bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity
Authors: Wiczer Tracy , Dotson Emily , Tuten Amy , Phillips Gary , Maddocks Kami 
Published: July 2015

Introduction High-dose methotrexate (doses ≥1 g/m2) is a key component of several chemotherapy regimens used to treat patients with leukemia or lymphoma. Despite appropriate precautions with hydration, urine alkalinization, and leucovorin, nephrotoxicity remains a risk which can lead to significant morbidity and mortality. Current reports of risk factors for nephrotoxicity focus on patients with nephrotoxicity with a lack of comparison to those without toxicity. This study aimed to describe the incidence of high-dose methotrexate-induced nephrotoxicity at our institution and determined risk factors for high-dose methotrexate-induced nephrotoxicity by examining characteristics of patients with and without nephrotoxicity. Methods This was a retrospective, single-center, chart review. Adult patients with a diagnosis of leukemia or lymphoma who received high-dose methotrexate were included. Serum creatinine values were used to evaluate nephrotoxicity according to Common Terminology Criteria for Adverse Events criteria v4.03. Data related to the following proposed risk factors were collected: age, sex, body mass index, methotrexate dose, number of high-dose methotrexate exposures, leucovorin administration route, baseline renal function, albumin, hydration status, Clostridium difficile infection, urine pH, and concomitant interacting and nephrotoxic medications. The primary endpoint was evaluated with exact binomial methods and risk factors were identified using multivariable random-effects logistic regression. Results Final analyses included 140 patients with 432 high-dose methotrexate exposures. There were no differences in baseline demographical characteristics. Fifty-four patients (38.6%) experienced nephrotoxicity of any grade: 27.9% with grade 1, 5.7% with grade 2, 3.6% grade 3, 0% with grade 4, and 1.4% with grade 5 toxicity. More patients in the toxicity group received doses of methotrexate ≥3 g/m2 (58.3% versus 57.2%, p < 0.001), had an albumin level <3 g/dL (31.9% versus 15.9%, p = 0.04), and received an interacting medication during high-dose methotrexate clearance (44.4% versus 24.7%, p = 0.003). Male gender (OR 2.3, 95% CI: 1.27–4.18, p = 0.006), albumin (OR 0.44, 95% CI: 0.26–0.75, p = 0.002), number of drug interactions (OR 1.60, 95% CI: 1.15–2.21, p = 0.005), and use of furosemide (OR 2.56, 95% CI 1.46–4.48, p = 0.001) were all independent risk factors for the development of nephrotoxicity. Conclusions Nephrotoxicity is a possible complication of therapy with high-dose methotrexate with most instances comprising grade 1–2 toxicity. Male gender, low albumin, and administration of interacting drugs or furosemide during high-dose methotrexate clearance may predispose patients to nephrotoxicity.
Scientific Competencies in the Social Sciences
Authors: Dietrich Heike , Zhang Ying , Klopp Eric , Brünken Roland , Krause Ulrike-Marie , Spinath Frank M. , Stark Robin , Spinath Birgit 
Published: July 2015

The aim of the present study was to introduce a general theoretical model of scientific competencies in higher education and to adapt it to three social sciences, namely psychology, sociology, and political science, by providing evidence from expert interviews and program regulations. Within our general model, we distinguished and specified four building blocks of scientific competencies: input, operations, and output, as well as personal characteristics. We defined input as content students are exposed to in their respective domains, operations as cognitive processes stated by Anderson et al. (2001), and output as content students create as a result of applying operations on input. We considered scientific competencies to be the constructive use of operations on input and the creation of output thereby. Furthermore, we considered personal characteristics that are relevant for competency acquisition and for working in a scientifically competent manner. In the present article we provide main results for the four building blocks of scientific competencies in psychology, sociology, and political science. Furthermore, we discuss limitations of our current model such as the necessity to determine criteria to further clarify what the constructive use of operations on input looks like in the different cycles of higher education.
The relationship between vitamin D status and cardiac autonomic neuropathy in patients with type 2 diabetes mellitus
Authors: Jung Chan-Hee , Jung Sang-Hee , Kim Kyu-Jin , Kim Bo-Yeon , Kim Chul-Hee , Kang Sung-Koo , Mok Ji-Oh 
Published: July 2015

