Miracle-dz/UniFAR-FTUs huggingface dataset:
MUTATIONS IN BETATUBULIN MAP TO DOMAINS INVOLVED IN REGULATION OF MICROTUBULE STABILITY IN EPOTHILONE-RESISTANT CELL LINES

The epothilones (Epos) are a group of natural products isolated from the myxobacterium, Sorangium cellulosum . They have a mechanism of action similar to that of Taxol, i.e. , they stabilize microtubules and induce the formation of microtubule bundles in cells. Because they are simpler in structure than Taxol and preserve their activity in P-glycoprotein-expressing cells, they are being studied as potential antitumor drugs. In this work, a series of Epo-resistant A549 and HeLa cell lines have been selected and analyzed. Class I β-tubulin, the major isotype of β-tubulin in these Epo-resistant cell lines, has been sequenced in a search for mutations. In the Epo B-resistant A549 cells, there is a mutation at β292 from Gln to Glu, in the Epo A-resistant HeLa cell line there is a mutation at β173 from Pro to Ala, and in the Epo B-resistant HeLa cell line there is a heterozygous mutation at β422 from Tyr to a mixture of Tyr and Cys. These mutations are close to the M-loop, the nucleotide-binding site, and the microtubule-associated protein binding sites, respectively. It is likely that these mutations in β-tubulin provide cells with a mechanism of resistance to the Epos and taxanes. Among these resistant cell lines, A549.EpoB40 is hypersensitive to microtubule-destabilizing drugs, such as vinblastine and colchicine, and HeLa.EpoB1. 8 is dependent on the Epos or taxanes for growth. Our studies provide evidence that the M-loop, the GTP binding site, and the microtubule-associated protein binding sites at the COOH terminus in β-tubulin are critical for the regulation of microtubule stability.
The relationship between shoot number and vigor in grapevines: Physiological causes and practical implications.

By Laura Susan Deyermond, M.S. Washington State University May 2010 Chair: Markus Keller One of the first lessons a viticulturist is taught is that high quality grapes are dependent on the ideal balance between grapevine shoot and fruit growth. As most of the vegetative growth occurs before fruit set, i.e. before the berries become strong sinks, it seems that competition between berry and shoot growth cannot be the reason for the reduction of vigor. A hydraulic limitation was believed to be the cause of the differences in vigor of vines with varying shoot numbers. The hydraulic limitation hypothesis was tested by pruning field-grown Merlot vines to a large range of bud numbers and exposing the vines to repeated water stress and irrigation. The resulting differences in vigor were assessed by measuring shoot length and final pruning weight, gas exchange, water potential, and the resistance to water flow through the vine at key stages of development. The study was conducted with field-grown, own-rooted grapevines. 100 vines were pruned in winter leaving between 5 and 200 buds per vine, and the clusters thinned to one cluster per shoot at bloom. It was found that the inverse relationship between shoot number and vigor was not caused by a hydraulic limitation as the vines’ resistance to water flow was higher in
Vole diet on experimentally managed reforestation areas in northern Sweden

In northern Sweden two field experiments with the reforestation techniques soil scarification, ploughing, burning and grass herbicidal treatment were performed. Small rodents were trapped regularly on the managed plots and their stomachs were examined microscopically for diet composition. Both bank voles Clethrionomys glareolus and field voles Microtus agrestis were common on the reforestation areas while only a small number of grey-sided voles Clethrionomys rufocanus were taken. All three species underwent a population cycle during the studies. The management techniques generally resulted in small and irregular effects on the food selection. The most pronounced changes were lower intake of grasses by M. agrestis after herbicidal treatment and of filamentous tree lichens by C. glareolus after most treatments. Both bank voles and field voles ate predominantly forbs in the summer half of the year, whereas the field voles took also a considerable amount of grass. As a complement to green vegetable-matter bank voles ate berries and fungi in summer-autumn and tree lichens at other times of the year, but seeds and animals food only in very small amounts. Ail three species consumed large quantities of dwarf-shrubs in autumn and especially in winter. Considerable amounts of bark were eaten by field voles and a smaller proportion by bank voles in autumn-winter. Both for bank and field voles there were indications of worsening food conditions as the population cycle went on, There were, for example, an increase in grass and bark intake in field voles and a decrease in seeds and berries for the hank vole.
Learning in the Wild with Incremental Skeptical Gaussian Processes

