bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real‐world impact of direct acting antiviral therapy on health‐related quality of life in HIV/Hepatitis C co‐infected individuals
Authors: Saeed Sahar , Moodie Erica E. M. , Strumpf Erin , Gill John , Wong Alexander , Cooper Curtis , Walmsley Sharon , Hull Mark , Martel‐Laferriere Valerie , Klein Marina B. ,   For the Canadian Co‐Infection Cohort Study Investigators
Published: August 2018

SummaryClinical trial results of direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) have shown improvements in health‐related quality of life (HR‐QoL). However, the extent to which these results are broadly generalizable to real‐world settings is unknown. We investigated the real‐world impact of oral DAA therapy on HR‐QoL among individuals coinfected with HIV/HCV. We used data from the Canadian HIV/HCV Co‐Infection Cohort Study that prospectively follows 1795 participants from 18 centres. Since 2007, clinical, lifestyle, and HR‐QoL data have been collected biannually through self‐administered questionnaires and chart review. HR‐QoL was measured using the EQ‐5D instrument. Participants initiating oral DAAs, having at least one visit before treatment initiation and at least one visit after DAA treatment response was ascertained, were included. Successful treatment response was defined as a sustained viral response (SVR). Segmented multivariate linear mixed models were used to evaluate the impact of SVR on HR‐QoL, controlling for pretreatment trends. 227 participants met our eligibility criteria, 93% of whom achieved SVR. Before treatment, the EQ‐5D utility index decreased 0.6 percentage‐point/y (95% CI, −0.9, −0.3) and health state was constant over time. The immediate effect of SVR resulted in an increase of 2.3‐units (−0.1, 4.7) in patients’ health state and 2.0 percentage‐point increase (−0.2, 4.0) in utility index. Health state continued to increase post‐SVR by 1.4 units/y (−0.9, 3.7), while utility trends post‐SVR plateaued over the observation period. Overall using real‐world data, we found modest improvements in HR‐QoL following SVR, compared to previously published clinical trials.
Medical costs associated with chronic kidney disease progression in an Asian population with type 2 diabetes mellitus
Authors: Low Serena , Lim Su C , Zhang Xiao , Wang Jiexun , Yeo Su J D , Yeoh Lee Y , Liu Yan L , Subramaniam Tavintharan , Sum Chee F 
Published: August 2018

ABSTRACTAimWe aim to examine difference in incremental direct medical costs between non‐progressive and progressive chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) in Singapore.MethodsThis was a prospective study on 676 patients with T2DM attending a diabetes centre in a regional hospital. Annual direct medical costs were extracted from the administrative database. Ordinary least squares regression was used to estimate contribution of CKD progression to annual costs, adjusting for demographics and baseline clinical covariates.ResultsOver mean follow‐up period of 2.8 ± 0.4 years, 266 (39.3%) had CKD progression. The excess total follow‐up medical costs from baseline was S$4243 higher in progressors compared to non‐progressors (P = 0.002). The mean cost differential between the two groups increased from S$2799 in Stages G1–G2 to S$11180 in Stage G4. Inpatient cost accounted for 63.4% of total cost of progression. When stratified by glomerular filtration rate stages, the respective total mean annual costs at stages glomerular filtration rate Stages G3a–G3b and G4 were S$3290 (132%; P = 0.001) and S$4416 (135%; P = 0.011) higher post‐progression.ConclusionChronic kidney disease progression in T2DM is associated with high medical costs. The cost of progression is higher with higher severity of CKD stage at baseline and could be largely driven by inpatient admission.
Rejecting Supererogationism
Authors: Tarsney Christian 
Published: August 2018

AbstractEven if I think it very likely that some morally good act is supererogatory rather than obligatory, I may nonetheless be rationally required to perform that act. This claim follows from an apparently straightforward dominance argument, which parallels Jacob Ross's argument for ‘rejecting’ moral nihilism. These arguments face analogous pairs of objections that illustrate general challenges for dominance reasoning under normative uncertainty, but (I argue) these objections can be largely overcome. This has practical consequences for the ethics of philanthropy – in particular, it means that donors are often rationally required to maximize the positive impact of their donations.
Identification and validation of number of pod ‐ and seed ‐ related traits QTLs in soybean
Authors: Li Candong , Zou Jianan , Jiang Hongwei , Yu Jingyao , Huang Shiyu , Wang Xinyu , Liu Chunyan , Guo Tai , Zhu Rongsheng , Wu Xiaoxia , Hu Zhenbang , Wang Zhixin , Zheng Wei , Zhang Zhenyu , Zhao Haihong , Wang Nannan , Cheng Chunguang , Xin Dawei , Chen Qingshan , Qi Zhaoming 
Published: August 2018

