Miracle-dz/UniFAR-FTUs huggingface dataset:
An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab

Rationale: Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitors.
Chufa Drink: Potential in Developing a New Plant-Based Fermented Dessert

Plant-based foods with desirable texture and nutritional value have attracted considerable interest from consumers. In order to meet the growing demand for more sustainable and health-focused products, new sources for plant-based products are needed. In this study, we aimed to develop an innovative plant-based dessert based on the underutilized crop chufa tubers (Cyperus esculentus). The chufa extract was fermented with plant-adapted lactic acid bacteria and formulated with the purpose of imitating the Danish summer dessert “cold butter-milk soup”. The effect of various bacterial fermentations and formulations on steady and oscillatory rheology, stability, dry matter, pH, and sugar profile of the product were studied and compared to a commercial cold buttermilk soup sample. A strain of Leuconostoc mesenteroides was found to create the most similar taste to a commercial sample. By adding lemon juice, sucrose, xanthan gum, and vanilla to the fermented chufa drink, the drink was found to mimic the pH, texture, acid profile, and stability of a commercial dairy-based sample, while containing a lower concentration of carbohydrates.
Localization and Distribution of Testicular Angiotensin I Converting Enzyme (ACE) in Neck and Mid-Piece of Spermatozoa from Infertile Men in Relation to Sperm Motility

Testicular angiotensin converting enzyme (ACE) is known to play an essential role in the male reproduction and fertility. Data about tACE in cases of male infertility are quite scarce, and in this respect we aimed to study localization and distribution of tACE protein in the neck and mid-piece of spermatozoa from pathological samples in relation to sperm motility. The enzyme expression during capacitation and acrosome reaction was quantitatively assessed. In human ejaculated spermatozoa tACE is localized on sperm plasma membrane of the head, the neck and mid-piece of the tail. The immunoreactivity becomes stronger in capacitated spermatozoa followed by a decrease in acrosome reacted sperm. In different cases of semen pathology (oligozoospermia, asthenozoospermia and teratozoospermia) fluorescent signals in the neck and mid-piece are in punctate manner whereas in normozoospermia they were uniformly distributed. The expression area of tACE the neck and mid-piece was decreased in ejaculated and capacitated sperm from pathological semen samples compared to normospermia. Significant positive correlation was established between tACE area and progressive sperm motility, whereas with immotile sperm the correlation was negative. Our data suggest that proper distribution of tACE in the neck and mid-piece is required for normal sperm motility that could be used as a novel biomarker for male infertility.
Household motor vehicle ownership and use : How much does residential density matter ?

The question of whether population density affects the amount of household automobile travel in the United States is revisited. Controls for income and demographics are included in a multivariate regression model of vehicle travel that includes vehicle ownership as an intermediate factor and that treats a household's pick of neighborhood density and the amount of travel as a simultaneous relationship. The data come from the 1990 Nationwide Personal Transportation Survey. It is found that density matters, but not much. A 10 percent increase in density leads to only a 0.7 percent reduction in household automobile travel. By comparison, a 10 percent increase in household income leads to a 3 percent increase in automobile travel. The results are similar when vehicle trips are used as the dependent variable. The effect of density is so small that even a relatively large-scale shift to urban densities would have a negligible impact on total vehicle travel.
Molecular subtyping for source tracking of Escherichia coli using core genome multilocus sequence typing at a food manufacturing plant

When harmful bacteria are detected in the final product at a food manufacturing plant, it is necessary to identify and eliminate the source of contamination so that it does not occur again. In the current study, the source of contamination was tracked using core genome multilocus sequence typing (cgMLST) analysis in cases where Escherichia coli was detected in the final product at a food manufacturing plant. cgMLST analysis was performed on 40 strains of E. coli collected from the environment [floor (26 strains), drainage ditch (5 strains), container (4 strains), post-heating production line (1 strain)] and products [final product (3 strains) and intermediate product (1 strain)]. In total, 40 E. coli isolates were classified into 17 genogroups by cgMLST analysis. The 4 E. coli strains isolated from the intermediate and final products were classified into two genogroups (I and II). Certain isolates collected from the environment also belonged to those genogroups, it was possible to estimate the transmission of E. coli in the manufacturing plant. Thus, the dynamics of E. coli in the food manufacturing location were clarified by using cgMLST analysis. In conclusion, our results indicate that cgMLST analysis can be effectively used for hygiene management at food manufacturing locations.
Urine-Based Metabolomics and Machine Learning Reveals Metabolites Associated with Renal Cell Carcinoma Stage

