Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects

Purpose A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. Methods The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Results Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0–t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0–t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353–0.9846) and 0.9431 (0.8698–1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0–t (FDC/concomitant administration) were 0.9829 (0.9143–1.0567) and 0.9632 (0.8798–1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. Conclusion CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments.
Role of Wasp and the small GTPases RhoA, RhoB, and Cdc42 during capacitation and acrosome reaction in spermatozoa of English guinea pigs

Cytoskeleton remodeling is necessary for capacitation and the acrosome reaction in spermatozoa. F‐actin is located in the acrosome and equatorial region during capacitation, but is relocated in the post‐acrosomal region during the acrosome reaction in spermatozoa from bull, rat, mice, and guinea pig. Actin polymerization and relocalization are generally regulated by small GTPases that activate Wasp protein, which coordinates with Arp2/3, profilin I, and profilin II to complete cytoskeletal remodeling. This sequence of events is not completely described in spermatozoa, though. Therefore, the aim of this study was to determine if Wasp interacts with small GTPases (RhoA, RhoB, and Cdc42) and proteins (Arp2/3, profilin I, and profilin II) that co‐localize with F‐actin during capacitation and the acrosome reaction in English guinea pig spermatozoa obtained from the vas deferens. The spermatozoa were capacitated in calcium‐free medium, incubated with an activator or an inhibitor of GTPases, and then induced to acrosome react using calcium. The distribution patterns of F‐actin were compared to the patterns of Wasp and its putative interaction partners: Wasp and RhoB, but not RhoA or Cdc42, localization overlap with F‐actin during capacitation and the acrosome reaction. Activation of small GTPases localized RhoB to the post‐acrosomal region whereas their inhibition prevented acrosome exocytosis. Arp2/3 and profilin II appear to interact with Wasp in the post‐acrosomal region and flagellum, while profilin I and Wasp could be found in the equatorial region. Thus, Wasp and F‐actin distribution overlap during capacitation and acrosome reaction, and small GTPases play an important role in cytoskeleton remodeling during these processes in spermatozoa. Mol. Reprod. Dev. 83: 927–937, 2016 © 2016 Wiley Periodicals, Inc.
The Association between Gene Polymorphism of TCF7L2 and Type 2 Diabetes in Chinese Han Population: A Meta-Analysis

In recent years, it has been widely accepted that transcription factor 7-like 2 (TCF7L2) is associated with type 2 diabetes mellitus (T2DM) in multiple ethnic groups, especially its single nucleotide polymorphisms of rs7903146C/T, rs12255372G/T and rs290487T/C. However, the results previously obtained in Chinese Han population are often inconsistent. For clearing this issue, herein we performed meta-analysis based on the reports that can be found to assess the association. In the meta-analysis, Odds ratio (OR) and 95% confidence interval (95% CI) were calculated with random-effect model or fixed-effect model based on the heterogeneity analysis. The quality of included studies was evaluated by using the Newcastle-Ottawa Scale. The sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. In total, 20 case-control studies with 9122 cases of T2DM and 8017 controls were included. Among these case-control studies, we selected 13 ones on rs7903146 C/T, 5 ones on rs12255372 G/T, 8 ones on rs290487 T/C. The results indicated that rs7903146C/T polymorphism was significantly associated with T2DM (T vs. C, OR = 1.73, 95% CI = 1.39–2.16). There was no evidence that rs12255372G/T and rs290487T/C polymorphisms increased T2DM risk (T vs. G, OR = 1.77, 95% CI = 0.88–3.56; C vs. T, OR = 1.08, 95% CI = 0.93–1.25). Subgroup analysis of different regions proved the relationship between rs7903146C/T polymorphism and T2DM risk in both the northern and the southern China. The association of rs290487 with T2DM was affected by body mass index, whereas the association of rs7903146 and rs290487 with T2DM was influenced neither by age nor by sex. In conclusion, this study indicated that the rs7903146C/T polymorphism of the TCF7L2 gene had a significant effect on T2DM risk in Chinese Han population, with rs12255372G/T and rs290487T/C polymorphisms showing no significant effect.
Nightmare Themes: An Online Study of Most Recent Nightmares and Childhood Nightmares.

