bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study
Authors: Wootton Robyn E , Lawn Rebecca B , Millard Louise A C , Davies Neil M , Taylor Amy E , Munafò Marcus R , Timpson Nicholas J , Davis Oliver S P , Davey Smith George , Haworth Claire M A 
Published: September 2018

Abstract

Objectives
To investigate whether the association between subjective wellbeing (subjective happiness and life satisfaction) and cardiometabolic health is causal.

Design
Two sample, bidirectional mendelian randomisation study.

Setting
Genetic data taken from various cohorts comprised of the general population (mostly individuals of European ancestry, plus a small proportion of other ancestries); follow-up analysis included individuals from the United Kingdom.

Participants
Summary data were used from previous genome wide association studies (number of participants ranging from 83 198 to 339 224), which investigated traits related to cardiovascular or metabolic health, had the largest sample sizes, and consisted of the most similar populations while minimising sample overlap. A follow-up analysis included 337 112 individuals from the UK Biobank (54% female (n=181 363), mean age 56.87 years (standard deviation 8.00) at recruitment).

Main outcome measures
Subjective wellbeing and 11 measures of cardiometabolic health (coronary artery disease; myocardial infarction; total, high density lipoprotein, and low density lipoprotein cholesterol; diastolic and systolic blood pressure; body fat; waist to hip ratio; waist circumference; and body mass index).

Results

Evidence of a causal effect of body mass index on subjective wellbeing was seen; each 1 kg/m
2
increase in body mass index caused a −0.045 (95% confidence interval −0.084 to −0.006, P=0.02) standard deviation reduction in subjective wellbeing. Follow-up analysis of this association in an independent sample from the UK Biobank provided strong evidence of an effect of body mass index on satisfaction with health (β=−0.035 unit decrease in health satisfaction (95% confidence interval −0.043 to −0.027) per standard deviation increase in body mass index, P<0.001). No clear evidence of a causal effect was seen between subjective wellbeing and the other cardiometabolic health measures, in either direction.

Conclusions
These results suggest that a higher body mass index is associated with a lower subjective wellbeing. A follow-up analysis confirmed this finding, suggesting that the effect in middle aged people could be driven by satisfaction with health. Body mass index is a modifiable determinant, and therefore, this study provides further motivation to tackle the obesity epidemic because of the knock-on effects of higher body mass index on subjective wellbeing.
Production costs and potential prices for biosimilars of human insulin and insulin analogues
Authors: Gotham Dzintars , Barber Melissa J , Hill Andrew 
Published: September 2018

IntroductionHigh prices for insulin pose a barrier to treatment for people living with diabetes, with an estimated 50% of 100 million patients needing insulin lacking reliable access. As insulin analogues replace regular human insulin (RHI) globally, their relative prices will become increasingly important. Three originator companies control 96% of the global insulin market, and few biosimilar insulins are available. We estimated the price reductions that could be achieved if numerous biosimilar manufacturers entered the insulin market.MethodsData on the price of active pharmaceutical ingredient (API) exported from India were retrieved from an online customs database. Manufacturers of insulins were contacted for price quotes. Where market API prices could not be identified, prices were estimated based on comparison of similarity, in terms of manufacturing process, with APIs for which prices were available. Potential biosimilar prices were estimated by adding costs of excipients, formulation, transport, development and regulatory costs, and a profit margin.ResultsThe manufacturing processes for RHI and insulin analogues are similar. API prices were US$24 750/kg for RHI, US$68 757/kg for insulin glargine and an estimated US$100 000/kg for other analogues. Estimated biosimilar prices were US$48–71 per patient per year for RHI, US$49–72 for neutral protamine Hagedorn (NPH) insulin and US$78–133 for analogues (except detemir: US$283–365).ConclusionTreatment with biosimilar RHI and insulin NPH could cost ≤US$72 per year and with insulin analogues ≤US$133 per year. Estimated biosimilar prices were markedly lower than the current prices for insulin analogues. Widespread availability at estimated prices may allow substantial savings globally.
Pressure-induced reversible metallization and phase transition in Zinc Telluride
Authors: Zhuang Yukai , Dai Lidong , Li Heping , Hu Haiying , Liu Kaixiang , Yang Linfei , Pu Chang , Hong Meiling 
Published: September 2018

