bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus: Results of 24‐month interim analysis of a long‐term post‐marketing study (J‐STEP/LT)
Authors: Utsunomiya Kazunori , Kakiuchi Seigo , Senda Masayuki , Fujii Shoko , Kurihara Yuji , Gunji Ryoji , Koshida Ryusuke , Kameda Hiroyuki , Tamura Masahiro , Kaku Kohei 
Published: February 2020

AbstractAims/IntroductionTofogliflozin is a potent and highly selective sodium–glucose cotransporter 2 inhibitor, and is currently used to treat patients with type 2 diabetes mellitus. We designed a 3‐year study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness in routine clinical practice. The 3‐ and 12‐month interim analysis showed tofogliflozin was well‐tolerated, safe and clinically effective. Here, we report the results of the 24‐month interim analysis.Materials and MethodsThis is a 3‐year prospective, observational and multicenter post‐marketing study (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term).ResultsOf the 6,897 patients enrolled, 6,712 and 6,461 patients were analyzed for the safety and effectiveness of tofogliflozin, respectively. During the 24‐month observation period, the incidence rates of adverse drug reactions (ADRs) and serious adverse drug reactions were 11.25 and 1.21%, respectively. As to adverse drug reactions of special interest, the incidence rates of hypoglycemia, polyuria/pollakiuria, volume depletion‐related events, urinary tract infections and genital infection were 0.83, 1.28, 1.46, 1.18 and 1.62%, respectively. Renal disorders, and cardiovascular and cerebrovascular disorders occurred in 0.63 and 0.76% of the patients, respectively. Glycated hemoglobin A1c and bodyweight decreased significantly by −0.70% (P < 0.0001) and −2.95 kg (P < 0.0001), respectively, from baseline to week 104 (last observation carried forward).ConclusionsSignificant safety concerns have not been observed, and clinical benefit including a long‐term reduction in glycated hemoglobin A1c over a 104‐week (24 months) observation period with weight loss was suggested in this 24‐month interim analysis of the 3‐year Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term in routine clinical practice.
Attitudes toward preimplantation genetic testing for aneuploidy among patients with recurrent pregnancy loss in Japan
Authors: Takeda Eri , Sugiura‐Ogasawara Mayumi , Ebara Takeshi , Kitaori Tamao , Goto Shinobu , Yoshihara Hiroyuki , Sato Takeshi 
Published: February 2020

AbstractAimTo examine attitudes toward preimplantation genetic testing for aneuploidy (PGT‐A) in patients with recurrent pregnancy loss (RPL) because it has been performed worldwide in spite of little evidence regarding whether it can improve the live birth rate and prevent miscarriage. There has been no study to examine attitudes toward PGT‐A in patients with RPL.MethodsWe conducted a cross‐sectional study that used a questionnaire to examine attitudes toward PGT‐A, the desire for PGT‐A and the factors associated with this desire in 386 patients with RPL between November 2014 and January 2019.ResultsOverall, 25.1% of patients desired PGT‐A and 35.2% answered that they knew about it. Regarding the reasons for wanting PGT‐A, 42.3% thought that it would insure a live birth and with complete case analysis, showed that the patients' wish for PGT‐A as a means of giving live birth was affected by their IVF‐ET history (adjusted odds ratio 2.7, 95% CI 1.2–7.2) and whether they had any knowledge of PGT‐A (2.4, 1.1–5.3). Those with a higher total family income (3.5, 1.2–10.1) and a previous IVF‐ET (4.6, 2.0–10.3) tended to want PGT‐A as a means of avoiding miscarriage.ConclusionThe majority had no opinion or a poor knowledge of PGT‐A. More patients who self‐assessed as knowing about PGT‐A or who had undergone IVF‐ET had the above type of misunderstanding. Accurate and up‐to‐date information from facilities different from those in which PGT‐A is performed is necessary before reaching a decision on PGT‐A.
Brain-derived neurotrophic factor fused with a collagen-binding domain inhibits neuroinflammation and promotes neurological recovery of traumatic brain injury mice via TrkB signalling
Authors: Yin Rui , Zhao Shufa , Qiu Caixia 
Published: February 2020

Abstract

Objectives
As one of the vital nutrient factors in central nervous system (CNS), brain-derived neurotrophic factor (BDNF) can significantly attenuate neuron damage and promote neurogenesis. Nevertheless, little research has been conducted on regulating the effect of BDNF on the inflammatory response after traumatic brain injury (TBI).

