bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Common Vascular Anatomy to Cannulated Catheters
Authors: Gagne Paul , Sharma Karun
Published: December 2017

Superficial veins of the upper extremity are the primary location for placement of peripheral IV catheters (PIVC). It is believed that a significant portion of PIVCs placed may cross or abut valves and branching veins or occlude a significant portion of the vein, limiting the ability to aspirate blood from the PIVC. Two separate clinical investigations using ultrasound were performed to understand the potential interaction between PIVCs and the vein lumen and the venous valves and branches of the superficial veins of the upper extremity. One study with 35 adult volunteers interrogated 210 vein segments where a PIV would likely be placed. A second pediatric study evaluated 35 vein segments central to indwelling PIVCs. The combined data from the two studies showed that over 80% of adult veins and 85% of pediatric veins can properly accommodate 20-gauge and 22-gauge PIVC, respectively. Venous valves are frequent findings, either immediately peripheral to branching veins or at periodic 5 to 7 cm points. Antegrade blood flow can be restricted by a placed PIVC, while retrograde flow is very likely to be restricted by venous valves. Together, these findings may explain the difficulty in reliable aspiration of blood from PIVC.
Antidepressant Flavonoids and Their Relationship with Oxidative Stress
Authors: Hritcu Lucian , Ionita Radu , Postu Paula Alexandra , Gupta Girish Kumar , Turkez Hasan , Lima Tamires Cardoso , Carvalho Caroline Uchôa Souza , de Sousa Damião Pergentino
Published: December 2017

Depression is a serious disorder that affects hundreds of millions of people around the world and causes poor quality of life, problem behaviors, and limitations in activities of daily living. Therefore, the search for new therapeutic options is of high interest and growth. Research on the relationship between depression and oxidative stress has shown important biochemical aspects in the development of this disease. Flavonoids are a class of natural products that exhibit several pharmacological properties, including antidepressant‐like activity, and affects various physiological and biochemical functions in the body. Studies show the clinical potential of antioxidant flavonoids in treating depressive disorders and strongly suggest that these natural products are interesting prototype compounds in the study of new antidepressant drugs. So, this review will summarize the chemical and pharmacological perspectives related to the discovery of flavonoids with antidepressant activity. The mechanisms of action of these compounds are also discussed, including their actions on oxidative stress relating to depression.
Focus on Mesenchymal Stem Cell-Derived Exosomes: Opportunities and Challenges in Cell-Free Therapy
Authors: Cheng Lin , Zhang Kun , Wu Shuying , Cui Manhua , Xu Tianmin
Published: December 2017

Mesenchymal stem cells have been at the forefront of regenerative medicine for many years. Exosomes, which are nanovesicles involved in intercellular communication and the transportation of genetic material transportation that can be released by mesenchymal stem cells, have been recently reported to play a role in cell-free therapy of many diseases, including myocardial infarction, drug addiction, and status epilepticus. They are also thought to help ameliorate inflammation-induced preterm brain injury, liver injury, and various types of cancer. This review highlights recent advances in the exploration of mesenchymal stem cell-derived exosomes in therapeutic applications. The natural contents, drug delivery potency, modification methods, and drug loading methods of exosomes are also discussed.
The Crosstalk between ROS and Autophagy in the Field of Transplantation Medicine
Authors: Van Erp Anne C. , Hoeksma Dane , Rebolledo Rolando A. , Ottens Petra J. , Jochmans Ina , Monbaliu Diethard , Pirenne Jacques , Leuvenink Henri G. D. , Decuypere Jean-Paul
Published: December 2017

Many factors during the transplantation process influence posttransplant graft function and survival, including donor type and age, graft preservation methods (cold storage, machine perfusion), and ischemia‐reperfusion injury. Successively, they will lead to cellular and molecular alterations that determine cell and ultimately organ fate. Oxidative stress and autophagy are implicated in posttransplant outcome since they are both affected by the stress responses triggered in each step (donor, preservation, and recipient) of the transplantation process. Furthermore, oxidative stress influences autophagy and vice versa. Interestingly, both processes have positive as well as negative effects on graft outcome, suggesting they are tightly linked during the transplantation process. In this review, we discuss the importance, regulation and crosstalk of oxidative signals, and autophagy in the field of transplantation medicine.
Experimental Study on Vibration Reduction Characteristics of Gear Shafts Based on ISFD Installation Position
Authors: Lu Kaihua , He Lidong , Zhang Yipeng
Published: December 2017

A novel type of integral squeeze film damper (ISFD) is proposed to reduce and isolate vibration excitations of the gear system through bearing to the foundation. Four ISFD designs were tested experimentally with an open first-grade spur gear system. Vibration reduction characteristics were experimentally studied at different speeds for cases where ISFD elastic damping supports were simultaneously installed on the driving and driven shafts, installed on the driven shaft, or only installed on the driving shaft. Experimental results show that the ISFD elastic damping support can effectively reduce shock vibration of the gear system. Additionally, resonant modulation in gear shafts caused by meshing impact was significantly reduced. Different vibration amplitudes of gear shafts with ISFD installed only on driven or driving shafts were compared. Results indicated that vibration reduction is better when ISFD is only installed on the driven shaft than on the driving shaft.
The Need for Focused Literacy Training in the Medical School Curriculum: A Cross‐Sectional Study of Undergraduate Students
Authors: Kling Joyce , Larsen Sanne , Thomsen Simon Francis
Published: December 2017

