bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposing Memory Access Patterns to Improve Instruction and Memory Efficiency in GPUs
Authors: Crago Neal C. , Stephenson Mark , Keckler Stephen W. 
Published: October 2018

Modern computing workloads often have high memory intensity, requiring high bandwidth access to memory. The memory request patterns of these workloads vary and include regular strided accesses and indirect (pointer-based) accesses. Such applications require a large number of address generation instructions and a high degree of memory-level parallelism. This article proposes new memory instructions that exploit strided and indirect memory request patterns and improve efficiency in GPU architectures. The new instructions reduce address calculation instructions by offloading addressing to dedicated hardware, and reduce destructive memory request interference by grouping related requests together. Our results show that we can eliminate 33% of dynamic instructions across 16 GPU benchmarks. These improvements result in an overall runtime improvement of 26%, an energy reduction of 18%, and a reduction in energy-delay product of 32%.
The Microbiomes of Pancreatic and Duodenum Tissue Overlap and Are Highly Subject Specific but Differ between Pancreatic Cancer and Noncancer Subjects
Authors: del Castillo Erika , Meier Richard , Chung Mei , Koestler Devin C. , Chen Tsute , Paster Bruce J. , Charpentier Kevin P. , Kelsey Karl T. , Izard Jacques , Michaud Dominique S. 
Published: October 2018

Abstract

Background:
In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.

Methods:
Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples.

Results:
Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus Lactobacillus was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of Fusobacterium spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects.

Conclusions:
Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined.

Impact:
Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria.
Ibrutinib Therapy Releases Leukemic Surface IgM from Antigen Drive in Chronic Lymphocytic Leukemia Patients
Authors: Drennan Samantha , Chiodin Giorgia , D'Avola Annalisa , Tracy Ian , Johnson Peter W. , Trentin Livio , Steele Andrew J. , Packham Graham , Stevenson Freda K. , Forconi Francesco 
Published: October 2018

Abstract

Purpose:
In chronic lymphocytic leukemia (CLL), disease progression associates with surface IgM (sIgM) levels and signaling capacity. These are variably downmodulated in vivo and recover in vitro, suggesting a reversible influence of tissue-located antigen. Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit. Circulating CLL cells persist in an inhibited state, offering a tool to investigate the effects of drug on BTK-inhibited sIgM.

Experimental Design:
We investigated the consequences of ibrutinib therapy on levels and function of sIgM in circulating leukemic cells of patients with CLL.

Results:
At week 1, there was a significant increase of sIgM expression (64% increase from pretherapy) on CLL cells either recently released from tissue or persisting in blood. In contrast, surface IgD (sIgD) and a range of other receptors did not change. SIgM levels remained higher than pretherapy in the following 3 months despite gradual cell size reduction and ongoing autophagy and apoptotic activity. Conversely, IgD and other receptors did not increase and gradually declined. Recovered sIgM was fully N-glycosylated, another feature of escape from antigen, and expression did not increase further during culture in vitro. The sIgM was fully capable of mediating phosphorylation of SYK, which lies upstream of BTK in the B-cell receptor pathway.

Conclusions:
This specific IgM increase in patients underpins the key role of tissue-based engagement with antigen in CLL, confirms the inhibitory action of ibrutinib, and reveals dynamic adaptability of CLL cells to precision monotherapy.
See related commentary by Burger, p. 2372
Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next-Generation Sequencing for Matching Patients to Targeted and Immune Therapies
Authors: Harding James J. , Nandakumar Subhiksha , Armenia Joshua , Khalil Danny N. , Albano Melanie , Ly Michele , Shia Jinru , Hechtman Jaclyn F. , Kundra Ritika , El Dika Imane , Do Richard K. , Sun Yichao , Kingham T. Peter , D'Angelica Michael I. , Berger Michael F. , Hyman David M. , Jarnagin William , Klimstra David S. , Janjigian Yelena Y. , Solit David B. , Schultz Nikolaus , Abou-Alfa Ghassan K. 
Published: October 2018

Abstract

Purpose:
Prior molecular profiling of hepatocellular carcinoma (HCC) has identified actionable findings that may have a role in guiding therapeutic decision-making and clinical trial enrollment. We implemented prospective next-generation sequencing (NGS) in the clinic to determine whether such analyses provide predictive and/or prognostic information for HCC patients treated with contemporary systemic therapies.