Objective: This study evaluates cardiac autonomic neuropathy and heart rate variability according to the vitamin D status in type 2 diabetes mellitus. Methods: A total of 163 patients were recruited. Cardiac autonomic neuropathy was assessed using five tests according to Ewing’s protocol. The time and frequency domains of the heart rate variability were also evaluated. Patients were separated into three groups: vitamin D sufficient [25(OH)D ⩾ 20 ng/mL], vitamin D insufficient [10 ⩽ 25(OH)D < 20] and vitamin D deficiency [25(OH)D < 10] groups. Results: Both standard deviation of normal-to-normal RR intervals and square root of the average of the sum of the squares of the differences between adjacent NN intervals in the supine position were significantly lower in vitamin D deficient group. Low frequency/high frequency ratio in the upright position was significantly higher in the vitamin D deficient group. 25(OH)D levels are positively correlated with standard deviation of normal-to-normal RR intervals in the supine position. In multivariate logistic analysis, patients with vitamin D levels of 10 < 25(OH)D < 20 ng/mL showed borderline significantly lower cardiac autonomic neuropathy risk than those with 25(OH)D levels <10 ng/mL (odds ratio = 0.45 (0.23–1.01), p = 0.051). Conclusion: Vitamin D deficiency was significantly correlated with heart rate variability parameters. However, there was only borderline significant association between vitamin D concentration and presence of cardiac autonomic neuropathy. Therefore, future studies are required to establish a relationship between vitamin D levels and cardiac autonomic neuropathy.
Blepharitis due to Cryptococcus neoformans in a cat from northern Portugal
Authors: Pimenta Paulo , Alves-Pimenta Sofia , Barros João , Pereira Maria J , Maltez Luís , Maduro A Paula , Cardoso Luís , Coelho Ana C 
Published: July 2015

Case summary We report a clinical case of blepharitis due to Cryptococcus neoformans yeasts in a 2-year-old stray cat from northern Portugal (Vila Real) without concurrent naso-ocular signs. Ophthalmological examination revealed mucopurulent discharge from an open wound in the right upper and lower lids. Slit-lamp biomicroscopy showed a normal anterior segment, and intraocular pressure was within the normal reference interval. No fundoscopic alterations were detected in either eye by direct and indirect ophthalmoscopic examination. Cytological examination of an appositional smear showed numerous polymorphic neutrophils and macrophages, together with spherical yeast cells compatible with Cryptococcus species. Molecular analysis by means of PCR and restriction fragment length polymorphism identified C neoformans genotype VNI. The cat was treated with itraconazole, and amoxicillin and clavulanic acid, combined with a commercial ear ointment and an imidacloprid/moxidectin spot-on application for bilateral parasitic otitis caused by Otodectes cynotis. One month after treatment, the clinical signs were completely resolved. Localised cutaneous lesions, as in the present case, probably result from contamination of cat-scratch injuries with viable encapsulated yeasts. Relevance and novel information This is, to the best of our knowledge, the first clinical report of feline blepharitis due to C neoformans without concurrent naso-ocular signs. The current findings, together with those from recent reports of the infection in domestic animals, should alert the veterinary community both in Portugal and in Europe to this underdiagnosed disease.
Hypertrophic osteopathy in a cat with a concurrent injection-site sarcoma
Authors: Salgüero Raquel , Demetriou Jackie , Constantino-Casas Fernando , Herrtage Michael 
Published: July 2015