The ability to learn from human supervision is fundamental for personal assistants and other interactive applications of AI. Two central challenges for deploying interactive learners in the wild are the unreliable nature of the supervision and the varying complexity of the prediction task. We address a simple but representative setting, incremental classification in the wild, where the supervision is noisy and the number of classes grows over time. In order to tackle this task, we propose a redesign of skeptical learning centered around Gaussian Processes (GPs). Skeptical learning is a recent interactive strategy in which, if the machine is sufficiently confident that an example is mislabeled, it asks the annotator to reconsider her feedback. In many cases, this is often enough to obtain clean supervision. Our redesign, dubbed ISGP , leverages the uncertainty estimates supplied by GPs to better allocate labeling and contradiction queries, especially in the presence of noise. Our experiments on synthetic and real-world data show that, as a result, while the original formulation of skeptical learning produces over-confident models that can fail completely in the wild, ISGP works well at varying levels of noise and as new classes are observed.
The interplay of pollinator diversity, pollination services and landscape change

Summary 1. Pollinators are a functional group with high relevance for ensuring cross-pollination in wild plant populations and yields in major crops. Both pollinator declines and losses of pollination services have been identified in the context of habitat destruction and land use intensification. 2. This editorial synthesizes and links the findings presented in seven papers in this Special Profile, focusing on pollinator diversity and plant‐pollinator interactions in natural habitats and agricultural landscapes. 3. The results contribute to our understanding of local and landscape scale effects of land use intensification on pollinator densities and diversity, and pollination functions in wild plant communities and crops. 4. Synthesis and applications . We emphasize the exceptional coverage in pollination ecology ranging from basic ecological relationships to applied aspects of ecosystem services and ecosystem management, and conclude with identifying gaps in current knowledge and challenging research areas for the future.
Effects of Patient Activation Intervention on Chronic Diseases: A Meta-Analysis

ABSTRACT Background Patient activation has been described as a potential strategy to improve chronic disease self-management. However, the effects of patient activation interventions on psychological and behavioral outcomes have not been systematically evaluated. Purpose This study was designed to evaluate the effects of patient activation interventions on physiological, psychological, behavioral, and health-related quality of life outcomes in patients with chronic diseases. Methods We systematically searched four databases (PubMed, Cochrane, CINAHL, and Embase) from inception to September 1, 2017. We identified English- and Chinese-language published reports of randomized controlled trials that evaluated the effects of patient activation interventions for adults with chronic diseases. Study selection, data extraction, and quality assessment were performed by two reviewers independently. We summarized the intervention effects with Hedges's g values and 95% confidence intervals using a random-effects model. We used the Cochrane Handbook to assess the methodological quality of the randomized controlled trials. Results Twenty-six randomized controlled trials were included in the qualitative synthesis and meta-analysis. In terms of overall study quality, most of the included studies were affected by performance and detection bias. Patient activation interventions produced significant effects on outcomes related to physiological, psychological, behavioral, and health-related quality of life in the context of chronic diseases. The following effect sizes were obtained: (a) physiological, namely, glycated hemoglobin = −0.31 (p < .01), systolic blood pressure = −0.20 (p < .01), diastolic blood pressure = −0.80 (p = .02), body weight = −0.12 (p = .03), and low-density lipoprotein = −0.21 (p = .01); (b) psychological, namely, depression = −0.16 (p < .01) and anxiety = −0.25 (p = .01); (c) behavioral, namely, patient activation = 0.33 (p < .01) and self-efficacy = 0.57 (p < .01); and (d) health-related quality of life = 0.25 (p = .01). Conclusions Patient activation interventions significantly improve patients' physiological, psychosocial, and behavioral health statuses. Healthcare providers should implement patient activation interventions that tailor support to the individual patients' level of patient activation and strengthen the patients' role in managing their healthcare to improve chronic-disease-related health outcomes.
Development of a Novel Flow Channel Apparatus and its Use in Testing the Adhesion Strength of Two Common New Zealand Algae

