bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tools in a clinical information system supporting clinical trials at a Swiss University Hospital
Authors: Weisskopf Michael , Bucklar Guido , Blaser Jürg 
Published: August 2014

Background: Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. Methods: In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient–trial–assignment–tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. Results: The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month. Conclusions: The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety.
Level of A1C control and its predictors among Lebanese type 2 diabetic patients
Authors: Noureddine Hanan , Nakhoul Nancy , Galal Amal , Soubra Lama , Saleh Mounzer 
Published: August 2014

Aim: Lebanon is among the top 10 countries with the highest prevalence of diabetes in the Middle East region with estimates reaching as high as 16.6% in adults aged 20–79 years. The objective of this study was to assess the level of A1C control among a cohort of type 2 diabetic patients and factors associated with uncontrolled A1C. Methods: We carried out a retrospective observational study among type 2 diabetes mellitus patients attending an outpatient endocrinologist’s clinic between June 2008 and July 2012 in Beirut, Lebanon. Two groups were compared, based on their diabetic control (A1C < 7% and A1C ≥ 7%). Results: A total of 551 patients were included in this study, where 31.8% attained A1C control. Crude analyses showed that some factors were significantly associated with uncontrolled A1C, and these were long-standing diabetes, diabetes-related complications, uncontrolled blood pressure, lipid profile, as well as the use of metformin, sulfonylurea, or insulin. When multivariate analysis was carried out, the chances of having uncontrolled A1C were significantly higher among patients who developed neuropathy (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11–3.90), had uncontrolled triglycerides (OR 1.98, 95% CI 1.33–2.94), used insulin (OR 4.52, 95% CI 2.32–8.83), and sulfonylureas (OR 2.88, 95% CI 1.88–4.40). Conclusion: Uncontrolled diabetes is more likely to exist in patients with neuropathy, uncontrolled triglycerides and those using insulin or sulfonylurea. Further research is needed to confirm the findings.
Olanzapine induced Q-Tc shortening
Authors: Shoja Shafti Saeed , Fallah Jahromi Parisa 
Published: August 2014

Introduction Prolongation of Q-Tc interval is commonly accepted as a surrogate marker for the ability of a drug to cause torsade de pointes. In the present study, safety of olanzapine versus risperidone was compared among a group of patients with schizophrenia to see the frequency of the electrocardiographic alterations induced by those atypical antipsychotics. Method Two hundred and sixty-eight female inpatients with schizophrenia entered in one of the two parallel groups to participate in an open study for random assignment to olanzapine ( n = 148) or risperidone ( n = 120). Standard 12-lead surface electrocardiogram (ECG) was taken from each patient at baseline, before initiation of treatment, and then at the end of management, just before discharge. The parameters that were assessed included heart rate (HR), P-R interval, QRS interval, Q-T interval (corrected = Q-Tc), ventricular activation time (VAT), ST segment, T wave, axis of QRS, and finally, interventricular conduction process. Results A total of 37.83% of cases in the olanzapine group and 30% in the risperidone group showed some Q-Tc changes; 13.51% and 24.32% of the patients in the olanzapine group showed prolongation and shortening of the Q-Tc, respectively, while changes in the risperidone group were restricted to only prolongation of Q-Tc. Comparison of means showed a significant increment in Q-Tc by risperidone ( p = 0.02). Also, comparison of proportions in the olanzapine group showed significantly more cases with shortening of Q-Tc versus its prolongation ( p = 0.01). No significant alterations with respect to other variables were evident. Conclusion Olanzapine and risperidone had comparable potentiality for induction of Q-Tc changes, while production of further miscellaneous alterations in ECG was more observable in the olanzapine group compared with the risperidone group. Also shortening of Q-Tc was specific to olanzapine.
Current Physical and Mental Health of Former Collegiate Athletes
Authors: Kerr Zachary Y. , DeFreese J.D. , Marshall Stephen W. 
Published: August 2014

