Miracle-dz/UniFAR-FTUs huggingface dataset:
Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation.

PURPOSE Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion. METHODS EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate-ICECaP-database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS Data for 10,350 patients were analyzed from 15 radiation therapy-based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall's tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy-based trials.
Genes of the extinct Caucasian bison still roam the Białowieża Forest and are the source of genetic discrepances between Polish and Belarusian populations of the European bison, Bison bonasus

European bison (Bison bonasus) populations from both the Polish (PL) and the Belarusian (BY) sides of the Bialowieza Forest represent the Lowland genetic line (LB line) – progeny of the Lowland bison (Bison bonasus bonasus) that inhabited western, central, and south-eastern Europe in historical times. During the species recovery, one of the founders was a descendant of the extinct Caucasian bison (Bison bonasus caucasicus) and its descendants formed the other genetic line – Lowland–Caucasian (LC). There have been justified suspicions that LB European bison in the former Soviet Union had undergone cross-mating with the LC line. We performed a comparative genetic analyses on European bison from the BY and PL parts of the Bialowieza Forest, the LC line and extinct Caucasian bison, based on a set of 19 microsatellite markers and 1512 bovine single nucleotide polymorphism (SNP) markers, polymorphic in at least one of the studied populations. Although genetic variability (mean allele number and expected heterozygosity) for both populations were similar, the FST jack-knifing and principal component analyses PCA revealed highly significant differences between PL and BY bison from the Bialowieza Forest. Examining DNA of the extinct Caucasian bison revealed that at least part of the genetic variants found in the BY, but not the PL, population were of Caucasian origin. The results indicate that the contemporary population of European bison from the BY part of the Bialowieza Forest should not be regarded as a LB line. The results also suggest that the actual global population size of the LB line European bison is only a half of its official status. Consideration of the presented results are crucial in determining management actions and policy decisions in order to conserve LB line bison within the Bialowieza Forest – its natural refuge. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114, 752–763.
Competitive Neurocognitive Functions Can Tell Us What to Learn and When: In Schools and Beyond

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.
Clonal hematopoietic mutations linked to platelet traits and the risk of thrombosis or bleeding

Platelets are key elements in thrombosis, particularly in atherosclerosis-associated arterial thrombosis (atherothrombosis), and hemostasis. Megakaryocytes in the bone marrow, differentiated from hematopoietic stem cells are generally considered as a uniform source of platelets. However, recent insights into the causes of malignancies, including essential thrombocytosis, indicate that not only inherited but also somatic mutations in hematopoietic cells are linked to quantitative or qualitative platelet abnormalities. In particular cases, these form the basis of thrombo-hemorrhagic complications regularly observed in patient groups. This has led to the concept of clonal hematopoiesis of indeterminate potential (CHIP), defined as somatic mutations caused by clonal expansion of mutant hematopoietic cells without evident disease. This concept also provides clues regarding the importance of platelet function in relation to cardiovascular disease. In this summative review, we present an overview of genes associated with clonal hematopoiesis and altered platelet production and/or functionality, like mutations in JAK2. We consider how reported CHIP genes can influence the risk of cardiovascular disease, by exploring the consequences for platelet function related to (athero)thrombosis, or the risk of bleeding. More insight into the functional consequences of the CHIP mutations may favor personalized risk assessment, not only with regard to malignancies but also in relation to thrombotic vascular disease.
Calcineurin mediates a-adrenergic stimulation ofNa+,K+-ATPase activity inrenal tubule cells

ABSTRACT The a-adrenergic agonist oxymetazoline in-creasedNa+,K+-ATPaseactivityofsingleproximalconvolutedtubulesdissectedfromratkidney. Activationoftheenzymebyoxymetazoline wasprevented byeither the a1-adrenergic an- tagonist prazosin or the a2-adrenergic antagoityohimbineandwasmimickedbythecalciumionophoreA23187.Theeffectofoxymetazoline on Na+,K+-ATPase activity waspreventedbyaspecific peptideinhibitorofcalcineurin, as wedasby FK 506, an immunosuppressantagent known to inhibit calcineu-rin; these results indicate that the action ofoxymetazoline ismediatedviaactivationofcalcineurin (a calcium/caimodulin- dependent protein phosphatase). Activation of the Na+,K+-ATPasebyeitheroxymetazolineorA23187 was aocited witha >2-fold increase in its affinity forNa+. Theresults provide a biochemical me s bywhich norepinephrine, releasedfromrenal nerve terminals, stimulates Na+ retention. Regulation ofsodiumexcretion byrenal sympathetic nerve activity plays a major role in the maintenance of Na+homeostasis (1). However,little is knownaboutthe mecha-nism bywhich this regulation occurs. Norepinephrine pro-
Liver stiffness value obtained by point shear wave elastography is significantly related with atrial septal defect size.

