bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological and medical applications of a brain-on-a-chip
Authors: Pamies David , Hartung Thomas , Hogberg Helena T 
Published: June 2014

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology.
Female college students’ beliefs about cervical cancer screening
Authors: Ackerson Kelly , Zielinski Ruth , Patel Heena 
Published: June 2014

Purpose To explore female college students’ perceived benefits and barriers to cervical cancer screening and perceived vulnerability to cervical cancer. Method The study was exploratory and cross sectional. The Pap Smear Belief Questionnaire was distributed online to a sample of 267 female undergraduate baccalaureate nursing students. Findings Students who obtained routine Pap smears perceived greater benefits and fewer barriers to routine screening than the students who did not obtain routine Pap smears. Personal vulnerability to cervical cancer was not a significant finding. Students who were in a long-term relationship, non-smoking and initiated sexual intercourse at a younger age were more likely to obtain routine screening. Conclusion Stressing importance of preventive health care associated with routine cervical cancer screening is important to promote women’s health regardless of age or level of education. Further studies with a broader range of college students as participants are needed to better understand their beliefs about the benefits and barriers to obtaining routine screening, and their perceptions of vulnerability to cervical cancer.
Management of variceal and nonvariceal upper gastrointestinal bleeding in patients with cirrhosis
Authors: Cremers Isabelle , Ribeiro Suzane 
Published: June 2014

Acute upper gastrointestinal haemorrhage remains the most common medical emergency managed by gastroenterologists. Causes of upper gastrointestinal bleeding (UGIB) in patients with liver cirrhosis can be grouped into two categories: the first includes lesions that arise by virtue of portal hypertension, namely gastroesophageal varices and portal hypertensive gastropathy; and the second includes lesions seen in the general population (peptic ulcer, erosive gastritis, reflux esophagitis, Mallory–Weiss syndrome, tumors, etc.). Emergency upper gastrointestinal endoscopy is the standard procedure recommended for both diagnosis and treatment of UGIB. The endoscopic treatment of choice for esophageal variceal bleeding is band ligation of varices. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the same time as endoscopy. Bleeding from portal hypertensive gastropathy is less frequent, usually chronic and treatment options include β-blocker therapy, injection therapy and interventional radiology. The standard of care of UGIB in patients with cirrhosis includes careful resuscitation, preferably in an intensive care setting, medical and endoscopic therapy, early consideration for placement of transjugular intrahepatic portosystemic shunt and, sometimes, surgical therapy or hepatic transplant.
Short-Term Effects of Patellar Kinesio Taping on Pain and Hop Function in Patients With Patellofemoral Pain Syndrome
Authors: Freedman Scott R. , Brody Lori Thein , Rosenthal Michael , Wise Justin C. 
Published: June 2014

Background: Patellofemoral pain syndrome (PFPS) is the most prevalent orthopaedic condition among physically active individuals, contributing to an estimated 30% to 40% of all sports medicine visits. Techniques using Kinesio Tape (KT) have become increasingly popular; however, there has been scant research supporting its use on patients with PFPS. Hypothesis: The use of patellar KT to treat patients with PFPS will provide a statistically significant improvement in short-term pain and single-leg hop measures as compared with sham placement of KT. Study Design: Nonrandomized controlled clinical trial with repeated-measures design. Level of Evidence: Level 3. Methods: Forty-nine subjects (41 females, 8 males) between the ages of 12 and 24 years with PFPS participated in this study. Each subject underwent patellar kinesio taping with both experimental and sham applications while completing 4 functional tasks and the single-leg triple jump test (STJT). The treatment outcome was analyzed using separate paired t tests to measure improvement on a numeric pain rating scale. A 2-way, 2 × 2 analysis of variance was used to analyze the relationship between taping condition (experimental vs sham) and side (involved vs uninvolved) for STJT scores. Results: Separate paired t tests found step-up, step-down, and STJT pain improvement statistically significant between taping conditions. The 2-factor analysis of variance yielded a significant main effect for taping condition, but the main effect for side was not significant. The interaction between taping condition and side was significant. This showed there was little change in STJT distance between repeated measures performed on the untaped, noninvolved leg. However, subjects’ STJT distances were significantly greater for the experimental KT application than the sham application for the involved side. Conclusion: Patellar kinesio taping provided an immediate and statistically significant improvement in pain and single-leg hop function in patients with PFPS when compared with a sham application. However, improvement in STJT scores did not surpass the minimally detectable change value, and therefore, the clinical effectiveness of KT for improving single-leg hop function was not established in the current study. Clinical Relevance: Kinesio Tape provides a viable, short-term method to control pain.
Microparticles and sudden cardiac death due to coronary occlusion. The TIDE (Thrombus and Inflammation in sudden DEath) study
Authors: Empana Jean-Philippe , Boulanger Chantal M , Tafflet Muriel , Renard Jean M , Leroyer Aurelie S , Varenne Olivier , Prugger Christof , Silvain Johanne , Tedgui Alain , Cariou Alain , Montalescot Gilles , Jouven Xavier , Spaulding Christian 
Published: June 2014

