bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury
Authors: Hirano Yohei , Aziz Monowar , Yang Weng-Lang , Wang Zhimin , Zhou Mian , Ochani Mahendar , Khader Adam , Wang Ping 
Published: February 2015

AbstractIntroductionSepsis refers to severe systemic inflammation leading to acute lung injury (ALI) and death. Introducing novel therapies can reduce the mortality in ALI. Osteopontin (OPN), a secretory glycoprotein produced by immune reactive cells, plays a deleterious role in various inflammatory diseases. However, its role in ALI caused by sepsis remains unexplored. We hypothesize that treatment with an OPN-neutralizing antibody (anti-OPN Ab) protects mice against ALI during sepsis.MethodsSepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Anti-OPN Ab or non-immunized IgG as control, at a dose of 50 μg/mouse, was intravenously injected at the time of CLP. After 20 hours, the expression of OPN and proinflammatory cytokines in tissues and plasma was examined by real-time PCR, Western blot, and ELISA. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) and the lung myeloperoxidase (MPO) levels were determined by colorimetric assays. Lung damage and neutrophil infiltrations were determined by histological H&E and Gr-1 staining, respectively. The effect of recombinant mouse OPN (rmOPN) on human neutrophil-like cell (HL-60) migration was performed by Boyden chamber assays and the involvement of intracellular signaling molecules in HL-60 cells was revealed by Western blot.ResultsAfter 20 hours of sepsis, mRNA and protein levels of OPN were significantly induced in lungs, spleen, and plasma. Treatment with an anti-OPN Ab in septic mice significantly reduced the plasma levels of ALT, AST, and LDH, and the proinflammatory cytokines IL-6, IL-1β and the chemokine MIP-2, compared with the vehicle group. Similarly, the lung mRNA and protein expressions of proinflammatory cytokines and chemokine were greatly reduced in anti-OPN Ab-treated animals. The lung histological architecture, MPO and neutrophil infiltration were significantly improved in anti-OPN Ab-treated mice compared with the vehicle animals. Treatment of rmOPN in HL-60 cells significantly increased their migration,in vitro. The neutrophils treated with rmOPN remarkably increased the levels of phospho focal adhesion kinase (pFAK), phospho extracellular signal-regulated kinase (pERK) and phospho p38.ConclusionsOur findings clearly demonstrate the beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic strategy in sepsis.
Serum progranulin levels are elevated in dermatomyositis patients with acute interstitial lung disease, predicting prognosis
Authors: Tanaka Atsushi , Tsukamoto Hiroshi , Mitoma Hiroki , Kiyohara Chikako , Ueda Naoyasu , Ayano Masahiro , Ohta Shun-ichiro , Kimoto Yasutaka , Akahoshi Mitsuteru , Arinobu Yojiro , Niiro Hiroaki , Tada Yoshifumi , Horiuchi Takahiko , Akashi Koichi 
Published: February 2015

Abstract
Introduction
Progranulin (PGRN), a pleiotropic growth factor, has emerged as an immunoregulatory molecule. Because the roles of PGRN in dermatomyositis (DM) are still unknown, we investigated whether serum PGRN levels are associated with disease activity and prognosis in DM patients, particularly in those with DM complicated with interstitial lung disease (ILD).

Methods
The serum levels of PGRN were measured by enzyme-linked immunosorbent assay in patients with DM (n =57; acute/subacute interstitial pneumonia (A/SIP): n =17, chronic interstitial pneumonia (CIP): n =24, without ILD: n =16), polymyositis (PM, n =21; including 6 with ILD) and normal healthy controls (NHCs, n =60). We assessed the correlation between the serum PGRN levels and the activity indexes of ILD or prognosis in DM patients with ILD.

Results
Serum PGRN levels were significantly higher in DM patients than in PM patients (P =0.0025) and in NHCs (P <0.0001). In DM patients, the levels were significantly higher in patients with A/SIP than in those with CIP (P <0.0001) or without ILD (P =0.0003). The serum PGRN levels in DM patients with ILD significantly correlated with serum ferritin (rS =0.77, P <0.0001), lactate dehydrogenase (rS =0.54, P =0.0003) and C-reactive protein (rS =0.48, P =0.0015) levels. Moreover, in DM patients with ILD, the cumulative survival rate for 6 months was significantly lower in the group with serum PGRN levels ≥200 ng/ml (67%) than in the group with serum PGRN levels <200 ng/ml (100%) (P =0.0009).

Conclusions
Serum PGRN is associated with disease activity and prognosis of DM with ILD. PGRN may play a role in the pathogenesis of DM and could be a useful biomarker.
Fixed points of dynamic processes of set-valued F-contractions and application to functional equations
Authors: Klim Dorota , Wardowski Dariusz 
Published: February 2015

AbstractThe article is a continuation of the investigations concerning F-contractions which have been recently introduced in [Wardowski in Fixed Point Theory Appl. 2012:94,2012]. The authors extend the concept of F-contractive mappings to the case of nonlinear F-contractions and prove a fixed point theorem via the dynamic processes. The paper includes a non-trivial example which shows the motivation for such investigations. The work is summarized by the application of the introduced nonlinear F-contractions to functional equations.
Cost analysis of pharmaceutical care provided to HIV-infected patients: an ambispective controlled study
Authors: Carnevale Renata Cavalcanti , de Godoi Rezende Costa Molino Caroline , Visacri Marília Berlofa , Mazzola Priscila Gava , Moriel Patricia 
Published: February 2015

Abstract

Background
Studies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients.

