bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-reported Conflicts of Interest and Trial Sponsorship of Clinical Trials in Prostate Cancer Involving Radiotherapy
Authors: Moraes Fabio Ynoe de , Leite Elton Trigo Teixeira , Hamstra Dan A. , Feng Felix Y. , Arruda Fernando Freire , Gadia Rafael , Abreu Carlos Eduardo Cintra Vita , Marta Gustavo Nader , Hanna Samir Abdallah , Silva João Luis Fernandes da , Carvalho Heloisa de Andrade , Spratt Daniel E. 
Published: December 2015

Objectives:
To examine the association between trial sponsorship and conflicts of interest (COI) with clinical trial conclusions for prostate cancer trials related to radiotherapy.

Materials and Methods:
The MEDLINE database was searched for all prostate cancer clinical trials published between 2004 and 2013 and identified 1396 studies. Two investigators independently identified trials published in the English language of ≥30 patients, and extracted relevant data. Clinical trials were classified according to trial characteristics, sponsorship source and type, COI, and study conclusion, and analyzed by univariable and multivariable logistic regression.

Results:
Of 240 eligible trials, 160 (67.5%) evaluated drugs without radiotherapy, 60 (25%) involved radiotherapy, and 18 (7.5%) involved procedures without radiotherapy. Of the 60 radiotherapy trials eligible for analysis, positive sponsorship and potential COI were present in 58.3% and 20% of trials, respectively. Study conclusions were positive, negative, or neutral in 78.3%, 5%, and 16.7% of trials, respectively. No association was found between positive conclusions and either industry support of potential COI. Positive conclusions were reported in 86.7% and 83.3% of trials with sponsorship and COI, respectively, as compared with 75.6% and 77.1% of those without sponsorship (P=0.37) and COI (P=0.64). Sponsorship was significantly associated with radiotherapy trials combined with drugs (odds ratio 5.5, P=0.01) and higher-risk disease (odds ratio 4.71, P=0.01).

Conclusions:
The presence of sponsorship was associated with radiotherapy trials involving drugs or studying higher-risk prostate cancer. However, there were no identified associations between study conclusion and sponsorship type or COI.
The Benefit of Adjuvant Radiotherapy in High-grade Nonmetastatic Retroperitoneal Soft Tissue Sarcoma
Authors: Bates James E. , Dhakal Sughosh , Mazloom Ali , Constine Louis S. 
Published: December 2015

Objectives:Controversy persists on the use of adjuvant radiotherapy (RT) in patients with retroperitoneal sarcoma (RPS). High-grade disease is known to be associated with decreased local control and overall survival (OS). Because RT has proven beneficial for local control and OS in patients with high-grade extremity soft tissue sarcoma, we evaluated the efficacy of adjuvant RT in high-grade RPS.Methods:The Surveillance, Epidemiology, and End Results database was used to identify patients with pathology-confirmed RPS from 1973 to 2010. Clinical characteristics and outcomes were analyzed.Results:Of 480 total patients, 144 (30.0%) received postoperative radiation. Patients who received adjuvant RT had improved median OS (36 mo) compared with those who did not (27 mo, hazard ratio [HR]=0.79,P=0.023). On multivariate analysis the use of adjuvant RT (HR=0.80; 95% confidence interval [CI], 0.65-0.98;P=0.029), male sex (HR=1.32; 95% CI, 1.10-1.59;P=0.003), age above 65 years (HR=1.38; 95% CI, 1.15-1.67;P=0.001), and increasing the Surveillance, Epidemiology, and End Results historical stage (HR=1.46; 95% CI, 1.21-1.76;P<0.001) were all prognostic factors for OS.Conclusions:In a large retrospective analysis, postoperative RT improved OS in high-grade RPS patients. As such, adjuvant RT should be strongly considered in all patients with high-grade RPS. The optimal timing of RT relative to surgery requires further study.
A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma
Authors: Cohen Steven J. , Zalupski Mark M. , Conkling Paul , Nugent Francis , Ma Wen Wee , Modiano Manuel , Pascual Rolan , Lee Fa Chyi , Wong Lucas , Hersh Evan 
Published: December 2015

Background:
Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study.

