bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the acute care of COPD patients across Gloucestershire: a quality improvement project.
Authors: Miller Craig , Cushley Claire , Redler Kasey , Mitchell Claire , Aynsley Day Elizabeth , Mansfield Helen , Nye Abigail 
Published: November 2015

AbstractAdmissions for exacerbations of chronic obstructive pulmonary disease (COPD) present a significant proportion of patients in the acute medical take. The British Thoracic Society (BTS) provides guidelines for time specific interventions, that should be delivered to those with an acute exacerbation of COPD through the admission care bundle. These include correct diagnosis, correct assessment of oxygenation, early administration of treatment, recognition of respiratory failure, and specialist review. Gloucestershire Hospitals NHS Foundation Trust (GHNHSFT) chose improvement in acute COPD care to be a local Commissioning for Quality and Innovation (CQUIN) scheme, which enables commissioners to reward excellence by linking a proportion of English healthcare providers’ income to the achievement of local quality improvement goals. The effects of initiatives put in place by senior clinicians had waned, and further improvements were required to meet the CQUIN target.The aim of the scheme was to improve compliance with the BTS guidelines and CQUIN scheme for patients admitted with an exacerbation of COPD.Specific bundle paperwork to be used for all patients admitted to the Trust with an exacerbation of COPD was introduced to the Trust in June 2014, with training and education of medical staff at that time. This had improved compliance rates from 10% to 63% by September 2014. Compliance with each intervention was audited through the examination of notes of patients admitted with an exacerbation of COPD. Compliance rates had plateaued over the last three months, and so a focus group involving junior medical staff met in September 2014 to try to increase awareness further, in order to drive greater improvements in care, and meet the CQUIN requirements. Their strategies were implemented, and then compliance with the CQUIN requirements was reaudited as described above.The December 2014 audit results showed a further improvement in overall COPD care, with 73% of patients receiving all elements of the COPD admission care bundle, versus 63% in September 2014. Appropriate blood gas analysis, nebuliser administration, and respiratory review also improved. Prescription of steroids and antibiotics remained static, with 96% of patients receiving these treatments within four hours in the emergency department (ED). The only criteria which showed a decline was appropriate oxygen prescription, which dipped from 97% to 87%.After the effect of initial strategies plateaued, this quality improvement project facilitated a further increase in compliance with the CQUIN targets, both improving patient care, and safeguarding continued CQUIN funding. There is further work to be done to maintain and support further improvement in standards, and to encourage use of the COPD admission bundle paperwork for documentation purposes.
Method for identification ofCryptococcus neoformansandCryptococcus gattiiuseful in resource-limited settings
Authors: Ogundeji Adepemi O , Albertyn Jacobus , Pohl Carolina H , Sebolai Olihile M 
Published: November 2015

AimsThe high HIV/AIDS burden in Sub-Saharan Africa has led to cryptococcosis becoming a public health concern. In this resource-limited setting, conventional identification methods are mainly used to diagnose cryptococcal infections. However, these methods are often inconsistent, and importantly, cannot discriminate between the aetiological agents,Cryptococcus neoformansandC. gattii. Therefore, there is a need for an alternative reliable method to identify these species.MethodsWe examined the usefulness of a PCR method, including a restriction digest, in identifying clinicalC. neoformansandC. gattiiisolates. In addition, matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-ToF MS) was performed for validation purposes.ResultsThe intraspecific variation between tested strains allowed for their delineation into three traditional varieties ofC. neoformans, that is, varietal forms:neoformans,grubiiandgattii. Furthermore, we uncovered a restriction site (signature sequence: 5′-AATATT-3′) that is present only in the distinct speciesC. neoformans(varietal formsneoformansandgrubii), and is, importantly, absent in the distinct speciesC. gattii(C. neoformansvar.gattii). Thus, we were able to discriminate the distinct species by directly digesting the PCR amplicons using the endonucleaseSspI. It was also possible to delineate some tested isolates as eitherC. neoformansorC. gattiiusing our MALDI-ToF MS data.ConclusionsThe possibility of performing only a restriction digest makes the outlined method, similar to conventional techniques, economical and easy to optimise for routine use in resource-limited settings.
A qualitative study to assess the potential of the human papillomavirus vaccination programme to encourage under-screened mothers to attend for cervical screening
Authors: Spencer Angela M , Brabin Loretta , Roberts Stephen A , Patnick Julietta , Elton Peter , Verma Arpana 
Published: November 2015