STUDY OBJECTIVES Even though the common diagnostic criteria (ICSD-3, DSM-5) acknowledge that nightmares do not only contain anxiety/fear (definition of the ICD-10) but also other emotions such as grief, disgust, and anger, the definition of a nightmare still focuses on threats to survival, security, or physical integrity. However, empirical studies on nightmare content in larger samples are scarce. METHODS The current study elicited 1,216 of the most recent nightmares including childhood nightmares of a population-based sample. RESULTS The findings show that nightmares encompass a diversity of different topics, being chased, physical aggression, including death/injury of close persons. Infrequent themes like being the aggressor and suicide are of special interest as they might be related to waking-life psychopathology. CONCLUSIONS The variety of nightmare topics clearly indicate that current definitions of nightmare content are too narrow. Future studies should look into nightmare content of persons in whom nightmare disorder has been diagnosed.
Augmentation of mechanical and bond strength of coconut shell concrete using quarry dust

The properties of concrete using quarry dust (QD) as fine aggregate and coconut shell (CS) as coarse aggregate were examined in this investigation. Workability, density of concrete, compressive, flexural, splitting tensile strengths, impact resistance and bond strength were considered and evaluated with the theoretical values as recommended by IS 456 and BS 8110 standards. For comparison, both conventional and CS concrete mixes are selected with sand and QD have been considered to study. The bond strength was determined as per IS 2770 (Part-I 1987) and ASTM C 234. This study proves that the use of QD in place of sand augmented the mechanical and bond properties of both CSs concrete and conventional concrete as well.
A 2-Year Field Study Shows Little Evidence That the Long-Term Planting of Transgenic Insect-Resistant Cotton Affects the Community Structure of Soil Nematodes

Transgenic insect-resistant cotton has been released into the environment for more than a decade in China to effectively control the cotton bollworm (Helicoverpa armigera) and other Lepidoptera. Because of concerns about undesirable ecological side-effects of transgenic crops, it is important to monitor the potential environmental impact of transgenic insect-resistant cotton after commercial release. Our 2-year study included 1 cotton field where non-transgenic cotton had been planted continuously and 2 other cotton fields where transgenic insect-resistant cotton had been planted for different lengths of time since 1997 and since 2002. In 2 consecutive years (2009 and 2010), we took soil samples from 3 cotton fields at 4 different growth stages (seedling, budding, boll-forming and boll-opening stages), collected soil nematodes from soil with the sugar flotation and centrifugation method and identified the soil nematodes to the genus level. The generic composition, individual densities and diversity indices of the soil nematodes did not differ significantly between the 2 transgenic cotton fields and the non-transgenic cotton field, but significant seasonal variation was found in the individual densities of the principal trophic groups and in the diversity indices of the nematodes in all 3 cotton fields. The study used a comparative perspective to monitor the impact of transgenic insect-resistant cotton grown in typical ‘real world’ conditions. The results of the study suggested that more than 10 years of cultivation of transgenic insect-resistant cotton had no significant effects–adverse or otherwise–on soil nematodes. This study provides a theoretical basis for ongoing environmental impact monitoring of transgenic plants.
The elderly liver transplant recipients: anxiety, depression, fatigue and life satisfaction

Abstract Introduction Older patients are neglected in clinical trials and are likely to be excluded from liver transplantation (LT). The aim of this study was to assess fatigue, anxiety, depression, and health-related quality of life (HRQoL) in elderly LT recipients. Methods Questionnaires were mailed to patients who underwent LT between 1993 and 2013. Three groups were created: patients ≥ 70, 60 – 69, and < 60 years old. Mental-health status, life satisfaction, and fatigue were assessed using, respectively, the Hospital Anxiety and Depression Scale (HADS), Questions on Life Satisfaction (FLZ-M), and the Multidimensional Fatigue Inventory (MFI-20). Results In total, 276 eligible questionnaires (40.1 %) were received out of 689 patients with a history of LT. No age-related differences were found with regard to anxiety or depression in the study sample. Patients ≥ 70 years old had significantly better life satisfaction in regards to income (p = 0.003) and work (p = 0.005) compared to patients < 60 years. The overall fatigue scores were the highest in patients < 60 years (52.7, SD = 15.8) and ≥ 70 years (52.7, SD = 17.7) compared to patients 60 – 69 years old (48.2, SD = 17.3, p = 0.037). Discussion Advanced age alone should not be considered a contraindication for LT due to potentially poor quality of life outcomes.
Increased Atmospheric SO2 Detected from Changes in Leaf Physiognomy across the Triassic–Jurassic Boundary Interval of East Greenland

