bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the Dipeptidyl Peptidase 4 Inhibitor Alogliptin on Blood Pressure in Hypertensive Patients with Type 2 Diabetes Mellitus
Authors: Kishimoto Shinji , Kinoshita Yoshihiko , Matsumoto Takeshi , Maruhashi Tatsuya , Kajikawa Masato , Matsui Shogo , Hashimoto Haruki , Takaeko Yuji , Kihara Yasuki , Chayama Kazuaki , Goto Chikara , Mohamad Yusoff Farina , Nakashima Ayumu , Noma Kensuke , Higashi Yukihito 
Published: April 2019

Abstract

BACKGROUND
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors on blood pressure in patients with diabetes mellitus (DM) are controversial. There is no information on the effect of DPP-4 inhibitors on blood pressure and arterial stiffness in hypertensive patients with DM. We evaluated the effects of alogliptin on blood pressure and arterial stiffness in hypertensive patients with type 2 diabetes mellitus (T2DM).

METHODS
Blood pressure and brachial-ankle pulse wave velocity (baPWV) were measured before and after 3, 6, and 12 months of treatment with alogliptin in 22 hypertensive patients with T2DM.

RESULTS
After 3, 6, and 12 months, alogliptin treatment decreased hemoglobin A1c from 7.0 ± 0.97% to 6.4 ± 0.61%, 6.3 ± 0.58%, and 6.3 ± 0.75% (P &lt; 0.01, respectively), glucose from 8.6 ± 4.39 mmol/l to 7.05 ± 2.16, 7.05 ± 2.28, and 6.44 ± 1.50 mmol/l (P &lt; 0.01, respectively), systolic blood pressure from 137 ± 18 mm Hg to 127 ± 13, 125 ± 15, and 120 ± 17 mm Hg (P &lt; 0.01, respectively), diastolic blood pressure from 79 ± 13 mm Hg to 74 ± 8, 74 ± 10, and 70 ± 8 mm Hg (P &lt; 0.01, respectively) and baPWV from 1,947 ± 349 cm/second to 1,774 ± 259, 1,856 ± 361, and 1,756 ± 286 cm/second (P &lt; 0.01, respectively). A baseline baPWV value of 1,643 cm/second was the optimal cut-off value for patients who had reduced blood pressure after treatment with alogliptin (sensitivity of 83.3% and specificity of 75.0%).

CONCLUSIONS
Alogliptin was associated with improvements not only in glucose metabolism but also in blood pressure and arterial stiffness in hypertensive patients with T2DM. The cut-off value of baPWV may enable identification of responders of decrease in blood pressure by alogliptin in hypertensive patients with T2DM.

CLINICAL TRIALS REGISTRATION
Registration Number for Clinical Trial: UMIN000007722.
iCircDA-MF: identification of circRNA-disease associations based on matrix factorization
Authors: Wei Hang , Liu Bin 
Published: April 2019

AbstractCircular RNAs (circRNAs) are a group of novel discovered non-coding RNAs with closed-loop structure, which play critical roles in various biological processes. Identifying associations between circRNAs and diseases is critical for exploring the complex disease mechanism and facilitating disease-targeted therapy. Although several computational predictors have been proposed, their performance is still limited. In this study, a novel computational method called iCircDA-MF is proposed. Because the circRNA-disease associations with experimental validation are very limited, the potential circRNA-disease associations are calculated based on the circRNA similarity and disease similarity extracted from the disease semantic information and the known associations of circRNA-gene, gene-disease and circRNA-disease. The circRNA-disease interaction profiles are then updated by the neighbour interaction profiles so as to correct the false negative associations. Finally, the matrix factorization is performed on the updated circRNA-disease interaction profiles to predict the circRNA-disease associations. The experimental results on a widely used benchmark dataset showed that iCircDA-MF outperforms other state-of-the-art predictors and can identify new circRNA-disease associations effectively.
Stability Indicating TLC Method for Quantification of Brexpiprazole in Bulk and Its Pharmaceutical Dosage Form and Determination of Content Uniformity
Authors: Thakkar Anjali M , Chhalotiya Usmangani K , Parekh Nikunj , Desai Jaineel V , Shah Dimal A 
Published: April 2019