Aims: The pattern of coronary occlusion might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD). We hypothesized that the concentrations of microparticles might differ between SCD and ST-elevation myocardial infarction (STEMI) patients without rhythmic disturbances. Methods and results: The study sample includes consecutive patients hospitalized in two French tertiary centres between 2006 and 2011 for SCD with angiographically-proven acute coronary occlusion ( n=23), for STEMI ( n=61) and for a planned percutaneous coronary angioplasty (PCI) ( n=35, controls). During PCI blood was collected in the arch of aorta (systemic blood) before and after the procedure and in the culprit coronary lesion with an aspiration catheter. Microparticles were analysed by flow cytometry in a blinded manner to quantify endothelial (CD144+), platelet (CD41+), leucocyte (CD11a+) and erythrocyte (CD235a+) derived microparticles. After multivariate analysis, intracoronary concentrations of endothelial-derived microparticles were significantly higher in SCD than in STEMI patients (129 (74–185) vs. 50 (21–118) nb/µl; p < 0.01). Intracoronary and systemic blood concentrations of platelet-derived microparticles were not different between SCD and controls, suggesting limited impact of cardiac massage and electric defibrillation in microparticle concentrations. Conclusion: The higher concentrations of endothelial-derived microparticles in SCD due to acute coronary occlusion compared with STEMI without rhythmic disturbances suggests different patterns of acute coronary occlusion.
Intraoperative ureteric injuries and litigation in the NHS
Authors: Nachiappan S , Currie A , Askari A , Faiz O 
Published: June 2014

Objectives: The objective of this article is to analyse medicolegal claims arising from intraoperative ureteric injuries across all surgical specialties and the consequent financial costs to the National Health Service (NHS) in the United Kingdom. Materials and methods: We conducted a retrospective review of medicolegal claims reported to the NHS Legal Authority between April 2007 and March 2013. Results: A total of 191 claims were reported with 122 claims being resolved at the time of data collation. Of these, 97 were successful with a total of £9.66 million paid by the NHS in indemnity, averaging £99,611 per successful claim. There was an increasing number of claims filed over the study years and a slight decrease in the average pay-out per successful claim. Gynaecology and obstetrics accounted for over two-thirds of successful claims, with the remainder being divided equally among urology and colorectal surgery. However, claims arising from colorectal surgery had higher indemnity pay-outs on average. Conclusion: This is the first study analysing medicolegal claims and cost burden pertaining to ureteric injuries across different specialties. The findings concur with clinical studies which indicate gynaecological procedures and other pelvic (e.g. colorectal) procedures are at increased risk of causing ureteric injury.
The Impact of Fatigue on the Kinematics of Collegiate Baseball Pitchers
Authors: Grantham W. Jeffrey , Byram Ian R. , Meadows Molly C. , Ahmad Christopher S. 
Published: June 2014