Introduction. Medical education programs have increasingly included compulsory research skills components but rarely include explicit academic literacy instruction for medical research. This article presents results from a project that developed methods of bridging the gap between textbook literacy and scientific literacy in a setting where English coexists with the local language. Methods. A paper‐based, revised version of a validated self‐report instrument (32 questions) designed to assess readers’ metacognitive awareness and perceived use of academic reading strategies was used to collect information about medical students’ awareness of reading strategies in English for academic purposes. Results. Students reported a total overall average of 3.25 (scale 1–5) for reading strategy use, falling within a medium range for usage. They reported using problem‐solving reading strategies to the greatest extent (3.76), with global reading strategies (3.29) being second, and support reading strategies (2.85) to the least extent. Based on the data, a curricular intervention was designed to support critical reading of empirical literature in English. Conclusion. The results from this study suggest the need for inclusion of focused training on academic and scientific literacy, in particular, strategy instruction in relation to foreign language reading comprehension skills in medical school curricula.
Mesenchymal Stem Cells as New Therapeutic Agents for the Treatment of Primary Biliary Cholangitis
Authors: Arsenijevic Aleksandar , Harrell C. Randall , Fellabaum Crissy , Volarevic Vladislav
Published: December 2017

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by the progressive destruction of small- and medium-sized intrahepatic bile ducts with resultant cholestasis and progressive fibrosis. Ursodeoxycholic acid and obethicholic acid are the only agents approved by the US Food and Drug Administration (FDA) for the treatment of PBC. However, for patients with advanced, end-stage PBC, liver transplantation is still the most effective treatment. Accordingly, the alternative approaches, such as mesenchymal stem cell (MSC) transplantation, have been suggested as an effective alternative therapy for these patients. Due to their immunomodulatory characteristics, MSCs are considered as promising therapeutic agents for the therapy of autoimmune liver diseases, including PBC. In this review, we have summarized the therapeutic potential of MSCs for the treatment of these diseases, emphasizing molecular and cellular mechanisms responsible for MSC-based effects in an animal model of PBC and therapeutic potential observed in recently conducted clinical trials. We have also presented several outstanding problems including safety issues regarding unwanted differentiation of transplanted MSCs which limit their therapeutic use. Efficient and safe MSC-based therapy for PBC remains a challenging issue that requires continuous cooperation between clinicians, researchers, and patients.
Optimization Design of IGV Profile in Centrifugal Compressor
Authors: Sun Qi , Ji Chunjun , Fang Junyi , Li Chunyang , Zhang Xiaolin
Published: December 2017

Variable inlet guide vane (IGV) is used to control the mass flow and generate prewhirl in centrifugal compressors. The efficient operation of IGV is limited to the range of aerodynamic characteristics of their vane profiles. In order to find out the best vane profile for IGV regulation, the modern optimization method was adopted to optimize the inlet guide vane profile. The main methodology idea was to use artificial neural network for continuous fitness evaluation and use genetic algorithm for global optimization. After optimization, the regulating performance of IGV has improved significantly, the prewhirl ability has been enhanced greatly, and the pressure loss has been reduced. The mass flow and power of compressor reduced by using the optimized guide vane at large setting angles, and the efficiency increased significantly; the flow field distribution has been improved obviously, since the nonuniform distribution of flow and flow separation phenomenon greatly weakened or even completely disappeared. The achievement of this research can effectively improve the regulation ability of IGV and the performance of compressor.
Soil Metals and Ectomycorrhizal Fungi Associated with American Chestnut Hybrids as Reclamation Trees on Formerly Coal Mined Land
Authors: Bauman J. M. , Adamson J. , Brisbin R. , Cline E. T. , Keiffer C. H.
Published: December 2017

Hybrid chestnut(Castanea dentata×C. mollissima)has the potential to provide a valuable agroforestry crop on formerly coal mined landscapes. However, the soil interactions of mycorrhizal fungi and buried metals associated with mining are not known. This study examined soil, plant tissue, and ectomycorrhizal (ECM) root colonization on eight-year-old hybrid (BC1F3and BC2F3) and American chestnuts on a reclaimed coal mine in Ohio, USA. Chestnut trees were measured and ECM colonization on roots was quantified. Leaves, flowers, and soil were analyzed for heavy metals. Differences were not detected among tree types regarding metal accumulation in plant tissue or ECM colonization. BC2F3hybrids had greater survival and less cankers than American chestnuts (P= 0.006 and <0.0001). Taller trees were associated with greater ECM root colonization and correlated with an increase in Al uptake (P= 0.02 and 0.01). When comparing tissue, manganese and aluminum were in higher concentrations in leaves than flowers, where copper and selenium were significantly higher in floral tissue (P< 0.05). All trees were flowering at this time meriting further examination in nut tissue. Block effects for selenium and zinc indicate the variability in reclaimed soils requiring further monitoring for possible elemental transfer to nut and wood tissue.
The CARMA3–Bcl10–MALT1 Signalosome Drives NFκB Activation and Promotes Aggressiveness in Angiotensin II Receptor–Positive Breast Cancer
Authors: Ekambaram Prasanna , Lee Jia-Ying (Lloyd) , Hubel Nathaniel E. , Hu Dong , Yerneni Saigopalakrishna , Campbell Phil G. , Pollock Netanya , Klei Linda R. , Concel Vincent J. , Delekta Phillip C. , Chinnaiyan Arul M. , Tomlins Scott A. , Rhodes Daniel R. , Priedigkeit Nolan , Lee Adrian V. , Oesterreich Steffi , McAllister-Lucas Linda M. , Lucas Peter C.
Published: December 2017

