bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of trelagliptin in combination with insulin therapy in Japanese patients with type 2 diabetes: Results from a randomized, Phase IV study
Authors: Kaku Kohei , Kuroda Shingo , Ishida Kazuyuki , Umeda Yuusuke 
Published: June 2018

We aimed to explore the efficacy and safety of once‐weekly trelagliptin 100 mg as an add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control. Patients with haemoglobin A1c (HbA1c) 7.5% to 10.0% who were receiving 8 to 40 units of insulin per day were randomized to receive, with insulin, trelagliptin 100 mg (A/A, n = 116) or placebo (P/A, n = 124) for a 12‐week double‐blind (DB) phase, after which all received trelagliptin for a 40‐week open‐label phase. Primary endpoints were HbA1c change from baseline to the end of the DB phase and adverse events (AEs).HbA1c significantly decreased in the A/A group vs the P/A group at the end of the DB phase (least square mean difference, −0.63% [95% CI, −0.83 to −0.44]: P < .0001). The frequency of treatment‐emergent AEs during the DB phase was 44.0% in the A/A group and 47.6% in the P/A group. No patient experienced severe hypoglycaemia during trelagliptin treatment. Once‐weekly trelagliptin 100 mg therapy with insulin demonstrated a significant reduction in HbA1c. Long‐term treatment was well‐tolerated, with no clinically significant hypoglycaemia, suggesting that trelagliptin with insulin is a meaningful treatment option in this patient population.
Index insurance and climate risk management: Addressing social equity
Authors: Fisher Eleanor , Hellin Jon , Greatrex Helen , Jensen Nathaniel 
Published: June 2018

AbstractFair distribution of benefits from index insurance matters. Lack of attention to social equity can reinforce inequalities and undermine the potential index insurance holds as a tool for climate risk management that is also pro‐poor. The aims of this article are to: (a) examine social equity concerns raised by index insurance in the context of climate risk management, (b) consider how greater attention can be paid to social equity in index insurance initiatives, and (c) reflect on the policy challenges raised by taking social equity into account as a mechanism for climate risk reduction. The article draws on learning from the CGIAR's Research Program on Climate Change, Agriculture and Food Security (CCAFS) and presents the cases of the Index Based Livelihoods Insurance (IBLI) and Agriculture and Climate Risk Enterprise Ltd. (ACRE) in East Africa. It proposes a framework for unpacking social equity related to equitable access, procedures, representation and distribution within index insurance schemes. The framework facilitates identification of opportunities for building outcomes that are more equitable, with greater potential for inclusion and fairer distribution of benefits related to index insurance. The article argues that systematically addressing social equity raises hard policy choices for index insurance initiatives without straightforward solutions. Attention to how benefits and burdens of index insurance are distributed, suggests the unpalatable truth for development policy that the poorest members of rural society can be excluded. Nevertheless, a focus on social equity—facilitated by the framework—opens up opportunities to ensure index insurance is linked to more socially just climate risk management. At the very least, it may prevent index insurance from generating greater inequality. Taking social equity into account, thus, shifts the focus from agricultural systems in transition per se to systems with potential to incorporate societal transformation through distributive justice.
Off‐label use of 4‐factor prothrombin complex concentrate is common despite little known benefit: A retrospective study
Authors: Scharman Carlton D. , Shatzel Joseph J. , Kim Edward , DeLoughery Thomas G. 
Published: June 2018

AbstractBackground/ObjectiveWhile four‐factor prothrombin complex concentrate (4F‐PCC) is FDA‐approved for reversal of warfarin‐induced major bleeding, its use in real‐world settings is unclear. This study's objective was to identify indications leading to 4F‐PCC use and associated outcomes at a single university hospital.MethodsThis was a retrospective cohort study of patients receiving 4F‐PCC over a 22‐month period. A dose was “on‐label” if given for reversal of warfarin‐induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were “off‐label”.ResultsA total of 165 doses of 4F‐PCC in 154 patients were given. Sixty‐one percent of doses were on‐label, while 39% were off‐label. Intracranial hemorrhage was the most common indication (55% of doses). On‐label patients had significantly higher rate of INR normalization and survival to hospital discharge than off‐label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications.ConclusionsOff‐label use of 4F‐PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger‐scale prospective trials studying specific indications are needed for validation in off‐label settings. Until such evidence is available, given potential harms historically displayed by off‐label use of other hemostatic agents, limiting off‐label 4F‐PCC use is recommended.
Role of PPAR‐α agonist fenofibrate in the treatment of induced benign prostatic hyperplasia with dysplastic changes in rats
Authors: Refaie Marwa M.M. , Rifaai Rehab A. , Zenhom Nagwa M. 
Published: June 2018