The crystalline and electronic structural properties of Zinc Telluride (ZnTe) are investigated systematically up to [Formula: see text]25 GPa using a diamond anvil cell (DAC) in conjunction with a series of advanced optical and electrical testing methods at both non-hydrostatic and hydrostatic conditions. Based on Raman spectroscopy and AC impedance spectroscopy, ZnTe undergoes two phase transitions from initial zinc-blende phase to cinnabar phase at 7–9 GPa, then it transforms to Cmcm phase at 11–13 GPa under the non-hydrostatic condition. Meantime, the semiconductor to metal phase transition is verified by the temperature-dependent conductivity measurements. In these studies, the pressure points of phase transition and metallization of ZnTe are approximately same under the hydrostatic condition. The feeble influence of non-hydrostatic and hydrostatic conditions on the phase transition and metallization of ZnTe can be reasonably explained by its own crystalline structure from atomic force microscopy and high-resolution transmission electron microscopy.
Production geochemistry: fluids don't lie and the devil is in the detail
Authors: van Bergen Pim F. , Gordon Marc 
Published: September 2018

Abstract

The application of production geochemistry techniques has been shown to provide abundant and often low-cost high-value fluid information that helps to maximize and safeguard production. Critical aspects to providing successful data relate to the appropriate sampling strategy and sampling selection which are generally project-aim-specific. In addition, the continuous direct integration of the production geochemistry data with subsurface and surface understanding is pivotal. Examples from two specific areas have been presented including: (a) the effective use of IsoTubes in the production realm; and (b) the application of geochemical fingerprinting primarily based on multidimensional gas chromatography. Mud gas stable carbon isotopes from low-cost IsoTubes have been shown to be very effective in recognizing within-well fluid compartments, as well as recognizing specific hydrocarbon seals in overburden section, including the selective partial seal for only C
2+
gas species. With respect to geochemical fingerprinting, examples have been presented related to reservoir surveillance including compartmentalization, lateral and vertical connectivity, as well as fluid movements and fault/baffle breakthrough. The production-related examples focus on fluid allocation within a single well, as well as on its application for pipeline residence times, fluid identification and well testing.
FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease
Authors: Jen Emily Y. , Xu Qing , Schetter Aaron , Przepiorka Donna , Shen Yuan Li , Roscoe Donna , Sridhara Rajeshwari , Deisseroth Albert , Philip Reena , Farrell Ann T. , Pazdur Richard 
Published: September 2018

Abstract
On March 29, 2018, the FDA granted accelerated approval for blinatumomab (Blincyto; Amgen, Inc.) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. Blinatumomab is a CD3xCD19 bispecific antibody approved previously for the treatment of relapsed or refractory BCP ALL. The basis for this accelerated approval was a single-arm trial. For the 86 patients in first and second complete remission with MRD ≥ 0.1%, conversion to MRD &lt; 0.01% was achieved after one cycle of blinatumomab by 85.2% [95% confidence interval (CI): 73.8%, 93.0%] and 72.0% (95% CI: 50.6%, 87.9%), respectively, and the estimated median hematologic relapse-free survivals (RFS) were 35.2 months (95% CI: 0.4–53.5) and 12.3 months (95% CI: 0.7–42.3), respectively. Hematologic RFS was considered substantial independent of whether patients underwent subsequent allogeneic stem cell transplantation. The safety profile for blinatumomab was established in prior studies, and no new safety signals were observed in the new population. Cytokine release syndrome and neurotoxicity remain significant risks. The FDA is requiring confirmation of clinical benefit in a randomized trial.
Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in KRAS-Mutant Non–Small Cell Lung Cancer
Authors: Nangia Varuna , Siddiqui Faria M. , Caenepeel Sean , Timonina Daria , Bilton Samantha J. , Phan Nicole , Gomez-Caraballo Maria , Archibald Hannah L. , Li Chendi , Fraser Cameron , Rigas Diamanda , Vajda Kristof , Ferris Lorin A. , Lanuti Michael , Wright Cameron D. , Raskin Kevin A. , Cahill Daniel P. , Shin John H. , Keyes Colleen , Sequist Lecia V. , Piotrowska Zofia , Farago Anna F. , Azzoli Christopher G. , Gainor Justin F. , Sarosiek Kristopher A. , Brown Sean P. , Coxon Angela , Benes Cyril H. , Hughes Paul E. , Hata Aaron N. 
Published: September 2018

