Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic analysis of physical activity in twins.

BACKGROUND The reduced contribution of physical activity (PA) to daily energy expenditure contributes to the increased prevalence of obesity. A genetic control of activity-induced energy expenditure (AEE) may contribute to a genetic susceptibility to obesity. OBJECTIVE Our aim was to investigate the relative contribution of genetic and environmental factors to the variation and covariation in AEE and PA. DESIGN Twelve monozygotic and 8 same-sex dizygotic (including 2 same-sex sibling pairs; age differences: 2 and 2.5 y) twin pairs aged between 18 and 39 y participated. AEE was measured in a respiration chamber for 24 h and with doubly labeled water in daily life for 2 wk. PA was recorded simultaneously with a triaxial accelerometer. Structural equation modeling was used to separate and quantify the observed variance into sex-adjusted additive genetic and common and unique environmental contributions. RESULTS In the respiration chamber, common and unique environmental factors explained the variance in AEE and PA, and no genetic contribution was found. In daily life, genetic factors explained 72% of the variance in AEE and 78% of the variance in PA. Unique environmental factors explained the remaining variance. The same additive genetic factors explained 67% of the covariance in AEE and PA in daily life. CONCLUSIONS In the present exploratory study that used gold standard measurements for AEE and PA but a limited sample size, genetic influence explained a large part of the variation in AEE and PA in daily life, whereas both AEE and PA were influenced by environment only within the confined area of the respiration chamber.
A literature review of empirical research on learning analytics in medical education

The number of publications in the field of medical education is still markedly low, despite recognition of the value of the discipline in the medical education literature, and exponential growth of publications in other fields. This necessitates raising awareness of the research methods and potential benefits of learning analytics (LA). The aim of this paper was to offer a methodological systemic review of empirical LA research in the field of medical education and a general overview of the common methods used in the field in general. Search was done in Medline database using the term “LA. ” Inclusion criteria included empirical original research articles investigating LA using qualitative, quantitative, or mixed methodologies. Articles were also required to be written in English, published in a scholarly peer-reviewed journal and have a dedicated section for methods and results. A Medline search resulted in only six articles fulfilling the inclusion criteria for this review. Most of the studies collected data about learners from learning management systems or online learning resources. Analysis used mostly quantitative methods including descriptive statistics, correlation tests, and regression models in two studies. Patterns of online behavior and usage of the digital resources as well as predicting achievement was the outcome most studies investigated. Research about LA in the field of medical education is still in infancy, with more questions than answers. The early studies are encouraging and showed that patterns of online learning can be easily revealed as well as predicting students’ performance.
Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature

Recently developed potent and selective CDK4/6 inhibitors fall into two classes based on structure and toxicity profiles in clinical studies. One class, exemplified by palbociclib and ribociclib, exhibits neutropenia as a dose-limiting toxicity and requires discontinuous dosing. In contrast, the structurally distinct CDK4/6 inhibitor abemaciclib is dosed continuously, and has diarrhea and fatigue as dose-limiting toxicities. In preclinical models, palbociclib has been extensively studied and induces cell cycle inhibition in an RB-dependent manner. Thus far, abemaciclib has been less extensively evaluated. We found that abemaciclib cell cycle inhibitory activity is RB-dependent at clinically achievable concentrations. Abemaciclib elicited potent suppression of RB/E2F regulated genes associated with prognosis in ER-positive breast cancer. However, unlike palbociclib, at 250nM-1 µM doses abemaciclib induced cell death in RB-deficient cell lines. This response was associated with a rapidly-induced multi-vacuolar phenotype indicative of lysosomal membrane permeabilization that could be ameliorated with chloroquine. This event was not a reflection of inhibition of other CDK family members, but could be recapitulated with CBX4945 that inhibits casein and DYRK/HIPK kinases. To determine if these “off-target” features of abemaciclib were observed in vivo, mice harboring matched RB-positive and negative xenografts were treated with palbociclib and abemaciclib. In vivo, all of the apparent activity of abemaciclib was RB-dependent and strongly elicited suppression of cell cycle regulatory genes in a fashion markedly similar to palbociclib. Using gene expression data from cell lines and tumors treated with abemaciclib and palbociclib a composite signature of response to CDK4/6 inhibition was developed that included many genes that are individually required for tumor cell proliferation or viability. These data indicate that while abemaciclib and palbociclib can exert distinct biological and molecular effects, there are common gene expression features that could be broadly utilized in measuring the response to CDK4/6 inhibition.
Research on taking values of elastic modulus of concrete perforated brick masonry and its materials