Materials and Methods:
Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m2 days 1, 8, and 15 with either imexon, 875 mg/m2 or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate.

Results:
A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822.

Conclusions:
The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.
CRYSTALLINE RETINOPATHY FROM HYPEROXALURIA: LONG-TERM FOLLOW-UP
Authors: Sangave Amit A. , Gearinger Matthew D. , Diloreto David A. 
Published: December 2015

Purpose:
To report long-term follow-up in a patient with retinal oxalosis from primary hyperoxaluria.

Methods:
Retrospective chart review was performed for this patient. Patients: A 6-year-old girl that presented to our clinic before and after combined kidney/liver transplant.

Results:
Optical coherence tomography and fundus findings consistent with oxalate crystal deposition.

Conclusion:
Progressive macular changes, including atrophy and fibrosis can occur in crystalline retinopathy, secondary to hyperoxaluria, after combined hepatorenal transplant.
Direct Costs of Acute Recurrent and Chronic Pancreatitis in Children in the INSPPIRE Registry
Authors: Ting Jie , Wilson Leslie , Schwarzenberg Sarah Jane , Himes Ryan , Barth Bradley , Bellin Melena D. , Durie Peter R. , Fishman Douglas S. , Freedman Steven D. , Gariepy Cheryl E. , Giefer Matthew J. , Gonska Tanja , Husain Sohail Z. , Kumar Soma , Morinville Veronique D. , Lowe Mark E. , Ooi Chee Y. , Pohl John F. , Troendle David , Usatin Danielle , Werlin Steven L. , Wilschanski Michael , Heyman Melvin B. , Uc Aliye 
Published: December 2015

ABSTRACTObjective:To estimate selected direct medical care costs of children with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP).Methods:We performed a cross‐sectional study of data from International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE), a multinational registry of children with ARP or CP. We determined health care utilization and estimated costs of hospitalizations, surgical and endoscopic procedures, and medications in our study population. Health care utilization data were obtained from all subjects enrolled in the study, and costs were calculated using national United States costs.Results:We included 224 subjects (median age 12.7 years), 42% of whom had CP. Mean number of hospitalizations, including for surgery and endoscopic retrograde cholangiopancreatography, was 2.3 per person per year, costing an estimated average $38,755 per person per year. Including outpatient medications, estimated total mean cost was $40,589 per person per year. Subjects using surgical procedures or endoscopic retrograde cholangiopancreatography incurred mean annual costs of $42,951 per person and $12,035 per person, respectively. Estimated annual costs of pancreatic enzyme replacement therapy, diabetic medications, and pain medications were $4114, $1761, and $614 per person, respectively. In an exploratory analysis, patients with the following characteristics appear to accrue higher costs than those without them: more frequent ARP attacks per year, reported constant or episodic pain, family history of pancreatic cancer, and use of pain medication.Conclusions:ARP and CP are uncommon childhood conditions. The severe burden of disease associated with these conditions and their chronicity results in high health care utilization and costs. Interventions that reduce the need for hospitalization could lower costs for these children and their families.
Antioxidative Activity of Colostrum and Human Milk
Authors: Marinković Vesna , Ranković‐Janevski Milica , Spasić Snežana , Nikolić‐Kokić Aleksandra , Lugonja Nikoleta , Djurović Dijana , Miletić Srdjan , Vrvić Miroslav M. , Spasojević Ivan 
Published: December 2015