AbstractTraits related to the number of pods and seeds are important yield factors on soybean. The relationships between phenotype and quantitative trait loci (QTLs) of these traits may reveal the mechanisms underlying productivity. Our study objectives were to analyse phenotypic correlations, detect stable QTLs and identify candidate genes useful for marker‐assisted selection. Phenotypic analyses revealed that NThSP (number of three‐seeded pods) was positively correlated with NPPP (number of pods per plant) and SNPP (number of seeds per plant). Seventy‐five QTLs were identified based on the mean phenotypic data for at least 2 years. We detected two to 15 and one to three significant QTLs identified at the same location, respectively. Six consensus QTLs associated with at least two NPS‐related (number of pods and seeds related) traits were identified. Two of these were verified in another population. The QTLs for NPPP, SNPP and NThSP formed a consensus QTL cluster on GM02. Another 27 QTLs also formed clusters in five regions. Fifteen candidate genes were mined and discussed. The results will provide more information to soybean breeding.
An open label clinical trial to evaluate the utility of a hydrolysed fish and rice starch elimination diet for the diagnosis of adverse food reactions in dogs
Authors: Matricoti Irina , Noli Chiara 
Published: August 2018

BackgroundThe diagnosis of adverse food reaction (AFR) is based on an eight week elimination diet (ED) and is confirmed by relapse upon re‐challenge with the previously fed diet. Hydrolysed EDs are commonly used for this purpose.ObjectiveTo evaluate a commercially available hydrolysed fish protein and rice starch ED for the diagnosis of AFR.AnimalsFifty nonseasonally pruritic dogs.Methods and materialsPruritus was assessed with a Visual Analog Scale, lesions with the Canine Atopic Dermatitis Lesions Index and quality of life with a validated questionnaire on days 0 and 56. Antimicrobial treatments were permitted during the first four weeks, and corticosteroids and oclacitinib during the first six weeks. Dogs showing at least 50% pruritus improvement were separately challenged with their prior diet, fish and rice.ResultsThirty eight dogs completed the ED, four were dropped out due to worsening clinical signs, three to low palatability and five were lost to follow‐up. In 24 dogs, pruritus improved by >50% and 22 underwent dietary challenges. Of these, 15 reacted to their prior diets and were diagnosed with AFR, whereas seven did not relapse (and a diagnosis of AFR was considered to be doubtful). Five dogs reacted to fish and four to rice. Of the 14 dogs in which pruritus did not improve, some underwent a second ED and others were successfully treated for atopic dermatitis.Conclusion and clinical importanceThe hydrolysed fish and rice diet seemed to be a useful ED for the diagnosis of AFR, even in dogs allergic to fish or rice.
Effect of Using a Sit-Stand Desk on Ratings of Discomfort, Fatigue, and Sleepiness Across a Simulated Workday in Overweight and Obese Adults
Authors: Kowalsky Robert J. , Perdomo Sophy J. , Taormina John M. , Kline Christopher E. , Hergenroeder Andrea L. , Balzer Jeffrey R. , Jakicic John M. , Gibbs Bethany Barone 
Published: August 2018

Background: Limited research examines the influence of sit-stand desks on ratings of discomfort, sleepiness, and fatigue. This study evaluated the time course of these outcomes over 1 day. Methods: Adults (N = 25) completed a randomized cross-over study in a laboratory with two 8-hour workday conditions: (1) prolonged sitting (SIT) and (2) alternating sitting and standing every 30 minutes (SIT-STAND). Sleepiness was assessed hourly. Discomfort, physical fatigue, and mental fatigue were measured every other hour. Linear mixed models evaluated whether these measures differed across conditions and the workday. Effect sizes were calculated using Cohen’s d. Results: Participants were primarily white (84%) males (64%), with mean (SD) body mass index of 31.9 (5.0) kg/m2 and age 42 (12) years. SIT-STAND resulted in decreased odds of discomfort (OR = 0.37, P = .01) and lower overall discomfort (β = −0.19, P < .001, d = 0.42) versus SIT. Discomfort during SIT-STAND was lower in the lower and upper back, but higher in the legs (all Ps< .01, d = 0.26–0.42). Sleepiness (β = −0.09, P = .01, d = 0.15) and physical fatigue (β = −0.34, P = .002, d = 0.34) were significantly lower in SIT-STAND. Mental fatigue was similar across conditions. Conclusions: Sit-stand desks may reduce acute levels of sleepiness, physical fatigue, and both overall and back discomfort. However, levels of lower extremity discomfort may be increased with acute exposure.
Association betweenHelicobacter pyloriinfection and tumor markers: an observational retrospective study
Authors: Xu Mei-Yan , Cao Bing , Chen Yan , Musial Natalie , Wang Shuai , Yin Jian , Liu Lan , Lu Qing-Bin 
Published: August 2018

