bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of the association between dietary acid load, alkaline water and cancer
Authors: Fenton Tanis R , Huang Tian 
Published: June 2016

ObjectivesTo evaluate the evidence for a causal relationship between dietary acid/alkaline and alkaline water for the aetiology and treatment of cancer.DesignA systematic review was conducted on published and grey literature separately for randomised intervention and observational studies with either varying acid–base dietary intakes and/or alkaline water with any cancer outcome or for cancer treatment.Outcome measuresIncidence of cancer and outcomes of cancer treatment.Results8278 citations were identified, and 252 abstracts were reviewed; 1 study met the inclusion criteria and was included in this systematic review. No randomised trials were located. No studies were located that examined dietary acid or alkaline or alkaline water for cancer treatment. The included study was a cohort study with a low risk of bias. This study revealed no association between the diet acid load with bladder cancer (OR=1.15: 95% CI 0.86 to 1.55, p=0.36). No association was found even among long-term smokers (OR=1.72: 95% CI 0.96 to 3.10, p=0.08).ConclusionsDespite the promotion of the alkaline diet and alkaline water by the media and salespeople, there is almost no actual research to either support or disprove these ideas. This systematic review of the literature revealed a lack of evidence for or against diet acid load and/or alkaline water for the initiation or treatment of cancer. Promotion of alkaline diet and alkaline water to the public for cancer prevention or treatment is not justified.
Competence of health workers in emergency obstetric care: an assessment using clinical vignettes in Brong Ahafo region, Ghana
Authors: Lohela Terhi Johanna , Nesbitt Robin Clark , Manu Alexander , Vesel Linda , Okyere Eunice , Kirkwood Betty , Gabrysch Sabine 
Published: June 2016

ObjectivesTo assess health worker competence in emergency obstetric care using clinical vignettes, to link competence to availability of infrastructure in facilities, and to average annual delivery workload in facilities.DesignCross-sectional Health Facility Assessment linked to population-based surveillance data.Setting7 districts in Brong Ahafo region, Ghana.ParticipantsMost experienced delivery care providers in all 64 delivery facilities in the 7 districts.Primary outcome measuresHealth worker competence in clinical vignette actions by cadre of delivery care provider and by type of facility. Competence was also compared with availability of relevant drugs and equipment, and to average annual workload per skilled birth attendant.ResultsVignette scores were moderate overall, and differed significantly by respondent cadre ranging from a median of 70% correct among doctors, via 55% among midwives, to 25% among other cadres such as health assistants and health extension workers (p<0.001). Competence varied significantly by facility type: hospital respondents, who were mainly doctors and midwives, achieved highest scores (70% correct) and clinic respondents scored lowest (45% correct). There was a lack of inexpensive key drugs and equipment to carry out vignette actions, and more often, lack of competence to use available items in clinical situations. The average annual workload was very unevenly distributed among facilities, ranging from 0 to 184 deliveries per skilled birth attendant, with higher workload associated with higher vignette scores.ConclusionsLack of competence might limit clinical practice even more than lack of relevant drugs and equipment. Cadres other than midwives and doctors might not be able to diagnose and manage delivery complications. Checking clinical competence through vignettes in addition to checklist items could contribute to a more comprehensive approach to evaluate quality of care.Trial registration numberNCT00623337.
Medication double-checking procedures in clinical practice: a cross-sectional survey of oncology nurses' experiences
Authors: Schwappach D L B , Pfeiffer Yvonne , Taxis Katja 
Published: June 2016

BackgroundDouble-checking is widely recommended as an essential method to prevent medication errors. However, prior research has shown that the concept of double-checking is not clearly defined, and that little is known about actual practice in oncology, for example, what kind of checking procedures are applied.ObjectiveTo study the practice of different double-checking procedures in chemotherapy administration and to explore nurses' experiences, for example, how often they actually find errors using a certain procedure. General evaluations regarding double-checking, for example, frequency of interruptions during and caused by a check, or what is regarded as its essential feature was assessed.MethodsIn a cross-sectional survey, qualified nurses working in oncology departments of 3 hospitals were asked to rate 5 different scenarios of double-checking procedures regarding dimensions such as frequency of use in practice and appropriateness to prevent medication errors; they were also asked general questions about double-checking.ResultsOverall, 274 nurses (70% response rate) participated in the survey. The procedure of jointly double-checking (read-read back) was most commonly used (69% of respondents) and rated as very appropriate to prevent medication errors. Jointly checking medication was seen as the essential characteristic of double-checking—more frequently than ‘carrying out checks independently’ (54% vs 24%). Most nurses (78%) found the frequency of double-checking in their department appropriate. Being interrupted in one's own current activity for supporting a double-check was reported to occur frequently. Regression analysis revealed a strong preference towards checks that are currently implemented at the responders' workplace.ConclusionsDouble-checking is well regarded by oncology nurses as a procedure to help prevent errors, with jointly checking being used most frequently. Our results show that the notion of independent checking needs to be transferred more actively into clinical practice. The high frequency of reported interruptions during and caused by double-checks is of concern.
Compendium of models from a gauge U(1) framework
Authors: Ma Ernest 
Published: June 2016

