bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there a correlation between an eGFR slope measured over a 5-year period and incident cardiovascular events in the following 5 years among a Flemish general practice population: a retrospective cohort study
Authors: Van Pottelbergh Gijs , Mamouris Pavlos , Opdeweegh Nele , Vaes Bert , Goderis Geert , Van Den Akker Marjan 
Published: November 2018

ObjectivesTo examine if the estimated glomerular filtration rate (eGFR) slope over a 5-year period is related to incident cardiovascular (CV) events in the following 5 years.DesignRetrospective cohort study.SettingPrimary care.ParticipantsAll patients aged ≥50 years with at least four eGFR measurements between 01 January 2006 and 31 December 2010 were included in the study.Outcome measuresDuring the follow-up period (01 January 2011 until 31 December 2015), CV events (acute myocardial infarction, stroke (cerebrovascular accident (CVA)/transient ischemic attack (TIA)), peripheral arterial disease and acute heart failure) were identified.MethodsThe slope was calculated by the least square method (in mL/min/year). The following slope categories were considered: (−1 to 1), (−3 to −1) (−5 to −3), ≤−5, (1 to 3), (3 to 5) and ≥5.00 mL/min/year. Cox proportional hazards model was used to assess the association between eGFR slope and incidence of CV events. Survival probability from CV events was estimated per slope category.Results19 567 patients had at least four eGFR measurements, of whom 52% was female. 12% of the ≤−5 slope category developed a new CV event in comparison to 7.8% of the reference group and 5.4% of the ≥5 slope category. Survival rates were worst in those with a slope ≤−5. Patients with a slope of (−5 to −3) and ≤−5 had an adjusted HR of 1.37 and 1.55, respectively. Most patients with a slope <−3 mL/min had an eGFR still >60 mL/min.ConclusionsNegative eGFR slopes of at least 3 mL/min/year give irrespectively of the eGFR itself a higher risk of CV events compared with patient groups with stable or improved kidney function. So the eGFR slope identifies an easy to define group of patients with a high risk for developing CV events.
Mechanical thrombectomy in children and adolescents: report of five cases and literature review
Authors: Bhogal Pervinder , Hellstern Victoria , AlMatter Muhammad , Ganslandt Oliver , Bäzner Hansjörg , Aguilar Pérez Marta , Henkes Hans 
Published: November 2018

BackgroundPaediatric arterial ischaemic stroke is an important cause of morbidity and mortality among children. Currently, there are no recommendations regarding mechanical thrombectomy in children despite overwhelming evidence of improved outcomes in adults. Therefore, the need for individual case reports and case series is important to highlight potential advantages and disadvantages in this approach.Case descriptionsWe retrospectively searched our prospectively maintained database of patients undergoing mechanical thrombectomy for ischaemic stroke. We describe five children, aged between 7 and 17, who underwent mechanical thrombectomy for acute ischaemic stroke. We provide an account of their clinical presentations, operative treatment and postoperative outcome.DiscussionMechanical thrombectomy in children, especially older children, can be performed safely and with existing devices. Although a randomised controlled trial would provide compelling evidence of the potential advantages to this technique, the lack of this should not prevent the use of this procedure by trained neurointerventionists.
A GPU-Based Automatic Approach for Guide Wire Tracking in Fluoroscopic Sequences
Authors: Chen Ken , Wang Cheng , Xie Yaoqin , Zhou Shoujun 
Published: November 2018

