bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entry of a Recombinant, Full-Length, Atoxic Tetanus Neurotoxin into Neuro-2a Cells
Authors: Blum Faith C. , Przedpelski Amanda , Tepp William H. , Johnson Eric A. , Barbieri Joseph T. 
Published: December 2013

ABSTRACT
Tetanus neurotoxin (TeNT) and botulinum neurotoxin (BoNT) are clostridial neurotoxins (CNTs) responsible for the paralytic diseases tetanus and botulism, respectively. CNTs are AB toxins with an N-terminal zinc-metalloprotease light chain that is linked by a disulfide bond to a C-terminal heavy chain that includes a translocation domain and a receptor-binding domain (HCR). Current models predict that the HCR defines how CNTs enter and traffic in neurons. Recent studies implicate that domains outside the HCR contribute to CNT trafficking in neurons. In the current study, a recombinant, full-length TeNT derivative, TeNT(RY), was engineered to analyze TeNT cell entry. TeNT(RY) was atoxic in a mouse challenge model. Using Neuro-2a cells, a mouse neuroblastoma cell line, TeNT HCR (HCR/T) and TeNT(RY) were found to bind gangliosides with similar affinities and specificities, consistent with the HCR domain containing receptor binding function. Temporal studies showed that HCR/T and TeNT(RY) entered Neuro-2a cells slower than the HCR of BoNT/A (HCR/A), transferrin, and cholera toxin B. Intracellular localization showed that neither HCR/T nor TeNT(RY) localized with HCR/A or synaptic vesicle protein 2, the protein receptor for HCR/A. HCR/T and TeNT(RY) exhibited only partial intracellular colocalization, indicating that regions outside the HCR contribute to the intracellular TeNT trafficking. TeNT may require this complex functional entry organization to target neurons in the central nervous system.
Rb Loss Is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma
Authors: Tan Hsueh-Li , Sood Akshay , Rahimi Hameed A. , Wang Wenle , Gupta Nilesh , Hicks Jessica , Mosier Stacy , Gocke Christopher D. , Epstein Jonathan I. , Netto George J. , Liu Wennuan , Isaacs William B. , De Marzo Angelo M. , Lotan Tamara L. 
Published: December 2013

Abstract
Purpose: Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor.
Experimental Design: We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin-fixed paraffin-embedded specimens.
Results: We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in 63% of small cell carcinomas (17 of 27), with 38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation.
Conclusions: Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target. Clin Cancer Res; 20(4); 890–903. ©2013 AACR.
Teaching an Old Dog New Tricks: Drug Repositioning in Small Cell Lung Cancer
Authors: Wang Jing , Byers Lauren Averett 
Published: December 2013

Abstract
Summary: Jahchan and colleagues report the use of a biostatistical analysis to identify effective therapeutics for small cell lung cancer (SCLC). Their results reveal a new use for the tricyclic antidepressant imipramine in SCLC and shed light on the therapeutic potential of drug repositioning in cancer and other diseases. Cancer Discov; 3(12); 1333–5. ©2013 AACR.
See related article by Jahchan et al., p. 1364
Nasal Endoscopy Is Recommended for Diagnosing Adults with Chronic Rhinosinusitis
Authors: Wuister Annemarie M. H. , Goto Namiko A. , Oostveen E. J. , de Jong Werner U. , van der Valk Eline S. , Kaper Nina M. , Aarts Mark C. J. , Grolman Wilko , van der Heijden Geert J. M. G. 
Published: December 2013