Elastic modulus of masonry is the basic mechanics index of masonry structure. The method of taking values of e-lastic modulus of concrete perforated brick masonry and its materials is studied from three different ways. That is: the formulae of elastic modulus of concrete perforated brick masonry, concrete perforated brick and mortar were derived on the basis of statistic regression of test results;the formulae of elastic modulus of masonry were derived on the basis of the constitutive relationship which was obtained from the axes compressive experiment;and the elastic modulus of brick masonry were derived from the formulae of elastic modulus of concrete perforated brick and mortar. The calculated results according to the three methods agreed better with the test results and current national codes. This has provided basic information for theoretical research and engineering design of concrete perforated brick masonry.
Methionine and 2-hydroxy-4-methylthiobutanoic acid are transported by distinct Na(+)-dependent and H(+)-dependent systems in the brush border membrane of the chick intestinal epithelium.

The pathways that facilitate the uptake of L-methionine (L-Met), D-methionine (D-Met) and L-2-hydroxy-4-methylthiobutanoic acid (L-HMB) were characterized in chick intestinal brush border membrane vesicles. A model of high affinity transport (Km approximating 0.1 mmol/L) converged to the data obtained for 35S-L-Met uptake under Na(+)-gradient and Na(+)-free conditions. The maximal velocity of 35S-L-Met transport was almost threefold greater in the presence of a Na(+)-gradient. Concentrations (100 mmol/L) of D-Met, the L-isomers of neutral amino acids and 2-aminobicyclo[2.2. 1]heptane-2-carboxylic acid completely inhibited 35S-L-Met transport. A model of low affinity competitive inhibition (Ki approximately 17 mmol/L) described D-Met inhibition of 35S-L-Met transport. These data indicate that L- and D-Met are transported by a broad specificity system B type transporter. Maximal rates of 3H-L-HMB uptake were obtained under conditions of an internally directed H(+)-gradient (pHin = 7.5, pHout = 5.5). A model of intermediate affinity transport (Km approximately 1 mmol/L) described H(+)-dependent 3H-L-HMB uptake across the vesicles. The data from this and other studies indicate that a H(+)-dependent, nonstereo-specific system facilitates the uptake of the hydroxy analogues of linear amino acids, including HMB.
Osteoblast‐like MC3T3‐E1 Cells Prefer Glycolysis for ATP Production but Adipocyte‐like 3T3‐L1 Cells Prefer Oxidative Phosphorylation

Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3‐E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3‐E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3‐E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3‐L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research.
Reversal of Mutualism as a Mechanism for Adaptive Radiation in Yucca Moths

Species interactions are a major source of adaptive radiation. In mutualisms, such diversification can take the form of evolution of parasites that exploit the resources needed for maintenance of the mutualism. Mutualistic associations often have associated parasitic species, and in some cases, parasitic species have indeed evolved from the mutualists. For example, obligate mutualisms, such as those involving seed‐eating pollinators, have on a few occasions given rise to nonmutualist species. These systems are relatively simple and provide models for identifying factors that facilitate the stable reversal of a mutualistic interaction. We used ecological data in a phylogenetic framework to analyze the origins of two nonmutualist cheater yucca moths. Phylogenetic analysis suggests that the evolution of cheating may be preceded by a change in oviposition behavior. Two different modes of oviposition among moth species cause density‐dependent moth egg mortality through flower abscission in one case (locule‐ovipositing species) but density‐independent mortality in the other (superficially ovipositing species). A mtDNA‐based phylogeny indicated that cheating and superficial oviposition have evolved twice each and that the cheater clades are sisters to the superficially ovipositing species clades. Consideration of the fitness consequences of two trait changes—loss of pollination and phenological delay in oviposition—in which cheaters have diverged from ancestral pollinators suggest that the shift to oviposition into fruit may have occurred first and that loss of pollination behavior was a secondary event. We suggest that secondary coexistence of two pollinator species of opposite oviposition modes may facilitate the shift to fruit oviposition and cheating and that this is applicable in the best documented of the cheater yucca moths. Superficially ovipositing species suffer dual sources of egg mortality when in coexistence with locule‐ovipositing species. Shift to fruit oviposition under this circumstance can be facilitated by access to a seed resource not available to the copollinator, preadaptations in ovipositor morphology, and pollinator phenology late relative to the copollinator. Thus the adaptive radiation of nonmutualists from mutualists may have taken place in specific ecological contexts through few trait changes, and the reversal of mutualism would be a by‐product of a shift to reliance on a previously inaccessible seed resource.
The concurrent validity and intrarater reliability of the Microsoft Kinect to measure thoracic kyphosis

