bluuebunny/crossref_metadata_2025 huggingface dataset:
High Incidence of Gastrointestinal Ulceration and Cytogenetic Aberration of Trisomy 8 as Typical Features of Behçet’s Disease Associated with Myelodysplastic Syndrome: A Series of 16 Consecutive Chinese Patients from the Shanghai Behçet’s Disease Database and Comparison with the Literature
Authors: Shen Yan , Ma Hai-Fen , Luo Dan , Cai Jian-Fei , Zou Jun , Guan Jian-Long
Published: April 2018

This study aimed to investigate the characteristics of Chinese patients with Behçet disease (BD) and myelodysplastic syndrome (MDS) and explore the role played by trisomy 8. This was a retrospective study of patients with BD and MDS from the Shanghai Behçet’s disease database who were diagnosed between October 2012 and July 2017. There were 805 patients with BD and 16 also had MDS. Trisomy 8 was examined in patients with BD-MDS and some patients with gastrointestinal (GI) BD. Patients with BD and MDS (16/805; 2%) were more likely to be female and older; display fever and intestinal lesions; have lower leukocyte count, hemoglobin, platelet count; and show higher C-reactive protein and erythrocyte sedimentation rate (ESR) than patients with BD without MDS (all P<0.05). Trisomy 8 was common (81.3%) in patients with BD-MDS. Ulcers in the ileocecal region were more frequently seen in intestinal patients with BD-MDS than in BD without MDS (90.0% versus 48.9%; P=0.032). GI ulceration is common in patients with BD-MDS. Cytogenetic aberrations, especially trisomy 8, may play a role in the pathogenesis of intestinal involvement in patients with BD-MDS.
Reliability Modeling of Electromechanical System with Meta-Action Chain Methodology
Authors: Zhang Genbao , Wang Yang
Published: April 2018

To establish a more flexible and accurate reliability model, the reliability modeling and solving algorithm based on the meta-action chain thought are used in this thesis. Instead of estimating the reliability of the whole system only in the standard operating mode, this dissertation adopts the structure chain and the operating action chain for the system reliability modeling. The failure information and structure information for each component are integrated into the model to overcome the given factors applied in the traditional modeling. In the industrial application, there may be different operating modes for a multicomponent system. The meta-action chain methodology can estimate the system reliability under different operating modes by modeling the components with varieties of failure sensitivities. This approach has been identified by computing some electromechanical system cases. The results indicate that the process could improve the system reliability estimation. It is an effective tool to solve the reliability estimation problem in the system under various operating modes.
Therapeutic Effect of Anti-VEGF for Age-Related Macular Degeneration in the Untreated Fellow Eye
Authors: Isildak Hacer , Schwartz Stephen G. , Flynn Harry W.
Published: April 2018

Intravitreal injections of antivascular endothelial growth factor (anti-VEGF) agents have been reported to occasionally produce a therapeutic effect in the uninjected fellow eye. Here, three patients with bilateral neovascular age-related macular degeneration are presented. In all three patients, unilateral anti-VEGF injection resulted in bilateral reduction of macular thickness as measured by spectral domain optical coherence tomography.
Page Kidney: An Unusual Complication of a Renal Transplant Biopsy
Authors: McFadden Jacob D. , Hawksworth Jason S.
Published: April 2018

Page kidney, a rare phenomenon whereby external compression of renal parenchyma can induce hypertension, can be caused by subcapsular hematoma following renal transplant biopsy. Surgical intervention is often warranted to salvage the transplant kidney. This is a case report of a patient with acute T-cell-mediated rejection and no other risk factors for postprocedural bleeding that developed Page kidney. The patient had no signs or symptoms for >24 hours from the time of biopsy, underscoring the need for awareness of this rare but potentially catastrophic complication of renal transplant biopsies.
Evidence-Based Clinical Algorithm for Hypotonia Assessment: To Pardon the Errs
Authors: Govender Pragashnie , Joubert Robin Wendy Elizabeth
Published: April 2018

Despite the many advances in diagnostics, the clinical assessment of children with hypotonia presents a diagnostic challenge for clinicians due to the current subjectivity of the initial clinical assessment. The aim of this paper is to report on an evidence-based clinical algorithm (EBCA) that was developed for the clinical assessment of hypotonia in children as part of the output of a multiphased study towards assisting clinicians in more accurate assessments. This study formed part of a larger advanced mixed methods design. The preceding phases of the study included a systematic review, a survey amongst clinicians, a consensus process (Delphi technique), and a qualitative critique with multiple focus groups. Samples were drawn from three professional groups (occupational therapists, physiotherapists, and paediatricians). Data were analysed at each stage and merged in the development of the EBCA. The EBCA followed a rigorous process of development and critique. The methods for formulating changes in the revision and development of the EBCA are presented together with a description and presentation of the final algorithm for practice. The overarching concepts that guided the development and refinement of the EBCA are described, taking into consideration knowledge translation, evidence-based practice, and the value of EBCAs in addition to recommendations for stakeholder uptake. The EBCA is envisaged to be useful in practice for clinicians who are faced with the assessment of a child that is suspected as having hypotonia via a systematic process in identifying specific characteristics that are associated with low muscle tone.
Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen (Salvia miltiorrhiza)
Authors: Zou Jia , Chen Yang , Hoi Maggie Pui Man , Li Jun , Wang Tao , Zhang Ying , Feng Yu , Gao Jianli , Lee Simon Ming Yuen , Cui Guozhen
Published: April 2018