A gauge U(1) framework was established in 2002 to extend the supersymmetric Standard Model. It has many possible realizations. Whereas all have the necessary and sufficient ingredients to explain the possible 750 GeV diphoton excess, observed recently by the ATLAS and CMS Collaborations at the large hadron collider (LHC), they differ in other essential aspects. A compendium of such models is discussed.
A DFT study of pressure-induced phase transitions, structural and electronic properties of Cu2ZnSnS4
Authors: Zhao Yifen , Li Decong , Liu Zuming 
Published: June 2016

The structural properties, phase transitions, and electronic structures of Cu2ZnSnS4 (CZTS) in the three structures have been researched using the first-principles density functional theory (DFT). The results indicate that the energies of stannite (ST) and pre-mixed Cu–Au (PMCA) CZTS are higher than those of kesterite (KS) CZTS, indicating that the KS CZTS is more stable. We found the phase transition pressure between the KS and ST structures of CZTS is about 32 GPa. Moreover, for KS- and PMCA-CZTS, there exists in the mischcrystal phase between 52 GPa and 65 GPa. The band structures show that the KS- and ST-CZTS are direct band gap semiconductors. The band gaps of three-type CZTS increase with increasing pressure, and the maximum band gap of KS and ST structures for CZTS occurs at 50 GPa. However, PMCA CZTS possesses metal property. Furthermore, the PMCA CZTS translates from metal to the indirect semiconductor with increasing pressure. The results play an important role in future experimental and theoretical work for CZTS materials.
Innovation and critical thinking: contributions of the history and philosophy of geological sciences to teaching, especially undergraduate teaching
Authors: Figueirôa Silvia F. de M. 
Published: June 2016

Abstract
This article discusses some important relations between the history and philosophy of science and the education of future professional geoscientists and teachers. A brief survey is presented of the discussions about the relations between these fields over the past 50 years, with an emphasis on the pedagogical role of the history and philosophy of science. A recent geological example is considered to pull together the conclusions advanced by some classic papers in science and geoscience. These conclusions reinforce the relevance of historical and epistemological reflections in improving the development of the profession and renewing educational practices, pointing out the potential of interdisciplinary learning and new innovative teaching methods. The careful, well-selected and documented utilization of controversial historical cases can foster experimentation and the comprehension of diverse examples of important scientific changes, thus contributing to a better education in the geosciences.
Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein–Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression
Authors: Jones Richard J. , Iempridee Tawin , Wang Xiaobin , Lee Hans C. , Mertz Janet E. , Kenney Shannon C. , Lin Heather C. , Baladandayuthapani Veerabhadran , Dawson Christopher W. , Shah Jatin J. , Weber Donna M. , Orlowski Robert Z. 
Published: June 2016

