bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ratcheting Prediction at the Notch Root of Steel Samples Over Asymmetric Loading Cycles
Authors: Shekarian A. , Varvani-Farahani A. 
Published: October 2019

Abstract
The present study intends to evaluate local ratcheting and stress relaxation of medium carbon steel samples under various asymmetric load levels by means of two kinematic hardening rules of Chaboche (CH) and Ahmadzadeh-Varvani (A-V). The Neuber's rule was coupled with the hardening rules to predict ratcheting and stress relaxation at the vicinity of the notch root. Stress-strain hysteresis loops generated by the CH and A-V models were employed to simultaneously control ratcheting progress over stress cycles and stress relaxation at notch root while strain range kept constant in each cycle. The higher cyclic load levels applied at the notch root accelerated shakedown over smaller number of cycles and resulted in lower relaxation rate. The larger notch diameter of 9 mm on the other hand induced lower stress concentration and smaller plastic zone at the notch root promoting ratcheting progress with less materials constraint over loading cycles compared with notch diameter d = 3 mm. Predicted ratcheting results through the A-V and CH models as coupled with the Neuber's rule were found in good agreements with the experimental data. The choice of the A-V and CH hardening rules in assessing ratcheting of materials was attributed to the number of terms/coefficients and complexity of their frameworks and computational time/central processing unit (CPU) required to run a ratcheting program.
Estimating the effect of calorie menu labeling on calories purchased in a large restaurant franchise in the southern United States: quasi-experimental study
Authors: Petimar Joshua , Zhang Fang , Cleveland Lauren P , Simon Denise , Gortmaker Steven L , Polacsek Michele , Bleich Sara N , Rimm Eric B , Roberto Christina A , Block Jason P 
Published: October 2019

AbstractObjectiveTo evaluate whether calorie labeling of menus in large restaurant chains was associated with a change in mean calories purchased per transaction.DesignQuasi-experimental longitudinal study.SettingLarge franchise of a national fast food company with three different restaurant chains located in the southern United States (Louisiana, Texas, and Mississippi) from April 2015 until April 2018.Participants104 restaurants with calorie information added to in-store and drive-thru menus in April 2017 and with weekly aggregated sales data during the pre-labeling (April 2015 to April 2017) and post-labeling (April 2017 to April 2018) implementation period.Main outcome measuresPrimary outcome was the overall level and trend changes in mean purchased calories per transaction after implementation of calorie labeling compared with the counterfactual (ie, assumption that the pre-intervention trend would have persisted had the intervention not occurred) using interrupted time series analyses with linear mixed models. Secondary outcomes were by item category (entrees, sides, and sugar sweetened beverages). Subgroup analyses estimated the effect of calorie labeling in stratums defined by the sociodemographic characteristics of restaurant census tracts (defined region for taking census).ResultsThe analytic sample comprised 14 352 restaurant weeks. Over three years and among 104 restaurants, 49 062 440 transactions took place and 242 726 953 items were purchased. After labeling implementation, a level decrease was observed of 60 calories/transaction (95% confidence interval 48 to 72; about 4%), followed by an increasing trend of 0.71 calories/transaction/week (95% confidence interval 0.51 to 0.92) independent of the baseline trend over the year after implementation. These results were generally robust to different analytic assumptions in sensitivity analyses. The level decrease and post-implementation trend change were stronger for sides than for entrees or sugar sweetened beverages. The level decrease was similar between census tracts with higher and lower median income, but the post-implementation trend in calories per transaction was higher in low income (change in calories/transaction/week 0.94, 95% confidence interval 0.67 to 1.21) than in high income census tracts (0.50, 0.19 to 0.81).ConclusionsA small decrease in mean calories purchased per transaction was observed after implementation of calorie labeling in a large franchise of fast food restaurants. This reduction diminished over one year of follow-up.
Is seniority of emergency physician associated with the weekend mortality effect? An exploratory analysis of electronic health records in the UK
Authors: Han Larry , Fine Jason , Robinson Susan M , Boyle Adrian A , Freeman Michael , Scholtes Stefan 
Published: October 2019