Danshen (Salvia miltiorrhiza) is a well‐known herb in Traditional Chinese Medicine (TCM) for treating cardiovascular diseases, but the underlying mechanism remains to be fully elucidated. Here, we showed that Danshen and its active ingredient rosmarinic acid exhibited antiplatelet effects through the inhibition of ERp57, a member of protein disulfide isomerase (PDI) with potential roles in platelet aggregation. Danshen extract (DSE) exhibited potent inhibitory effects on the platelet aggregation induced by arachidonic acid‐ (AA‐) induced platelet aggregation and the enzymatic activity of ERp57. Rosmarinic acid was identified by virtual screening and molecular docking as one of the hit compounds for ERp57. In line with this, rosmarinic acid displayed significant inhibitory effect on ERp57 activity and inhibited AA‐induced platelet aggregation. Taken together, we demonstrated for the first time that DSE and rosmarinic acid displayed inhibitory effects on the catalytic activity of ERp57, providing evidence of the regulatory role of ERp57 underlying the antiplatelet effects of Danshen.
The Inhibitory NKR-P1B:Clr-b Recognition Axis Facilitates Detection of Oncogenic Transformation and Cancer Immunosurveillance
Authors: Tanaka Miho , Fine Jason H. , Kirkham Christina L. , Aguilar Oscar A. , Belcheva Antoaneta , Martin Alberto , Ketela Troy , Moffat Jason , Allan David S.J. , Carlyle James R.
Published: April 2018

Natural killer (NK) cells express receptors specific for MHC class I (MHC-I) molecules involved in “missing-self” recognition of cancer and virus-infected cells. Here we elucidate the role of MHC-I-independent NKR-P1B:Clr-b interactions in the detection of oncogenic transformation by NK cells. Ras oncogene overexpression was found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells, mediated in part via the Raf/MEK/ERK and PI3K pathways. Ras-driven Clr-b downregulation occurred at the level of the Clrb (Clec2d) promoter, nascent Clr-b transcripts, and cell surface Clr-b protein, in turn promoting missing-self recognition via the NKR-P1B inhibitory receptor. Both Ras- and c-Myc–mediated Clr-b loss selectively augmented cytotoxicity of oncogene-transformed leukemia cells by NKR-P1B+ NK cells in vitro and enhanced rejection by WT mice in vivo. Interestingly, genetic ablation of either one (Clr-b+/−) or two Clr-b alleles (Clr-b−/−) enhanced survival of Eμ-cMyc transgenic mice in a primary lymphoma model despite preferential rejection of Clr-b−/− hematopoietic cells previously observed following adoptive transfer into naïve wild-type mice in vivo. Collectively, these findings suggest that the inhibitory NKR-P1B:Clr-b axis plays a beneficial role in innate detection of oncogenic transformation via NK-cell–mediated cancer immune surveillance, in addition to a pathologic role in the immune escape of primary lymphoma cells in Eμ-cMyc mice in vivo. These results provide a model for the human NKR-P1A:LLT1 system in cancer immunosurveillance in patients with lymphoma and suggest it may represent a target for immune checkpoint therapy.

Significance: A mouse model shows that an MHC-independent NK-cell recognition axis enables the detection of leukemia cells, with implications for a novel immune checkpoint therapy target in human lymphoma. Cancer Res; 78(13); 3589–603. ©2018 AACR.
Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo
Authors: Thakur Shilpa , Daley Brianna , Gaskins Kelli , Vasko Vasyl V. , Boufraqech Myriem , Patel Dhaval , Sourbier Carole , Reece Jeff , Cheng Sheue-Yann , Kebebew Electron , Agarwal Sunita , Klubo-Gwiezdzinska Joanna
Published: April 2018

Purpose: Mitochondrial glycerophosphate dehydrogenase (MGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin in the liver. There are no data on the expression and role of MGPDH as a metformin target in cancer. In this study, we evaluated MGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism.

Experimental Design: We analyzed MGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer–derived cell lines (FTC133, BCPAP) by confocal microscopy. The effects of metformin on MGPDH expression were determined by qRT-PCR and Western blot analysis. Seahorse analyzer was utilized to assess the effects of metformin on OXPHOS and glycolysis in thyroid cancer cells. We analyzed the effects of metformin on tumor growth and MGPDH expression in metastatic thyroid cancer mouse models.

Results: We show for the first time that MGPDH is overexpressed in thyroid cancer compared with normal thyroid. We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro. Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro. Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivo.

Conclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin. Clin Cancer Res; 24(16); 4030–43. ©2018 AACR.
Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies
Authors: Odegaard Justin I. , Vincent John J. , Mortimer Stefanie , Vowles James V. , Ulrich Bryan C. , Banks Kimberly C. , Fairclough Stephen R. , Zill Oliver A. , Sikora Marcin , Mokhtari Reza , Abdueva Diana , Nagy Rebecca J. , Lee Christine E. , Kiedrowski Lesli A. , Paweletz Cloud P. , Eltoukhy Helmy , Lanman Richard B. , Chudova Darya I. , Talasaz AmirAli
Published: April 2018

Purpose: To analytically and clinically validate a circulating cell-free tumor DNA sequencing test for comprehensive tumor genotyping and demonstrate its clinical feasibility.