Methods
A controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year.

Results
Intervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm3. None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US$1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm3, and optimal immune response, respectively.

Conclusion
This work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.
Optimization of upstream and downstream process parameters for cellulase-poor-thermo-solvent-stable xylanase production and extraction by Aspergillus tubingensis FDHN1
Authors: Adhyaru Dharmesh N , Bhatt Nikhil S , Modi Hasmukh A 
Published: February 2015

AbstractBackgroundXylanases are important members of the hemicellulolytic enzyme system. Xylanase plays a vital role in the hydrolysis of major hemicellulosic component xylan and converts it into xylooligosaccharides and ultimately yields xylose. Cellulase-lacking or cellulase-poor xylanase with high temperature and pH stability has gained special attention, especially in paper and pulp industries. Most of the available literature highlighted the fungal xylanase production by optimizing environmental and cultural parameters. However, the importance of enzyme recovery from fermented biomass still needs attention. In this study, upstream and downstream process parameters were studied for enhancing xylanase production and extraction by a newly isolatedAspergillus tubingensisFDHN1 under solid-state fermentation using low-cost agro-residues.ResultsIn the present study,A. tubingensisFDHN1 was used for the xylanase, with very low level of cellulase, production under solid-state fermentation (SSF). Among various agro-residues, sorghum straw enhanced the xylanase production. Under optimized upstream conditions, the highest xylanase production 2,449 ± 23 U/g was observed. Upon characterization, crude xylanase showed stability over a broad range of pH 3.0 to 8.0 up to 24 h. The temperature stability revealed the nature of the xylanase to be thermostable. Native polyacrylamide gel electrophoresis (native PAGE) and zymogram analysis revealed the multiple forms of the xylanase. Due to the many industrially important characteristics of the xylanases, the study was elaborated for optimizing the downstream process parameters such as volume of extractant, extraction time, temperature and agitation speed to recover maximum xylanase from fermented sorghum straw. The highest amount of xylanase (4,105 ± 22 U/g) was recovered using 0.05 M sodium citrate buffer (pH 6.5) at 12:1 (v/w) extractant/solid ratio, 90-min extraction time, 150-rpm agitation speed and 40°C. Finally, detailed bioprocess optimization shows an overall 6.66-fold enhancement in the xylanase yield.ConclusionsThe present study consolidates the importance of upstream and downstream process optimization for the overall enhancement in the xylanase production. The xylanase fromA. tubingensisFDHN1 shows the stability at different pH and temperature, and it was also active in the presence of organic solvents. These properties of xylanase are very much important from an industrial application point of view.
Does Aggressive Surgery Improve Outcomes? Interaction Between Preoperative Disease Burden and Complex Surgery in Patients With Advanced-Stage Ovarian Cancer: An Analysis of GOG 182
Authors: Horowitz Neil S. , Miller Austin , Rungruang Bunja , Richard Scott D. , Rodriguez Noah , Bookman Michael A. , Hamilton Chad A. , Krivak Thomas C. , Maxwell G. Larry 
Published: February 2015

Purpose To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction. Patients and Methods Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis. Results Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS. Conclusion In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD.
Health-Related Quality of Life in Stable, Long-Term Survivors of Low-Grade Glioma
Authors: Boele Florien W. , Douw Linda , Reijneveld Jaap C. , Robben Rianne , Taphoorn Martin J.B. , Aaronson Neil K. , Heimans Jan J. , Klein Martin 
Published: February 2015

PurposePatients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoastrocytoma with clinically and radiologically stable disease.Patients and MethodsPatients completed self-report measures of generic HRQOL (Short Form-36 [SF-36]) and disease-specific HRQOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Cancer Module). Assessments took place at midterm and long-term follow-up, on average 6 and 12 years after histologic diagnosis and initial treatment, respectively. Comparisons between patients with LGG and individually matched healthy controls were made, and change within the patients with LGG was calculated, as was minimal detectable change.ResultsAlthough no statistically significant differences between patients with LGG and healthy matched controls were found at midterm follow-up, patients with LGG had worse physical role functioning (P = .004) and general health perceptions (P = .004) than controls at long-term follow-up. Within patients with stable LGG (n = 65), physical HRQOL (the SF-36 physical component summary and the physical functioning subscale) was significantly worse at long-term than at midterm follow-up (both P < .001). Although 48% of patients improved or remained stable on all HRQOL scales, 38.5% of patients experienced detectable decline on one or more scales.ConclusionAlthough HRQOL remains mostly preserved in the majority of patients with LGG, a subset of patients experience detectable decline on one or more HRQOL scales despite long-term stable disease. For this subgroup, further research is recommended to better aid patients in dealing with the consequences of LGG.
Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus–Related Oropharyngeal Carcinomas
Authors: Huang Shao Hui , Xu Wei , Waldron John , Siu Lillian , Shen Xiaowei , Tong Li , Ringash Jolie , Bayley Andrew , Kim John , Hope Andrew , Cho John , Giuliani Meredith , Hansen Aaron , Irish Jonathan , Gilbert Ralph , Gullane Patrick , Perez-Ordonez Bayardo , Weinreb Ilan , Liu Fei-Fei , O'Sullivan Brian 
Published: February 2015

