bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Chinese Medicine Injections in the Treatment of Diabetic Foot: A Systematic Review and Meta‐Analysis
Authors: Tan Lizi , Shi Qingyang , Liu Chunxiang , Zhang Junhua , Wang Hui , Zhai Jingbo
Published: October 2018

Context. The role of traditional Chinese medicine injections (TCMIs) in diabetic foot (DF) has not been well estimated. Objective. To evaluate the clinical effective rate, safety, and the financial cost of TCMIs in treating DF and ulcer wound healing. Methods. We searched PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CNKI), VIP database, and Wanfang database from inception to May 2018 to find all randomized control trials (RCTs) related to TCMIs in DF treatment. The search items were “Traditional Chinese Medicine Injection” AND “Diabetic foot or Diabetic foot ulcer” AND “random”. Study Selection and Synthesis. Only RCTs of TCMIs combined conventional therapies versus conventional therapies and that can be quantitatively synthesized were included. Finally, 17 studies and 1294 participants were included after extraction. Two investigators independently extracted and analyzed the data using RevMan5.3 software. Results. The overall clinical effective rate of TCMI groups is higher than that of control groups [RR=1.27, 95CI % (1.20, 1.34), P<0.00001] based on fixed effect model analysis. Regarding motor nerve conduction velocity of median nerve and peroneal nerve, TCMI group showed a significant improvement (MD=3.84[2.28, 5.41], P<0.00001; MD=2.89[0.63, 5.15], P=0.01). Regarding plasma viscosity TCMI group showed a statistically difference (MD=0.27[0.04, 0.49], P=0.02). In terms of blood viscosity at high shear rate, there was an improvement of TCMI group (MD=0.36[0.05, 0.67], P=0.02). However, sensory nerve conduction velocity of peroneal nerve and median nerve showed a contradiction to motor nerve conduction velocity, respectively (MD=2.59[‐1.69, 6.87], p=0.24; MD=2.73[‐0.96, 6.43], P=0.15). Conclusion. The data of this study shows that TCMIs can bring benefits to patients with diabetic foot. However, due to low methodological quality of included RCTs, more rigorous designed RCTs with large sample size are recommended to provide more high‐quality evidence.
Protective Effects of Chinese Traditional Medicine Longhu Rendan against Atherosclerosis via Negative Regulation of LOX‐1
Authors: Yan Sishan , Wu Teng , Li Ning , Zhang Lingyi , Song Jun , Xu Yunzheng , Wang Shumei , Ding Liqin , Jin Jiahua , Liu Ying , Lan Tian
Published: October 2018

Longhu Rendan (LHRD), a Chinese traditional compound medicine, has a remarkable treatment effect on motion sickness for about half a century. However, the role of LHRD in atherosclerosis treatment is still unclear. In this study, LHRD treatment significantly diminished total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) levels in apolipoprotein E gene‐knockout (ApoE-/-) mice fed with high fat and high cholesterol diet (western diet). Besides, LHRD treatment significantly reduced atherosclerotic lesion and plaques formation in both aortic roots and aortic trees. Furthermore, immunofluorescence staining in aortic roots demonstrated that LHRD treatment inhibited lectin‐like oxidized low‐density‐lipoprotein receptor‐1 (LOX‐1) expression in atherosclerotic plaques. These results indicated that LHRD ameliorated atherosclerosis via reducing serum levels of TC, TG, and LDL‐C as well as LOX‐1 expression, subsequently attenuating atherosclerotic lesion and lipid deposition. In conclusion, LHRD could significantly attenuate experimental atherosclerosis and might be a novel potential drug for the prevention and treatment of atherosclerosis.
Application of the Variable Precision Rough Sets Model to Estimate the Outlier Probability of Each Element
Authors: Pérez Francisco Maciá , Martienz Jose Vicente Berna , Oliva Alberto Fernández , Ortega Miguel Abreu
Published: October 2018

In a data mining process, outlier detection aims to use the high marginality of these elements to identify them by measuring their degree of deviation from representative patterns, thereby yielding relevant knowledge. Whereas rough sets (RS) theory has been applied to the field of knowledge discovery in databases (KDD) since its formulation in the 1980s; in recent years, outlier detection has been increasingly regarded as a KDD process with its own usefulness. The application of RS theory as a basis to characterise and detect outliers is a novel approach with great theoretical relevance and practical applicability. However, algorithms whose spatial and temporal complexity allows their application to realistic scenarios involving vast amounts of data and requiring very fast responses are difficult to develop. This study presents a theoretical framework based on a generalisation of RS theory, termed the variable precision rough sets model (VPRS), which allows the establishment of a stochastic approach to solving the problem of assessing whether a given element is an outlier within a specific universe of data. An algorithm derived from quasi‐linearisation is developed based on this theoretical framework, thus enabling its application to large volumes of data. The experiments conducted demonstrate the feasibility of the proposed algorithm, whose usefulness is contextualised by comparison to different algorithms analysed in the literature.
Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells
Authors: Fu Qingjie , Ohnishi Shunsuke , Sakamoto Naoya
Published: October 2018

Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis in animal models. However, the mechanism for the prevention of liver fibrosis is poorly understood. In this study, we investigated the effects, and underlying mechanisms, of a conditioned medium obtained from hAMSC cultures (hAMSC-CM) on a primary culture of rat hepatic stellate cells (HSCs). We observed that in routine culture, hAMSC-CM in HSCs significantly inhibited the expression of alpha-smooth muscle actin (α-SMA), an activation marker of HSCs, and the production of collagen type 1 (COL1), a dominant component of the extracellular matrix (ECM) in the culture medium. In addition, hAMSC-CM upregulated the expression of ECM degradation-related genes, such as metalloproteinase- (Mmp-) 2, Mmp-9, Mmp-13, and tissue inhibitor of metalloproteinase- (Timp-) 1; however, it did not affect the expression of collagen type 1α1 (Col1a1). These regulatory effects on HSCs were concentration-dependent. A cell proliferation assay indicated that hAMSC-CM significantly suppressed HSC proliferation and downregulated the expression of cyclin B (Ccnb), a proliferation-related gene. Transforming growth factor-beta (TGF-β) treatment further activated HSCs and hAMSC-CM significantly inhibited the upregulation of α-Sma and Col1a1 induced by TGF-β. These findings demonstrated that hAMSC-CM can modulate HSC function via secretory factors and provide a plausible explanation for the protective role of hAMSCs in liver fibrosis.
Breg Cells in Celiac Disease Isolated or Associated to Hashimoto’s Thyroiditis
Authors: Santaguida Maria Giulia , Gatto Ilenia , Mangino Giorgio , Virili Camilla , Stramazzo Ilaria , Fallahi Poupak , Antonelli Alessandro , Gargiulo Patrizia , Romeo Giovanna , Centanni Marco
Published: October 2018

Hashimoto’s thyroiditis (HT) may occur associated with celiac disease (CD). Regulatory B cells (Breg) subsets have been shown to play a significant role in autoimmune processes. Therefore, we have characterized their distribution in the peripheral blood obtained from 10 patients with isolated HT, 10 patients with HT + CD, 9 patients with isolated CD, and 9 healthy donors (HD). Th17 cells were significantly increased in patients with HT and in patients bearing both HT and CD, while patients with isolated CD exhibited a lower percentage of Th17, as compared with healthy donors. CD24hiCD38hiBreg cells were significantly higher in patients with HT + CD and in patients with isolated CD as compared to both HD patients and patients with isolated HT (p=0.0010). On the contrary, Breg memory phenotypes (CD24hiCD38−and CD24hiCD27+) significantly decreased in patients with HT + CD as compared with the isolated disorders. Following CpG oligodeoxynucleotide stimulation, IL-10+CD24hiCD38hiBreg cells were similar in all groups of patients, despite these cells would have been higher in CD patients. In conclusion, celiac disease, isolated and even more when associated with HT, determines a peculiar behavior of Breg cells which are increased in number but possibly functionally defective. Furthermore, the association CD + HT was characterized by a reduction of Breg memory subsets as compared with the isolated disorders. The behavior of Th17 subset in patients with celiac disease associated with HT might have been sensitive to the effect of long-lasting GFD, and it is essentially determined by the presence of thyroid autoimmunity.
Electrochemical Properties of Oxide Scale on Steel Exposed in Saturated Calcium Hydroxide Solutions with or without Chlorides
Authors: Ahlström Johan , Tidblad Johan , Tang Luping , Sederholm Bror , Leijonmarck Simon
Published: October 2018

The electrochemical properties of various iron oxide scales on steel exposed in saturated calcium hydroxide solutions were investigated. The iron oxide scales were manufactured by different heat treatments and grinding processes and characterized using X-ray diffraction and scanning electron microscope. The electrochemical properties of the scales were assessed by measuring the corrosion potential and using electrochemical impedance spectroscopy and potentiodynamic polarization curves. It was found that wustite and magnetite are less noble compared to hematite but are more effective as cathodic surfaces. The results show that the electrochemical properties of the mill scale can be an important contributing factor in the corrosion of steel in concrete.
Acer palmatum thumb. Ethanol Extract Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation
Authors: Kim Kwang-Youn , Oh Tae-Woo , Do Hyun Ju , Yang Ju-Hye , Yang In Jun , Jeon Yong Hyun , Go Young-Hoon , Ahn Soon-Cheol , Ma Jin-Yeul , Park Kwang-Il
Published: October 2018

Ulcerative colitis is one inflammatory bowel disease (IBD) and is caused by diverse factors, including the extent and duration of intestinal inflammation. We investigated the effect of Acer palmatum thumb. ethanol extract (KIOM-2015E) on the expression of tight junction proteins and the levels of inflammation in the cell model induced with interleukin-6- (IL-6-) and mouse model of dextran sodium sulfate (DSS) induced with acute colitis. KIOM-2015E (100 mg/kg) was orally administered once per day to BALB/C mice with colitis induced by administration of 5% DSS in drinking water. KIOM-2015E did not affect viability in Caco-2 cells. Also, KIOM-2015E repaired the IL-6-induced intestinal barrier dysfunction in Caco-2 cells. Furthermore, KIOM-2015E recovered the loss of body weight and the abnormally short colon lengths in the DSS-induced model of acute colitis. Moreover, KIOM-2015E significantly inhibited the decrease of zonula occluden-1 and occludin in colonic tissue relative to the DSS-treated control group. KIOM-2015E also significantly inhibited the expression of IL-6 and tumor necrosis factor-α in the level of serum relative to the control group. Collectively, these data suggest that KIOM-2015E protects colitis principally by improving intestinal barrier function and promoting anti-inflammatory responses. In turn, these effects inhibit macrophage infiltration into the colon and thus may be a candidate treatment for IBD.
Nonlinear Dynamics and Analysis of a Planar Multilink Complex Mechanism with Clearance
Authors: Chen Xiulong , Jiang Shuai , Deng Yu , Wang Qing
Published: October 2018

