bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examination of Various Bending Moments on the Run Side and on the Branch Side for the Stress Index C2 of ASME NB-3600 Class 1 Branch Connections
Authors: Faraz Umar , Gurdal Robert 
Published: December 2016

Previous stress analyses have shown that the requirement of exclusively using the branch pipe cross-section properties for the NB-3600 Class 1 branch connection stress analyses can be very severe (conservative), when compared with using the branch nozzle cross-section properties. In the analyses performed for a 2015 PVP technical paper (Ref. 2), one of the questions raised was the fact that only two specified bending moments were used in those previous stress analyses: 1,000,000 in-lbf as the run bending moment and 20,000 in-lbf as the branch bending moment. In fact, that was the main question that was raised. Therefore, the purpose of this technical paper is to perform additional stress analyses, based on various bending moments on the run side and on the branch side. The impact of using these various bending moments will be evaluated.
The 2001 Edition of the ASME-Code removed a note at the bottom of the branch connection NB-3600 Figure. This note is required to be able to perform more accurate NB-3600 piping stress analyses of the branch connection. There is at this time a suggestion to restore that note.
Internet-based cognitive–behavioural therapy for insomnia (ICBT-i): a meta-analysis of randomised controlled trials
Authors: Ye Yuan-yuan , Chen Ni-ka , Chen Jia , Liu Juan , Lin Ling , Liu Ya-zhen , Lang Ying , Li Xun-jun , Yang Xin-ju , Jiang Xiao-jiang 
Published: December 2016

ObjectiveTo evaluate the effectiveness of internet-based cognitive–behavioural therapy for insomnia (ICBT-i) in adults.DesignA meta-analysis of ICBT-i.Data sourcesSystematic searches of randomised controlled trials of ICBT-i were performed in the PubMed, EMBASE, PsycINFO and Cochrane Library databases up to 19 June 2016.Review method2 reviewers independently performed study selection, quality assessment and data extraction. Outcomes of interest included sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of nocturnal awakenings (NWAK), and Insomnia Severity Index (ISI). RevMan 5.2 and Stata 13.0 meta-analysis software were used to perform statistical analysis.Results14 records for 15 studies (1013 experimental group participants, 591 waiting list group participants) were included. The meta-analysis indicated that, at the post-test time point, SOL decreased by 18.41 min (95% CI 13.60 to 23.21), TST increased by 22.30 min (95% CI 16.38 to 28.23), SE increased by 9.58% (95% CI 7.30% to 11.85%), WASO decreased by 22.31 min (95% CI 13.50 to 31.11), NWAK decreased by 0.52 (95% CI 0.28 to 0.76), and ISI decreased by 5.88 points (95% CI 4.29 to 7.46). Additionally SOL, TST, SE, and WASO exhibited statistically significant improvements at follow-up versus before treatment.ConclusionsICBT-i is an effective treatment for adults with insomnia. This conclusion should be verified in further studies.
Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank
Authors: Nevado-Holgado Alejo J , Kim Chi-Hun , Winchester Laura , Gallacher John , Lovestone Simon 
Published: December 2016

ObjectiveTo investigate medications associated with cognitive function.DesignPopulation-based cross-sectional cohort study.SettingUK Biobank.ParticipantsUK Biobank participants aged 37–73 years who completed cognitive tests at the baseline visit in 2006–2010.Main outcome measuresCognitive test outcomes on verbal–numerical reasoning test (n=165 493), memory test (n=482 766) and reaction time test (n=496 813).ResultsMost drugs (262 of 368) were not associated with any cognitive tests after adjusting for age, gender, education, household income, smoking, alcohol status, psychostimulant/nootropic medication use, assessment centre, and concurrent diagnoses and medications. Drugs used for nervous system disorders were associated with poorer cognitive performance (antiepileptics, eg, topiramate breasoning(score)−0.65 (95% CI −1.05 to −0.24), bmemory(score)−1.41 (−1.79 to −1.04); antipsychotics, eg, risperidone breaction time(ms)−33 (−46 to −20), negative values indicate poor cognitive performance and vice versa). Drugs used for non-nervous system conditions also showed significant negative association with cognitive score, including those where such an association might have been predicted (antihypertensives, eg, amlodipine breasoning−0.1 (−0.15 to −0.06), bmemory−0.08 (−0.13 to −0.03), breaction time−3 (−5 to −2); antidiabetics, eg, insulin breaction time−13 (−17 to −10)) and others where such an association was a surprising observation (proton pump inhibitors, eg, omeprazole breasoning−0.11 (−0.15 to −0.06), bmemory−0.08 (−0.12 to −0.04), breaction time−5 (−6 to −3); laxatives, eg, contact laxatives breaction time−13 (−19 to −8)). Finally, only a few medications and health supplements showed association towards a positive effect on cognitive function (anti-inflammatory agents, eg, ibuprofen breasoning0.05 (0.02 to 0.08), breaction time4 (3, 5); glucosamine breasoning0.09 (0.03 to 0.14), breaction time5 (3 to 6)).ConclusionsIn this large volunteer study, some commonly prescribed medications were associated with poor cognitive performance. Some associations may reflect underlying diseases for which the medications were prescribed, although the analysis controlled for the possible effect of diagnosis. Other drugs, whose association cannot be linked to the effect of any disease, may need vigilance for their implications in clinical practice.
Keeping Weight Off: study protocol of an RCT to investigate brain changes associated with mindfulness-based stress reduction
Authors: Fulwiler Carl , Siegel Julia A , Allison Jeroan , Rosal Milagros C , Brewer Judson , King Jean A 
Published: December 2016