Adhesives produced by marine organisms are fascinating in that they often possess an ability to adsorb rapidly and robustly to a range of substrates, in a range of environmental conditions and in the presence of signi cant surface contamination. On top of this, they undergo curing while in contact with water. Many of the properties that make marine bioadhesives so e ective remain elusive to engineers designing synthetic adhesives. An increased understanding of marine bioadhesives would allow for the design of e ective, biologically-inspired adhesives with applications in the engineering, maritime and health sectors. Conversely, better understanding of the adhesives produced by fouling organisms could help with the design of new fouling-resistant surfaces. One essential element for characterising a bioadhesive is to assess its adhesion strength to the substrate. In this thesis, I present a novel ow channel apparatus for testing the adhesion strength of marine organisms to help characterise their associated adhesives. The ow channel was used with Hormosira banksii and Durvillaea antarctica, two marine macroalgae endemic to New Zealand, and assessments of adhesion strength are made with substrates of varied chemistry and topography. H. banksii zygotes were found to exhibit a settlement-time dependent increase in adhesion strength across all of the biomedical substrates, which included poly(methyl methacrylate) (PMMA) and three hydrogels, two of which were gelatin-based approximations of human skin. H. banksii did not exhibit any substrate-dependent variation in adhesive strength, suggesting an adhesive that is able to interact with a range of substrate types. D. antarctica exhibited more rapid adhesion to glass, PMMA, PTFE and stainless steel than did H. banksii, forming a particularly strong bond with stainless steel. On substrates with simple, de ned topographies, H. banksii zygotes were found to adhere most e ectively to a surface with a feature size slightly larger than the size of the zygote. A feature size smaller than the zygote resulted in a minor disruption of adhesion strength that diminished with settlement time.
Digestibilidade de dietas a base de grao umido de milho ou de sorgo ensilados

In vivo digestibility of diets with high moisture sorghum substituting corn was studied in 12 female bovines. Experimental design was completely randomized with three treatments, substituting high moisture corn by sorghum at 0, 50 and 100% levels. Diets contained high moisture corn or sorghum, soybean, urea, oat hay ( Avena sativa sp.), minerals and monensin. In situ degradability of corn and sorghum in cracking, grinding and silage processes was evaluated. There was no difference in apparent digestibility of crude protein, crude fiber, neutral detergent fiber and ethereal extract. Negative lineal effect was observed (P < 0,05) for apparent digestibility of starch with sorghum inclusion. Processing interacted with grain when effective degradation of dry matter was concerned (P < 0,01). Corn had the highest degradation in high moisture silage; the worst degradation occurred with cracked; an intermediate degradation occurred in grinding (P < 0,01). Degradation in silage was similar as that of cracked degradation in sorghum; it was worst in grinding (P < 0,01).
COVID-19–associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network