The angiotensin II receptor AGTR1, which mediates vasoconstrictive and inflammatory signaling in vascular disease, is overexpressed aberrantly in some breast cancers. In this study, we established the significance of an AGTR1-responsive NFκB signaling pathway in this breast cancer subset. We documented that AGTR1 overexpression occurred in the luminal A and B subtypes of breast cancer, was mutually exclusive of HER2 expression, and correlated with aggressive features that include increased lymph node metastasis, reduced responsiveness to neoadjuvant therapy, and reduced overall survival. Mechanistically, AGTR1 overexpression directed both ligand-independent and ligand-dependent activation of NFκB, mediated by a signaling pathway that requires the triad of CARMA3, Bcl10, and MALT1 (CBM signalosome). Activation of this pathway drove cancer cell–intrinsic responses that include proliferation, migration, and invasion. In addition, CBM-dependent activation of NFκB elicited cancer cell–extrinsic effects, impacting endothelial cells of the tumor microenvironment to promote tumor angiogenesis. CBM/NFκB signaling in AGTR1+ breast cancer therefore conspires to promote aggressive behavior through pleiotropic effects. Overall, our results point to the prognostic and therapeutic value of identifying AGTR1 overexpression in a subset of HER2-negative breast cancers, and they provide a mechanistic rationale to explore the repurposing of drugs that target angiotensin II–dependent NFκB signaling pathways to improve the treatment of this breast cancer subset.

Significance: These findings offer a mechanistic rationale to explore the repurposing of drugs that target angiotensin action to improve the treatment of AGTR1-expressing breast cancers. Cancer Res; 78(5); 1225–40. ©2017 AACR.
LSD1 Stimulates Cancer-Associated Fibroblasts to Drive Notch3-Dependent Self-Renewal of Liver Cancer Stem–like Cells
Authors: Liu Chungang , Liu Limei , Chen Xuejiao , Cheng Jiamin , Zhang Heng , Zhang Chengcheng , Shan Juanjuan , Shen Junjie , Qian Cheng
Published: December 2017

Cancer stem-like cells (CSC) in hepatocellular carcinoma (HCC) are thought to mediate therapeutic resistance and poor survival outcomes, but their intrinsic and extrinsic control is not well understood. In this study, we found that the chromatin modification factor LSD1 is highly expressed in HCC CSC where it decreases during differentiation. LSD1 was responsible for maintaining CSC self-renewal and tumorigenicity in HCC, and its overexpression was sufficient to drive self-renewal of non-CSC. Levels of acetylated LSD1 were low in CSC with high LSD1 activity, and these CSC were capable of self-renewal. Notch signaling activated LSD1 through induction of the sirtuin SIRT1, leading to deacetylation and activation of LSD1 and CSC self-renewal. Notably, we found that LSD1 expression was increased in cancer-associated fibroblasts (CAF) as an upstream driver of Notch3-mediated CSC self-renewal. In clinical specimens of HCC, the presence of CAF, LSD1, and Notch3 strongly associated with poor patient survival. Overall, our results reveal that CAF-induced expression of Notch3 is responsible for LSD1 activation in CSC, driving their self-renewal in HCC.

Significance: These seminal findings illuminate a complex pathway in the tissue microenvironment of liver cancer, which is responsible for orchestrating the self-renewal of stem-like cancer cells, with potential implications to improve therapy and limit relapses. Cancer Res; 78(4); 938–49. ©2017 AACR.
Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression
Authors: De Smedt Eva , Maes Ken , Verhulst Stefaan , Lui Hui , Kassambara Alboukadel , Maes Anke , Robert Nicolas , Heirman Carlo , Cakana Andrew , Hose Dirk , Breckpot Karine , van Grunsven Leo A. , De Veirman Kim , Menu Eline , Vanderkerken Karin , Moreaux Jérôme , De Bruyne Elke
Published: December 2017

RAS mutations occur frequently in multiple myeloma (MM), but apart from driving progression, they can also stimulate antitumor effects by activating tumor-suppressive RASSF proteins. Although this family of death effector molecules are often silenced in cancers, functional data about RASSF proteins in MM are lacking. Here, we report that RASSF4 is downregulated during MM progression and correlates with a poor prognosis. Promoter methylation analysis in human cell lines revealed an inverse correlation between RASSF4 mRNA levels and methylation status. Epigenetic modulating agents restored RASSF4 expression. Enforced expression of RASSF4 induced G2-phase cell-cycle arrest and apoptosis in human cell lines, reduced primary MM cell viability, and blocked MM growth in vivo. Mechanistic investigations showed that RASSF4 linked RAS to several pro-death pathways, including those regulated by the kinases MST1, JNK, and p38. By activating MST1 and the JNK/c-Jun pathway, RASSF4 sensitized MM cells to bortezomib. Genetic or pharmacological elevation of RASSF4 levels increased the anti-MM effects of the clinical relevant MEK1/2 inhibitor trametinib. Kinome analysis revealed that this effect was mediated by concomitant activation of the JNK/c-Jun pathway along with inactivation of the MEK/ERK and PI3K/mTOR/Akt pathways. Overall, our findings establish RASSF4 as a tumor-suppressive hub in MM and provide a mechanistic rationale for combining trametinib with HDAC inhibitors or bortezomib to treat patients with tumors exhibiting low RASSF4 expression.