AbstractNearly all men who reach average life expectancy have prostate disease. The most common is benign prostatic hyperplasia (BPH). Peroxisome proliferator‐activated receptor alpha (PPARα) had protective effect in different models, but still, there are no studies explain its role in BPH. So that we investigated the effect of fenofibrate (FEN) on induced BPH by testosterone propionate (TP) (3 mg/kg/day for 4 weeks) subcutaneous injection followed by FEN (300 mg/kg/day) was given orally for 4 weeks. We measured prostate weights changes, prostatic tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Prostate‐specific antigen (PSA), dihydrotestosterone (DHT), and total antioxidant capacity (TAC) in serum were determined. The mRNA gene expressions of proliferating cell nuclear antigen (PCNA), PPARα, and glutathione peroxidase (GPx) in prostatic tissue were also measured by quantitative real‐time polymerase chain reaction. In addition, the histopathological changes and activated caspase3 immunoexpression were evaluated. Our results showed that TP succeeded in induction of BPH, which was detected by significant increase in prostate weights, prostatic tissue MDA, serum levels of DHT, PSA, and mRNA gene expression of PCNA but significant decrease in PPARα and GPx gene expression. Moreover, TAC in serum and SOD level in prostate tissue decreased. The histopathological examination showed typical changes of BPH with dysplastic changes with marked decrease in activated caspase3 immunoexpression indicating marked suppression of the apoptotic process. FEN significantly improved all disturbed parameters of BPH model. Moreover, there are no dysplastic changes with co‐administration of FEN to BPH induced group.
Evaluation of pan‐TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis‐like neural tumour and histological mimics
Authors: Hung Yin P , Fletcher Christopher D M , Hornick Jason L 
Published: June 2018

AimsInfantile fibrosarcoma is characterised by intersecting fascicles of spindle cells and ETV6–NTRK3 gene fusion in most cases. Given histological overlap with other spindle‐cell tumours, the diagnosis can be challenging and often requires molecular confirmation. A recently developed pan‐TRK antibody shows promise for identifying tumours with NTRK fusions. The purpose of this study was to evaluate the potential diagnostic utility of pan‐TRK immunohistochemistry for infantile fibrosarcoma.Methods and resultsWe evaluated whole‐tissue sections from 210 cases, including 15 infantile fibrosarcomas; five each lipofibromatosis‐like neural tumour and lipofibromatosis; 10 each primitive myxoid mesenchymal tumour of infancy (PMMTI) and low‐grade myofibroblastic sarcoma; 15 each fibrous hamartoma of infancy (FHI), myofibroma/myofibromatosis and desmoid‐type fibromatosis; and 20 each low‐grade fibromyxoid sarcoma, synovial sarcoma, spindle‐cell rhabdomyosarcoma, malignant peripheral nerve sheath tumour, fibrosarcomatous dermatofibrosarcoma protuberans (F‐DFSP) and nodular fasciitis. Immunohistochemistry was performed using a rabbit monoclonal pan‐TRK antibody. Immunoreactivity for pan‐TRK was observed in all 15 (100%) infantile fibrosarcomas, including diffuse immunoreactivity (>50% of cells) in 14 (93%) cases. Pan‐TRK was positive in all five (100%) lipofibromatosis‐like neural tumours. Of the 190 histological mimics, diffuse pan‐TRK immunoreactivity was noted in 16 (8%) cases, including five PMMTI, five FHI (highlighting predominantly the primitive myxoid spindle‐cell components), three F‐DFSP, one low‐grade myofibroblastic sarcoma, one myofibroma and one spindle‐cell rhabdomyosarcoma.ConclusionsDiffuse pan‐TRK immunoreactivity is a highly sensitive but not entirely specific diagnostic marker for infantile fibrosarcoma, and may be helpful in selecting patients for TRK‐targeted therapy. As expected, lipofibromatosis‐like neural tumours, which harbour NTRK1 fusions, also show diffuse pan‐TRK immunoreactivity.
Survival in HIV‐infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study
Authors: Focà E , Cavaglià G , Rusconi S , Cascavilla A , Cenderello G , Re A , Casari S , van den Bogaart L , Zinzani PL , Caracciolo D , Di Perri G , Bonito A , Lucchini A , Cassola G , Viale P , Calcagno A 
Published: June 2018