Experimental Design: Analytic validation was conducted according to established principles and guidelines. Blood-to-blood clinical validation comprised blinded external comparison with clinical droplet digital PCR across 222 consecutive biomarker-positive clinical samples. Blood-to-tissue clinical validation comprised comparison of digital sequencing calls to those documented in the medical record of 543 consecutive lung cancer patients. Clinical experience was reported from 10,593 consecutive clinical samples.

Results: Digital sequencing technology enabled variant detection down to 0.02% to 0.04% allelic fraction/2.12 copies with ≤0.3%/2.24–2.76 copies 95% limits of detection while maintaining high specificity [prevalence-adjusted positive predictive values (PPV) >98%]. Clinical validation using orthogonal plasma- and tissue-based clinical genotyping across >750 patients demonstrated high accuracy and specificity [positive percent agreement (PPAs) and negative percent agreement (NPAs) >99% and PPVs 92%–100%]. Clinical use in 10,593 advanced adult solid tumor patients demonstrated high feasibility (>99.6% technical success rate) and clinical sensitivity (85.9%), with high potential actionability (16.7% with FDA-approved on-label treatment options; 72.0% with treatment or trial recommendations), particularly in non–small cell lung cancer, where 34.5% of patient samples comprised a directly targetable standard-of-care biomarker.

Conclusions: High concordance with orthogonal clinical plasma- and tissue-based genotyping methods supports the clinical accuracy of digital sequencing across all four types of targetable genomic alterations. Digital sequencing's clinical applicability is further supported by high rates of technical success and biomarker target discovery. Clin Cancer Res; 24(15); 3539–49. ©2018 AACR.
Tryptophan Metabolism Contributes to Radiation-Induced Immune Checkpoint Reactivation in Glioblastoma
Authors: Kesarwani Pravin , Prabhu Antony , Kant Shiva , Kumar Praveen , Graham Stewart F. , Buelow Katie L. , Wilson George D. , Miller C. Ryan , Chinnaiyan Prakash
Published: April 2018

Purpose: Immune checkpoint inhibitors designed to revert tumor-induced immunosuppression have emerged as potent anticancer therapies. Tryptophan metabolism represents an immune checkpoint, and targeting this pathway's rate-limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).

Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma. Immunocompetent mice were injected orthotopically with genetically engineered murine glioma cells and treated with GDC-0919 alone or combined with RT. Flow cytometry was performed on isolated tumors to determine immune consequences of individual treatments.

Results: Integrated cross-platform analyses coupling global metabolomic and gene expression profiling identified aberrant tryptophan metabolism as a metabolic node specific to the mesenchymal and classical subtypes of glioblastoma. GDC-0919 demonstrated potent inhibition of this node and effectively crossed the blood–brain barrier. Although GDC-0919 as a single agent did not demonstrate antitumor activity, it had a strong potential for enhancing RT response in glioblastoma, which was further augmented with a hypofractionated regimen. RT response in glioblastoma involves immune stimulation, reflected by increases in activated and cytotoxic T cells, which was balanced by immune checkpoint reactivation, reflected by an increase in IDO1 expression and regulatory T cells (Treg). GDC-0919 mitigated RT-induced Tregs and enhanced T-cell activation.

Conclusions: Tryptophan metabolism represents a metabolic node in glioblastoma, and combining RT with IDO1 inhibition enhances therapeutic response by mitigating RT-induced immunosuppression. Clin Cancer Res; 24(15); 3632–43. ©2018 AACR.
Assessment of Placental Perfusion in the Preeclampsia L-NAME Rat Model with High-Field Dynamic Contrast-Enhanced MRI
Authors: Lémery Magnin Marie , Fitoussi Victor , Siauve Nathalie , Pidial Laetitia , Balvay Daniel , Autret Gwennhael , Cuenod Charles André , Clément Olivier , Salomon Laurent Julien
Published: April 2018

Purpose: To evaluate placental function and perfusion in a rat model of preeclampsia infused with L-nitro-arginine methyl ester (L-NAME) by dynamic contrast-enhanced (DCE) MRI using gadolinium chelates. Methods: Pregnant female Sprague-Dawley rats were fitted on embryonic day 16 (E16) with subcutaneous osmotic minipumps loaded to deliver, continuously, L-NAME (50 mg/day per rat; case group) or saline solution (control group). DCE MRI was performed on E19 using gadolinium chelates and a 4.7-T MRI apparatus for small animals. Quantitative analysis was performed using an image software program: placental blood flow (perfusion in mL/min/100 mL of placenta) and fractional volume of the maternal vascular placental compartment (ratio between the placental blood volume and the placental volume, Vb in %) were calculated by compartmental analysis. Results: A total of 176 placentas (27 rats) were analyzed by DCE MRI (97 cases and 79 controls). The model was effective, inducing intrauterine growth retardation, as there was a significant difference between the two groups for placental weight (p < 0.01), fetal weight (p = 0.019), and fetal length (p < 0.01). There was no significant difference in placental perfusion between the L-NAME and control groups (140.1 ± 74.1 vs. 148.9 ± 97.4, respectively; p = 0.496). There was a significant difference between the L-NAME and control groups for Vb (53 ± 12.9 vs. 46.7 ± 9%, respectively; p < 0.01). Conclusion: In the L-NAME preeclampsia model, placental perfusion is normal and the fractional blood volume is increased, suggesting that preeclampsia is not always expressed as a result of decreased placental perfusion. This highlights the usefulness of MRI for investigating the physiopathology of preeclampsia.
Brunsting-Perry Type Pemphigoid Causing Secondary Cicatricial Alopecia in 2 Patients
Authors: Reis Gavazzoni Dias Maria Fernanda , Aparecida Guedes Vilar Enöi , de Oliveira Bento Camila , Barreto Ibanez Raquel , Falci Loures Aline , Barreto Oliveira Campos Maria , Monaco Santos Júlia
Published: April 2018