ObjectiveHelicobacter pyloriinfection is a major cause of several cancers such as gastric, pancreatic and lung. The relationship betweenH. pyloriand tumour markers continues to remain unclear. The primary goal of this study is to clarify the associations betweenH. pyloriinfection and six tumour markers (ie, carcinoembryonic antigen (CEA), cancer antigen (CA) 153, CA199, CA724, CA125 and alpha-fetoprotein (AFP)). The secondary goal is to provide understanding for further research aboutH. pyloriinfection and gastrointestinal cancer.DesignObservational retrospective study.SettingThe study was performed in Beijing, China, where enrolled subjects had all passed health examinations during the period of 2012–2016. Subjects were categorised intoH. pylori(+) andH. pylori(–) group according to their infection status and the measured six biomarkers. We used logistic regression models and generalised linear models to explore the associations betweenH. pyloriinfection and six tumour markers (ie, CEA, CA153, CA199, CA724, CA125 and AFP).ParticipantsA total of 14 689 subjects were included and 6493 (44.2%) subjects were infected byH. pylori. The subjects had a mean age (1SD) of 45 (18) years. There were 4530 (31.0%) female subjects.ResultsAfter adjusting for the confounding factors, infections withH. pyloriwere found to be significantly associated with abnormal ratios in CEA, AFP and CA724 ofH. pylori(+) toH. pylori(–) groups. Significant positive correlation was found betweenH. pyloriinfection and CEA values (adjusted β=0.056; 95% CI 0.005 to 0.107; p=0.033).ConclusionsIn this observational retrospective study, we observed theH. pyloriinfections in a Chinese population and found higher CEA level inH. pylori-infected subjects and abnormal ratios in CEA, AFP and CA724 in infected subjects to uninfected subjects. These findings may provide a basis for future exploration withH. pyloriand tumour markers.
Workflow model for the digitization of mudrocks
Authors: Buckman Jim , Mahoney Carol , Bankole Shereef , Couples Gary , Lewis Helen , Wagner Thomas , März Christian , Blanco Vladimir , Stow Dorrik 
Published: August 2018

Abstract
Mudrocks are highly heterogeneous in a range of physical and chemical properties, including: porosity and permeability, fissility, colour, particle composition, size, orientation, carbon loading, degree of compaction, and diagenetic overprint. It is therefore important that the maximum information be extracted as efficiently and completely as possible. This can be accomplished through high-resolution analysis of polished thin sections by scanning electron microscopy (SEM), with the collection of large-area images and X-ray elemental map montages, and the application of targeted particle analysis. A workflow model, based on these techniques, for the digitization of mudrocks is presented herein. A range of the data that can be collected and the variety of analyses that can be achieved are also illustrated. Data collection is discussed in terms of inherent problems with acquisition, storage, transfer and manipulation, which can be time-consuming and non-trivial. Similar information and resolutions can be achieved through other techniques, such as QEMSCAN and infra-red (IR)/Raman spectroscopic mapping. These can be seen as complementary to the workflow described herein.
Phantom Ray-Hair Intersector
Authors: Reshetov Alexander , Luebke David 
Published: August 2018

We present a new approach to ray tracing swept volumes along trajectories defined by cubic Bézier curves. It performs at two-thirds of the speed of ray-triangle intersection, allowing essentially even treatment of such primitives in ray tracing applications that require hair, fur, or yarn rendering.
At each iteration, we approximate a radially symmetric swept volume with a tangential cone. A distance from the ray-cone intersection to the cone's base is then used to compute the next curve parameter t. When this distance is zero, the ray intersects the swept volume and the cone at the same point and we stop the iterations. To enforce continuity of the iterative root finding, we introduce "phantom" intersection, padding the cone until it touches the ray if the ray-cone intersection does not exist.
Increased thin filament activation enhances alternans in human chronic atrial fibrillation
Authors: Zile Melanie A. , Trayanova Natalia A. 
Published: August 2018

