bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat-Labile Enterotoxin IIa, a Platform To Deliver Heterologous Proteins into Neurons
Authors: Chen Chen , Przedpelski Amanda , Tepp William H. , Pellett Sabine , Johnson Eric A. , Barbieri Joseph T. 
Published: August 2015

ABSTRACTCholera toxin (CT) and the related heat-labile enterotoxins (LT) ofEscherichia colihave been implicated as adjuvants in human therapies, but reactivity upon intranasal delivery dampened efforts to develop other clinical applications. However, each CT family member variant has unique biological properties that may warrant development as therapeutic platforms. In the current study, a nontoxic variant of the heat-labile enterotoxin IIa (LTIIa) was engineered to deliver heterologous, functional proteins into the cytosol of neurons. As proof of principle, the LTIIa variant delivered two cargos into neurons. LTIIa delivered β-lactamase efficiently into cells containing complex gangliosides, such as GD1b, as host receptors. LTIIa delivery of β-lactamase was sensitive to brefeldin A, an inhibitor that collapses the Golgi compartment into the endoplasmic reticulum, but not sensitive to treatment with botulinum neurotoxin D (BoNT/D), an inhibitor of synaptic vesicle cycling. LTIIa delivered a single-chain, anti-BoNT/A camelid antibody that inhibited SNAP25 cleavage during post-BoNT/A exposure of neurons. Delivery of functional, heterologous protein cargos into neurons demonstrates the potential of LTII variants as platforms to deliver therapies to inactivate toxins and microbial infections and to reverse the pathology of human neurodegenerative diseases.IMPORTANCEThis study engineered a protein platform to deliver functional, heterologous proteins into neurons. The protein platform developed was a variant of the heat-labile enterotoxin IIa (LTIIa) which lacked the catalytic domain, yielding a nontoxic protein. As proof of principle, LTIIa variants delivered two functional proteins into neurons, β-lactamase and a camelid antibody. These studies show the utility of LTIIa variants to deliver therapies into neurons, which could be extended to inactivate toxins and microbial infections and potentially to reverse the progression of neurological diseases, such as Alzheimer's disease and Parkinson's disease.
Findings from a novel approach to publication guideline revision: user road testing of a draft version of SQUIRE 2.0
Authors: Davies Louise , Donnelly Kyla Z , Goodman Daisy J , Ogrinc Greg 
Published: August 2015

BackgroundThe Standards for Quality Improvement Reporting Excellence (SQUIRE) Guideline was published in 2008 (SQUIRE 1.0) and was the first publication guideline specifically designed to advance the science of healthcare improvement. Advances in the discipline of improvement prompted us to revise it. We adopted a novel approach to the revision by asking end-users to ‘road test’ a draft version of SQUIRE 2.0. The aim was to determine whether they understood and implemented the guidelines as intended by the developers.MethodsForty-four participants were assigned a manuscript section (ie, introduction, methods, results, discussion) and asked to use the draft Guidelines to guide their writing process. They indicated the text that corresponded to each SQUIRE item used and submitted it along with a confidential survey. The survey examined usability of the Guidelines using Likert-scaled questions and participants’ interpretation of key concepts in SQUIRE using open-ended questions. On the submitted text, we evaluated concordance between participants’ item usage/interpretation and the developers’ intended application. For the survey, the Likert-scaled responses were summarised using descriptive statistics and the open-ended questions were analysed by content analysis.ResultsConsistent with the SQUIRE Guidelines’ recommendation that not every item be included, less than one-third (n=14) of participants applied every item in their section in full. Of the 85 instances when an item was partially used or was omitted, only 7 (8.2%) of these instances were due to participants not understanding the item. Usage of Guideline items was highest for items most similar to standard scientific reporting (ie, ‘Specific aim of the improvement’ (introduction), ‘Description of the improvement’ (methods) and ‘Implications for further studies’ (discussion)) and lowest (<20% of the time) for those unique to healthcare improvement (ie, ‘Assessment methods for context factors that contributed to success or failure’ and ‘Costs and strategic trade-offs’). Items unique to healthcare improvement, specifically ‘Evolution of the improvement’, ‘Context elements that influenced the improvement’, ‘The logic on which the improvement was based’, ‘Process and outcome measures’, demonstrated poor concordance between participants’ interpretation and developers’ intended application.ConclusionsUser testing of a draft version of SQUIRE 2.0 revealed which items have poor concordance between developer intent and author usage, which will inform final editing of the Guideline and development of supportingsupplementary materials. It also identified the items that require special attention when teaching about scholarly writing in healthcare improvement.
Do critically ill liver patients experience negative bias? A web-based survey examining doctors opinions to critical care escalation
Authors: Berry Philip A , Peck Marcus , Standley Tom , Thomson Sam J 
Published: August 2015