Experimental Design:
Matched tumor/normal DNA from patients with HCC (N = 127) were analyzed using a hybridization capture–based NGS assay designed to target 341 or more cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles.

Results:
WNT/β-catenin pathway (45%) and TP53 (33%) alterations were frequent and represented mutually exclusive molecular subsets. In sorafenib-treated patients (n = 81), oncogenic PI3K–mTOR pathway alterations were associated with lower disease control rates (DCR, 8.3% vs. 40.2%), shorter median progression-free survival (PFS; 1.9 vs. 5.3 months), and shorter median overall survival (OS; 10.4 vs. 17.9 months). For patients treated with immune checkpoint inhibitors (n = 31), activating alteration WNT/β-catenin signaling were associated with lower DCR (0% vs. 53%), shorter median PFS (2.0 vs. 7.4 months), and shorter median OS (9.1 vs. 15.2 months). Twenty-four percent of patients harbored potentially actionable alterations including TSC1/2 (8.5%) inactivating/truncating mutations, FGF19 (6.3%) and MET (1.5%) amplifications, and IDH1 missense mutations (&lt;1%). Six percent of patients treated with systemic therapy were matched to targeted therapeutics.

Conclusions:
Linking NGS to routine clinical care has the potential to identify those patients with HCC likely to benefit from standard systemic therapies and can be used in an investigational context to match patients to genome-directed targeted therapies.
See related commentary by Pinyol et al., p. 2021
TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis
Authors: da Silva Sabrina Daniela , Xu Bin , Maschietto Mariana , Marchi Fabio Albuquerque , Alkailani Maisa I. , Bijian Krikor , Xiao Dingzhang , Alaoui-Jamali Moulay A. 
Published: October 2018

Abstract
TRAF2, a RING finger adaptor protein, plays an important function in tumor necrosis factor (TNF)- and TNF-like weak inducer of apoptosis (TWEAK)-dependent signaling, in particular during inflammatory and immune responses. We identified a functional interaction of TRAF2 with focal adhesion (FA) signaling involving the focal adhesion kinase (FAK) in the regulation of cell susceptibility to anoikis. Comparison of TRAF2-proficient (TRAF2+/+) versus TRAF2-deficient (TRAF2−/−), and FAK-proficient (FAK+/+) versus FAK-deficient (FAK−/−) mouse embryonic fibroblasts and their matched reconstituted cells demonstrated that TRAF2 interacts physically with the N-terminal portion of FAK and colocalizes to cell membrane protrusions. This interaction was found to be critical for promoting resistance to cell anoikis. Similar results were confirmed in the human breast cancer cell line MDA-MB-231, where TRAF2 and FAK downregulation promoted cell susceptibility to anoikis. In human breast cancer tissues, genomic analysis of The Cancer Genome Atlas database revealed coamplification of TRAF2 and FAK in breast cancer tissues with a predictive value for shorter survival, further supporting a potential role of TRAF2–FAK cooperative signaling in cancer progression.
Description of Acrobeles aenigmaticus sp. n. (Rhabditida: Cephalobidae), an unusual species with a poorly developed vulva, from the Kalahari Desert (Ngamiland, Botswana)
Authors: Abolafia Joaquín , Shokoohi Ebrahim , Du Preez Gerhard , Fourie Hendrika 
Published: October 2018

