Miracle-dz/UniFAR-FTUs huggingface dataset:
Contraction and relaxation of isolated cardiac myocytes of the frog under varying mechanical loads.

The mechanics of cardiac systole and relaxation have been studied primarily at the level of the whole heart or intact muscle. End-systolic pressure-volume relations of frog hearts have been found to be load dependent, whereas those of the mammal are relatively load independent. On the other hand, myocardial relaxation as studied at the muscle level is load independent in the frog but markedly load dependent in the mammal. Interpretation of these studies is complicated because of the unknown contribution of extracellular connective tissue, neurohumoral factors, and, in the case of the heart, the complex chamber geometry. Therefore, it is valuable to study cardiac mechanics at the level of the basic unit of contractile activity--the isolated myocyte. The goal of this study was to subject isolated frog cardiomyocytes to mechanical loading paradigms that mimic those presented to the cells within the heart. In the first part of this study, the afterload and preload of contracting cells were varied to study their effects on the end-systolic force-length relation, which was consistently found to be load independent over the range of isotonic shortening tested (typically 5%). We also investigated the force-length-time response of the cells to test the concept of the heart behaving as a time-varying elastance. Our results suggest that in this regard the frog myocyte behaves like mammalian muscle, and they are consistent with the presence of a small viscosity within the cell. We conclude that the tissue structure of the frog heart may contribute to disparity in mechanical behavior at the different structural levels. In the second part of this study, we subjected isolated frog cardiomyocytes to four different loading paradigms to test the hypothesis that myocardial relaxation in the frog is independent of load. These sequences consisted of afterloaded contractions followed by conventional isotonic-isometric relaxation (ACCR) or afterloaded contractions followed by physiologically reversed isometric-isotonic relaxation (ACPR). Relaxation was measured under isometric conditions using a variable afterload with either the ACCR or ACPR paradigms. The decay of force was independent of the cell length at which it occurred or the amount of shortening prior to it within the contractile cycle. Relaxation also was measured as relengthening of the cell under isotonic late-load conditions, using the ACPR paradigm either with a variable afterload or variable late load. Relengthening had a time course that was unaffected by changes in afterload (i.e., extents of shortening) or late load (equivalent to the filling pressure for the heart). (ABSTRACT TRUNCATED AT 400 WORDS)
Melt Diversity and Magmatic Evolution in the Dali Picrites, Emeishan Large Igneous Province

Picrites are potentially near‐primary melts that offer rare insights into the earliest stages of magmatic evolution. However, without detailed investigation of magmatic processes, robust records of early melt evolution and mantle melting behavior cannot be acquired. Here petrological and geochemical interrogations of the Dali picrites were conducted to investigate the magmatic processes. Compositional variation observed in the Dali picrites is dominated by variable accumulation of a wehrlitic assemblage, transported by a low MgO carrier melt. Groundmass clinopyroxenes were produced by direct crystallization of the carrier melt. In contrast, compositions of olivine‐hosted melt inclusions and clinopyroxene macrocrysts indicate that olivine and clinopyroxene macrocrysts crystallized from diverse melt batches that are genetically related to the carrier melt, which formed as a consequence of magma mixing. The compositional range of melts in equilibrium with clinopyroxene macrocrysts with Mg# < 88 (> 88) is similar to (notably smaller than) the range of melt inclusions hosted in olivine macrocrysts with equivalent forsterite values. This observation can be explained by coupling between major and trace elements during partial melting in the mantle. Overall, a process involving periodic magma replenishment, tapping, and fractional crystallization in deep magma chamber(s) can explain the compositional variations recorded in the Dali macrocryst assemblage. Close genetic relationships between macrocrysts and carrier melts appear to be common to many primitive mafic rocks, which may reflect common deep magma chamber processes whereby diverse mantle‐derived melts are injected and evolved, and the primitive macrocrysts thus formed are subsequently transported by mixed liquids, producing macrocryst‐bearing primitive mafic rocks.
Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?

CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. OBJECTIVE To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. DESIGN Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). MAIN OUTCOME MEASURE Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. RESULTS The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.
ASPHALT AND POLYMER MODIFIED ASPHALT PROPERTIES RELATED TO THE PERFORMANCE OF ASPHALT CONCRETE MIXES (WITH DISCUSSION)

Some of the physical properties of polymer modified asphalts are exceptional when compared with conventional asphalts. Does the exceptional performance in such tests equate to improved performance in asphalt mixes? To address this question, five asphalts were studied: three conventional asphalts representing the extremes of temperature susceptibility and two polymer-modified asphalts, each containing 5% polymer. The following areas were studied: rheology and physical properties; thermally induced cracking; flexural fatigue life; permanent deformation; aging - chemical and rheological changes; and binder tolerance to mix variables. Discussion of each of these research areas is presented in this paper. The study indicates that the exceptional performance of the polymer modified asphalts in tests such as temperature susceptibility, force ductility, toughness-tenacity and low temperature ductility does not correlate with exceptional performance of the modified binders in mixes. Such tests may characterize modified binders, but they do not indicate improved performance in asphalt concrete mixes. A focus of this research was to identify the properties of the binder which did correlate with mix performance properties. Some conventional tests, and parameters derived from those tests, did correlate well with the mix performance. The correlations are discussed. A major result of this research was to establish that fundamental viscoelastic properties of the binders are well correlated with and help explain the behavior of the binders in asphalt concrete. Dynamic mechanical analysis of the five test asphalts was extensively used in the course of this study. Measurements of the viscoelastic properties of the binders over a range of possible road temperatures is shown to be well correlated with the behavior of the binders in properly designed and prepared asphalt concrete. It was interesting (and unexpected) to find that a conventional asphalt included in this study performed better than the polymer modified asphalts. The proper balance of viscoelastic properties in the binder which is necessary for good mix performance is shown to exist naturally in some asphalts. Data are shown which suggest that the proper balance occurs when an effective elastic network is created by natural, molecular associations.
Non-pharmacological treatment for depressed older patients in primary care: A systematic review and meta-analysis

Background Late-life depression is most often treated in primary care, and it usually coincides with chronic somatic diseases. Given that antidepressants contribute to polypharmacy in these patients, and potentially to interactions with other drugs, non-pharmacological treatments are essential. In this systematic review and meta-analysis, we aimed to present an overview of the non-pharmacological treatments available in primary care for late-life depression. Method The databases of PubMed, PsychINFO, and the Cochrane Central Register of Controlled Trials were systematically searched in January 2017 with combinations of MeSH-terms and free text words for “general practice,” “older adults,” “depression,” and “non-pharmacological treatment”. All studies with empirical data concerning adults aged 60 years or older were included, and the results were stratified by primary care, and community setting. We narratively reviewed the results and performed a meta-analysis on cognitive behavioral therapy in the primary care setting. Results We included 11 studies conducted in primary care, which covered the following five treatment modalities: cognitive behavioral therapy, exercise, problem-solving therapy, behavioral activation, and bright-light therapy. Overall, the meta-analysis showed a small effect for cognitive behavioral therapy, with one study also showing that bright-light therapy was effective. Another 18 studies, which evaluated potential non-pharmacological interventions in the community suitable for implementation, indicated that bibliotherapy, life-review, problem-solving therapy, and cognitive behavioral therapy were effective at short-term follow-up. Discussion We conclude that the effects of several treatments are promising, but need to be replicated before they can be implemented more widely in primary care. Although more treatment modalities were effective in a community setting, more research is needed to investigate whether these treatments are also applicable in primary care. Trial registration PROSPERO CRD42016038442.
Differential Effect of Ticagrelor Versus Prasugrel on Coronary Blood Flow Velocity in Patients With Non–ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: An Exploratory Study

