bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-recursive make considered harmful: build systems at scale
Authors: Mokhov Andrey , Mitchell Neil , Peyton Jones Simon , Marlow Simon 
Published: July 2018

Most build systems start small and simple, but over time grow into hairy monsters that few dare to touch. As we demonstrate in this paper, there are a few issues that cause build systems major scalability challenges, and many pervasively used build systems (e.g. Make) do not scale well.
This paper presents a solution to the challenges we identify. We use functional programming to design abstractions for build systems, and implement them on top of the Shake library, which allows us to describe build rules and dependencies. To substantiate our claims, we engineer a new build system for the Glasgow Haskell Compiler. The result is more scalable, faster, and spectacularly more maintainable than its Make-based predecessor.
Antibody Responses to Streptococcus Gallolyticus Subspecies Gallolyticus Proteins in a Large Prospective Colorectal Cancer Cohort Consortium
Authors: Butt Julia , Blot William J. , Teras Lauren R. , Visvanathan Kala , Le Marchand Loïc , Haiman Christopher A. , Chen Yu , Bao Ying , Sesso Howard D. , Wassertheil-Smoller Sylvia , Ho Gloria Y. , Tinker Lesley F. , Peek Richard M. , Potter John D. , Cover Timothy L. , Hendrix Laura H. , Huang Li-Ching , Waterboer Tim , Pawlita Michael , Epplein Meira 
Published: July 2018

Abstract
Background: Antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG) proteins, especially pilus protein Gallo2178, have been consistently associated with colorectal cancer risk. Previous case–control studies and prospective studies with up to 8 years of follow-up, however, were unable to decipher the temporality of antibody responses to SGG in the context of the long-term multistep development of colorectal cancer. In this study, we analyzed a large U.S. colorectal cancer cohort consortium with follow-up beyond 10 years for antibody responses to SGG.
Methods: We applied multiplex serology to measure antibody responses to 9 SGG proteins in participants of 10 prospective U.S. cohorts (CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS, and WHI) including 4,063 incident colorectal cancer cases and 4,063 matched controls. Conditional logistic regression was used to assess whether antibody responses to SGG were associated with colorectal cancer risk, overall and by time between blood draw and diagnosis.
Results: Colorectal cancer risk was increased among those with antibody responses to Gallo2178, albeit not statistically significant [OR, 1.23; 95% confidence interval (CI), 0.99–1.52]. This association was stronger for cases diagnosed &lt;10 years after blood draw (OR, 1.40; 95% CI, 1.09–1.79), but was not found among cases diagnosed ≥10 years after blood draw (OR, 0.79; 95% CI, 0.50–1.24).
Conclusions: In a large cohort consortium, we reproduced the association of antibody responses to SGG Gallo2178 with colorectal cancer risk for individuals diagnosed within 10 years after blood draw.
Impact: This timing-specific finding suggests that antibody responses to SGG are associated with increased colorectal cancer risk only after tumorigenesis has begun. Cancer Epidemiol Biomarkers Prev; 27(10); 1186–94. ©2018 AACR.
Two HLA Class II Gene Variants Are Independently Associated with Pediatric Osteosarcoma Risk
Authors: Zhang Chenan , Wiemels Joseph L. , Hansen Helen M. , Gonzalez-Maya Julio , Endicott Alyson A. , de Smith Adam J. , Smirnov Ivan V. , Witte John S. , Morimoto Libby M. , Metayer Catherine , Walsh Kyle M. 
Published: July 2018

