bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Different Demineralization‐Inhibiting Methods on the Shear Bond Strength of Glass‐Ceramics
Authors: Dilber Erhan , Akın Mehmet , Yavuz Tevfik , Erdem Ali 
Published: October 2014

AbstractPurposeThis in vitro study was undertaken to evaluate the effects of different demineralization‐inhibiting methods on the shear bond strength (SBS) of glass‐ceramics.Materials and MethodsNinety extracted intact human mandibular lateral insicors were randomly divided into six equal groups. Group C was left untreated, while enamel subsurface demineralization was induced in the other groups. In group D, porcelain discs (3 mm in diameter) were cemented to demineralized enamel by using total‐etch photopolymerizing luting composite resin without pretreatment. Demineralized specimens in groups F, CA, M, and I were pretreated with fluoride gel, CPP‐ACP paste, microabrasion, and resin infiltration, respectively, and then porcelain discs were cemented. SBS (MPa) was calculated from the failure load (N) per bonded area (mm2). Fracture types were examined by optical microscopy (40× magnification). Data were analyzed with ANOVA, Tukey's test, and G‐test.ResultsANOVA revealed significant intergroup differences (p < 0.01). No significant differences in SBS (MPa) were found between groups C (19.48 ± 2.0) and I (20.02 ± 1.6). Lower SBS values were recorded in groups D (7.93 ± 0.8), F (12.51 ± 1.5), CA (17.08 ± 1.3), and M (14.84 ± 1.4). Mixed and cohesive failures were the most prevalent in groups M and I, respectively.ConclusionResin infiltration enhanced the SBS of porcelain discs bonded to demineralized enamel when compared with the other demineralization‐inhibiting methods. Clinical Relevance: Resin infiltration could be useful to enhance adhesion of glass‐ceramics to teeth with white spot lesions.
Treatment options beyond IFNα and NUCs for chronic HBV infection: expectations for tomorrow
Authors: Baltayiannis G. , Karayiannis P. 
Published: October 2014

SummaryChronic hepatitis B virus (HBV) infection may progress to cirrhosis, hepatocellular carcinoma (HCC) and end‐stage liver failure with time. Interruption of this process can only be achieved through effective antiviral treatment. This approach has so far involved the use of immunomodulators such as pegylated interferon alpha (Peg‐IFNα) for a finite period of up to a year and nucleos‐(t)ide analogues (NUCs) for treatment over much longer periods of time. The latter act by suppressing HBV replication at the level of DNA synthesis by inhibiting the viral reverse transcriptase/DNA polymerase and causing premature termination of DNA synthesis. The ideal treatment end point is loss of HBsAg in both HBeAg+ve and HBeAg−ve patients following monotherapy. This, however, is only achievable in a minority of patients. Secondary outcomes are durable HBeAg loss and seroconversion to anti‐HBe, which occur in about 18–30% of HBeAg+ve patients depending on the antiviral used, and sustained suppression of HBV‐DNA accompanied by biochemical normalization and histological improvement in non‐HBeAg+ve seroconverting and HBeAg−ve patients. There is therefore a need for additional direct‐acting antivirals (DAAs) targeting different stages of the life cycle of the virus, as well as immunotherapeutic approaches. Such developments may pave the way for their use either alone or more likely in combination in the fight against chronic HBV infection. Such drugs or approaches, which are currently undergoing preclinical or clinical testing, are the subject of this review.
Kinematics of terrestrial locomotion in harbor seals and gray seals: Importance of spinal flexion by amphibious phocids
Authors: Garrett Jennifer N. , Fish Frank E. 
Published: October 2014

AbstractPinnipeds are amphibious mammals with flippers, which function for both aquatic and terrestrial locomotion. Evolution of the flippers has placed constraints on the terrestrial locomotion of phocid seals. The detailed kinematics of terrestrial locomotion of gray (Halichoerus grypus) and harbor (Phoca vitulina) seals was studied in captivity and in the wild using video analysis. The seals exhibited dorsoventral undulations with the chest and pelvis serving as the main contact points. An anteriorly directed wave produced by spinal flexion aided in lifting the chest off the ground as the fore flippers were retracted to pull the body forward. The highest length‐specific speeds recorded were 1.02 BL/s for a gray seal in captivity and 1.38 BL/s for a harbor seal in the wild. The frequency and amplitude of spinal movement increased directly with speed, but the duty factor remained constant. Substrate did not influence the kinematics except for differences due to moving up or down slopes. The highly aquatic nature of phocids seals has restricted them to locomote on land primarily using spinal flexion, which can limit performance in speed and duration.
Sleep in the intensive care unit – nurses' documentation and patients' perspectives
Authors: Ritmala‐Castren Marita , Axelin Anna , Kiljunen Kaija , Sainio Carita , Leino‐Kilpi Helena 
Published: October 2014

