bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic Prophylaxis Regimens in Trauma and Orthopaedic Surgery
Authors: Tucker Adam , Henderson L. , Moffatt R. , Abela R. , Troughton J. , McMullan R. , Wilson A. 
Published: November 2015

Trauma, elective orthopaedics, and an aging population will result in an increasing health burden and work load. The move to surgical podiatrists in the National Health Service within the United Kingdom will shift the surgical workload away from orthopaedic surgeons. A devastating complication of foot and ankle surgery is postoperative infection. While postoperative infection is multifactorial in etiology, concomitant diabetes mellitus increases the general risk of trauma and orthopaedic surgical site infections up to 8-fold. We therefore undertook a prospective study of our unit antibiotic prophylaxis regimes. Fifty patients participated. Swabs were obtained using aseptic technique from the plantar aspect of the feet, between the toes, and subsequently cultured on agar plates. Specimens were then incubated for 48 hours before being exposed to antibiotic plates. Cultured organisms were classified as susceptible to an antibiotic regimen if susceptibility to cefuroxime, or susceptibility to either drug of the flucloxacillin/gentamicin combination, was demonstrated. Statistical analysis e was performed. A P value <.05 was considered significant. Fifty patients were recruited, 26 (52%) were male. Mean age of 53 ± 19.4 years. The cohort included 15 diabetic, of which 11 (73.3%) insulin-dependent, and 35 nondiabetic patients. Comparing flucloxacillin/gentamicin against cefuroxime overall, susceptibility was noted in 84% and 70%, respectively (P = .096). Resistance to cefuroxime was significantly higher in diabetics than in nondiabetics (53% vs 25%, P = .046). The same pattern was observed for the flucloxacillin/gentamicin regimen (33% vs 9%, P = .049). While both regimens are active against colonizing organisms in this prospective observational study, flucloxacillin and gentamicin provide greater coverage overall. We have demonstrated that the use of flucloxacillin/gentamicin provides better coverage against commensal bacterial flora compared with cefuroxime alone. This is of even greater importance in the case of the specific high-risk subgroups, such as diabetic patients. Levels of Evidence: Level IV: Case Series
Combinatorial targeting of nuclear export and translation of RNA inhibits aggressive B-cell lymphomas
Authors: Culjkovic-Kraljacic Biljana , Fernando Tharu M. , Marullo Rossella , Calvo-Vidal Nieves , Verma Akanksha , Yang ShaoNing , Tabbò Fabrizio , Gaudiano Marcello , Zahreddine Hiba , Goldstein Rebecca L. , Patel Jayeshkumar , Taldone Tony , Chiosis Gabriela , Ladetto Marco , Ghione Paola , Machiorlatti Rodolfo , Elemento Olivier , Inghirami Giorgio , Melnick Ari , Borden Katherine L. B. , Cerchietti Leandro 
Published: November 2015

Key Points
eIF4E, a protein highly elevated in poor-prognostic lymphomas, simultaneously sustains expression of known driver oncogenes BCL6, BCL2, MYC. The tumorigenic form of Hsp90 is a novel partner protein in the process underlying a new therapeutic strategy for these aggressive lymphomas.
Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease
Authors: Solomon Joshua J. , Chung Jonathan H. , Cosgrove Gregory P. , Demoruelle M. Kristen , Fernandez-Perez Evans R. , Fischer Aryeh , Frankel Stephen K. , Hobbs Stephen B. , Huie Tristan J. , Ketzer Jill , Mannina Amar , Olson Amy L. , Russell Gloria , Tsuchiya Yutaka , Yunt Zulma X. , Zelarney Pearlanne T. , Brown Kevin K. , Swigris Jeffrey J. 
Published: November 2015

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a “definite” or “possible” usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.
A voyage to Terra Australis: human-mediated dispersal of cats
Authors: Koch K. , Algar D. , Searle J. B. , Pfenninger M. , Schwenk K. 
Published: November 2015