Abstract
A sensitive, selective and precise high performance thin layer chromatographic method has been developed and validated for the quantification of Brexpiprazole in bulk drug and in pharmaceutical dosage form. The method employed HPTLC aluminum plates (pre-coated with silica gel 60 F254) as stationary phase while n-butanol was used as mobile phase. The Rf value of Brexpiprazole was observed to be 0.38. The densitometric analysis was carried out in absorbance mode at 215 nm. The linear regression analysis data for the calibration plots showed a good linear relationship for Brexpiprazole over a concentration range of 200–1,600 ng band−1. The limit of detection and limit of quantification for Brexpiprazole was found to be 66 and 200 ng band−1. To find out the possible degradation pathway, forced degradation studies were performed. The stock solutions of Brexpiprazole (1,000 μg mL−1) were subjected to acid and alkali hydrolysis, chemical oxidation, dry heat degradation and photo degradation. The drug was found to be susceptible to acid and alkali hydrolysis, chemical oxidation, photo degradation and dry heat. The degraded product peaks were well resolved from the pure drug peak with significant difference in their Rf values. Stressed samples were analyzed using developed HPTLC method. The proposed method was validated with respect to linearity, accuracy, precision and robustness. The method was successfully applied to the estimation of Brexpiprazole in marketed formulation and determination of content uniformity of tablet formulation. Statistical analysis showed that the method is repeatable, selective, and precise.
Male and female guppies differ in problem-solving abilities
Authors: Lucon-Xiccato Tyrone , Gatto Elia , Bisazza Angelo 
Published: April 2019

AbstractIn a number of species, males and females have different ecological roles and therefore might be required to solve different problems. Studies on humans have suggested that the 2 sexes often show different efficiencies in problem-solving tasks; similarly, evidence of sex differences has been found in 2 other mammalian species. Here, we assessed whether a teleost fish species, the guppy, Poecilia reticulata, displays sex differences in the ability to solve problems. In Experiment 1, guppies had to learn to dislodge a disc that occluded a feeder from which they had been previously accustomed to feed. In Experiment 2, guppies had to solve a version of the detour task that required them to learn to enter a transparent cylinder from the open sides to reach a food reward previously freely available. We found evidence of sex differences in both problem-solving tasks. In Experiment 1, females clearly outperformed males, and in Experiment 2, guppies showed a reversed but smaller sex difference. This study indicates that sex differences may play an important role in fish’s problem-solving similar to what has previously been observed in some mammalian species.
The role of RcsA in the adaptation and survival of Escherichia coli K92
Authors: Navasa Nicolás , Ferrero Miguel Ángel , Rodríguez-Aparicio Leandro B , Monteagudo-Mera Andrea , Gutiérrez Sergio , Martínez-Blanco Honorina 
Published: April 2019

ABSTRACT
The Rcs phosphorelay is a two-component signal transduction system that senses stressful environmental signals such as desiccation or low temperatures, which serve as natural inducers in bacteria. RcsA is an important coregulator in this system involved in some functions regulated by the Rcs system, including biofilm formation and capsule synthesis. In this sense, we previously showed that RcsA is necessary for colanic acid synthesis in Escherichia coli K92. Here, using an E. coli K92ΔrcsA mutant lacking rcsA gene we further characterize the implications of RcsA on E. coli K92 survival under osmotic and oxidative stressful conditions, and bacterial attachment and biofilm formation on both biotic and abiotic surfaces. Our results show that RcsA protects E. coli K92 against osmotic and, especially, oxidative stress at low temperatures. In addition, RcsA did not interfere in biofilm formation in any surface tested, including polystyrene, stainless steel, silicone, Teflon, aluminum and glass. By contrast, deletion of rcsA increased bacterial attachment to the caco-2 cells monolayer used as biotic surface.
Inconvenient Truths About Human Longevity
Authors: Olshansky S Jay , Carnes Bruce A 
Published: April 2019