Abstract

BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in KRAS-mutant non–small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL1 or BCL-xL was determined by the differential binding of proapoptotic BCL2 proteins to MCL1 or BCL-xL, respectively. The efficacy of dual MEK + MCL1 blockade was augmented by prior transient exposure to BCL-xL inhibitors, which promotes the binding of proapoptotic BCL2 proteins to MCL1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL2 family proteins for KRAS-mutant NSCLC.

Significance:
Defining the molecular basis for MCL1 versus BCL-xL dependency will be essential for effective prioritization of BH3 mimetic combination therapies in the clinic. We discover a novel strategy for integrating BCL-xL and MCL1 inhibitors to drive and subsequently exploit apoptotic dependencies of KRAS-mutant NSCLCs treated with MEK inhibitors.
See related commentary by Leber et al., p. 1511.
This article is highlighted in the In This Issue feature, p. 1494
AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies
Authors: Caenepeel Sean , Brown Sean P. , Belmontes Brian , Moody Gordon , Keegan Kathleen S. , Chui Danny , Whittington Douglas A. , Huang Xin , Poppe Leszek , Cheng Alan C. , Cardozo Mario , Houze Jonathan , Li Yunxiao , Lucas Brian , Paras Nick A. , Wang Xianghong , Taygerly Joshua P. , Vimolratana Marc , Zancanella Manuel , Zhu Liusheng , Cajulis Elaina , Osgood Tao , Sun Jan , Damon Leah , Egan Regina K. , Greninger Patricia , McClanaghan Joseph D. , Gong Jianan , Moujalled Donia , Pomilio Giovanna , Beltran Pedro , Benes Cyril H. , Roberts Andrew W. , Huang David C. , Wei Andrew , Canon Jude , Coxon Angela , Hughes Paul E. 
Published: September 2018

Abstract

The prosurvival BCL2 family member MCL1 is frequently dysregulated in cancer. To overcome the significant challenges associated with inhibition of MCL1 protein–protein interactions, we rigorously applied small-molecule conformational restriction, which culminated in the discovery of AMG 176, the first selective MCL1 inhibitor to be studied in humans. We demonstrate that MCL1 inhibition induces a rapid and committed step toward apoptosis in subsets of hematologic cancer cell lines, tumor xenograft models, and primary patient samples. With the use of a human MCL1 knock-in mouse, we demonstrate that MCL1 inhibition at active doses of AMG 176 is tolerated and correlates with clear pharmacodynamic effects, demonstrated by reductions in B cells, monocytes, and neutrophils. Furthermore, the combination of AMG 176 and venetoclax is synergistic in acute myeloid leukemia (AML) tumor models and in primary patient samples at tolerated doses. These results highlight the therapeutic promise of AMG 176 and the potential for combinations with other BH3 mimetics.