ABSTRACTBackgroundInability to sleep is one of the most distressing factors for patients in the intensive care unit (ICU). Sleep is perceived as light and awakenings are numerous. Nurses' documentations of sleep are narrow, mainly concentrating on the quantity and general quality. Nurses should diversely evaluate, document and promote sleep to provide patient centered care.AimTo investigate the content of nurses' documentation about the sleep of ICU patients, patients' own perceptions of sleep, and the correspondence of the two.Design and methodsNurses' documentations (n = 90) were analysed retrospectively with quantitative content analysis. A cross‐sectional survey of patients' (n = 114) perspectives was collected with the five‐item Richards‐Campbell Sleep Questionnaire (RCSQ), on a visual analogue scale from 0 (the poorest quality sleep) to 100 (optimum sleep). The data was analysed statistically. Correspondence was tested with cross‐tabulation.ResultsNurses documented sleep quantity for 71% and quality for 27% of patients, along with the needs assessment, used interventions and their effect on sleep. Patients' perspectives varied widely. Sleep depth was rated the lowest and falling asleep highest of the RCSQ sleep domains. Age of the patients correlated positively with general quality of sleep, sleep depth and falling asleep. Nurses' documentations and patients' perceptions correlated in over half of the cases.ConclusionsNurses' documentation of ICU patients' sleep is not systematic or comprehensive and corresponds only partially with patients' own perception. The sleep of non‐intubated patients is light and awakenings are frequent. Documentation of ICU patients' sleep should include the whole nursing process, i.e. needs assessment, interventions used, and evaluation of sleep and the effects of the interventions, along with patients' own perspective to promote patient‐centered care.Relevance to clinical practiceEvaluation and documentation of patients' sleep must include patients' own perception to be comprehensive. Nurses' documentation should include all elements of nursing process.
Nontuberculous mycobacteria in diffuse panbronchiolitis
Authors: Tsuji Takahiro , Tanaka Eisaku , Yasuda Ikkoh , Nakatsuka Yoshinari , Kaji Yusuke , Yasuda Takehiro , Hashimoto Seishu , Hwang Moon Hee , Hajiro Takashi , Taguchi Yoshio 
Published: October 2014

AbstractBackground and objectiveNontuberculous mycobacterial (NTM) lung disease secondary to cystic fibrosis (CF) has been reported, but there is limited data about NTM prevalence in non‐CF bronchiectasis. We retrospectively investigated the prevalence of NTM associated with diffuse panbronchiolitis (DPB), a disorder also characterized by reduced mucociliary clearance with bronchiectasis.MethodsWe reviewed mycobacterial cultures, patient characteristics and computed tomography findings of 33 patients with DPB between January 2000 and December 2012. Prevalence was based on at least one positive NTM culture.ResultsMean patient age was 51.5 years. During a mean 162.8‐month follow‐up, the prevalence of NTM in sputum was 21.2% (seven patients). Of the seven positive patients, six had Mycobacterium avium complex, one had M. kansasii and M. chelonae co‐cultured with M. avium complex. Three patients were positive twice, and two had positive smears. The mean time from DPB diagnosis to the first positive result was 194.6 months. NTM‐positive patients tended to have lower forced expiratory volume in 1 s (% predicted) than NTM‐negative patients (50.0% vs 77.3%, P = 0.03), but there were no radiological or clinical differences between the two groups.ConclusionsOur observations suggest that NTM is found more often in DPB. Defects of mucociliary clearance may predispose individuals to NTM infection.
Wasting Our Time? Allocated Versus Accumulated Physical Activity in Afterschool Programs
Authors: Brazendale Keith , Beets Michael William , Weaver Robert Glenn , Huberty Jennifer , Beighle Aaron E. , Pate Russell R. 
Published: October 2014