A recent case report described the radiological features of a suspected COVID-19 necrotising haemorrhagic encephalopathy.1 We present here a description of clinical, biological, radiological and immunological features of a COVID-19 patient case, evocative of virus-associated acute necrotising encephalopathy (ANE) possibly mediated by antibodies. Patient’s representative consent has been obtained in agreement with the journal’s policy. A 51-year-old man without personal or family history of neurological disease was hospitalised after 10 days of fever and cough. COVID-19 was diagnosed by reverse-transcriptase PCR on nasal swab and bilateral ground-glass opacities on thoracic CT scan. At day 12, he was admitted in intensive care unit (ICU) for non-invasive ventilation. The result of the neurological examination was normal. At day 21, while the patient had been weaned off oxygen, he became unresponsive and rapidly comatose (Glasgow Coma Scale 6: E1, V1, M4) with a disconjugated gaze. The patient was groaning and showing rhythmic movements of the right upper limb. An urgent brain MRI, including diffusion-weighted imaging (DWI) and MR angiogram, ruled out vertebrobasilar ischaemic stroke; gradient echo T2*-weighted images excluded haemorrhage and thrombus in the venous system. It revealed only subtle hyperintensities in bilateral thalami on FLAIR sequence (figure 1). Consciousness impairment required tracheal intubation. He was hyperthermic (39°C) without shock. Blood and cerebrospinal fluid (CSF) samples revealed thrombopenia and lymphopenia, mild inflammatory response (C reactive protein, ferritin and fibrinogen), CSF albumin-cytological dissociation with increased CSF IgG antibodies (91.9 mg/L, normal 10–30 mg/L) and altered blood–brain barrier integrity (CSF/serum albumin index=17.3, normal <6.5) (online supplementary material). An electroencephalogram revealed symmetrical background activity of low-voltage delta waves without spatial organisation, triphasic waves or paroxysmal activity. He showed unresponsive coma (Glasgow Coma Scale=3), pyramidal syndrome, right-sided sixth nerve palsy and no corneal reflex. A second brain contrast-enhanced MRI at day 22 revealed progressing lesions with diffuse hyperintense …
Genomic Profiling of Prostate Cancers from Men with African and European Ancestry

Purpose: African American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies. Experimental Design: To identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained from four publicly available datasets comprising 250 AFR and 611 European American (EUR) men and a targeted sequencing dataset from a commercial platform of 436 AFR and 3018 EUR men. Results: Mutations in ZFHX3 as well as focal deletions in ETV3 were more frequent in tumors from AFR men. TP53 mutations were associated with increasing Gleason score. MYC amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from AFR men. KMT2D truncations and CCND1 amplifications were more frequent in primary PCa from AFR men. Genomic features that could impact clinical decision making were not significantly different between the two groups including tumor mutation burden, MSI status, and genomic alterations in select DNA repair genes, CDK12, and in AR. Conclusions: Although we identified some novel differences in AFR men compared with other populations, the frequencies of genomic alterations in current therapeutic targets for PCa were similar between AFR and EUR men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.
The effect of the CONSORT statement on the amount of “unclear” Risk of Bias reporting in Cochrane Systematic Reviews

Background The Consolidated Standards of Reporting Trials (CONSORT) statement aims to improve clarity and consistency of transparency of reporting in Randomized Controlled Trials (RCTs). The Cochrane Risk of Bias (RoB) tool for RCTs helps authors to judge the RoB. as ‘‘low”, “high” or “unclear”. Objective In this study we aimed to assess whether the implementation and updates of the CONSORT statement influenced the trend of “unclear” RoB scores of RCTs included in Cochrane systematic reviews. Methods All Cochrane reviews published in December to October 2016 were retrieved. The publication year of RCTS included in the reviews were sorted into time frames (≤1995, 1996–2000, 2001–2009 and ≥2010) based on the release- and updates of the CONSORT statement (1996, 2001 and 2010). The association between “unclear” RoB versus “low or high” RoB and the year of publication in different time frames were calculated using a binary logistic regression. Results Data was extracted from 64 Cochrane reviews, with 989 RCTS (6471 items). The logistic regression showed that the odds of RCTs published ≥2010, compared to ≤1995 were more likely not to report an “unclear” RoB for the total data (Odds Ratio (OR) 0.69 (95% Confidence interval: 0.59–0.80)), random sequence generation (OR 0.32 (0.22–0.47), allocation concealment (0.64 (0.43–0.95)) and incomplete outcome data (OR 0.60 (0.39–0.91)). Conclusion A slight decrease of “unclear” RoB reporting over time was found. To improve quality of reporting authors are encouraged to adhere to reporting guidelines.
Increasing growth temperature alters the within-host competition of viral strains and influences virus genetic variation