In order to understand the nonlinear dynamic behavior of a planar mechanism with clearance, the nonlinear dynamic model of the 2‐DOF nine‐bar mechanism with a revolute clearance is proposed; the dynamic response, phase diagrams, Poincaré portraits, and largest Lyapunov exponents (LLEs) of mechanism are investigated. The nonlinear dynamic model of 2‐DOF nine‐bar mechanism containing a revolute clearance is established by using the Lagrange equation. Dynamic response of the slider’s kinematics characteristic, contact force, driving torque, shaft center trajectory, and the penetration depth for 2‐DOF nine‐bar mechanism are all analyzed. Chaos phenomenon existed in the mechanism has been identified by using the phase diagrams, the Poincaré portraits, and LLEs. The effects of the different clearance sizes, different friction coefficients, and different driving speeds on dynamic behavior are studied. Bifurcation diagrams with changing clearance value, friction coefficient, and driving speed are drawn. The research could provide important technical support and theoretical basis for the further study of the nonlinear dynamics of planar mechanism.
Minor Prime Factorization for n‐D Polynomial Matrices over Arbitrary Coefficient Field
Authors: Liu Jinwang , Li Dongmei , Zheng Licui
Published: October 2018

In this paper, we investigate two classes of multivariate (n‐D) polynomial matrices whose coefficient field is arbitrary and the greatest common divisor of maximal order minors satisfy certain condition. Two tractable criterions are presented for the existence of minor prime factorization, which can be realized by programming and complexity computations. On the theory and application, we shall obtain some new and interesting results, giving some constructive computational methods for carrying out the minor prime factorization.
Systematic Research on the Application of Steel Slag Resources under the Background of Big Data
Authors: Kang Le , Du Hui Ling , Zhang Hao , Ma Wan Li
Published: October 2018

The large‐scale and resourceful utilization of solid waste is one of the important ways of sustainable development. The big data brings hope for further development in all walks of life, because huge amounts of data insist on the principle of “turning waste into treasure”. The steel big data has been taken as the research object in this paper. Firstly, a big data collection and storage system has been set up based on the Hadoop platform. Secondly, the steel slag prediction model based on the convolution neural network (CNN) is established. The material data of steelmaking, the operation data of steelmaking process, and the data of steel slag composition are put into the model from the Hadoop platform, and the prediction of the slag composition is further realized. Then, the alternatives for resource recovery are obtained according to the predicted composition of the steel slag. And considering the three aspects of economic feasibility, resource suitability, and environmental acceptance, the comprehensive evaluation system based on AHP is established to realize the recommendation of the optimal resource approach. Finally, taking a steel plant in Hebei as an example, the alternatives according to the prediction of the composition of steel slag are blast furnace iron‐making, recycling waste steel, and cement admixture. The comprehensive evaluation values of the three resources are 0.48, 0.57, and 0.76, respectively, and the optimized resource of the steel slag produced by the steel plant is used as the cement admixture.
Wearable Lumbar-Motion Monitoring Device with Stretchable Strain Sensors
Authors: Nakamoto Hiroyuki , Yamaji Tokiya , Yamamoto Akio , Ootaka Hideo , Bessho Yusuke , Kobayashi Futoshi , Ono Rei
Published: October 2018

Low-back pain is a common affliction. Epidemiological analyses have reported that periodic cycles of lumbar flexion and rotation are major risk factors for low-back pain. To prevent low-back pain, a lumbar-motion monitoring device could help diagnosticians assess patients’ risk for low-back pain. This study proposes such a device that uses lightweight stretchable strain sensors. Six of these strain sensors form a parallel-sensor mechanism that measures rotation angles of lumbar motion in three axes. The parallel-sensor mechanism calculates rotation angles from the lengths of the strain sensors iteratively. Experimental results reveal that the prototype device is effective for lumbar-motion measurement and significantly improves in terms of wearability over comparable devices.
Successful Management of Blue Rubber Bleb Nevus Syndrome (BRBNS) with Sirolimus
Authors: Ogu Ugochi O. , Abusin Ghada , Abu-Arja Rolla F. , Staber Janice M.
Published: October 2018

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease with vascular malformations in several systems of the body, most commonly the skin and gastrointestinal tract. Bleeding from the gastrointestinal (GI) tract is a major complication, which may lead to chronic iron deficiency anemia and the need for frequent blood transfusions due to ongoing gastrointestinal blood loss. In this case report, we describe a now 19-year-old female with BRBNS who required six blood transfusions per year and after starting sirolimus is symptom- and transfusion-free.
Assessment of Diagnostic Values among CA-125, RMI, HE4, and ROMA for Cancer Prediction in Women with Nonfunctional Ovarian Cysts
Authors: Oranratanaphan Shina , Wanishpongpan Sinee , Termrungruanglert Wichai , Triratanachat Surang
Published: October 2018