Background:Afterschool programs (ASPs) can provide opportunities for children to accumulate moderate-to-vigorous physical activity (MVPA). The optimal amount of time ASPs should allocate for physical activity (PA) on a daily basis to ensure children achieve policystated PA recommendations remains unknown.Methods:Children (n = 1248, 5 to 12 years) attending 20 ASPs wore accelerometers up to 4 nonconsecutive week days for the duration of the ASPs during spring 2013 (February–April). Daily schedules were obtained from each ASP.Results:Across 20 ASPs, 3 programs allocated ≤ 30min, 5 approximately 45 min, 4 60 min, 4 75 min, and 4 ≥ 105 min for PA opportunities daily (min·d-1). Children accumulated the highest levels of MVPA in ASPs that allocated ≥ 60 min·d-1 for PA opportunities (24.8–25.1 min·d-1 for boys and 17.1–19.4 min·d-1 for girls) versus ASPs allocating ≤ 45 min·d-1 for PA opportunities (19.7 min·d-1 and 15.6 min·d-1 for boys and girls, respectively). There were no differences in the amount of MVPA accumulated by children among ASPs that allocated 60 min·d-1 (24.8 min·d-1 for boys and 17.1 min·d-1 for girls), 75 min·d-1 (25.1 min·d-1 for boys and 19.4 min·d-1 for girls) or ≥ 105 min·d-1 (23.8 min·d-1 for boys and 17.8 min·d-1 for girls). Across ASPs, 26% of children (31% for boys and 14% for girls) met the recommended 30 minutes of MVPA.Conclusions:Allocating more than 1 hour of PA opportunities is not associated with an increase in MVPA during ASPs. Allocating 60 min·d-1, in conjunction with enhancing PA opportunities, can potentially serve to maximize children’s accumulation of MVPA during ASPs.
Metagenome-Wide Association of Microbial Determinants of Host Phenotype in Drosophila melanogaster
Authors: Chaston John M. , Newell Peter D. , Douglas Angela E. 
Published: October 2014

ABSTRACT

Animal-associated bacteria (microbiota) affect host behaviors and physiological traits. To identify bacterial genetic determinants of microbiota-responsive host traits, we employed a metagenome-wide association (MGWA) approach in two steps. First, we measured two microbiota-responsive host traits, development time and triglyceride (TAG) content, in
Drosophila melanogaster
flies monoassociated with each of 41 bacterial strains. The effects of monoassociation on host traits were not confined to particular taxonomic groups. Second, we clustered protein-coding sequences of the bacteria by sequence similarity
de novo
and statistically associated the magnitude of the host trait with the bacterial gene contents. The animals had been monoassociated with genome-sequenced bacteria, so the metagenome content was unambiguous. This analysis showed significant effects of pyrroloquinoline quinone biosynthesis genes on development time, confirming the results of a published transposon mutagenesis screen, thereby validating the MGWA; it also identified multiple genes predicted to affect host TAG content, including extracellular glucose oxidation pathway components. To test the validity of the statistical associations, we expressed candidate genes in a strain that lacks them. Monoassociation with bacteria that ectopically expressed a predicted oxidoreductase or gluconate dehydrogenase conferred reduced
Drosophila
TAG contents relative to the TAG contents in empty vector controls. Consistent with the prediction that glucose oxidation pathway gene expression increased bacterial glucose utilization, the glucose content of the host diet was reduced when flies were exposed to these strains. Our findings indicate that microbiota affect host nutritional status through modulation of nutrient acquisition. Together, these findings demonstrate the utility of MGWA for identifying bacterial determinants of host traits and provide mechanistic insight into how gut microbiota modulate the nutritional status of a model host.

IMPORTANCE
To understand how certain gut bacteria promote the health of their animal hosts, we need to identify the bacterial genes that drive these beneficial relationships. This task is challenging because the bacterial communities can vary widely among different host individuals. To overcome this difficulty, we quantified how well each of 41 bacterial species protected
Drosophila
fruit flies from high fat content. The genomes of the chosen bacterial strains were previously sequenced, so we could statistically associate specific bacterial genes with bacterially mediated reduction in host fat content. Bacterial genes that promote glucose utilization were strongly represented in the association, and introducing these genes into the gut bacteria was sufficient to lower the animal’s fat content. Our method is applicable to the study of many other host-microbe interactions as a way to uncover microbial genes important for host health.
Adult asthma increases dementia risk: a nationwide cohort study
Authors: Peng Yi-Hao , Wu Biing-Ru , Su Ching-Hua , Liao Wei-Chih , Muo Chih-Hsin , Hsia Te-Chun , Kao Chia-Hung 
Published: October 2014