Methods
In this study, we used BDNF fused with a collagen-binding domain (CBD-BDNF) to maintain a sufficient concentration of BDNF in the TBI hemisphere, and then, the regulatory effects of BDNF and CBD-BDNF on the inflammatory response of microglia were investigated both on a TBI mice model in vivo and LPS-stimulated microglia experiment in vitro.

Key findings
The results revealed that BDNF and CBD-BDNF had similar effects on attenuating the pro-inflammatory reactions but promoting anti-inflammatory responses of microglia induced by LPS in vitro. Furthermore, CBD-BDNF significantly improved the neurological behaviours of TBI mice and alleviated the inflammatory reaction after TBI, while BDNF had weaker effects compared with those of CBD-BDNF. Additionally, the TrkB inhibitor K252a significantly inhibited the above effects of CBD-BDNF.

Conclusions
In conclusion, CBD-BDNF can promote the anti-inflammatory function of microglia and neurological recovery of TBI mice through TrkB signalling.
Positive selection of digestive proteases in Daphnia: A mechanism for local adaptation to cyanobacterial protease inhibitors
Authors: Schwarzenberger Anke , Hasselmann Martin , Von Elert Eric 
Published: February 2020

AbstractDue to the combined effects of global warming and eutrophication, the frequency of deleterious cyanobacterial blooms in freshwater ecosystems has increased. In line with this, local adaptation of the aquatic keystone herbivore Daphnia to cyanobacteria has received major attention. Besides microcystins, the most frequent cyanobacterial secondary metabolites in such blooms are protease inhibitors (PIs). Recently, it has been shown that a protease gene showed copy number variation between four D. magna populations that differed in tolerance to PIs. From that study, we chose two distinct populations of D. magna which had or had not coexisted with cyanobacteria in the past. By calculating FST values, we found that the two populations were genetically more distant in the protease loci than in neutral loci. Population genetic tests applied to the tolerant population revealed that positive selection was most probably acting on the gene loci of the digestive protease CT448 and CT802. We conclude that the selection of digestive proteases and subsequent reduction in copy number is the molecular basis of evolutionary changes leading to local adaptation to PIs.
Cryptic and extensive hybridization between ancient lineages of American crows
Authors: Slager David L. , Epperly Kevin L. , Ha Renee R. , Rohwer Sievert , Wood Chris , Van Hemert Caroline , Klicka John 
Published: February 2020

AbstractMost species and therefore most hybrid zones have historically been defined using phenotypic characters. However, both speciation and hybridization can occur with negligible morphological differentiation. Recently developed genomic tools provide the means to better understand cryptic speciation and hybridization. The Northwestern Crow (Corvus caurinus) and American Crow (Corvus brachyrhynchos) are continuously distributed sister taxa that lack reliable traditional characters for identification. In this first population genomic study of Northwestern and American crows, we use genomic SNPs (nuDNA) and mtDNA to investigate the degree of genetic differentiation between these crows and the extent to which they may hybridize. Our results indicate that American and Northwestern crows have distinct evolutionary histories, supported by two nuDNA ancestry clusters and two 1.1%‐divergent mtDNA clades dating to the late Pleistocene, when glacial advances may have isolated crow populations in separate refugia. We document extensive hybridization, with geographic overlap of mtDNA clades and admixture of nuDNA across >900 km of western Washington and western British Columbia. This broad hybrid zone consists of late‐generation hybrids and backcrosses, but not recent (e.g., F1) hybrids. Nuclear DNA and mtDNA clines had concordant widths and were both centred in southwestern British Columbia, farther north than previously postulated. Overall, our results suggest a history of reticulate evolution in American and Northwestern crows, perhaps due to recurring neutral expansion(s) from Pleistocene glacial refugia followed by lineage fusion(s). However, we do not rule out a contributing role for more recent potential drivers of hybridization, such as expansion into human‐modified habitats.
Smad3 signalling affects high glucose‐induced podocyte injury via regulation of the cytoskeletal protein transgelin
Authors: Jiang Lina , Cui Hong , Ding Jie 
Published: February 2020