AbstractBackgroundCats have been transported as human commensals worldwide giving rise to many feral populations. In Australia, feral cats have caused decline and extinction of native mammals, but their time of introduction and origin is unclear. Here, we investigate hypotheses of cat arrival pre- or post-European settlement, and the potential for admixture between cats of different invasion events. We analyse the genetic structure and diversity of feral cats from six locations on mainland Australia, seven Australian islands and samples from Southeast Asia and Europe using microsatellite and mitochondrial DNA data.ResultsOur results based on phylogeographic model selection are consistent with a European origin of cats in Australia. We find genetic distinctiveness of Australian mainland samples compared with Dirk Hartog Island, Flinders Island, Tasman Island and Cocos (Keeling) Island samples, and genetic similarities between some of the island populations. Historical records suggest that introduction of cats to these islands occurred at the time of European exploration and/or in connection with the pearling, whaling and sealing trades early in the 19th century. On-going influx of domestic cats into the feral cat population is apparently causing the Australian mainland populations to be genetically differentiated from those island populations, which likely are remnants of the historically introduced cat genotypes.ConclusionA mainly European origin of feral cats in Australia, with possible secondary introductions from Asia following the initial establishment of cats in Australia is reasonable. The islands surrounding Australia may represent founding populations and are of particular interest. The results of the study provide an important timeframe for the impact of feral cats on native species in Australia.
Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?
Authors: Carr Anitra C. , Shaw Geoffrey M. , Fowler Alpha A. , Natarajan Ramesh 
Published: November 2015

AbstractSevere systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.
Survival and Clinical Outcomes in Surgically Treated Patients With Metastatic Epidural Spinal Cord Compression: Results of the Prospective Multicenter AOSpine Study
Authors: Fehlings Michael G. , Nater Anick , Tetreault Lindsay , Kopjar Branko , Arnold Paul , Dekutoski Mark , Finkelstein Joel , Fisher Charles , France John , Gokaslan Ziya , Massicotte Eric , Rhines Laurence , Rose Peter , Sahgal Arjun , Schuster James , Vaccaro Alexander 
Published: November 2015

Purpose Although surgery is used increasingly as a strategy to complement treatment with radiation and chemotherapy in patients with metastatic epidural spinal cord compression (MESCC), the impact of surgery on health-related quality of life (HRQoL) is not well established. We aimed to prospectively evaluate survival, neurologic, functional, and HRQoL outcomes in patients with MESCC who underwent surgical management. Patients and Methods One hundred forty-two patients with a single symptomatic MESCC lesion who were treated surgically were enrolled onto a prospective North American multicenter study and were observed at least up to 12 months. Clinical data, including Brief Pain Inventory, ASIA (American Spinal Injury Association) impairment scale, SF-36 Short Form Health Survey, Oswestry Disability Index, and EuroQol 5 dimensions (EQ-5D) scores, were obtained preoperatively, and at 6 weeks and 3, 6, 9, and 12 months postoperatively. Results Median survival time was 7.7 months. The 30-day and 12-month mortality rates were 9% and 62%, respectively. There was improvement at 6 months postoperatively for ambulatory status (McNemar test, P < .001), lower extremity and total motor scores (Wilcoxon signed rank test, P < .001), and at 6 weeks and 3, 6, and 12 months for Oswestry Disability Index, EQ-5D, and pain interference (paired t test, P < .013). Moreover, at 3 months after surgery, the ASIA impairment scale grade was improved (Stuart-Maxwell test P = .004). SF-36 scores improved postoperatively in six of eight scales. The incidence of wound complications was 10% and 2 patients required a second surgery (screw malposition and epidural hematoma). Conclusion Surgical intervention, as an adjunct to radiation and chemotherapy, provides immediate and sustained improvement in pain, neurologic, functional, and HRQoL outcomes, with acceptable risks in patients with a focal symptomatic MESCC lesion who have at least a 3 month survival prognosis.
Prospective Evaluation of the 21-Gene Recurrence Score Assay for Breast Cancer Decision-Making in Ontario
Authors: Levine Mark N. , Julian Jim A. , Bedard Philippe L. , Eisen Andrea , Trudeau Maureen E. , Higgins Brian , Bordeleau Louise , Pritchard Kathleen I. 
Published: November 2015