ObjectiveTo assess the diagnostic value of nasal endoscopic findings in adults suspected of chronic rhinosinusitis.Data SourcesPubMed, EMBASE, and the Cochrane Library.Review MethodsA comprehensive search was performed up to March 5, 2013. Articles that assessed the diagnostic value of nasal endoscopy in adults suspected of chronic rhinosinusitis were included. For selected articles, the study design was assessed for directness of evidence and risk of bias. Prevalence, positive, and negative predictive values were extracted from reported data.ResultsOut of 3899 unique publications, we included 3 diagnostic studies with a high directness of evidence and a low or moderate risk of bias for data extraction. They showed a prevalence of chronic rhinosinusitis (diagnosed with computed tomography) of. 40 to. 56. Compared with posterior probabilities we found an added value for ruling in chronic rhinosinusitis by a positive nasal endoscopy of 25% to 28% and an added value for ruling out chronic rhinosinusitis by a negative nasal endoscopy of 5% to 30%.Conclusion and RecommendationComputed tomography is not considered necessary in case of a positive nasal endoscopy. While nasal endoscopy cannot rule out chronic rhinosinusitis, we advise computed tomography only for patients with a prolonged or complicated course of rhinosinusitis.
Objective duplex ultrasound evaluation of the extracranial circulation in multiple sclerosis patients undergoing venoplasty of internal jugular vein stenoses: A pilot study
Authors: Thibault P , Lewis W , Niblett S 
Published: December 2013

Objective Chronic cerebrospinal venous insufficiency (CCSVI) is a condition associated with multiple sclerosis (MS) and manifested by stenoses in the extracranial venous circulation. There is a need for an objective non-invasive assessment of CCSVI that is able to accurately identify the location of stenoses and quantify physiological changes in blood flows following treatment. Method A duplex ultrasound method, extracranial duplex ultrasound (ECDU), is described where the internal jugular veins (IJVs) and vertebral veins (VVs) were examined in the supine and sitting position before and after venoplasty in eight patients with clinically diagnosed MS. High-resolution B-mode imaging was used to detect obvious stenoses, intra-luminal membranes, valve abnormalities and vein wall thickening. ECDU was then used to assess blood flow including reflux. To assess obstruction, venous blood volume flows (BVFs) were taken bilaterally from the proximal (J1), mid (J2) and distal (J3) segments of the IJVs and the mid cervical VVs. To assess cerebral perfusion, bilateral BVF measurements were taken, in the supine position only, from the proximal internal carotid arteries (ICA) and mid cervical vertebral arteries (VA). The global arterial cerebral blood flow (GACBF) was then calculated as the sum of the ICA and VA measurements. Results Pre-venography ECDU detected IJV stenoses or obstruction in all patients. Venography findings were consistent with those of the pre-treatment ECDU with the exception of the detection of bilateral IJV stenoses in two patients diagnosed with unilateral IJV stenosis by ECDU. A significant improvement in GACBF was evident following venoplasty ( p < 0.05). A trend to improvement in the post-treatment BVFs of both the IJVs and the mid cervical VVs was also observed. This improvement was most marked in the left VVs ( p = 0.052) and the J2 segment of right IJVs ( p < 0.05). Conclusion The ECDU examination described provides a reliable objective assessment of IJV and VV stenoses and, with the use of BVFs, can quantify the degree of obstruction. These results support the use of ECDU as a non-invasive post-operative assessment of the success of venoplasty. The ability of ECDU to measure GACBF provides an additional parameter to monitor vascular pathophysiology in MS patients. The current findings support the view that the early symptomatic benefits observed after venoplasty for stenoses in the extracranial venous circulation may be the result of increased cerebral perfusion.
A randomized trial of telephone-based motivational interviewing for adolescent chronic headache with medication overuse
Authors: Stevens Jack , Hayes John , Pakalnis Ann 
Published: December 2013

