bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Analysis of Multiple Biomarkers from Circulating Tumor Cells Enabled by Exclusion-Based Analyte Isolation
Authors: Sperger Jamie M. , Strotman Lindsay N. , Welsh Allison , Casavant Benjamin P. , Chalmers Zachery , Horn Sacha , Heninger Erika , Thiede Stephanie M. , Tokar Jacob , Gibbs Benjamin K. , Guckenberger David J. , Carmichael Lakeesha , Dehm Scott M. , Stephens Philip J. , Beebe David J. , Berry Scott M. , Lang Joshua M. 
Published: July 2016

Abstract
Purpose: There is a critical clinical need for new predictive and pharmacodynamic biomarkers that evaluate pathway activity in patients treated with targeted therapies. A microscale platform known as VERSA (versatile exclusion-based rare sample analysis) was developed to integrate readouts across protein, mRNA, and DNA in circulating tumor cells (CTC) for a comprehensive analysis of the androgen receptor (AR) signaling pathway.
Experimental Design: Utilizing exclusion-based sample preparation principles, a handheld chip was developed to perform CTC capture, enumeration, quantification, and subcellular localization of proteins and extraction of mRNA and DNA. This technology was validated across integrated endpoints in cell lines and a cohort of patients with castrate-resistant prostate cancer (CRPC) treated with AR-targeted therapies and chemotherapies.
Results: The VERSA was validated in cell lines to analyze AR protein expression, nuclear localization, and gene expression targets. When applied to a cohort of patients, radiographic progression was predicted by the presence of multiple AR splice variants and activity in the canonical AR signaling pathway. AR protein expression and nuclear localization identified phenotypic heterogeneity. Next-generation sequencing with the FoundationOne panel detected copy number changes and point mutations. Longitudinal analysis of CTCs identified acquisition of multiple AR variants during targeted treatments and chemotherapy.
Conclusions: Complex mechanisms of resistance to AR-targeted therapies, across RNA, DNA, and protein endpoints, exist in patients with CRPC and can be quantified in CTCs. Interrogation of the AR signaling pathway revealed distinct patterns relevant to tumor progression and can serve as pharmacodynamic biomarkers for targeted therapies. Clin Cancer Res; 23(3); 746–56. ©2016 AACR.
Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma
Authors: Li Qingguo , Qin Yi , Wei Ping , Lian Peng , Li Yaqi , Xu Ye , Li Xinxiang , Li Dawei , Cai Sanjun 
Published: July 2016

Abstract
Growth arrest–specific 1 (Gas1) plays a critical role in growth suppression. Previous study indicated that Gas1 was closely associated with survival in patients with colorectal cancer; however, the underlying molecular mechanism remains unclear. In this study, we sought to determine the role of Gas1 in tumorigenesis and metastasis, and elucidate the possible mechanism. First, Gas1 was determined as a negative regulator of oncogenesis and metastasis in colorectal cancer. Mechanistically, Gas1 negatively regulated the aerobic glycolysis, a process that contributed to tumor progression and metastasis by providing energy source and building blocks for macromolecule synthesis. To further consolidate the role of Gas1 in glycolysis, the impact of Gas1 in the transcription of key glycolytic enzymes for glucose utilization was examined. As expected, GLUT4, HK2, and LDHB exhibited a decreased expression pattern. Consistent with this observation, an in vivo subcutaneous xenograft mouse model also confirmed the hypothesis that Gas1 is a negative regulator of glycolysis as reflected by the decreased 18FDG uptake in PET/CT system. Moreover, Gas1 negatively regulated the AMPK/mTOR/p70S6K signaling axis, a well-established cascade that regulates malignant cancer cell behaviors including proliferation, metastasis, and aberrant cancer metabolism. In the end, it was determined that Gas1 is a transcriptional target of FOXM1, whose role in colorectal cancer has been widely studied. Taken together, these studies establish Gas1 as a negative regulator in colorectal cancer.
Implications: Gas1 suppresses cell proliferation, invasion, and aerobic glycolysis of colorectal cancer both in vitro and in vivo. Mechanistically, Gas1 inhibited EMT and the Warburg effect via AMPK/mTOR/p70S6K signaling, and Gas1 itself was directly regulated by the transcription factor FOXM1. Mol Cancer Res; 14(9); 830–40. ©2016 AACR.
Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome
Authors: Gordon Leslie B. , Kleinman Monica E. , Massaro Joe , D’Agostino Ralph B. , Shappell Heather , Gerhard-Herman Marie , Smoot Leslie B. , Gordon Catherine M. , Cleveland Robert H. , Nazarian Ara , Snyder Brian D. , Ullrich Nicole J. , Silvera V. Michelle , Liang Marilyn G. , Quinn Nicolle , Miller David T. , Huh Susanna Y. , Dowton Anne A. , Littlefield Kelly , Greer Maya M. , Kieran Mark W. 
Published: July 2016