ObjectivesLymphoproliferative disorders are often observed in HIV‐positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge.MethodsA retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV‐positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival.ResultsA total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B‐cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T‐cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)‐based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based and in 18 it was integrase strand transfer inhibitor (INSTI)‐based (the remaining 20 individuals received other regimens). The 5‐year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI‐based ART compared with other compounds was associated with worse survival in non‐Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P < 0.001); grade 3–4 haematological toxicities were more commonly observed in PI‐treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival.ConclusionsPI‐based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV‐positive patients with lymphoma.
Insights into the phenolic compounds present in jambolan (Syzygium cumini) along with their health‐promoting effects
Authors: Singh Balwinder , Singh Jatinder Pal , Kaur Amritpal , Singh Narpinder 
Published: June 2018

SummaryJambolan is a rich source of bioactive phenolic compounds that have many potential health benefits. Phenolic acids, flavonoids (mainly anthocyanins, flavonols, flavanols and flavanonols) and tannins are the major phenolic compounds present in different parts of jambolan plant. Jambolan fruit skin mainly contains anthocyanins (such as delphinidin, petunidin, malvidin in glycosylated forms), while the pulp is primarily rich in phenolic acids (such as gallic acid and ellagic acid) and tannins (mostly ellagitannins). Moreover, many other compounds have been reported to be present in jambolan fruit. Apart from fruit skin and pulp, jambolan leaves contain flavonoids such as quercetin, myricetin and flavonol glycosides, while seeds are known to contain ellagic acid, gallic acid and quercetin. Health‐promoting activities of phenolic compounds present in jambolan reported in the literature are functioning as anti‐inflammatory, anti‐allergic, antihyperglycaemic, anticancer, cardioprotective, radioprotective, antibacterial, chemopreventive and antioxidant agents.
Reproductive management of the Orinoco river dolphin Inia geoffrensis humboldtiana in Venezuela
Authors: Boede E. O. , Mujica‐Jorquera E. , Boede F. , Varela C. 
Published: June 2018

The Orinoco river dolphin Inia geoffrensis humboldtiana is included in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. The International Union for Conservation of Nature Red List used to categorize the Orinoco river dolphin as Vulnerable; however, it is now considered Data Deficient because current information about threats, ecology and the population are limited and out of date. The Red Book of Venezuelan Wildlife categorizes the species as ‘vulnerable’, and the Venezuelan National Biodiversity Strategy and Action Plan identifies ex situ conservation actions for threatened species. The distribution of this river dolphin in Venezuela extends from the Casiquiare canal, upper/mid‐/lower Orinoco River, tributaries, through the delta, where its populations are threatened by the deterioration of habitat, illegal hunting and accidental capture in fishing nets. Captive‐breeding programmes for cetacean river species worldwide, including the Orinoco river dolphin, have led to an increase in knowledge about reproductive parameters and biological data, which is helpful for future conservation planning. Detailed husbandry manuals and management procedures, which were insufficient at the time the data were collected, are of vital importance for the sustained survival and reproduction of this species ex situ, especially if the conservation status should change from Vulnerable to Critically Endangered. Valencia Aquarium, Venezuela, housed Orinoco river dolphins for 41 years, from 1975 onwards. In 1994 a reproductive group was established with one male and two females. Over the next 22 years (1994–2016) eight calves were born. The following report details the prenatal management, birthing events, lactation periods, and sizes, weights and survival of the young.
Restitution Post Bellum: Property, Inheritance, and Corrective Justice
Authors: Butt Daniel 
Published: June 2018

AbstractWhen should property which was unjustly taken in wartime be returned to the victims of misappropriation, or their heirs? This article argues that Cécile Fabre's Cosmopolitan Peace understates the force of arguments favouring restitution. Rather than seeing claims for restitution made by the descendants of victims as concerned with the redress of harm, they can be understood as resting on enduring entitlements to property. This allows for an account of corrective justice which is robust across generations, and which can be justified aside from, and even sometimes in opposition to, concerns of distributive justice.
Patient and facility variation in costs of catheter ablation for atrial fibrillation
Authors: Perino Alexander C. , Fan Jun , Schmitt Susan K. , Kaiser Daniel W. , Heidenreich Paul A. , Narayan Sanjiv M. , Wang Paul J. , Chang Andrew Y. , Turakhia Mintu P. 
Published: June 2018