Objectives. To evaluate the diagnostic performance among CA-125, RMI, HE4, and ROMA for cancer detection in women with nonfunctional ovarian cysts at King Chulalongkorn Memorial Hospital (KCMH). Secondary objective is to reconsider the proper cutoff value of HE4. Methods. This is a prospective analytic study in women with nonfunctional ovarian cysts larger than 3 cm who scheduled for surgery at KCMH during 3rd June 2015 to 31st May 2016. Ultrasonogram and blood sample collection were completed before the operation. Patients’ demographic information and pathologic results were obtained. SPSS software version 17 was used for statistical evaluation. Results. A total of 281 participants were evaluated. 19.9% of them were malignant. Compared with CA-125, HE4 had lower sensitivity (53.4% vs. 87.9%) and NPV (89% vs. 93.6%) but higher specificity (97.8% vs. 46.2%) and PPV (86.1% vs. 29.8%). ROMA had slightly lower sensitivity (79.3% vs. 87.9%) and similar NPV (93.7% vs. 93.6%), but higher specificity (79.8% vs. 46.2%) and PPV (50.5% vs. 29.8%) compared with CA-125. The model that achieves the highest area under the ROC curve in differentiating benign versus malignant ovarian tumor was ROMA. Cutoff value of HE4 at 70 pMol/L (from 150 pMol/L) would give sensitivity 74.1% and specificity 86.5% that are comparable with ROMA. Conclusions. HE4 and ROMA had better performance (higher specificity, PPV) compared to CA-125 and RMI. HE4 at 70 pMol/L could be the new cutoff value for Thai women with ovarian cysts, giving higher sensitivity and specificity.
Tillage Effects on Soil Biochemical Properties and Maize Grown in Latosolic Red Soil of Southern China
Authors: Asenso Evans , Li Jiuhao , Hu Lian , Issaka Fuseini , Tian Kai , Zhang Lina , Zhang Luyong , Chen Haibo
Published: October 2018

Based on the hypothesis that soil biochemical and maize yield components should be affected by different tillage methods, a field experiment was conducted to study the effects of subsoiling (SS), two passes of rotary tillage (2RT), two passes of rotary tillage + subsoiling (2RTSS), and zero tillage (ZT) on distribution of organic C, available NPK and soil enzyme, and its effects on maize yield in latosolic red soil of southern China in 2016 and 2017. ZT treatment had significantly higher organic C and available NPK than the other treatments, whereas the SS treatment had higher concentration of soil urease, catalase, and acid phosphatase. Also, maximum grain yield, dry matter, harvest index, and 1000-grain weight were recorded under SS treatment. Overall, although ZT facilitated more organic C and available NPK, soil with ZT had lower soil enzyme and maize yield components compared to SS treatment, and therefore SS treatment could be exploited as a strategy for soil health and productivity resulting in a sustainable agricultural system.
Preferential Water Infiltration Path in a Slow-Moving Clayey Earthslide Evidenced by Cross-Correlation of Hydrometeorological Time Series (Charlaix Landslide, French Western Alps)
Authors: Bièvre Grégory , Joseph Agnès , Bertrand Catherine
Published: October 2018

Slow-moving clayey earthslides frequently exhibit seasonal activity suggesting that deformation processes do not only depend on slope and intrinsic geomechanical parameters. On the contrary, seasonal motion patterns are frequently observed with acceleration during the wet season and deceleration during the dry season. Within landslides, it is mainly the phreatic water table which is monitored. However, in the case of deep-seated landslides made of heterogeneous lithological units and with several slip surfaces, the characterization of the phreatic water table does not allow to relate satisfactorily the activity of the landslide with environmental parameters such as rainfall and subsequent water infiltration at depth. This paper presents a seasonal analysis of water infiltration within a slow-moving clayey landslide. Results of an extensive geotechnical and geophysical prospect are first exposed. Then, rainfall and water table level time series are analysed for two water tables using the cross-correlation technique: the phreatic water table located a few metres deep and a water table located above a shear surface located 12 m deep. Results show that water infiltrates faster down to the deepest water table. Then, time series were split between “dry” and “wet” seasons and the effective rainfall was computed from the original rainfall time series. Cross-correlation results show that the phreatic water table responds identically to rainfall in both seasons. On the contrary, the water table located above the shear surface has a very contrasting behaviour between summer (mainly drainage) and winter (behaviour similar to the phreatic water table with storage of water during a few weeks). This difference in behaviour is in agreement with the landslide kinematics.
Targeting PARP1 in XRCC1-Deficient Sporadic Invasive Breast Cancer or Preinvasive Ductal Carcinoma In Situ Induces Synthetic Lethality and Chemoprevention
Authors: Ali Reem , Al-Kawaz Abdulbaqi , Toss Michael S. , Green Andrew R. , Miligy Islam M. , Mesquita Katia A. , Seedhouse Claire , Mirza Sameer , Band Vimla , Rakha Emad A , Madhusudan Srinivasan
Published: October 2018

Targeting PARP1 for synthetic lethality is a new strategy for breast cancers harboring germline mutations in BRCA. However, these mutations are rare, and reactivation of BRCA-mediated pathways may result in eventual resistance to PARP1 inhibitor therapy. Alternative synthetic lethality approaches targeting more common sporadic breast cancers and preinvasive ductal carcinoma in situ (DCIS) are desirable. Here we show that downregulation of XRCC1, which interacts with PARP1 and coordinates base excision repair, is an early event in human breast cancer pathogenesis. XRCC1-deficient DCIS were aggressive and associated with increased risk of local recurrence. Human invasive breast cancers deficient in XRCC1 and expressing high PARP1 levels also manifested aggressive features and poor outcome. The PARP1 inhibitor olaparib was synthetically lethal in XRCC1-deficient DCIS and invasive breast cancer cells. We conclude that targeting PARP1 is an attractive strategy for synthetic lethality and chemoprevention in XRCC1-deficient breast cancers, including preinvasive DCIS.