Simple Summary Every year, hundreds of thousands of cases of renal carcinoma (RCC) are reported worldwide. Accurate staging of the disease is important for treatment and prognosis purposes; however, contemporary methods such as computerized tomography (CT) and biopsies are expensive and prone to sampling errors, respectively. As such, a non-invasive diagnostic assay for staging would be beneficial. This study aims to investigate urine metabolites as potential biomarkers to stage RCC using machine learning techniques to mine the complex datasets produced. We present a 24-metabolite panel that discriminates between early stage and advanced stage RCC with 87% accuracy in our study cohort. Abstract Urine metabolomics profiling has potential for non-invasive RCC staging, in addition to providing metabolic insights into disease progression. In this study, we utilized liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and machine learning (ML) for the discovery of urine metabolites associated with RCC progression. Two machine learning questions were posed in the study: Binary classification into early RCC (stage I and II) and advanced RCC stages (stage III and IV), and RCC tumor size estimation through regression analysis. A total of 82 RCC patients with known tumor size and metabolomic measurements were used for the regression task, and 70 RCC patients with complete tumor-nodes-metastasis (TNM) staging information were used for the classification tasks under ten-fold cross-validation conditions. A voting ensemble regression model consisting of elastic net, ridge, and support vector regressor predicted RCC tumor size with a R2 value of 0.58. A voting classifier model consisting of random forest, support vector machines, logistic regression, and adaptive boosting yielded an AUC of 0.96 and an accuracy of 87%. Some identified metabolites associated with renal cell carcinoma progression included 4-guanidinobutanoic acid, 7-aminomethyl-7-carbaguanine, 3-hydroxyanthranilic acid, lysyl-glycine, glycine, citrate, and pyruvate. Overall, we identified a urine metabolic phenotype associated with renal cell carcinoma stage, exploring the promise of a urine-based metabolomic assay for staging this disease.
Bioactive Inks Development for Osteochondral Tissue Engineering: A Mini-Review

Nowadays, a prevalent joint disease affecting both cartilage and subchondral bone is osteoarthritis. Osteochondral tissue, a complex tissue unit, exhibited limited self-renewal potential. Furthermore, its gradient properties, including mechanical property, bio-compositions, and cellular behaviors, present a challenge in repairing and regenerating damaged osteochondral tissues. Here, tissue engineering and translational medicine development using bioprinting technology provided a promising strategy for osteochondral tissue repair. In this regard, personalized stratified scaffolds, which play an influential role in osteochondral regeneration, can provide potential treatment options in early-stage osteoarthritis to delay or avoid the use of joint replacements. Accordingly, bioactive scaffolds with possible integration with surrounding tissue and controlling inflammatory responses have promising future tissue engineering perspectives. This minireview focuses on introducing biologically active inks for bioprinting the hierarchical scaffolds, containing growth factors and bioactive materials for 3D printing of regenerative osteochondral substitutes.
The Hippo Signaling Pathway in Cancer: A Cell Cycle Perspective