Abstract
Background: The genetic etiology of osteosarcoma remains poorly understood despite the publication of a genome-wide association study. Association between HLA genetic variants and risk of several cancers has been observed, but HLA variation is not well captured by standard SNP arrays.
Methods: We genotyped 207 Californian pediatric osteosarcoma cases and 696 controls of European ancestry using a custom genome-wide array supplemented with approximately 6,000 additional probes across the MHC region. We subsequently imputed 4-digit classical HLA alleles using a reference panel of 5,225 individuals who underwent high-resolution HLA typing via next-generation sequencing. Case–control comparisons were adjusted for ancestry-informative principal components, and top associations from the discovery analysis underwent replication in an independent dataset of 657 cases and 1,183 controls.
Results: Three highly correlated HLA class II variants (r2 = 0.33–0.98) were associated with osteosarcoma risk in discovery analyses, including HLA-DRB1*0301 (OR = 0.52; P = 3.2 × 10−3), HLA-DQA1*0501 (OR = 0.74; P = 0.031), and HLA-DQB1*0201 (OR = 0.51; P = 2.7 × 10−3). Similar associations were observed in the replication data (Prange = 0.011–0.037). Meta-analysis of the two datasets identified HLA-DRB1*0301 as the most significantly associated variant (ORmeta = 0.62; Pmeta = 1.5 × 10−4), reaching Bonferroni-corrected statistical significance. The meta-analysis also revealed a second significant independent signal at HLA-DQA1*01:01 (ORmeta = 1.33, Pmeta = 1.2 × 10−3), and a third suggestive association at HLA-DQB1*0302 (ORmeta = 0.73, Pmeta = 6.4 × 10−3).
Conclusions: Multiple independent HLA class II alleles may influence osteosarcoma risk.
Impact: Additional work is needed to extend our observations to other patient populations and to clarify the potential causal mechanisms underlying these associations. Understanding immunologic contributions to the etiology of osteosarcoma may inform rational therapeutic targets. Cancer Epidemiol Biomarkers Prev; 27(10); 1151–8. ©2018 AACR.
Integrated Analysis of RNA and DNA from the Phase III Trial CALGB 40601 Identifies Predictors of Response to Trastuzumab-Based Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer
Authors: Tanioka Maki , Fan Cheng , Parker Joel S. , Hoadley Katherine A. , Hu Zhiyuan , Li Yan , Hyslop Terry M. , Pitcher Brandelyn N. , Soloway Matthew G. , Spears Patricia A. , Henry Lynn N. , Tolaney Sara , Dang Chau T. , Krop Ian E. , Harris Lyndsay N. , Berry Donald A. , Mardis Elaine R. , Winer Eric P. , Hudis Clifford A. , Carey Lisa A. , Perou Charles M. 
Published: July 2018

Abstract
Purpose: Response to a complex trastuzumab-based regimen is affected by multiple features of the tumor and its microenvironment. Developing a predictive algorithm is key to optimizing HER2-targeting therapy.
Experimental Design: We analyzed 137 pretreatment tumors with mRNA-seq and DNA exome sequencing from CALGB 40601, a neoadjuvant phase III trial of paclitaxel plus trastuzumab with or without lapatinib in stage II to III HER2-positive breast cancer. We adopted an Elastic Net regularized regression approach that controls for covarying features within high-dimensional data. First, we applied 517 known gene expression signatures to develop an Elastic Net model to predict pCR, which we validated on 143 samples from four independent trials. Next, we performed integrative analyses incorporating clinicopathologic information with somatic mutation status, DNA copy number alterations (CNA), and gene signatures.
Results: The Elastic Net model using only gene signatures predicted pCR in the validation sets (AUC = 0.76). Integrative analyses showed that models containing gene signatures, clinical features, and DNA information were better pCR predictors than models containing a single data type. Frequently selected variables from the multiplatform models included amplifications of chromosome 6p, TP53 mutation, HER2-enriched subtype, and immune signatures. Variables predicting resistance included Luminal/ER+ features.
Conclusions: Models using RNA only, as well as integrated RNA and DNA models, can predict pCR with improved accuracy over clinical variables. Somatic DNA alterations (mutation, CNAs), tumor molecular subtype (HER2E, Luminal), and the microenvironment (immune cells) were independent predictors of response to trastuzumab and paclitaxel-based regimens. This highlights the complexity of predicting response in HER2-positive breast cancer. Clin Cancer Res; 24(21); 5292–304. ©2018 AACR.
Autophagy Governs Protumorigenic Effects of Mitotic Slippage–induced Senescence
Authors: Jakhar Rekha , Luijten Monique N.H. , Wong Alex X.F. , Cheng Bing , Guo Ke , Neo Suat P. , Au Bijin , Kulkarni Madhura , Lim Kah J. , Maimaiti Jiamila , Chong Han C. , Lim Elaine H. , Tan Tee B.K. , Ong Kong W. , Sim Yirong , Wong Jill S.L. , Khoo James B.K. , Ho Juliana T.S. , Chua Boon T. , Sinha Indrajit , Wang Xiaomeng , Connolly John E. , Gunaratne Jayantha , Crasta Karen C. 
Published: July 2018