Case summary An 11-year old neutered female domestic shorthair cat presented for investigation of a large, partially ulcerated skin mass in the area of the left scapula. The cat had been vaccinated 6 weeks previously in the same area. Haematology showed a marked neutrophilia and monocytosis. Tru-cut biopsies were taken and histopathology was consistent with a high-grade soft tissue sarcoma. Thoracic radiographs and abdominal ultrasound revealed no abnormalities. Moderate mixed (palisading, brush border and smooth) periosteal reaction was seen on the diaphysis of long bones at the time of the radiographic examination. Magnetic resonance imaging of the mass showed infiltration within deeper tissues and the owners elected euthanasia. Post-mortem examination confirmed the presence of hypertrophic osteopathy with a concurrent injection-site sarcoma. No evidence of intra-thoracic or intra-abdominal disease was found. Relevance and novel information To our knowledge, this is the first report where hypertrophic osteopathy has been described in a cat with a soft tissue sarcoma, most likely an injection-site sarcoma.
Stewardship Challenges Abortion: A Proposed Means to Mitigate Abortion's Social Divisiveness
Authors: Tardiff Robert G. 
Published: July 2015

Since 1973 the legislated constitutional right to abortion has produced a political dichotomy (anti-abortion versus pro-abortion) within the United States, even while witnessing a gradual decline in the rate of abortions. A third paradigm, moral stewardship, is advanced as an effective means to ameliorate this social divisiveness. Incorporating the concept of stewardship into deliberations of pregnancy termination would require recognition, through fact-based education programs, of the life circumstances that prompt the consideration to terminate a pregnancy. Based on collective responsibility, policies, and programs are needed to foster social justice for parents and for the offspring brought to term, without creating excessive burdens on women faced with an unwanted pregnancy. Moral stewardship is perceived as humanitarian to family and community and advantageous to society overall. It also offers a serious opportunity to reshape our society from divisiveness to inclusiveness, and to guide science policy judgment that enhances and strengthens social justice. Lay summary Differing opinions over the ethics of human abortion have been legion since Roe v. Wade (1973). The disputes between pro- and anti-abortion factions have segregated society with few improvements in social justice. This study offers an alternative approach, one capable of social assimilation and justice for unwanted offspring and pregnant mothers bearing them. It promotes moral stewardship toward the unborn whose humanity and personhood are recognized genetically and supported philosophically by long-standing ethical principles. Stewardship incorporates all people at all levels of society based on collective responsibility, supported by government policies, yet not restricting a mother's choices for the future of her unborn offspring.
A mutation in the Gardos channel is associated with hereditary xerocytosis
Authors: Rapetti-Mauss Raphael , Lacoste Caroline , Picard Véronique , Guitton Corinne , Lombard Elise , Loosveld Marie , Nivaggioni Vanessa , Dasilva Nathalie , Salgado David , Desvignes Jean-Pierre , Béroud Christophe , Viout Patrick , Bernard Monique , Soriani Olivier , Vinti Henri , Lacroze Valérie , Feneant-Thibault Madeleine , Thuret Isabelle , Guizouarn Hélène , Badens Catherine 
Published: July 2015

Key PointsThe Gardos channel is a potassium channel involved in red cell volume modification. A mutation in KCNN4 encoding the Gardos channel is presented as the genetic basis for a new type of hereditary xerocytosis.
Preparation of Core-Shell Hybrid Materials by Producing a Protein Corona Around Magnetic Nanoparticles
Authors: Weidner A , Gräfe C , von der Lühe M , Remmer H , Clement J H , Eberbeck D , Ludwig F , Müller R , Schacher F H , Dutz S 
Published: July 2015