PURPOSE The increase in volume and pressure in the right atrium (RA) and right ventricle (RV) has been shown to increase the liver stiffness (LS). In the literature, there is no information about the changes in LS value in patients with atrial septal defect (ASD). The aim of our study was to investigate the change of LS values obtained by point shear-wave elastography (pSWE) in patients with ASD and the clinical utility of pSWE for this disease. METHODS This cross-sectional study included 66 patients with ostium secundum ASD: 21 patients with no indication for ASD closure (Group I), 38 patients who underwent ASD closure (Group II), and 7 patients who had ASD with Eisenmenger syndrome (Group III). All patients underwent echocardiography and pSWE. Increased LS was accepted as ≥7 kPa. RESULTS LS values as well as transaminases, clinical signs of heart failure and functional and structural heart abnormalities (increase of RA and RV diastolic dimensions, tricuspid regurgitation pressure gradient [TRPG], ASD size and decrease of ejection fraction, tricuspid annular plane systolic excursion) significantly increased from Group I to Group III (P < 0.001 for all comparisons). Mean LS values for Group I, Group II, and Group III were 5.16±1.55 kPa, 7.48±1.99 kPa, and 13.9±2.58 kPa, respectively. In multivariate linear regression analysis, ASD size and TRPG were significantly associated with LS increase. Only ASD size independently predicted abnormal LS increase ≥7 kPa according to multivariate logistic regression. Clinical value of LS increase was comparable to TRPG for detection of Eisenmenger syndrome; in the receiver operating curve analysis, area under the curve was 0.995 for LS (P < 0.001) and 0.990 for TRPG (P < 0.001). At 10 kPa threshold, LS determined the Eisenmenger syndrome with 100% sensitivity and 91.5% specificity. CONCLUSION LS value assessed by pSWE was significantly increased in ASD patients with closure indication and Eisenmenger syndrome compared to patients without ASD closure indication and was comparable with TRPG in regards to Eisenmenger syndrome identification. ASD size significantly associated with LS and independently predicted abnormal LS increase ≥7 kPa.
Strain improvement studies on Kurthia species for the production of alkaline phosphatase

Alkaline phosphatase (E.C.3.1.3.1) or orthophosphoric monoester phosphohydrolase is a hydrolase enzyme responsible for dephosphorylation at alkaline pH. The enzymes are wide spread in environment. Applications of alkaline phosphatases in molecular biology, diagnostics, dairy, biosensors, agriculture and aquatic ecosystem have been studied (Suresh and Das, 2014; Bel-Ochi et al., 2013; Tekaya et al., 2013; Rankin et al., 2010; Durrieu et al., 2003; Jordan et al., 1995). The constant increase of alkaline phosphatase applications in diverse areas demands the enhanced production of alkaline phosphatase. Highest possible yield of the fermented product can be majorly obtained with utilized microorganism where the potential productivity of the microorganism can be attained by strain improvement. Strain improvement has been essential in the development of process for fermentation products. Improved strains can be achieved with mutations in natural strain and subsequent screening.
Artificial Insemination (AI) by Raw Semen: its Advantages and Disadvantages in Deshi Chicken (Gallus domesticus)

To judge the advantages and disadvantages of Artificial Insemination (AI) by raw semen in deshi chicken a test experiment was conducted in Bangladesh Agricultural University (BAU) poultry farm, Mymensingh, Bangladesh. Male birds (RIR) were collected from the BAU poultry farm, whereas the female birds (deshi hens) were purchased from nearby local village market. Both types of birds were kept in individual cage with adlibitum food and water and were given abdominal massage at least for three days (at the same time of the day) prior to AI. Collected semen was inseminated (0.20-0.25 ml/hen) directly by soft dropper into the female genital tract. The result of the present experiment showed that 1-2 females could be covered by semen collected from single ejaculate from one cock. It was also found that very small amount of semen was wastage by container. Thus it can be concluded that AI by raw semen is not profitable (except experimental point of view) until we use semen diluents for commercial purpose.
Avaliação da atividade antimibrobiana de Eugenia uniflora L.

BEZERRA, N. A. Avaliacao da atividade antimibrobiana de Eugenia uniflora L. 2012. 16f. Trabalho de Conclusao de Curso (Graduacao em Ciencias Biologicas)- Universidade Estadual da Paraiba, Campina Grande, 2012.
Chemical composition and antimicrobial activity of the flower and root hexane extracts of Althaea officinalis in

