Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety, Pharmacokinetics, and Pharmacodynamics of TD‐0714, a Novel Potent Neprilysin Inhibitor in Healthy Adult and Elderly Subjects

TD‐0714 is an orally active, potent, and selective inhibitor of human neprilysin (NEP) in development for the treatment of chronic heart failure. Oral administration of TD‐0714 in rats resulted in dose‐dependent and sustained increases in plasma cyclic guanosine monophosphate (cGMP) over 24 hours consistent with NEP target engagement. Randomized, double‐blind, placebo controlled, single ascending dose (50–600 mg TD‐0714) and multiple ascending dose (10–200 mg TD‐0714 q.d. for 14 days) studies were conducted in healthy volunteers. TD‐0714 was generally well‐tolerated and no serious adverse events or clinically significant effects on vital signs or electrocardiogram parameters were observed. TD‐0714 exhibited dose‐proportional pharmacokinetics (PKs) with high oral bioavailability, minimal accumulation after once daily dosing, and negligible renal elimination. Pharmacodynamic (PD) responses were observed at all dose levels studied, as reflected by statistically significant increases in plasma cGMP concentrations. The increases in cGMP were significantly above the baseline (~ 50–100%) on day 14 for the entire 24‐hour interval indicating that sustained cGMP elevations are achieved at steady‐state. Maximal steady‐state cGMP response was observed in plasma and urine at doses ≥ 50 mg. The TD‐0714 PK‐PD relationship and safety profile were similar in elderly vs. younger adult subjects. The TD‐0714 PK and PD profiles support further clinical development of TD‐0714 and suggest the potential for once‐daily administration and predictable exposure in patients with cardiorenal diseases regardless of their renal function.
Seasonal changes in the reproductive and life‐history traits of Chrysomela populi L. (Coleoptera: Chrysomelidae)

Seasonal changes in the reproductive and life‐history traits of Chrysomela populi L. were investigated in Shobara (34°52′N, 133°01′E), Japan, in 2004 and 2005. Larvae were hatched and reared under natural photoperiod and temperature in 8 different periods between late April and early September in 2004. The incidence of adult diapause increased with progression of the season in 2004. The critical timing of diapause induction, as defined by 50% of females entering diapause, was estimated to occur between late July and early August. No effects of season on the survival rate from hatching to adult emergence, percentage ovipositing females and percentage females that deposited viable eggs were clearly detected. Adult weight at emergence fluctuated seasonally, which was probably caused by air temperature. No effect of season on the oviposition period was observed among females that averted diapause. Females that entered diapause in 2004 started oviposition from the first day of May in 2005. Reproductive output was significantly greater in diapause females than in non‐diapause females. This increase in the reproductive output of diapause females was caused by elongation of the oviposition period and consequently by enlargement of the number of egg clutches deposited. These results suggest that the seasonal timing of diapause induction in females of C. populi would be affected by various risks and benefits to reproduction and survival.
On the importance of getting fine‐scale temperature records near any surface

The pressing need to identify the ecological consequences of climate changes boosted the development of macroecological approaches as well as climatological tools. Nevertheless, the major pitfall remains that the actual climatic conditions experienced by organisms in their microhabitat and across their home range are largely ignored. In this context, Lembrechts et al. (2020) are initiating a new global database of near-surface temperatures, especially focusing on above ground (up to 2 m) and below ground soil temperatures. This approach is welcome to assess the amplitude of microclimate change around the world and across biomes. Here, we extend this approach by highlighting that fine-scale temperature heterogeneity can be large over short times frames (minutes to hours) and short distances (centimeters to meters) in forest covers. This mosaic of microclimates likely influences the response of organisms to climate change. Further, the SoilTemp database could be expanded to other interfaces with the atmosphere.
Numerical simulation of the ENF test for the mode-II fracture characterization of bonded joints

