bluuebunny/crossref_metadata_2025_split huggingface dataset:
A trial of in-hospital, electronic alerts for acute kidney injury: Design and rationale
Authors: Wilson Francis Perry , Reese Peter P , Shashaty Michael GS , Ellenberg Susan S , Gitelman Yevgeniy , Bansal Amar D , Urbani Richard , Feldman Harold I , Fuchs Barry 
Published: July 2014

Background: Acute kidney injury is common in hospitalized patients, increases morbidity and mortality, and is under-recognized. To improve provider recognition, we previously developed an electronic alert system for acute kidney injury. To test the hypothesis that this electronic acute kidney injury alert could improve patient outcome, we designed a randomized controlled trial to test the effectiveness of this alert in hospitalized patients. The study design presented several methodologic, ethical, and statistical challenges. Purpose: To highlight the challenges faced and the solutions employed in the design and implementation of a clinical trial to determine whether the provision of an early electronic alert for acute kidney injury would improve outcomes in hospitalized patients. Challenges included how to randomize the delivery of the alert system and the ethical framework for waiving informed consent. Other methodologic challenges included the selection and statistical evaluation of our study outcome, a ranked-composite of a continuous covariate (creatinine) and two dichotomous outcomes (dialysis and death), and the use of the medical record as a source of trial data. Methods: We have designed a randomized trial to assess the effectiveness of an electronic alert system for acute kidney injury. With broad inclusion criteria, and a waiver of informed consent, we enroll and randomize virtually every patient with acute kidney injury in our hospital. Results: As of 31 March 2014, we have enrolled 2373 patients of 2400 targeted. Pre-alert data demonstrated a strong association between severity of acute kidney injury and inpatient mortality with a range of 6.4% in those with mild, stage 1 acute kidney injury, to 29% among those with stage 3 acute kidney injury (p < 0.001). We judged that informed consent would undermine the scientific validity of the study and present harms that are out of proportion to the very low risk intervention. Conclusion: Our study demonstrates the feasibility of designing an ethical randomized controlled trial of an early electronic alert for acute kidney injury without obtaining informed consent from individual participants. Our study outcome may serve as a model for other studies of acute kidney injury, insofar as our paradigm accounts for the effect that early death and dialysis have on assessment of acute kidney injury severity as defined by maximum achieved serum creatinine.
Good intentions and ICH-GCP: Trial conduct training needs to go beyond the ICH-GCP document and include the intention-to-treat principle
Authors: Browne Lois H , Graham Peter H 
Published: July 2014

Background: It is assumed investigators and statisticians fully understand the importance of avoiding missing outcomes and the intention-to-treat principle during design and analysis phases of a randomised controlled trial in order to obtain the most valuable and reliable results. However, many personnel undertaking day-to-day trial conduct and data collection commonly rely exclusively for guidance on the widely implemented, indeed regulated, International Conference on Harmonisation–Good Clinical Practice document as the guideline and standard for trial conduct. Purpose: This article describes adverse consequences of omission of intention-to-treat principles from training for trial personnel and explores the need for training in addition to the International Conference on Harmonisation–Good Clinical Practice guideline document. Methods: Data from the Breast Boost Study were used to illustrate a comparison of actual results, where vigilant senior investigators re-enforced intention-to-treat requirements throughout all aspects of trial conduct with results that could easily have occurred if study personnel did not understand the importance of intention-to-treat principles. Experience as a co-ordinating centre for an international trial (Trans-Tasman Radiation Oncology Group 08.06 Breast STARS) acted as an audit of data-management culture regarding intention-to-treat in Australia and New Zealand. Results: Despite the Breast Boost Study exceeding planned accrual, it was demonstrated that the study, which found a statistically significant result, could have reported a negative or inconclusive result under the scenario of trial conduct personnel having lack of understanding of the importance of avoiding losses to follow-up. Trans-Tasman Radiation Oncology 08.06 co-ordination experience verified that data-management culture in Australia and New Zealand does not adequately recognise intention-to-treat principles, and this is reflected in trial conduct. Limitations: Trial data described are limited to two trials and in the Australian and New Zealand setting. Conclusion: To be both scientifically and ethically valid, guidelines for trial conduct should include and stress the importance of the intention-to-treat principle and in particular avoiding missing outcomes. Our discussion highlights the vitally important role played by personnel involved in day-to-day trial conduct. Inclusion of scientific principles in guideline documents and/or training which goes beyond International Conference on Harmonisation–Good Clinical Practice to include intention-to-treat is essential to achieve robust research results. Related aspects of randomised trial consent and ethics are discussed.
Do partial thickness, bursal side cuff tears affect outcome following arthroscopic subacromial decompression? A prospective comparative cohort study
Authors: Lawson-Smith Matthew , Al-Maiyah Mohammed , Goodchild Lorna , Fourie J M Brendan , Finn Paul , Rangan Amar 
Published: July 2014