ABSTRACTObjectives:Milk banks collect, pasteurize, and freeze/store human milk. The processing may alter redox properties of milk, but the effects have not been fully examined.Methods:We collected 10 mature milk and 10 colostrum samples and applied a battery of biochemical assays and electron paramagnetic resonance spectroscopy to inspect changes that milk undergoes with pasteurization and 30 days storage at −20°C.Results:Pasteurization and storage of raw milk did not affect total nonenzymatic antioxidative capacity, but specific components and features were altered. Urate radical and ascorbyl radical emerge as products of exposure of milk to hydroxyl radical‐generating system. Processing shifted the load of antioxidative activity from ascorbate to urate and lowered the capacity of milk to diminish hydroxyl radical. Pasteurization caused a significant drop in the activity of 2 major antioxidative enzymes—superoxide dismutase and glutathione peroxidase, whereas freezing/storage of raw milk affected only superoxide dismutase. Colostrum showed drastically higher total nonenzymatic antioxidative capacity, hydroxyl radical scavenging ability, and glutathione reductase activity compared with mature milk.Conclusions:Pasteurization and storage affect nonenzymatic and enzymatic antioxidative agents in human milk. It appears that nonenzymatic antioxidative systems in colostrum and milk are different. The effects of processing may be partially compensated by fortification/spiking with ascorbate before use.
Gastroesophageal Reflux Burden, Even in Children That Aspirate, Does Not Increase Pediatric Hospitalization
Authors: Duncan Daniel R. , Amirault Janine , Johnston Nikki , Mitchell Paul , Larson Kara , Rosen Rachel L. 
Published: December 2015

ABSTRACTObjectives:Gastroesophageal reflux is common but remains a controversial disease to diagnose and treat and little is known about the role of reflux testing in predicting clinical outcomes, particularly in children at risk for extraesophageal reflux complications. The aim of this study was to determine if rates of hospitalization were affected by reflux burden even after adjusting for aspiration risk.Methods:We prospectively recruited, between 2009 and 2014, a cohort of pediatric patients with suspected extraesophageal reflux disease who were referred for reflux testing and underwent both multichannel intraluminal impedance with pH (pH‐MII) and modified barium swallow studies. A subset of patients also underwent bronchoalveolar lavage with pepsin analysis. We determined their rates of hospitalization for a minimum of 1 year following pH‐MII testing.Results:We prospectively enrolled 116 pediatric patients who presented for care at Boston Children's Hospital and underwent both pH‐MII and modified barium swallow studies. There was no statistically significant relationship between reflux burden measured by pH‐MII or bronchoalveolar pepsin and total number of admissions or number of admission nights even after adjusting for aspiration status (P > 0.2). There were no statistically significant relationships between reflux burden by any method and the number or nights of urgent pulmonary admissions before or after adjusting for aspiration risk (P > 0.08).Conclusions:Even in aspirating children, reflux burden did not increase the risk of hospitalization. Based on these results, routine reflux testing cannot be recommended even in aspirating children, because the results do not impact clinically significant outcomes.
Plasminogen Activator Inhibitor‐1 Predicts Quantity of Hepatic Steatosis Independent of Insulin Resistance and Body Weight
Authors: Holzberg Jeffrey R. , Jin Ran , Le Ngoc‐Anh , Ziegler Thomas R. , Brunt Elizabeth M. , McClain Craig J. , Konomi Juna V. , Arteel Gavin E. , Vos Miriam B. 
Published: December 2015