Summary
Acrobeles aenigmaticus sp. n. is described from the North-West District (Ngamiland) of Botswana, which forms part of the Kalahari Desert. This new species is characterised by its body length, ‘double’ cuticle bearing numerous interannular punctations, lateral fields with two longitudinal incisures, lips triangular bearing triangular tines with variation in their morphology, labial probolae bifurcated with prongs bearing triangular tines, pharyngeal corpus 2.8-3.8 times the isthmus length, spermatheca 0.8-1.8 times the body diam., post-vulval sac 1.3-2.2 times the body diam., vagina bent to the left side, vulva located left subventral and very reduced, female tail conoid-elongate, male tail conoid, spicules 24-29 μm and gubernaculum 13-17 μm in length. Molecular characterisation of 18S and 28S rRNA shows the relationship of this species with other species of Acrobeles that also present a ‘double’ cuticle, as well as with other cephalobids (e.g., Cervidellus alutus) with the same characteristic in terms of its cuticle.
Armenians, Diplomats, and Commercial Agents of Shah ʿAbbās: The European Journey of Khvāja Safar (c. 1609–14)
Authors: Cutillas Ferrer José 
Published: October 2018

AbstractIn the first quarter of the seventeenth century, Safavid–Spanish relations took a substantial leap forward when Shah ʿAbbāsI, together with a plan of alliance against the Ottomans, proposed a trade agreement that would reroute the silk market from Ottoman territory. This scheme and other factors highlighted the need to send to Iran, for the first time, a Spanish ambassador who was not linked to a religious order. Recent studies of the circumstances of this embassy have appeared; however, there has been little discussion of the people involved in the events, save for the Spanish ambassador Don García de Silva y Figueroa. This paper reconstructs and analyzes the journey of the Armenian Khvāja Safar through Europe and the problems he faced in his mission as a commercial agent and emissary for Shah ʿAbbās. It tries to explain why there was such an unexpected change in Shah ʿAbbās’ attitude towards Spain.
100 Years of Progress in Atmospheric Observing Systems
Authors: Stith Jeffrey L. , Baumgardner Darrel , Haggerty Julie , Hardesty R. Michael , Lee Wen-Chau , Lenschow Donald , Pilewskie Peter , Smith Paul L. , Steiner Matthias , Vömel Holger 
Published: October 2018

AbstractAlthough atmospheric observing systems were already an important part of meteorology before the American Meteorological Society was established in 1919, the past 100 years have seen a steady increase in their numbers and types. Examples of how observing systems were developed and how they have enabled major scientific discoveries are presented. These examples include observing systems associated with the boundary layer, the upper air, clouds and precipitation, and solar and terrestrial radiation. Widely used specialized observing systems such as radar, lidar, and research aircraft are discussed, and examples of applications to weather forecasting and climate are given. Examples drawn from specific types of chemical measurements, such as ozone and carbon dioxide, are included. Sources of information on observing systems, including other chapters of this monograph, are also discussed. The past 100 years has been characterized by synergism between societal needs for weather observations and the needs of fundamental meteorological research into atmospheric processes. In the latter half of the period, observing system improvements have been driven by the increasing demands for higher-resolution data for numerical models, the need for long-term measurements, and for more global coverage. This has resulted in a growing demand for data access and for integrating data from an increasingly wide variety of observing system types and networks. These trends will likely continue.
Of Climate and Weather: Examining Canadian Farm and Livestock Organization Discourses from 2010 to 2015
Authors: Tourangeau Wesley , Sherren Kate , Kent Carlisle , MacDonald Bertrum H. 
Published: October 2018

