bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro selection technologies to enhance biomaterial functionality
Authors: Rosch Jonah C , Hollmann Emma K , Lippmann Ethan S 
Published: May 2016

Cells make decisions and fate choices based in part on cues they receive from their external environment. Factors that affect the interpretation of these cues include the soluble proteins that are present at any given time, the cell surface receptors that are available to bind these proteins, and the relative affinities of the soluble proteins for their cognate receptors. Researchers have identified many of the biological motifs responsible for the high-affinity interactions between proteins and their receptors, and subsequently incorporated these motifs into biomaterials to elicit control over cell behavior. Common modes of control include localized sequestration of proteins to improve bioavailability and direct inhibition or activation of a receptor by an immobilized peptide or protein. However, naturally occurring biological motifs often possess promiscuous affinity for multiple proteins and receptors or lack programmable actuation in response to dynamic stimuli, thereby limiting the amount of control they can exert over cellular decisions. These natural motifs only represent a small fraction of the biological diversity that can be assayed by in vitro selection strategies, and the discovery of “artificial” motifs with varying affinity, specificity, and functionality could greatly expand the repertoire of engineered biomaterial properties. This minireview provides a brief summary of classical and emerging techniques in peptide phage display and nucleic acid aptamer selections and discusses prospective applications in the areas of cell adhesion, angiogenesis, neural regeneration, and immune modulation.
Information time scales for interim analyses of randomized clinical trials
Authors: Freidlin Boris , Othus Megan , Korn Edward L 
Published: May 2016

Background: Interim monitoring is a key component of randomized clinical trial design from both ethical and efficiency perspectives. In studies with time-to-event endpoints, timing of interim analyses is typically based on observing a pre-specified proportion of the total number of events required for the final analysis. While most randomized clinical trial designs pool events over the experimental and control arms in determining the analysis times, some designs use only the control-arm events for scheduling interim looks. Purpose: To evaluate the performance of the pooled and control-arm-based interim monitoring approaches and to propose a new procedure, the earliest information time procedure, that combines the benefits of the two approaches. Methods: The analytical and logistical considerations for the procedures are presented. The methodology is illustrated on data from three published randomized clinical trials. The procedures are compared in a simulation study. Results: The control-arm approach results in a slight inflation of the study type I error in one-sided randomized clinical trial designs. When the new treatment is no better than the control treatment, the pooled-arm approach results in, on average, earlier stopping times than the control-arm approach. When the new treatment works exceptionally well, the average stopping times under the control-arm approach are earlier than those under the pooled approach. The proposed earliest information time procedure is shown to result in stopping times corresponding to the best (earliest) of the two approaches over the entire range of alternatives. Limitations: The earliest information time procedure may result in a slight inflation of the type I error (especially in small trials); when exact control of the type I error is required, it is necessary to use a simulation-based method to correct the inflation. Conclusion: In time-to-event settings, the earliest information time procedure is an attractive alternative to the pooled and control-arm approaches. Improving the timing of interim analyses helps to minimize patient exposure to inferior treatments and to accelerate dissemination of the study results.
Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France
Authors: Kabeshova Anastasiia , Ben Hariz Soumaia , Tsakeu Elyonore , Benamouzig Robert , Launois Robert 
Published: May 2016

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events. Methods: A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY). Results: The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis. Conclusion: For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes.
Probiotics modify tight-junction proteins in an animal model of nonalcoholic fatty liver disease
Authors: Briskey David , Heritage Mandy , Jaskowski Lesley-Anne , Peake Jonathan , Gobe Glenda , Subramaniam V. Nathan , Crawford Darrell , Campbell Catherine , Vitetta Luis 
Published: May 2016