Abstract
Purpose: Lenalidomide, thalidomide, and pomalidomide (LTP) are immunomodulatory agents approved for use in multiple myeloma, but in some settings, especially with alkylating agents, an increase in Hodgkin lymphoma and other secondary primary malignancies (SPM) has been noted. Some of these malignancies have been linked to Epstein–Barr virus (EBV), raising the possibility that immunomodulatory drugs disrupt latent EBV infection.
Experimental Design: We studied the ability of LTP to reactivate latently infected EBV-positive cell lines in vitro and in vivo, and evaluated the EBV viral load in archived serum samples from patients who received a lenalidomide, thalidomide, and dexamethasone (LTD) combination.
Results: Treatment of EBV-infected B-cell lines with LTP at physiologically relevant concentrations induced the immediate early gene BZLF1, the early gene BMRF1, and the late proteins VCA and BCFR1. This occurred in the potency order pomalidomide &gt; lenalidomide &gt; thalidomide, and the nucleoside analogue ganciclovir enhanced the cytotoxic effects of lenalidomide and pomalidomide in Burkitt lymphoma cells in vitro and in vivo. EBV reactivation was related to PI3K stimulation and Ikaros suppression, and blocked by the PI3Kδ inhibitor idelalisib. Combinations of lenalidomide with dexamethasone or rituximab increased EBV reactivation compared with lenalidomide alone and, importantly, lenalidomide with melphalan produced even greater reactivation.
Conclusions: We conclude LTP may reactivate EBV-positive resting memory B cells thereby enhancing EBV lytic cycle and host immune suppression. Clin Cancer Res; 22(19); 4901–12. ©2016 AACR.
Upregulation of AKT3 Confers Resistance to the AKT Inhibitor MK2206 in Breast Cancer
Authors: Stottrup Casey , Tsang Tiffany , Chin Y. Rebecca 
Published: June 2016

Abstract
Acquired resistance to molecular targeted therapy represents a major challenge for the effective treatment of cancer. Hyperactivation of the PI3K/AKT pathway is frequently observed in virtually all human malignancies, and numerous PI3K and AKT inhibitors are currently under clinical evaluation. However, mechanisms of acquired resistance to AKT inhibitors have yet to be described. Here, we use a breast cancer preclinical model to identify resistance mechanisms to a small molecule allosteric AKT inhibitor, MK2206. Using a step-wise and chronic high-dose exposure, breast cancer cell lines harboring oncogenic PI3K resistant to MK2206 were established. Using this model, we reveal that AKT3 expression is markedly upregulated in AKT inhibitor–resistant cells. Induction of AKT3 is regulated epigenetically by the bromodomain and extra terminal domain proteins. Importantly, knockdown of AKT3, but not AKT1 or AKT2, in resistant cells restores sensitivity to MK2206. AKT inhibitor–resistant cells also display an epithelial to mesenchymal transition phenotype as assessed by alterations in the levels of E-Cadherin, N-Cadherin, and vimentin, as well as enhanced invasiveness of tumor spheroids. Notably, the invasive morphology of resistant spheroids is diminished upon AKT3 depletion. We also show that resistance to MK2206 is reversible because upon drug removal resistant cells regain sensitivity to AKT inhibition, accompanied by reexpression of epithelial markers and reduction of AKT3 expression, implying that epigenetic reprogramming contributes to acquisition of resistance. These findings provide a rationale for developing therapeutics targeting AKT3 to circumvent acquired resistance in breast cancer. Mol Cancer Ther; 15(8); 1964–74. ©2016 AACR.
The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas
Authors: Peh Jessie , Fan Timothy M. , Wycislo Kathryn L. , Roth Howard S. , Hergenrother Paul J. 
Published: June 2016

Abstract
The development of vemurafenib resistance limits the long-term efficacy of this drug for treatment of metastatic melanomas with the V600EBRAF mutation. Inhibition of downstream MAPK signaling with vemurafenib induces apoptotic cell death mediated by caspase-3, suggesting that addition of a procaspase-3 activator could enhance anticancer effects. Here, we show that the combination of PAC-1, a procaspase-activating compound, and vemurafenib is highly synergistic in enhancing caspase-3 activity and apoptotic cell death in melanoma cell lines harboring the V600EBRAF mutation. In vivo, the combination displays a favorable safety profile in mice and exerts significant antitumor effects. We further demonstrate that addition of PAC-1 to the clinically useful combination of vemurafenib and a MEK inhibitor, trametinib, starkly enhances the caspase-3 activity and proapoptotic effect of the combination. Moreover, addition of low concentration PAC-1 also delays the regrowth of cells following treatment with vemurafenib. Finally, PAC-1 remains potent against vemurafenib-resistant A375VR cells in cell culture and synergizes with vemurafenib to exert antitumor effects on A375VR cell growth in vivo. Collectively, our data suggest that inhibition of MAPK signaling combined with concurrent procaspase-3 activation is an effective strategy to enhance the antitumor activity of vemurafenib and mitigate the development of resistance. Mol Cancer Ther; 15(8); 1859–69. ©2016 AACR.
Autocrine Complement Inhibits IL10-Dependent T-cell–Mediated Antitumor Immunity to Promote Tumor Progression
Authors: Wang Yu , Sun Sheng-Nan , Liu Qing , Yu Yang-Yang , Guo Jian , Wang Kun , Xing Bao-Cai , Zheng Qing-Feng , Campa Michael J. , Patz Edward F. , Li Shi-You , He You-Wen 
Published: June 2016