Significance:

These findings show that loss of XRCC1, which is associated with more malignant DCIS, can be exploited by PARP inhibition, suggesting its application as a promising therapeutic and chemoprevention strategy in XRCC1-deficient tumor cells.
Pathologic Oxidation of PTPN12 Underlies ABL1 Phosphorylation in Hereditary Leiomyomatosis and Renal Cell Carcinoma
Authors: Xu Yang , Taylor Paul , Andrade Joshua , Ueberheide Beatrix , Shuch Brian , Glazer Peter M. , Bindra Ranjit S. , Moran Michael F. , Linehan W. Marston , Neel Benjamin G.
Published: October 2018

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an inherited cancer syndrome associated with a highly aggressive form of type 2 papillary renal cell carcinoma (PRCC). Germline inactivating alterations in fumarate hydratase (FH) cause HLRCC and result in elevated levels of reactive oxygen species (ROS). Recent work indicates that FH−/− PRCC cells have increased activation of ABL1, which promotes tumor growth, but how ABL1 is activated remains unclear. Given that oxidation can regulate protein-tyrosine phosphatase (PTP) catalytic activity, inactivation of an ABL-directed PTP by ROS might account for ABL1 activation in this malignancy. Our group previously developed “q-oxPTPome,” a method that globally monitors the oxidation of classical PTPs. In this study, we present a refined q-oxPTPome, increasing its sensitivity by >10×. Applying q-oxPTPome to FH-deficient cell models showed that multiple PTPs were either highly oxidized (including PTPN12) or overexpressed. Highly oxidized PTPs were those with relatively high sensitivity to exogenous H2O2. Most PTP oxidation in FH-deficient cells was reversible, although nearly 40% of PTPN13 was irreversibly oxidized to the sulfonic acid state. Using substrate-trapping mutants, we mapped PTPs to their putative substrates and found that only PTPN12 could target ABL1. Furthermore, knockdown experiments identified PTPN12 as the major ABL1 phosphatase, and overexpression of PTPN12 inhibited ABL1 phosphorylation and HLRCC cell growth. These results show that ROS-induced oxidation of PTPN12 accounts for ABL1 phosphorylation in HLRCC-associated PRCC, revealing a novel mechanism for inactivating a tumor suppressor gene product and establishing a direct link between pathologic PTP oxidation and neoplastic disease.

Significance:

This work identifies a novel mechanism of activation of the oncogenic kinase ABL1 via ROS-induced, oxidation-mediated inactivation of cognate protein tyrosine phosphatases.
Relationship between Circulating Inflammation Proteins and Lung Cancer Diagnosis in the National Lung Screening Trial
Authors: Brown Derek , Zingone Adriana , Yu Yunkai , Zhu Bin , Candia Julián , Cao Liang , Ryan Bríd M.
Published: October 2018

Background:

Previously, we observed a strong relationship between circulating serum inflammation proteins in relation to lung cancer diagnosis and risk, both in case–control and prospective cohorts. Low-dose computed tomography (LDCT) screening has a high prevalence of false-positive nodules, thus companion noninvasive biomarkers that can distinguish between benign and malignant nodules could have clinical utility and positive impact on patient outcomes.

Methods:

We conducted a nested case–control study within the National Lung Screening Trial. Concentrations of 30 inflammation proteins were measured on plasma samples of 262 cases and 528 controls using a highly sensitive and analytically validated electrochemiluminescence V-PLEX immunoassay.

Results:

Comparing the fourth quartile with the first quartile, we found increased IFNγ and IL12/IL23p40 associated with increased odds of a lung cancer diagnosis [OR 1.89, 95% confidence intervals (CI), 1.16–3.09; OR 2.49, 95% CI, 1.46–4.23, respectively]. Confirming our previous observations, we also detected a relationship between increased IL6, IL8, and C-reactive protein (CRP) with lung cancer diagnosis. These relationships were significant after adjustment for age, gender, race, smoking, body mass index (BMI), family history of lung cancer, and previous diagnoses of inflammatory conditions. However, none of these proteins could distinguish between a benign and malignant lung nodule (IL6: OR 1.25, 95% CI, 0.59–2.64; IL8: OR 1.40, 95% CI, 0.70–2.81; CRP: OR 0.98, 95% CI, 0.45–2.12).

Conclusions:

We have discovered new associations for IFNγ and IL12/IL23p40 with lung cancer but have no evidence that these proteins can distinguish between benign and malignant lung nodules.

Impact:

Circulating inflammation proteins are unlikely to have utility as companion LDCT biomarkers.
Long-Term Survival in Patients Responding to Anti–PD-1/PD-L1 Therapy and Disease Outcome upon Treatment Discontinuation
Authors: Gauci Marie-Léa , Lanoy Emilie , Champiat Stéphane , Caramella Caroline , Ammari Samy , Aspeslagh Sandrine , Varga Andrea , Baldini Capucine , Bahleda Rastilav , Gazzah Anas , Michot Jean-Marie , Postel-Vinay Sophie , Angevin Eric , Ribrag Vincent , Hollebecque Antoine , Soria Jean-Charles , Robert Caroline , Massard Christophe , Marabelle Aurélien
Published: October 2018

Purpose:

Anti–PD-(L)1 can provide overall survival (OS) benefits over conventional treatments for patients with many different cancer types. However, the long-term outcome of cancer patients responding to these therapies remains unknown. This study is an exploratory study that aimed to describe the long-term survival of patients responding to anti–PD-(L)1 monotherapy across multiple cancer types.

Patients and Methods: Data from patients treated with an anti–PD-(L)1 monotherapy in a phase I trial at Gustave Roussy were retrospectively analyzed over a period of 5 years. All cancer types (n = 19) were included. Clinical and biological factors associated with response, long-term survival, and secondary refractory disease were studied.