Brunsting-Perry type pemphigoid (BPP) is a rare subepidermal blistering disease and a cause of secondary cicatricial alopecia. It was originally described by Brunsting and Perry in 1957 as a rare variant of cicatricial pemphigoid, characterized by bullous lesions limited to the head, neck, scalp, and upper trunk with mild or no mucosal involvement. We report 2 cases of BPP cicatricial alopecia with histopathology of subepidermal blister formation, different clinical presentation, and different salt-split test results. One patient had features of bullous pemphigoid (BP) with important oral mucosal involvement (not yet reported in the literature), and the second patient had typical features of epidermolysis bullosa acquisita (EBA). The secondary cicatricial alopecia may be due to different antigens associated with either BP or EBA. The phenomenon of epitope spreading could explain the association between 2 distinctive bullous diseases in the same patient, justifying the divergent findings of the immunofluorescence. The specific target antigen of BPP is yet to be defined.
Differential Fatty Acid-Binding Protein Expression in Persistent Radial Glia in the Human and Sheep Subventricular Zone
Authors: Dieriks Birger Victor , Dean Justin M. , Aronica Eleonora , Waldvogel Henry J. , Faull Richard L.M. , Curtis Maurice A.
Published: April 2018

Fatty acid-binding proteins (FABPs) are a family of transport proteins that facilitate intracellular transport of fatty acids. Despite abundant expression in the brain, the role that FABPs play in the process of cell proliferation and migration in the subventricular zone (SVZ) remains unclear. Our results provide a detailed characterisation of FABP3, 5, and 7 expression in adult and fetal human and sheep SVZ. High FABP5 expression was specifically observed in the adult human SVZ and co-labelled with polysialylated neural cell adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP), GFAPδ, and proliferating cell nuclear antigen (PCNA), indicating a role for FABP5 throughout the full maturation process of astrocytes and neuroblasts. Some FABP5+ cells had a radial glial-like appearance and co-labelled with the radial glia markers vimentin (40E-C) and GFAP. In the fetal human brain, FABP5 was expressed by radial glia cells throughout the ventricular zone. In contrast, radial glia-like cells in sheep highly expressed FABP3. Taken together, these differences highlight the species-specific expression profile of FABPs in the SVZ. In this study, we demonstrate the distribution of FABP in the adult human SVZ and fetal ventricular zone and reveal its expression on persistent radial glia that may be involved in adult neurogenesis.
Pulmonary Perfusion Using Intrabronchial Capnography in Pulmonary Artery Stenosis
Authors: Nishine Hiroki , Muraoka Hiromi , Inoue Takeo , Miyazawa Teruomi , Mineshita Masamichi
Published: April 2018

Stenting at the flow-limiting segment can improve the ventilation-perfusion ratio in patients with central airway stenosis. However, there is no quantitative examination for assessing the perfusion status during interventional bronchoscopy. Intrabronchial capnography can estimate regional gas exchange by measuring carbon dioxide concentration. We herein report a case of bilateral bronchial stenosis where stenting was able to improve ventilation-perfusion ratio using intrabronchial capnography. A 44-year-old man was admitted to our institution with orthopnea. Chest computed tomography showed an extrinsic compression at the bilateral main bronchus and right pulmonary artery due to a mediastinal mass. After introduction of general anesthesia, arterial oxygen tension suddenly decreased in the supine position. After initial stenting, an increase was seen in ventilation at the right lung; however, a ventilation-perfusion mismatch occurred due to an increase in dead-space ventilation at the right pulmonary artery stenosis. Intrabronchial capnography was an effective modality to confirm the regional perfusion status during interventional bronchoscopy in real time.
Hidradenitis Suppurativa Associated with Down Syndrome Is Characterized by Early Age at Diagnosis
Authors: Giovanardi Giulia , Chiricozzi Andrea , Bianchi Luca , De Simone Clara , Dini Valentina , Franceschini Chiara , Garcovich Simone , Oranges Teresa , Di Raimondo Cosimo , Caposiena Caro Dante Raffaele , Romanelli Marco , Peris Ketty
Published: April 2018