AbstractAimThe aim of the present study was to characterize the role of Smad3 signalling on high glucose‐induced podocyte injury.MethodsSynchronized conditionally immortalized mouse podocyte cell line (MPC5) cells were treated with either D‐glucose alone or D‐glucose plus the Smad3 inhibitor SIS3. The distribution of F‐actin and transgelin in a high glucose‐induced model of podocyte injury were examined by immunofluorescence. Levels of transgelin and Smad3 signalling proteins in MPC5 cells were determined by Western blot.ResultsA disordered distribution of F‐actin, as well as co‐localization of F‐actin and transgelin, was observed in podocytes exposed to high glucose. Increased levels of transgelin were first observed 10 minutes after treatment with glucose, suggesting that this protein is sensitive to hyperglycaemic injury. Levels of phosphorylated Smad3 and cleaved caspase 3 increased significantly with glucose stimulation. Moreover, expression of the downstream protein c‐Myc, but not JAK1/STAT3, was induced in conditions of high glucose. The Smad3‐specific inhibitor SIS3 prevented the effects of high glucose on Smad3 phosphorylation, expression of transgelin and c‐Myc, caspase 3 cleavage and cytoskeletal organization. Expression of the tumour suppressor protein p15INK4B increased after podocyte injury but was unaffected by Smad3 inhibition, suggesting that Smad3 regulation of high glucose‐induced podocyte injury occurs through a p15INK4B‐independent mechanism.ConclusionSmad3 signalling plays a critical role in the modulation of hyperglycaemic injury. Targeted inhibition of the Smad3 pathway may offer a novel route for treatment of podocyte damage, especially in cases of diabetic nephropathy.
Ageist attitudes among healthcare professionals and older patients in a geriatric rehabilitation facility and their association with patients' satisfaction with care
Authors: Heyman Noemi , Osman Iyad , Ben Natan Merav 
Published: February 2020

AbstractAimThe aim of this study was to explore the prevalence of ageist attitudes among older adults hospitalised in a geriatric rehabilitation facility, as well as the association between satisfaction with care and ageist attitudes. In addition, this study also explores the prevalence of ageist attitudes among healthcare professionals.BackgroundAn ageist environment may potentially increase internalisation of stereotypes by older adults, which in turn may have a negative impact on care outcomes.MethodsIn this quantitative correlational study, a questionnaire was completed by 100 older patients hospitalised in a rehabilitation department of a geriatric medical centre located in North‐Central Israel, and 87 healthcare professionals working in the same department.ResultsThe attitudes of older patients towards their peers were neither definitely positive nor definitely negative, as were the attitudes held among healthcare professionals working in the facility. Patients with lower knowledge about old age, women and patients born in former Soviet Republics had more ageist attitudes. Older patients' satisfaction with care was relatively high and was not associated with ageist attitudes towards their peers.ConclusionsBoth healthcare professionals and older patients held ageist attitudes to some extent. Certain older patients' sociodemographic characteristics, as well as lower knowledge about old age, have been found associated with more ageist attitudes towards their peers. In contrast, satisfaction with care does not seem to affect older patients' attitudes towards their peers. Healthcare professionals working in a geriatric facility should be aware of the prevalence of ageism among older patients.Implications for practiceThe findings highlight the importance of educational interventions among healthcare professionals to increase awareness of the prevalence of ageism among older patients in a geriatric setting.
Efficacy Analysis of Separation Surgery Combined with SBRT for Spinal Metastases—A Long‐Term Follow‐Up Study Based on Patients with Spinal Metastatic Tumor in a Single‐Center
Authors: Xiaozhou Liu , Xing Zhou , Xin Shi , Chengjun Li , Lei Zhang , Guangxin Zhou , Sujia Wu 
Published: February 2020