AbstractThe rise in human longevity is one of humanity’s crowning achievements. Although advances in public health beginning in the 19th century initiated the rise in life expectancy, recent gains have been achieved by reducing death rates at middle and older ages. A debate about the future course of life expectancy has been ongoing for the last quarter century. Some suggest that historical trends in longevity will continue and radical life extension is either visible on the near horizon or it has already arrived; whereas others suggest there are biologically based limits to duration of life, and those limits are being approached now. In “inconvenient truths about human longevity” we lay out the line of reasoning and evidence for why there are limits to human longevity; why predictions of radical life extension are unlikely to be forthcoming; why health extension should supplant life extension as the primary goal of medicine and public health; and why promoting advances in aging biology may allow humanity to break through biological barriers that influence both life span and health span, allowing for a welcome extension of the period of healthy life, a compression of morbidity, but only a marginal further increase in life expectancy.
A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age
Authors: Ryan Joanne , Wrigglesworth Jo , Loong Jun , Fransquet Peter D , Woods Robyn L 
Published: April 2019

Abstract
DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual’s chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13–.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10; Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI −0.50 to 0.73; Horvath β:0.18, 95% CI −0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.
Nursing Staff Time and Care Quality in Long-Term Care Facilities: A Systematic Review
Authors: Armijo-Olivo Susan , Craig Rodger , Corabian Paula , Guo Bing , Souri Sepideh , Tjosvold Lisa 
Published: April 2019

AbstractBackground and ObjectivesIn long-term care (LTC) facilities, nursing staff are important contributors to resident care and well-being. Despite this, the relationships between nursing staff coverage, care hours, and quality of resident care in LTC facilities are not well understood and have implications for policy-makers. This systematic review summarizes current evidence on the relationship between nursing staff coverage, care hours, and quality of resident care in LTC facilities.Research Design and MethodsA structured literature search was conducted using four bibliographic databases and gray literature sources. Abstracts were screened by two independent reviewers using Covidence software. Data from the included studies were summarized using a pretested extraction form. The studies were critically appraised, and their results were synthesized narratively.ResultsThe systematic searched yielded 15,842 citations, of which 54 studies (all observational) were included for synthesis. Most studies (n = 53, 98%) investigated the effect of nursing staff time on resident care. Eleven studies addressed minimum care hours and quality of care. One study examined the association between different nursing staff coverage models and resident outcomes. Overall, the quality of the included studies was poor.Discussion and ImplicationsBecause the evidence was inconsistent and of low quality, there is uncertainty about the direction and magnitude of the association between nursing staff time and type of coverage on quality of care. More rigorously designed studies are needed to test the effects of different cutoffs of care hours and different nursing coverage models on the quality of resident care in LTC facilities.
Impact of Changing Treatment Strategies on Outcomes in Pediatric Ulcerative Colitis
Authors: Bolia Rishi , Rajanayagam Jeremy , Hardikar Winita , Alex George 
Published: April 2019

AbstractBackgroundIn recent years, treatment strategies for ulcerative colitis have evolved with an early step-up approach, the availability of biologicals, and therapeutic drug monitoring.We carried out this study to evaluate the effect of these changes on disease outcomes.MethodsIn this retrospective review, 2 time periods were defined: Group 1 (2005–2010) and Group 2 (2011–2016). Baseline demographic, endoscopic parameters, and medication use were compared. Overall colectomy rate, number of disease flares per year, and number of hospital admissions per year were compared between the 2 groups.ResultsGroup 1 had 71 children, and in children in Group 2. The use of 5-ASA increased in Group 2 (Group 2, 99.2% vs. Group 1, 84.5%, P = 0.0007). In addition, infliximab and thiopurines were introduced earlier in the disease course.The 2-year cumulative probability of colectomy decreased from 14% to 3% (P = 0.02) between the 2 periods. No change in median number of flares per year [Group 1, 0.41 (IQR 0.6) vs. Group 2, 0.62 (IQR 0.91), P = 0.28] or median number of hospital admissions per year [Group 1, 0.30 (IQR 0.77) vs. Group 2, 0.21 (IQR 0.75), P = 0.52] was seen.Thereafter, we proceeded to identify the changes in treatment strategies that were responsible for the reduction in colectomy and we found that the use of infliximab OR 3.7 (95% CI 1.1–11.7), P = 0.02, was independently associated with it.ConclusionsA reduction in 2-year colectomy rates has been observed in patients with pediatric ulcerative colitis since biologics have become available for its treatment. The numbers of disease-flares rates and hospital admissions remain unchanged.
Antiemetic prophylaxis with temozolomide: an audit from a tertiary care center
Authors: Patil Vijay M , Chandrasekharan Arun , Vallathol Dilip Harindran , Malhotra Mridul , Abhinav Ram , Agarwal Priti , Rajpurohit Anu , Tonse Raees , Bhattacharjee Atanu , Jalali Rakesh 
Published: April 2019