Significance: These findings provide a mechanistic rationale for combining trametinib with HDAC inhibitors or bortezomib in patients with multiple myeloma whose tumors exhibit low RASSF4 expression. Cancer Res; 78(5); 1155–68. ©2017 AACR.
ER Stress Signaling Promotes the Survival of Cancer “Persister Cells” Tolerant to EGFR Tyrosine Kinase Inhibitors
Authors: Terai Hideki , Kitajima Shunsuke , Potter Danielle S. , Matsui Yusuke , Quiceno Laura Gutierrez , Chen Ting , Kim Tae-jung , Rusan Maria , Thai Tran C. , Piccioni Federica , Donovan Katherine A. , Kwiatkowski Nicholas , Hinohara Kunihiko , Wei Guo , Gray Nathanael S. , Fischer Eric S. , Wong Kwok-Kin , Shimamura Teppei , Letai Anthony , Hammerman Peter S. , Barbie David A.
Published: December 2017

An increasingly recognized component of resistance to tyrosine kinase inhibitors (TKI) involves persistence of a drug-tolerant subpopulation of cancer cells that survive despite effective eradication of the majority of the cell population. Multiple groups have demonstrated that these drug-tolerant persister cells undergo transcriptional adaptation via an epigenetic state change that promotes cell survival. Because this mode of TKI drug tolerance appears to involve transcriptional addiction to specific genes and pathways, we hypothesized that systematic functional screening of EGFR TKI/transcriptional inhibitor combination therapy would yield important mechanistic insights and alternative drug escape pathways. We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib + THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. As expected, suppression of multiple genes associated with transcriptional complexes (EP300, CREBBP, and MED1) enhanced erlotinib/THZ1 synergy. Unexpectedly, we uncovered nearly every component of the recently described ufmylation pathway in the synergy suppressor group. Loss of ufmylation did not affect canonical downstream EGFR signaling. Instead, absence of this pathway triggered a protective unfolded protein response associated with STING upregulation, promoting protumorigenic inflammatory signaling but also unique dependence on Bcl-xL. These data reveal that dysregulation of ufmylation and ER stress comprise a previously unrecognized TKI drug tolerance pathway that engages survival signaling, with potentially important therapeutic implications.

Significance: These findings reveal a novel function of the recently described ufmylation pathway, an ER stress survival signaling in drug-tolerant persister cells, which has important biological and therapeutic implications. Cancer Res; 78(4); 1044–57. ©2017 AACR.
FIH Is an Oxygen Sensor in Ovarian Cancer for G9a/GLP-Driven Epigenetic Regulation of Metastasis-Related Genes
Authors: Kang Jengmin , Shin Seung-Hyun , Yoon Haejin , Huh June , Shin Hyun-Woo , Chun Yang-Sook , Park Jong-Wan
Published: December 2017

The prolyl hydroxylase domain-containing proteins (PHD1-3) and the asparaginyl hydroxlyase factor inhibiting HIF (FIH) are oxygen sensors for hypoxia-inducible factor-driven transcription of hypoxia-induced genes, but whether these sensors affect oxygen-dependent epigenetic regulation more broadly is not known. Here, we show that FIH exerts an additional role as an oxygen sensor in epigenetic control by the histone lysine methyltransferases G9a and GLP. FIH hydroxylated and inhibited G9a and GLP under normoxia. When the FIH reaction was limited under hypoxia, G9a and GLP were activated and repressed metastasis suppressor genes, thereby triggering cancer cell migration and peritoneal dissemination of ovarian cancer xenografts. In clinical specimens of ovarian cancer, expression of FIH and G9a were reciprocally associated with patient outcomes. We also identified mutations of FIH target motifs in G9a and GLP, which exhibited excessive H3K9 methylation and facilitated cell invasion. This study provides insight into a new function of FIH as an upstream regulator of oxygen-dependent chromatin remodeling. It also implies that the FIH-G9a/GLP pathway could be a potential target for inhibiting hypoxia-induced cancer metastasis.

Significance: These findings deepen understanding of oxygen-dependent gene regulation and cancer metastasis in response to hypoxia. Cancer Res; 78(5); 1184–99. ©2017 AACR.
In utero Plastic Surgery in Zurich: Successful Use of Distally Pedicled Random Pattern Transposition Flaps for Definitive Skin Closure during Open Fetal Spina Bifida Repair
Authors: Meuli Martin , Meuli-Simmen Claudia , Mazzone Luca , Tharakan Sasha J. , Zimmermann Roland , Ochsenbein Nicole , Moehrlen Ueli
Published: December 2017

