bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Human T-Cell Leukemia Virus Type 1 Particles by Using Cryo-Electron Tomography
Authors: Cao Sheng , Maldonado José O. , Grigsby Iwen F. , Mansky Louis M. , Zhang Wei 
Published: December 2014

ABSTRACT
The particle structure of human T-cell leukemia virus type 1 (HTLV-1) is poorly characterized. Here, we have used cryo-electron tomography to analyze HTLV-1 particle morphology. Particles produced from MT-2 cells were polymorphic, roughly spherical, and varied in size. Capsid cores, when present, were typically poorly defined polyhedral structures with at least one curved region contacting the inner face of the viral membrane. Most of the particles observed lacked a defined capsid core, which likely impacts HTLV-1 particle infectivity.
Influence of observers, threshold values, and measurement methods on volumetric analysis of cerebral aneurysms with three-dimensional rotational angiography
Authors: Cho Won-Sang , Shin Dong Hoon , Lee Joongyub , Lee Seung Jin 
Published: December 2014

IntroductionExact measurements of cerebral aneurysms are important in terms of their treatment. However, there is no definitive way to estimate the exact volume of an aneurysm. Our aim was to compare aneurysm volume measured under different conditions: threshold values, observers, and measurement methods.Methods40 aneurysms and 7 phantom models were included in the study. Three-dimensional rotational angiography was used, and volumes were compared based on the following factors: two methods (two-dimensional formula calculation and three-dimensional software measurement); three observers; and three threshold values for imaging. In addition, in the phantom models, measured volumes were compared with real volumes. The consistency of the volume measurements under different conditions was assessed using the intraclass correlation coefficient (ICC).ResultsThe consistency of the measured volumes was excellent in both the patient aneurysms (ICC >0.98) and phantom models (ICC >0.95), irrespective of the influencing factors. Median volume differences were small for observers, threshold values, and methods. When the measured and real volumes of the phantom models were compared, the software measurement achieved the highest reproducibility for real volumes compared with the formula calculation (ICC=0.86–0.93 vs 0.71–0.80).ConclusionsMeasurement of aneurysm volume showed high agreement within each influencing factor, such as methods, observers, and threshold values.
Nasopupillary Asymmetry
Authors: Arenas Eduardo , Muñoz Diana , Matheus Evelyn , Morales Diana 
Published: December 2014

Purpose. To establish the prevalence of nasopupillary asymmetry (difference in nasopupillary distances) in the population and its relation with the interpupillary distance.Methods. A retrospective descriptive study was conducted by reviewing of 1262 medical records. The values of nasopupillary asymmetry and the interpupillary distance were obtained. A statistical analysis was made and the correlation between these variables was established.Results. Seventy-nine percent of the population presented some degree of nasopupillary asymmetry. The interpupillary distance had a very low correlation with the nasopupillary asymmetry(r=0.074, P=0.0).Conclusion. It is advisable to use the nasopupillary distance of each eye as a standard measurement.
Development of a Model System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2
Authors: Geller David S. , Singh Michael Y. , Zhang Wendong , Gill Jonathan , Roth Michael E. , Kim Mimi Y. , Xie Xianhong , Singh Christopher K. , Dorfman Howard D. , Villanueva-Siles Esperanza , Park Amy , Piperdi Sajida , Gorlick Richard 
Published: December 2014

Abstract
Purpose: It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence.
Experimental Design: An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed.
Results: Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 μm resulted in local control following surgery alone. Margins greater than 36 μm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 μm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence.
Conclusions: This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model. Clin Cancer Res; 21(13); 3003–12. ©2014 AACR.
See related commentary by Weiss, p. 2889
Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype
Authors: Sawyer Sarah L. , Tian Lei , Kähkönen Marketta , Schwartzentruber Jeremy , Kircher Martin ,   University of Washington Centre for Mendelian Genomics,   FORGE Canada Consortium, Majewski Jacek , Dyment David A. , Innes A. Micheil , Boycott Kym M. , Moreau Lisa A. , Moilanen Jukka S. , Greenberg Roger A. 
Published: December 2014