Background: The present study aimed to compare medium-term clinical outcomes of patients following arthroscopic subacromial decompression (ASAD): those with intact rotator cuff with two groups of increasing size of partial thickness bursal-side tears. Methods: Patients undergoing shoulder arthroscopy by a single surgeon had pre- and postoperative Constant scores prospectively recorded. Arthroscopic surgery included the assessment of any supraspinatus tears using the Ellman criteria, as well as ASAD and cuff debridement. Groups were created based on the status of rotator cuff and size of bursal tear. Outcome in these patient groups was then compared and analyzed Results: Seventy-four patients were suitable for inclusion in the study: 32 patients without a cuff tear; 21 patients with a cuff tear of 9 mm or less in length; and 21 patients with a cuff tear of 10 mm or more in length. Baseline characteristics of the three groups were similar. All three groups showed a significant improvement in their Constant scores following surgery. There was, however, no significant difference in Constant scores between the three groups. Conclusions: The results of the present study show that patients with varying sizes of bursal-side tears respond to ASAD as well as those with no rotator cuff tear.
Static Versus Dynamic Musculoskeletal Ultrasound for Detection of Plantar Plate Pathology
Authors: Feuerstein Catherine A. , Weil Lowell , Weil Lowell Scott , Klein Erin E. , Fleischer Adam , Argerakis Nicholas G. 
Published: July 2014

Musculoskeletal ultrasound (US) is a common modality used to examine plantar plate pathology. Comparison of the diagnostic accuracy of static versus dynamic ultrasound has not been previously published. The objective of this study was to prospectively compare the value of using preoperative static and dynamic ultrasound findings to diagnose plantar plate pathology using intraoperative inspection as the standard of reference. Patients attending a single foot and ankle specialty clinic from August 2012 to June 2013 with clinically suspected plantar plate pathology that was unresponsive to conservative care served as the study population. Static and dynamic ultrasound exams were performed by a single experienced rater and compared to intraoperative findings. The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value were determined for static and dynamic ultrasound exams. Thirty-six patients (45 lesser metatarsophalangeal joints) were included in this analysis. Of the 36 patients, 29 were females and 7 were males with average age of 57.9 ± 7.8 years (range, 38-73). There were 38 plantar plate tears (84.4%) noted on intraoperative examination. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for the static US exam were 80.0%, 81.6%, 71.4%, 93.9%, and 41.7%, respectively. The same values for the dynamic US exam were 88.9%, 100%, 28.6%, 88.3%, and 100%, respectively. Static and dynamic ultrasound techniques are each highly sensitive methods for assessing plantar plate pathology. However, the sensitivity and accuracy of the exam is best when dynamic assessment of the plantar plate is employed. Caution should be used when relying solely on static images to diagnose subtle injuries in this area of the foot. Levels of Evidence: Diagnostic Level II, Prospective
A prospective study of mediastinal gray-zone lymphoma
Authors: Wilson Wyndham H. , Pittaluga Stefania , Nicolae Alina , Camphausen Kevin , Shovlin Margaret , Steinberg Seth M. , Roschewski Mark , Staudt Louis M. , Jaffe Elaine S. , Dunleavy Kieron 
Published: July 2014