Abstract
Nanoparticles experience increasing interest for a variety of medical and pharmaceutical applications. When exposing nanomaterials, e.g., magnetic iron oxide nanoparticles (MNP), to human blood, a protein corona consisting of various components is formed immediately. The composition of the corona as well as its amount bound to the particle surface is dependent on different factors, e.g., particle size and surface charge. The actual composition of the formed protein corona might be of major importance for cellular uptake of magnetic nanoparticles. The aim of the present study was to analyze the formation of the protein corona during in vitro serum incubation in dependency of incubation time and temperature. For this, MNP with different shells were incubated in fetal calf serum (FCS, serving as protein source) within a water bath for a defined time and at a defined temperature. Before and after incubation the particles were characterized by a variety of methods. It was found that immediately (seconds) after contact of MNP and FCS, a protein corona is formed on the surface of MNP. This formation led to an increase of particle size and a slight agglomeration of the particles, which was relatively constant during the first minutes of incubation. A longer incubation (from hours to days) resulted in a stronger agglomeration of the FCS incubated MNP. Quantitative analysis (gel electrophoresis) of serum-incubated particles revealed a relatively constant amount of bound proteins during the first minutes of serum incubation. After a longer incubation (>20 min), a considerably higher amount of surface proteins was determined for incubation temperatures below 40 °C. For incubation temperatures above 50 °C, the influence of time was less significant which might be attributed to denaturation of proteins during incubation. Overall, analysis of the molecular weight distribution of proteins found in the corona revealed a clear influence of incubation time and temperature on corona composition.
Quantifying the healthcare costs of treating severely bleeding major trauma patients: a national study for England
Authors: Campbell Helen E. , Stokes Elizabeth A. , Bargo Danielle N. , Curry Nicola , Lecky Fiona E. , Edwards Antoinette , Woodford Maralyn , Seeney Frances , Eaglestone Simon , Brohi Karim , Gray Alastair M. , Stanworth Simon J. 
Published: July 2015

Abstract
Introduction
Severely bleeding trauma patients are a small proportion of the major trauma population but account for 40 % of all trauma deaths. Healthcare resource use and costs are likely to be substantial but have not been fully quantified. Knowledge of costs is essential for developing targeted cost reduction strategies, informing health policy, and ensuring the cost-effectiveness of interventions.

Methods
In collaboration with the Trauma Audit Research Network (TARN) detailed patient-level data on in-hospital resource use, extended care at hospital discharge, and readmissions up to 12 months post-injury were collected on 441 consecutive adult major trauma patients with severe bleeding presenting at 22 hospitals (21 in England and one in Wales). Resource use data were costed using national unit costs and mean costs estimated for the cohort and for clinically relevant subgroups. Using nationally available data on trauma presentations in England, patient-level cost estimates were up-scaled to a national level.

Results
The mean (95 % confidence interval) total cost of initial hospital inpatient care was £19,770 (£18,177 to £21,364) per patient, of which 62 % was attributable to ventilation, intensive care, and ward stays, 16 % to surgery, and 12 % to blood component transfusion. Nursing home and rehabilitation unit care and re-admissions to hospital increased the cost to £20,591 (£18,924 to £22,257). Costs were significantly higher for more severely injured trauma patients (Injury Severity Score ≥15) and those with blunt injuries. Cost estimates for England were £148,300,000, with over a third of this cost attributable to patients aged 65 years and over.

Conclusions
Severely bleeding major trauma patients are a high cost subgroup of all major trauma patients, and the cost burden is projected to rise further as a consequence of an aging population and as evidence continues to emerge on the benefits of early and simultaneous administration of blood products in pre-specified ratios. The findings from this study provide a previously unreported baseline from which the potential impact of changes to service provision and/or treatment practice can begin to be evaluated. Further studies are still required to determine the full costs of post-discharge care requirements, which are also likely to be substantial.
Psychosocial and Neurocognitive Outcomes in Adult Survivors of Adolescent and Early Young Adult Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Prasad Pinki K. , Hardy Kristina K. , Zhang Nan , Edelstein Kim , Srivastava Deokumar , Zeltzer Lonnie , Stovall Marilyn , Seibel Nita L. , Leisenring Wendy , Armstrong Gregory T. , Robison Leslie L. , Krull Kevin 
Published: July 2015