Significance:
AMG 176 is a potent, selective, and orally bioavailable MCL1 inhibitor that induces a rapid commitment to apoptosis in models of hematologic malignancies. The synergistic combination of AMG 176 and venetoclax demonstrates robust activity in models of AML at tolerated doses, highlighting the promise of BH3-mimetic combinations in hematologic cancers.
See related commentary by Leber et al., p. 1511.
This article is highlighted in the In This Issue feature, p. 1494
Association Between Preoperative Vitamin D Status and Short-Term Physical Performance after Total Hip Arthroplasty: A Prospective Study
Authors: Visser Edith , de Roos Nicole M. , Oosting Ellen , Endenburg Silvia C. , Dronkers Jaap J. 
Published: September 2018

<b><i>Background:</i></b> Insufficient serum vitamin D concentrations (50–75 nmol/L) are prevalent in 40–65% of patients who require total hip arthroplasty (THA). This could impair physical recovery after surgery. This study investigated the association between preoperative vitamin D status and physical performance after THA. Additionally, postoperative changes in vitamin D concentrations were measured. <b><i>Methods:</i></b> We included 87 patients scheduled for elective THA and aged ≥65 years. Three groups were recruited: patients classified as vitamin D deficient (&#x3c; 50 nmol/L, <i>n</i> = 23), insufficient (50–75 nmol/L, <i>n</i> = 32), or sufficient (&#x3e; 75 nmol/L, <i>n</i> = 32). Serum 25-hydroxyvitamin D<sub>3</sub> (25[OH]D<sub>3</sub>) concentration and physical performance were measured perioperatively. Linear mixed models were used to examine differences between groups. <b><i>Results:</i></b> Change in physical performance over time was not affected by preoperative vitamin D status. In contrast, for physical activity, both vitamin D (<i>p</i> = 0.021) and time (<i>p</i> &#x3c; 0.001) effect was seen: from 80.2 ± 25.8 to 58.1 ± 17.8 min/day in the deficient group, 143.7 ± 19.8 to 92.9 ± 11.5 min/day in the insufficient group, and 108.1 ± 20.9 to 62.3 ± 12.9 min/day in the sufficient group. The Chair Stand Test, Timed Up and Go test, and 10-Meter Walking Test also improved significantly over time, but independent of vitamin D status. An increase in 25(OH)D<sub>3</sub> concentration 6 weeks postoperatively was correlated with improved hip function (Pearson’s <i>r</i> = –0.471, <i>p</i> = 0.018). Overall, serum 25(OH)D<sub>3</sub> declined with 32% one day after surgery (<i>p</i> &#x3c; 0.001), to nearly return to baseline values 6 weeks later in all groups. <b><i>Conclusion:</i></b> Vitamin D status did not appear to affect physical recovery after THA. The drop in vitamin D after surgery deserves further investigation, but could possibly be explained by hemodilution.
Comparison of Ultrasound and Fluoroscopically Guided Percutaneous Transhepatic Biliary Drainage
Authors: Nennstiel Simon , Treiber Matthias , Faber Alexander , Haller Bernhard , von Delius Stefan , Schmid Roland M. , Neu Bruno 
Published: September 2018