Simple Summary Cancer is increasingly viewed as a cell cycle disease in that the dysregulation of the cell cycle machinery is a common feature in cancer. The Hippo signaling pathway consists of a core kinase cascade as well as extended regulators, which together control organ size and tissue homeostasis. The aberrant expression of cell cycle regulators and/or Hippo pathway components contributes to cancer development, and for this reason, we specifically focus on delineating the roles of the Hippo pathway in the cell cycle. Improving our understanding of the Hippo pathway from a cell cycle perspective could be used as a powerful weapon in the cancer battlefield. Abstract Cell cycle progression is an elaborate process that requires stringent control for normal cellular function. Defects in cell cycle control, however, contribute to genomic instability and have become a characteristic phenomenon in cancers. Over the years, advancement in the understanding of disrupted cell cycle regulation in tumors has led to the development of powerful anti-cancer drugs. Therefore, an in-depth exploration of cell cycle dysregulation in cancers could provide therapeutic avenues for cancer treatment. The Hippo pathway is an evolutionarily conserved regulator network that controls organ size, and its dysregulation is implicated in various types of cancers. Although the role of the Hippo pathway in oncogenesis has been widely investigated, its role in cell cycle regulation has not been comprehensively scrutinized. Here, we specifically focus on delineating the involvement of the Hippo pathway in cell cycle regulation. To that end, we first compare the structural as well as functional conservation of the core Hippo pathway in yeasts, flies, and mammals. Then, we detail the multi-faceted aspects in which the core components of the mammalian Hippo pathway and their regulators affect the cell cycle, particularly with regard to the regulation of E2F activity, the G1 tetraploidy checkpoint, DNA synthesis, DNA damage checkpoint, centrosome dynamics, and mitosis. Finally, we briefly discuss how a collective understanding of cell cycle regulation and the Hippo pathway could be weaponized in combating cancer.
Drivers for Adopting Public Private Partnerships—Empirical Comparison between China and Hong Kong Special Administrative Region

The private sector has long been involved in delivering public sector projects, whether its role has been as a partner or just as a contractor for the government. Over recent years the interest in adopting public private partnerships (PPPs) has increased internationally. Many research studies have presented positive reasons for the governments and the private sector to welcome this form of procurement, rather than continue adopting the traditional options. This paper aims to explore and compare the key drivers for adopting PPP in China and the Hong Kong Special Administrative Region (referred to as Hong Kong from here onwards). An empirical questionnaire survey was conducted in both of these administrative systems and survey respondents were invited to rate their perceptions on the importance of 15 different drivers identified. Eighty-seven completed survey questionnaires were returned for analysis. The findings indicated that respondents from China rated economy-related drivers higher, whereas Hong Kong .
Chemoprophylaxis to Prevent Deep Venous Thrombosis in Patients Hospitalized for Pancreatitis: Beneficial or Harmful?

Introduction: Vascular complications in pancreatitis generally occur in the form of hemorrhage or thrombosis. Pancreatitis resulting in splanchnic thrombosis has been well studied, but the cause of this correlation has not been studied in the current era of increasing anticoagulant use for deep venous thrombosis (DVT) prophylaxis. Hemorrhagic pancreatitis and peri-pancreatic bleeding are also known phenomena encountered in relation to pancreatitis, but these risks are not well established in the setting of chemical prophylaxis for DVT. Objectives: Our objective was to identify whether chemical DVT prophylaxis in pancreatitis harms the patient by increasing the risk of hemorrhagic conversion of pancreatitis or peri-pancreatic hemorrhage or if it is beneficial by preventing splanchnic venous thrombosis in the abdominal vasculature that surrounds the pancreas. Methods: We undertook a retrospective chart review with approval from the Institutional Review Board on patients who were hospitalized for or developed pancreatitis during their hospital stay from April 2014 to July 2015. We reviewed the charts for imaging suggestive of venous thrombosis or the development of intra-abdominal hemorrhage at admission during hospitalization and within 30 days after hospitalization. We also reviewed the methods of DVT prophylaxis to identify any correlation with the risk of hemorrhage or thrombosis. A bedside index of severity in acute pancreatitis score was used within 24 hours of admission to calculate the severity of the patients’ pancreatitis. The data collected were analyzed for descriptive statistics, correlation using Pearson’s coefficient, and multivariate regression analysis using Microsoft Excel and SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc. Results: This study included 389 patients who met the inclusion criteria. Of these, 74.6% of patients received chemical prophylaxis, mostly low molecular weight heparin, and 18.5% of patients were not on chemical or mechanical means of DVT prophylaxis. Only 12 patients (3%) had complications related to thrombosis and hemorrhage. Seven patients had splanchnic venous thrombosis, one had a hemorrhagic conversion of pancreatitis, three had a peri-pancreatic hemorrhage, and one had both the hemorrhagic conversion of pancreatitis and peri-pancreatic hemorrhage. Ten patients out of 12 patients had complications before admission, and nine of the 12 patients were on chemical prophylaxis. Pearson’s coefficient showed no statistically significant correlation between the incidence of complications and the use of chemical DVT prophylaxis. Multivariate analysis showed no specific variable that increased the risk of complications. Conclusions: Our study showed that chemoprophylaxis for DVT in patients hospitalized for acute pancreatitis is neither harmful by causing hemorrhagic conversion of pancreatitis, peri-pancreatic hemorrhage nor beneficial by preventing splanchnic venous thrombosis.
Effects of Gamification on the Benefits of Student Response Systems in Learning of Human Anatomy: Three Experimental Studies