IntroductionObesity is a growing epidemic fuelled by unhealthy behaviours and associated with significant comorbidities and financial costs. While behavioural interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. This may partially be due to failure to target stress and emotional reactivity. Mindfulness-based stress reduction (MBSR) reduces stress and emotional reactivity and may be a useful tool for behaviour change maintenance. This study seeks to provide a mechanistic understanding for clinical trials of the benefits of MBSR for weight loss maintenance by examining changes in functional connectivity (FC) and the association of these changes with clinical outcomes.Methods and analysisCommunity-dwelling individuals (n=80) who intentionally lost ≥5% of their body weight in the past year will be recruited and randomised to an MBSR programme or educational control. FC using resting-state functional MRI will be measured at baseline and 8 weeks. Psychological factors, health behaviours, body mass index and waist circumference will be measured at baseline, 8 weeks and 6 months post intervention. A 12-month telephone follow-up will assess self-reported weight. Analyses will characterise FC changes in response to MBSR in comparison with a control condition, assess the relationship between baseline FC status and pre–post MBSR changes in FC and investigate the association of FC change with changes in psychological factors and weight loss maintenance.Ethics and disseminationThe University of Massachusetts Medical School Institutional Review Board has approved this study, Declaration of Helsinki protocols are being followed, and patients will give written informed consent. The Independent Monitoring Committee will monitor protocol adherence. Results from the study will be disseminated to the medical community at conferences and submitted for publication in peer-reviewed journals when the last patient included has been followed up for 12 months.Trial registration numberNCT02189187.
Leveraging ongoing research to evaluate the health impacts of South Africa's salt reduction strategy: a prospective nested cohort within the WHO-SAGE multicountry, longitudinal study
Authors: Charlton Karen , Ware Lisa J , Menyanu Elias , Biritwum Richard Berko , Naidoo Nirmala , Pieterse Chiné , Madurai Savathree (Lorna) , Baumgartner Jeannine , Asare George A , Thiele Elizabeth , Schutte Aletta E , Kowal Paul 
Published: December 2016

IntroductionAttempting to curb the rising epidemic of hypertension, South Africa implemented legislation in June 2016 mandating maximum sodium levels in a range of manufactured foods that contribute significantly to population salt intake. This natural experiment, comparing two African countries with and without salt legislation, will provide timely information on the impact of legislative approaches addressing the food supply to improve blood pressure in African populations. This article outlines the design of this ongoing prospective nested cohort study.Methods and analysisBaseline sodium intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) wave 2 (2014–2015), a multinational longitudinal study on the health and well-being of adults and the ageing process. The South African cohort consisted of randomly selected households (n=4030) across the country. Spot and 24-hour urine samples are collected in a random subsample (n=1200) and sodium, potassium, creatinine and iodine analysed. Salt behaviour and sociodemographic data are captured using face-to-face interviews, alongside blood pressure and anthropometric measures. Ghana, the selected control country with no formal salt policy, provided a nested subsample (n=1200) contributing spot and 24-hour urine samples from the SAGE Ghana cohort (n=5000). Follow-up interviews and urine collection (wave 3) in both countries will take place in 2017 (postlegislation) to assess change in population-level sodium intake and blood pressure.Ethics and disseminationSAGE was approved by the WHO Ethics Review Committee (reference number RPC149) with local approval from the North-West University Human Research Ethics Committee and University of the Witwatersrand Human Research Ethics Committee (South Africa), and University of Ghana Medical School Ethics and Protocol Review Committee (Ghana). The results of the study will be published in peer-reviewed international journals, presented at national and international conferences, and summarised as research and policy briefs.
Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction
Authors: Nishiyama Steven K. , Zhao Jia , Wray D. Walter , Richardson Russell S. 
Published: December 2016

Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH [area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml], and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) ( P < 0.05). Administration of ET-1 also reduced FMD (control: 2.4 ± 0.3%, ET-1: 0.5 ± 0.5%) and FMD normalized for shear rate (control: 10.5 × 10−4 ± 2.0 × 10−4%/s−1, ET-1: 0.9 × 10−4 ± 2.8 ×10−4%/s−1). These findings reveal that elevated levels of ET-1 have a significant impact on vascular function, indicating that studies employing RH and FMD as markers of microvascular function and nitric oxide bioavailability, respectively, should exercise caution, as ET-1 can impact these assessments by tipping the balance between vasodilation and vasoconstriction, in favor of the latter. NEW & NOTEWORTHY Endothelin-1 (ET-1) is recognized as the body’s most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function.
A PAM50-Based Chemoendocrine Score for Hormone Receptor–Positive Breast Cancer with an Intermediate Risk of Relapse
Authors: Prat Aleix , Lluch Ana , Turnbull Arran K. , Dunbier Anita K. , Calvo Lourdes , Albanell Joan , de la Haba-Rodríguez Juan , Arcusa Angels , Chacón José Ignacio , Sánchez-Rovira Pedro , Plazaola Arrate , Muñoz Montserrat , Paré Laia , Parker Joel S. , Ribelles Nuria , Jimenez Begoña , Bin Aiderus Abdul Aziz , Caballero Rosalía , Adamo Barbara , Dowsett Mitch , Carrasco Eva , Martín Miguel , Dixon J. Michael , Perou Charles M. , Alba Emilio 
Published: December 2016

Abstract
Purpose: Hormone receptor–positive (HR+) breast cancer is clinically and biologically heterogeneous, and subgroups with different prognostic and treatment sensitivities need to be identified.
Experimental Design: Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR+/HER2− disease randomly assigned to neoadjuvant multiagent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based chemoendocrine score (CES). CES's predictive ability was evaluated in 4 independent neoadjuvant data sets (n = 675) and 4 adjuvant data sets (n = 1,505). The association of CES, intrinsic biology, and PAM50 risk of relapse (ROR) was explored across 6,007 tumors.
Results: Most genes associated with endocrine sensitivity were also found associated with chemotherapy resistance. In the chemotherapy test/validation data sets, CES was independently associated with pathologic complete response (pCR), even after adjusting for intrinsic subtype. pCR rates of the CES endocrine–sensitive (CES-E), uncertain (CES-U), and chemotherapy-sensitive (CES-C) groups in both data sets combined were 25%, 11%, and 2%, respectively. In the endocrine test/validation data sets, CES was independently associated with response. Compared with ROR, &gt;90% of ROR-low and ROR-high tumors were identified as CES-E and CES-C, respectively; however, each CES group represented &gt;25% of ROR-intermediate disease. In terms of survival outcome, CES-C was associated with poor relapse-free survival in patients with ROR-intermediate disease treated with either adjuvant endocrine therapy only or no adjuvant systemic therapy, but not in patients treated with (neo)adjuvant chemotherapy.
Conclusions: CES is a genomic signature capable of estimating chemoendocrine sensitivity in HR+ breast cancer beyond intrinsic subtype and risk of relapse. Clin Cancer Res; 23(12); 3035–44. ©2016 AACR.
Astrocyte Elevated Gene-1 Regulates β-Catenin Signaling to Maintain Glioma Stem-like Stemness and Self-Renewal
Authors: Hu Bin , Emdad Luni , Kegelman Timothy P. , Shen Xue-Ning , Das Swadesh K. , Sarkar Devanand , Fisher Paul B. 
Published: December 2016

AbstractGlioblastoma multiforme is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSC) are responsible for glioblastoma multiforme escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers, including glioblastoma multiforme, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology. Primary glioblastoma multiforme cells were isolated from tumor specimens and cultured as neurospheres. Using the surface marker CD133, negative and positive cells were separated as nonstem and stem populations by cell sorting. Tissue samples and low passage cells were characterized and compared with normal controls. Functional biological assays were performed to measure stemness, self-renewal, differentiation, adhesion, protein–protein interactions, and cell signaling. AEG-1 was upregulated in all glioblastoma multiforme neurospheres compared with normal neural stem cells. Expression of AEG-1 was strongly associated with stem cell markers CD133 and SOX2. AEG-1 facilitated β-catenin translocation into the nucleus by forming a complex with LEF1 and β-catenin, subsequently activating Wnt signaling downstream genes. Through an AEG-1/Akt/GSK3β signaling axis, AEG-1 controlled phosphorylation levels of β-catenin that stabilized the protein.Implications: This study discovers a previously unrecognized role of AEG-1 in GSC biology and supports the significance of this gene as a potential therapeutic target for glioblastoma multiforme. Mol Cancer Res; 15(2); 225–33. ©2016 AACR.
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations
Authors: Shin Daniel Sanghoon , Zaretsky Jesse M. , Escuin-Ordinas Helena , Garcia-Diaz Angel , Hu-Lieskovan Siwen , Kalbasi Anusha , Grasso Catherine S. , Hugo Willy , Sandoval Salemiz , Torrejon Davis Y. , Palaskas Nicolaos , Rodriguez Gabriel Abril , Parisi Giulia , Azhdam Ariel , Chmielowski Bartosz , Cherry Grace , Seja Elizabeth , Berent-Maoz Beata , Shintaku I. Peter , Le Dung T. , Pardoll Drew M. , Diaz Luis A. , Tumeh Paul C. , Graeber Thomas G. , Lo Roger S. , Comin-Anduix Begoña , Ribas Antoni 
Published: December 2016