Action potential duration (APD) alternans (APD-ALT), defined as beat-to-beat oscillations in APD, has been proposed as an important clinical marker for chronic atrial fibrillation (cAF) risk when it occurs at pacing rates of 120–200 beats/min. Although the ionic mechanisms for occurrence of APD-ALT in human cAF at these clinically relevant rates have been investigated, little is known about the effects of myofilament protein kinetics on APD-ALT. Therefore, we used computer simulations of single cell function to explore whether remodeling in myofilament protein kinetics in human cAF alters the occurrence of APD-ALT and to uncover how these mechanisms are affected by sarcomere length and the degree of cAF-induced myofilament remodeling. Mechanistically based, bidirectionally coupled electromechanical models of human right and left atrial myocytes were constructed, incorporating both ionic and myofilament remodeling associated with cAF. By comparing results from our electromechanical model with those from the uncoupled ionic model, we found that intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD-ALT (APD-ANM) at slower rates (150 beats/min) due to the cooperativity between strongly bound cross-bridges and Ca2+-troponin C binding affinity. We also discovered that cAF-induced enhanced thin filament activation enhanced APD-ANM at these clinically relevant heart rates (150 beats/min). In addition, longer sarcomere lengths increased APD-ANM, suggesting that atrial stretch is an important modulator of APD-ALT. Together, these findings demonstrate that myofilament kinetics mechanisms play an important role in altering APD-ALT in human cAF. NEW & NOTEWORTHY Using a single cell simulation approach, we explored how myofilament protein kinetics alter the formation of alternans in action potential duration (APD) in human myocytes with chronic atrial fibrillation remodeling. We discovered that enhanced thin filament activation and longer sarcomere lengths increased the magnitude of APD alternans at clinically important pacing rates of 120–200 beats/min. Furthermore, we found that altered intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD alternans.
Cripto-1 Plasmid DNA Vaccination Targets Metastasis and Cancer Stem Cells in Murine Mammary Carcinoma
Authors: Witt Kristina , Ligtenberg Maarten A. , Conti Laura , Lanzardo Stefania , Ruiu Roberto , Wallmann Tatjana , Tufvesson-Stiller Helena , Chambers Benedict J. , Rolny Charlotte , Lladser Alvaro , Lundqvist Andreas , Cavallo Federica , Kiessling Rolf 
Published: August 2018

Abstract
Metastatic breast cancer is a fatal disease that responds poorly to treatment. Cancer vaccines targeting antigens expressed by metastatic breast cancer cells and cancer stem cells could function as anticancer therapies. Cripto-1 is an oncofetal protein overexpressed in invasive breast cancer and cancer-initiating cells. In this study, we explored the potential of a Cripto-1–encoding DNA vaccine to target breast cancer in preclinical mouse models. BALB/c mice and BALB-neuT mice were treated with a DNA vaccine encoding mouse Cripto-1 (mCr-1). BALB/c mice were challenged with murine breast cancer 4T1 cells or TUBO spheres; BALB-neuT mice spontaneously developed breast cancer. Tumor growth was followed in all mouse models and lung metastases were evaluated. In vitro assays were performed to identify the immune response elicited by vaccination. Vaccination against mCr-1 reduced primary tumor growth in the 4T1 metastatic breast cancer model and reduced lung metastatic burden. In BALB-neuT mice, because the primary tumors are Cripto-1 negative, vaccination against mCr-1 did not affect primary tumors but did reduce lung metastatic burden. Spheroid-cultured TUBO cells, derived from a BALB/neuT primary tumor, develop a cancer stem cell–like phenotype and express mCr-1. We observed reduced tumor growth in vaccinated mice after challenge with TUBO spheres. Our data indicate that vaccination against Cripto-1 results in a protective immune response against mCr-1 expressing and metastasizing cells. Targeting Cripto-1 by vaccination holds promise as an immunotherapy for treatment of metastatic breast cancer. Cancer Immunol Res; 6(11); 1417–25. ©2018 AACR.
PPAR-Induced Fatty Acid Oxidation in T Cells Increases the Number of Tumor-Reactive CD8+ T Cells and Facilitates Anti–PD-1 Therapy
Authors: Chowdhury Partha S. , Chamoto Kenji , Kumar Alok , Honjo Tasuku 
Published: August 2018