ABSTRACTObjective:The aim of the present study was to examine the association between plasminogen activator inhibitor‐1 (PAI‐1), an acute phase protein strongly associated with cardiovascular disease risk, and adiposity, insulin resistance, and inflammation among overweight and obese children with a wide range of hepatic steatosis.Methods:Plasma PAI‐1 levels were measured in a prospectively recruited cohort of 39 overweight or obese children who underwent comprehensive anthropometric assessment and metabolic measurements. Hepatic steatosis was quantified using magnetic resonance spectroscopy and participants were divided into 3 groups based on whether they had normal hepatic steatosis (<5%), low hepatic steatosis (≥5%–10%), and high hepatic steatosis (>10%).Results:Plasma PAI‐1 levels significantly increased across the severity of hepatic steatosis in overweight and obese children, and this association was independent of body mass index z score, visceral fat, insulin resistance, and inflammatory markers (P < 0.05).Conclusion:Hepatic steatosis in children is positively associated with circulating levels of PAI‐1 independent of body mass index, insulin resistance, and inflammatory markers. Further studies are needed to clarify the potential role of PAI‐1 as a therapeutic target in pediatric nonalcoholic fatty liver disease.
Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort
Authors: Nimgaonkar Vishwajit L. , Yolken Robert H. , Wang Tianxiu , Chang Chung-Chou H. , McClain Lora , McDade Eric , Snitz Beth E. , Ganguli Mary 
Published: December 2015

Background:
Numerous cross-sectional studies have related exposure to neurotropic infectious agents with cognitive dysfunction in older adults, however, the temporal sequence is uncertain.

Methods:
In a representative, well-characterized, population-based aging cohort, we determined whether the temporal trajectories of multiple cognitive domains are associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1 (HSV-1), Herpes Simplex virus, type 2 (HSV-2), or Toxoplasma gondii (TOX). Complex attention, executive functions, memory, language, and visuospatial function were assessed annually for 5 years among consenting individuals. Study entry IgG antibody titers indexing exposure to each infectious agent were examined in relation to slopes of subsequent temporal cognitive decline using multiple linear regressions adjusted for potential confounders.

Results:
The IgG levels for HSV-2 were significantly associated with baseline cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2, TOX, and CMV, but not HSV-1 were significantly associated with greater temporal cognitive decline that varied by type of infection.

Conclusions:
Exposure to CMV, HSV-2, or TOX is associated with cognitive deterioration in older individuals, independent of general age–related variables. An increased understanding of the role of infectious agents in cognitive decline may lead to new methods for its prevention and treatment.
Optimizing and evaluating the operational factors affecting the cyanide leaching circuit of the Aghdareh gold processing plant using a CCD model
Authors: Azizi Asghar , Ghaedrahmati Reza 
Published: December 2015

A response surface method using a central composite design was employed to evaluate, model and optimize the influence of five main factors in the gold cyanidation process. These factors were pH, solid percentage, NaCN concentration, particle size and leaching time. A second-order equation was proposed and developed for the relationship between the gold recoveries and influential factors. The modelling results indicated that the factors influencing the degree of cyanide leaching of gold were in the order of leaching time > NaCN concentration
2
> particle size > pH > NaCN concentration > leaching time
2
> solid percentage × particle size > solid percentage × NaCN concentration > solid percentage. Also, we obtained a coefficient of determination (
R
2
) greater than 93%, which showed that the developed model was well fitted to the experimental data. In addition, the model equation was individually optimized by using quadratic programming to maximize gold recoveries within the experimental range. The optimum condition was found to be pH 10.11 for the solution, 36.07% for the solids content, 729.56 ppm for the NaCN concentration, 37.52
μ
m for the particle size and 23.2 h for the leaching time. Under these conditions, the highest recovery of gold was achieved of approximately 91.5%.
Hybrid Systems Modeling for (Cancer) Systems Biology
Authors: Dobbe Roel , Tomlin Claire J. 
Published: December 2015