Background—Prasugrel and ticagrelor provide a superior anti-ischemic action than clopidogrel, with some of ticagrelor’s benefits possibly attributed to adenosine-mediated mechanisms. We aimed to compare the effect of maintenance dose of ticagrelor versus prasugrel on coronary blood flow velocity (CBFV) during increasing doses of intravenously administered adenosine. Methods and Results—In a prospective, single-center, single-blind, crossover study, 56 patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention were randomized to receive either ticagrelor 90 mg BID or prasugrel 10 mg OD with a 15-day treatment period. At the end of each treatment period, CBFV by transthoracic Doppler echocardiography was assessed at baseline and under incremental doses (50 &mgr;g/kg per minute, 80 &mgr;g/kg per minute, 110 &mgr;g/kg per minute, and 140 &mgr;g/kg per minute) of adenosine infusion. Maximal CBFV area under the curve was higher for ticagrelor-treated than for prasugrel-treated patients, with a least squares mean difference of 7.16 (95% confidence interval, 2.61–11.7; P=0.003). Maximal CBFV/baseline CBFV ratio was higher with ticagrelor than prasugrel at 50, 80, and 110 &mgr;g/kg per minute but not at 140 &mgr;g/kg per minute adenosine infusion rate, with mean difference (95% confidence interval) of 0.17 (0.08–0.26; P<0.001), 0.21 (0.02–0.41; P=0.03), 0.24 (0.01–0.47; P=0.04), and 0.14 (−0.12 to 0.4; P=0.3), respectively. Conclusions—In patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention, ticagrelor augments CBFV to a greater extent than prasugrel when incremental doses of adenosine are administered. Although exploratory, these results may represent a pleiotropic action of ticagrelor, possibly contributing to its beneficial effects in such patients. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT01642966
Plasmin Generation Plays different Roles in the Formation and Removal of Arterial and Venous Thrombus in Mice

Summary The role of plasminogen (Plg) and α2-antiplasmin (α2-AP) in vascular thrombolysis in vivo was investigated in mice deficient in plasminogen (Plg−/−) or α2-AP (α2-AP−/−) or their wild type (PAI-1+/+, α2AP+/+). A thrombus was induced in the murine carotid artery or the internal jugular vein by endothelial injury. Blood flow was continuously monitored for 90 min and for 6 h 30 min after the initiation of endothelial injury. The times to occlusion by the developing thrombus in the carotid artery and the jugular vein of wild type mice were 12 ± 1.8 and 7.2 ± 1.9 min, respectively. The arterial thrombus formation in α2AP−/− mice was indistinguishable from the one in wild type mice, whereas the time to occlusion in Plg−/− was significantly shortened to 5.9 ± 1.7 min. Vascular patency after spontaneous reperfusion was markedly improved in α2-AP−/− mice. On the contrary, arterial patency in Plg−/− mice was aggravated. In venous thrombus formation, the time to occlusion in α2-AP−/− mice was significantly prolonged (27.1 ± 5.2 min), whereas in Plg−/− it was slightly shortened to 6.5 ± 2.5 min. Vascular patency after spontaneous reperfusion was also improved in α2-AP−/− mice, but not in Plg−/− mice. Histological observations using SEM indicated that fibrin nets were firmly fixed on the injured area in Plg−/− mice, but not in α2-AP−/− mice. The tail bleeding time was not different in any type of mice. However, re-bleeding time using a template bleeding device was significantly prolonged in α2-AP−/− as compared with that of wild type mice. In conclusion, lack of plasminogen markedly reduces the antithrombotic activities in vivo, whereas α2-AP plays a more important role in the formation and removal of venous thrombus in mice. Consequently, the inhibition of α2-AP could be a useful tool for the therapy of venous thrombosis and the prevention of re-thrombus formation.
Photosynthesis in lightfleck areas of homobaric and heterobaric leaves

Leaves within a canopy are exposed to a spatially and temporally fluctuating light environment which may cause lateral gradients in leaf internal CO2 concentration and diffusion between shaded and illuminated areas. In previous studies it was hypothesized that lateral CO2 diffusion may support leaf photosynthesis, but the magnitude of this effect is still not well understood. In the present study homobaric leaves of Vicia faba or heterobaric leaves of Glycine max were illuminated with lightflecks of different sizes, mimicking sunflecks. Photosynthetic properties of the lightfleck areas were assessed with combined gas exchange measurements and chlorophyll fluorescence imaging. Lateral diffusion in homobaric leaves with an interconnected intercellular air space stimulated photosynthesis and the effect was largest in small lightfleck areas, in particular when plants were under drought stress. Such effects were not observed in the heterobaric leaves with strongly compartmented intercellular gas spaces. It is concluded that lateral diffusion may significantly contribute to photosynthesis of lightfleck areas of homobaric leaves depending on lightfleck size, lateral diffusivity, and stomatal conductance. Since homobaric leaf structures have been reported for many plant species, it is hypothesized that leaf homobary may have an impact on overall plant performance under conditions with a highly heterogeneous light environment.
Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

Hereditary non-polyposis colorectal cancer (HNPCC) is the commonest form of inherited colorectal cancer (CRC) predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI)—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs) and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.
Observer agreement in endoscopic assessment of ulcerative colitis.