Abstract
Deficiency in BRCA-dependent DNA interstrand crosslink (ICL) repair is intimately connected to breast cancer susceptibility and to the rare developmental syndrome Fanconi anemia. Bona fide Fanconi anemia proteins, BRCA2 (FANCD1), PALB2 (FANCN), and BRIP1 (FANCJ), interact with BRCA1 during ICL repair. However, the lack of detailed phenotypic and cellular characterization of a patient with biallelic BRCA1 mutations has precluded assignment of BRCA1 as a definitive Fanconi anemia susceptibility gene. Here, we report the presence of biallelic BRCA1 mutations in a woman with multiple congenital anomalies consistent with a Fanconi anemia–like disorder and breast cancer at age 23. Patient cells exhibited deficiency in BRCA1 and RAD51 localization to DNA-damage sites, combined with radial chromosome formation and hypersensitivity to ICL-inducing agents. Restoration of these functions was achieved by ectopic introduction of a BRCA1 transgene. These observations provide evidence in support of BRCA1 as a new Fanconi anemia gene (FANCS).
Significance: We establish that biallelic BRCA1 mutations cause a distinct FA-S, which has implications for risk counselling in families where both parents harbor BRCA1 mutations. The genetic basis of hereditary cancer susceptibility syndromes provides diagnostic information, insights into treatment strategies, and more accurate recurrence risk counseling to families. Cancer Discov; 5(2); 135–42. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 97
Untangling the Fiber Yarn: Butyrate Feeds Warburg to Suppress Colorectal Cancer
Authors: Sebastián Carlos , Mostoslavsky Raul 
Published: December 2014

Abstract
Summary: Dietary composition has an important role in shaping the gut microbiota. In turn, changes in the diet directly impinge on bacterial metabolites present in the intestinal lumen. Whether such metabolites play a role in intestinal cancer has been a topic of hot debate. In this issue of Cancer Discovery, Donohoe and colleagues show that dietary fiber protects against colorectal carcinoma in a microbiota-dependent manner. Furthermore, fiber-derived butyrate acts as a histone deacetylase inhibitor, inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells experiencing the Warburg effect. Cancer Discov; 4(12); 1368–70. ©2014 AACR.
See related article by Donohoe and colleagues, p. 1387
Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure
Authors: Healey Jeff S. , Brueckmann Martina , Eikelboom John W. , Ezekowitz Michael D. , Fraessdorf Mandy , Noack Herbert , Oldgren Jonas , Reilly Paul , Spyropoulos Alex C. , Wallentin Lars , Connolly Stuart J. , Douketis James D. 
Published: December 2014

SummaryIn patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain. We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders. Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p < 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs 1.8 %, p < 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p < 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/ procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.
SUBSIDIARITEIT, SOEVEREINITEIT IN EIGEN KRING EN DE BOUWFRAUDE
Authors: en Johan Graafland Mathilde Blok 
Published: December 2014