This study aims to investigate the concurrent validity and intrarater reliability of the Microsoft Kinect to measure thoracic kyphosis against the Flexicurve. Thirty-three healthy individuals (age: 31±11.0 years, men: 17, height: 170.2±8.2 cm, weight: 64.2±12.0 kg) participated, with 29 re-examined for intrarater reliability 1–7 days later. Thoracic kyphosis was measured using the Flexicurve and the Microsoft Kinect consecutively in both standing and sitting positions. Both the kyphosis index and angle were calculated. The Microsoft Kinect showed excellent concurrent validity (intraclass correlation coefficient=0.76–0.82) and reliability (intraclass correlation coefficient=0.81–0.98) for measuring thoracic kyphosis (angle and index) in both standing and sitting postures. This study is the first to show that the Microsoft Kinect has excellent validity and intrarater reliability to measure thoracic kyphosis, which is promising for its use in the clinical setting.
Reactive oxygen species: key regulators in vascular health and diseases

ROS are a group of small reactive molecules that play critical roles in the regulation of various cell functions and biological processes. In the vascular system, physiological levels of ROS are essential for normal vascular functions including endothelial homeostasis and smooth muscle cell contraction. In contrast, uncontrolled overproduction of ROS resulting from an imbalance of ROS generation and elimination leads to the development of vascular diseases. Excessive ROS cause vascular cell damage, the recruitment of inflammatory cells, lipid peroxidation, activation of metalloproteinases and deposition of extracellular matrix, collectively leading to vascular remodelling. Evidence from a large number of studies has revealed that ROS and oxidative stress are involved in the initiation and progression of numerous vascular diseases including hypertension, atherosclerosis, restenosis and abdominal aortic aneurysm. Furthermore, considerable research has been implemented to explore antioxidants that can reduce ROS production and oxidative stress in order to ameliorate vascular diseases. In this review, we will discuss the nature and sources of ROS, their roles in vascular homeostasis and specific vascular diseases and various antioxidants as well as some of the pharmacological agents that are capable of reducing ROS and oxidative stress. The aim of this review is to provide information for developing promising clinical strategies targeting ROS to decrease cardiovascular risks.
Cloning and functional expression of rNBC, an electrogenic Na+-[Formula: see text]cotransporter from rat kidney.

We have recently cloned the renal electrogenic Na+-bicarbonate cotransporter of the salamander Ambystoma tigrinum(aNBC) (M. F. Romero, M. A. Hediger, E. L. Boulpaep, and W. F. Boron. FASEB J. 10: 89, 1996; and Nature 387: 409-413, 1997). Here we report the cloning of a mammalian homolog of aNBC, named rNBC for rat Na+-bicarbonate cotransporter. NBC constitutes the major route for[Formula: see text] reabsorption and assists in Na+ reabsorption across the basolateral membrane of the renal proximal tubule (PT). We used aNBC as a probe to screen a rat kidney cortex cDNA library in λgt10 and identified several clones. Each has an initiator Met and a large open-reading frame followed by a 3'-untranslated region of ∼500 bp. The 7.5-kb mRNA for rNBC is present in kidney, liver, lung, brain, and heart. In situ hybridization with the rNBC probe in the rat kidney revealed staining in the S2 segment of PT. rNBC encodes a protein of 1,035 amino acids, with a predicted molecular mass of 116 kDa. Its deduced amino acid sequence is 86% identical to that of aNBC. Comparison of both the aNBC and rNBC sequences to the GenBank database reveals a low level of amino acid identity (∼30%) to the AE family of Cl-/[Formula: see text]exchangers. Injection of rNBC cRNA into Xenopus oocytes leads to expression of an electrogenic Na+-[Formula: see text]cotransporter that is qualitatively similar to that of aNBC but at a much lower level. Placement of the rNBC cDNA into the context of a Xenopus expression vector produces a substantial increase in rNBC expression. Addition of 1.5% CO2/10 mM[Formula: see text] elicits a hyperpolarization of >50 mV and a rapid decrease of intracellular pH (pHi), followed by an increase in pHi. Subsequent removal of Na+ in the presence of CO2/[Formula: see text]causes a depolarization of >50 mV and a concomitant decrease of pHi. Thus rNBC is in the same newly identified family of Na+-linked[Formula: see text] transporters as is aNBC.
Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition (⁎P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant (⁎P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine.
Comparison of health-related quality of life with epirubicin, cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil chemotherapy regimens as first-line systemic therapy in locally advanced inoperable or metastatic gastric or gastro-esophageal junction adenocarcinoma: A prospecti