Results:

Among 262 eligible patients, the overall objective response rate was 29%. The median progression-free survival of responder patients (RP) at 3 months was 30 months, and the median OS of RP was not reached after a median follow-up of 34 months. In RPs, 3- and 5-year OS percentages were 84% and 64%, respectively. No death occurred in the 21 complete responders (CR) during the overall follow-up. However, many partial responders (PR) showed subsequent tumor relapses to treatment. Long responders (response ≥2 years) represented 11.8% of the overall population. These findings should be validated in further prospective studies.

Conclusions:

There are currently no differences in therapeutic strategies between CRs and PRs to anti–PD-(L)1. We found a striking difference in OS between these two types of responses. Our results are in favor of evaluating patient stratification strategies and intensification of treatments when tumor lesions of a partial responder to immunotherapy stop improving.

See related commentary by Cohen and Flaherty, p. 910
AXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer
Authors: Axelrod Haley D. , Valkenburg Kenneth C. , Amend Sarah R. , Hicks Jessica L. , Parsana Princy , Torga Gonzalo , DeMarzo Angelo M. , Pienta Kenneth J.
Published: October 2018

Prostate cancer bone metastasis remains lethal and incurable, and often arises years after elimination of the primary tumor. It is unclear what underlies the decades-long clinical latency before recurrence, but evidence points to the existence of dormant residual tumor cells that disseminated before the primary tumor was eliminated. To design therapies to prevent progression of disseminated tumor cells (DTC) into lethal metastases, it is crucial to understand the mechanism(s) underlying this dormancy. The current study functionally validated our previous observation that implicated the GAS6/AXL axis in mediating DTC dormancy in the bone marrow. AXL-null and AXL-overexpressing prostate cancer cell lines were generated to determine if AXL was necessary and/or sufficient for dormancy. Characterization of these cells in vitro and using in vivo mouse models of DTC growth demonstrated that AXL was indeed sufficient to induce dormancy, but was unable to maintain it long-term and was not absolutely required for a dormancy period. Clinically, AXL expression correlated with longer survival in prostate cancer patients, and AXL was not expressed by cancer cells in primary or metastatic tissue. These data point to a tumor-suppressive role for AXL in prostate cancer, and future work is required to determine if AXL is expressed on human bone marrow DTCs.

Implications:

The ability of AXL to initiate but not maintain dormancy, coupled with its dispensability, suggests that targeting AXL alone will not prevent lethal metastatic outgrowth, and likely a cooperative network of factors exists to mediate long-term cellular dormancy.
Sicherheit der Kombinationstherapie von inhaliertem Indacaterol/Glycopyrronium bei älteren COPD-Patienten: Eine elektrokardiographische Evaluation
Authors: Frohnhofen Helmut
Published: October 2018

Cardiovascular (CV) comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality, especially in old and very old subjects. The question if long-acting beta-agonist and long-acting muscarinic antagonist could be associated with the increased prevalence of CV-related adverse effects has puzzled, particularly in the past, specialists involved in the management of respiratory diseases. The safety of these compounds has scarcely been tested in patients aged ≥ 65 years with CV comorbidities, since randomized controlled trials rarely include this subpopulation. However, the fixed combination indacaterol/glycopyrronium has shown a favorable CV safety profile in both healthy volunteers and COPD patients. Thus, we aimed to assess the CV safety profile of the fixed combination indacaterol/glycopyrronium 110/50 μg in a series of COPD patients aged ≥ 80 years with several comorbidities. Our results indicate that this combination is safe in the comorbid elderly, since no significant electrocardiographic abnormalities were recorded after the administration of the inhaled therapy. Only rare and nonclinically significant changes in heart rate and corrected QT interval duration were evident, mainly in females and in patients with concomitant impaired kidney function.
Ein Bewertungssystem zur Vorhersage der Erhöhung des mittleren Pulmonalarteriendrucks bei idiopathischer Lungenfibrose
Authors: Drakopanagiotakis Fotios , Günther Andreas
Published: October 2018

Ein erhöhter mittlerer pulmonaler arterieller Druck (mPAP ≥ 21 mmHg) hat eine negative Auswirkung auf das Überleben von Patienten mit idiopathischer Lungenfibrose (idiopathic pulmonary fibrosis, IPF). Es gibt bis dato kein etabliertes nicht invasives Screeningtool für die Diagnose der präkapillären pulmonalen Hypertonie (PH). Die Daten von 273 Patienten mit IPF - die einem Rechtsherzkatheter (right heart catheterisation, RHC) unterzogen wurden - wurden bezüglich ihrer Aussagekraft für die nicht invasive Diagnose einer PH retrospektiv analysiert. Bei 55 Patienten wurde mittels RHC ein erhöhter mittlerer Pulmonalarteriendruck (mean pulmonary artery pressure, mPAP) (definiert als mPAP ≥ 21 mmHg), bei 18 Patienten eine präkapilläre PH (definiert als mPAP > 25 mmHg) diagnostiziert. In einer multivariablen Analyse zeigten sich die Kohlenmonoxid-Diffusionskapazität (diffusing capacity of the lung for carbon monoxide, DLCO) <50% vom Soll, ein Sauerstoffpartialdruck (pO2) <80 mmHg und ein PA/AO ≥0,9 im CT-Thorax als unabhängige Faktoren für die Diagnose einer PH. Es wurde jedem der 3 statistisch signifikanten Variablen ein einziger Punkt zugewiesen, sodass eine 4-Punkte-Skalierung entstand. Die Prävalenz des erhöhten mPAP mit einer Punktzahl von 0, 1, 2 oder 3 Punkten stieg von 6,7% auf 16,0%, 29,1% und schließlich 65,4% an.
Calculating Standard Kt/V during Hemodialysis Based on Urea Mass Removed
Authors: Leypoldt John K. , Vonesh Edward F.
Published: October 2018

Background/Aims: We derived a novel equation for calculating weekly urea standard Kt/V (stdKt/V) during hemodialysis (HD) based on urea mass removed, comparable to the approach during peritoneal dialysis. Methods: Theoretical consideration of urea mass balance during HD led to the following equation for stdKt/V, namely, stdKt/V = N × (URR + UFV/V), where N is the number of treatments per week, URR is urea reduction ratio per treatment, UFV is ultrafiltration volume per treatment, and V is postdialysis urea distribution volume. URR required corrections for postdialysis rebound and intradialytic urea generation. We compared the accuracy of this approach with previous equations for stdKt/V by numerical simulations using a 2-compartment model of urea kinetics for thrice-weekly and more frequent HD prescriptions. Results: The proposed equation based on urea mass removed predicted values of stdKt/V that are equivalent to those calculated by previous equations for stdKt/V. Conclusion: This work provides a novel approach for calculating stdKt/V during HD and strengthens the theoretical understanding of stdKt/V.
Structure-Activity Relationship of the GPR55 Antagonist, CID16020046
Authors: Brown Andrew J. , Castellano-Pellicena Irene , Haslam Carl P. , Nichols Paula L. , Dowell Simon J.
Published: October 2018

Background/Aims: CID16020046 blocks the effect of the lipid lysophosphatidylinositol (LPI) at its receptor, GPR55. CID16020046 and another antagonist, ML193, have been used to investigate GPR55-mediated effects of LPI on cells, tissues, and in vivo. Here we describe the structure-activity relationship of CID16020046. Methods: Yeast or human cells were engineered to express GPR55 or control receptors. Cells were pretreated with a test agent before agonist challenge. Functional responses were quantified by yeast gene-reporter or calcium imaging. Results: Three substituents around the central pyrazololactam core of CID16020046 are each tolerant to substitution without abolishing GPR55 activity. Analogues of CID16020046 with potency at GPR55 ranging >1,000-fold are described, including several lacking activity up to the top concentration tested. One analogue, compound 1 (GSK875734A), has approximately 50-fold greater potency than CID16020046 in an inverse agonist assay. CID16020046, ML193 and 2 further antagonists (ML191 and ML192) all block the effect of a surrogate agonist at human GPR55. ML193, CID16020046 and several other examples of the pyrazololactam chemotype were also shown to antagonise rat GPR55. Conclusion: These data confirm the utility of CID16020046 and ML193 as tools to investigate the physiological role of GPR55, and offer starting points for GPR55 antagonists with optimised pharmacokinetic or other properties.
A corrupção como violadora de direitos humanos: a apropriação indevida de políticas públicas.
Authors: Gomes Ana Cristina , Fernandes Fernando Andrade
Published: October 2018

Na ordem do dia, a corrupção é pauta em todas as agendas políticas. No mesmo sentido, o desenvolvimento humano dentro dos Estados é tema recorrente nas discussões acadêmicas, políticas, econômicas. Para que este desenvolvimento ocorra e assim o Estado possa realizar uma de suas finalidades, – o desenvolvimento individual e coletivo de maneira a não violar direitos humanos e atender as necessidades garantidas pela maioria das Constituições modernas, liberdade, segurança, dignidade humana – Políticas Públicas são implementadas. Todavia, a necessidade de um maior investimento nas áreas sociais, muitas vezes, resulta no repasse de verbas públicas para setores privados por meio de contratos públicos tendo em vista a insuficiência do Estado quanto a infraestrutura humana e técnica. É sob este aspecto que analisamos alguns fatores que somados resultam no fenômeno criminológico corrupção e uma vez que esta adentra o campo das Ciências Jurídico-Penais, é necessário apontar em que aspectos estas podem contribuir ou não com o enfrentamento da corrupção.
Gênese, desenvolvimento e instituições: comparando ALADI, MERCOSUL e UNASUL
Authors: De Sousa Ribeiro Elisa , Vigna Edelcio
Published: October 2018

O artigo objetiva estabelecer comparações entre Aladi, Mercosul e Unasul, instituições regionais de integração regional sul-americanas, com o propósito de explorar os níveis de democratização que cada instituição construiu, a partir das controvérsias entre os Estados Partes, que as integram, e das organizações da sociedades civil, que delas participam. O estudo ressalta o papel dos Estados nacionais nas relações multilaterais da região que, ao edificar os blocos econômicos, respondem às exigências da formação de um novo contexto econômico internacional e de uma nova fase de acumulação do capitalismo pelo capital financeiro.
Las elites en México: su arribo, circulación y desempeño en los años 80 y 90
Authors: De la torre Oropeza Verónica
Published: October 2018

Estudiamos al grupo de tecnócratas que ocuparon los cargos más altos de las principales instituciones de gobierno entre 1980 y 1990. ¿Cómo entran, circulan y salen de la elite del poder? Retomamos el criterio de elite del poder de Wright Mills y de John Scott dada la importancia de las instituciones donde este se ejerce y donde se toman las decisiones trascendentales del país. Adscribimos la idea paretiana de circulación de las elites porque encaja con algunas características de quienes ingresan a la elite del poder. También, es útil para entender ciertas prácticas antidemocráticas de la clase política para mantenerse en el poder.
Embodying Memories: The Women Rights Movement „#NiUnaMenos “ and the Women Narratives about State Repression in Argentina
Authors: Abrego Verónica Ada
Published: October 2018