In this work, the End Notched Flexure (ENF) test is analyzed in order to obtain the critical strain energy release rate in mode-II fracture of bonded joints. A cohesive model based on specially developed interface elements, including a linear softening damage process, is employed. The adequacy of the experimental ENF test is evaluated by numerical simulation. The objective is to compare the critical strain energy release rate in mode-II (G II c ) obtained by different data reduction schemes with the real value which is an inputted parameter in the cohesive model. The effect of the Fracture Process Zone (FPZ) ahead of the crack tip is evaluated. A crack equivalent concept is proposed in order to account for the energy dissipated in the FPZ. A data reduction scheme avoiding the need to measure crack length is proposed. A good agreement with the inputted value of G II c was obtained.
Diurnal Changes of the Exudation Rate and the Mineral Concentration in Xylem Sap after Decapitation of Grafted and Non-grafted Cucumbers

The xylem sap in cucumbers (Cucumis sativus L.) which were or were not grafted onto figleaf gourd (Cucurbita ficifolia Bouche) was collected after decapitation from the cut end of the stems hourly. The exudation rate was highest in the first one hour collection regardless of grafting, and then decreased rapidly with time. However, there was a diurnal change in the exudation rate with the maxima occurring at 1:00 to 3:00 PM and the minima at 7:00 to 8:00 AM, irrespective of decapitation time. The grafted cucumbers were smaller in amplitude than the non-grafted ones.The rate of xylem exudation and the concentrations of NO3-N, P, Ca and Mg in the first one hour exudate were higher in the grafted cucumbers than in the non-grafted ones. Only the K concentration was higher in the non-grafted cucumbers. The mineral concentration in the exudate changed remarkably with time after decapitation; the NO3-N, K and Ca concentrations decreased and the P concentration increased rapidly for the first several hours. The Mg concentration scarcely changed. Thereafter, the NO3-N and K concentrations of the exudate in the grafted cucumbers fell below the NO3-N and K concentrations in the nutrient solution, while in the non-grafted cucumbers the former was kept always above the latter.From these results, the grafted cucumbers were considered to be superior to the non-grafted ones, in water uptake and nutrient absorption except for K and also to depend more intensely in NO3-N and K absorptions on some metabolities from the upper parts of the plants.
Exercise: The ultimate treatment to all ailments?

Abstract Extensive clinical research has provided robust evidence that exercise is a cost‐effective measure to substantially alleviate the burden of a large number of diseases, many of which belong to the cardiovascular (CV) spectrum. In terms of cardiac benefit, the positive effects of exercise are attributed to improvements in standard risk factors for atherosclerosis, as well as to its positive impact on several pathophysiological mechanisms for CV diseases. For secondary prevention, exercise, optimally in the context of a cardiac rehabilitation program, has been shown to improve functional capacity and survival. Clinicians should encourage physical activity and provide exercise recommendations for all patients, taking into consideration any underlying pathology. In the present review, the benefits of exercise for the prevention and treatment of major CV risk factors and heart conditions are analyzed.
Determining Genetic Similarities and Relationships among Cowpea Breeding Lines and Cultivars by Microsatellite Markers

Cowpea [Vigna unguiculata (L.) Walp] is an important grain legume crop grown for its protein rich grains. It is an inexpensive source of protein in the diets of people in sub-Saharan Africa. The International Institute of Tropical Agriculture (IITA) has been working on the improvement of cowpea for more than 30 yr. Over 60 countries receive cowpea cultivars improved by IITA for testing and adoption where needed. Many of these cultivars have identical parentage but look very different morphologically when grown in the field. Forty-six microsatellite DNA markers were used to evaluate genetic similarities among 90 cowpea breeding lines developed at IITA. Twenty-seven primer pairs could amplify polymorphic single-locus microsatellites from all of these materials. Two to seven alleles per primer were detected with a polymorphic information content varying from 0.02 to 0.73. By means of only five polymorphic microsatellite primers, 88 of the 90 cowpea lines could be distinguished. A dendrogram based on the microsatellite polymorphisms generally agreed with the pedigree of the cowpea lines.
Ontogenteic alteration of activity and habitat selection by Bufo marinus