Abstract
The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and “slip” into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment.
Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625–40. ©2018 AACR.
SWI/SNF Complexes in Ovarian Cancer: Mechanistic Insights and Therapeutic Implications
Authors: Fukumoto Takeshi , Magno Elizabeth , Zhang Rugang 
Published: July 2018

Abstract

Ovarian cancer remains the most lethal gynecologic malignancy in the developed world. Despite the unprecedented progress in understanding the genetics of ovarian cancer, cures remain elusive due to a lack of insight into the mechanisms that can be targeted to develop new therapies. SWI/SNF chromatin remodeling complexes are genetically altered in approximately 20% of all human cancers. SWI/SNF alterations vary in different histologic subtypes of ovarian cancer, with ARID1A mutation occurring in approximately 50% of ovarian clear cell carcinomas. Given the complexity and prevalence of SWI/SNF alterations, ovarian cancer represents a paradigm for investigating the molecular basis and exploring therapeutic strategies for SWI/SNF alterations. This review discusses the recent progress in understanding SWI/SNF alterations in ovarian cancer and specifically focuses on: (i) ARID1A mutation in endometriosis-associated clear cell and endometrioid histologic subtypes of ovarian cancer; (ii) SMARCA4 mutation in small cell carcinoma of the ovary, hypercalcemic type; and (iii) amplification/upregulation of CARM1, a regulator of BAF155, in high-grade serous ovarian cancer. Understanding the molecular underpinning of SWI/SNF alterations in different histologic subtypes of ovarian cancer will provide mechanistic insight into how these alterations contribute to ovarian cancer. Finally, the review discusses how these newly gained insights can be leveraged to develop urgently needed therapeutic strategies in a personalized manner.
Effect of the transversus abdominis plane block on postoperative pain and recovery in patients with hepatic echinococcosis
Authors: Su Wenjie , Deng Xiaofan , Li Xiangkui , Deng Jia , Li Peng , Yang Mengchang 
Published: July 2018

Objectives Hepatic echinococcosis (HE) is a severe parasitic disease that occurs worldwide, and radical surgery is the recommended therapy. This study was performed to investigate the efficacy of using a transversus abdominis plane (TAP) block during surgery on postoperative pain and recovery of patients with HE under the guidelines of an enhanced recovery after surgery (ERAS) protocol. Methods Fifty-eight patients from the Tibetan plateau who underwent surgery for treatment of HE by the same surgeons under the guidance of ERAS were included in the present study. A TAP block was conducted before closing the abdominal cavity. Results The consumption of sufentanil was significantly lower in patients of the TAP than control group. Patients had a significantly shorter time to first flatus in the TAP than control group. Other parameters showed no significant differences between the two groups. Conclusions Use of the TAP block could reduce the consumption of analgesic medication and promote recovery of patients from the Tibetan plateau under the guidance of an ERAS protocol.
Cytotoxicity of long-term denture base materials
Authors: Çakırbay Tanış Merve , Akay Canan , Sevim Handan 
Published: July 2018