Since 2015 a new human rights movement struggle against violence against women, Ni una menos. From the perspective of cultural studies, there is a strong link between these women struggling for cultural transformation and the long lasting battle against oblivion carried out by Argentinas Human Rights Movement and especially, by the Mother and Grandmother of Plaza the Mayo. Against the background of state terrorism and its literature written by women, this contribution reflects on methodology studying Argentina women’s literature on state repression and also on the role of women as agents of social transformation.
Protagonismo indígena, Constituição Plurinacional e interculturalidade na Bolívia
Authors: Huertas Bruna Muriel
Published: October 2018

Tomando como ponto de partida a recente Constituição do Estado Plurinacional da Bolívia (2009), o artigo analisa o processo histórico que resultou no protagonismo indígena durante a Assembleia Constituinte, além de explorar os inovadores princípios e artigos constitucionais que surgem desse diálogo. Verificou-se que a participação dos indígenas como sujeitos políticos fundamentais durante o processo de escritura do texto constitucional, assim como o seu conteúdo inovador, pelo caráter descolonizador, evidenciam um exercício de interculturalidade inédito no âmbito jurídico e político na América Latina.
Antonio Bento e Romero Brest: o movimento abstrato como fluxo universal
Authors: Bedtche Araceli Barros da Silva Jellmayer
Published: October 2018

Este artigo apresenta uma análise das contribuições do crítico de arte argentino, Jorge Romero Brest, para o panorama artístico brasileiro, estabelecendo aproximações políticas e culturais entre Brasil e Argentina. Enfatiza-se a importância da Revista argentina Ver y Estimar como veículo de difusão das idéias vanguardistas e a atuação de uma crítica de arte especializada no Brasil, como a de Antonio Bento de Araújo Lima e Sérgio Milliet, no processo de divulgação da arte abstrata como fluxo universal. Constituem as principais fontes utilizadas: Revista Ver y Estimar (1951) e textos críticos de Antonio Bento da década de 1950.
CARTA AOS LEITORES
Authors: Suzuki Júlio César
Published: October 2018

Apresentação dos artigos do número 31 (2017)
Rompendo fronteiras entre "nós" e "eles"
Authors: Balestro Ana Cristina , De Almeida Luiz Roberto
Published: October 2018

Este livro, Estranhos à Nossa Porta, publicado no Reino Unido em 2016, traduzido por Carlos Alberto Medeiros e publicado no Brasil pela editora Zahar em 2017, é um dos últimos livros publicados do sociólogo e filósofo da pós-modernidade Zygmunt Bauman. Com seis capítulos e 119 páginas, trata-se de um ensaio sobre as questões envoltas nos movimentos migratórios do século XXI. Nele, Bauman, que também teve sua história de vida marcada pela migração, analisa algumas questões que já havia abordado no livro Vidas Desperdiçadas, de 2004. Com foco na aceleração do influxo de pessoas na União Europeia, Bauman tece sua argumentação pautada em dados recentes sobre o tema: pesquisas de opinião e discursos de políticos que exercem papéis de liderança nos principais países pretendidos como destino desses migrantes. Convicto de que esses movimentos migratórios em massa não vão se interromper, o autor referencia também alguns teóricos cujos conceitos se mostram necessários e relevantes para construir um pensamento atual sobre as questões decorrentes do tema, como por exemplo Immanuel Kant e Hannah Arendt.
Neuron-Derived Orphan Receptor-1 (NOR-1) Modulates Vascular Smooth Muscle Cell Proliferation
Authors: Martínez-González José , Rius Jordi , Castelló Ana , Cases-Langhoff Claudia , Badimon Lina
Published: October 2018

Vascular smooth muscle cells (VSMCs) migration and proliferation play a key role in the pathophysiology of cardiovascular disease. However, the transcription factors that regulate VSMC activation are not completely characterized. By a mRNA-differential display approach, we have identified neuron-derived orphan receptor-1 (NOR-1), a transcription factor within the NGFI-B subfamily of nuclear receptors, as a immediate-early gene in VSMCs. Two NOR-1 isoforms (α and β) were identified and cloned from serum-induced porcine VSMC that shared high homology with the human isoforms. Northern blot analysis revealed a strong and transient (1 to 6 hours) upregulation of NOR-1 in both porcine and human coronary SMCs by growth factors (serum, platelet-derived growth factor-BB, and epidermal growth factor) and α-thrombin but not by cytokines. NOR-1 upregulation is processed through G protein–coupled receptors and tyrosine kinase receptors, and involves Ca
2+
mobilization, protein kinase C activation, and the mitogen-activated protein kinase pathway. This induction was closely dependent of the cAMP response elements present in NOR-1 promoter as transfection assays indicate. Human coronary atherosclerotic lesions overexpress NOR-1, and balloon angioplasty transiently induces NOR-1 in porcine coronary arteries with a pattern similar to that observed in VSMCs in culture. Antisense oligonucleotides against NOR-1 inhibited human coronary SMC proliferation (reduced de novo DNA synthesis, cell cycle progression, and VSMC wound repair) as efficiently as antisense against the protooncogene c-
fos
. These results show that NOR-1 modulates VSMC proliferation, and suggest that this transcription factor may play a role in both spontaneous and accelerated atherosclerosis.