The emergence of viral diseases in plant crops hamper the sustainability of food production, and this may be boosted by global warming. Concurrently, mixed viral infections are becoming common in plants, of which epidemiology are unpredictable due to within-host virus-virus interactions. However, the extent in which the combined effect of variations in the abiotic components of the plant ecological niche (e.g., temperature) and the prevalence of mixed infections (i.e., within-host interactions among viruses) affect the evolutionary dynamics of viral populations is not well understood. Here, we explore the interplay between ecological and evolutionary factors during viral infections, and show that two individual strains of pepino mosaic virus (PepMV) coexisted in a temperature-dependent continuum between neutral and antagonistic interactions in tomato plants. After a long-term infection, the mutational analysis of the evolved viral genomes revealed strain-specific single-nucleotide polymorphisms that were modulated by the interaction between the type of infection and temperature. Mathematical modeling allowed us to asses a thermal reaction norm for both strains, which indicated that viral replication rates were increased along with increasing temperature in mixed infections, with a remarkable strain-dependent effect. These results suggest that the growth temperature is an ecological driver of virus-virus interactions, with an effect on the genetic diversity of individual viruses co-infecting a host. This research provides insights into the effect that climate change will have on the evolutionary dynamics of viral populations.
A Structural Equation Model of Gratitude, Self-efficacy, and Medication Adherence in Patients With Stage B Heart Failure.

BACKGROUND Consistent self-care slows the progression of heart failure (HF). Gratitude, the practice of appreciating the positive aspects of life, may influence self-efficacy, which in turn is known to improve self-care. However, little is known about the relationships among gratitude, self-efficacy, and medication adherence in HF. OBJECTIVE The aim of this study was to test a model to determine if self-efficacy mediates the relationship between gratitude and medication adherence in asymptomatic patients with HF. METHOD This is a secondary analysis of data from a prospective observational study. Data were analyzed using a structural equation model to examine associations between gratitude, cardiac-specific self-efficacy, and medication adherence in 153 patients with HF. Gratitude, self-efficacy, and medication adherence were assessed using the Gratitude Questionnaire-6, Cardiac Self-efficacy Scale-Maintain Function Subscale, and the Morisky Medication Adherence Scale, respectively. RESULTS Patient mean (SD) age was 66 (11) years, and 95% of the participants were men. Patients were primarily white (79%), black (12%), or Asian (6%). Gratitude exerted an indirect effect on medication adherence through self-efficacy (b = 0.16; P < .05). Gratitude was positively related to self-efficacy (b = 0.50; P < .05), and self-efficacy was positively related to medication adherence (b = 0.31; P < .05). The model fit was acceptable (comparative fit index = 0.92, Tucker-Lewis index = 0.90, root-mean-square error of approximation = 0.08). CONCLUSION In this study, we found evidence that self-efficacy was a mechanism through which gratitude was associated with medication adherence in asymptomatic patients with HF, suggesting a way to improve self-care nonpharmacologically. Future work will examine whether gratitude intervention results in improved self-care.
Early Lycophyte Evolution

Abstract Lycophytes, comprising the groups historically known as the lycopsids and zosterophylls, have the longest history of any group of vascular land plants. The early evolution of the group is reviewed concentrating on the Late Silurian and Devonian record of Lycopsida and Zosterophyllopsida. Distinct root-like and shoot-like axes in zosterophyllopsids and lycopsids are first recorded in the Early Devonian and can be compared to the later development of pseudobipolar growth of tree-shaped lycopsids with upward-growing trunks and branch systems and downward-growing rooting systems. The development of stigmarian rootlets postdates the evolution of pseudobipolar growth, first recorded in the Middle Devonian, according to current evidence. Other important events in early lycophyte evolution during the Devonian include changes in leaf morphology, modification of sporophylls, and the eventual appearance of the lycopsid strobili.