Background: We have investigated the effects of a multispecies probiotic preparation containing a combination of probiotic bacterial genera that included Bifidobacteria, Lactobacilli and a Streptococcus in a mouse model of high-fat diet or obesity-induced liver steatosis. Methods: Three groups of C57B1/6J mice were fed either a standard chow or a high-fat diet for 20 weeks, while a third group was fed a high-fat diet for 10 weeks and then concomitantly administered probiotics for a further 10 weeks. Serum, liver and large bowel samples were collected for analysis. Results: The expression of the tight-junction proteins ZO-1 and ZO-2 was reduced ( p < 0.05) in high-fat diet-fed mice compared to chow-fed mice. Probiotic supplementation helped to maintain tight ZO-1 and ZO-2 expression compared with the high-fat diet group ( p < 0.05), but did not restore ZO-1 or ZO-2 expression compared with chow-fed mice. Mice fed a high-fat diet ± probiotics had significant steatosis development compared with chow-fed mice ( p < 0.05); steatosis was less severe in the probiotics group compared with the high-fat diet group. Hepatic triglyceride concentration was higher in mice fed a high-fat diet ± probiotics compared with the chow group ( p < 0.05), and was lower in the probiotics group compared with the high-fat diet group ( p < 0.05). Compared with chow-fed mice, serum glucose, cholesterol concentration and the activity of alanine transaminase were higher ( p < 0.05), whereas serum triglyceride concentration was lower ( p < 0.05) in mice fed a high-fat diet ± probiotics. Conclusions: Supplementation with a multispecies probiotic formulation helped to maintain tight-junction proteins ZO-1 and ZO-2, and reduced hepatic triglyceride concentration compared with a high-fat diet alone.
Evaluation of the Effect of Carbohydrate Intake on Postprandial Glucose in Patients With Type 1 Diabetes Treated With Insulin Pumps
Authors: James Mariel L. , Green Louisa , Amiel Stephanie A. , Choudhary Pratik 
Published: May 2016

Background: It has been suggested that dietary freedom in functional insulin therapy may be detrimental to glycemic control in type 1 diabetes. This study evaluates the effect of carbohydrate intake on glycemic control and postprandial blood glucose concentrations. Methods: Insulin pump data from 148 adults with type 1 diabetes, trained in functional insulin therapy, using pumps for ≥6 months, with ≥2 weeks of consecutive downloaded data, ≥80% use of a bolus calculator, ≥3 capillary blood glucose tests/day, and a concurrent HbA1C, were analyzed. More detailed periprandial data (pre- and postmeal glucose, carbohydrate intake, insulin bolus) were collected from a subset of 105 downloads (3495 meals). Results: Mean (± SD) age of contributors was 43 ± 13 years, HbA1C 7.84% ± 0.93 (62.19 mmol/mol); daily carbohydrate intake 166 ± 71 g. HbA1C reduced with increased meals/day ( r = –.370, P < .0005) and increased with mean carbohydrate content/meal ( r = .198, P = .043). However, total daily carbohydrate intake had a weak but significant negative association with HbA1C ( r = –.181, P = .027). There was no association between standard deviation of carbohydrate intake and HbA1C ( r = .021, P = .802) or between meal carbohydrate content and postprandial change in blood glucose ( r = –.004, P = .939) for meals with early postprandial (1-3 hours; n = 390) readings. There was a weak positive correlation ( r = .184, P = .008) between meal carbohydrate content and late (4-7 hours; n = 390) postprandial readings. Discussion: With appropriate training, patients using insulin pumps can accommodate a flexible diet with variable carbohydrate intake, without detriment to glycemic control. However, large carbohydrate meals may contribute to poorer outcomes, through impact on late postprandial glycemia.
Contemporary Hospitalization Rate Among Adults With Complex Congenital Heart Disease
Authors: Cedars Ari , Benjamin Lawrence , Vyhmeister Ross , Harris Kathryn , Bradley Elisa A. , Wadia Subeer , Awad Ahmed J. , Novak Eric 
Published: May 2016