BackgroundCoverage of the UK National Health Service Cervical Screening Programme is declining. Under-screened women whose daughters participate in the human papillomavirus (HPV) vaccination programme could be stimulated to attend. We investigated whether factors associated with the vaccination programme changed mothers’ intentions for future screening.MethodsQuestionnaires were sent to mothers of girls aged 12–13 years across two North West primary care trusts (n=2387) to assess the effect of the HPV vaccination programme on screening intentions. This identified mothers whose intentions had changed. Consent was sought to contact them for a semi-structured interview to discuss their screening intentions. Key themes were identified using framework analysis.Results97/606 women responding to the questionnaire had changed their views about cervical screening. 23 women were interviewed, 10 of whom expressed a positive change and 13 no change. Most had discussed the vaccine information, including cervical screening, with their daughters. Mothers who made a positive change decision recognised their daughters’ risk of cervical cancer, the need for future screening, and the importance of their own example. In this way daughters became ‘significant others’ in reinforcing their mothers’ cervical screening motivation.ConclusionsA daughter's invitation for HPV vaccination instigates a reassessment of cervical screening intention in some under-screened mothers.
Comparing clay mineral diagenesis in interbedded sandstones and mudstones, Vienna Basin, Austria
Authors: Gier Susanne , Worden Richard H. , Krois Peter 
Published: November 2015

Abstract
There is no consensus about the rate and style of clay mineral diagenesis in progressively buried sandstones v. interbedded mudstones. The diagenetic evolution of interbedded Miocene sandstones and mudstones from the Vienna Basin (Austria) has therefore been compared using core-based studies, petrography, X-ray diffraction and X-ray fluorescence. There was a common provenance for the coarse- and fine-grained sediments, and the primary depositional environment of the host sediment had no direct effect on illitization. The sandstones are mostly lithic arkoses dominated by framework grains of quartz, altered feldspars and carbonate rock fragments. Sandstone porosity has been reduced by quartz overgrowths and calcite cement; their pore-filling authigenic clay minerals consist of mixed-layer illite–smectite, illite, kaolinite and chlorite. In sandstones, smectite illitization progresses with depth; at 2150 m there is a transition from randomly interstratified to regular interstratified illite–smectite. The overall mineralogy of mudstones is surprisingly similar to the sandstones. However, for a given depth, feldspars are more altered to kaolinite, and smectite illitization is more advanced in sandstones than in mudstones. The higher permeability of sandstones allowed faster movement of material and pore fluid necessary for illitization and feldspar alteration than in mudstones. The significance of this work is that it has shown that open-system diagenesis is important for some clay mineral diagenetic reactions in sandstones, while closed-system diagenesis seems to operate for clay mineral diagenesis in mudstones.
Elucidation and Pharmacological Targeting of Novel Molecular Drivers of Follicular Lymphoma Progression
Authors: Bisikirska Brygida , Bansal Mukesh , Shen Yao , Teruya-Feldstein Julie , Chaganti Raju , Califano Andrea 
Published: November 2015