AbstractBackgroundCost‐effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the US healthcare system and the relationship between cost and outcomes.Methods and resultsWe performed a retrospective cohort study using data from the MarketScan® commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 to 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30‐day and 1‐year outcomes. The analysis cohort included 9,415 AF ablations (59±11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced healthcare utilization in higher cost quintiles with reductions in rehospitalization at 30‐days (Quintile 1: 16.1%, Quintile 5: 8.8%, P < 0.001) and 1‐year (Quintile 1: 34.8%, Quintile 5: 25.6%, P < 0.001), which remained significant in multivariate analysis.ConclusionsAlthough median costs of AF ablation are below amounts used in prior cost‐effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects.
Activity of xanthine oxidase in plasma correlates with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus and metabolic syndrome: A pilot exploratory study
Authors: Sunagawa Sumito , Shirakura Takashi , Hokama Noboru , Kozuka Chisayo , Yonamine Masato , Namba Toyotaka , Morishima Satoko , Nakachi Sawako , Nishi Yukiko , Ikema Tomomi , Okamoto Shiki , Matsui Chieko , Hase Naoki , Tamura Mizuho , Shimabukuro Michio , Masuzaki Hiroaki 
Published: June 2018

AbstractAims/IntroductionThere is controversy as to whether hyperuricemia is an independent risk factor for cardiometabolic diseases. The serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. In contrast, evidence has accumulated that locally‐ and systemically‐activated xanthine oxidase (XO), a rate‐limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus and metabolic syndrome (MetS).Materials and MethodsWe enrolled 60 patients with type 2 diabetes mellitus and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly‐sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters.ResultsThe value of plasma XO activity was correlated with indices of insulin resistance and the level of circulating liver transaminases. In contrast, the level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with the serum uric acid level.ConclusionsPlasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with type 2 diabetes mellitus and MetS. Through assessing the plasma XO activity, patients showing normal levels of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncovering metabolic risks in type 2 diabetes mellitus and MetS patients.
Risk factors of post‐endoscopic submucosal dissection electrocoagulation syndrome for colorectal neoplasm
Authors: Ito Sayo , Hotta Kinichi , Imai Kenichiro , Yamaguchi Yuichiro , Kishida Yoshihiro , Takizawa Kohei , Kakushima Naomi , Tanaka Masaki , Kawata Noboru , Yoshida Masao , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki 
Published: June 2018

AbstractBackground and AimColorectal endoscopic submucosal dissection (ESD) is used for the treatment of large colorectal superficial neoplasms. However, there have been no large studies on electrocoagulation syndrome developing after colorectal ESD. The aim of this study was to clarify the incidence and clinical risk factors of post‐ESD electrocoagulation syndrome (PECS).MethodsA total of 692 patients (median age: 70 years; 395 men) with 692 lesions, who underwent colorectal ESD at a tertiary cancer center between July 2010 and December 2015, were eligible. PECS was clinically diagnosed based on the presence of localized abdominal tenderness matching the ESD enforcement site and fever (> 37.5 °C) or an inflammatory response (C‐reactive protein level > 0.5 mg/dL or leukocytosis > 10 000 cells/μL), without obvious findings of perforation, which developed at > 6 h post‐ESD. Outcomes of the procedure, the incidence of PECS, and risk factors associated with PECS were assessed.ResultsThe incidence of PECS was 4.8% (33 patients), and all patients improved by conservative treatment. On multivariate analysis, the female sex (odds ratio [OR] 2.6; 95% confidence interval [95% CI]: 1.2–5.7), tumor location at the cecum (OR 14.5; 95% CI: 3.7–53.7 vs rectum), and the presence of submucosal fibrosis (OR 2.8; 95% CI: 1.1–7.5) were found to be independent risk factors of PECS.ConclusionsThis study identified the risk factors for PECS. Patients with high‐risk factors of PECS require careful management after colorectal ESD.
The subfornical organ: A novel site for prolactin action
Authors: Kamesh A. , Black E. A. E. , Ferguson A. V. 
Published: June 2018

Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL‐R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood‐brain barrier. Accordingly, areas of the brain that do not possess a blood‐brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL‐R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real‐time polymerase chain reaction, we found that PRL‐R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch‐clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 μmol L‐1 PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, −6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L‐1 to 1 μmol L‐1, the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K+ current in 67% of SFO neurones in voltage‐clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL‐R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.