Abstract
Producer organizations representing Canada’s farm and livestock sectors are powerful change agents and advocates for their industries, particularly during challenging times such as climate- or weather-related hardships. Such organizations have a complex role: engaging with policy-makers, as well as their memberships and the public, to pursue the interests of their specific communities. This paper includes an examination of how farm producer organizations communicate about climate and weather to these various audiences, and the specific needs and recommendations they advance. Of particular interest are commodities related to pasture-based grazing, which is underrepresented in the climate adaptation literature. A collection of 95 publicly available documents is analyzed, representing a snapshot of climate- and weather-related public and policy engagement of Canadian and Albertan farm and livestock producer organizations from 2010 to 2015. Qualitative coding by scale, commodity, and audience revealed three significant patterns within this exploratory study. First, while national “umbrella” organizations speak climate to government, Alberta-based livestock/forage organizations speak to their members with a focus on weather. Second, while the two national umbrella organizations examined are politically divergent, they appear to be united on the topic of climate change. Third, common ground was also found between climate and weather discourses around on-farm management, specifically rotational grazing. These three patterns reveal a disjointed dialogue within the Canadian farm and livestock sectors on topics of climate adaptation and mitigation, as well as opportunities for future cooperation, and the need for further research on farm organization beliefs and their capacity to create/manage climate knowledge.
Pediatric Sialorrhea: Submandibular Duct Rerouting and Intraparotid Botulinum Toxin A Injection With Literature Review
Authors: Calim Omer Faruk , Hassouna Hasan N. H. , Yildirim Yavuz Selim , Dogan Remzi , Ozturan Orhan 
Published: October 2018

Objectives: The aim of this study was to assess the effectiveness of bilateral submandibular duct relocation and bilateral sublingual gland excision in combination with botulinum toxin A injection into the parotid glands in children with sialorrhea. Previously in the literature, either surgery or botulinum toxin injection but not their combination has been reported. Methods: Preoperative and at least 6-month postoperative assessments using the Drooling Severity Scale and Drooling Frequency Scale (Thomas-Stonell and Greenberg classification) and the Teacher Drooling Scale and by interviewing parents and caregivers face to face or via telephone were performed. Also, decreases in the daily number of bib changes and hourly frequency of saliva wiping were recorded as success. Complications were recorded. Results: The Drooling Frequency and Severity Scale, the Teacher Drooling Scale, daily number of bib changes, and hourly frequency of saliva wiping decreased significantly in 21 patients (95.5%) and remained unchanged in 1 patient (4.5%). Postoperative bleeding was observed in 1 patient (4.5%). Conclusions: Drooling is a complex problem that benefits from a multidisciplinary approach. Many treatment methods exist, each with advantages and disadvantages. In this study botulinum toxin A injection was applied in conjunction with bilateral submandibular duct relocation and bilateral sublingual gland excision surgery, achieving a success rate of 95.5%. Moreover, minimal complications and no recurrence after at least 6-month follow-up were observed. The authors therefore recommend further use of this combination treatment. Larger and longer term studies may also help clarify its effectiveness.
Workplace-Related Factors Associated With Employees’ Standing Time at Work: A Research Brief
Authors: Wilkerson Amanda H. , Usdan Stuart L. , Knowlden Adam P. , Leeper James L. , Birch David A. , Hibberd Elizabeth E. 
Published: October 2018

Purpose: The purpose of this study was to identify the relationship between work-related, individual, and environmental factors and self-reported standing time during the workday. Design: Cross-sectional study design. Setting: Participants were recruited from a large, public university in the southeastern United States. Measures: Data were collected through an 87-item online survey using previously validated scales that assessed workplace standing time, demographic variables, work-related psychosocial factors, and workplace environment factors. Analysis: One-way analysis of variance, Pearson correlation coefficients, and nonparametric tests were used to determine univariate relationships between standing time and independent work-related variables and demographic factors. Results: Mean standing time among the sample (n = 502) was 72.49 minutes (standard deviation = 73.48) daily. There was a significant relationship between standing time and barrier self-efficacy for standing at work, self-regulation strategies, social norms, local connectivity in the workplace, overall connectivity in the workplace, and proximity of coworkers. Standing time was significantly higher for men, employees with an advanced degree, employees with a standing desk, and faculty. Conclusion: Health promotion researchers and practitioners should consider factors at multiple levels of influence when designing studies to explore workplace sedentary behavior. The findings regarding variations in workplace behavior by employee subgroups should be taken into consideration when designing future studies in the workplace.
Help at hand: Women’s experiences of using a mobile health application upon diagnosis of asymptomatic osteoporosis
Authors: Ravn Jakobsen Pernille , Hermann Anne Pernille , Søndergaard Jens , Wiil Uffe Kock , Clemensen Jane 
Published: October 2018