Purpose To characterize psychological and neurocognitive function in long-term cancer survivors diagnosed during adolescence and early young adulthood (AeYA). Methods Six thousand one hundred ninety-two survivors and 390 siblings in the Childhood Cancer Survivor Study completed the Brief Symptom Inventory-18 and a Neurocognitive Questionnaire. Treatment and demographic predictors were examined, and associations with social attainment (employment, education, and living independently) were evaluated. Logistic regression models were used to compute odds ratios (ORs) and corresponding 95% CIs. Results Among survivors, 2,589 were diagnosed when AeYA (11 to 21 years old). Adjusted for current age and sex, these survivors, compared with siblings, self-reported higher rates of depression (11.7% v 8.0%, respectively; OR, 1.55; 95% CI, 1.04 to 2.30) and anxiety (7.4% v 4.4%, respectively; OR, 2.00; 95% CI, 1.17 to 3.43) and more problems with task efficiency (17.2% v 10.8%, respectively; OR, 1.72; 95% CI, 1.21 to 2.43), emotional regulation (19.1% v 14.1%, respectively; OR, 1.74; 95% CI, 1.26 to 2.40), and memory (25.9% v 19.0%, respectively; OR, 1.44; 95% CI, 1.09 to 1.89). Few differences were noted between survivors diagnosed with leukemia or CNS tumor before 11 years old versus during later adolescence, although those diagnosed with lymphoma or sarcoma during AeYA were at reduced risk for self-reported psychosocial and neurocognitive problems. Unemployment was associated with self-reports of impaired task efficiency (OR, 2.93; 95% CI, 2.28 to 3.77), somatization (OR, 2.29; 95% CI, 1.77 to 2.98), and depression (OR, 1.94; 95% CI, 1.43 to 2.63). Conclusion We demonstrated that risk for poor functional outcome is not limited to survivors' diagnoses in early childhood. AeYA is a critical period of development, and cancer during this period can impact neurocognitive and emotional function and disrupt vocational attainment.
Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
Authors: Meves Alexander , Nikolova Ekaterina , Heim Joel B. , Squirewell Edwin J. , Cappel Mark A. , Pittelkow Mark R. , Otley Clark C. , Behrendt Nille , Saunte Ditte M. , Lock-Andersen Jorgen , Schenck Louis A. , Weaver Amy L. , Suman Vera J. 
Published: July 2015

Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.
Fenofibrate in cancer: mechanisms involved in anticancer activity
Authors: Koltai Tomas 
Published: July 2015

Objective: To review the mechanisms of anti-cancer activity of fenofibrate (FF) and other Peroxisome Proliferator Activator Receptor α (PPARα) agonists based on evidences reported in the published literature.Methods: We extensively reviewed the literature concerning FF as an off target anti-cancer drug. Controversies regarding conflicting findings were also addressed.Results:The main mechanism involved in anti-cancer activity is anti-angiogenesis through down-regulation of Vascular Endothelial Growth Factor (VEGF), Vascular Endothelial Growth Factor Receptor (VEGFR) and Hypoxia Inducible factor-1 α (HIF-1α), inhibition of endothelial cell migration, up-regulation of endostatin and thrombospondin-1, but there are many other contributing mechanisms like apoptosis and cell cycle arrest, down-regulation of Nuclear Factor Kappa B (NF-kB) and Protein kinase B (Akt) and decrease of cellular energy by impairing mitochondrial function. Growth impairment is related to down-regulation of Phospho-Inositol 3 Kinase (PI3K)/Akt axis and down-regulation of the p38 map kinase (MAPK) cascade. A possible role should be assigned to FF stimulated over-expression of Tribbles Homolog-3 (TRIB3) which inhibits Akt phosphorylation. Important anti-cancer and anti-metastatic activities are due to down-regulation of MCP-1 (monocyte chemotactic protein-1), decreased Metalloprotease-9 (MMP-9) production, weak down-regulation of adhesion molecules like E selectin, intercellular adhesion molecules (ICAM) and Vascular Endothelial Adhesion Molecules (VCAM), and decreased secretion of chemokines like Interleukin-6 (IL-6), and down-regulation of cyclin D-1. There is no direct link between FF activity in lipid metabolism and anticancer activity, except for the fact that many anticancer actions are dependent from PPARα agonism. FF exhibits also PPARα independent anti-cancer activities.Conclusions: There are strong evidences indicating that FF can disrupt growth-related activities in many different cancers, due to anti-angiogenesis and anti-inflammatory effects. Therefore FF may be useful as a complementary adjunct treatment of cancer, particularly included in anti-angiogenic protocols like those currently increasingly used in glioblastoma. There are sound reasons to initiate well planned phase II clinical trials for FF as a complementary adjunct treatment of cancer.