Purpose To evaluate the 21-gene recurrence score (RS) on decision-making in a population-based cohort. Patients and Methods Patients with axillary node-negative or nodal micrometastases, estrogen receptor–positive, and human epidermal growth factor receptor 2–negative breast cancer being considered for chemotherapy were eligible. All cancer treatment centers in Ontario, Canada, participated. Oncologists made a preliminary recommendation for endocrine therapy with or without chemotherapy on the basis of Adjuvant! Online (AOL) risk estimation. Patients were asked for their preference regarding chemotherapy. After RSs were available, patients returned for final decision-making. Patient satisfaction was measured by using the decisional conflict scale. Results Between January 2012 and July 2013, 1,000 patients were recruited. RSs were available for 979 patients. In 58% of patients, risk was categorized as low (RS, 0 to 18); in 33%, intermediate (RS, 19 to 30); and in 9%, high (RS, ≥ 31). Oncologists' recommendations pretest and post-test remained the same in 464 patients (48%), changed from unsure or chemotherapy to no chemotherapy in 365 (38%), and changed from unsure or no chemotherapy to chemotherapy in 143 (15%). After the test, oncologists recommended chemotherapy for 236 patients, 81% of whom received chemotherapy. Of 151 patients in whom risk was classified as intermediate by means of AOL, 41% were a low risk and 44% intermediate risk with RS. Of 298 patients at high risk with AOL, 16% had a high risk RS. None of 236 patients with grade I tumors had a high-risk RS. Mean total decisional conflict scale score significantly improved from pretest to post-test from 34 to 19 (P < .001). Conclusion The RS substantially influenced both oncologists' recommendations and patients' preferences for chemotherapy. The major effect was avoidance of chemotherapy when AOL indicated high or intermediate risk.
Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease
Authors: Geyer Holly , Scherber Robyn , Kosiorek Heidi , Dueck Amylou C. , Kiladjian Jean-Jacques , Xiao Zhijian , Slot Stefanie , Zweegman Sonja , Sackmann Federico , Fuentes Ana Kerguelen , Hernández-Maraver Dolores , Döhner Konstanze , Harrison Claire N. , Radia Deepti , Muxi Pablo , Besses Carlos , Cervantes Francisco , Johansson Peter L. , Andreasson Bjorn , Rambaldi Alessandro , Barbui Tiziano , Bonatz Karin , Reiter Andreas , Boyer Francoise , Etienne Gabriel , Ianotto Jean-Christophe , Ranta Dana , Roy Lydia , Cahn Jean-Yves , Maldonado Norman , Barosi Giovanni , Ferrari Maria L. , Gale Robert Peter , Birgegard Gunnar , Xu Zefeng , Zhang Yue , Sun Xiujuan , Xu Junqing , Zhang Peihong , te Boekhorst Peter A.W. , Commandeur Suzan , Schouten Harry , Pahl Heike L. , Griesshammer Martin , Stegelmann Frank , Lehmann Thomas , Senyak Zhenya , Vannucchi Alessandro M. , Passamonti Francesco , Samuelsson Jan , Mesa Ruben A. 
Published: November 2015

Purpose Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden. Patients and Methods Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly). Results The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S). Conclusion The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.
Racial Variation in the Uptake of Oncotype DX Testing for Early-Stage Breast Cancer
Authors: Roberts Megan C. , Weinberger Morris , Dusetzina Stacie B. , Dinan Michaela A. , Reeder-Hayes Katherine E. , Carey Lisa A. , Troester Melissa A. , Wheeler Stephanie B. 
Published: November 2015