AbstractIn contrast to its inhibitory effects on many cells, IL10 activates CD8+ tumor-infiltrating lymphocytes (TIL) and enhances their antitumor activity. However, CD8+ TILs do not routinely express IL10, as autocrine complement C3 inhibits IL10 production through complement receptors C3aR and C5aR. CD8+ TILs from C3-deficient mice, however, express IL10 and exhibit enhanced effector function. C3-deficient mice are resistant to tumor development in a T-cell– and IL10-dependent manner; human TILs expanded with IL2 plus IL10 increase the killing of primary tumors in vitro compared with IL2-treated TILs. Complement-mediated inhibition of antitumor immunity is independent of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint pathway. Our findings suggest that complement receptors C3aR and C5aR expressed on CD8+ TILs represent a novel class of immune checkpoints that could be targeted for tumor immunotherapy. Moreover, incorporation of IL10 in the expansion of TILs and in gene-engineered T cells for adoptive cell therapy enhances their antitumor efficacy.Significance: Our data suggest novel strategies to enhance immunotherapies: a combined blockade of complement signaling by antagonists to C3aR, C5aR, and anti–PD-1 to enhance anti–PD-1 efficacy; a targeted IL10 delivery to CD8+ TILs using anti–PD-1–IL10 or anti-CTLA4–IL10 fusion proteins; and the addition of IL10 in TIL expansion for adoptive cellular therapy. Cancer Discov; 6(9); 1022–35. ©2016 AACR.See related commentary by Peng et al., p. 953.This article is highlighted in the In This Issue feature, p. 932
Balloon Dilatation and Stenting for Aortic Coarctation
Authors: Salcher Maximilian , Naci Huseyin , Law Tyler J. , Kuehne Titus , Schubert Stephan , Kelm Marcus ,   on behalf of Cardioproof Consortium, Morley-Fletcher Edwin , Kuehne Titus , Hennemuth Anja , Manset David , Mcguire Alistair , Plank Gernot , Ecabert Olivier , Pongiglione Giacomo , Muthurangu Vivek 
Published: June 2016

Background—
There is no systematic assessment of available evidence on effectiveness and comparative effectiveness of balloon dilatation and stenting for aortic coarctation.

Methods and Results—
We systematically searched 4 online databases to identify and select relevant studies of balloon dilatation and stenting for aortic coarctation based on a priori criteria (PROSPERO 2014:CRD42014014418). We quantitatively synthesized results for each intervention from single-arm studies and obtained pooled estimates for relative effectiveness from pairwise and network meta-analysis of comparative studies. Our primary analysis included 15 stenting (423 participants) and 12 balloon dilatation studies (361 participants), including patients ≥10 years of age. Post-treatment blood pressure gradient reduction to ≤20 and ≤10 mm Hg was achieved in 89.5% (95% confidence interval, 83.7–95.3) and 66.5% (44.1–88.9%) of patients undergoing balloon dilatation, and in 99.5% (97.5–100.0%) and 93.8% (88.5–99.1%) of patients undergoing stenting, respectively. Odds of achieving ≤20 mm Hg were lower with balloon dilatation as compared with stenting (odds ratio, 0.105 [0.010–0.886]). Thirty-day survival rates were comparable. Numerically more patients undergoing balloon dilatation experienced severe complications during admission (6.4% [2.6–10.2%]) compared with stenting (2.6% [0.5–4.7%]). This was supported by meta-analysis of head-to-head studies (odds ratio, 9.617 [2.654–34.845]) and network meta-analysis (odds ratio, 16.23, 95% credible interval: 4.27–62.77) in a secondary analysis in patients ≥1 month of age, including 57 stenting (3397 participants) and 62 balloon dilatation studies (4331 participants).