Abstract
Follicular lymphoma, the most common indolent subtype of non-Hodgkin lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from the time of diagnosis. However, in 20% to 60% of follicular lymphoma patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of follicular lymphoma transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases. Therefore, to identify candidate drivers of follicular lymphoma transformation, we performed systematic analysis of a B-cell–specific regulatory model exhibiting follicular lymphoma transformation signatures using the Master Regulator Inference algorithm (MARINa). This analysis revealed FOXM1, TFDP1, ATF5, HMGA1, and NFYB to be candidate master regulators (MR) contributing to disease progression. Accordingly, validation was achieved through synthetic lethality assays in which RNAi-mediated silencing of MRs individually or in combination reduced the viability of (14;18)-positive DLBCL (t-DLBCL) cells. Furthermore, specific combinations of small-molecule compounds targeting synergistic MR pairs induced loss of viability in t-DLBCL cells. Collectively, our findings indicate that MR analysis is a valuable method for identifying bona fide contributors to follicular lymphoma transformation and may therefore guide the selection of compounds to be used in combinatorial treatment strategies. Cancer Res; 76(3); 664–74. ©2015 AACR.
Balancing Efficacy and Safety of an Anti-DLL4 Antibody through Pharmacokinetic Modulation
Authors: Couch Jessica A. , Zhang Gu , Beyer Joseph C. , de Zafra Christina L. Zuch , Gupta Priyanka , Kamath Amrita V. , Lewin-Koh Nicholas , Tarrant Jacqueline , Allamneni Krishna P. , Cain Gary , Yee Sharon , Ross Sarajane , Cook Ryan , Tsai Siao Ping , Ruppel Jane , Ridgway John Brady , Paluch Maciej , Hass Philip E. , Franklin Jayme , Yan Minhong 
Published: November 2015

Abstract
Purpose: Although agents targeting Delta-like ligand 4 (DLL4) have shown great promise for angiogenesis-based cancer therapy, findings in recent studies have raised serious safety concerns. To further evaluate the potential for therapeutic targeting of the DLL4 pathway, we pursued a novel strategy to reduce toxicities related to DLL4 inhibition by modulating the pharmacokinetic (PK) properties of an anti-DLL4 antibody.
Experimental Design: The F(ab′)2 fragment of anti-DLL4 antibody (anti-DLL4 F(ab′)2) was generated and assessed in efficacy and toxicity studies.
Results: Anti-DLL4 F(ab′)2 enables greater control over the extent and duration of DLL4 inhibition, such that intermittent dosing of anti-DLL4 F(ab′)2 can maintain significant antitumor activity while markedly mitigating known toxicities associated with continuous pathway inhibition.
Conclusions: PK modulation has potentially broad implications for development of antibody-based therapeutics. Our safety studies with anti-DLL4 F(ab′)2 also provide new evidence reinforcing the notion that the DLL4 pathway is extremely sensitive to pharmacologic perturbation, further underscoring the importance of exercising caution to safely harness this potent pathway in humans. Clin Cancer Res; 22(6); 1469–79. ©2015 AACR.
AGS16F Is a Novel Antibody Drug Conjugate Directed against ENPP3 for the Treatment of Renal Cell Carcinoma
Authors: Doñate Fernando , Raitano Arthur , Morrison Kendall , An Zili , Capo Linnette , Aviña Hector , Karki Sher , Morrison Karen , Yang Peng , Ou Jimmy , Moriya Ryuichi , Shostak Yuriy , Malik Faisal , Nadell Rossana , Liu Wendy , Satpayev Daulet , Atkinson John , Joseph Ingrid B.J. , Pereira Daniel S. , Challita-Eid Pia M. , Stover David R. 
Published: November 2015

Abstract
Purpose: New cancer-specific antigens are required for the design of novel antibody–drug conjugates (ADC) that deliver tumor-specific and highly potent cytotoxic therapy.
Experimental Design: Suppression subtractive hybridization identified ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3 or CD203c) as a potential human cancer-specific antigen. Antibodies targeting the extracellular domain of human ENPP3 were produced and selected for specific binding to ENPP3. Expression of ENPP3 in normal and cancer tissue specimens was evaluated by immunohistochemistry (IHC). ADCs comprising anti-ENPP3 Ab conjugated with maleimidocaproyl monomethyl auristatin F via a noncleavable linker (mcMMAF) were selected for therapeutic potential using binding and internalization assays, cytotoxicity assays, and tumor growth inhibition in mouse xenograft models. Pharmacodynamic markers were evaluated by IHC in tissues and ELISA in blood.
Results: ENPP3 was highly expressed in clear cell renal cell carcinoma: 92.3% of samples were positive and 83.9% showed high expression. By contrast, expression was negligible in normal tissues examined, with the exception of the kidney. High expression was less frequent in papillary renal cell carcinoma and hepatocellular carcinoma samples. AGS16F, an anti-ENPP3 antibody–mcMMAF conjugate, inhibited tumor growth in three different renal cell carcinoma (RCC) xenograft models. AGS16F localized to tumors, formed the active metabolite Cys-mcMMAF, induced cell-cycle arrest and apoptosis, and increased blood levels of caspase-cleaved cytokeratin-18, a marker of epithelial cell death.
Conclusions: AGS16F is a promising new therapeutic option for patients with RCC and is currently being evaluated in a phase I clinical trial. Clin Cancer Res; 22(8); 1989–99. ©2015 AACR.
Taselisib (GDC-0032), a Potent β-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing ActivatingPIK3CAAlterations
Authors: Zumsteg Zachary S. , Morse Natasha , Krigsfeld Gabriel , Gupta Gaorav , Higginson Daniel S. , Lee Nancy Y. , Morris Luc , Ganly Ian , Shiao Stephan L. , Powell Simon N. , Chung Christine H. , Scaltriti Maurizio , Baselga José 
Published: November 2015