ObjectiveTo test the hypothesis that there is negative bias towards escalating levels of care in decompensated cirrhosis, compared with other patient groups.DesignAn electronic survey containing eight acute clinical scenarios with equivalent physiological derangement, in which respondents were asked to score the degree to which they would advocate for intensive care unit admission on a scale of 1–10. Scenarios included respiratory, haematology, vascular, renal, gastrointestinal, postoperative and hepatological conditions. Follow-up questions examined the reasons why the patient should or should not be transferred, and enquired about ceilings of care, end-of-life decisions, degree of organ support and healthcare financial rationing. 273 doctors responded.SettingSecondary care hospitals in south of England.PatientsNone involved.InterventionsNone.Main outcome measuresAdvocacy score (1–10) and subsidiary responses.ResultsThe hepatology patient ranked 4th of 8 with a mean advocacy score of 7.2. There were no significant differences between intensivists and physicians or between grades of seniority. Of those less likely to escalate (score 1–5, n=42), the reasons given were based on unsurvivability or excessive burden of treatment rather than aetiology. One-fifth cited ‘lifestyle decision’. 25 (62.5%) respondents not favouring escalation would make the patient DNACPR, 17 (42.5%) would stipulate ward-based care only and a small minority would instigate active palliation. Of those favouring escalation (advocacy score 6–10), 70% (n=122) would consider unlimited organ support. Fifty-four (29.5% of those who answered) said they ‘sometimes’ or ‘frequently’ consider resource allocation when making decisions about escalation of care.ConclusionsWhen compared with a variety of acute medical scenarios, doctors did not overly appear to exhibit therapeutic nihilism for patients with decompensated liver disease; however, significant variation in interpretation of the data and management approaches was identified.
Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus erythematosus: results of phase II study
Authors: Urowitz Murray B , Isenberg David A , Wallace Daniel J 
Published: August 2015

ObjectiveTo evaluate the safety and efficacy of hCDR1 (Edratide) in patients with systemic lupus erythematosus (SLE).MethodsPatients (n=340) with SLE ≥4 ACR criteria (4–11, mean 7) with active disease (SLEDAI-2K of 6–12). Patients were on average 7.1 years post-diagnosis and their organ involvement was mainly musculoskeletal, mucocutaneous and haematologic. Placebo or Edratide was administered subcutaneously weekly at doses of 0.5, 1.0 or 2.5 mg. The co-primary endpoints were SLEDAI-2K SLE Disease Activity and Adjusted Mean SLEDAI (AMS) reduction in patients compared with controls using a landmark analysis. Secondary outcomes were improvement in British Isles Lupus Assessment Group (BILAG) Responder Index and medicinal flare analysis.ResultsEdratide was safe and well tolerated. The primary endpoints based solely on SLEDAI-2K and AMS were not met. The secondary predefined endpoint, BILAG, was met for the 0.5 mg Edratide arm in the intention to treat (ITT) cohort (N=316) (OR=2.09, p=0.03) with trends in the 1.0 and 2.5 mg doses. There was also a positive trend in the Composite SLE Responder Index of the ITT cohort. Post hoc analysis showed that the BILAG secondary endpoint was also met for the 0.5 mg Edratide for a number of subgroup dose levels, including low or no steroids, seropositivity and patients with 2 grade BILAG improvement.ConclusionsThe favourable safety profile and encouraging clinically significant effects noted in some of the endpoints support the need for additional longer term Edratide studies that incorporate recent advances in the understanding and treatment of SLE, including steroid treatment algorithms, and using a composite primary endpoint which is likely to include BILAG.Trial registration numberNCT00203151.
A Light Weight Text Extraction Technique for Hand-Held Device
Authors: Angadi S. A. , Kodabagi M. M. 
Published: August 2015