Background: One of the intraoperative challenges of fetal spina bifida repair is skin closure when there is an extended skin defect. Thus, we examined whether distally pedicled random pattern transposition flaps (TFs) are a valid option to overcome this problem. Subjects and Methods: All patients undergoing in utero repair of spina bifida with application of a TF for back skin closure were analyzed focusing on intraoperative flap characteristics and postoperative flap performance. Results: In 30 (70%) of the 43 fetuses a primary skin closure was achieved, in 5 (12%) a skin substitute was used, and in 8 (18%) a TF was applied. Flap raising and insertion was uneventful and perfusion was sufficient in all 8 fetuses (100%). In 3 fetuses (37%) the donor sites were closed primarily, and in 5 (63%) a skin substitute was used for coverage. At birth, 7 flaps were viable and provided robust skin coverage over the center of the former lesion. Complications included a small skin defect with CSF leakage in 1 patient (13%). Conclusion: During open fetal spina bifida repair, TFs can be safely and efficaciously used to obtain solid and durable skin coverage over lesions too large to allow conventional primary skin closure.
Clinical Significance of Bmi1 Expression in Inflammatory Bowel Disease
Authors: Yamada Mitsunari , Sakurai Toshiharu , Komeda Yoriaki , Nagai Tomoyuki , Kamata Ken , Minaga Kosuke , Yamao Kentaro , Takenaka Mamoru , Hagiwara Satoru , Matsui Shigenaga , Watanabe Tomohiro , Nishida Naoshi , Kashida Hiroshi , Kudo Masatoshi
Published: December 2017

Background: Although the stem cell marker Bmi1 is overexpressed in many malignancies, its role in inflammation-associated cancer is unclear. Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD). Methods: To assess the involvement of Bmi1 in the development of CAC, we analyzed the gene expression of colon tissues collected from 111 patients with IBD and CAC. Results: In the colonic mucosa of patients with ulcerative colitis, the expression of Bmi1 correlated significantly with the expression of inflammatory cytokines such as IL-6, IL-17, IL-23, and tumor necrosis factor α (TNF-α). In the colonic mucosa of patients with Crohn's disease, the expression of Bmi1 correlated significantly with the expression of TNF-α and IL-23. The expression of Bmi1 was enhanced in the colonic mucosae of refractory IBD, suggesting that Bmi1 expression might be related to increased cancer risk. In addition, patients with high Bmi1 expression showed significantly lower response rates upon subsequent anti-TNF-α therapy as compared to patients with low Bmi1 expression. In human CAC specimens, the expression of Bmi1 was upregulated in nontumor tissues as well as tumors. Conclusions: Bmi1 expression is related to a refractory clinical course of IBD and upregulated in refractory IBD and CAC. Measurement of Bmi1 expression is a promising approach for the advanced treatment and personalized management of IBD patients.
Risk Factors for Postoperative Bleeding in Endoscopic Submucosal Dissection of Colorectal Tumors
Authors: Okamoto Kazuki , Watanabe Tomohiro , Komeda Yoriaki , Kono Tatsuya , Takashima Kouta , Okamoto Ayana , Kono Masashi , Yamada Mitsunari , Arizumi Tadaaki , Kamata Ken , Minaga Kosuke , Yamao Kentaro , Nagai Tomoyuki , Asakuma Yutaka , Takenaka Mamoru , Sakurai Toshiharu , Matsui Shigenaga , Nishida Naoshi , Chikugo Takaaki , Kashida Hiroshi , Kudo Masatoshi
Published: December 2017

Background: Colonoscopic removal of adenomatous polyps or early cancer prevents death from colorectal cancer. Endoscopic submucosal dissection (ESD), which enables endoscopists to perform en bloc resection of flat or depressed colorectal tumors >20 mm, has recently been introduced and become a standard procedure in Japan. Although postoperative bleeding (POB) is a major complication associated with ESD, risk factors for POB have not been fully identified. Methods: A total of 451 patients (509 lesions) who underwent colorectal ESD were retrospectively analyzed to identify clinical parameters associated with POB. Results: POB occurred in 14 patients, and 7 of them had received antithrombotic therapy before ESD. Uni- and multivariate analyses revealed that antithrombotic therapy and rectal tumor location were strongly associated with POB following colorectal ESD. The incidence of POB was higher in patients on heparin bridge therapy (HBT) for the replacement of antithrombotic therapy than in patients with no HBT. Four of 7 patients (57.1%) on antithrombotic therapy experienced POB from the rectal lesions. Conclusion: Antithrombotic therapy and rectal lesions result in a higher POB incidence after colorectal ESD.
Immuno-Oncology in Hepatocellular Carcinoma: 2017 Update
Authors: Kudo Masatoshi
Published: December 2017

Clinical trials are currently ongoing to evaluate the utility of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as monotherapy or combination therapy in patients with hepatocellular carcinoma (HCC). Results of combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab in HCC were presented at the 2017 annual meeting of the ASCO (American Society of Clinical Oncology). Response rates were 25% in all 40 patients and 40% in the 20 uninfected patients, both of which are encouraging. Transcatheter arterial chemoembolization and radiofrequency ablation can activate tumor immunogenicity by releasing tumor-associated antigen and by inducing the migration of cytotoxic T lymphocytes to small intrahepatic metastatic nodules. Subsequent administration of anti-PD-1 antibody could control these small intrahepatic metastatic nodules. In a nonclinical study, the combination of pembrolizumab and lenvatinib inhibited the cancer immunosuppressive environments induced by tumor-associated macrophages and regulatory T cells. This, in turn, decreased the levels of TGF-β and IL-10, the expression of PD-1, and the inhibition of Tim-3, triggering anticancer immunity mediated by immunostimulatory cytokines such as IL-12. Studies such as these may provide insight into the appropriate molecular targeted agents to be used with immune checkpoint inhibitors.
Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Naik Girish S. , Ming Wai K. , Magodoro Itai M. , Akinwunmi Babatunde , Dar Sara , Poulsen Henrik E. , Kristensen Lars E. , Ellervik Christina
Published: December 2017