Background: There is a dearth of research on the current health of former collegiate athletes. Purpose: To examine the current health and related correlates in a cohort of former collegiate athletes who played in a diverse range of men’s and women’s sports with various levels of contact. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Former collegiate athletes (N = 3657) were asked to complete an online questionnaire addressing sports history, medical history, and demographics. The questionnaire also included the Veterans RAND 12-Item Health Survey (VR-12), which yielded 2 composite scores for physical (PCS) and mental (MCS) health. The VR-12 PCS and MCS scores were compared with published US normative data using t tests and analyses of variance. Results: Mean PCS and MCS scores of the 797 respondents with complete data (21.9% of target sample; average, 14.5 years since last played collegiate sport) were 53.0 ± 6.1 and 51.7 ± 9.4, respectively. When stratified by age and sex, PCS and MCS scores were similar to normative scores in the United States. Lower PCS scores were associated with sustaining ≥3 concussions, playing in collision sports during college, and sustaining a career-ending injury (all, P < .001). No association was found between concussion and MCS scores ( P = .06). Among former collegiate athletes, prevalent medical conditions included anxiety (16.2%), hypercholesterolemia/high cholesterol (10.6%), and depression (10.4%). Additionally, 5.8% screened positive for alcohol dependence, and 5.8% screened positive for disordered eating (eg, binge eating, purging). These findings were more prevalent than those reported by the World Health Organization as representative of the US population. Conversely, there was a lower prevalence of depression, bipolar disorders, and attention deficit disorder, with or without hyperactivity (ADD/ADHD), than in the World Health Organization US population data sample. Conclusion: Former collegiate athletes appear similar to the general US population on many aspects of mental and physical health. However, observed health deficits associated with previous sports injuries warrant ongoing monitoring of the health and well-being of former collegiate athletes.
Prevalence of Osteochondritis Dissecans of the Capitellum in Young Baseball Players
Authors: Matsuura Tetsuya , Suzue Naoto , Iwame Toshiyuki , Nishio Susumu , Sairyo Koichi 
Published: August 2014

Background: Osteochondritis dissecans (OCD) of the capitellum is a well-recognized cause of elbow pain and disability in adolescent athletes. However, little is known about the prevalence of OCD in adolescent baseball players. Purpose: To determine the prevalence of OCD in baseball players aged 10 to 12 years based on ultrasonographic findings and to investigate the clinical characteristics of those with OCD lesions. Study Design: Descriptive epidemiology study. Methods: A total of 1040 players aged 10 to 12 years completed a questionnaire, ultrasound imaging, and radiographic examination to investigate OCD. Sonographic findings were classified into 5 grades (0, 1a, 1b, 2, and 3). Subjects with grade 1a, 1b, 2, or 3 were considered to have abnormal findings of the capitellum and were advised to undergo radiography. Radiographic and ultrasonographic findings were then compared. The prevalence of OCD was calculated, and differences by age and player position were determined. Results: Of the 1040 players, 33 (3.2%) had an abnormal finding on initial ultrasonography screening, and all 33 agreed to undergo radiography. Of them, 22 (66.7%) were found to have OCD of the capitellum on radiographs, giving an overall prevalence of 2.1%. Seven subjects (31.8%) had no history of elbow pain. Based on the radiographic classification, 20 subjects (90.9%) had stage I lesions. Analysis of OCD by age and player position revealed no significant differences. Conclusion: The prevalence of OCD of the capitellum was 2.1% in 1000 baseball players aged 10 to 12 years, with no differences in prevalence according to age or player position.
Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8K108E mutation
Authors: Salem Sandra , Langlais David , Lefebvre François , Bourque Guillaume , Bigley Venetia , Haniffa Muzz , Casanova Jean-Laurent , Burk David , Berghuis Albert , Butler Karina M. , Leahy Timothy Ronan , Hambleton Sophie , Gros Philippe 
Published: August 2014

Key Points
IRF8K108E mutation causes dendritic cell depletion, defective antigen presentation, and anergic T cells. IRF8K108E mutant protein is functionally null and shows defective nuclear targeting and increased proteasomal degradation.
Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis
Authors: Khor Sara , Beca Jaclyn , Krahn Murray , Hodgson David , Lee Linda , Crump Michael , Bremner Karen E , Luo Jin , Mamdani Muhammad , Bell Chaim M , Sawka Carol , Gavura Scott , Sullivan Terrence , Trudeau Maureen , Peacock Stuart , Hoch Jeffrey S 
Published: August 2014

Abstract

Background
Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.