Automated systems for understanding display boards are finding many applications useful in guiding tourists, assisting visually challenged and also in providing location aware information. Such systems require an automated method to detect and extract text prior to further image analysis. In this paper, a new approach that uses zonewise profile features to identify and segment text regions from low resolution images of display boards captured from mobile phone cameras is presented. The method computes zonewise profile features on every 40 × 40 pixel image block and identifies potential text blocks using newly defined discriminant functions. Further, a merging algorithm is used to merge text blocks to obtain text regions. The method is implemented using the android software development kit and experimented on Sony X-PeriaTM Z C6603/C6602 mobile. The proposed methodology is evaluated on 3240 low resolution images of display boards captured from 2 and/or 5 mega pixel cameras on mobile phones at various pixel sizes 240 × 320, 480 × 640 and 960 × 1280 and reports an average processing time of 13 s and detection rate of 95.5%. The proposed method is found to be robust and insensitive to the variations in size and style of font, thickness and spacing between characters.
Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort
Authors: Pathak Anand , Adams Charleen D. , Loud Jennifer T. , Nichols Kathryn , Stewart Douglas R. , Greene Mark H. 
Published: August 2015

AbstractBackground: Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown.Methods: We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat.Results: Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1–23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6–48.6).Conclusions: Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer.Impact: Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. Cancer Epidemiol Biomarkers Prev; 24(10); 1614–21. ©2015 AACR.
Impact of Risk Assessment and Tailored versus Nontailored Risk Information on Colorectal Cancer Testing in Primary Care: A Randomized Controlled Trial
Authors: Skinner Celette Sugg , Halm Ethan A. , Bishop Wendy Pechero , Ahn Chul , Gupta Samir , Farrell David , Morrow Jay , Julka Manjula , McCallister Katharine , Sanders Joanne M. , Marks Emily , Rawl Susan M. 
Published: August 2015

Abstract
Background: Colorectal cancer screening is effective but underused. Guidelines for which tests are recommended and at what intervals depend on specific risks. We developed a tablet-based Cancer Risk Intake System (CRIS) that asks questions about risk prior to appointments and generates tailored printouts for patients and physicians summarizing and matching risk factors with guideline-based recommendations.
Methods: Randomized controlled trial among patients who: (i) used CRIS and they and their physicians received tailored printouts; (ii) used CRIS to answer questions but received standard information about cancer screening while their physicians received a standard electronic chart prompt indicating they were age-eligible but not currently adherent for colorectal cancer screening; or (iii) comprised a no-contact group that neither used CRIS nor received any information while their physicians received the standard prompt. Participation in testing was assessed via electronic medical record at 12 months.
Results: Participation in any colorectal cancer testing was three times higher for those who used the CRIS and received any printed materials, compared with no-contact controls (47% vs. 16%; P &lt; 0.0001). Among CRIS users ages 50 and older, participation in any testing was higher in the tailored group (53% vs. 44%, P = 0.023).
Conclusion: Use of CRIS and receipt of any information facilitated participation in testing. There was more testing participation in the CRIS-tailored than nontailored group.
Impact: Asking patients questions about their specific risk factors and giving them and their providers information just prior to an appointment may increase participation in colorectal cancer testing. Tailoring the information has some added benefit. Cancer Epidemiol Biomarkers Prev; 24(10); 1523–30. ©2015 AACR.
Prognostic and Chemotherapy Predictive Value of Gene-Expression Phenotypes in Primary Lung Adenocarcinoma
Authors: Ringnér Markus , Jönsson Göran , Staaf Johan 
Published: August 2015

Abstract
Purpose: Primary lung adenocarcinoma remains a deadly disease. Gene-expression phenotypes (GEPs) in adenocarcinoma have potential to provide clinically relevant disease stratification for improved prognosis and treatment prediction, given appropriate clinical and methodologic validation.
Experimental Design: 2,395 transcriptional adenocarcinoma profiles were assembled from 17 public cohorts and classified by a nearest centroid GEP classifier into three subtypes: terminal respiratory unit (TRU), proximal-proliferative, and proximal-inflammatory, and additionally scored by five transcriptional metagenes representing different biologic processes, including proliferation. Prognostic- and chemotherapy-predictive associations of the subtypes were analyzed by univariate and multivariate analysis using overall survival or distant metastasis-free survival as endpoints.
Results: Overall, GEPs were associated with patient outcome in both univariate and multivariate analyses, although not in all individual cohorts. The prognostically relevant division was between TRU- and non-TRU–classified cases, with expression of proliferation-associated genes as a key prognostic component. In contrast, GEP classification was not predictive of adjuvant chemotherapy response. GEP classification showed stability to random perturbations of genes or samples and alterations to classification procedures (typically &lt;10% of cases/cohort switching subtype). High classification variability (&gt;20% of cases switching subtype) was observed when removing larger or entire fractions of a single subtype, due to gene-centering shifts not addressable by the classifier.
Conclusions: In a large-scale evaluation, we show that GEPs add prognostic value to standard clinicopathologic variables in lung adenocarcinoma. Subject to classifier refinement and confirmation in prospective cohorts, GEPs have potential to affect the prognostication of adenocarcinoma patients through a molecularly driven disease stratification. Clin Cancer Res; 22(1); 218–29. ©2015 AACR.
Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression
Authors: Shang Zhiqun , Li Yanjun , Zhang Minghao , Tian Jing , Han Ruifa , Shyr Chih-Rong , Messing Edward , Yeh Shuyuan , Niu Yuanjie , Chang Chawnshang 
Published: August 2015