ObjectiveFollow‐up data of patients with spinal metastatic tumors were analyzed to investigate the effect of separation surgery combined with SBRT on clinical outcomes.MethodsThe clinical data of 52 patients with spinal metastatic tumors admitted to our hospital from January 2015 to December 2018 were retrospectively analyzed. There were 24 males and 28 females, aged 25–77 years, with an average of 56.7 ± 7.4 years. The separation surgery of all patients was successfully completed and followed up. Frankel neurological function grading, Karnofsky performance scores, VAS scores, Epidural spinal cord compression (ESCC) grading and muscle strength grading were used to assess the patients’ condition. Kaplan‐Meier analysis and the Log⁃rank test were used to calculate the hazard ratio (HR) and the 95% feasible interval for patients with different ages, genders, and treatments. The multivariate Cox regression model was used to calculate the risk value HR and the 95% feasible interval in patients undergoing only separation surgery or separation surgery combined with SBRT.ResultsAfter separation surgery, 46 patients had pain relief (88.5%), and the average VAS score decreased to 2.17 ± 0.52 points, which was significantly improved compared with preoperative score (P < 0.01). Muscle strength grading decreased in seven cases, showed no change in two cases, and recovered in 19 cases. Postoperative Frankel neurological function grading and Karnofsky performance scores were also significantly improved compared with preoperative scores (P < 0.01). The patients who accepted separation surgery were followed up for 9–47 months (26.3 ± 18.1 months), and 15 patients died due to the deterioration of the primary tumor. Thirteen patients received SBRT after surgery, including 12 cases of pain relief. The average VAS score of these 13 patients decreased to 1.64±0.41 points, which was significantly improved compared with preoperative and postoperative (P < 0.01), and muscle strength recovered in eight cases. Frankel neurological function grading and Karnofsky performance scores of these patients were also significantly improved compared with preoperative and postoperative Frankel neurological function grading and Karnofsky performance scores (P < 0.01). The patients who accepted separation surgery combined with SBRT were followed up for 11–38 months (mean 22.5 ± 10.2 months), and five cases died of primary tumor. Univariate and multivariate analysis showed that separation surgery combined with SBRT was an independent predictor of overall survival rate (OS).ConclusionsSeparation surgery combined with SBRT is an effective way to treat spinal metastatic tumors as it not only has smaller surgical trauma, but can also significantly relieve pain, improve nerve function, and relieve spinal cord compression.
No effect of increasing protein intake during military exercise with severe energy deficit on body composition and performance
Authors: Øfsteng Sjur Johansen , Garthe Ina , Jøsok Øyvind , Knox Silje , Helkala Kirsi , Knox Ben , Ellefsen Stian , Rønnestad Bent R. 
Published: February 2020

In this study, we compare the effects of isocaloric high‐ (HIGH: 2 g kg−1 d−1, n = 19) and low‐protein diet (LOW: 1 g kg−1 d−1, n = 19) on changes in body composition, muscle strength, and endocrine variables in response to a 10‐day military field exercise with energy deficit, followed by 7 days of recovery. Body composition (DXA), one repetition maximum (1RM) bench and leg press, counter‐movement jump height (CMJ) and blood variables were assessed before and after the exercise. Performance and blood variables were reassessed after 7 days of recovery. The 10‐day exercise resulted in severe energy deficit in both LOW and HIGH (−4373 ± 1250, −4271 ± 1075 kcal d−1) and led to decreased body mass (−6.1%, −5.2%), fat mass (−40.5%, −33.4%), 1RM bench press (−9.5%, −9.7%), 1RM leg press (−7.8%, −8.3%), and CMJ (−14.7%, −14.6%), with no differences between groups. No change was seen for fat‐free mass. In both groups, the exercise led to a switch toward a catabolic physiological milieu, evident as reduced levels of anabolic hormones (testosterone, IGF‐1) and increased levels of cortisol (more pronounced in HIGH, P < .05). Both groups also displayed substantial increases in creatine kinase. After 7 days of recovery, most variables had returned to close‐to pre‐exercise levels, except for CMJ, which remained at reduced levels. In conclusion, increased protein intake during 10‐day military field exercise with severe energy deficiency did not mitigate loss of body mass or impairment of physical performance.
Novel procedure for testing of soil field test kits involving paper strips
Authors: Golicz Karolina , Hallett Stephen , Sakrabani Ruben 
Published: February 2020