ObjectiveAdmission to hospital over a weekend is associated with increased mortality, but the underlying causes of the weekend effect are poorly understood. We explore to what extent differences in emergency department (ED) admission and discharge processes, severity of illness and the seniority of the treating physician explain the weekend effect.MethodsWe analysed linked ED attendances to hospital admissions to Cambridge University Hospital over a 7-year period from 1 January 2007 to 31 December 2013, with 30-day in-hospital death as the primary outcome and discharge as a competing risk. The primary exposure was day of the week of arrival. Subdistribution hazards models controlled for multiple confounders, including physician seniority, calendar year, mode of arrival, triage category, referral from general practice, sex, arrival time, prior attendances and admissions, diagnosis group and age.Results229 401 patients made 424 845 ED attendances, of which 158 396 (37.3%) were admitted to the hospital. The case-mix of admitted patients was more ill at weekends: 2530 (6.4%) admitted at a weekend required immediate resuscitation compared with 6450 (5.4%) admitted on a weekday (p<0.0001). Senior doctors admitted 24.8% of patients on weekdays and 24.0% at weekends, but junior doctors admitted 61.7% of patients on weekdays and 44.2% at weekends. 3947 (3.3%) patients admitted on a weekday and 1454 (3.7%) patients admitted at a weekend died within 30 days. In the adjusted subdistribution hazards model, the HR of in-hospital death was 1.11 (95% CI 1.04 to 1.18) for weekend arrivals. After controlling for confounders, the in-hospital mortality of patients admitted by junior doctors was greater at the weekend (adjusted HR (aHR) 1.15, 95% CI 1.06 to 1.24). In-hospital mortality for patients admitted by senior doctors was not statistically different at the weekend (aHR 1.08, 95% CI 0.98 to 1.19).ConclusionsOur findings suggest that the weekend effect was driven by a higher proportion of admitted patients requiring immediate resuscitation at the weekend. Junior doctors admitted a lower proportion of relatively healthy patients at the weekend compared with the weekday, thus diluting the risk pool of weekday admissions and contributing to the weekend effect. Senior doctors’ admitting behaviour did not change at the weekend, and the corresponding weekend effect was reduced.
Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-naïve patients with chronic hepatitis B in Korea: a large-scale, propensity score analysis
Authors: Lee Sung Won , Kwon Jung Hyun , Lee Hae Lim , Yoo Sun Hong , Nam Hee Chul , Sung Pil Soo , Nam Soon Woo , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew , Han Nam Ik , Jang Jeong Won 
Published: October 2019

ObjectiveThe use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality.DesignA total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used.ResultsNo difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis.ConclusionThis study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate-term risk of HCC and mortality or LT between the two drugs.
New perspective on geographical mortality divide in Russia: a district-level cross-sectional analysis, 2008–2012
Authors: Timonin Sergey , Jasilionis Domantas , Shkolnikov Vladimir M. , Andreev Evgeny 
Published: November 2019

BackgroundPrior studies on spatial inequalities in mortality in Russia were restricted to the highest level of administrative division, ignoring variations within the regions. Using mortality data for 2239 districts, this study is the first analysis to capture the scale of the mortality divide at a more detailed level.MethodsAge-standardised death rates are calculated using aggregated deaths for 2008–2012 and population exposures from the 2010 census. Inequality indices and decomposition are applied to quantify both the total mortality disparities across the districts and the contributions of the variations between and within regions.ResultsRegional variations in mortality mask one-third (males) and one-half (females) of the inequalities observed at the district level. A comparison of the 5% of individuals residing in the districts with the highest and the lowest mortality shows a gap of 15.5 years for males and 10.3 years for females. The lowest life expectancy levels are in the shrinking areas of the Far East and Northwest of Russia. The highest life expectancy clusters are in the intercity districts of Moscow and Saint Petersburg, and in several science cities. Life expectancy in these best-practice districts is close to the national averages of Poland and Estonia, but is still substantially below the averages in Western countries.ConclusionThe large between-regional and within-regional disparities suggest that national-level mortality could be lowered if these disparities are reduced by improving health in the laggard areas. This can be achieved by introducing policies that promote health convergence both within and between the Russian regions.
A Design Flow Engine for the Support of Customized Dynamic High Level Synthesis Flows
Authors: Lattuada Marco , Ferrandi Fabrizio 
Published: October 2019

High Level Synthesis is a set of methodologies aimed at generating hardware descriptions starting from specifications written in high-level languages. While these methodologies share different elements with traditional compilation flows, there are characteristics of the addressed problem which require ad hoc management. In particular, differently from most of the traditional compilation flows, the complexity and the execution time of the High Level Synthesis techniques are much less relevant than the quality of the produced results. For this reason, fixed-point analyses, as well as successive refinement optimizations, can be accepted, provided that they can improve the quality of the generated designs.
This article presents a design flow engine for the description and the execution of complex and customized synthesis flows. It supports dynamic addition of passes and dependencies, cyclic dependencies, and selective pass invalidation. Experimental results show the benefits of such type of design flows with respect to static linear design flows when applied to High Level Synthesis.
Iron insufficiency diminishes the erythropoietic response to moderate altitude exposure
Authors: Okazaki Kazunobu , Stray-Gundersen James , Chapman Robert F. , Levine Benjamin D. 
Published: October 2019