Introduction: The aim of this study was to evaluate the cytotoxic effect of various denture base materials following four different aging periods. Methods: In total, 48 disc-shaped specimens per each group were prepared: Group I: acrylic resin polymerized in cool water and heated up to 100°C over 45 min and boiled for 15 min; Group II: acrylic resin polymerized under pressure in 40°C–45°C water bath for 10 min; Group III: autopolymerized hard relining resin Cold Liner Rebase; Group IV: autopolymerized hard relining resin Truliner; Group V: soft relining resin DentuSil. Then the specimens were stored in water for 24 h or 15 days, or thermocycled 2500 times or 10,000 times. Cytotoxicity was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L929 cells after 72-h cell incubation. Cell viability percentages were counted and statistical analyses were performed. The results were also evaluated according to ISO standard 10993-5. Results: All materials showed similar cell viability percentages following 24-h water storage and 2500 and 10,000 thermal cycles. Following 15-day water storage, a statistically significant difference was observed between the materials. Comparisons of the aging periods for each material showed statistically significant differences. Groups III and IV showed moderately cytotoxic effect following 15-day water storage. The remaining groups showed slightly cytotoxic or non-cytotoxic effect. Discussion: Polymerizing acrylic resins under pressure can be an alternative to conventional polymerizing to ensure a faster denture repair while providing similar cell viability values. Heat-cured acrylic resins provide higher cell viability than hard chairside lining materials in a 15-day period.
Migrations and Federations
Authors: Heiss Johann 
Published: July 2018

This contribution focuses on the beginnings of the tribal federation called Khawlān in the north of what today is Yemen. Al-Hamdānī, the Yemeni philosopher, genealogist and astronomer writes about these beginnings in two of his works; a passage from Nashwān’s ‘Shams al-‘ulūm’ will complete the picture. At first, a son of Khawlan migrates from Ma’rib to Ṣirwāḥ, in the territory of another group called Khawlān. From there, a grandson of the first migrant goes on to the region of Ṣa‘da, where he forms a federation with another tribal group. Both settle in the plain of Ṣa‘da or in the mountainous region west of it. To accomplish that, they have to wage war against Hamdān who are the original settlers there. These are the basic facts deducible from the texts. Khawlān really comes into view when the tribal groups wage war. The groups of the original migrants and their allies are not related. Religion plays no part in the occurrences put forward in the texts. As far as possible, these narrations are interpreted and brought into relation to the tribal situation of Yemen at the time.
Unexpected complications during insertion of a central venous catheter
Authors: Tirumala Sridhar , Hyatali Farees , Eskander John , Leandre Mario , Patil Shilpadevi , Cornette Elyse 
Published: July 2018

Introduction Central venous catheters are essential and widely used in medical practice. Their use may be accompanied with complications during insertion and removal. Complications related to the guidewire are rare, and information about appropriate management is scarce. We report a case of a 34-year-old patient admitted for a left femur fracture. Venous access was deemed difficult, so a decision was made to place a central venous catheter before surgery. During insertion of the central venous catheter, there was difficulty in advancing the guidewire. Attempts were made to remove the guidewire through the introducer, but the guidewire would not thread out of the introducer. The introducer and guidewire were then removed as a unit with ease. The guidewire had lost its shape and uncoiled itself, becoming much more flimsy and fragile. Conclusion While this case had no adverse outcome secondary to the removal of the guidewire and introducer as a unit, careful attention should be noted when attempting to remove the guidewire during central venous catheter placement. If faced with a similar scenario where the guidewire is stuck and does not thread out easily, removing the guidewire and introducer as a unit is a safe method of action.
Heart rate recovery is associated with ventilatory constraints and excess ventilation during exercise in patients with chronic obstructive pulmonary disease
Authors: Crisafulli Ernesto , Vigna Matteo , Ielpo Antonella , Tzani Panagiota , Mangia Angelo , Teopompi Elisabetta , Aiello Marina , Alfieri Veronica , Bertorelli Giuseppina , Palange Paolo , Chetta Alfredo 
Published: July 2018