Methods
We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).

Results
Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087‒$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60–79 years old and $110,100/LYG for patients ≥80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.

Conclusions
Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.
Carbon nanotubes on nanoporous alumina: from surface mats to conformal pore filling
Authors: Fang Jinghua , Levchenko Igor , Han Zhao Jun , Yick Samuel , Ostrikov Kostya Ken 
Published: August 2014

Abstract
Control over nucleation and growth of multi-walled carbon nanotubes in the nanochannels of porous alumina membranes by several combinations of posttreatments, namely exposing the membrane top surface to atmospheric plasma jet and application of standard S1813 photoresist as an additional carbon precursor, is demonstrated. The nanotubes grown after plasma treatment nucleated inside the channels and did not form fibrous mats on the surface. Thus, the nanotube growth mode can be controlled by surface treatment and application of additional precursor, and complex nanotube-based structures can be produced for various applications. A plausible mechanism of nanotube nucleation and growth in the channels is proposed, based on the estimated depth of ion flux penetration into the channels.

PACS

63.22.Np Layered systems; 68. Surfaces and interfaces; Thin films and nanosystems (structure and non-electronic properties); 81.07.-b Nanoscale materials and structures: fabrication and characterization
Carbon nanotubes: properties, synthesis, purification, and medical applications
Authors: Eatemadi Ali , Daraee Hadis , Karimkhanloo Hamzeh , Kouhi Mohammad , Zarghami Nosratollah , Akbarzadeh Abolfazl , Abasi Mozhgan , Hanifehpour Younes , Joo Sang Woo 
Published: August 2014

AbstractCurrent discoveries of different forms of carbon nanostructures have motivated research on their applications in various fields. They hold promise for applications in medicine, gene, and drug delivery areas. Many different production methods for carbon nanotubes (CNTs) have been introduced; functionalization, filling, doping, and chemical modification have been achieved, and characterization, separation, and manipulation of individual CNTs are now possible. Parameters such as structure, surface area, surface charge, size distribution, surface chemistry, and agglomeration state as well as purity of the samples have considerable impact on the reactivity of carbon nanotubes. Otherwise, the strength and flexibility of carbon nanotubes make them of potential use in controlling other nanoscale structures, which suggests they will have a significant role in nanotechnology engineering.
Cloning, secretory expression and characterization of recombinant β-mannanase from Bacillus circulans NT 6.7
Authors: Piwpankaew Yotthachai , Sakulsirirat Supa , Nitisinprasert Sunee , Nguyen Thu-Ha , Haltrich Dietmar , Keawsompong Suttipun 
Published: August 2014

Abstract
The mannanase gene of B. circulans NT 6.7 was cloned and expressed in an Escherichia coli expression system. The B. circulans NT 6.7 mannanase gene consists of 1,083 nucleotides encoding a 360-amino acid residue long polypeptide, belonging to glycoside hydrolase family 26. The full-length mannanase gene including its native signal sequence was cloned into the vector pET21d and expressed in E. coli BL21 (DE3). β-Mannanase activities in the culture supernatant and crude cell extract were 37.10 and 515 U per ml, respectively, with most of the activity in the cell extract attributed to the periplasmic fraction. In contrast, expression of mannanase was much lower when using the B. circulans NT 6.7 mannanase gene without its signal sequence. The optimum temperature of recombinant β-mannanase activity was 50°C and the optimum pH was 6.0. The enzyme was very specific for β-mannan substrates with a preference for galactomannan. Hydrolysis products of locust bean gum were various mannooligosaccharides including mannohexaose, mannopentaose, mannotetraose, mannotriose and mannobiose, while mannose could not be detected. In conclusion, this expression system is efficient for the secretory production of recombinant β-mannanase from B. circulans NT 6.7, which shows good characteristics for various applications.
Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint
Authors: Ossipova Elena , Cerqueira Cátia Fernandes , Reed Evan , Kharlamova Nastya , Israelsson Lena , Holmdahl Rikard , Nandakumar Kutty Selva , Engström Marianne , Harre Ulrike , Schett Georg , Catrina Anca I , Malmström Vivianne , Sommarin Yngve , Klareskog Lars , Jakobsson Per-Johan , Lundberg Karin 
Published: August 2014