BackgroundStudies on the association between adult asthma and dementia are few. We investigated the risk of dementia in patients diagnosed with adult asthma compared with that of people without asthma who were age and sex matched to the study patients.MethodsWe used data from the National Health Insurance Research Database. A total of 12 771 patients with newly diagnosed asthma between 2001 and 2003 were evaluated and 51 084 people without asthma were used as the comparison cohort. Cox proportional hazard regression analysis was used to measure the HR of dementia for the asthmatic cohort, compared with that of the non-asthmatic cohort.ResultsThe HR of dementia was 1.27 (95% confidence interval (CI) 1.15 to 1.41) for the asthmatic cohort, compared with the non-asthmatic cohort after adjusting for age, sex, comorbidities, annual outpatient department visits and medicine used. The HR of dementia development increased substantially as frequency of asthma exacerbation and hospitalisation increased.ConclusionsThis nationwide cohort study suggests that the risk of dementia development is significantly increased in patients with asthma compared with that of the general population. In addition, dementia risk increases substantially with asthma exacerbation and hospitalisation frequency increases.
ATR Inhibitors VE-821 and VX-970 Sensitize Cancer Cells to Topoisomerase I Inhibitors by Disabling DNA Replication Initiation and Fork Elongation Responses
Authors: Jossé Rozenn , Martin Scott E. , Guha Rajarshi , Ormanoglu Pinar , Pfister Thomas D. , Reaper Philip M. , Barnes Christopher S. , Jones Julie , Charlton Peter , Pollard John R. , Morris Joel , Doroshow James H. , Pommier Yves 
Published: October 2014

AbstractCamptothecin and its derivatives, topotecan and irinotecan, are specific topoisomerase I (Top1) inhibitors and potent anticancer drugs killing cancer cells by producing replication-associated DNA double-strand breaks, and the indenoisoquinoline LMP-400 (indotecan) is a novel Top1 inhibitor in clinical trial. To develop novel drug combinations, we conducted a synthetic lethal siRNA screen using a library that targets nearly 7,000 human genes. Depletion of ATR, the main transducer of replication stress, came as a top candidate gene for camptothecin synthetic lethality. Validation studies using ATR siRNA and the ATR inhibitor VE-821 confirmed marked antiproliferative synergy with camptothecin and even greater synergy with LMP-400. Single-cell analyses and DNA fiber combing assays showed that VE-821 abrogates the S-phase replication elongation checkpoint and the replication origin–firing checkpoint induced by camptothecin and LMP-400. As expected, the combination of Top1 inhibitors with VE-821 inhibited the phosphorylation of ATR and Chk1; however, it strongly induced γH2AX. In cells treated with the combination, the γH2AX pattern changed over time from the well-defined Top1-induced damage foci to an intense peripheral and diffuse nuclear staining, which could be used as response biomarker. Finally, the clinical derivative of VE-821, VX-970, enhanced the in vivo tumor response to irinotecan without additional toxicity. A key implication of our work is the mechanistic rationale and proof of principle it provides to evaluate the combination of Top1 inhibitors with ATR inhibitors in clinical trials. Cancer Res; 74(23); 6968–79. ©2014 AACR.
Paclitaxel Therapy Promotes Breast Cancer Metastasis in a TLR4-Dependent Manner
Authors: Volk-Draper Lisa , Hall Kelly , Griggs Caitlin , Rajput Sandeep , Kohio Pascaline , DeNardo David , Ran Sophia 
Published: October 2014

Abstract
Emerging evidence suggests that cytotoxic therapy may actually promote drug resistance and metastasis while inhibiting the growth of primary tumors. Work in preclinical models of breast cancer has shown that acquired chemoresistance to the widely used drug paclitaxel can be mediated by activation of the Toll-like receptor TLR4 in cancer cells. In this study, we determined the prometastatic effects of tumor-expressed TLR4 and paclitaxel therapy and investigated the mechanisms mediating these effects. While paclitaxel treatment was largely efficacious in inhibiting TLR4-negative tumors, it significantly increased the incidence and burden of pulmonary and lymphatic metastasis by TLR4-positive tumors. TLR4 activation by paclitaxel strongly increased the expression of inflammatory mediators, not only locally in the primary tumor microenvironment but also systemically in the blood, lymph nodes, spleen, bone marrow, and lungs. These proinflammatory changes promoted the outgrowth of Ly6C+ and Ly6G+ myeloid progenitor cells and their mobilization to tumors, where they increased blood vessel formation but not invasion of these vessels. In contrast, paclitaxel-mediated activation of TLR4-positive tumors induced de novo generation of deep intratumoral lymphatic vessels that were highly permissive to invasion by malignant cells. These results suggest that paclitaxel therapy of patients with TLR4-expressing tumors may activate systemic inflammatory circuits that promote angiogenesis, lymphangiogenesis, and metastasis, both at local sites and premetastatic niches where invasion occurs in distal organs. Taken together, our findings suggest that efforts to target TLR4 on tumor cells may simultaneously quell local and systemic inflammatory pathways that promote malignant progression, with implications for how to prevent tumor recurrence and the establishment of metastatic lesions, either during chemotherapy or after it is completed. Cancer Res; 74(19); 5421–34. ©2014 AACR.
New Strategies in Acute Promyelocytic Leukemia: Moving to an Entirely Oral, Chemotherapy-Free Upfront Management Approach
Authors: Zeidan Amer M. , Gore Steven D. 
Published: October 2014