The Triassic–Jurassic boundary (Tr–J; ∼201 Ma) is marked by a doubling in the concentration of atmospheric CO2, rising temperatures, and ecosystem instability. This appears to have been driven by a major perturbation in the global carbon cycle due to massive volcanism in the Central Atlantic Magmatic Province. It is hypothesized that this volcanism also likely delivered sulphur dioxide (SO2) to the atmosphere. The role that SO2 may have played in leading to ecosystem instability at the time has not received much attention. To date, little direct evidence has been presented from the fossil record capable of implicating SO2 as a cause of plant extinctions at this time. In order to address this, we performed a physiognomic leaf analysis on well-preserved fossil leaves, including Ginkgoales, bennettites, and conifers from nine plant beds that span the Tr–J boundary at Astartekløft, East Greenland. The physiognomic responses of fossil taxa were compared to the leaf size and shape variations observed in nearest living equivalent taxa exposed to simulated palaeoatmospheric treatments in controlled environment chambers. The modern taxa showed a statistically significant increase in leaf roundness when fumigated with SO2. A similar increase in leaf roundness was also observed in the Tr–J fossil taxa immediately prior to a sudden decrease in their relative abundances at Astartekløft. This research reveals that increases in atmospheric SO2 can likely be traced in the fossil record by analyzing physiognomic changes in fossil leaves. A pattern of relative abundance decline following increased leaf roundness for all six fossil taxa investigated supports the hypothesis that SO2 had a significant role in Tr–J plant extinctions. This finding highlights that the role of SO2 in plant biodiversity declines across other major geological boundaries coinciding with global scale volcanism should be further explored using leaf physiognomy.
Long‐Term Outcome of Consecutive Patients With Previous Coronary Bypass Surgery, Treated With Newer‐Generation Drug‐Eluting Stents

Background Percutaneous coronary intervention (PCI) in patients with previous coronary artery bypass grafting (CABG) is associated with adverse clinical events. Although newer generation drug‐eluting stents showed favorable short‐term safety profiles, there is a lack of long‐term outcome data. We evaluated the impact of previous CABG on 5‐year clinical outcomes of patients treated with PCI using newer‐generation drug‐eluting stents. Methods and Results In this patient‐level pooled analysis of the prospective TWENTE (The Real‐World Endeavor Resolute versus Xience V Drug‐Eluting Stent Study in Twente) trial and nonenrolled TWENTE registry, we assessed a consecutive series of patients who underwent PCI with newer‐generation drug‐eluting stents for non–ST‐segment–elevation acute coronary syndromes or stable angina. Of all 1709 patients, 202 (11.8%) had a history of CABG. Patients with previous CABG had significantly higher 5‐year rates of cardiac death (10.4% versus 4.3%; P<0.001) and target vessel revascularization (25.0% versus 8.1%; P<0.001). These differences remained statistically significant after adjustment for differences in baseline characteristics. Landmark analysis revealed that from 1‐ to 5‐year follow‐up, the rates of cardiac death (8.1% versus 3.2%; P<0.001) and target vessel revascularization (17.1% versus 5.9%; P<0.001) were significantly higher in patients with previous CABG. Among patients with a history of CABG, PCI of an obstructed vein graft was associated with a higher rate of 5‐year target vessel revascularization (P=0.003). Conclusions At 5‐year follow‐up after PCI with newer‐generation drug‐eluting stents, the risk of cardiac death and target vessel revascularization was significantly higher in patients with previous CABG. The target vessel revascularization rate was highest in patients who underwent PCI of obstructed vein grafts.
Does Herbivorous Fish Protection Really Improve Coral Reef Resilience? A Case Study from New Caledonia (South Pacific)