<b><i>Background:</i></b> Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the palliation of an endoscopically inaccessible biliary system. Since a standard technique of PTBD is not defined, we compared a fluoroscopically guided technique (F-PTBD) with an ultrasound (US-PTBD) guided approach. <b><i>Patients and Methods:</i></b> Procedure characteristics, success-rates and complication-rates of the different PTBD techniques were compared in patients who underwent PTBD between October 1, 2006, and ­December 31, 2014. <b><i>Results:</i></b> In 195 patients, 251 PTBDs (207 F-PTBDs, 44 US-PTBDs) were performed. F-PTBDs were mostly inserted from the right and US-PTBDs from the left. Patient age, gender and physical status were comparable in both techniques. There was no difference regarding overall procedure success (90%/86.4%), overall interventional complication rates (10.6%/9.1%), fluoroscopy times, intervention times or sedatives dosages. However, major complications were only encountered in F-PTBDs. There was a higher success rate for F-PTBD vs. US-PTBD from the right side (91.9 vs. 75%; <i>p</i> = 0.033) and a trend towards a higher success rate for US guidance from the left side (82.9 vs. 95.8%; <i>p</i> = 0.223). <b><i>Conclusions:</i></b> For drainage of the right biliary system F-PTBD seems superior over the US-PTBD technique used in this study. However, major complications can occur more frequently in F-PTBD.
The Incidence Prognosis and Risk Factors of Cognitive Impairment in Maintenance Haemodialysis Patients
Authors: Lu Renhua , Xu Chenqi , Li Yan , Yu Ling , Shao Xinghua , Xie Kewei , Gu Jiaqi , Yu Zanzhe , Yan Yucheng , Guan Yangtai , Ni Zhaohui , Ronco Claudio , Gu Leyi 
Published: September 2018

<b><i>Objective:</i></b> To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. <b><i>Methods:</i></b> Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA &#x3c; 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. <b><i>Results:</i></b> In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients’ MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (<i>p</i> &#x3c; 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (<i>p</i> = 0.046). <b><i>Conclusion:</i></b> CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.
Effects of Coenzyme Q10 on Statin‐Induced Myopathy: An Updated Meta‐Analysis of Randomized Controlled Trials
Authors: Qu Hua , Guo Ming , Chai Hua , Wang Wen‐ting , Gao Zhu‐ye , Shi Da‐zhuo 
Published: September 2018

Background
Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin‐induced myopathy. However, whether CoQ10 supplementation ameliorates statin‐induced myopathy remains unclear.

Methods and Results

PubMed,
EMBASE
, and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin‐induced myopathy. We calculated the pooled weighted mean difference (
WMD
) using a fixed‐effect model and a random‐effect model to assess the effects of CoQ10 supplementation on statin‐associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the
Cochrane Handbook
. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg‐Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin‐associated muscle symptoms, such as muscle pain (
WMD
, −1.60; 95% confidence interval [
CI
], −1.75 to −1.44;
P
<0.001), muscle weakness (
WMD
, −2.28; 95%
CI
, −2.79 to −1.77;
P
=0.006), muscle cramp (
WMD
, −1.78; 95%
CI
, −2.31 to −1.24;
P
<0.001), and muscle tiredness (
WMD
, −1.75; 95%
CI
, −2.31 to −1.19;
P
<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation (
WMD
, 0.09; 95%
CI
, −0.06 to 0.24;
P
=0.23).

Conclusions
CoQ10 supplementation ameliorated statin‐associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin‐induced myopathy.
A Call for the Evaluation of Web-Based Climate Data and Analysis Tools
Authors: VanderMolen Kristin , Wall Tamara U. , Daudert Britta 
Published: September 2018

AbstractResearchers are producing an ever greater number of web-based climate data and analysis tools in support of natural resource research and management. Yet the apparent absence or underreporting of evaluation in the development of these applications has raised questions as to whether, by whom, and for what they are utilized, and, relatedly, whether they meet the rationale for their development. This paper joins recent efforts to address these questions by introducing one approach to evaluation—developmental evaluation—and reporting on its use in the evaluation of the Southwest Climate and Environmental Information Collaborative (SCENIC). A web interface under development at the Western Regional Climate Center, SCENIC provides access to climate data and analysis tools to environmental scientists in support of natural resource research and management in the southwestern United States. Evaluation findings highlight subtlety in the improvements necessary for ensuring a useful and usable application that could not have been ascertained in the absence of end-user feedback. We therefore urge researchers to systematically evaluate web-based climate data and analysis tools in the interest of ensuring their usefulness, usability, and fulfillment of the proposed rationale. In so doing, we recommend that researchers test and apply established evaluation frameworks, thereby engaging end users directly in the process of application development.