Background:

Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in
LMNA
yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation.

Methods:
Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial.

Results:

No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (
P
<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (
P
=0.001) and volumetric (
P
<0.001–0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (
P
<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%;
P
=0.001) and femoral (0% to 12%;
P
=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%;
P
=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial.

Conclusions:
Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00879034 and NCT00916747.
Estimating Lightning from Microwave Remote Sensing Data
Authors: Magi Brian I. , Winesett Thomas , Cecil Daniel. J. 
Published: July 2016

AbstractThis study evaluates a method for estimating the cloud-to-ground (CG) lightning flash rate from microwave remote sensing data. Defense Meteorological Satellite Program satellites have been in operation since 1987 and include global-viewing microwave sensors that capture thunderstorms as brightness temperature depressions. The National Lightning Detection Network (NLDN) has monitored CG lightning in the United States since 1997. This study investigates the relationship between CG lightning and microwave brightness temperature fields for the contiguous United States from April to September for the years 2005–12. The findings suggest that an exponential function, empirically fit to the NLDN and SSM/I data, provides lightning count measurements that agree to within 60%–70% with NLDN lightning, but with substantial misses and false alarms in the predictions. The discrepancies seem to be attributable to regional differences in thunderstorm characteristics that require a detailed study at smaller spatial scales to truly resolve, but snow at higher elevations also produces some anomalous microwave temperature depressions similar to those of thunderstorms. The results for the contiguous United States in this study are a step toward potentially using SSM/I data to estimate CG lightning around the world, although the sensitivity of the results to regional differences related to meteorological regimes would need further study.
Adaptive Dealiasing for Doppler Velocities Scanned from Hurricanes and Typhoons
Authors: Jiang Yuan , Xu Qin 
Published: July 2016

AbstractBy fitting a parametric vortex model directly to aliased radar radial velocities scanned from a hurricane, the maximum tangential velocity and its radial distance from the hurricane vortex center can be estimated by the recently developed alias-robust vortex analysis. This vortex analysis can be refined to produce a suitable reference radial velocity field on each tilt of a radar scan for the reference check in the first main step of dealiasing. This paper presents the techniques developed for the refinements and shows how and to what extent the refined vortex analysis can improve the reference check and thus enhance the dealiased data coverage, especially over severely aliased data areas around the vortex core of a hurricane or typhoon. In addition, stringent threshold conditions are used in the reference check and the subsequent continuity check to ensure the accepted data are free of alias or almost so. The robustness and improved performance of the method are exemplified by the results tested with severely aliased radial velocities scanned by operational WSR-88D radars from hurricanes in the United States and by operational China New Generation Weather Radar (CINRAD) base data format SA radars from typhoons in China.
Burying the Alliance: Interment, Repatriation and the Politics of the Sacred in Occupied Germany
Authors: Bernstein Seth 
Published: July 2016