AbstractThe advent of biological data of increasingly higher resolution in space and time has triggered the use of dynamic models to explain and predict the evolution of biological systems over space and time. Computer-aided system modeling and analysis in biology has led to many new discoveries and explanations that would otherwise be intractable to articulate without the available data and computing power. Nevertheless, the complexity in biology still challenges many labs in capturing studied phenomena in models that are tractable and simple enough to analyze. Moreover, the popular use of ordinary differential equation models have their limitations in that they solely capture continuous dynamics, while we observe many discrete dynamic phenomena in biology such as gene switching or mutations. Hybrid systems modeling provides a framework in which both continuous and discrete dynamics can be simulated and analyzed. Moreover, it provides techniques to develop approximations and abstractions of complex dynamics that are tractable to analyze.
A protein truncating R179X variant inRNF186confers protection against ulcerative colitis
Authors: Rivas MA , Graham D , Sulem P , Stevens C , Desch AN , Goyette P , Gudbjartsson D , Jonsdottir I , Thorsteinsdottir U , Degenhardt F , Mucha S , Kurki MI , Li D , D’Amato M , Annese V , Vermeire S , Weersma R , Halfvarson J , Paavola-Sakki P , Lappalainen M , Lek M , Cummings B , Tukianen T , Haritunians T , Halme L , Koskinen LLE , Ananthakrishnan A , Luo Y , Heap GA , Visschedijk M ,   NIDDK IBD Genetics Consortium,   UK IBD Genetics Consortium, MacArthur DG , Neale BM , Ahmad T , Anderson CA , Brant SR , Duerr R , Silverberg M , Cho J , Palotie A , Saavalainen P , Kontula K , Färkkilä M , McGovern DPB , Franke A , Stefansson K , Rioux JD , Xavier RJ , Daly MJ 
Published: December 2015

AbstractWe conducted a search for protein truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. We found that a protein truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF = up to 0.78%) inRNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overallP= 6.89×10−7, odds ratio (OR) = 0.30). We further demonstrate that the truncated protein is expressed, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization or loss of an essential protein element.
Agent-based modeling of cancer stem cell driven solid tumor growth
Authors: Poleszczuk Jan , Macklin Paul , Enderling Heiko 
Published: December 2015

SummaryComputational modeling of tumor growth has become an invaluable tool to simulate complex cell-cell interactions and emerging population-level dynamics. Agent-based models are commonly used to describe the behavior and interaction of individual cells in different environments. Behavioral rules can be informed and calibrated byin vitroassays, and emerging population-level dynamics may be validated with bothin vitroandin vivoexperiments. Here, we describe the design and implementation of a lattice-based agent-based model of cancer stem cell driven tumor growth.
Serum C‐reactive protein levels in Japanese patients with psoriasis and psoriatic arthritis: Long‐term differential effects of biologics
Authors: Asahina Akihiko , Umezawa Yoshinori , Yanaba Koichi , Nakagawa Hidemi 
Published: December 2015

AbstractPsoriasis has been shown to accompany systemic inflammation. We aimed to examine serum C‐reactive protein (CRP) levels in Japanese psoriatic patients, and to elucidate their long‐term as well as short‐term changes by treatment with different biologics. A retrospective study was conducted in those who initiated and successfully continued the treatment for up to 24 months with either infliximab, adalimumab or ustekinumab, at the psoriasis special clinic of Jikei University School of Medicine. A total of 212 patients were included, 171 with plaque‐type psoriasis (PsV) and 41 with psoriatic arthritis (PsA). A statistically significant elevation of CRP values was found in the group with a Psoriasis Area and Severity Index (PASI) of 12 or more compared with the PASI of less than 12 for both PsV and PsA. The CRP‐positive patients had a higher proportion of PsA compared with the CRP‐negative patients, and they had significantly higher PASI scores. Serum CRP values declined as early as at 3 months after systemic treatment with biologics. Tumor necrosis factor (TNF)‐α antagonists did lead to a notable and sustained CRP decline up to 24 months. Infliximab showed rapid decline, while CRP decline by adalimumab treatment was time‐dependent. The interleukin‐12/23 p40 antagonist, ustekinumab, appeared to be less potent than TNF‐α antagonists in stabilizing CRP values at low levels despite good control of cutaneous lesions. In conclusion, serum CRP levels can be used to assess disease severity in Japanese psoriatic patients as a marker of systemic inflammation. TNF‐α antagonists may be more beneficial than ustekinumab in this regard.