Purpose To refine stage and prognostic group for human papillomavirus (HPV) –related nonmetastatic (M0) oropharyngeal cancer (OPC). Methods All patients with nonmetastatic (M0) p16-confirmed OPC treated with radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors. Results The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC (stage I, II, III, and IV 5-year OS: 70%, 58%, 50%, and 30%, respectively; P = .004) but not for patients with HPV-related OPC (stage I, II, III, and IV 5-year OS: 88%, 78%, 71%, and 74%, respectively; P = .56). RPA divided HPV-related OPC into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3; 5-year OS: 82%, 76%, and 54%, respectively; P < .001). AHR also yielded a valid classification, but RPA stage demonstrated better survival prediction. A further RPA (including RPA stage, age, and smoking pack-years [PYs]) derived the following four valid prognostic groups for survival: group I (T1-3N0-N2c_≤ 20 PY), group II (T1-3N0-N2c_> 20 PY), group III (T4 or N3_age ≤ 70), and group IVA (T4 or N3_age > 70; 5-year OS: 89%, 64%, 57%, and 40%, respectively; P < .001). Conclusion An RPA-based TNM stage grouping (stage I/II/III: T1-3N0-N2b/T1-3N2c/T4 or N3, with M1 as stage IV) is proposed for HPV-related OPC as a result of significantly improved survival prediction compared with the seventh edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the American Joint Committee on Cancer/Union for International Cancer Control TNM framework for HPV-related OPC.
Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses
Authors: Blumenthal Gideon M. , Karuri Stella W. , Zhang Hui , Zhang Lijun , Khozin Sean , Kazandjian Dickran , Tang Shenghui , Sridhara Rajeshwari , Keegan Patricia , Pazdur Richard 
Published: February 2015

Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect.
Prostate Cancer Survivorship Care Guideline: American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Resnick Matthew J. , Lacchetti Christina , Bergman Jonathan , Hauke Ralph J. , Hoffman Karen E. , Kungel Terrence M. , Morgans Alicia K. , Penson David F. 
Published: February 2015

Purpose The guideline aims to optimize health and quality of life for the post-treatment prostate cancer survivor by comprehensively addressing components of follow-up care, including health promotion, prostate cancer surveillance, screening for new cancers, long-term and late functional effects of the disease and its treatment, psychosocial issues, and coordination of care between the survivor's primary care physician and prostate cancer specialist. Methods The American Cancer Society (ACS) Prostate Cancer Survivorship Care Guidelines were reviewed for developmental rigor by methodologists. The American Society of Clinical Oncology (ASCO) Endorsement Panel reviewed the content and recommendations, offering modifications and/or qualifying statements when deemed necessary. Results The ASCO Endorsement Panel determined that the recommendations from the 2014 ACS Prostate Cancer Survivorship Care Guidelines are clear, thorough, and relevant, despite the limited availability of high-quality evidence to support many of the recommendations. ASCO endorses the ACS Prostate Cancer Survivorship Care Guidelines, with a number of qualifying statements and modifications. Recommendations Assess information needs related to prostate cancer, prostate cancer treatment, adverse effects, and other health concerns and provide or refer survivors to appropriate resources. Measure prostate-specific antigen (PSA) level every 6 to 12 months for the first 5 years and then annually, considering more frequent evaluation in men at high risk for recurrence and in candidates for salvage therapy. Refer survivors with elevated or increasing PSA levels back to their primary treating physician for evaluation and management. Adhere to ACS guidelines for the early detection of cancer. Assess and manage physical and psychosocial effects of prostate cancer and its treatment. Annually assess for the presence of long-term or late effects of prostate cancer and its treatment.
Napping Reverses the Salivary Interleukin-6 and Urinary Norepinephrine Changes Induced by Sleep Restriction
Authors: Faraut Brice , Nakib Samir , Drogou Catherine , Elbaz Maxime , Sauvet Fabien , De Bandt Jean-Pascal , Léger Damien 
Published: February 2015

Context:
Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep.

Objectives:
Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown.

Design:
This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects.

Setting:
The study was conducted in a laboratory-based study.

Participants:
The subjects were 11 healthy young men.

Intervention:
We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00.

Main Outcome Measures:
Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods.

Results:
The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition.

Conclusions:
Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.