Guide wire tracking in fluoroscopic images has done a significant task in assisting the physicians during radiology-aided interventions. Many groups have tried to detect the guide wire from the fluoroscopic images based on the image properties. The main challenge is that manual intervention is required during the detection. Other groups try to introduce localizers to track guide wires during intervention, which requires additional hardware equipment, and may intervene with the traditional clinical routines. Machine learning methods are also exploited. Although such methods may provide accurate tracking, they often require large amount of data and training time. In this paper, we propose a GPU-based fast and automatic approach to track guide wires in fluoroscopic sequences. We propose a multi-scale filtering and gradient vector field-based real-time tracking method for guide wire tracking from fluoroscopic images. To improve calculation efficiency and meet real-time application requirement, we propose a GPU-based acceleration scheme, and also a Bayesian filter-like motion tracking method to limit the guide wire tracking to a smaller range to improve calculation efficiency. We test our proposed method on two test data sets of fluoroscopic sequences of 102 frames and 72 frames. We achieve an average guide wire detection rate of 96.7%, a false detection rate of 0.0011% and an error distance measure of 0.83 pixels for the first sequence, and 98.8%, 0.000069% and 0.85 pixels, respectively, for the second sequence. With the proposed acceleration method, we finish calculation for the first sequence in nine seconds, thus, efficiency is enhanced by 100 times with the unaccelerated algorithm.
Low Tristetraprolin Expression Is Associated with Lethal Prostate Cancer
Authors: Gerke Travis , Beltran Himisha , Wang Xiaodong , Lee Gwo-Shu Mary , Sboner Andrea , Karnes R. Jeffrey , Klein Eric A. , Davicioni Elai , Yousefi Kasra , Ross Ashley E. , Börnigen Daniela , Huttenhower Curtis , Mucci Lorelei A. , Trock Bruce J. , Sweeney Christopher J. 
Published: November 2018

Abstract

Background:
Inflammation is linked to prostate cancer progression and is mediated by NF-κB. Tristetraprolin is a key node of NF-κB activation and we investigated its biological and prognostic role in lethal prostate cancer.

Methods:
In vitro assays assessed the function of tristetraprolin and the association between low mRNA tristetraprolin levels and lethal prostate cancer (metastatic disease or death) was assessed across independent prostatectomy cohorts: (i) nested case-control studies from Health Professionals Follow-up Study and Physicians’ Health Study, and (ii) prostatectomy samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and Memorial Sloan Kettering Cancer Center. Tristetraprolin expression levels in prostatectomy samples from patients with localized disease and biopsies of metastatic castration–resistant prostate cancer (mCRPC) were assessed in a Cornell University cohort.

Results:
In vitro tristetraprolin expression was inversely associated with NF-κB–controlled genes, proliferation, and enzalutamide sensitivity. Men with localized prostate cancer and lower quartile of tumor tristetraprolin expression had a significant, nearly two-fold higher risk of lethal prostate cancer after adjusting for known clinical and histologic prognostic features (age, RP Gleason score, T-stage). Tristetraprolin expression was also significantly lower in mCRPC compared with localized prostate cancer.

Conclusions:
Lower levels of tristetraprolin in human prostate cancer prostatectomy tissue are associated with more aggressive prostate cancer and may serve as an actionable prognostic and predictive biomarker.

Impact:
There is a clear need for improved biomarkers to identify patients with localized prostate cancer in need of treatment intensification, such as adjuvant testosterone suppression, or treatment de-intensification, such as active surveillance. Tristetraprolin levels may serve as informative biomarkers in localized prostate cancer.
Dietary Acrylamide Is Not Associated with Renal Cell Cancer Risk in the CPS-II Nutrition Cohort
Authors: McCullough Marjorie L. , Hodge Rebecca A. , Um Caroline Y. , Gapstur Susan M. 
Published: November 2018

Abstract

Background:
Acrylamide, an industrial chemical and probable human carcinogen, can be formed in primarily carbohydrate-containing foods during high-heat cooking or processing. Most epidemiologic studies show no associations of dietary acrylamide intake with most cancer outcomes, but limited prospective evidence suggests a positive association with renal cell carcinoma (RCC).

Methods:
In 1999, 102,154 men and women from the Cancer Prevention Study-II Nutrition Cohort completed a questionnaire on diet, lifestyle, and cancer risk factors and were followed through June 30, 2013. Cox proportional hazards regression was used to estimate the HR and 95% confidence interval (CI) for the association between estimated dietary acrylamide intake and risk of RCC.