This paper presents three experiments to assess the impact of gamifying an audience response system on the perceptions and educational performance of students. An audience response system called SIDRA (Immediate Audience Response System in Spanish) and two audience response systems with gamification features, R-G-SIDRA (gamified SIDRA with ranking) and RB-G-SIDRA (gamified SIDRA with ranking and badges), were used in a General and Descriptive Human Anatomy course. Students participated in an empirical study. In the academic year 2019–2020, a total of 90 students used RB-G-SIDRA, 90 students employed R-G-SIDRA in the academic year 2018–2019, and 92 students used SIDRA in the academic year 2017–2018. Statistically significant differences were found between final exam grades obtained by using RB-G-SIDRA and SIDRA, U = 39.211 adjusted p = 0.001 and RB-G-SIDRA and R-G-SIDRA U = 31.157 adjusted p = 0.015, thus finding strong evidence with respect to the benefit of the badges used in RB-G-SIDRA. Moreover, in the students’ SIDRA systems scores, statistically significant differences were found between RB-G-SIDRA and SIDRA, U = −90.521 adjusted p < 0.001, and between R-G-SIDRA and SIDRA, U = −87.998 adjusted p < 0.001. Significant correlations between individual and team scores were also found in all of the tests in RB-G-SIDRA and G-SIDRA. The students expressed satisfaction, engagement, and motivation with SIDRA, R-G-SIDRA, and RB-G-SIDRA, thus obtaining a final average assessment of 4.28, 4.61, and 4.47 out of 5, respectively. Students perform better academically with gamified versus non-gamified audience response systems. Findings can be used to build a gamified adaptive learning system.
Effects of Substituting Sedentary Behavior with Light-Intensity or Moderate-to-Vigorous Physical Activity on Obesity Indices in Adults: A Prospective Short-Term Follow-Up Study

Background: Sedentary behavior (SB) is an independent risk factor for cardiovascular diseases. We hypothesized that there may be benefits of replacing SB with light-intensity (LIPA) and moderate-to-vigorous (MVPA) physical activity. Substituting SB with LIPA and MVPA might be associated with body composition changes. Methods: We assessed body weight, body mass index (BMI), fat body mass (FBM), and physical activity level, as well as one-year changes, in 780 adults (EPIMOV Study). Results: We analyzed into 10-min blocks SB, LIPA, MVPA, and total wear time. After 14 ± 3 months of follow-up, there were 242 completed procedures. We reallocated time spent in SB to LIPA or MVPA and assessed cross-sectional and prospective associations with the outcomes using isotemporal substitution models. In cross-sectional analysis, substituting 10-min blocks of SB with MVPA led to significant decreases of 1.23 kg in body weight, 0.30 kg/m² in BMI, and 0.38% in FBM. 10-min blocks substituting SB with LIPA produced significantly lower body weight (1 kg) and BMI (0.1 kg/m²) values. In longitudinal analysis, reallocating SB to MVPA was only associated with FBM decline (−0.31%). Conclusions: Substituting SB with MVPA is associated with significant improvement in obesity indices in both cross-sectional and follow-up. Replacing SB with LIPA produced a less consistent impact.
Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas

Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3+ and MAC+ cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q+ microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases.
Study on the Architecture and Motion Control of the Traverse Robot

In order to keep the problem of robot obstacle avoidance and the traversal motion control simple, the performance and characteristics of the traverse robot are described firstly, followed the architecture of horizontal and vertical was adopted, and the traversal robots based on hybrid architecture was designed independently, also, the architecture met the performance needs of the traverse robot. Then the kinematic model of the robot was created and analyzed, and the motion control strategy based on the traversal robot was obtained. The strategy not only simplified the movement of the traversal robot, but it also completed the different methods of obstacle avoidance, which ensure the efficiency and reliability of the overall running of traversal robots.