AbstractPurpose: Activating PIK3CA genomic alterations are frequent in head and neck squamous cell carcinoma (HNSCC), and there is an association between phosphoinositide 3-kinase (PI3K) signaling and radioresistance. Hence, we investigated the therapeutic efficacy of inhibiting PI3K with GDC-0032, a PI3K inhibitor with potent activity against p110α, in combination with radiation in HNSCC.Experimental Design: The efficacy of GDC-0032 was assessed in vitro in 26 HNSCC cell lines with crystal violet proliferation assays, and changes in PI3K signaling were measured by Western blot analysis. Cytotoxicity and radiosensitization were assessed with Annexin V staining via flow cytometry and clonogenic survival assays, respectively. DNA damage repair was assessed with immunofluorescence for γH2AX foci, and cell cycle analysis was performed with flow cytometry. In vivo efficacy of GDC-0032 and radiation was assessed in xenografts implanted into nude mice.Results: GDC-0032 inhibited potently PI3K signaling and displayed greater antiproliferative activity in HNSCC cell lines with PIK3CA mutations or amplification, whereas cell lines with PTEN alterations were relatively resistant to its effects. Pretreatment with GDC-0032 radiosensitized PIK3CA-mutant HNSCC cells, enhanced radiation-induced apoptosis, impaired DNA damage repair, and prolonged G2–M arrest following irradiation. Furthermore, combined GDC-0032 and radiation was more effective than either treatment alone in vivo in subcutaneous xenograft models.Conclusions: GDC-0032 has increased potency in HNSCC cell lines harboring PIK3CA-activating aberrations. Further, combined GDC-0032 and radiotherapy was more efficacious than either treatment alone in PIK3CA-altered HNSCC in vitro and in vivo. This strategy warrants further clinical investigation. Clin Cancer Res; 22(8); 2009–19. ©2015 AACR.
Establishment of reference intervals for aldosterone and renin in a Caucasian population using the newly developed Immunodiagnostic Systems specialty immunoassay automated system
Authors: O’Shea Paula , Brady Jennifer J , Gallagher Noelle , Dennedy Michael C , Fitzgibbon Maria 
Published: November 2015

Background Measurement of aldosterone and/or renin is essential to aid the differential diagnosis of secondary hypertension, guide strategy for therapeutic management of hypertension and assess adequacy of mineralocorticoid replacement. Aim The objective was to establish normative data for aldosterone and renin using the Immunodiagnostic Systems specialty immunoassay system platform in a Caucasian population. Methods Following informed consent, 365 subjects were recruited to this study. Subjects were ambulatory and attended clinic for blood pressure measurement and phlebotomy between the hours of 7:00 and 11:00. Blood pressure was measured according to the 2013 European Society of Hypertension/Cardiology guidelines. The inclusion criteria: age ≥18 years, BMI <30 kg/m2, non-pregnant, blood pressure <140/90, normal electrolytes and kidney function and not taking prescribed/over the counter medications. Ninety-four subjects were excluded based on these criteria. A total of 271 volunteers (females n = 145), aged 18–65 years formed the reference cohort. Blood for aldosterone/renin was collected into ethylenediaminetetraacetic acid specimen tubes. Samples were kept at room temperature and transported within 30 min of blood draw to the laboratory for immediate processing (centrifugation, separation and freezing of plasma). Plasma was stored at −20℃ prior to analysis on the Immunodiagnostic Systems specialty immunoassay system instrument. Results The established reference intervals in an Irish Caucasian population for renin: females: 6.1–62.7 mIU/L, males: 9.0–103 mIU/L, for aldosterone: females: <138–1179 pmol/L, males: <138–670 pmol/L, respectively. Conclusion This study demonstrates that reference intervals for aldosterone and renin should be gender specific. These automated immunoassays offer rapid stratification of patients with refractory hypertension and will better facilitate the optimization of therapeutic management.
Medical burden, body mass index and the outcome of psychosocial interventions for bipolar depression
Authors: Peters Amy T , Shesler Leah W , Sylvia Louisa , da Silva Magalhaes Pedro Vieira , Miklowitz David J , Otto Michael W , Frank Ellen , Berk Michael , Dougherty Darin D , Nierenberg Andrew A , Deckersbach Thilo 
Published: November 2015