Background: Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α antagonists as first-line biologic agents. We determined the overall treatment effect of Th17 pathway inhibitors compared to placebo or active control on American College of Rheumatology (ACR) 20 response at week 12 (primary objective), risk of infections, discontinuation of treatment due to adverse events, and serious adverse events during the placebo-controlled period (12-24 weeks) in adults with active PsA in published randomized controlled trials. Methods: The SCOPUS database was searched. The Cochrane risk of bias tool was used for assessing quality. The pooled relative risk (RR) was derived from random effects models. Results: Seven randomized controlled trials were included which randomized 1,718 patients to Th17 inhibitors and 840 to placebo. Patients treated with Th17 inhibitors had an RR of 2.04 (95% CI: 1.79-2.33; p < 0.001) for achieving an ACR20 response at week 12 (I2 = 0%; p = 0.89) compared to placebo-treated patients. There was no evidence of publication bias. The result was consistent for study phase and outcome (ACR50/70), mechanism of action and TNF-α naivety. RR of infections was 1.06 (0.91-1.23), that of candida infections was 3.35 (0.75-14.95), that of serious adverse events was 0.82 (0.42-1.59) and that of discontinuation of treatment was 0.54 (0.31-0.93) among treated versus placebo subjects. No incident cases of tuberculosis were reported. Conclusion: In patients with active PsA, biologics targeting the Th17 axis produce a clinically significant improvement in joint disease activity with acceptable safety and tolerability for short-term treatment compared to placebo.
Familial Duplication/Deletion of 1q42.13q43 as Meiotic Consequence of an Intrachromosomal Insertion in Chromosome 1
Authors: Silipigni Rosamaria , Monfrini Edoardo , Baccarin Marco , Giangiobbe Sara , Lalatta Faustina , Guerneri Silvana , Bedeschi Maria Francesca
Published: December 2017

Rearrangements of the region 1q42.13q43 are rare, with only 7 cases reported to date. The imbalances described are usually the result of inherited translocations with other chromosomes. Moreover, few cases of both inter- and intrachromosomal deletions/duplications detected cytogenetically have been described. We report the molecular cytogenetic characterization of an inverted insertion involving the region 1q42.13q43 and segregating in 2 generations of a family. The deletion and the duplication of the same segment were detected in 2 affected family members. SNP array analysis showed the familial origin of the deletion/duplication due to the occurrence of a crossing-over during meiosis. Our report underlines the importance of determining the correct origin of chromosomal aberrations using different molecular cytogenetic tests in order to provide a good estimation of the reproductive risk for the members of the family.
Vitamin D Status and Resting Metabolic Rate May Modify through Expression of Vitamin D Receptor and Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene in Overweight and Obese Adults
Authors: Sajjadi Seyedeh Forough , Mirzaei Khadijeh , Khorrami-Nezhad Leila , Maghbooli Zhila , Keshavarz Seyed Ali
Published: December 2017

Background: Resting metabolic rate (RMR) used to prognosticate and measure the amount of energy required. Vitamin D is known as a new predictor of RMR. The aim of this study is to investigate the relationship between vitamin D effects on RMR in connection with the vitamin D receptor (VDR) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) gene expression. Methods: We enrolled 298 overweight and obese adults in this cross-sectional study. Body mass index (BMI), fat mass, fat-free mass, insulin level, visceral fat, and vitamin D status were assessed. RMR was measured by means of indirect calorimetry. The real-time polymerase chain reaction using specific primer pairs for VDR and PGC-1α was performed. Results: There were significant differences in terms of fat free mass, fat percentage, insulin levels, RMR/kg body weight, and RMR/BMI, VDR, and PGC-1α among participants were categorized based on the vitamin D status. But after using general linear model for adjusting, all significant results missed their effectiveness except RMR/kg body weight and VDR. Linear regression analysis used to show the mediatory role of VDR and PGC-1α on the RMR/kg body weight and vitamin D status relationship. Our results showed that VDR had a mediatory effect on the relationship between RMR/kg body weight and vitamin D status (β = 0.38, 95% CI –0.48 to 1.60; β = –1.24, 95% CI –5.36 to 1.70). However, PGC-1α did not affect the relationship between RMR/kg body weight and vitamin D status (β = 0.50, 95% CI = –0.02 to 3.42; β = 0.59, 95% CI 0.14–3.90). Conclusion: Our study showed the mediatory effect of VDR gene expression in the association of 25(OH)2D plasma levels and resting metabolic rate among obese individuals.
The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis
Authors: Csiky Botond , Sági Balázs , Peti Attila , Lakatos Orsolya , Prémusz Viktória , Sulyok Endre
Published: December 2017