BACKGROUND Colonoscopy is the investigation of choice to evaluate ulcerative colitis, but the reliability of the assessment of endoscopic signs is not clear. AIMS The aim of this study was to evaluate interobserver agreement for the identification of endoscopic lesions typical of ulcerative colitis, and the influence of training. MATERIAL AND METHODS Four experienced observers and 11 endoscopists under training assessed 49 still images selected from endoscopic video recordings. RESULTS The agreement rate between experienced observers was excellent or good (k > 0.39) for recognition of 10 out of 14 signs or patterns (loss of vascular pattern, erythema, oedema, granular mucosa, blood, pseudopolyp, erosion, ulcer, normal pattern, severe activity), and was poor for pus, stricture, mild activity, moderate activity. The rates between endoscopists under training were excellent or good for 6 items (loss of vascular pattern, erythema, oedema, pseudopolyp, normal pattern, severe activity). CONCLUSIONS Trained observers can reproducibly record most endoscopic signs of ulcerative colitis. A reliable overall scoring of severity should be based on a simple three-grading scale, i.e. normal pattern, moderate activity, severe activity. Acceptable agreement rates can be obtained by endoscopists under training on some well-defined endoscopic appearances.
Estradiol metabolism in isolated human endometrial epithelial glands and stromal cells.

Intact epithelial glands and stromal cells were isolated from normal proliferative and secretory endometrial specimens by digesting the tissue fragments with 0.1% collagenase solution. These components were identified by the structure of the glands and the distinct morphology of the cell cultures. The same morphological characteristics and estradiol dehydrogenase (E2DH) activity were maintained from generation to generation in the primary cell cultures derived from either glands or stroma. The generation time of cultured stromal cells was shorter than that of glandular epithelial cells. The growth rate of both cell cultures was accelerated by addition of estradiol (E2) and medroxyprogesterone acetate in culture medium. Metabolism of E2 was studied in the freshly isolated glands and stromal cells by incubating these components, with radioactive E2 or estrone (E1) at various concentrations and time intervals. Qualitative and quantitative variations in the metabolic pattern of E2 were distinguished in epithe.
Temperature and food concentration have limited influence on the mixture toxicity of copper and Microcystis aeruginosa to Daphnia magna

Standard ecotoxicity tests are conducted under constant and favorable experimental conditions. In natural communities, however, the toxicity of chemicals may be influenced by abiotic and biotic environmental factors. Firstly, the authors examined the influence of temperature and total food concentration on the nature of the combined effects of copper (Cu) and the cyanobacterium Microcystis aeruginosa to Daphnia magna (i.e., whether the combined effects deviated from noninteraction). Secondly, the authors investigated the relative influence of the percentage of M. aeruginosa in the diet, temperature, and total food concentration on chronic Cu toxicity to D. magna. The nature of the combined effects between Cu and M. aeruginosa (i.e., synergism according to the independent action reference model and noninteraction according to concentration addition reference model) was not affected by temperature and total food concentration. In line with other studies, the concentration addition reference model gave rise to more protective predictions of mixture toxicity than the independent action reference model, thus confirming the former model's suitability as a conservative scenario for evaluating mixture toxicity of Cu and M. aeruginosa under the temperature and food concentrations tested. Further, the 21‐d median effective concentration for Cu based on reproduction varied between 20 μg/L and 100 μg/L, and the results indicate that the percentage of M. aeruginosa explained 76% of the variance in the Cu median effective concentration for reproduction, whereas the effects of temperature and total food were limited (together explaining 11% of the variance). The present study suggests that environmental risk assessment of Cu should consider specific situations where harmful M. aeruginosa blooms can co‐occur with elevated Cu exposure. Environ Toxicol Chem 2016;35:742–749. © 2015 SETAC