Results:
After 1,137,441 person-years of follow-up, 412 cases of invasive RCC occurred. In multivariable-adjusted models, there was no association between acrylamide intake and risk of RCC (HR = 1.09; 95% CI, 0.82–1.43) for the highest versus lowest quartile of intake. Associations were not modified by sex or smoking history.

Conclusions:
We found no associations between dietary acrylamide exposure and risk of invasive RCC.

Impact:
The findings from this large, prospective analysis do not support a positive association between higher dietary acrylamide intake and RCC risk.
Preclinical Efficacy of Endoglin-Targeting Antibody–Drug Conjugates for the Treatment of Ewing Sarcoma
Authors: Puerto-Camacho Pilar , Amaral Ana Teresa , Lamhamedi-Cherradi Salah-Eddine , Menegaz Brian A. , Castillo-Ecija Helena , Ordóñez José Luis , Domínguez Saioa , Jordan-Perez Carmen , Diaz-Martin Juan , Romero-Pérez Laura , Lopez-Alvarez Maria , Civantos-Jubera Gema , Robles-Frías María José , Biscuola Michele , Ferrer Cristina , Mora Jaume , Cuglievan Branko , Schadler Keri , Seifert Oliver , Kontermann Roland , Pfizenmaier Klaus , Simón Laureano , Fabre Myriam , Carcaboso Ángel M. , Ludwig Joseph A. , de Álava Enrique 
Published: November 2018

Abstract

Purpose:
Endoglin (ENG; CD105) is a coreceptor of the TGFβ family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGFβ, and as a soluble matricellular protein (sENG) when cleaved by matrix metalloproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma, an aggressive bone cancer that primarily occurs in adolescents and young adults. However, the therapeutic value of ENG targeting has not been fully explored in this disease.

Experimental Design:
We characterized the expression pattern of transmembrane ENG, sENG, and MMP14 in preclinical and clinical samples. Subsequently, the antineoplastic potential of two novel ENG-targeting monoclonal antibody–drug conjugates (ADC), OMTX503 and OMTX703, which differed only by their drug payload (nigrin-b A chain and cytolysin, respectively), was assessed in cell lines and preclinical animal models of Ewing sarcoma.

Results:
Both ADCs suppressed cell proliferation in proportion to the endogenous levels of ENG observed in vitro. Moreover, the ADCs significantly delayed tumor growth in Ewing sarcoma cell line–derived xenografts and patient-derived xenografts in a dose-dependent manner.

Conclusions:
Taken together, these studies demonstrate potent preclinical activity of first-in-class anti-ENG ADCs as a nascent strategy to eradicate Ewing sarcoma.
E3611—A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma
Authors: Tarhini Ahmad A. , Lee Sandra J. , Li Xiaoxue , Rao Uma N.M. , Nagarajan Arun , Albertini Mark R. , Mitchell Jerry W. , Wong Stuart J. , Taylor Mark A. , Laudi Noel , Truong Phu V. , Conry Robert M. , Kirkwood John M. 
Published: November 2018