Background/Aims: The association between hidradenitis suppurativa (HS) and multiple comorbidities has been widely investigated but data about the coexistence of Down syndrome (DS) are scarce. We sought to evaluate the prevalence of DS among a population of HS patients and assess their clinical features. Methods: We collected demographic and clinical data of patients affected with HS referred to three Italian outpatient dermatology clinics. Results: A total of 257 HS patients were enrolled, 62% females and 38% males (mean age [±SD]: 23.3 ± 10.7 years); 9 of the 257 patients (3.5%), 7 females and 2 males, had concomitant HS and DS. The patients with DS and HS had a significantly earlier age of onset (mean age: 14.3 ± 3.6 vs. 23.4 ± 12.31 years; p = 0.029), a significantly younger age at diagnosis (mean age: 21.1 ± 11.1 vs. 31.8 ± 13.5 years; p = 0.015), and were significantly younger (mean age: 23.3 ± 10.7 vs. 34.6 ± 13.07 years; p = 0.005). No significant differences about other clinical data were found between the two groups. Conclusion: The prevalence of DS in HS patients corresponds to a not negligible 3.5% of cases, who experienced an onset of HS at a younger age compared to patients with HS only.
Brachyonychia Associated with Acroosteolysis in Chronic Kidney Disease: How Phalange Shape Influences Nail Morphology
Authors: Rosales Figueroa José David , Chang Patricia
Published: April 2018

Brachyonychia is a rare manifestation in patients with chronic kidney disease. Longtime disease, secondary hyperparathyroidism, and hemodialysis are common conditions among those who present it. We evaluated 8 cases who presented brachyonychia in the nephrology department and compared the clinical versus the radiographic findings, and evaluated how the tissue adjusts to the underlying bone structure, giving different forms to the nails. We conclude that brachyonychia and acroosteolysis in chronic kidney disease suggest long-term disease, secondary hyperparathyroidism, and hemodialysis, besides it being a good model on how the bony structure defines the soft tissue morphology.
Athlete’s Hepatitis in a Young Healthy Marathon Runner
Authors: Khan Hafiz , Phillipose Jobin , Ahmed Moiz , Deeb Liliane
Published: April 2018

Athlete’s hepatitis is an uncommon clinical condition characterized by a significant ischemic insult to the liver. The most likely pathogenesis is decreased blood supply to the liver resulting in significant hypoxic hepatocyte injury. We report a case of a 48-year-old healthy young male who presented with athlete’s hepatitis confirmed by liver biopsy after a 14-mile marathon run. To our knowledge, this is the second case of athlete’s ischemic hepatitis reported in the literature. It is a diagnosis worth considering in patients involved in extreme exercise programs.
Small Bowel Obstruction Caused by Dried Persimmon
Authors: Yamamoto Mami , Yamamoto Kentaroh , Bian Xueyi , Guo Qiang , Sasaki Takamitsu , Yamamoto Fumio , Yamamoto Hiroshi
Published: April 2018

Dried persimmon is a well-known dried fruit in Asian countries such as Japan, Korea, and China. Small bowel obstruction caused by phytobezoar is a rare but interesting pathogenesis that accounts for 2–4% of all small bowel obstructions. We present the case of an 87-year-old female who suffered from small bowel obstruction caused by ingestion of a huge, dried astringent persimmon. She was initially treated conservatively, but removal by enterotomy was performed after relief failed to be achieved with conservative therapy.
Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress
Authors: Luong Trang T. D. , Schelski Nadeshda , Boehme Beate , Makridakis Manousos , Vlahou Antonia , Lang Florian , Pieske Burkert , Alesutan Ioana , Voelkl Jakob
Published: April 2018

Background/Aims: Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification. Methods: Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress. Results: Treatment with calcification medium significantly increased calcium deposition in HAoSMCs, an effect significantly blunted by additional treatment with Fibulin-3. Moreover, phosphate-induced alkaline phosphatase activity and mRNA expression of osteogenic and chondrogenic markers MSX2, CBFA1, SOX9 and ALPL were all significantly reduced by addition of Fibulin-3. These effects were paralleled by similar regulation of oxidative stress in HAoSMCs. Phosphate treatment significantly up-regulated mRNA expression of the oxidative stress markers NOX4 and CYBA, down-regulated total antioxidant capacity and increased the expression of downstream effectors of oxidative stress PAI-1, MMP2 and MMP9 as well as BAX/BLC2 ratio in HAoSMCs, all effects blocked by additional treatment with Fibulin-3. Furthermore, the protective effects of Fibulin-3 on phosphate-induced osteogenic and chondrogenic markers expression in HAoSMCs were reversed by additional treatment with hydrogen peroxide. Conclusions: Fibulin-3 attenuates phosphate-induced osteo-/ chondrogenic transdifferentiation and calcification of VSMCs, effects involving inhibition of oxidative stress. Up-regulation or supplementation of Fibulin-3 may be beneficial in reducing the progression of vascular calcification during hyperphosphatemic conditions such as CKD.
Molecular Regulation of Bone Metastasis Pathogenesis
Authors: Wu Meng-Yu , Li Chia-Jung , Yiang Giou-Teng , Cheng Yeung-Leung , Tsai Andy Po-Yi , Hou Yueh-Tseng , Ho Yu-Chieh , Hou Ming-Feng , Chu Pei-Yi
Published: April 2018

Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.
Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy
Authors: Tong Fei , Zhang Hua
Published: April 2018