Key Points
MGZL with pathologic features in between NSHL and PMBL is very rare and most frequently occurs in young patients. A prospective study of DA-EPOCH-R without mediastinal radiation in MGZL demonstrated an inferior outcome compared to patients with PMBL.
Genome-wide analysis of DNA methylation patterns in horse
Authors: Lee Ja-Rang , Hong Chang Pyo , Moon Jae-Woo , Jung Yi-Deun , Kim Dae-Soo , Kim Tae-Hyung , Gim Jeong-An , Bae Jin-Han , Choi Yuri , Eo Jungwoo , Kwon Yun-Jeong , Song Sanghoon , Ko Junsu , Yang Young Mok , Lee Hak-Kyo , Park Kyung-Do , Ahn Kung , Do Kyoung-Tag , Ha Hong-Seok , Han Kyudong , Yi Joo Mi , Cha Hee-Jae , Cho Byung-Wook , Bhak Jong , Kim Heui-Soo 
Published: July 2014

Abstract

Background
DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known.

Results
We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density.

Conclusions
We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.
Nylon 6 electrospun nanofibers mat as effective sorbent for the removal of estrogens: kinetic and thermodynamic studies
Authors: Qi Fei-Fei , Cao Yang , Wang Min , Rong Fei , Xu Qian 
Published: July 2014

Abstract
Nylon 6 electrospun nanofibers mat was prepared via electrospinning for the removal of three estrogens, namely, diethylstilbestrol (DES), dienestrol (DS), and hexestrol (HEX) from aqueous solution. Static adsorption as well as the dynamic adsorption was evaluated by means of batch and dynamic disk flow mode, respectively. The kinetic study indicated that the adsorption of the target compounds could be well fitted by the pseudo-second-order equation, suggesting the intra-particle/membrane diffusion process as the rate-limiting step of the adsorption process. The adsorption equilibrium data were all fitted well to the Freundlich isotherm models, with a maximum adsorption capacity values in the range of 97.71 to 208.95 mg/g, which can be compared to or moderately higher than other sorbents published in the literatures. The dynamic disk mode studies indicated that the mean removal yields of three model estrogens were over 95% with a notable smaller amount of adsorbent (4 mg). Thermodynamic study revealed that the adsorption process was exothermic and spontaneous in nature. Desorption results showed that the adsorption capacity can remain up to 80% after seven times usage. It was suggested that Nylon 6 electrospun nanofibers mat has great potential as a novel effective sorbent material for estrogens removal.
The obtaining of high-density specimens and analysis of mechanical strength characteristics of a composite based on ZrO2-WC nanopowders
Authors: Gevorkyan Edwin , Melnik Olga , Chishkala Vladimir 
Published: July 2014

Abstract
The structures, processes of shrinkage, and phase composition of the compact system ZrO2-WC, obtained by hot pressing with the transmission of high current, are considered in the article. We found that as a result of compaction, the ZrO2-WC-ceramics have uniform density distribution, with the following optimal mode consolidation values T = 1,350°C, P = 30 MPa and t = 2 min. These conditions allow us to achieve the best combination of ceramic properties by criteria density and strength.
The immunological benefit of higher dose N-acetyl cysteine following mechanical ventilation in critically ill patients
Authors: Najafi Atabak , Mojtahedzadeh Mojtaba , Ahmadi Keyvan Haji , Abdollahi Mohammad , Mousavi Maryam , Chelkeba Legese , Najmeddin Farhad , Ahmadi Arezoo 
Published: July 2014

Abstract

Background
Sepsis complication is a major cause of death in multiple trauma critically ill patients. Defensin (cysteine rich anti-microbial peptides), as an important component of immune system, might play an important role in this process. There is also rising data on immunological effects of N-acetyl-cysteine (NAC), a commonly used anti-oxidant in oxidative stress conditions and glutathione (GSH) deficiencies. The aim of the present study was to evaluate the potential beneficial effects of NAC administration on multiple trauma patients with sepsis.

Methods
In a prospective, randomized controlled study, 44 multiple trauma critically ill patients who were mechanically ventilated and met the criteria of sepsis and admitted to the intensive care unit (ICU) were randomized into two groups . Control group received all standard ICU therapies and NAC group received intravenous NAC 3 gr every 6 hours for 72 hours in addition to standard therapies. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality were recorded. Levels of serum Immunoglobulin M (IgM), Human β-Defensin 2 (HβD2) and GSH were assessed at baseline and 24, 72, 120 hours after intervention.