In 1945 Europe was a vast graveyard. The diaspora of the dead was perhaps most prominent in Germany, where the dead of the four occupying forces were spread across the country. As the allies worked through the postwar settlement with Germany, they considered another pressing question: How to treat the dead? The case of occupied Germany highlights different approaches to commemoration. Soviet officials commemorated the war dead as symbols of the collective sacrifice of the USSR in Eastern Europe, while the western allies desired to identify and rebury fallen soldiers to meet the expectations of their domestic audiences. Despite these differences, the politics of the sacred surrounding the dead necessitated that the allies engage one another. As the occupation regimes of France, the United Kingdom and the United States of America embarked on their mission to retrieve their dead from the Soviet zone, USSR officials reacted with skepticism and hostility. But rather than rejecting what they viewed as attempts at espionage, Soviet officers traded the western dead for their own sacred mission – the chance to return living Soviet repatriates from the western zones of occupation. Even as animosity grew in the emerging Cold War, occupation officials made uneasy compromises across the iron curtain.
Book Review: Mukul Dube, India Since 2002: Articles Published in Mainstream, Yogesh Atal and Sunil K. Choudhary, Right Turn in Indian Polity—Modi on BJP’s Chariot
Authors: Chaturvedi Shashank 
Published: July 2016

Mukul Dube, India Since 2002: Articles Published in Mainstream, New Delhi, AlterNotes Press, 2015, 198 pp., ₹380, ISBN: 978-81-908923-6-0. Yogesh Atal and Sunil K. Choudhary, Right Turn in Indian Polity—Modi on BJP’s Chariot, New Delhi, Har-Anand Publication, 2015, 248 pp., ₹695, ISBN: 978-81-241-1888-7.
Evaluating Diabetes Educational Interventions With a Skill Development Component in Adolescents With Type 1 Diabetes
Authors: Abualula Nada A. , Jacobsen Kathryn H. , Milligan Renee A. , Rodan Margaret F. , Conn Vicki S. 
Published: July 2016

Purpose Adolescents with type 1 diabetes mellitus (T1DM) may have reduced quality of life (QOL) when compared with their peers. This systematic review evaluated the effectiveness of diabetes self-management education (DSME) interventions with a skills development component on the QOL of adolescents with T1DM. Methods Six databases were systematically searched for studies on the QOL outcomes of DSME interventions for adolescents with T1DM. Fourteen studies published between 1994 and 2014 met the inclusion criteria. Results Of the 14 studies, only 4 had significant QOL outcomes for the intervention participants. Successful DSME interventions had indirect behavioral skills foci or a combination of indirect and direct behavioral skills foci and a duration ≥2 months. Conclusion This review provides evidence that educational interventions with an indirect behavioral skills development that facilitates diabetes management may improve QOL among adolescents with T1DM. Structured interventions targeting adolescents’ QOL are needed to determine which are most effective in improving QOL. Adolescents with T1DM should be routinely screened and monitored for low QOL and referred to QOL-improving interventions.
Preoperative hemoglobin level: the best predictor of transfusion of packed red cells
Authors: de Boer Wiebe J. , Visser Cornelis , Ganushchak Yuri M. 
Published: July 2016

Blood transfusions could have serious consequences for patients. A reduction in the transfusion rate could be accomplished by an optimized blood management. Clear guidelines and awareness among all employees at a single institution have resulted in a reduction in transfusion rates in recent years. Identification of the group of patients who still received a blood transfusion in recent years could result in a further reduction. This study enrolled 4022 patients undergoing cardiothoracic surgery between 2008 and 2013. Patients were divided into three groups: “no blood transfusion”, “transfusion of packed red cells only” and “any other combinations of blood transfusion”. In total, 16 variables were tested for their association with the administration of homologous blood. The variables associated with blood transfusion were included in a stepwise multinomial logistic regression analysis to find the variables with the strongest association. For the transfusion of packed red cells only and any other combinations of blood transfusion, the following predictors are found: gender, age, weight, type of surgery, reoperation, unstable angina pectoris, endocarditis, recent myocardial infarction, preoperative creatinine level, preoperative hemoglobin level and preoperative platelet count. The best predictor for the transfusion of packed red cells is preoperative hemoglobin level (4.1 to 7.8 mmol/l). For other blood products, the strongest association was found with type of surgery (aortic surgery, ventricular septal rupture and intracardiac tumour).
Platelet-Rich Plasma Activates Proinflammatory Signaling Pathways and Induces Oxidative Stress in Tendon Fibroblasts
Authors: Hudgens Joshua L. , Sugg Kristoffer B. , Grekin Jeremy A. , Gumucio Jonathan P. , Bedi Asheesh , Mendias Christopher L. 
Published: July 2016