Abstract
Introduction
A major subset of patients with rheumatoid arthritis (RA) is characterized by the presence of circulating autoantibodies directed to citrullinated proteins/peptides (ACPAs). These autoantibodies, which are commonly detected by using an enzyme-linked immunosorbent assay (ELISA) based on synthetic cyclic citrullinated peptides (CCPs), predict clinical onset and a destructive disease course. In the present study, we have used plasma and synovial fluids from patients with RA, for the affinity purification and characterization of anti-CCP2 reactive antibodies, with an aim to generate molecular tools that can be used in vitro and in vivo for future investigations into the pathobiology of the ACPA response. Specifically, this study aims to demonstrate that the surrogate marker CCP2 can capture ACPAs that bind to autoantigens expressed in vivo in the major inflammatory lesions of RA (that is, in the rheumatoid joint).

Methods
Plasma (n = 16) and synovial fluid (n = 26) samples were collected from RA patients with anti-CCP2 IgG levels of above 300 AU/mL. Total IgG was isolated on Protein G columns and subsequently applied to CCP2 affinity columns. Purified anti-CCP2 IgG was analyzed for reactivity and specificity by using the CCPlus® ELISA, in-house peptide ELISAs, Western blot, and immunohisto-/immunocytochemistry.

Results
Approximately 2% of the total IgG pool in both plasma and synovial fluid was CCP2-reactive. Purified anti-CCP2 reactive antibodies from different patients showed differences in binding to CCP2 and differences in binding to citrullinated peptides from α-enolase, vimentin, fibrinogen, and collagen type II, illustrating different ACPA fine-specificity profiles. Furthermore, the purified ACPA bound not only in vitro citrullinated proteins but, more importantly, in vivo-generated epitopes on synovial fluid cells and synovial tissues from patients with RA.

Conclusions
We have isolated ACPAs from plasma and synovial fluid and demonstrated that the CCP2 peptides, frequently used in diagnostic ELISAs, de facto act as surrogate antigens for at least four different, well-characterized, largely non-cross-reactive, ACPA fine specificities. Moreover, we have determined the concentration and proportion of CCP2-reactive IgG molecules in rheumatoid plasma and synovial fluid, and we have shown that the purified ACPAs can be used to detect both in vitro- and in vivo-generated citrullinated epitopes by various techniques. We anticipate that these antibodies will provide us with new opportunities to investigate the potential pathogenic effects of human ACPAs.
Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study
Authors: Sun Bing , He Hangyong , Wang Zheng , Qu Jiuxin , Li Xuyan , Ban Chengjun , Wan Jun , Cao Bin , Tong Zhaohui , Wang Chen 
Published: August 2014

Abstract
Introduction
Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking.

Methods
We conducted a prospective, single-center observational study of pneumonia with ARDS in immunocompetent adults admitted to our respiratory ICU. We prospectively collected and analyzed clinical, laboratory, radiological characteristics, sequential tests of viral load in respiratory tract and blood, treatments and outcomes.

Results
The results for a total of five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays (CXRs) and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 × 108 copies in three patients and was 1 × 104 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation (NPPV) failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four (80%) of the five patients died despite receiving appropriate respiratory support.

Conclusions
HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The NPPV and IMV failure rates were very high, but ECMO may still be the respiratory support therapy of choice.

Trial registration
Clinicaltrials.gov NCT01585922. Registered 20 April 2012