Objectives: This study aims to test a mobile health application (mHealth app) developed to meet the needs of women newly diagnosed with asymptomatic osteoporosis. We investigate how the women experience using an mHealth app upon diagnosis of osteoporosis and whether the app can help them to be prepared for treatment decision-making and support them in osteoporosis self-management. We also tested the usability of the app, to find out whether any adjustments were necessary prior to implementation. Methods: A test was conducted at a Danish university hospital with 18 women aged 50–65, newly diagnosed with asymptomatic osteoporosis. On presenting for a bone density scan at the hospital, they were provided with the app, which was named ‘My Osteoporosis Journey’. Data were collected through semi-structured interviews. Giorgi’s descriptive phenomenological method guided the data analysis in four steps. Findings: In total, 17 women succeeded in downloading the app, thereby accessing information on asymptomatic osteoporosis, their bone density scan results and treatment recommendations prior to visiting their general practitioner. Three overall themes were identified. Women experienced that the app (1) gave a feeling of confidence and reassurance, (2) prepared the women on treatment decision-making in the general practitioner visit and (3) provided help at hand in self-management of osteoporosis. Conclusion: Our findings show that the mHealth app helps women to feel confident and reassured upon diagnosis of asymptomatic osteoporosis. The women felt that the app promoted an equal dialogue in the osteoporosis consultation since they felt prepared for visiting their general practitioner and were able to articulate their individual needs regarding treatment. After diagnosis, the women felt that the app provided support in self-management, right at their fingertips.
What is the cost of endoscopic submucosal dissection (ESD)? A medico‐economic study
Authors: Dahan Martin , Pauliat Emmanuelle , Liva-Yonnet Sandra , Brischoux Sonia , Legros Romain , Tailleur Arnaud , Carrier Paul , Charissoux Aurélie , Valgueblasse Virginie , Loustaud-Ratti Véronique , Taibi Abdelkader , Durand-Fontanier Sylvaine , Valleix Denis , Sautereau Denis , Kerever Sébastien , Jacques Jérémie 
Published: October 2018

IntroductionEndoscopic submucosal dissection (ESD) is the gold‐standard treatment for superficial lesions of the digestive tract. No medico‐economic study has been conducted in Europe.Material and methodsA monocentric study was conducted including all patients undergoing ESD between January 2015 and December 2017. The global cost of hospital stays was measured by microcosting, and revenue was based on the diagnosis‐related group (DRG) system. The primary objective was to assess the cost/revenue balance. A medico‐economic comparison with surgery was performed as a secondary outcome.ResultsA total of 193 patients were prospectively included. The cost per procedure was €3463.79, subtracted from a €2726.84 revenue, with a deficit of −€736.96 per stay. Presence of comorbidities/complications increasing DRG value was the only predictive factor for a positive budgetary balance in a multivariate analysis (odds ratio 49.21, 95% confidence interval 11.3–214.25, p < 0.0001). In comparison with surgery, ESD was associated with shorter length of stay (11 vs 2 days; p < 0.0001) and lower morbidity (28% vs 14%; p = 0.061), lower cost (€8960 vs €1770; p < 0.0001).ConclusionThe ESD cost/revenue balance is negative in 80% of cases. Given the benefits of ESD in terms of patient morbidity and financial savings compared with surgery, the implementation of a specific ESD reimbursement is warranted.