Objective: Individuals with bipolar disorder experience a disproportionately high incidence of medical co-morbidity and obesity. These health-related problems are a barrier to recovery from mood episodes and have been linked with unfavorable responses to pharmacological treatment. However, little is known about whether and how these characteristics affect responses to adjunctive psychotherapy. Method: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy plus pharmacotherapy with collaborative care (a three-session psycho-educational intervention) plus pharmacotherapy. We conducted a post-hoc analysis to evaluate whether medical burden and body mass index predicted and/or moderated the likelihood of recovery and time until recovery from a depressive episode among patients in the two treatments. Results: Participants who had medical co-morbidity and body mass index data constituted 199 of the 293 patients in the original Systematic Treatment Enhancement Program for Bipolar Disorder trial. Higher medical burden predicted a lower likelihood of recovery from depression in both treatment conditions (odds ratio = 0.89), but did not moderate responses to intensive psychotherapy vs collaborative care. Intensive psychotherapy yielded superior recovery rates for individuals of normal body mass index (odds ratio= 2.39) compared with collaborative care, but not among individuals who were overweight or obese. Conclusion: Medical co-morbidity and body weight impacts symptom improvement and attention to this co-morbidity may inform the development of more personalized treatments for bipolar disorder.
Mortality associated with anxiolytic and hypnotic drugs—A systematic review and meta-analysis
Authors: Parsaik Ajay K , Mascarenhas Soniya S , Khosh-Chashm Darrow , Hashmi Aqeel , John Vineeth , Okusaga Olaoluwa , Singh Balwinder 
Published: November 2015

Background: Use of hypnotics or anxiolytic drugs is common and various studies have reported increased mortality with hypnotics or anxiolytic use. Objective: To consolidate the evidence on mortality risk associated with hypnotics or anxiolytic use Methods: Major databases were searched through April 2014 for studies reporting mortality risk associated with hypnotics or anxiolytics use. A pooled hazard ratio with 95% confidence interval was estimated using random-effects model. Results: After screening 2188 articles, 25 studies (24 cohort, 1 case-control) enrolling 2,350,093 patients with 59% females (age 18–102 years) were included in the meta-analysis. Hypnotics or anxiolytic users had 43% higher risk of mortality than non-users (hazard ratio, 1.43; 95% confidence interval, [1.12, 1.84]). Eight studies reported risk estimates for each gender category and pooled results from these studies showed increased risk of mortality among men (hazard ratio = 1.60, 95% confidence interval = [1.29,1.99]) and women (hazard ratio = 1.68, 95% confidence interval = [1.38, 2.04]). Pooled results from 10 studies showed higher mortality among benzodiazepine users compared to non-users (hazard ratio = 1.60, 95% confidence interval = [1.03, 2.49]), while pooled results from five studies showed an increased risk of mortality with Z-drugs use although the effect could not reach statistical significance (hazard ratio = 1.73, 95% confidence interval = [0.95, 3.16]). Significant heterogeneity was observed in the analyses and the quality of included studies was good. Conclusion: This meta-analysis suggests that hypnotics or anxiolytics drugs use is associated with increased mortality and hence should be used with caution. Future studies focused on underlying mechanism of increased mortality with hypnotics or anxiolytics use are required.