Background: Many factors are believed to contribute to throwing injuries in baseball pitchers, in particular overuse and poor throwing mechanics. The impact of fatigue on pitching biomechanics in live-game situations is not well understood. Hypothesis: Pitchers will demonstrate significant deviation in their pitching motions with increasing levels of fatigue. Study Design: Descriptive laboratory study. Methods: Eleven National Collegiate Athletic Association (NCAA) Division I collegiate baseball pitchers were filmed in multiple live-game situations throughout a single season using 2 orthogonal high-speed cameras at 120 Hz. The first fastball of each inning and, when available, the fastball subsequent to the 15th and 30th pitch of each inning were recorded and analyzed for 26 kinematic parameters. Pitch count and velocity were recorded. Kinematic differences were assessed for association with pitch count and subjective fatigue measures over the course of each inning and game through the season. Results: Twenty-six games were recorded. Pitchers had a mean of 97.2 ± 16.1 pitches per start and 1079 ± 251 pitches per collegiate season. Increased hip lean at hand separation, elbow height at foot contact, and hip flexion and shoulder tilt at maximum external rotation were seen in innings lasting longer than 15 pitches. Maximum external rotation of the shoulder and elbow height at foot contact decreased over the course of a game. Hip lean at hand separation and elbow height at foot contact increased over the course of the season. Season pitch count was weakly correlated with increased shoulder external rotation and shoulder alignment at maximum external rotation and with shoulder abduction at ball release. Elbow flexion decreased with greater season pitch counts. Conclusion: Hip lean, elbow height, and shoulder external rotation were the most sensitive kinematic parameters to inning, game, and season fatigue. Pitch count and fatigue have a significant impact on live-game pitching kinematics. Clinical Relevance: Fatigue likely alters pitching mechanics. Recognition of kinematic alterations may better demonstrate fatigue-related injury risk and may assist injury prevention in addition to standardized limitations of innings and pitches thrown.
Rapamycin relieves lentiviral vector transduction resistance in human and mouse hematopoietic stem cells
Authors: Wang Cathy X. , Sather Blythe D. , Wang Xuefeng , Adair Jennifer , Khan Iram , Singh Swati , Lang Shanshan , Adams Amie , Curinga Gabrielle , Kiem Hans-Peter , Miao Carol H. , Rawlings David J. , Torbett Bruce E. 
Published: June 2014

Key PointsRapamycin significantly enhances lentiviral vector gene delivery to hematopoietic stem cells while preserving engraftment potential. Rapamycin-mediated transduction enhancement is not accompanied by alterations in lentiviral integration profile.
Acute graft-versus-host disease: a bench-to-bedside update
Authors: Holtan Shernan G. , Pasquini Marcelo , Weisdorf Daniel J. 
Published: June 2014

AbstractOver the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.
The biology of graft-versus-host disease: experimental systems instructing clinical practice
Authors: Markey Kate A. , MacDonald Kelli P. A. , Hill Geoffrey R. 
Published: June 2014

AbstractThe last 6 decades have seen major advances in the understanding of immunologic diseases, driven by preclinical animal models. Indeed, bone marrow transplantation (BMT) has its genesis in rodent models dating back to the 1950s. Allogeneic BMT and its major complication, graft-versus-host disease (GVHD), represent a paradigm for the translation of preclinical concepts into clinical practice. The appreciation that GVHD can be thought of as a stepwise escalation in immune activation characterized by eventual massive target tissue apoptosis has allowed the design of rational approaches to better manage patients. Here, we describe the pathophysiology of GVHD as defined in preclinical models, focusing on the successes and failures of this research to instruct and translate clinical practice. We also provide a commentary on the limitations of these models so that they may be better appreciated and addressed in future studies. Notable preclinical successes include the definition of modern immune suppression, reductions in conditioning intensity, posttransplant cyclophosphamide, and the promotion of regulatory T-cell reconstitution. New strategies including naïve T-cell depletion, focused cytokine and chemokine inhibition, and the blockade of costimulation now also appear highly promising and very likely to translate into patients in the near future.
Fraud in a population-based study of headache: prevention, detection and correction
Authors: Ahmed Bilal , Ahmad Ali , Herekar Akbar A , Uqaili Umer L , Effendi Jahanzeb , Alvi S Zia , Herekar Arif D , Steiner Timothy J 
Published: June 2014

Abstract

Background
In medicine, research misconduct is historically associated with laboratory or pharmaceutical research, but the vulnerability of epidemiological surveys should be recognized. As these surveys underpin health policy and allocation of limited resources, misreporting can have far-reaching implications. We report how fraud in a nationwide headache survey occurred and how it was discovered and rectified before it could cause harm.