Recently metamorphosed Bufo marinus exhibit patterns of activity and habitat use that vary in relation to changes in weather and moisture availability. Activity adjacent to water is greatest on moist substrates at high daytime temperatures in windy weather. Conditions that inhibit evaporative cooling (no wind, dry substrates, high humidity), or are likely to lead to low body temperatures (cool temperatures at night under windy conditions) restrict activity. Activity in habitats away from permanent water is dependent on metamorphlings having grown large enough to allow night-time activity on dry substrates. Growth leads to a change in activity from diurnal as metarnorphlings, to nocturnal and diurnal as juveniles (30-70 mm SVL), and to nocturnal as adulthood approaches. Size-dependent changes in patterns of activity and habitat use are accompanied by changes in pelvic patch morphology and body pigmentation. The morphological changes may have resulted from selection acting to minimise time spent in the smaller size classes which are vulnerable to predators, competitors and the environment, and size-dependent optimisation of chemical defences.
Tectonic sliding within the Moinian Loch Eil Division near Kinlocheil, W. Inverness-shire: comment

SIRS Strachan (1982) sub-divided the Loch Eil Division psammites (Johnstone et al. 1969) of the Kinlocheil area into a series of mappable units, and produced a welcome refinement of the stratigraphy in this area. He argued that both the impersistence of some units, and the apparent stratigraphic repetitions, are the result of tectonic sliding, on the grounds that the stratigraphy determined south of Loch Eil (the 'type' stratigraphy) was also the original stratigraphy north of Loch Eil. My mapping along the Glenfinnan/Loch Eil Division junction, between Glenfinnan and Glen Affric, confirms Strachan's view that there is a more complex stratigraphy in this zone than that proposed by Johnstone et al. (1969), and shows, moreover, that there is a lateral variation in the lithostratigraphy. However, poor exposure in the area where the 'type' stratigraphy is defined (Strachan 1982, pp. 189-90) means that control on the lateral persistence of units is there less precise than in the well exposed Na h-Uamhachan/Gulvain area (Strachan 1982, fig 1) where complex sliding is invoked to explain lateral changes. Hence it might have been appropriate to use the sequence in the northern area to interpret the southern area. In the light of the new field observations I have reservations about the interpretation of the Kinlochcil area as a zone of sliding. Lithostratigraphic, metamorphic fabric and geometrical evidence argue against the published conclusions. Detailed re-examination of the area suggests that there are no suitable field criteria for distinguishing the lithologies of the Basal Psammites from those of the Glen Garvan Psammites; beds within the Kinlocheil Cross-Bedded Quartzites are also commonly indistinguishable from beds within these two formations, e.g. the eastern slope of Druim Fearna [NM 96 77] consists of locally cross-bedded psammites with little or no quartzite. Poor exposure south of Loch Eil means that here the lateral persistence of the Kinlocheil Banded Quartzites cannot be proved, and their distribution north of Loch Eil suggests that while they are a distinctive lithology, they are not a unique lithostratigraphic formation. In the Na hUamhachan area (Strachan 1982, fig. 1), north of Loch Eil, quartzites identical to the Kinlocheil Banded Quartzites occur within a unit designated the Gulvain Psammitic Gneisses (Glenfinnan Division). These quartzites occur intcrbanded with gneissose psammite on a metre scale, and as a lens, mappable at 1:10 000 scale [NM 975 849]. The latter occurs within in situ psammitic gneisses to the north of the slides shown by Strachan; it might be better interpreted as a small sedimentary
Medicinal Flowers. Part 29. Acylated Oleanane‐Type Triterpene Bisdesmosides: Perennisaponins G, H, I, J, K, L, and M with Pancreatic Lipase Inhibitory Activity from the Flowers of Bellis perennis