Background/Aims: This cross-sectional study was designed to assess the relationship between vascular stiffness (VS) and bone-related proteins involved in the development of arteriosclerosis in patients on regular hemodialysis (HD). Methods: 68 consecutive patients in stable clinical condition who received regular HD in the FMC Dialysis Center, Pécs were included. VS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index - AIx) were determined by applanation tonometry (SphygmoCor, AtCor Medical, Sidney) and the routine latoratory test were completed with measurements of osteocalcin (OC), osteopontin (OP) and osteoprotegerin (OPG) by using commercially available ELISA kits. 35 heathcare workers served as controls. Results: In patients on regular HD PWV markedly increased and there was several-fold elevation in the interrelated bone-specific proteins (OC, OP, OPG). PWV was found to be independently associated only with OC (β:-0.25, p<0.029) and age (r=0.411,p<0.000), but risk factors for arterial calcification had significant impact on OC (systolic blood pressure, hsCRP, BMI), OPG (age, BMI) and OP (LDL-cholesterol). Conclusion: Except for OC, our results failed to document direct association of vascular lesion with OP and OPG, therefore their high circulating levels may be an epiphenomenon or they may have counter-regulatory role to attenuate the uremic calcification process.
Phage Abp1 Rescues Human Cells and Mice from Infection by Pan-Drug Resistant Acinetobacter Baumannii
Authors: Yin Supeng , Huang Guangtao , Zhang Yulong , Jiang Bei , Yang Zichen , Dong Zhiwei , You Bo , Yuan Zhiqiang , Hu Fuquan , Zhao Yan , Peng Yizhi
Published: December 2017

Background/Aims: As an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.
Effects of aging and base of support in postural control
Authors: Lahr Silvana Lopes Nogueira , Ugrinowitsch Herbert , Santos Leonardo Luiz Portes dos , Andrade André Gustavo Pereira de , Benda Rodolfo Novellino
Published: December 2017

Este estudo teve como objetivos avaliar o controle postural de jovens e idosos em relação à direção predominante e à área de deslocamento do centro de pressão, buscando verifi car se diferentes bases de suporte evidenciam diferenças entre os grupos para estas duas variáveis. A amostra foi composta por oito adultos jovens (22,6±2,33 anos) e oito idosos (75,4±5,7 anos), e a tarefa consistiu em permanecer de pé sobre uma plataforma de força por 30 segundos, em duas bases de suporte: normal (BSN) e semi-tandem (BSST), sendo realizadas três tentativas em cada uma delas. Avaliou-se as variáveis “área” e “direção” de oscilação, ambas derivadas no centro de pressão. Os resultados mostraram que idosos apresentaram maior oscilação corporal que jovens e a restrição na base de suporte ampliou a oscilação de ambos os grupos etários. Conclui-se que idosos e jovens apresentam comportamentos distintos em relação à oscilação corporal e que o aumento na difi culdade da tarefa é capaz de evidenciar parcialmente essas diferenças.
Physical Education in the nursery: thematising bodily practices
Authors: Macedo Elina Elias de , Neira Marcos Garcia
Published: December 2017

A investigação aqui apresentada analisou e interpretou uma experiência pedagógica de Educação Física na creche. No percurso metodológico valeu-se de diversas ferramentas de base etnográfi ca (observação participante e registros em caderno de campo) e nos referenciais teóricos dos Estudos Culturais. O trabalho pedagógico desenvolvido, ao abordar e problematizar as lutas por legitimidade que permeiam as práticas corporais, contribuiu para potencializar as vozes das crianças, ampliando as oportunidades de reconhecimento das diferenças e promovendo o estabelecimento de relações sociais mais democráticas.
Extroversion, mental practice and imagery in the acquisition of the cartwheel
Authors: Moura Mariana , Souza Marina Mompean , Neiva Jaqueline Freitas Oliveira , Meira Junior Cássio Miranda
Published: December 2017

O presente trabalho teve como objetivos (1) investigar os efeitos da prática física (PF) associada à prática mental (PM) com mentalização interna (MI) e externa (ME) na aprendizagem da habilidade “estrela” da ginástica artística e (2) correlacionar escores de extroversão e de desempenho na tarefa. Trinta adolescentes (12,93 ± 0,73 anos) foram designadas a dois grupos: 1) PF seguida de PM com ME (n=15) e 2) PF seguida de PM com MI (n=15). O delineamento constou de pré-teste, aquisição, pós-teste, retenção e transferência (todas as fases foram fi lmadas, exceto a aquisição). Os registros em vídeo foram analisados por meio de uma lista de checagem da estrela. O Eysenck Personality Questionnaire foi utilizado para classifi car as participantes quanto a níveis de extroversão. As análises apontaram que houve melhora de desempenho dentro de cada grupo (do pré-teste para os outros testes), mas que em nenhuma das fases houve qualquer diferença signifi cativa entre os grupos. No entanto, uma correlação positiva e moderada foi detectada entre os escores de extroversão e de desempenho no grupo ME. Esses achados reforçam a importância da PM como estratégia complementar à PF e sinalizam a existência de relação entre extroversão, desempenho da estrela e perspectiva de mentalização.
Integralidade da assistência terapêutica e farmacêutica: um debate necessário
Authors: Vieira Fabiola Sulpino
Published: December 2017

A polêmica em torno de diferentes interpretações sobre a integralidade da assistência terapêutica e farmacêutica levou à delimitação de sua abrangência por meio de uma lei, mas sem que a questão tenha sido completamente pacificada. Como contribuição a esse debate, o objetivo deste texto é o de discutir os desafios à garantia da integralidade da assistência terapêutica e farmacêutica, a partir de uma abordagem conceitual sobre os sentidos da integralidade no Sistema Único de Saúde (SUS). Identificam-se desafios importantes para a garantia da integralidade da assistência terapêutica e farmacêutica no SUS. Esses desafios estão relacionados às práticas profissionais, à organização das ações e serviços e à resposta governamental para problemas de saúde ou para tratamento de grupos populacionais específicos. Isso exige dos governos ações estruturantes e eficiência no uso dos recursos disponíveis, a fim de que os problemas existentes sejam superados.
Genetic Architecture of the Cardiovascular Risk Proteome
Authors: Benson Mark D. , Yang Qiong , Ngo Debby , Zhu Yineng , Shen Dongxiao , Farrell Laurie A. , Sinha Sumita , Keyes Michelle J. , Vasan Ramachandran S. , Larson Martin G. , Smith J. Gustav , Wang Thomas J. , Gerszten Robert E.
Published: December 2017