AbstractPurpose:Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis.Patients and Methods:E3611 followed a 2-by-2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipilimumab doses) and (ii) ipi3 versus ipi10 (across HDI status). We hypothesized that median progression-free survival (PFS) would improve from 3 to 6 months with HDI versus no HDI and with ipi10 versus ipi3.Results:For eligible and treated patients (N = 81) at a median follow-up time of 29.8 months, median PFS was 4.4 months [95% confidence interval (CI), 2.7–8.2] when ipilimumab was used alone and 7.5 months (95% CI, 5.1–11.0) when HDI was added. Median PFS was 3.8 months (95% CI, 2.6–7.5) with 3 mg/kg ipilimumab and 6.5 months (95% CI, 5.1–13.5) with 10 mg/kg. By study arm, median PFS was 8.0 months (95% CI, 2.8–20.2) in arm A, 6.2 months (95% CI, 2.7–25.7) in B, 5.7 months (95% CI, 1.5–11.1) in C, and 2.8 months (95% CI, 2.6–5.7) in D. The differences in PFS and overall survival (OS) did not reach statistical significance. Adverse events were consistent with the known profiles of ipilimumab and HDI and significantly higher with HDI and ipi10.Conclusions:Although PFS was increased, the differences resulting from adding interferon-α or a higher dose of ipilimumab did not reach statistical significance and do not outweigh the added toxicity risks.
Targeting Purinergic Receptor P2Y2 Prevents the Growth of Pancreatic Ductal Adenocarcinoma by Inhibiting Cancer Cell Glycolysis
Authors: Hu Li-Peng , Zhang Xiao-Xin , Jiang Shu-Heng , Tao Ling-Ye , Li Qing , Zhu Li-Li , Yang Ming-Wei , Huo Yan-Miao , Jiang Yong-Sheng , Tian Guang-Ang , Cao Xiao-Yan , Zhang Yan-Li , Yang Qin , Yang Xiao-Mei , Wang Ya-Hui , Li Jun , Xiao Gary Guishan , Sun Yong-Wei , Zhang Zhi-Gang 
Published: November 2018

Abstract

Purpose:
Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to prevent cancer progression. We aimed to determine whether blocking extracellular ATP–P2RY2 axis could be a potential therapeutic approach for PDAC treatment.

Experimental Design:
Expression of P2RY2 was determined in 264 human PDAC samples and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity, and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression.

Results:
P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT–mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevated expression of c-Myc and HIF1α, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacologic inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. In addition, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice.

Conclusions:
These findings reveal the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.
Predicting Novel Therapies and Targets: Regulation of Notch3 by the Bromodomain Protein BRD4
Authors: Villar-Prados Alejandro , Wu Sherry Y. , Court Karem A. , Ma Shaolin , LaFargue Christopher , Chowdhury Mamur A. , Engelhardt Margaret I. , Ivan Cristina , Ram Prahlad T. , Wang Ying , Baggerly Keith , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel , Yang Shyh-Ming , Maloney David J. , Yoshioka Makoto , Strovel Jeffrey W. , Roszik Jason , Sood Anil K. 
Published: November 2018

Abstract
Systematic approaches for accurate repurposing of targeted therapies are needed. We developed and aimed to biologically validate our therapy predicting tool (TPT) for the repurposing of targeted therapies for specific tumor types by testing the role of Bromodomain and Extra-Terminal motif inhibitors (BETi) in inhibiting BRD4 function and downregulating Notch3 signaling in ovarian cancer.
Utilizing established ovarian cancer preclinical models, we carried out in vitro and in vivo studies with clinically relevant BETis to determine their therapeutic effect and impact on Notch3 signaling.
Treatment with BETis or siRNA-mediated BRD4 knockdown resulted in decreased cell viability, reduced cell proliferation, and increased cell apoptosis in vitro. In vivo studies with orthotopic mouse models demonstrated that treatment with BETi decreased tumor growth. In addition, knockdown of BRD4 with doxycycline-inducible shRNA increased survival up to 50% (P &lt; 0.001). Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both in vitro and in vivo. BRD4 inhibition also decreased the expression of NOTCH3 targets, including HES1. Chromatin immunoprecipitation revealed that BRD4 was present at the NOTCH3 promoter.
Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression.
The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.
Water bugs (Insecta: Hemiptera: Heteroptera) of Himalayan and sub-Himalayan regions of West Bengal, India
Authors: Basu Srimoyee , Chandra Kailash , Subramanian Kumrapuram Apadodharanan , Saha Goutam Kumar 
Published: November 2018