Abstract
Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti–PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair–deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti–PD-1 therapy. Two out of 48 human melanoma cell lines had JAK1/2 mutations, which led to a lack of PD-L1 expression upon interferon gamma exposure mediated by an inability to signal through the interferon gamma receptor pathway. JAK1/2 loss-of-function alterations in The Cancer Genome Atlas confer adverse outcomes in patients. We propose that JAK1/2 loss-of-function mutations are a genetic mechanism of lack of reactive PD-L1 expression and response to interferon gamma, leading to primary resistance to PD-1 blockade therapy.
Significance: A key functional result from somatic JAK1/2 mutations in a cancer cell is the inability to respond to interferon gamma by expressing PD-L1 and many other interferon-stimulated genes. These mutations result in a genetic mechanism for the absence of reactive PD-L1 expression, and patients harboring such tumors would be unlikely to respond to PD-1 blockade therapy. Cancer Discov; 7(2); 188–201. ©2016 AACR.
See related commentary by Marabelle et al., p. 128.
This article is highlighted in the In This Issue feature, p. 115
Translating Science into Survival: Report on the Second International Cancer Immunotherapy Conference
Authors: Brodsky Arthur N. , Hubbard-Lucey Vanessa M. 
Published: December 2016

Abstract
On September 25–28, 2016, in New York City, the Second International Cancer Immunotherapy Conference was cohosted by the Cancer Research Institute, the American Association for Cancer Research, the Association for Cancer Immunotherapy, and the European Academy of Tumor Immunology. This exciting conference brought together more than 1,400 participants, including scientists, clinicians, investors, and regulators, to discuss the latest scientific advances within the field of cancer immunotherapy. This conference report reviews the chief themes that emerged during the 4-day meeting. Cancer Immunol Res; 4(12); 996–1000. ©2016 AACR.
Idarucizumab does not have procoagulant effects: Assessment of thrombosis biomarkers in healthy volunteers
Authors: Schmohl Michael , Glund Stephan , Harada Akiko , Imazu Susumu , Smet Marina De , Moschetti Viktoria , Ramael Steven , Ikushima Ippei , Grünenfelder Fredrik , Reilly Paul , Stangier Joachim 
Published: December 2016

SummaryIdarucizumab, a humanised monoclonal antibody fragment, binds dabigatran with high affinity and immediately, completely and sustainably reverses dabigatran-induced changes on blood coagulation. The present analysis focuses on the evaluation of potential procoagulant properties of idarucizumab when administered in the absence of dabigatran. As part of two Phase I studies conducted in healthy Caucasian and Japanese male volunteers, the effect of idarucizumab (8 g as a 1-hour [h] infusion and 4 g as a 5-minute [min] infusion) and placebo on calibrated automated thrombography (CAT) was assessed using platelet-poor plasma samples. Measures were made before and 15 min after the end of infusion in Caucasian subjects, as well as predose, 15 min, 4 h and 8 h in Japanese subjects. The levels of the thrombosis markers D-dimer and prothrombin fragment 1 + 2 (F1.2) were assessed over time in plasma samples up to 72 h after the end of infusion of idarucizumab and placebo. Idarucizumab had no apparent effect on endogenous thrombin formation as measured by CAT. D-dimer and F1.2 levels were highly variable in all dose groups but did not increase when compared with placebo or pre-dose levels. In conclusion, idarucizumab had no effect on endogenous thrombin generation. Additional markers of thrombosis, F1.2 and D-dimer, did not differ between placebo and idarucizumab, indicating a lack of procoagulant properties of idarucizumab.
Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A
Authors: Giangrande Paul , Andreeva Tatiana , Chowdary Pratima , Ehrenforth Silke , Hanabusa Hideji , Leebeek Frank W. G. , Lentz Steven R. , Nemes Laszlo , Poulsen Lone Hvitfeldt , Santagostino Elena , You Chur Woo , Ong Clausen Wan Hui , Jönsson Peter G. , Oldenburg Johannes ,   for the Pathfinder™2 Investigators
Published: December 2016

SummaryTuroctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20–75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00–4.61), the mean ABR was 3.70 (95 % confidence interval 2.94–4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.