Methods
The context was a door-to-door survey to estimate the prevalence and burden of headache disorders in Pakistan. Data were collected from all four provinces of Pakistan by non-medical interviewers and collated centrally. Measures to ensure data integrity were preventative, detective and corrective. We carefully selected and trained the interviewers, set rules of conduct and gave specific warnings regarding the consequences of falsification. We employed two-fold fraud detection methods: comparative data analysis, and face-to-face re-contact with randomly selected participants. When fabrication was detected, data shown to be unreliable were replaced by repeating the survey in new samples according to the original protocol.

Results
Comparative analysis of datasets from the regions revealed unfeasible prevalences and gender ratios in one (Multan). Data fabrication was suspected. During a surprise-visit to Multan, of a random sample of addresses selected for verification, all but one had been falsely reported. The data (from 840 cases) were discarded, and the survey repeated with new interviewers. The new sample of 800 cases was demographically and diagnostically consistent with other regions.

Conclusion
Fraud in community-based surveys is seldom reported, but no less likely to occur than in other fields of medical research. Measures should be put in place to prevent, detect and, where necessary, correct it. In this instance, had the data from Multan been pooled with those from other regions before analysis, a damaging fraud might have escaped notice.
Structured RNAs and synteny regions in the pig genome
Authors: Anthon Christian , Tafer Hakim , Havgaard Jakob H , Thomsen Bo , Hedegaard Jakob , Seemann Stefan E , Pundhir Sachin , Kehr Stephanie , Bartschat Sebastian , Nielsen Mathilde , Nielsen Rasmus O , Fredholm Merete , Stadler Peter F , Gorodkin Jan 
Published: June 2014

Abstract

Background
Annotating mammalian genomes for noncoding RNAs (ncRNAs) is nontrivial since far from all ncRNAs are known and the computational models are resource demanding. Currently, the human genome holds the best mammalian ncRNA annotation, a result of numerous efforts by several groups. However, a more direct strategy is desired for the increasing number of sequenced mammalian genomes of which some, such as the pig, are relevant as disease models and production animals.

Results
We present a comprehensive annotation of structured RNAs in the pig genome. Combining sequence and structure similarity search as well as class specific methods, we obtained a conservative set with a total of 3,391 structured RNA loci of which 1,011 and 2,314, respectively, hold strong sequence and structure similarity to structured RNAs in existing databases. The RNA loci cover 139 cis-regulatory element loci, 58 lncRNA loci, 11 conflicts of annotation, and 3,183 ncRNA genes. The ncRNA genes comprise 359 miRNAs, 8 ribozymes, 185 rRNAs, 638 snoRNAs, 1,030 snRNAs, 810 tRNAs and 153 ncRNA genes not belonging to the here fore mentioned classes. When running the pipeline on a local shuffled version of the genome, we obtained no matches at the highest confidence level. Additional analysis of RNA-seq data from a pooled library from 10 different pig tissues added another 165 miRNA loci, yielding an overall annotation of 3,556 structured RNA loci. This annotation represents our best effort at making an automated annotation. To further enhance the reliability, 571 of the 3,556 structured RNAs were manually curated by methods depending on the RNA class while 1,581 were declared as pseudogenes. We further created a multiple alignment of pig against 20 representative vertebrates, from which predicted 83,859 de novo RNA loci with conserved RNA structures. 528 of the predictions overlapped with the homology based annotation or novel miRNAs. We further present a substantial synteny analysis which includes 1,004 lineage specific de novo RNA loci and 4 ncRNA loci in the known annotation specific for Laurasiatheria (pig, cow, dolphin, horse, cat, dog, hedgehog).

Conclusions
We have obtained one of the most comprehensive annotations for structured ncRNAs of a mammalian genome, which is likely to play central roles in both health modelling and production. The core annotation is available in Ensembl 70 and the complete annotation is available at http://rth.dk/resources/rnannotator/susscr102/version1.02.