The hexane extracts of flower and root of Althaea officinalis which were collected from northwestern Iran (Khalkhal) were obtained by Soxhlet apparatus. The fatty acids were derived from methyl esters and determined by gas chromatography/flame ionization detector (GC/FID) and gas chromatograph/mass spectrometry (GC/MS) systems. The hexane extract from the flower and root contained omega-3 (20.5 and 14.9%, respectively). The other main compounds of the flower extract were palmitic acid (13.0%), heptacosane (9.3%) and nonacosane (11.2%). In the root extract, palmitic acid (16.8%), linoleic acid (omega-6) (28.0%) and naphthalene decahydro 2, 6- dimethyl (16.4%) were the main components. The antimicrobial activity of the hexane extracts of those samples were determined against some Gram-positive and Gram-negative bacteria (Escherichia coli , Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacillus subtilis , Enterococcus faecalis , Staphylococcus aureus and Staphylococcus epidermidis ), as well as three fungi ( Aspergillus niger, Candida albicans and Saccharomyces cerevisiae ). The bioassay showed that the both extracts exhibited good antimicrobial activity. This study reveals that all the parts of this plant are attractive sources of fatty acid components.
Vascular Protection by Exercise in Obesity: Inflammasome-associated Mechanisms

Supplemental digital content is available in the text. ABSTRACT Purpose The nodlike receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical player in vascular pathology as it regulates caspase-1-mediated interleukin (IL)-1β processing. Physical activity ameliorates obesity-induced inflammation and vascular dysfunction, but the mechanisms responsible for these positive changes are incompletely understood. Here, the protective effect of physical activity on the inflammasome-associated vascular dysfunction in obesity and its putative mechanisms were investigated. Methods Mice were fed a control low-fat diet (LFD) or a high-fat diet (HFD; 45% of calories from fat) and provided with running wheel access (LF-RUN or HF-RUN) or denied wheel access for our sedentary condition (LF-SED or HF-SED). The NLRP3 inflammasome-associated pathway, including NLRP3, caspase-1, and IL-1β, in mice aorta was examined by RT-qPCR and FLICA and DAB staining. The protein expression of zonula occluden-1 (ZO-1), ZO-2, adiponectin (APN), and adiponectin receptor 1 (AdipoR1) in aortic endothelial cells was determined by immunofluorescence double staining. Intracellular reactive oxidative stress and nitric oxide (NO) production were monitored with fluorescence probes, dihydroethidium, and diaminofluorecein. Results HFD increased caspase-1 and IL-1β at mRNA and protein levels in endothelial cells of the aorta, and this was attenuated by voluntary running. HFD decreased ZO-1 and ZO-2 expression and reduced APN and AdipoR1 signaling; these were restored by running. The elevated intracellular superoxide (O2.-) production observed in HF-SED was ameliorated in HF-RUN. Finally, HF-RUN improved NO production in the aorta compared with HF-SED. Conclusions Our findings suggest that voluntary running ameliorates mechanisms associated with vascular dysfunction by suppressing NLRP3 inflammasome, improving NO production, and reducing oxidative stress. Such benefits of physical activity may be, at least in part, associated with APN–AdipoR1 signaling and tight junction protein expression.
The Effectiveness of Laminectomy Surgery in Marital Adjustment of Patients with Chronic Low Back Pain

Background: Chronic low back pain is a common problem in primary care. Low back pain is one of the most common causes of disability that affects different aspects of these patients’ lives. One of the aspects that are affected by chronic low back pain is couples’ marital adjustment. Objectives: This study aimed to investigate the effectiveness of laminectomy surgery in marital adjustment of patients with chronic low back pain. Methods: The study design was quasi-experimental. The statistical population of this research consisted of all patients with chronic back pain referred to Fatemi Hospital in Ardabil. The instrument used in this research to collect data was Spanier Dyadic Adjustment scale (DAS) distributed once before surgery and once 3 months after surgery. The data were analyzed by dependent t-test using SPSS software. Results: Forty persons (55.6%) were female, and 32 persons (44.4%) were male. The results showed that marital adjustment significantly increased after the laminectomy surgery in terms of the following dimensions, marital satisfaction, solidarity, affection, and mutual trust compared to the before surgery (P < 0.05). Conclusions: Considering the obtained results, the laminectomy surgery in patients with chronic back pain causes an increase in marital adjustment in terms of all dimensions.
The Effect of Halcoholic Extract of Celery Leaves on the Delivery Rate (Fertilization and Stillbirths), the Number, Weight and Sex Ratio of Rat off Spring