Abstract
Although PD-1 blockade cancer immunotherapy has shown potential for a wide range of patients with cancer, its efficacy is limited, in part, due to the loss of effector cytotoxic T lymphocytes (CTLs) via terminal differentiation–induced apoptosis. We previously demonstrated that mitochondrial activation, by the agonists of peroxisome proliferator–activated receptor γ (PPARγ) coactivator 1-α (PGC-1α)/transcription factor complexes, had synergistic effects with a PD-1–blocking monoclonal antibody in a mouse tumor model. In the current study, we examined the molecular mechanism of the synergistic effects of bezafibrate, an agonist of PGC-1α/ PPAR complexes, which enhanced the tumoricidal effects of PD-1 blockade. Bezafibrate activated CTL mitochondria and upregulated oxidative phosphorylation as well as glycolysis, resulting in more proliferation of naïve T cells and improved effector function in CTLs. Bezafibrate also increased fatty acid oxidation (FAO) and mitochondrial respiratory capacity, which supports the extra energy demands of cells in emergencies, allowing cell survival. Carnitine palmitoyl transferase 1 (Cpt1), which is needed for FAO, and Bcl2 were both upregulated. Cpt1 and Bcl2 can form a complex to prevent apoptosis of CTLs. Together, these results indicate that bezafibrate increases or maintains the number of functional CTLs by activating mitochondrial and cellular metabolism, leading in turn to enhanced antitumor immunity during PD-1 blockade. Cancer Immunol Res; 6(11); 1375–87. ©2018 AACR.
A Randomized Controlled Trial on Efficacy and Safety of Trocar-Site Infiltration with Lidocaine for Postoperative Pain Relief after Diagnostic Laparoscopy
Authors: Joe-Ikechebelu Ngozi N. , Eleje George Uchenna , Ugwu Emmanuel Onyebuchi , Okafor Chidimma Donatus , Nwachukwu Cyril Emeka , Okam Princeston C. , Ogboji Obinna E. , Ikechebelu Joseph Ifeanyichukwu 
Published: August 2018

<b><i>Background/Aims:</i></b> To compare the efficacy and safety of trocar-site infiltration with lidocaine and no intervention for postoperative pain relief after diagnostic laparoscopy. <b><i>Methods:</i></b> A randomized clinical trial of women with infertility scheduled for diagnostic laparoscopy without additional procedures in Life Institute for Endoscopy at Life Specialist Hospital, Nnewi, Nigeria. One hundred and ninety nine women were assigned at random to either trocar-site infiltration with lidocaine (<i>n</i> = 100) or no intervention (<i>n</i> = 99). Pain was assessed using visual analogue scale (VAS) scores at 2 and 4 h post surgery. The primary endpoints were postoperative pain control and time to first request of analgesia, while the secondary endpoints were total analgesic consumption, shoulder pain, and side effects. Evaluations between the groups were done according to the principle of intention-to-treat. <b><i>Results:</i></b> Baseline characteristics were similar. A nonsignificant reduction was observed in the VAS in the intervention group at base line, 2 and 4 hours into the postoperative period in comparison with no intervention (<i>p</i> &#x3e; 0.05), and the time to first analgesic requirement was not significantly prolonged (<i>p</i> &#x3e; 0.05). The mean total consumption of rescue analgesia was not significantly reduced (<i>p</i> &#x3e; 0.05). <b><i>Conclusions:</i></b> Postoperative injection of lidocaine in laparoscopy port sites did not significantly improve pain scores after diagnostic laparoscopy. Clinical trial registration: PACTR201611001263105
The Effects of Native Language and Gender on Procedure Performance
Authors: Peres S. Camille , Johnson William D. , Thomas Sarah E. , Ritchey Paul 
Published: August 2018

Objective: Evaluation of effects of native language—native (L1) versus nonnative (L2)—on procedure performance. Background: Written procedures are used by global industries to facilitate accurate and safe performance of hazardous tasks. Often companies require that all employees be sufficiently literate in English and to use only English versions. Method: Industrial tasks were tested using a virtual reality industrial environment (Second Life®) to explore effects on procedural performance and safety statement adherence. Fifty-four engineering students (27 L2) participated in the study to explore the native language variable. The participants completed the procedures under time pressure and were scored according to procedure performance and hazard comprehension. Results: Analysis of eight procedures showed significant differences between L1 and L2 for procedure performance (specifically for L2 females). There were no language fluency or hazard comprehension differences found between the two groups. Conclusion: The results suggest that (a) the lower procedure performance of L2 readers was not due to English proficiency but more likely to time pressure; (b) implications regarding single language procedures are not fully understood, particularly with regard to gender differences. Application: This research is applicable to high-risk industries providing single language, time critical procedures to multilingual workforces.