The effects of iron stores and supplementation on erythropoietic responses to moderate altitude in endurance athletes were examined. In a retrospective study, red cell compartment volume (RCV) responses to 4 wk at 2,500 m were assessed in athletes with low ( n = 9, ≤20 and ≤30 ng/mL for women and men, respectively) and normal ( n = 10) serum ferritin levels ([Ferritin]) without iron supplementation. In a subsequent prospective study, the same responses were assessed in athletes ( n = 26) with a protocol designed to provide sufficient iron before and during identical altitude exposure. The responses to a 4-wk training camp at sea level were assessed in another group of athletes ( n = 13) as controls. RCV and maximal oxygen uptake (V̇o2max) were determined at sea level before and after intervention. In the retrospective study, athletes with low [Ferritin] did not increase RCV (27.0 ± 2.9 to 27.5 ± 3.8 mL/kg, mean ± SD, P = 0.65) or V̇o2max (60.2 ± 7.2 to 62.2 ± 7.5 mL·kg−1·min−1, P = 0.23) after 4 wk at altitude, whereas athletes with normal [Ferritin] increased both (RCV: 27.3 ± 3.1 to 29.8 ± 2.4 mL/kg, P = 0.002; V̇o2max: 62.0 ± 3.1 to 66.2 ± 3.7 mL·kg−1·min−1, P = 0.003). In the prospective study, iron supplementation normalized low [Ferritin] observed in athletes exposed to altitude ( n = 14) and sea level ( n = 6) before the altitude/sea-level camp and maintained [Ferritin] within normal range in all athletes during the camp. RCV and V̇o2max increased in the altitude group but remained unchanged in the sea-level group. Finally, the increase in RCV correlated with the increase in V̇o2max [( r = 0.368, 95% confidence interval (CI): 0.059–0.612, P = 0.022]. Thus, iron deficiency in athletes restrains erythropoiesis to altitude exposure and may preclude improvement in sea-level athletic performance. NEW & NOTEWORTHY Hypoxic exposure increases iron requirements and utilization for erythropoiesis in athletes. This study clearly demonstrates that iron deficiency in athletes inhibits accelerated erythropoiesis to a sojourn to moderate high altitude and may preclude a potential improvement in sea-level athletic performance with altitude training. Iron replacement therapy before and during altitude exposure is important to maximize performance gains after altitude training in endurance athletes.
Systemic Resolvin E1 (RvE1) Treatment Does Not Ameliorate the Severity of Collagen-Induced Arthritis (CIA) in Mice: A Randomized, Prospective, and Controlled Proof of Concept Study
Authors: de Molon Rafael Scaf , Thurlings Rogier M. , Walgreen Birgitte , Helsen Monique M. , van der Kraan Peter M. , Cirelli Joni Augusto , Koenders Marije I. 
Published: October 2019

Specialized proresolving mediators (SPRM), which arise from n-3 long-chain polyunsaturated fatty acids (n-3FA), promote resolution of inflammation and may help to prevent progression of an acute inflammatory response into chronic inflammation in patients with arthritis. Thus, this study is aimed at determining whether systemic RvE1 treatment reduces arthritis onset and severity in murine collagen-induced arthritis (CIA) and spontaneous cytokine production by human rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1 μg RvE1, 1 μg RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1 μg of RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by RvE1 or anti-TNF for 10 days. Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of RvE1, and cytokine levels (IL-1β, IL-6, IL-8, IL-10, INF-γ, and TNF-α) were measured using Luminex bead array. CIA triggered significant inflammation in the synovial cavity, proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint inflammation, bone erosion, and proteoglycan depletion, but additional RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of RvE1 did not decrease the expression of proinflammatory cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of RvE1.
YAP1 Mediates Resistance to MEK1/2 Inhibition in Neuroblastomas with Hyperactivated RAS Signaling
Authors: Coggins Grace E. , Farrel Alvin , Rathi Komal S. , Hayes Colin M. , Scolaro Laura , Rokita Jo Lynne , Maris John M. 
Published: October 2019