Purpose Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake. Methods We used data from the Carolina Breast Cancer Study, phase III, a longitudinal, population-based study of 2,998 North Carolina women who received a diagnosis of breast cancer between 2008 and 2014. Our primary analysis used modified Poisson regression to determine the association between race and whether ODX testing was ordered among two strata: node-negative and node-positive breast cancer. Results A total of 1,468 women with estrogen receptor–positive, human epidermal growth factor receptor-2–negative, stage I or II breast cancer met inclusion criteria. Black patients had higher-grade and larger tumors, more comorbidities, younger age at diagnosis, and lower socioeconomic status than non-black women. Overall, 42% of women had ODX test results in their pathology reports. Compared with those who did not receive ODX testing, women who received ODX testing tended to be younger and have medium tumor size and grade. Our regression analyses indicated no racial disparities in ODX uptake among node-negative patients. However, racial differences were detected among node-positive patients, with black patients being 46% less likely to receive ODX testing than non-black women (adjusted relative risk, 0.54; 95% CI, 0.35 to 0.84; P = .006). Conclusion We did not find racial disparities in ODX testing for node-negative patients for whom ODX testing is guideline recommended and widely covered by insurers. However, our findings suggest that a newer, non–guideline-concordant application of ODX testing for node-positive breast cancer was accessed less by black women than by non-black women, reflecting more guideline concordant care among black women.
DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer
Authors: Thorsen Lise Bech Jellesmark , Offersen Birgitte Vrou , Danø Hella , Berg Martin , Jensen Ingelise , Pedersen Anders Navrsted , Zimmermann Sune Jürg , Brodersen Hans-Jürgen , Overgaard Marie , Overgaard Jens 
Published: November 2015

Purpose It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer. Patients and Methods In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat. Results A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease. Conclusion In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer.
VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling
Authors: Benn Andreas , Bredow Clara , Casanova Isabel , Vukičević Slobodan , Knaus Petra 
Published: November 2015

ABSTRACT
Several vascular disorders, such as aberrant angiogenesis, atherosclerosis and pulmonary hypertension, have been linked to dysfunctional BMP signaling. Vascular hyperpermeability via distortion of endothelial cell adherens junctions is a common feature of these diseases, but the role of BMPs in this process has not been investigated. BMP signaling is initiated by binding of ligand to, and activation of, BMP type I (BMPRI) and type II (BMPRII) receptors. Internalization of VE-cadherin as well as c-Src kinase-dependent phosphorylation have been implicated in the loosening of cell–cell contacts, thereby modulating vascular permeability. Here we demonstrate that BMP6 induces hyperpermeabilization of human endothelial cells by inducing internalization and c-Src-dependent phosphorylation of VE-cadherin. Furthermore, we show BMP-dependent physical interaction of VE-cadherin with the BMP receptor ALK2 (BMPRI) and BMPRII, resulting in stabilization of the BMP receptor complex and, thereby, the support of BMP6-Smad signaling. Our results provide first insights into the molecular mechanism of BMP-induced vascular permeability, a hallmark of various vascular diseases, and provide the basis for further investigations of BMPs as regulators of vascular integrity, both under physiological and pathophysiological conditions.
Convergence of joint mechanics in independently evolving, articulated coralline algae
Authors: Janot Kyra , Martone Patrick T. 
Published: November 2015

ABSTRACT
Flexible joints are a key innovation in the evolution of upright coralline algae. These structures have evolved in parallel at least three separate times, allowing the otherwise rigid, calcified thalli of upright corallines to achieve flexibility when subjected to hydrodynamic stress. As all bending occurs at the joints, stress is amplified, which necessitates that joints be made of material that is both extensible and strong. Data presented here indicate that coralline joints are in fact often stronger and more extensible, as well as tougher, than fleshy seaweed tissues. Corallinoids are particularly strong and tough, which is largely due to the presence of secondary cell walls that strengthen the joint tissue without adding bulk to the joint itself. Cell wall thickness is shown to be a large contributing factor to strength across all groups, with the exception of the corallinoid Cheilosporum sagittatum, which likely possesses distinct chemical composition in its walls to increase strength beyond that of all other species tested.