Background: Health-related quality of life (HRQOL) is an important oncologic end point for upper gastrointestinal malignancies. Unfortunately, till date, there is no published prospective data from India, comparing the HRQOL parameters between first-line chemotherapy regimens in advanced/metastatic gastric cancer. Materials and Methods: The present study aimed to compare the HRQOL of first-line systemic chemotherapy with epirubicin, cisplatin plus 5-FU (ECF) and docetaxel, cisplatin plus 5-FU (DCF) regimens in patients with locally advanced inoperable or metastatic gastric or gastro-esophageal junction adenocarcinoma. The secondary end points were overall response rate, progression-free survival (PFS), overall survival (OS), and toxicity profile. Results: Between December 2014 and December 2016, 65 patients were treated with ECF (n = 34) or DCF (n = 31) regimen. The baseline HRQOL scores were comparable between the two study groups, with the exception of significantly poor pain and sleep difficulties symptom score in the DCF group. After three cycles of treatment, both the groups showed improvements in most of the quality of life (QOL) parameters including global QOL score, compared with their baseline status. After six cycles of chemotherapy, the ECF group showed nonsignificant deterioration for most of the QOL parameters; but on the contrary, the DCF group maintained improved scores for most of the QOL parameters. The median survival until a definitive deterioration of global QOL score was significantly better in the DCF arm in comparison to the ECF arm (7.1 vs. 5.6 months, respectively, P = 0.000). The median OS was 9.2 months with ECF and 12.5 months with DCF regimen (P = 0.000), while median PFS was 5.7 and 7.4 months with ECF and DCF regimens, respectively (P = 0.002). Conclusions: This prospective study highlighted a better impact of DCF chemotherapy on the HRQOL of patients with advanced/metastatic gastric cancer and showed the importance of QOL assessments in clinical trials to complement the risk–benefit judgment.
Creating Knowledge Repositories from Biomedical Reports: The MEDSYNDIKATE Text Mining System

MEDSYNDIKATE is a natural language processor for automatically acquiring knowledge from medical finding reports. The content of these documents is transferred to formal representation structures which constitute a corresponding text knowledge base. The system architecture integrates requirements from the analysis of single sentences, as well as those of referentially linked sentences forming cohesive texts. The strong demands MEDSYNDIKATE poses to the availability of expressive knowledge sources are accounted for by two alternative approaches to (semi)automatic ontology engineering. We also present data for the knowledge extraction performance of MEDSYNDIKATE for three major syntactic patterns in medical documents.
Arginase modulates nitric oxide production in activated macrophages.

In macrophages and many other cell types,l-arginine is used as a substrate by both nitric oxide synthase (NOS) and arginase to produce nitric oxide (NO) and urea, respectively. Because the availability ofl-arginine is a major determinant for NO synthesis in the activated macrophage, we hypothesized that NO production may be reduced by arginase via depleting the common substrate in this cell type. To test this hypothesis, we investigated the effect of an arginase inhibitor,l-norvaline, on NO production in J774A.1 mouse macrophages activated by lipopolysaccharide (LPS, 1.0 μg/ml) for 22 h. In the absence of LPS, macrophages produced a low level of NO. In contrast, NO production from these cells was significantly increased in the presence of LPS. Increasing extracellular levels ofl-arginine (0.01-0.8 mM) produced a concomitant increase in NO production of activated macrophages. l-Norvaline (10 mM), which specifically inhibits arginase activity (i.e., reducing urea production by 50%) without altering NOS activity, enhanced NO production (by 55%) from activated macrophages. The enhancement of NO production by l-norvaline was inversely related to the extracellular level ofl-arginine. A more pronounced increase in NO production was observed at the lower level of extracellular l-arginine, i.e., a 55 vs. 28% increase for 0.05 and 0.1 mM extracellularl-arginine, respectively. When the l-arginine concentration exceeded 0.5 mM, thel-norvaline effect was abolished. These results indicate that arginase can compete with NOS for their common substrate and thus inhibit NO production. This regulatory mechanism may be particularly important when the extracellular supply ofl-arginine is limited.