Background: Adults with congenital heart disease are hospitalized at increasing rates in the Western world. Identification of rates of and risk factors for hospitalization is essential for research and improving patient outcomes. Methods: We conducted a single-center retrospective analysis of patients with a primary diagnosis of tetralogy of Fallot (TOF), transposition of the great arteries (both d- and l-transposition of the great arteries [TGAs]), or single ventricle (SV). We investigated the rates of mortality, annual hospitalization, and patient-specific risk factors for unplanned cardiac hospitalization. Results: Adult patients with complex congenital heart disease are hospitalized at a rate four to eight times greater than the general US population ( P < .001). In addition, there are significant differences between the rates of hospitalization in TOF and TGA (0.39 and 0.41 hospitalizations per patient-year, respectively) and SV (0.72 hospitalizations per patient-year). The majority of excess hospitalizations in the study group were due to cardiac disease ( P < .001 for all three groups). Risk factors for unplanned cardiac hospitalization in TOF included pulmonary atresia, depressed left ventricular and right ventricular ejection fraction, and smoking; in TGA, they included Ebstein malformation, surgeries other than primary repair, noncardiac diagnoses, atrial arrhythmias, atrioventricular nodal block, left ventricular ejection fraction, and smoking; and in SV, they included atrial arrhythmias and cyanosis. Conclusions: Patients born with complex congenital heart disease are hospitalized far more frequently than the general US population, primarily for cardiac-related illness. Future research should focus on confirming the present findings and on identification of strategies to improve outcomes in this growing group of patients.
Tracheostomy Following Surgery for Congenital Heart Disease
Authors: Benneyworth Brian D. , Shao Jenny M. , Cristea A. Ioana , Ackerman Veda , Rodefeld Mark D. , Turrentine Mark W. , Brown John W. 
Published: May 2016

Background: Tracheostomy following congenital heart disease (CHD) surgery is a rare event and associated with significant mortality. Hospital survival has been reported from 20% to 40%. Late mortality for these patients is not well characterized. Methods: We performed a retrospective observational study of patients who had a tracheostomy following CHD surgery (excluding isolated patent ductus arteriosus ligation) between January 2000 and December 2013. Patients were categorized into single-ventricle or biventricular physiology groups. Demographics, genetic syndromes, pulmonary disease, and comorbidities were collected. Outcomes including hospital survival, long-term survival, and weaning from positive pressure ventilation are reported. Bivariate and time-to-event models were used. Results: Over a 14-year period, 61 children (0.9% incidence) had a tracheostomy placed following CHD surgery. There were 12 single-ventricle patients and 49 biventricular patients. Prematurity, genetic syndromes, lung/airway disease, and other comorbidities were common in both CHD groups. Gastrostomy tubes were used more frequently in biventricular physiology patients (91.8%) versus single-ventricle patients (66.7%, P = .04). Survival to hospital discharge was 50% in the single-ventricle group compared to 86% in biventricular patients ( P = .01). Long-term survival continued to be poor in the single-ventricle group comparatively (three years, 27.8% vs 64.8%, P = .01). Gastrostomy tube placement was independently associated with survival in both groups ( P = .002). Conclusion: Tracheostomy is performed following many types of surgery for CHD and is commonly associated with other comorbidities. Both hospital and long-term survival are substantially lower in children with single-ventricle physiology as compared to patients with biventricular physiology.
Effectiveness of a Multidisciplinary Clinical Pathway for Elderly Patients With Hip Fracture
Authors: Kalmet P. H. S. , Koc B. B. , Hemmes B. , ten Broeke R. H. M. , Dekkers G. , Hustinx P. , Schotanus M. G. , Tilman P. , Janzing H. M. J. , Verkeyn J. M. A. , Brink P. R. G. , Poeze M. 
Published: May 2016

Introduction: The use of a multidisciplinary clinical pathway (MCP) for patients with hip fracture tends to be more effective than usual care (UC). The aim of this study was to evaluate the effects of an MCP approach on time to surgery, length of stay, postoperative complications, and 30-day mortality, compared to UC. Materials and Methods: This multicenter retrospective cohort study included patients aged 50 years or older with a proximal hip fracture who underwent surgery in one of the 6 hospitals in the Limburg trauma region of the Netherlands in 2012. Data such as demographics, process outcome measures, and clinical outcome were collected. Results: This study included a total of 1193 patients (665 and 528 patients in the MCP and UC groups, respectively). There were no differences in patient demographics present. Time to surgery was significantly shorter in the MCP compared to the UC group (19.2 vs 24.4 hours, P < .01). The mean length of stay was 10 versus 12 days ( P < .01). In the MCP group, significantly lower rates of postoperative complications were observed and significantly more patients were institutionalized than in the UC group. Mortality within 30 days after admission was comparable between the groups (overall mortality 6%). Conclusion: An MCP approach is associated with reduced time to surgery, postoperative complications, and length of stay, without a significant difference in 30-day mortality. The institutionalization rate was significantly higher in the MCP group.
Erwin: Raising the science to greater heights through collaboration
Authors: Geary Andrew 
Published: May 2016