AbstractThe need for facilitation of access to soil information has never been greater. Growing human population, shrinking land and water resources, soil pollution, climate change and unequal distribution of agriculture‐oriented technology impact negatively on global food security. There has been a long‐standing interest in developing low‐cost and easily accessible soil field kits to measure different properties of agricultural soils in order to improve their agronomic capacity. Test strips in particular have provided a favoured method of obtaining soil nutrient status information since the 1970s. Today there is renewed interest in using semi‐quantitative colorimetric methods in soil assessment due to incorporation of modern technological solutions, such as smartphones, which could in turn increase the accuracy and precision of the existing methods. In this paper, we propose streamlined testing procedures based on experience gathered that may be conducted prior to a field kit development involving test strips. Results from laboratory and field experiments are presented, highlighting important factors which ought to be taken into account at the commencement of test strip‐oriented studies.
Donor‐derived transmission through lung transplantation of carbapenem‐resistant Acinetobacter baumannii producing the OXA‐23 carbapenemase during an ongoing healthcare facility outbreak
Authors: Bardossy Ana C. , Snavely Emily A. , Nazarian Elizabeth , Annambhotla Pallavi , Basavaraju Sridhar V. , Pepe Dana , Maloney Meghan , Musser Kimberlee A. , Haas Wolfgang , Barros Nicolas , Pierce Virginia M. , Walters Maroya , Epstein Lauren 
Published: February 2020

AbstractWe describe a rare instance of donor‐derived OXA‐23‐producing carbapenem‐resistant Acinetobacter baumannii transmission during lung transplantation and the subsequent public health response. This investigation highlights how transplantation can introduce rare multidrug‐resistant organisms into different healthcare facilities and regions.
Late onset CMV disease presenting as a colonic stricture in a liver transplant recipient
Authors: Zeidan Joseph H. , Kamionek Michal , Noell Bennett C. , Schmeltzer Paul A. , deLemos Andrew S. , Gajurel Kiran 
Published: February 2020

AbstractCytomegalovirus (CMV) is a common opportunistic infection in solid organ transplant (SOT) recipients in the first 6 months after transplant. Late onset CMV infection or disease outside the classical risk period is uncommon and can present with atypical signs and symptoms. Here, we report a case of late onset CMV presenting as a colonic stricture more than 10 years after liver transplantation in the absence of traditional CMV risk factors. We also briefly review CMV colitis presenting as a mass or stricture in SOT recipients.
The QuantiFERON Monitor® assay is predictive of infection post allogeneic hematopoietic cell transplantation
Authors: Douglas Abby P. , Yu Lijia , Sundararajan Vijaya , Szer Jeff , Ritchie David , Slavin Monica A , Sasadeusz Joe , Visvanathan Kumar 
Published: February 2020

AbstractIntroductionFollowing allogeneic hematopoietic stem cell transplantation (alloHCT), excessive immunosuppression can be complicated by infection, while inadequate immunosuppression can result in graft‐vs‐host disease (GVHD). An accurate method to assess overall immune status post HCT is lacking. The QuantiFERON Monitor® (QFM) assay measures interferon gamma (IFN‐γ) release from whole blood following incubation with both innate (Toll‐like receptor 7, TLR7) and adaptive (CD3 antibody) stimulants and may result in a more complete assessment of the immune system.MethodsWhole blood samples were prospectively collected from alloHCT recipients at conditioning followed by days 10, 30, 60, 90, 120, and 180 post‐transplant and assayed by the QFM test. IFN‐γ levels were correlated to time post HCT and episodes of infection and GVHD.ResultsForty patients were enrolled in the study (68% male; median age 47 years; 58% matched related donors, 42% unrelated; 33% myeloablative). Post‐stimulation IFN‐γ levels rose steadily over the first 180 days post transplantation. IFN‐γ levels were significantly lower in those with active infection compared to those without during the neutropenic period (P < .001). The assay was predictive of CMV reactivation (VL > 1000 copies/mL) post alloHCT (P = .001).ConclusionThis is a promising assay to demonstrate immune recovery and predict risk of infection after alloHCT and may allow tailoring of immunosuppression, antimicrobial treatment, and prophylaxis.