Conclusions—
Despite the limitations of the evidence base consisting predominantly of single-arm studies, our review indicates that stenting achieves superior immediate relief of a relevant pressure gradient compared with balloon dilatation.
Two-Year Outcomes in Patients With Severe Aortic Valve Stenosis Randomized to Transcatheter Versus Surgical Aortic Valve Replacement
Authors: Søndergaard Lars , Steinbrüchel Daniel Andreas , Ihlemann Nikolaj , Nissen Henrik , Kjeldsen Bo Juel , Petursson Petur , Ngo Anh Thuc , Olsen Niels Thue , Chang Yanping , Franzen Olaf Walter , Engstrøm Thomas , Clemmensen Peter , Olsen Peter Skov , Thyregod Hans Gustav Hørsted 
Published: June 2016

Background—
The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize all-comers with severe native aortic valve stenosis to either transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding bioprosthesis or surgical aortic valve replacement (SAVR), including a lower-risk patient population than previous trials. This article reports 2-year clinical and echocardiographic outcomes from the NOTION trial.

Methods and Results—

Two-hundred eighty patients from 3 centers in Denmark and Sweden were randomized to either TAVR (n=145) or SAVR (n=135) with follow-up planned for 5 years. There was no difference in all-cause mortality at 2 years between TAVR and SAVR (8.0% versus 9.8%, respectively;
P
=0.54) or cardiovascular mortality (6.5% versus 9.1%;
P
=0.40). The composite outcome of all-cause mortality, stroke, or myocardial infarction was also similar (15.8% versus 18.8%,
P
=0.43). Forward-flow hemodynamics were improved following both procedures, with effective orifice area significantly more improved after TAVR than SAVR (effective orifice area, 1.7 versus 1.4 cm
2
at 3 months). Mean valve gradients were similar after TAVR and SAVR. When patients were categorized according to Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (<4% versus ≥4%), there was no statistically significant difference for TAVR and SAVR groups in the composite outcome for low-risk (14.7%, 95% confidence interval, 8.3–21.2 versus 16.8%; 95% confidence interval, 9.7–23.8;
P
=0.58) or intermediate-risk patients (21.1% versus 27.1%;
P
=0.59).

Conclusions—
Two-year results from the NOTION trial demonstrate the continuing safety and effectiveness of TAVR in lower-risk patients. Longer-term data are needed to verify the durability of this procedure in this patient population.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01057173.
Coronary Computed Tomography (CT) Angiography as a Predictor of Cardiac and Noncardiac Vascular Events in Asymptomatic Type 2 Diabetics: A 7‐Year Population‐Based Cohort Study
Authors: Halon David A. , Azencot Mali , Rubinshtein Ronen , Zafrir Barak , Flugelman Moshe Y. , Lewis Basil S. 
Published: June 2016

Background

Type 2 diabetics are at increased risk for vascular events, but the value of further risk stratification for coronary heart disease (
CHD
) in asymptomatic subjects is unclear. We examined the added value of coronary computed tomography angiography over clinical risk scores (United Kingdom Prospective Diabetes Study), and coronary artery calcium in a population‐based cohort of asymptomatic type 2 diabetics.

Methods and Results

Subjects (n=630) underwent baseline clinical assessment and computed tomography angiography (64‐slice scanner). Plaque site, volume, calcific content, and arterial remodeling were recorded using dedicated software. Coronary, macrovascular, and microvascular‐related events were assessed over 6.6±0.6 (mean±
SD
) (range 5.4–7.5) years and all
CHD
events were adjudicated. Discrimination of
CHD
events (cardiovascular death, myocardial infarction, unstable angina, or new‐onset angina requiring intervention) (n=41) was improved by addition of total plaque burden to the clinical risk and coronary artery calcium scores combined (C=0.789 versus 0.763,
P
=0.034) and further improved by addition of an angiographic score (C=0.824,
P
=0.021). Independent predictors of a
CHD
event were United Kingdom Prospective Diabetes Study risk score (hazard ratio 1.3 per 10% 10‐year risk,
P
=0.003) and the angiographic score (hazard ratio 3.2 per quartile,
P
<0.0001). Classification was improved over that by United Kingdom Prospective Diabetes Study and coronary artery calcium scores alone (overall net reclassification improvement 0.24). In subjects with coronary plaque (N=500), mild plaque calcification independently predicted a
CHD
event (hazard ratio 3.0,
P
=0.02). Computed tomography angiography predicted combined macrovascular but not microvascular‐related events.

Conclusions
Computed tomography angiography provides additional prognostic information in asymptomatic type 2 diabetics not obtainable from clinical risk assessment and coronary artery calcium alone.