This SEG Wiki interview, the third of the 2016 series, features Maitri Erwin, senior geophysicist and manager at Nexen Petroleum USA and chair of the Women's Network Committee (WNC). Erwin joins Andrew Geary, SEG publications outreach editor, to discuss how SEG members can contribute to the Society and elevate the science. [Figure: see text]
Evolving eating disorder psychopathology: Conceptualising
muscularity-oriented disordered eating
Authors: Murray Stuart B. , Griffiths Scott , Mond Jonathan M. 
Published: May 2016

SummaryEating disorders, once thought to be largely confined to females, are
increasingly common in males. However, the presentation of disordered eating
among males is often distinct to that observed in females and this diversity
is not accommodated in current classification schemes. Here, we consider the
diagnostic and clinical challenges presented by these distinctive
presentations.
Deinstitutionalisation does not increase imprisonment or
homelessness
Authors: Salisbury Tatiana Taylor , Thornicroft Graham 
Published: May 2016

SummaryClosing long-stay psychiatric beds remains contentious. The review by
Winkler et al in this issue examines 23 studies of
deinstitutionalisation for the outcomes of people discharged from
psychiatric hospitals after an admission of 1 year or longer. The majority
of these studies identified no cases of homelessness, incarceration or
suicide after discharge from hospital.
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Authors: Nanda Rita , Chow Laura Q.M. , Dees E. Claire , Berger Raanan , Gupta Shilpa , Geva Ravit , Pusztai Lajos , Pathiraja Kumudu , Aktan Gursel , Cheng Jonathan D. , Karantza Vassiliki , Buisseret Laurence 
Published: May 2016

Purpose Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC. Methods KEYNOTE-012 ( ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1–positive (expression in stroma or ≥ 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort. Results Among 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1–positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade ≥ 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to ≥ 47.3 weeks). Conclusion This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks ( ClinicalTrials.gov identifier: NCT02447003) is ongoing.
Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer
Authors: Huang Yan-qi , Liang Chang-hong , He Lan , Tian Jie , Liang Cui-shan , Chen Xin , Ma Ze-lan , Liu Zai-yi 
Published: May 2016

Purpose To develop and validate a radiomics nomogram for preoperative prediction of lymph node (LN) metastasis in patients with colorectal cancer (CRC). Patients and Methods The prediction model was developed in a primary cohort that consisted of 326 patients with clinicopathologically confirmed CRC, and data was gathered from January 2007 to April 2010. Radiomic features were extracted from portal venous–phase computed tomography (CT) of CRC. Lasso regression model was used for data dimension reduction, feature selection, and radiomics signature building. Multivariable logistic regression analysis was used to develop the predicting model, we incorporated the radiomics signature, CT-reported LN status, and independent clinicopathologic risk factors, and this was presented with a radiomics nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. An independent validation cohort contained 200 consecutive patients from May 2010 to December 2011. Results The radiomics signature, which consisted of 24 selected features, was significantly associated with LN status (P < .001 for both primary and validation cohorts). Predictors contained in the individualized prediction nomogram included the radiomics signature, CT-reported LN status, and carcinoembryonic antigen level. Addition of histologic grade to the nomogram failed to show incremental prognostic value. The model showed good discrimination, with a C-index of 0.736 (C-index, 0.759 and 0.766 through internal validation), and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (C-index, 0.778 [95% CI, 0.769 to 0.787]) and good calibration. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful. Conclusion This study presents a radiomics nomogram that incorporates the radiomics signature, CT-reported LN status, and clinical risk factors, which can be conveniently used to facilitate the preoperative individualized prediction of LN metastasis in patients with CRC.