Results
During a period of 13-month screening, 44 patients underwent randomization but 5 patients had to be excluded. 21 patients in NAC group and 18 patients in control group completed the study. For both groups the length of ICU stay, SOFA score and systemic oxygenation were similar. Mortality rate (40% vs. 22% respectively, p = 0.209) and ventilator days (Mean ± SD 19.82 ± 19.55 days vs. 13.82 ± 11.89 days respectively, p = 0.266) were slightly higher for NAC group. IgM and GSH levels were similar between two groups (p = 0.325, 0.125 respectively), HβD2 levels were higher for NAC group (at day 3).

Conclusion
High dose of NAC administration not only did not improve patients’ outcome, but also raised the risk of inflammation and was associated with increased serum creatinine.
Diet-induced (epigenetic) changes in bone marrow augment atherosclerosis
Authors: van Kampen Erik , Jaminon Armand , van Berkel Theo J C , Van Eck Miranda 
Published: July 2014

ABSTRACTAlterations in DNA methylation patterns in peripheral blood leukocytes precede atherosclerotic lesion development in mouse models of atherosclerosis and have been linked to cardiovascular death in patients. The aim of this study is to investigate the long-term changes induced by WTD feeding on BM cells and the consequences for atherosclerosis susceptibility. Hereto, WTD BM or Chow BM was transplanted into LDLR KO mice on chow. BM from WTD BM recipient mice exhibited hypomethylation of CpG regions in the genes encoding Pu.1 and IRF8, key regulators of monocyte proliferation and macrophage differentiation. In agreement, in blood, the numbers of leukocytes were 40% (P&lt;0.05) higher as a result of an increase in F4/80+ monocytes (3.4-fold; P&lt;0.01). An increase of CD11c++ cells was also found (2.4-fold; P&lt;0.05). Furthermore, spleens were enlarged, and the percentage of F4/80+ cells expressing CD86 was induced (1.8-fold; P&lt;0.01), indicating increased activation of splenic macrophages. Importantly, mice reconstituted with WTD BM showed a significant, 1.4-fold (P&lt;0.05) increase in aortic root plaque size in the absence of changes in serum cholesterol. We conclude that WTD challenge induces transplantable epigenetic changes in BM, alterations in the hematopoietic system, and increased susceptibility to atherosclerosis. Manipulation of the epigenome, when used in conjunction with blood lipid reduction, could thus prove beneficial to treat cardiovascular disorders.
Increased Serum Free Light Chains Precede the Presentation of Immunoglobulin Light Chain Amyloidosis
Authors: Weiss Brendan M. , Hebreo Joseph , Cordaro Daniel V. , Roschewski Mark J. , Baker Thomas P. , Abbott Kevin C. , Olson Stephen W. 
Published: July 2014

Purpose Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis. Patients and Methods We obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples. Results An M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001). Conclusion Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.
Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: An Integrated Safety Analysis
Authors: Diéras Véronique , Harbeck Nadia , Budd G. Thomas , Greenson Joel K. , Guardino Alice E. , Samant Meghna , Chernyukhin Nataliya , Smitt Melanie C. , Krop Ian E. 
Published: July 2014

Purpose The antibody–drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) –targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile. Patients and Methods Six studies in patients with HER2-positive MBC who received T-DM1 3.6 mg/kg every 3 weeks and follow-up data from patients in an extension study were analyzed. Analyses included adverse events (AEs) by grade; AEs leading to death, drug discontinuation, or dose reduction; and select AEs. Results Among 884 T-DM1–exposed patients, the most commonly reported all-grade AEs were fatigue (46.4%), nausea (43.0%), thrombocytopenia (32.2%), headache (29.4%), and constipation (26.5%). The most common grade 3 to 4 AEs were the laboratory abnormalities of thrombocytopenia (11.9%) and increased AST serum concentration (4.3%). These were manageable and not generally associated with clinical symptoms. There were 12 AE-related deaths. AEs resulted in dose reductions in 17.2% of patients and drug discontinuations in 7.0%. Conclusion In this analysis of 884 T-DM1–exposed patients, grade 3 or greater AEs were infrequent and typically asymptomatic and manageable. This favorable safety profile makes T-DM1 treatment suitable for exploration in other breast cancer settings.