The present study reports a total of 61 Species belonging to 34 genera and 14 families from Darjeeling Himalaya and Jalpaiguri sub Himalaya regions of West Bengal. The study documented 11 new species to science, which were already published, 15 new records to the state and one new record to India. The study showed that the Nepomorphan families are mostly restricted to the slow flowing or to the stagnant ecosystems like ponds or lakes and the running waters are dominated mainly by the Gerromorpha. The key to all family, genera and species of aquatic Hemiptera are provided with their distribution in India and globally. The description of all species with their detail photographs and distribution map were also presented here. The diagnostic characters supported with photographs for each species are also presented here.
Systematic fast-track transition from oncological treatment to dyadic specialized palliative home care: DOMUS – a randomized clinical trial
Authors: Nordly Mie , Skov Benthien Kirstine , Vadstrup Eva S , Kurita Geana P , von Heymann-Horan Annika B , von der Maase Hans , Johansen Christoffer , Timm Helle , Kjellberg Jakob , Sjøgren Per 
Published: November 2018

Background: The focus of specialized palliative care is to improve quality of life for patients with incurable cancer and their relatives including an increased opportunity to make their own choice of place of care and death. Aim: To investigate whether a systematic fast-track transition from oncological treatment to specialized palliative care at home for patients with incurable cancer reinforced with a psychological dyadic intervention could result in more time spent at home and death at home. Secondary aims were to investigate effects on quality of life, symptomatology and survival. Design: A prospective, single-centre, randomized controlled trial ( Clinicaltrials.gov : NCT01885637). Setting/participants: In all, 340 patients with incurable cancer and no or limited antineoplastic treatment options. Results: No statistically significant difference was found regarding number of deaths (4%, p = 0.460) and time spent at home (3%, p = 0.491). The secondary outcomes indicated that the intervention resulted in improved quality of life (−11.6 ± 25.5, p = 0.005, effect size = −0.44, 95% confidence interval = −0.77; −0.11), social functioning (−15.8 ± 31.4, p = 0.001, effect size = −0.50, 95% confidence interval = −0.84; −0.17) and emotional functioning (−9.1 ± 21.2, p = 0.039, effect size = −0.43, 95% confidence interval = −0.76; −0.10) after 6 months. A linear mixed-effect regression model confirmed a possible effect on emotional and social functioning at 6 months. Regarding survival, no differences were found between groups ( p = 0.605). No adverse effects were seen as consequence of the intervention. Conclusions: The main findings indicated that the intervention had no effect on time spent at home or place of death. However, the intervention resulted in a weak improvement of quality of life, social functioning and emotional functioning after 6 months.
Preoperative smoking history is associated with decreased risk of early postoperative cognitive dysfunction in patients of advanced age after noncardiac surgery: a prospective observational cohort study
Authors: Wang Runjia , Wang Gongming , Liu Yang , Zhang Mengyuan 
Published: November 2018

Objective Prevention of postoperative cognitive dysfunction (POCD) in patients of advanced age remains unclear. Studies have shown that the cholinergic anti-inflammatory pathway contributes to a decreased risk of POCD and that nicotine stimulates the cholinergic anti-inflammatory pathway. We investigated whether patients of advanced age with a preoperative smoking history have a decreased risk of POCD. Methods In total, 382 patients (190 smokers, 192 nonsmokers) aged ≥60 years who underwent major noncardiac surgery were enrolled. Cognitive function was assessed, and multivariate logistic regression analyses were performed to identify risk factors. Results On postoperative days 5 and 7, 111 (29.05%) and 90 (23.56%) patients exhibited POCD, respectively. A preoperative smoking history was significantly correlated with a decreased risk of POCD. A high serum tumor necrosis factor-α (TNF-α) level on the operative day was significantly associated with an increased risk of POCD. Early POCD was significantly associated with the sufentanil dosage, age, and education level. The hospital stay in patients with and without POCD was 10.54 ± 2.03 and 8.33 ± 1.58 days, respectively. Conclusion A preoperative smoking history was associated with a decreased risk of early POCD, and a high serum TNF-α level was significantly associated with an increased risk of POCD.