Abstract

Background
In our previous experience, a significant proportion of patients who received 5-HT3 antagonist monotherapy with adjuvant temozolomide (150-200 mg/m2) had chemotherapy-induced nausea and vomiting (CINV). This is an audit comparing the multiple antiemetic therapies in the prevention of temozolomide-associated CINV.

Methods
This was a retrospective audit. Adult glioma patients treated with temozolomide at a dose of 150-200 mg/m2 between October 2017 and June 2018 were selected for this analysis. Three antiemetic prophylaxis were used in this time period: ondansetron (October 2017 to November 2017), ondansetron + domperidone (December 2017 to February 2018), and ondansetron + olanzapine (March 2018 to June 2018). The rates of nausea and vomiting were compared among the 3 cohorts using the chi-squared test with Bonferroni correction. A P value of less than .016 was considered significant.

Results
A total of 360 patients were selected for this analysis. There were 91 patients in the ondansetron prophylaxis group (25.3%), 113 (31.4%) in the ondansetron plus domperidone group, and 156 (43.3%) in the ondansetron plus olanzapine group. The overall incidence of nausea and vomiting was 25.0% (n = 90) and 7.2% (n = 26). Overall the rates of nausea (P = .052) and vomiting (P = .481) were similar in all 3 cohorts. However, the rates of grade 2 and above nausea (P = .012) and vomiting (P = .015) were significantly lower in the olanzapine group.

Conclusion
The combination of ondansetron with olanzapine leads to a statistically significant decrease in the rate of moderate-to-severe emesis and nausea and needs to be explored in a prospective study.
Comparative cardiovascular risk of allopurinol versus febuxostat in patients with gout: a nation-wide cohort study
Authors: Kang Eun Ha , Choi Hyon K , Shin Anna , Lee Yun Jong , Lee Eun Bong , Song Yeong Wook , Kim Seoyoung C 
Published: April 2019

Abstract

Objective
To compare cardiovascular (CV) risk among gout patients initiating allopurinol vs febuxostat.

Methods
Using 2002–2015 Korean National Health Insurance Service data for the entire Korean population, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite CV end point of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. Secondary outcomes were individual components of the primary outcome, and all-cause mortality. We used propensity score-matching with a 4:1 ratio for allopurinol and febuxostat initiators to control for confounding. Competing risk analyses were done for non-fatal outcomes accounting for deaths.

Results
We included 39 640 allopurinol initiators propensity score-matched on 9910 febuxostat initiators. The mean age was 59.1 years and 78.4% were male. The incidence rate per 100 person-years for the primary outcome was 1.89 for allopurinol and 1.84 for febuxostat initiators. The corresponding hazard ratio comparing allopurinol vs febuxostat initiators was 1.09 (95% CI: 0.90, 1.32). No significant difference was found for the secondary outcomes, including all-cause mortality (hazard ratio 0.96; 95% CI: 0.79, 1.16). Subgroup analyses limited to those at high CV risk and to equipotent-dose initiators (i.e. allopurinol ⩾300 mg/day vs febuxostat ⩾40 mg/day) showed similar results.