Abstract
Incorporation of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) into the management paradigms of acute promyelocytic leukemia (APL) has markedly improved outcomes. Significant progress occurred in understanding the molecular pathogenesis of APL. ATO, in contrast with ATRA, is capable of eradicating the APL-initiating cells and can result in cure. Preclinical and clinical data confirmed the synergy of ATO and ATRA, and the ATRA–ATO combination was proved noninferior to a standard ATRA–chemotherapy regimen in patients with non–high-risk APL. Oral formulations of arsenic exhibited excellent activity in advanced clinical testing and their combinations with ATRA offer an opportunity for a completely oral, chemotherapy-free regimen for curing APL. Nonetheless, significant challenges remain. Reducing early death due to bleeding complications is an important area of unmet need. Data suggest that delays in initiation of ATRA upon suspecting APL continue to occur in the community and contribute to early mortality. Questions remain about the optimal place and schedule of arsenic in the therapeutic sequence and the role of the oral formulations. Refining the role of minimal residual disease in directing treatment decisions is important. Development of novel targeted agents to treat relapsed disease requires deeper understanding of the secondary resistance mechanisms to ATRA and ATO. Clin Cancer Res; 20(19); 4985–93. ©2014 AACR.
Testing the Metal of ERCC2 in Predicting the Response to Platinum-Based Therapy
Authors: Turchi John J. , Woods Derek S. , Carozza Pamela VanderVere 
Published: October 2014

Abstract
Summary: DNA repair has been shown to affect the cellular response to platinum-based therapy in a variety of cancers; however, translating this knowledge to the clinic has proven difficult and yielded mixed results. In this issue of Cancer Discovery, Van Allen and colleagues have analyzed responders and nonresponders to neoadjuvant platinum-based therapy with locally advanced urothelial cancer and identified a series of mutations in the nucleotide excision repair (NER) gene ERCC2 that correlate with the response to platinum-based therapy. This work provides evidence that defects in NER can be exploited to maximize the efficacy of conventional platinum-based chemotherapy. Cancer Discov; 4(10); 1118–9. ©2014 AACR.
See related article by Van Allen and colleagues, p. 1140
Radiographic Predictors of Lead Conductor Fracture
Authors: Krahn Andrew D. , Morissette Josée , Lahm Ryan , Haddad Tarek , Baxter Walt W. , McVenes Rick , Crystal Eugene , Ayala-Paredes Félix , Cameron Doug , Verma Atul , Simpson Christopher S. , Exner Derek V. , Birnie David H. 
Published: September 2014

Background—
Lead fracture is a limiting factor in high voltage lead durability. Fractures noted with the Medtronic Fidelis leads provide an opportunity to examine factors captured on implant chest x-ray that correlate with risk for lead conductor fracture. We evaluated contributory factors in a large population of fractures.

Methods and Results—
We conducted a retrospective case–control study at 8 Canadian centers that routinely capture anterior posterior and lateral chest x-rays within 2 weeks of implant. Cases were patients that experienced confirmed Medtronic Fidelis 6949 lead fracture based on standard definitions, matched one-to-one to controls for date of implant, sex, and age with normally functioning Fidelis leads from the same center. Select chart data and x-rays were collected for all patients. Radiographic measurements by ≥2 individuals per case/control were blinded to patient status. The data were analyzed using a time to failure multivariable Cox proportional hazards model with stratification for each matched pair. X-ray pairs from 111 fracture patients were compared with 111 controls (age 61.5±12.8 years, 75% male, 221 model 6949 leads). Six parameters included in the statistical analysis were significantly associated with risk of fracture, including slack/tortuosity measures, pulse generator and superior vena cava coil location, and angle of lead exit from the pocket.

Conclusions—
Pocket, intravascular and intracardiac lead characteristics on x-ray correlate with risk of lead conductor fracture. These observations may be useful to direct implant technique to optimize lead durability. Validation in larger populations and other lead models may inform the application of these results.