Is Nederland een fraudeland geworden? Na alle berichten over boekhoudschandalen en het bekend worden van illegale prijsafspraken is het terecht dat die vraag wordt gesteld. Het oplichten van aandeelhouders of van klanten gaat in tegen verschillende ethische noties. Het verstrekken van onjuiste informatie is niet alleen vanuit een utilistisch standpunt verwerpelijk vanwege de economische schade die ontstaat doordat een optimale marktwerking belemmerd wordt. Ook vanuit een deontologisch perspectief staan de ethische seinen op rood: het bedriegen van aandeelhouders of klanten getuigt van weinig respect en is onrechtvaardig omdat dit zelfverrijking mogelijk maakt ten koste gaat van de stakeholders. Ook vanuit het perspectief van de deugdenethiek zijn deze praktijken verwerpelijk: het achterhouden van informatie getuigt van een gebrek aan integriteit en heeft een negatieve voorbeeldfunctie naar anderen. Toch kan men zich afvragen of boekhoudschandalen niet van andere orde zijn dan de bouwfraude. Wie zich verdiept in de bouwfraude ontdekt dat de misstanden niet enkel te wijten zijn aan het gedrag van bouwondernemingen. Ook de overheid heeft in het verleden aanleiding gegeven tot de praktijk van vooroverleg en is in zekere zin medeverantwoordelijk. Om de verdeling van verantwoordelijkheden tussen overheid en bedrijven nader te analyseren, maken wij in dit artikel gebruik van twee kernbegrippen uit de reformatorische en katholieke sociale leer die nauw aan elkaar verwant zijn: het beginsel van soevereiniteit in eigen kring en het subsidiariteitsbeginsel. De beginselen kunnen worden beschouwd als richtlijnen voor de manier waarop een samenleving dient te functioneren. In de Nederlandse literatuur worden beide beginselen vaak in één adem genoemd. Echter, hoewel er duidelijke overeenkomsten zijn, kennen beide beginselen een heel verschillende levensbeschouwelijke achtergrond, die doorwerkt in de implicaties van beide beginselen. Het doel van dit artikel is beide beginselen toe te passen op de bouwfraude om de verantwoordelijkheden van bouwondernemingen en de overheid nader te bepalen.
Is Nederland een fraudeland geworden? Na alle berichten over boekhoudschandalen en het bekend worden van illegale prijsafspraken is het terecht dat die vraag wordt gesteld. Het oplichten van aandeelhouders of van klanten gaat in tegen verschillende ethische noties. Het verstrekken van onjuiste informatie is niet alleen vanuit een utilistisch standpunt verwerpelijk vanwege de economische schade die ontstaat doordat een optimale marktwerking belemmerd wordt. Ook vanuit een deontologisch perspectief staan de ethische seinen op rood: het bedriegen van aandeelhouders of klanten getuigt van weinig respect en is onrechtvaardig omdat dit zelfverrijking mogelijk maakt ten koste gaat van de stakeholders. Ook vanuit het perspectief van de deugdenethiek zijn deze praktijken verwerpelijk: het achterhouden van informatie getuigt van een gebrek aan integriteit en heeft een negatieve voorbeeldfunctie naar anderen.
Stochastically Generated North American Megadroughts
Authors: Stevenson Samantha , Timmermann Axel , Chikamoto Yoshimitsu , Langford Sally , DiNezio Pedro 
Published: December 2014

Abstract
The importance of interannual-to-decadal sea surface temperature (SST) influences on drought in the United States is examined using a suite of simulations conducted with the T31×3 resolution version of the NCAR Community Earth System Model (CESM1.0.3). The model captures tropical Pacific teleconnections to North American precipitation reasonably well, although orographic features are somewhat enhanced at higher resolution. The contribution of SST anomalies is isolated by comparing two idealized, 1000-yr CESM1.0.3 experiments: a fully coupled control and an atmosphere-only (CAM4) run forced with the SST climatology from the control. Droughts are identified using the Palmer Drought Severity Index (PDSI), which is computed over four U.S. regions from the CESM1.0.3 experiments and compared with the North American Drought Atlas (NADA). The CESM1.0.3 reproduces the persistence of NADA droughts quite well, although the model underestimates drought severity. Within the CESM1.0.3 framework, SST forcing does not significantly affect drought intensity or frequency of occurrence, even for very persistent “megadroughts” of 15 yr or more in length. In both the CESM1.0.3 and NADA, with the exception of the Southeast United States, droughts in all regions have intensities, persistence lengths, and occurrence frequencies statistically consistent with a red noise null hypothesis. This implies that SST forcing is not the dominant factor in generating drought and therefore that many decadal megadroughts are caused by a combination of internal atmospheric variability and coupling with the land surface, with SST anomalies playing only a secondary role.
Significant Influences of Global Mean Temperature and ENSO on Extreme Rainfall in Southeast Asia
Authors: Villafuerte Marcelino Q. , Matsumoto Jun 
Published: December 2014