Conclusion
Overall, this large Korean population-based study suggests no difference in the risk of non-fatal CV events and all-cause mortality between allopurinol and febuxostat initiators. These findings are consistent with the recent US Medicare population study, although the current study population consisted of younger Asians.
Effects of supplementing organic microminerals and methionine with or without limiting growth during the rearing phase of replacement gilts on lameness, growth, and body composition1
Authors: Fabà Lluís , Gasa Josep , Tokach Mike D , Varella Evelia , Solà-Oriol David 
Published: April 2019

AbstractPrevious research suggested that lameness in growing pigs could be reduced using feeding strategies, such as limiting growth rate and supplementing trace minerals (TM) and (or) methionine (Met). The present study evaluates effects of 1) TM and Met and 2) limiting total lysine (Lys) during the rearing phase (90 d) of gilts (as a means to limit growth rate) on lameness, performance, and sow claw health and productivity (to first parity). Gilts (n = 240; 58.0 ± 11.1 kg body weight [BW]) were blocked, distributed into pens of 10 gilts, and pens were allocated to a 2 × 2 factorial arrangement. Factors were: 1) control or TM plus Met, which provided additional 10, 20, and 50 mg/kg of chelated copper, manganese, and zinc, respectively (0.1%, Aplomotec Plus, Tecnología & Vitaminas, S.L.; Alforja, Spain), and a 1.01 Met:Lys ratio and 2) standard Lys was formulated to meet growth requirements or low Lys to 19% below growth requirements. Feeding was provided through two phases, first between 119 and 163 d of age (phase I) and the second between 163 and 209 d of age (phase II). Diets had 2.43 and 2.31 Mcal net energy/kg for phases I and II, respectively, and were offered ad libitum. Low Lys did not affect feed intake but rather reduced average daily gain (ADG) by 6.35% and the final BW by 3.80% compared with standard Lys (P &lt; 0.001). Low Lys reduced ADG (P &lt; 0.001) and gain:feed (P = 0.012) during phase I but not during phase II. Lameness prevalence was 7.92% during rearing and increased with time (P &lt; 0.001). Final BW (151 kg) and ADG (989 g) were similar (P &gt; 0.05) whether gilts displayed lameness or not. Lameness was low in severity and not affected by dietary factors. However, TM- plus Met-fed gilts were 19.2 kg heavier (P = 0.016) than were control at lameness detection. On the sow farm, there was no evidence for differences in lameness or claw lesions among previous dietary treatments. In conclusion, lameness prevalence during the rearing phase was similar, independent of TM plus Met supplement, low Lys, or the interaction. Insufficient reduction of ADG and low severity in lameness may have limited the potential of dietary treatments. Moreover, a greater deficiency of Lys would be needed to achieve the degree of growth reduction previously reported to lessen lameness through feed restriction.
Metabolism and Lung Toxicity of Inhaled Naphthalene: Effects of Postnatal Age and Sex
Authors: Carratt Sarah A , Kovalchuk Nataliia , Ding Xinxin , Van Winkle Laura S 
Published: April 2019

Abstract
Human exposure to naphthalene (NA), an acute lung toxicant and possible human carcinogen, is primarily through inhalation. Acute lung toxicity and carcinogenesis are thought to be related because the target sites for both are similar. To understand susceptibility of the developing lung to cytotoxicity of inhaled NA, we exposed neonatal (7 days), juvenile (3 weeks), and adult mice to 5 or 10 ppm NA vapor for 4 h. We measured vacuolated airway epithelium morphometrically, quantified NA and NA-glutathione levels in plasma and lung, and quantified gene expression in microdissected airways. NA inhalation caused airway epithelial cytotoxicity at all ages, in both sexes. Contrary to a previous study that showed the greatest airway epithelial cytotoxicity in neonatal mice following intraperitoneal NA injection, we observed the most extensive airway epithelial toxicity in older, juvenile, animals exposed to NA by inhalation. Juvenile female animals were the most susceptible. Furthermore, NA inhalation in juvenile animals resulted in damage to conducting airway Club cells that was greater in proximal versus distal airways. We also found NA tissue burden and metabolism differed by age. Gene expression pathway analysis was consistent with the premise that female juvenile mice are more predisposed to damage; DNA damage and cancer pathways were upregulated. Our data demonstrate special susceptibility of young, juvenile mice to NA inhalation-induced cytotoxicity, highlight the importance of route of exposure and airway location in toxicity of chemicals in the developing lung, and provide metabolic and molecular insights for further identification of mechanisms underlying age and sex differences in NA toxicity.