Introduction Nearly 2% of youths suffer from chronic migraine or chronic tension-type headache (CTTH). A contributing factor in approximately 20%–50% of these youths is medication overuse, which involves taking analgesics three or more times per week for three months. The objective of this study was to test motivational interviewing (MI) as an approach to promote adherence to recommendations regarding not only analgesic overuse but also other aspects of treatment plans. Methods A randomized controlled trial was conducted comparing the experimental condition (standard of care clinic-based treatment with supplemental MI phone calls; n = 24) to a control condition (standard of care clinic-based treatment without these supplemental MI phone calls; n = 23). Four months after enrollment, a research assistant who was blinded to study condition telephoned adolescents inquiring about headache frequency, headache severity, and disability. Results Headache frequency was lower in the experimental condition versus control condition for those with relatively lower initial levels of headache frequency. In contrast, we did not find greater improvement in headache severity and disability for the experimental condition relative to the control condition. Discussion Our findings provided some preliminary, albeit limited, support for MI as an approach to improve outcomes for adolescent medication-overuse headache (MOH).
Increased Risk of Revision With Hamstring Tendon Grafts Compared With Patellar Tendon Grafts After Anterior Cruciate Ligament Reconstruction
Authors: Persson Andreas , Fjeldsgaard Knut , Gjertsen Jan-Erik , Kjellsen Asle B. , Engebretsen Lars , Hole Randi M. , Fevang Jonas M. 
Published: December 2013

Background: The graft choice for anterior cruciate ligament reconstruction (ACLR) is controversial. Hamstring tendon (HT) autografts and patellar tendon (PT) autografts are the most common grafts used and have shown similar subjective and objective outcomes. Purpose: To compare the revision rate between HT and PT autografts used in ACLR in Norway and to estimate the influence of patient age and sex. Study Design: Cohort study; Level of evidence, 2. Methods: The study included all patients who underwent primary ACLR without concomitant ligament injuries registered in the Norwegian Knee Ligament Registry from 2004 through 2012. The cohort was stratified by age group (15-19, 20-29, and ≥30 years) and autograft type (HT or PT). Revision rates at 1, 2, and 5 years were calculated using the Kaplan-Meier analysis, and hazard ratios (HRs) for revision were calculated using multivariate Cox regression models. Results: With a mean follow-up of 4.0 years, 12,643 primary ACLRs were identified, with 3428 PT and 9215 HT grafts, among which 69 revisions with PT grafts and 362 revisions with HT grafts were performed. The overall 5-year revision rate was 4.2%. A higher revision rate was recorded for HT versus PT grafts at all follow-up times. When adjusted for sex, age, and type of graft, the HR for revision was 2.3 (95% CI, 1.8-3.0) for HT grafts compared with PT grafts. The HR for revision in the youngest age group was 4.0 (95% CI, 3.1-5.2) compared with the oldest age group. Sex had no effect on the revision rate. Conclusion: Patients with HT grafts had twice the risk of revision compared with patients with PT grafts. Younger age was the most important risk factor for revision, and no effect was seen for sex. Further studies should be conducted to identify the cause of the increased revision rate found for HT grafts.
Theses on the Philosophy of History: The Work of Research in the Age of Digital Searchability and Distributability
Authors: Smith Marquard 
Published: December 2013

What is it to conduct research in the second decade of the 21st century? What is the nature (or what are the modalities) of the work that we as researchers do? What is research as a praxis? And how have recent shifts in paradigms of knowledge generation and distribution – especially around the archive and the Internet, and the Internet as archival – transformed profoundly what we as researchers do, how we do it, and in fact even our very capacity to do it? In this article, I begin from the idea of research as a praxis, and from the figure of the researcher as a locus for the discovery of knowledges by way of acts of searching and gathering. In 15 theses I engage critically with challenges raised recently for the idea of ‘history’ as a form of knowledge by our own épistémè of re-search; one whose conditions and conditions of possibility are delineated by the emergence of our late capitalist global algorithmic knowledge economy, and the Internet with its distinct operations of searchability and distributability. Because this is our present moment’s épistémè of re-search, I argue that our being in thrall of the archive has dangerous future consequences: in fact it is perilous for the very idea of the future itself as a category of historical time. Concerned by this situation and thus responding forcefully to it, in offering a few grains of dissent I will ‘look with care’ at how we might navigate our way fractiously and thus productively through such a predicament.
Usefulness of fitness testing to establish metabolic syndrome in perimenopausal Moroccan women
Authors: Aparicio Virginia A , Carbonell-Baeza Ana , Senhaji Meftaha , Martín Sandra , Camiletti-Moirón Daniel , Aranda Pilar 
Published: December 2013