The MeOH extract from the flowers of Bellis perennis was found to show pancreatic-lipase inhibitory activity (IC50 455 μg/ml). From the extract, seven new triterpene saponins named perennisaponins G (1; IC50 163 μM), H (2; 137 μM), I (3; 147 μM), J (4; 148 μM), K (5; 223 μM), L (6; 81.4 μM), and M (7; 195 μM) were isolated as pancreatic lipase inhibitors. The stereostructures of 1–7 were elucidated on the basis of chemical and spectroscopic evidence.
Comparison of short- and long-term outcomes following laparoscopy and open total gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND The aim of this study was to compare the short- and long-term outcomes of laparoscopic total gastrectomy (LTG) with those of open total gastrectomy (OTG) for the upper part of clinical Stage I gastric cancer. METHODS Between 2000 and 2015, 122 and 96 consecutive gastric cancer patients who had undergone curative LTG and OTG with lymphadenectomy were enrolled in the study. We performed the simple intracorporeal techniqueof esophagojejunostomy using a circular stapler in LTG. This technique comprised of laparoscopic trans-abdominal anvil insertion into the esophagus, which was assisted by lifting up the nasogastric tube connected to the anvil head. RESULTS By the Clavien-Dindo classification defined as grade II or high, the rate of postoperative complications was 14.8% (14/112: Grade II (7), IIIa (4), and IIIb (3)) in LTG and 15.6% (15/96) in OTG. There was no anastomotic leakage (0% (0/122)) and only 3.3% (4/122) of anastomotic stenosis in LTG. There was no significant difference in the short-term outcomes between both groups in all enrolled and propensity score-matched patients (LTG vs. OTG: 15.4% (10/65) vs. 16.9% (11/65)). Regarding the long-term outcomes, there was no significant difference in overall survival between both groups in all enrolled (P = 0.190) and propensity score-matched patients (P = 0.643). CONCLUSIONS LTG for the upper part of clinical Stage I gastric cancer is a safe and reliable procedure and could have similar short- and long-term outcomes as OTG.
Baseline Requirements for Novel Agents Being Considered for Phase II/III Brain Cancer Efficacy Trials:Conclusions from the Adult Brain Tumor Consortium's First Workshop on CNS Drug Delivery.

Author(s): Grossman, Stuart A; Romo, Carlos G; Rudek, Michelle A; Supko, Jeffrey; Fisher, Joy; Nabors, L Burt; Wen, Patrick Y; Peereboom, David M; Ellingson, Benjamin M; Elmquist, William; Barker, Fred G; Kamson, David; Sarkaria, Jann N; Timmer, William; Bindra, Ranjit S; Ye, Xiaobu
Prevalence and psychosocial correlates of subjectively perceived decline in five cognitive domains: Results from a population‐based cohort study in Germany

Subjective cognitive decline (SCD) was frequently investigated for memory in healthy aging or in relation to diseases like dementia. It was found to be related to sociodemographic and psychological variables as well as cognitive abilities. The prevalence of SCD in other cognitive domains and their relation to these variables is largely unknown to date. The present study aimed to fill this gap.
Factors Affecting the Plasma Prolactin Level in the Cow and the Goat as Determined by Radioimmunoassay

Plasma prolactin concentration of serial blood samples taken from cows and goats bearing indwelling jugular venous catheter was assayed by a radioimmunologic procedure. Using 9 lactating cows, the response of prolactin release to milking was investigated at different stages of lactation. In all cases, plasma prolactin levels rapidly increased and reached a peak 4-20 min after the start of milking. The magnitude of the response was considerably different with the stage of lactation in the same cow. The peak of plasma prolactin released by milking was highest in the early stage of lactation (189±34ng/ml, SE), and decreased thereafter with the advance of lactation. Conspicuous response of prolactin release with a 40-to 100-told increase by milking was also obtained in the lactating goats. Feeding could induce a rapid elevation of plasma prolactin in the lactating cow. Mimic-or sham-milking in heifers and in virgin goats in which teats were pulled and the udder was massaged by hands for 5 min, induced an acute prolactin release within 2 min after the start of stimulation, although there was no milk flow. Stressful stimulus associated with venipuncture also elevated the plasma prolactin in the lactating and non-lactating animals. These findings lead to the conclusion that prolactin is a hormone which can be released by various stimuli and that milking is the most powerful of the stimuli for the acute prolactin discharge from the anterior pituitary gland in the cow as well as in the goat at least in the early stage of lactation. At the same time, a variety of non-specific stimuli can also cause a rapid rise in plasma prolactin concentration.
The effect of surface sculpturing on the interpretation of opaque and hyaline zones in the orange roughy otolith