Abstract
This study investigates the changes in annual and seasonal maximum daily rainfall (RX1day) in Southeast Asia, obtained from gauge-based gridded precipitation data, to address the increasing concerns about climate change in the region. First, the nonparametric Mann–Kendall test was employed to detect significant trends in RX1day. Then, maximum likelihood modeling, which allows the incorporation of covariates in the location parameter of the generalized extreme value (GEV) distribution, was conducted to determine whether the rising global mean temperature, as well as El Niño–Southern Oscillation (ENSO), is influencing extreme rainfall over the region. The findings revealed that annual and seasonal RX1day is significantly increasing in Indochina and east-central Philippines while decreasing in most parts of the Maritime Continent during the past 57 yr (1951–2007). The trends in RX1day were further linked to the rising global mean temperature. It was shown that the location parameter of the GEV—and hence the RX1day on average—has significantly covaried with the annually averaged near-surface global mean temperature anomaly. Such covariation is pronouncedly observed over the regions where significant trends in RX1day were detected. Furthermore, the results demonstrated that, as ENSO develops in July–September, negative covariations between the location parameter of the GEV and the ENSO index, implying a higher (lower) likelihood of extreme rainfall during La Niña (El Niño), were observed over the Maritime Continent. Such conditions progress northward to the regions of Indochina and the Philippines as ENSO approaches its maturity in October–December and then retreat southward as the ENSO weakens in the ensuing seasons.
Neurenteric cyst presenting with stridor and dysphagia: case report and literature review
Authors: Visvanathan V , Crowther J , Taylor William 
Published: December 2014

Objective Neurenteric cysts are rare lesions that account for 0.7–1.3% of all spinal cord tumours. We report the first ever case of a neurenteric cyst presenting with stridor and dysphagia. A literature review on the presentation and management of these lesions is also included. Methods A MEDLINE search of articles using the terms ‘neurenteric cyst’, ‘intraspinal cyst’, ‘enterogenous cyst’, ‘intramedullary cyst’ along with diagnosis, presentation and management was performed. Suitable references from these articles were also reviewed. Results All published evidence on neurenteric cysts are either case series or case reports (level IV/V) with the largest case series reporting 23 patients from a single institution. Conclusion Neurenteric cysts are rare spinal cord lesions that usually present with focal neurological signs and managed within neurosurgical units. This is the first reported case of a neurenteric cyst presenting with upper aerodigestive tract symptoms warranting specialist ear, nose and throat input.
Radiographic Results After Hallux Metatarsophalangeal Joint Arthrodesis for Hallux Varus
Authors: Geaney Lauren E. , Myerson Mark S. 
Published: December 2014

Background: Hallux metatarsophalangeal (MP) joint arthrodesis for hallux varus is generally reserved for severe deformity, failed surgery or the development of osteoarthritis. The purpose of this study was to determine the radiologic results of arthrodesis of the hallux MP joint following treatment for hallux varus. Our hypothesis was that in the process of correcting the hallux valgus angle, the 1-2 intermetatarsal angle (1-2 IMA) and hallux valgus angle (HVA) will be improved due to correction of the deforming forces. Methods: A retrospective review was performed on 26 patients with 29 feet that had symptomatic hallux varus deformities treated with arthrodesis of the hallux MP joint between September 1, 2002, and December 31, 2012. The 1-2 IMA and HVA were measured on the preoperative and most recent postoperative films and compared. Twenty-nine patients were followed with postoperative weight-bearing radiographs. Two were men and 24 were women. Twelve were performed on the right foot, 17 on the left, including 3 bilateral cases. Fourteen patients had concomitant procedures on the ipsilateral forefoot. Results: The average 1-2 IMA changed from 4.8 degrees to 8.4 degrees, a difference of 3.6 degrees ( P < .05), and the average HVA changed from −20.7 degrees to 8.1 degrees ( P < .05). Conclusion: Our study showed that a hallux MP joint arthrodesis in patients with hallux varus resulted in a predictable increase in the 1-2 IMA. Level of Evidence: Level IV, case series.
Therapy for myeloproliferative neoplasms: when, which agent, and how?
Authors: Geyer Holly L. , Mesa Ruben A. 
Published: December 2014

Abstract
Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.
Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial
Authors: Roberts Ian , Prieto-Merino David , Manno Daniela 
Published: December 2014

Abstract
Introduction
To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days.

Methods
Exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov NCT00375258.

Results
The effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury (HR ≤3 hours = 0.78, 0.68 to 0.90; HR >3 hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise.

Conclusions
Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury.