discuss morphologic features of renal transplant rejections as well as major revisions and pitfalls of the Banff classification system, and provide future perspectives.