Background/Aims: The purpose of this study was to investigate the effect of administering particulate matter (PM2.5) to the lungs on the sensitivity to myocardial ischemia/reperfusion injury (MI/RI) and the role of farnesoid-X-receptor (FXR)-induced autophagy in this process. Methods: Male Sprague Dawley (SD) rats were subjected to 45 min of ischemia, and the lungs were exposed to 2.0 mg of PM2.5 in 0.3 mL of normal saline 5 min before reperfusion. After 24 h of reperfusion, the blood and myocardium were collected, and the myocardial infarct sizes, activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH), and levels of serum high sensitivity C-reactive protein (hsCRP), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cardiac troponin T (cTnT), P-selectin and D-dimer were measured via biochemical analysis. Additionally, the myeloperoxidase (MDA) content and superoxide dismutase (SOD) activity were measured in myocardial tissues via biochemical analysis, and the levels of reactive oxygen species (ROS), autophagosomes, microtubule-associated protein 1 light chain 3 (LC-I and II), macrophage inflammatory protein-2 (MIP-2) and farnesoid-X-receptor (FXR) were determined in myocardial tissues via biochemical analysis, immunohistochemical and biochemical techniques and western blot. In addition, the myocardial infarct sizes, LC-I and II expressions were determined in myocardial tissues through FXR-/- and WT mice. Results: Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in I/R group than that in Sham group, and Levels of IL-4 and SOD were lower in I/R group than that in Sham group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in I/R group than that in Sham group. Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in PM2.5 group than that in I/R group, and Levels of IL-4 and SOD were lower in PM2.5 group than that in I/R group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in PM2.5 group than that in I/R group. Conclusions: PM2.5 post-treatment exacerbated myocardial injury partly through upregulation of FXR to induce autophagy compared to MI/RI.
SIRT3 Facilitates Amniotic Fluid Stem Cells to Repair Diabetic Nephropathy Through Protecting Mitochondrial Homeostasis by Modulation of Mitophagy
Authors: Feng Jianxun , Lu Chang , Dai Qin , Sheng Junqin , Xu Min
Published: April 2018

Background/Aims: Amniotic fluid stem cells (AFSCs) transplantation is a promising therapeutic strategy for diabetic nephropathy. Sirtuin3 (SIRT3) is a novel mitochondrial protective factor. In the present study, we aimed to investigate whether SIRT3 protects against hyperglycemia-induced AFSCs damage and enhances the therapeutic efficiency of AFSCs in diabetic nephropathy. Methods: To establish the diabetic nephropathy model, db/ db mice were used. AFSCs were obtained and transplanted into the kidney tissue of db/ db mice. Gain-of-function assay with SIRT3 overexpression was performed in AFSCs via adenoviral transfections (Ad/SIRT3). Cellular viability and apoptosis were measured via MTT, TUNEL assay and western blotting. Mitochondrial function was assessed via JC1 staining, mPTP opening assay, mitochondrial respiratory function analysis, and immunofluorescence analysis of cyt-c. Mitophagy was assessed via western blotting and immunofluorescence analysis. Renal histopathology and morphometric analysis were conducted via H&E, Masson and PASM staining. Kidney function was detected via ELISA assay, western blotting and qPCR. Results: SIRT3 was downregulated in AFSCs under high glucose stimulation, where its expression was positively correlated with AFSCs survival and proliferation. Regaining SIRT3 activated mitophagy protecting AFSCs against high glucose-induced apoptosis via preserving mitochondrial function. Transplanting SIRT3-overexpressing AFSCs in db/db mice improved the abnormalities in glucose metabolic parameters, including the levels of glucose, insulin, C-peptide, HbA1c and inflammatory markers. In addition, the engraftment of SIRT3-modified AFSCs also reversed renal function, decreased renal hypertrophy, and ameliorated renal histological changes in db/db mice. Functional studies confirmed that SIRT3-modified AFSCs promoted glomerulus survival and reduced renal fibrosis. Conclusion: Collectively, our results demonstrate that AFSCs may be a promising therapeutic treatment for ameliorating diabetes and the development of diabetic nephropathy and that the overexpression of SIRT3 in AFSCs may further increase the efficiency of stem cell-based therapy.
Oxidative Stress Induces Neuronal Apoptosis Through Suppressing Transcription Factor EB Phosphorylation at Ser467
Authors: Su Qian , Zheng Bin , Wang Chen-yao , Yang Yun-zhi , Luo Wen-wen , Ma Shu-min , Zhang Xin-hua , Ma Dong , Sun Yan , Yang Zhan , Wen Jin-kun , Liu Zhi-xue
Published: April 2018

Background/Aims: This study determined the role and mechanism of action of transcription factor EB (TFEB) in H2O2-induced neuronal apoptosis. Methods: SH-SY5Y cells were treated with Akt inhibitor/activator and different concentrations of H2O2. Cell apoptosis was detected by flow cytometric analysis. Akt and TFEB phosphorylation and PARP cleavage were determined by Western blotting. HEK293T cells were transfected with different truncated TFEB mutants and HA-Akt-WT; SH-SY5Y cells were transfected with Flag-vector, Flag-TFEB, Flag-TFEB-S467A or Flag-TFEB-S467D; and TFEB interaction with Akt was determined by co-immunoprecipitation and GST pull-down assays. Results: A low concentration of H2O2 induces TFEB phosphorylation at Ser467 and nuclear translocation, facilitating neuronal survival, whereas a high concentration of H2O2 promotes SH-SY5Y cell apoptosis via suppressing TFEB Ser467 phosphorylation and nuclear translocation. The TFEB-S467D mutant is more easily translocated into the nucleus than the non-phosphorylated TFEB-S467A mutant. Further, Akt physically binds to TFEB via its C-terminal tail interaction with the HLH domain of TFEB and phosphorylates TFEB at Ser467. Mutation of TFEB-Ser467 can prevent the phosphorylation of TFEB by Akt, preventing inhibition of oxidative stress-induced apoptosis. Conclusions: Oxidative stress induces neuronal apoptosis through suppressing TFEB phosphorylation at Ser467 by Akt, providing a novel therapeutic strategy for neurodegenerative diseases.
MicroRNA-125b Affects Vascular Smooth Muscle Cell Function by Targeting Serum Response Factor
Authors: Chen Zhibo , Wang Mian , Huang Kai , He Qiong , Li Honghao , Chang Guangqi
Published: April 2018