Background:The use of fitness testing for the identification of women at high-risk of metabolic syndrome (MS), and therefore of cardiovascular disease, is clinically relevant.Objective:The purpose of this study was to determine the ability of a set of physical fitness tests to establish the risk of MS in perimenopausal Moroccan women.Methods:The study comprised 151 women (45–65 years) from the North of Morocco. We used standardized field-based fitness tests to assess cardiorespiratory fitness, muscular strength, flexibility and balance. Fatness was assessed by impedanciometry and anthropometry. We also measured resting heart rate, blood pressure and plasma fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol and triglycerides.Results:Women with MS performed worse in most of the fitness tests studied. Among the fitness test studied, the six-minute walk test was the most associated to MS. Receiver operating characteristics curve analyses revealed that the six-minute walk test threshold that best discriminated between the presence and absence of MS was 480.5 m (area under curve (AUC): 0.719, 95% confidence interval (CI): 0.62–0.82; p<0.001). Logistic regression after adjustment for age and weight showed that a distance ≤480 m is associated with 2.9 times higher risk (95% CI: 1.56–7.65; p<0.05) for having MS.Conclusions:Including cardiorespiratory fitness as a MS risk factor may improve early identification of at-risk Moroccan women. Fitness testing provides useful information and is cheap, easy to perform, and not time-consuming, which makes its use in this specific clinical settings feasible.
Anatomy and Histology of the Knee Anterolateral Ligament
Authors: Helito Camilo Partezani , Demange Marco Kawamura , Bonadio Marcelo Batista , Tírico Luis Eduardo Passarelli , Gobbi Riccardo Gomes , Pécora José Ricardo , Camanho Gilberto Luis 
Published: December 2013

Background: Reconstruction of the anterior cruciate ligament (ACL) is one of the most common procedures in orthopaedic surgery. However, even with advances in surgical techniques and implants, some patients still have residual anterolateral rotatory laxity after reconstruction. A thorough study of the anatomy of the anterolateral region of the knee is needed. Purpose: To study the anterolateral region and determine the measurements and points of attachments of the anterolateral ligament (ALL). Study Design: Descriptive laboratory study. Methods: Dissections of the anterolateral structures of the knee were performed in 20 human cadavers. After isolating the ALL, its length, thickness, width, and points of attachments were determined. The femoral attachment of the ALL was based on the anterior-posterior and proximal-distal distances from the attachment of the lateral collateral ligament (LCL). The tibial attachment point was based on the distance from the Gerdy tubercle to the fibular head and the distance from the lateral tibial plateau. The ligaments from the first 10 dissections were sent for histological analysis. Results: The ALL was found in all 20 knees. The femoral attachment of the ALL at the lateral epicondyle averaged 3.5 mm distal and 2.2 mm anterior to the attachment of the LCL. Two distal attachments were observed: one inserts into the lateral meniscus, the other between the Gerdy tubercle and the fibular head, approximately 4.4 mm distal to the tibial articular cartilage. The mean measurements for the ligament were 37.3 mm (length), 7.4 mm (width), and 2.7 mm (thickness). The histological analysis of the ligaments revealed dense connective tissue. Conclusion: The ALL is consistently present in the anterolateral region of the knee. Its attachment to the femur is anterior and distal to the attachment of the LCL. Moving distally, it bifurcates at close to half of its length. The ALL features 2 distal attachments, one at the lateral meniscus and the other between the Gerdy tubercle and the fibular head. Clinical Relevance: The ALL may be important in maintaining normal rotatory limits of knee motion; ALL rupture could be responsible for rotatory laxity after isolated intra-articular reconstruction of the ACL.
Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways
Authors: Beck Florian , Geiger Jörg , Gambaryan Stepan , Veit Johannes , Vaudel Marc , Nollau Peter , Kohlbacher Oliver , Martens Lennart , Walter Ulrich , Sickmann Albert , Zahedi René P. 
Published: December 2013