Summary Opaque and hyaline zones in orange roughy (Hoplostethus atlanticus: Trachichthydidae) otoliths (sagittae) were shown to correspond to both surface sculpturing of the otolith, and to light refractive opaque and hyaline zones within the otolith which are independant of the otolith surface sculpture. Three different patterns of opaque zones resulted from this effect, patterns which depend on whether the otolith is observed by transmitted light, incident light, or in section. Zusammenfassung Der Effekt der Oberflachenstrukturen auf die Interpretation der opaken und hyalinen Zonen des Otolithen Es wurden Oberflachenstrukturen aus Steroscanaufnahmen auf den Otolithen von Hopolstethus atlanticus mit den im Durchlicht, im Auflicht und in Schnitten erkennbaren opaken und hyalinen Zonen verglichen. Dabei liesen sich 2 Otolithentypen feststellen: In der einen Gruppe der Otolithen waren die Oberflachenstrukturen nur gering ausgebildet, mit deutlichen opaken Zonen. In der anderen Gruppe gab es opake Zonen, die unterschiedlich stark mit Oberflachenstrukturen korrespondierten. Die Konsequenzen fur Altersbestimmungen z. B. bei Sebastes alums unter Benutzung der Muster aus opaken Zonen werden diskutiert. Resume Effect des structures de la surface sur l'interpretation des zones opaques et hyalines de l'otolithe Les structures de la surface des otolithes de Hopolstethus atlanticus ont ete comparees avec les zones opaques et hyalines reconnaissables en transparence, par lumiere directe ou en coupe. Deux types d'otolithes ont ete constates: dans un groupe d'otolithes les structures de la surface n'etaient que peu apparentes avec des zones opaques bien definies. Dans l'autre groupe les zones opaques correspondaient, a des degres differents, aux structures de la surface. Les consequences pour la determination de l'âge, comme de Sebastes alutus par exemple, sont discutees sous consideration des formes des zones opaques.
Partitioning of dry mass and leaf area within plants of three species grown at elevated CO2.

1. We tested the hypothesis that the net partitioning of dry mass and dry mass:area relationships is unaltered when plants are grown at elevated atmospheric CO2 concentrations. 2. The total dry mass of Dactylis glomerata, Bellis perennis and Trifolium repens was higher for plants in 700 compared to 350 μmol CO2 mol–1 when grown hydroponically in controlled-environment cabinets. 3. Shoot:root ratios were higher and leaf area ratios and specific leaf areas lower in all species grown at elevated CO2. Leaf mass ratio was higher in plants of B. perennis and D. glomerata grown at elevated CO2. 4. Whilst these data suggest that CO2 alters the net partitioning of dry mass and dry mass:leaf area relationships, allometric comparisons of the components of dry mass and leaf area suggest at most a small effect of CO2. CO2 changed only two of a total of 12 allometric coefficients we calculated for the three species: ν relating shoot to root dry mass was higher in D. glomerata, whilst ν relating leaf area to total dry mass was lower in T. repens. 5. CO2 alone has very little effect on partitioning when the size of the plant is taken into account.
Fear of recurrence: A mediator of the relationship between physical symptoms and quality of life in head and neck cancer patients.

OBJECTIVE Head and neck cancer (HNC) patients suffer from symptoms and fear of recurrence (FoR), which both affect their quality of life (QoL). Based on a self-regulation model, the purpose of the study was to examine patients' FoR as a mediator of the relation between symptoms and QoL, and to identify which symptoms may trigger FoR. METHODS A cross-sectional study was conducted, using convenience sampling. Structured questionnaires were used to collect data at a medical centre in Northern Taiwan. The analytic methods included descriptive statistics, structural equation modelling and linear regression. RESULTS A total of 103 participants were recruited. Patients experienced a medium level of symptom severity and QoL but a moderate to high level of FoR. Symptom severity, FoR and QoL were significantly correlated. FoR was a significant partial mediator between symptom severity and QoL. The significant factors of the overall FoR and the subscale of health worry were "pain in general" and "pain in the mouth, throat or neck. " "Pain in general" was a significant factor for the subscale of cancer worry. CONCLUSIONS This theory-driven study supports a mediation model of FoR among HNC patients and provides a more comprehensive understanding of the antecedents and consequences of FoR.