Abstract
Recent studies suggest that the androgen receptor (AR) might play important roles in influencing bladder cancer progression, yet its clinical application remains unclear. Here, we developed a new combined therapy with Bacillus Calmette–Guérin (BCG) and the AR degradation enhancer ASC-J9 or antiandrogen hydroxyflutamide (HF) to better suppress bladder cancer progression. Mechanism dissection revealed that ASC-J9 treatment enhanced BCG efficacy to suppress bladder cancer cell proliferation via increasing the recruitment of monocytes/macrophages that involved the promotion of BCG attachment/internalization to the bladder cancer cells through increased integrin-α5β1 expression and IL6 release. Such consequences might then enhance BCG-induced bladder cancer cell death via increased TNFα release. Interestingly, we also found that ASC-J9 treatment could directly promote BCG-induced HMGB1 release to enhance the BCG cytotoxic effects for suppression of bladder cancer cell growth. In vivo approaches also concluded that ASC-J9 could enhance the efficacy of BCG to better suppress bladder cancer progression in BBN-induced bladder cancer mouse models. Together, these results suggest that the newly developed therapy combining BCG plus ASC-J9 may become a novel therapy to better suppress bladder cancer progress. Mol Cancer Ther; 14(11); 2586–94. ©2015 AACR.
Prospective Teachers Proportional Reasoning and Presumption of Student Work
Authors: Sapti Mujiyem 
Published: August 2015

This study aimed to describe the proportional reasoning of prospective teachers and their predictions about students' answers. Subjects were 4 prospective teacher 7th semester Department of Mathematics Education, Muhammadiyah University of Purworejo. Proportional reasoning task used to obtain research data. Subjects were asked to explain their reasoning and write predictions of student completion. Data was taken on October 15th, 2014. Interviews were conducted after the subjects completed the task and recorded with audio media. The research data were subject written work and interview transcripts. Data were analyzed using qualitative analysis techniques. In solving the proportional reasoning task, subjects using the cross product. However, they understand the meaning of the cross product. Subject also could predict students' reasoning on the matter.
Mannitol and Outcome in Intracerebral Hemorrhage
Authors: Wang Xia , Arima Hisatomi , Yang Jie , Zhang Shihong , Wu Guojun , Woodward Mark , Muñoz-Venturelli Paula , Lavados Pablo M. , Stapf Christian , Robinson Thompson , Heeley Emma , Delcourt Candice , Lindley Richard I. , Parsons Mark , Chalmers John , Anderson Craig S. 
Published: August 2015

Background and Purpose—
Mannitol is often used to reduce cerebral edema in acute intracerebral hemorrhage but without strong supporting evidence of benefit. We aimed to determine the impact of mannitol on outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).

Methods—
INTERACT2 was an international, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure allocated to intensive (target systolic blood pressure, <140 mm Hg within 1 hour) or guideline-recommended (target systolic blood pressure, <180 mm Hg) blood pressure–lowering treatment. Propensity score and multivariable analyses were performed to investigate the relationship between mannitol treatment (within 7 days) and poor outcome, defined by death or major disability on the modified Rankin Scale score (3–6) at 90 days.

Results—

There was no significant difference in poor outcome between mannitol (n=1533) and nonmannitol (n=993) groups: propensity score–matched odds ratio of 0.90 (95% confidence interval, 0.75–1.09;
P
=0.30) and multivariable odds ratio of 0.87 (95% confidence interval, 0.71–1.07;
P
=0.18). Although a better outcome was suggested in patients with larger (≥15 mL) than those with smaller (<15 mL) baseline hematomas who received mannitol (odds ratio, 0.52 [95% confidence interval, 0.35–0.78] versus odds ratio, 0.91 [95% confidence interval, 0.72–1.15];
P
homogeneity <0.03 in propensity score analyses), the association was not consistent in analyses across other cutoff points (≥10 and ≥20 mL) and for differing grades of neurological severity. Mannitol was not associated with excess serious adverse events.

Conclusions—
Mannitol seems safe but might not improve outcome in patients with acute intracerebral hemorrhage.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00716079.