AbstractRelapsed neuroblastomas are enriched with activating mutations of the RAS–MAPK signaling pathway. The MEK1/2 inhibitor trametinib delays tumor growth but does not sustain regression in neuroblastoma preclinical models. Recent studies have implicated the Hippo pathway transcriptional coactivator protein YAP1 as an additional driver of relapsed neuroblastomas, as well as a mediator of trametinib resistance in other cancers. Here, we used a highly annotated set of high-risk neuroblastoma cellular models to modulate YAP1 expression and RAS pathway activation to test whether increased YAP1 transcriptional activity is a mechanism of MEK1/2 inhibition resistance in RAS-driven neuroblastomas. In NLF (biallelic NF1 inactivation) and SK-N-AS (NRAS Q61K) cell lines, trametinib caused a near-complete translocation of YAP1 protein into the nucleus. YAP1 depletion sensitized neuroblastoma cells to trametinib, while overexpression of constitutively active YAP1 protein induced trametinib resistance. Mechanistically, significant enhancement of G1–S cell-cycle arrest, mediated by depletion of MYC/MYCN and E2F transcriptional output, sensitized RAS-driven neuroblastomas to trametinib following YAP1 deletion. These findings underscore the importance of YAP activity in response to trametinib in RAS-driven neuroblastomas, as well as the potential for targeting YAP in a trametinib combination.Significance:High-risk neuroblastomas with hyperactivated RAS signaling escape the selective pressure of MEK inhibition via YAP1-mediated transcriptional reprogramming and may be sensitive to combination therapies targeting both YAP1 and MEK.
Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade
Authors: Stein Julie E. , Lipson Evan J. , Cottrell Tricia R. , Forde Patrick M. , Anders Robert A. , Cimino-Mathews Ashley , Thompson Elizabeth D. , Allaf Mohamad E. , Yarchoan Mark , Feliciano Josephine , Wang Hao , Jaffee Elizabeth M. , Pardoll Drew M. , Topalian Suzanne L. , Taube Janis M. 
Published: October 2019

Abstract

Purpose:
Pathologic response assessment of tumor specimens from patients receiving systemic treatment provides an early indication of therapeutic efficacy and predicts long-term survival. Grading systems for pathologic response were first developed for chemotherapy in select tumor types. Immunotherapeutic agents have a mechanism of action distinct from chemotherapy and are being used across a broad array of tumor types. A standardized, universal scoring system for pathologic response that encompasses features characteristic for immunotherapy and spans tumor types is needed.

Experimental Design:
Hematoxylin and eosin–stained slides from neoadjuvant surgical resections and on-treatment biopsies were assessed for features of immune-related pathologic response (irPR). A total of 258 specimens from patients with 11 tumor types as part of ongoing clinical trials for anti-PD-(L)1 were evaluated. An additional 98 specimens from patients receiving anti-PD-(L)1 in combination with other treatments were also reviewed, including those from three additional tumor types.

Results:
Common irPR features (immune activation, cell death, tissue repair, and regression bed) were present in all tumor types reviewed, including melanoma, non–small cell lung, head and neck squamous cell, Merkel cell, and renal cell carcinoma, among others. Features were consistent across primary tumors, lymph nodes, and distant metastases. Specimens from patients treated with anti-PD-(L)1 in combination with another agent also exhibited irPR features.

Conclusions:
irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor irPR criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes.
Inhibition of Y Box Binding Protein 1 Suppresses Cell Growth and Motility in Colorectal Cancer
Authors: Kim Areumnuri , Shim Sehwan , Kim Young-heon , Kim Min-Jung , Park Sunhoo , Myung Jae Kyung 
Published: October 2019

Abstract
Although chemo- or radiotherapy is usually performed in patients with colorectal cancer, the response is highly variable in locally rectal cancer. Therefore, additional studies are needed on predictable markers and the molecular mechanisms of chemo- and radiotherapy. Y box binding protein 1 (YB1) is an oncoprotein that is aberrantly expressed in many cancers, including colorectal cancer. However, to date there are no targeting agents or strategies to inhibit YB1 expression. Here, we investigate the oncogenic function of YB1 in colorectal cancer and methods to control its expression. We observed that YB1 expression level is correlated with colorectal cancer survival rate. Moreover, YB1 overexpression was associated with colorectal cancer lymph node metastasis and invasion. We also found that radiation exposure increased YB1 expression, which led to radioresistant colorectal cancer, mediated through the activation of cancer stem cell marker CD44 and PI3K/AKT/mTOR signaling. This study revealed, by both in vitro and in vivo assays, that depletion of YB1 could reduce cell proliferation and motility in colorectal cancer. We further demonstrated that the PI3K/mTOR inhibitor BEZ235 suppressed YB1 expression and enhanced the cytotoxicity of radiation. In addition, combined treatment with BEZ235 and radiation showed a significant antitumor response in an in vivo mouse xenograft model. Taken together, our results provide evidence that the activation of YB1 is a major factor in radioresistance and suggest that targeting YB1-mediated signaling is a promising therapeutic strategy for colorectal cancer.