Background:

We recently identified 156 proteins in human plasma that were each associated with the net Framingham Cardiovascular Disease Risk Score using an aptamer-based proteomic platform in Framingham Heart Study Offspring participants. Here we hypothesized that performing genome-wide association studies and exome array analyses on the levels of each of these 156 proteins might identify genetic determinants of risk-associated circulating factors and provide insights into early cardiovascular pathophysiology.

Methods:

We studied the association of genetic variants with the plasma levels of each of the 156 Framingham Cardiovascular Disease Risk Score–associated proteins using linear mixed-effects models in 2 population-based cohorts. We performed discovery analyses on plasma samples from 759 participants of the Framingham Heart Study Offspring cohort, an observational study of the offspring of the original Framingham Heart Study and their spouses, and validated these findings in plasma samples from 1421 participants of the MDCS (Malmö Diet and Cancer Study). To evaluate the utility of this strategy in identifying new biological pathways relevant to cardiovascular disease pathophysiology, we performed studies in a cell-model system to experimentally validate the functional significance of an especially novel genetic association with circulating apolipoprotein E levels.

Results:

We identified 120 locus-protein associations in genome-wide analyses and 41 associations in exome array analyses, the majority of which have not been described previously. These loci explained up to 66% of interindividual plasma protein-level variation and, on average, accounted for 3 times the amount of variation explained by common clinical factors, such as age, sex, and diabetes mellitus status. We described overlap among many of these loci and cardiovascular disease genetic risk variants. Finally, we experimentally validated a novel association between circulating apolipoprotein E levels and the transcription factor phosphatase 1G. Knockdown of phosphatase 1G in a human liver cell model resulted in decreased apolipoprotein E transcription and apolipoprotein E protein levels in cultured supernatants.

Conclusions:

We identified dozens of novel genetic determinants of proteins associated with the Framingham Cardiovascular Disease Risk Score and experimentally validated a new role for phosphatase 1G in lipoprotein biology. Further, genome-wide and exome array data for each protein have been made publicly available as a resource for cardiovascular disease research.
New lichen species from Thailand, new combinations and new additions to the Thai lichen biota
Authors: KALB JUTARAT , KALB KLAUS
Published: December 2017

Several collecting trips by the authors (alone or together) over the last ten years in twenty-one provinces of Thailand afforded new additions to the most recent Thai lichen checklist. These are from seven families with an emphasis on the Graphidaceae reflecting the current interest of the authors. Three species are described as new to science: Glaucotrema palaeoprotocetraricum which differs from G. thailandicum in having larger ascospores and producing protocetraric acid, Platygramme subcalubrosa which differs from P. calubrosa in having non-pruinose labia and discs and smaller, less-septate ascospores and Ramonia minima, which differs from R. kandleri in having smaller ascomata, a lower hymenium and a partly brown to blackish exciple. Constrictolumina leucostoma is a new finding for the Palaeotropics and the genera Pseudotopeliopsis, Ramonia and Sclerophyton are new reports for Thailand. New records of Thai species of Hemithecium are transferred to Allographa and Graphis. This necessitated the following new combinations: Allographa stictilabiata (≡ Gra­phina stictilabiata), Graphis aphaneomicrospora (≡ Hemithecium aphaneomicrosporum) , G. balaghatensis (≡ Hemithecium balaghatense) and Graphis indica (a new name for Hemithecium norsticticum). Further new combinations include Glaucotrema protocetraricum (≡ Ocellularia protocetrarica) and Traponora varians (≡ Lecidea varians). Acanthothecis consocians, Caloplaca bassiae, Chapsa pulchra, Leucodecton occultum, Phaeographopsis palaeotropica, Platygramme australiensis, P. commutabilis, P. discurrens, Sclerophyton seriale, Psudotopeliopsis longisporum, Traponora macrospora and Trinathotrema stictideum are further new additions to the Thai lichen biota. Working keys are presented to all known species of Phaeographopsis and Trinathotrema and to the Thai species of Platygramme.
Typification of the name Botrychium lanuginosum (Ophioglossaceae)
Authors: JOSHI PUSHPESH , KUMAR BRIJESH , DWIVEDI HIMANSHU
Published: December 2017

The genus Botrychium Swartz (1801: 110) is represented by 50–60 species, distributed worldwide (Zhang et al. 2013). In India, the genus is represented by 8 taxa (Fraser- Jenkins et al. 2017). During revisionary study of the genus Botrychium in India, the authors realized the necessity to lectotypify the name Botrychium lanuginosum Wallich ex Hooker & Greville (1828: t.79) because no specific herbarium sheet is cited as holotype in the protologue and has not been lectotypified earlier (Fraser-Jenkins et al. 2017). Therefore it is lectotypified here to avoid any ambiguity in the application of the name. The guidelines of Art. 9.2 and Recommendations 9A, 9C and 9D of the ICN (McNeill et al. 2012) have been followed while designating the lectotype