Background: Tendon injuries are one of the most common musculoskeletal conditions in active patients. Platelet-rich plasma (PRP) has shown some promise in the treatment of tendon disorders, but little is known as to the mechanisms by which PRP can improve tendon regeneration. PRP contains numerous different growth factors and cytokines that activate various cellular signaling cascades, but it has been difficult to determine precisely which signaling pathways and cellular responses are activated after PRP treatment. Additionally, macrophages play an important role in modulating tendon regeneration, but the influence of PRP on determining whether macrophages assume a proinflammatory or anti-inflammatory phenotype remains unknown. Purpose: To use genome-wide expression profiling, bioinformatics, and protein analysis to determine the cellular pathways activated in fibroblasts treated with PRP. The effect of PRP on macrophage polarization was also evaluated. Study Design: Controlled laboratory study. Methods: Tendon fibroblasts or macrophages from rats were cultured and treated with either platelet-poor plasma (PPP) or PRP. RNA or protein was isolated from cells and analyzed using microarrays, quantitative polymerase chain reaction, immunoblotting, or bioinformatics techniques. Results: Pathway analysis determined that the most highly induced signaling pathways in PRP-treated tendon fibroblasts were TNFα and NFκB pathways. PRP also downregulated the expression of extracellular matrix genes and induced the expression of autophagy-related genes and reactive oxygen species (ROS) genes and protein markers in tendon fibroblasts. PRP failed to have a major effect on markers of macrophage polarization. Conclusion: PRP induces an inflammatory response in tendon fibroblasts, which leads to the formation of ROS and the activation of oxidative stress pathways. PRP does not appear to significantly modulate macrophage polarization. Clinical Relevance: PRP might act by inducing a transient inflammatory event, which could then trigger a tissue regeneration response.
Should We Limit Innings Pitched After Ulnar Collateral Ligament Reconstruction in Major League Baseball Pitchers?
Authors: Erickson Brandon J. , Cvetanovich Gregory L. , Bach Bernard R. , Bush-Joseph Charles A. , Verma Nikhil N. , Romeo Anthony A. 
Published: July 2016

Background: Ulnar collateral ligament reconstruction (UCLR) has become a common procedure among Major League Baseball (MLB) pitchers. It is unclear if a limit on innings pitched after UCLR should be instituted to prevent revision UCLR. Hypothesis: Number of innings pitched and number of pitches thrown after UCLR will not affect whether a pitcher requires a revision UCLR. Study Design: Descriptive laboratory study. Methods: All MLB pitchers between 1974 and 2015 who pitched at least 1 full season after UCLR were included in this study. Pitch counts and innings pitched for the first full season after UCLR as well as total pitch count and total innings pitched were recorded. Pitch counts and innings pitched were compared among players who required revision UCLR and those who did not. Results: Overall, 154 pitchers were included. Of these, 135 pitchers did not require revision UCLR while 19 underwent revision UCLR. No significant difference existed between pitchers who underwent revision UCLR and those who did not when comparing number of innings pitched in the season after UCLR (79.4 ± 46.7 vs 90.1 ± 58.6; P = .9016), number of pitches thrown in the season after UCLR (1233.2 ± 710.4 vs 1449.2 ± 904.1; P = .7337), number of innings pitched in the pitcher’s career after UCLR (357.4 ± 312.0 vs 399.3 ± 446.4; P = .6945), and number of pitches thrown in the pitcher’s career after UCLR (5632.7 ± 4583.9 vs 5674.7 ± 5755.4; P = .4789), respectively. Furthermore, no difference existed in revision rate between pitchers who pitched more or less than 180 innings in the first full season after UCLR ( P = .6678). Conclusion: The number of innings pitched and number of pitches thrown in the first full season as well as over a player’s career after UCLR are not associated with an increased risk of a pitcher requiring revision UCLR.
Predictors of Length of Career After Hip Arthroscopy for Femoroacetabular Impingement in Professional Hockey Players
Authors: Menge Travis J. , Briggs Karen K. , Philippon Marc J. 
Published: July 2016