Objectives: Infertility is one of the most common health problems in the world. Different plants are used in traditional medicine to treat infertility. Celery is rich in flavonoids and vitamins E and C. The present study investigated the effect of hydroalcoholic extract of celery leaves on the delivery rate, number, weight and sex ratio of rat offspring. Materials and Methods: In this experimental study, 45 Wistar rats were randomly divided into three groups of fifteen (five male and 10 female rats per group). The control group received 1 ml of distilled water, and experimental groups received respectively doses of 100 and 200 mg/kg/BW celery extract for five weeks by gavage. During the fifth week each male rat was mated with two female rats from the same group in a separate cage. After a week, every female rat was kept in the separate cages. Females received celery extract during pregnancy and until childbirth. Finally, the number of the delivery females, number, weight and sex ratio of offspring were recorded. The data were analyzed by one-way ANOVA test using SPSS15 software. Results: The number of the delivery rats in the experimental groups was not significantly different than the control group (P>0.05). The number of newborns was significantly increased in each experimental group compared to the control group (P 0.05). Conclusions: Celery improved fertility due to have flavonoid and antioxidant activity, and its consumption in both sexes can be useful in the treatment of infertility. © 2014 AENSI Publisher All rights reserved.
Small molecule glucagon receptor antagonists: an updated patent review (2015–2019)

ABSTRACT Introduction The peptide hormone glucagon acts as a counterregulatory response to hypoglycemia and as a key driver in the development of all forms of diabetes. Thus, inhibition of glucagon action, including through antagonism of the glucagon receptor by small molecule therapeutics, has been explored in clinical settings as a means to achieve glycemic control in patients with type 2 diabetes mellitus and mitigate associated comorbidities. Areas covered This review covers patent applications concerning small molecule glucagon receptor antagonists (GRAs) published between 2015 and 2019. With the exception of the cholesterol absorption inhibitor-GRA combination, patents, or applications pertaining to combination therapies or method of treatment were excluded. In addition, a discussion on findings from clinical trials is included. Expert opinion An evident trend toward declining discovery efforts in GRAs was observed. With respect to the structural novelty, most applications contain compounds broadly similar to earlier chemical matter. Based on findings from clinical trials, while GRAs are highly effective in lowering hemoglobin A1c (HbA1c) levels, key safety issues (cholesterol elevation, aminotransferase elevation, blood pressure effects) remain the primary hurdle for the field.
Redução do nível protéico da dieta, através da formulação baseada em aminoácidos digestíveis

One experiment was conducted to study the reduction of protein level, through formulation based in digestible amino acids, using broilers in the initial phase. Eight hundred one-day-old male chicks, Cobb, were weighted and distributed in a random design, envolving four treatments (22%, 20% and 18% crude protein with digestible aminoacids and one control treatment with 22% crude protein based on total amino acids), envolving 4 replications of 50 birds each. Data from weight gain, feed intake and feed conversion were collected. When broilers were fed control diet, the same weight gain and feed conversion were obtained when compared with birds fed 22% crude protein and total amino acids and 20% crude protein formulated on digestible amino acids. It is possible to work diets with less protein level (20% crude protein) without affecting the performance when diet is formulated based on digestible amino acids.
Canopy management for fruitfulness

This paper reviews the influence of canopy management practices on grapevine bud fruitfulness and fruit yield per node. These practices include trellis-training systems, shoot positioning, shoot orientation, shoot trimming, leaf removal in the fruiting zone, control of shoot number and spacing, and control of shoot vigour. An important theme of this review is the primary role that the light environment of the renewal zone plays in the regulation of shoots per node, bunches per shoot, weight per bunch and primary bud-axis necrosis (PBN). Such necrosis is a possible cause of the low number of bunches per shoot associated with high shoot vigour and canopy shading; increased incidence of PBN results in a greater proportion of secondary, compared with primary shoots. As a consequence, average shoot fruitfulness is decreased by the replacement of the relatively fruitful primary shoots with less fruitful secondary shoots.
Differential Monocyte Actuation in a Three‐Organ Functional Innate Immune System‐on‐a‐Chip

A functional, human, multiorgan, pumpless, immune system‐on‐a‐chip featuring recirculating THP‐1 immune cells with cardiomyocytes, skeletal muscle, and liver in separate compartments in a serum‐free medium is developed. This in vitro platform can emulate both a targeted immune response to tissue‐specific damage, and holistic proinflammatory immune response to proinflammatory compound exposure. The targeted response features fluorescently labeled THP‐1 monocytes selectively infiltrating into an amiodarone‐damaged cardiac module and changes in contractile force measurements without immune‐activated damage to the other organ modules. In contrast to the targeted immune response, general proinflammatory treatment of immune human‐on‐a‐chip systems with lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ) causes nonselective damage to cells in all three‐organ compartments. Biomarker analysis indicates upregulation of the proinflammation cytokines TNF‐α, IL‐6, IL‐10, MIP‐1, MCP‐1, and RANTES in response to LPS + IFN‐γ treatment indicative of the M1 macrophage phenotype, whereas amiodarone treatment only leads to an increase in the restorative cytokine IL‐6 which is a marker for the M2 phenotype. This system can be used as an alternative to humanized animal models to determine direct immunological effects of biological therapeutics including monoclonal antibodies, vaccines, and gene therapies, and the indirect effects caused by cytokine release from target tissues in response to a drug's pharmacokinetics (PK)/pharmacodynamics (PD) profile.