Background/Aims: Increasing evidence links microRNAs to the pathogenesis of peripheral vascular disease. We recently found microRNA-125b (miR-125b) to be one of the most significantly down‑regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO) of the lower extremities. However, its function in the process of ASO remains unclear. This study aimed to investigate the expression, regulatory mechanisms, and functions of miR-125b in the process of ASO. Methods: Using the tissue explants adherent method, vascular smooth muscle cells (VSMCs) were prepared for this study. A rat carotid artery balloon injury model was constructed to simulate the development of vascular neointima, and a lentiviral transduction system was used to overexpress serum response factor (SRF) or miR-125b. Quantitative real‑time PCR (qRT‑PCR) was used to detect the expression levels of miR‑125b and SRF mRNA. Western blotting was performed to determine the expression levels of SRF and Ki67. In situ hybridization analysis was used to analyze the location and expression levels of miR-125b. CCK-8 and EdU assays were used to assess cell proliferation, and transwell and wound closure assays were performed to measure cell migration. Flow cytometry was used to evaluate cell apoptosis, and a dual-luciferase reporter assay was conducted to examine the effects of miR‑125b on SRF. Immunohistochemistry and immunofluorescence analyses were performed to analyze the location and expression levels of SRF and Ki67. Results: miR-125b expression was decreased in ASO arteries and platelet-derived growth factor (PDGF)-BB-stimulated VSMCs. miR-125b suppressed VSMC proliferation and migration but promoted VSMC apoptosis. SRF was determined to be a direct target of miR-125b. Exogenous miR-125b expression modulated SRF expression and inhibited vascular neointimal formation in balloon-injured rat carotid arteries. Conclusions: These findings demonstrate a specific role of the miR-125b/SRF pathway in regulating VSMC function and suggest that modulating miR-125b levels might be a novel approach for treating ASO.
A função revisora dos tribunais na perspectiva histórica e jusfundamental: o direito de recorrer. Origens e limites externos
Authors: Feliciano Guilherme Guimarães
Published: April 2018

O artigo investiga as origens históricas do duplo grau de jurisdição, de Roma ao Estado Moderno, e a partir desse escorço examina se o direito de recorrer pode ser admitido, hoje, como um direito humano fundamental de caráter universal. Propõe especialmente uma revisão crítica do modelo recursal que se estabeleceu no processo do trabalho, encaminhando as bases ideais de uma reforma que prestigie as decisões de primeiro grau, quanto às questões de fato.
Apontamentos críticos para uma história do direito previdenciário no ocidente capitalista
Authors: Batista Flávio Roberto
Published: April 2018

Com o objetivo de compreender criticamente o processo histórico de formação do direito previdenciário, o ensaio o apresenta panoramicamente num contexto geral, debruçando-se mais especificamente sobre aspectos relevantes para desfazer alguns equívocos recorrentes do senso comum sobre o tema, tendo como lastro teórico o materialismo histórico-dialético.
Departamento Jurídico do Centro Acadêmico “XI de Agosto”: experiência histórica e perspectivas frente ao ensino jurídico
Authors: Pesso Ariel Engel
Published: April 2018

O Departamento Jurídico “XI de Agosto” é uma entidade fundada em 1919 por estudantes da Faculdade de Direito do Largo São Francisco que possui dois importantes traços distintivos: prestação de serviço de assistência jurídica gratuita e aplicação prática do Direito aprendido em sala de aula. Atualmente, o ensino do direito se resume ao conhecimento tecnológico da dogmática jurídica e da manipulação técnica de normas e leis, sem reflexão crítica. Neste contexto, o presente estudo busca demonstrar como a atividade da instituição modificou-se ao longo do tempo em conformidade com as mudanças sociais, políticas e econômicas do Estado brasileiro e entender como ela se insere no quadro do ensino jurídico brasileiro atual.
Two new species of obligatory termitophilous rove beetles from Brazil (Coleoptera: Staphylinidae: Termitomorpha Wasmann)
Authors: CARON EDILSON , BORTOLUZZI SIDNEI , ROSA CASSIANO S.
Published: April 2018

In recent surveys carried out in Brazil, we detected two new species of Termitomorpha Wasmann, a genus of Termitogastrina (Aleocharinae, Corotocini). This genus is easily recognizable in the subtribe by the evenly convex and smooth pronotum. The new species are: Termitomorpha sinuosa Caron, Bortoluzzi & Rosa sp. nov., and Termitomorpha alata Caron & Bortoluzzi, sp. nov. Both species are here described and illustrated, including scanning electron photographs. Their host termites were identified as species of Nasutitermes. The key to species of Termitomorpha is updated based on recent literature.
Morphology of the first zoea of Chaceon affinis (A. Milne-Edwards & Bouvier, 1894) and occurrence of Chaceon spp. larvae (Decapoda: Brachyura: Gerynonidae) in the Canary Islands waters, Northeastern Atlantic
Authors: LANDERIA JOSÉ M. , TAMURA HIROAKI
Published: April 2018