Background: Previous studies have shown that professional hockey players return to sport at a high rate after hip arthroscopy, although it is unknown how long players continue to compete at a professional level after surgery. Purpose: To determine the prevalence of athletes who continued playing in the National Hockey League (NHL) for a minimum of 5 years after hip arthroscopy for treatment of symptomatic femoroacetabular impingement (FAI) and to determine predictors associated with length of career. Study Design: Case series; Level of evidence, 4. Methods: A total of 60 professional hockey players (69 hips) underwent hip arthroscopy for FAI by a single surgeon between 2005 and 2010. Data were retrieved from NHL.com and Hockey-reference.com regarding information on each player’s professional career. Position played, age, surgical procedure, and intraoperative findings were also used in data analysis. Results: There were 12 centers, 15 defensemen, 16 goalies, and 17 wings studied. Of the 60 athletes, 40 (67%) continued to play professionally a minimum of 5 years after hip arthroscopy. As of the 2015 season, the mean length of a player’s NHL career was 13.7 years (range, 2-27 years), with an average of 5.9 years played after hip arthroscopy. There was no difference in length of career or years played when goalies were compared with other positions ( P = .760). Length of career and years played after arthroscopy correlated with age at surgery ( r = 0.799 and −0.408, respectively). Players who played ≥5 years after arthroscopy were significantly younger than those who did not (25 vs 30 years; P = .001). Athletes who played <5 years after arthroscopy had a longer average duration of symptoms before surgery when compared with those who played ≥5 years (20.2 vs 9.3 months; P = .049). There were no differences in length of career or years played after arthroscopy based on type of labral treatment. Conclusion: Professional NHL players who underwent hip arthroscopy for FAI were able to continue playing for an average of 5.9 years after surgery, with 67% playing a minimum of 5 years postoperatively. Younger age and shorter duration of symptoms at time of surgery correlated with greater length of career and years played after hip arthroscopy. Players who did not play a minimum of 5 years postoperatively had significantly longer duration of symptoms before surgery. The study data support early arthroscopic treatment of professional hockey players with symptomatic FAI.
The apoptotic effects of silibinin on MDA-MB-231 and MCF-7 human breast carcinoma cells
Authors: Bayram D , Çetin ES , Kara M , Özgöçmen M , Candan IA 
Published: July 2016

Background: Silibinin is a bioactive flavonolignan extracted from milk thistle, known as Silybum marianum. Silibinin exerts strong antiproliferative, proapoptotic, and anti-inflammatory effects. Many studies have shown that silibinin inhibits experimentally induced malignancies of the liver, prostate, skin, and colon as well as promotes inhibition of the proliferation of cancer cell lines in vitro. This study aimed to investigate the effects of silibinin on the human breast carcinoma cell lines MDA-MB-231 and MCF-7 in monolayer and spheroid cultures. Method: The MDA-MB-231 and MCF-7 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with silibinin at 24, 48, and 72 h of incubation. The 5-bromo-2′-deoxyuridine labeling index was used to determine the cells of the synthesis phase. Poly-ADP-ribose-polimerase immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick and labeling assay were used to determine the death of cells in both the monolayer and spheroid cultures. Results: An half maximal inhibitory concentration dose of silibinin in MDA-MB-231 and MCF-7 cells was 100 µM/mL at 24, 48, and 72 h of incubation. Terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase were detected after treatment with silibinin in both the monolayer and spheroid cultures. The dead cell count was higher in the MDA-MB-231 and MCF-7 cell lines with silibinin applied than in the controls. Conclusions: Our study demonstrated that silibinin applications enhanced terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase in comparison to the control in both the monolayer and spheroid cultures.