Key PointsFirst comprehensive and time-resolved characterization of platelet cAMP/PKA signaling upon iloprost treatment. More than 2700 phosphorylation sites quantified between 4 time points and from 3 individual healthy donors.
DNA transposon-based gene vehicles - scenes from an evolutionary drive
Authors: Skipper Kristian Alsbjerg , Andersen Peter Refsing , Sharma Nynne , Mikkelsen Jacob Giehm 
Published: December 2013

Abstract
DNA transposons are primitive genetic elements which have colonized living organisms from plants to bacteria and mammals. Through evolution such parasitic elements have shaped their host genomes by replicating and relocating between chromosomal loci in processes catalyzed by the transposase proteins encoded by the elements themselves. DNA transposable elements are constantly adapting to life in the genome, and self-suppressive regulation as well as defensive host mechanisms may assist in buffering ‘cut-and-paste’ DNA mobilization until accumulating mutations will eventually restrict events of transposition. With the reconstructed Sleeping Beauty DNA transposon as a powerful engine, a growing list of transposable elements with activity in human cells have moved into biomedical experimentation and preclinical therapy as versatile vehicles for delivery and genomic insertion of transgenes. In this review, we aim to link the mechanisms that drive transposon evolution with the realities and potential challenges we are facing when adapting DNA transposons for gene transfer. We argue that DNA transposon-derived vectors may carry inherent, and potentially limiting, traits of their mother elements. By understanding in detail the evolutionary journey of transposons, from host colonization to element multiplication and inactivation, we may better exploit the potential of distinct transposable elements. Hence, parallel efforts to investigate and develop distinct, but potent, transposon-based vector systems will benefit the broad applications of gene transfer. Insight and clever optimization have shaped new DNA transposon vectors, which recently debuted in the first DNA transposon-based clinical trial. Learning from an evolutionary drive may help us create gene vehicles that are safer, more efficient, and less prone for suppression and inactivation.
The relevance of socio-demographic and occupational variables for the assessment of work-related stress risk
Authors: Marinaccio Alessandro , Ferrante Pierpaolo , Corfiati Marisa , Di Tecco Cristina , Rondinone Bruna M , Bonafede Michela , Ronchetti Matteo , Persechino Benedetta , Iavicoli Sergio 
Published: December 2013

Abstract

Background
Work-related stress is widely recognized as one of the major challenges to occupational health and safety. The correlation between work-related stress risk factors and physical health outcomes is widely acknowledged. This study investigated socio-demographic and occupational variables involved in perceived risk of work-related stress.

Methods
The Italian version of the Health and Safety Executive Management Standards Indicator Tool was used in a large survey to examine the relationship between work-related stress risks and workers’ demographic and occupational characteristics. Out of 8,527 questionnaires distributed among workers (from 75 organizations) 6,378 were returned compiled (74.8%); a set of mixed effects models were adopted to test single and combined effects of the variables on work-related stress risk.

Results
Female workers reported lower scores on control and peer support and more negative perceptions of relationships and change at work than male workers, most of them with full-time contracts. Age, job seniority, and educational level appeared positively correlated with control at work, but negatively with job demands. Fixed-term workers had positive perceptions regarding job demands and relationships, but more difficulties about their role at work than permanent workers. A commuting time longer than one hour and shift work appeared to be associated with higher levels of risk factors for work-related stress (except for role), the latter having more negative effects, increasing with age.

Conclusions
The findings suggest that the assessment and management of work-related stress risk should consider specific socio-demographic and occupational risk factors such as gender, age, educational level, job status, shift work, commuting time, job contracts.