Parts of coral reefs from New Caledonia (South Pacific) were registered at the UNESCO World Heritage list in 2008. Management strategies aiming at preserving the exceptional ecological value of these reefs in the context of climate change are currently being considered. This study evaluates the appropriateness of an exclusive fishing ban of herbivorous fish as a strategy to enhance coral reef resilience to hurricanes and bleaching in the UNESCO-registered areas of New Caledonia. A two-phase approach was developed: 1) coral, macroalgal, and herbivorous fish communities were examined in four biotopes from 14 reefs submitted to different fishing pressures in New Caledonia, and 2) results from these analyses were challenged in the context of a global synthesis of the relationship between herbivorous fish protection, coral recovery and relative macroalgal development after hurricanes and bleaching. Analyses of New Caledonia data indicated that 1) current fishing pressure only slightly affected herbivorous fish communities in the country, and 2) coral and macroalgal covers remained unrelated, and macroalgal cover was not related to the biomass, density or diversity of macroalgae feeders, whatever the biotope or level of fishing pressure considered. At a global scale, we found no relationship between reef protection status, coral recovery and relative macroalgal development after major climatic events. These results suggest that an exclusive protection of herbivorous fish in New Caledonia is unlikely to improve coral reef resilience to large-scale climatic disturbances, especially in the lightly fished UNESCO-registered areas. More efforts towards the survey and regulation of major chronic stress factors such as mining are rather recommended. In the most heavily fished areas of the country, carnivorous fish and large targeted herbivores may however be monitored as part of a precautionary approach.
Interferon Gamma Release Assays for the Diagnosis of Latent TB Infection in HIV-Infected Individuals in a Low TB Burden Country

Background Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting. Methodology/Principal Findings T-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar’s test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1–1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02). Conclusions/Significance In low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts.
Competitive Interactions between Parasitoids Provide New Insight into Host Suppression

Understanding the dynamics of potential inter- and intraspecific competition in parasitoid communities is crucial in the screening of efficient parasitoid species and for utilization of the best parasitoid species combinations. In this respect, the host-parasitoid systems, Bemisia tabaci and two parasitoids, Eretmocerus hayati (exotic) and Encarsia sophia (existing) were studied under laboratory conditions to investigate whether interference competition between the exotic and existing species occurs as well as the influence of potential interference competition on the suppression of the host B. tabaci. Studies on interspecific-, intraspecific- and self-interference competition in two parasitoid species were conducted under both rich and limited host resource conditions. Results showed that (1) both parasitoid species negatively affect the progeny production of the other under both rich and limited host resource conditions; (2) both parasitoid species interfered intraspecifically on conspecific parasitized hosts when the available hosts are scarce and; 3) the mortality of B. tabaci induced by parasitoids via parasitism, host-feeding or both parasitism and host-feeding together varied among treatments under different host resource conditions, but showed promise for optimizing control strategies. As a result of our current findings, we suggest a need to investigate the interactions between the two parasitoids on continuous generations.
Symptom-Based Subgroups of Koreans With Obstructive Sleep Apnea.

STUDY OBJECTIVES Recently, the Icelandic Sleep Apnea Cohort (ISAC) identified three subgroups in patients with obstructive sleep apnea (OSA) recruited from the sleep clinic based on clinical symptoms and comorbidities: excessively sleepy, minimally symptomatic, and disturbed sleep. This study sought to determine whether the three OSA subgroups are applicable to a population-based cohort in Korea. METHODS Study subjects are participants of an ongoing cohort study in Korea. Of the 2,918 participants, 422 new moderate to severe OSA cases (apneahypopnea index [AHI] ≥ 15 events/h) were diagnosed by home sleep studies. All participants completed a detailed questionnaire on sleep-related symptoms, comorbidities, medication, and other information. A latent class analysis was performed. RESULTS When examining solutions for up to 10 clusters, the a priori three-cluster solution was the optimal clustering solution. The three-cluster solution demonstrated a subgroup presentation similar to the clusters identified in the ISAC. The minimally symptomatic subgroup was most prevalent (55.7%) in the Korean cohort. Among the three subgroups, there were no differences in mean AHI and body mass index; however, the disturbed sleep subgroup was older and had more females. CONCLUSIONS Combined with the ISAC data, we suggest that the three-symptom cluster solution for patients with OSA may be more widely applicable, irrespective of ethnicity and study population.