Background Heart rate recovery delay is a marker of cardiac autonomic dysfunction. In chronic obstructive pulmonary disease patients, the ventilatory response to exercise during incremental cardiopulmonary exercise test may add information about dynamic hyperinflation by low values of inspiratory capacity/total lung capacity ratio (at peak) and excess ventilation by the slope of minute ventilation to carbon dioxide output ratio (VE/VCO2 slope). We aimed to assess if the ventilatory response to exercise might be a determinant for heart rate recovery delay. Design An observational, prospective study. Methods Anthropometric characteristics, lung function and cardiopulmonary exercise test data were recorded in chronic obstructive pulmonary disease outpatients. A cut-off of heart rate recovery of 12 or more beats was used to define heart rate recovery delay. Results Of 254 patients enrolled, 156 (61%) showed heart rate recovery delay. As compared to patients with normal heart rate recovery, patients with delay were older, with a worse lung function and with lower values of peak oxygen uptake, maximal workload, oxygen pulse at rest and at peak, and inspiratory capacity/total lung capacity at peak. Conversely, VE/VCO2 slope and dyspnoea and leg fatigue perception at peak were higher in patients with heart rate recovery delay. In the multivariate regression model adjusted for age, sex, fat-free mass, heart rate at rest and use of β-blockers, we found that inspiratory capacity/total lung capacity at peak (<0.25) (odds ratio 2.61; P = 0.007) and VE/VCO2 slope (>32) (odds ratio 2.26; P = 0.018) predict the risk of heart rate recovery delay. Conclusions In chronic obstructive pulmonary disease outpatients, heart rate recovery is associated with dynamic hyperinflation and excess ventilation during exercise.
Day-case surgery is possible in the majority of men undergoing transurethral resection of the prostate – a report on over 1000 cases
Authors: Lavan L , Kyriazis G , Mbiabjeu D , Gormley R , Hall S , Robinson R , Hodgson D 
Published: July 2018

Objective: We describe our experience of performing bipolar transurethral resection in saline (Olympus Medical) as a day-case procedure over an initial five-year period. Patients and methods: All procedures coded as transurethral resection of the prostate over a 60-month period were analysed to determine whether the procedure was planned as a day-case or as an inpatient admission, and whether post-operative discharge proceeded as intended. Re-admission rates, reasons for re-admission and transfusion rates were also recorded. Results: Of the 1035 operations, 689 (66.57%) were planned as a day-case procedure (mean age 70.5 years) with 176 (25.5%) requiring inpatient admission, and 346 (33.43%) were planned for inpatient admission (mean age 73.6) but 58 (16.8%) were discharged the same day. Overall 571 (55.17%) procedures were performed as day cases. Readmission rates for day-case and inpatient procedures were 7.4%, and 6.3% respectively ( p=0.48). Transfusion rates were lower in the day-case group (0.7% vs 3.7%, p<0.05). Day-case rates improved from 48.70% in 2011 to 75.22% in 2016. Conversion from day case to inpatient fell from 34.6% in 2011 to 14.8% in 2016. Conclusions: Our experience indicates that day-case transurethral resection of the prostate can be performed safely in appropriately selected patients, without increased rates of re-admission or complications. Level of evidence: 4 (Oxford Centre for Evidence-Based Medicine (CEBM)).
Macular Changes on Optical Coherence Tomography Before, During, and After Silicone Oil Tamponade for Macula-On Retinal Detachment: A Case Series
Authors: Kheir Wajiha J. , Mehanna Carl-Joe , Koaik Mona , Bashshur Ziad 
Published: July 2018

Purpose: Assess changes on spectral domain optical coherence tomography (OCT) before, during, and after removal of silicone oil (SO). Methods: Retrospective series of patients who underwent SO tamponade for macula-on rhegmatogenous retinal detachment. OCT scans of the affected eye were taken before, during, and 3 months after SO tamponade. Qualitative assessment of foveal contour and quantitative comparison of OCT parameters (central macular, cube, ganglion cell layer [GCL], and outer retinal thicknesses) were done between 3 time points. Results: Ten eyes of 9 patients were included. Flattening of the foveal contour during SO tamponade was completely reversed after SO removal. Average cube and GCL thicknesses decreased with SO tamponade and increased after SO removal ( P = .01 and P = .02, respectively). Outer retinal thicknesses did not vary among 3 time points ( P = .09). Conclusions: SO tamponade causes foveal flattening and thinning of the inner retinal layers, which is reversible on removal.