The morphology of the first zoea stage of Chaceon affinis is described and illustrated in detail for the first time. Morphological comparison with the corresponding stage of other known species of Geryonidae allowed the differentiation between the genera Chaceon and Geryon, although it was impossible to distinguish among species of Chaceon using larval morphology. Thus, geryonid larvae collected in the plankton of Gran Canaria Island, NE Atlantic, during the years 2005 and 2006, could only be identified as Chaceon spp. The temporal distribution of larval abundance suggested that main hatching periods of Chaceon spp. occur in spring and summer. These results are useful to better understand the reproductive strategies of these deep-water crabs, which in turn will be useful for future fishery management of this resource of increasing interest in the Canary Islands.
A new species of Phasmatocoris from French Guiana, with short taxonomic notes on two described species and an updated key (Hemiptera: Heteroptera: Reduviidae: Emesinae)
Authors: GIL-SANTANA HÉLCIO R.
Published: April 2018

Phasmatocoris papei sp. nov. (Hemiptera: Heteroptera: Reduviidae: Emesinae: Emesini) is described from French Guiana based on two male specimens. Short taxonomical notes on Phasmatocoris praecellens (Bergroth, 1911) and Ph. spectrum Breddin, 1904 are provided. An updated key to the species of Phasmatocoris Breddin, 1904 is presented.
A taxonomic review of Lampris guttatus (Brünnich 1788) Lampridiformes; Lampridae) with descriptions of three new species
Authors: UNDERKOFFLER KAREN E. , LUERS MEAGAN A. , HYDE JOHN R. , CRAIG MATTHEW T.
Published: April 2018

The genus Lampris (Lampridae) currently comprises two species, Lampris guttatus (Brünnich 1788) and L. immaculatus (Gilchrist 1905) commonly known as Opah and Southern Opah, respectively. Hyde et al. (2014) presented DNA sequence data which revealed the presence of five distinct, monophyletic lineages within L. guttatus. In this paper, we present morphological and meristic data supporting the presence of five species previously subsumed within L. guttatus (Brünnich 1788). We restrict Lampris guttatus (Brünnich 1788), resurrect L. lauta (Lowe 1838), and describe three new species of Lampris. A key to the species of Lampris is provided.
Tibetan High and Upper Tropospheric Tropical Circulations during Northern Summer
Authors: Krishnamurti T. N. , Daggupaty S. M. , Fein Jay , Kanamitsu Masao , Lee John D.
Published: April 2018

The zonally asymmetric climatology of the tropical large-scale motion field is an interesting GARP topic. Understanding of the maintenance of various quasi-stationary features will be a challenging problem during the FGGE (the First GARP Global Experiment) and Monex (the Monsoon Experiment). In this paper we present some current thoughts that are relevant to the climatology of the tropical upper troposphere during the northern summer.

A review of some of the results from various numerical general circulation models and theoretical studies is presented for northern summer conditions. The relative success or failure of simulations of 200-mb climatology is discussed. It is pointed out that a proper simulation of the belt of anticyclones over the Asian highlands is somewhat crucial for a proper simulation of the summer climatology over the rest of the tropics.

Observations of the semipermanence of the Tibetan high pressure cell during northern summer at 200 mb suggests that it acts somewhat like a barrier. In order to illustrate this we consider a problem related to the evolution of barotropic non-divergent flows past a barrier. The flows are initially zonal, with speeds varying in the north-south direction according to northern summer observations. The barrier, whose shape is based on observations of a blocking thermal high, is impulsively introduced at initial time. The flows are kept zonal at frictionless walls at 25S and 45N. The initial north-south distribution of the zonal flows is shown to have no inflection point in its profile, thus it does not satisfy the necessary condition for barotropic instability. The presence of an impulsively introduced barrier, however, results in the evolution of transient as well as steady wave motions in long term numerical integrations. It is shown that a 30-day mean motion field contains many of the well known climatological features such as the African high, the mid-Atlantic trough, the mid-Pacific trough, the Mexican high and a weak easterly jet south of the Tibetan high. Calculations of kinetic energy exchanges between waves and zonal flow in this simple experiment is compared with corresponding calculations for tropical observations and recent general circulation experiments carried out by Abbott. The impulsively introduced barrier simulates an energy source for zonal wavenumber 1, quite similar to observations in a tropical belt. Although this experiment is fairly crude, it is found to be very illustrative in many respects. Many diverse experiments along these lines can be carried out to reveal various aspects of atmospheric circulations.
the Eole experiment: early results and current objectives
Authors: Morel Pierre , Bandeen William
Published: April 2018

The Eole Experiment with 480 constant level balloons released in the Southern Hemisphere is described. Each balloon, floating freely at approximately the 200-mb level, is a precise tracer of the horizontal motion of air masses, the accuracy of which is limited only by the laminated structure of the stratospheric flow, within an rms uncertainty of 1.5 m sec−1. The balloons were found after 2 months to distribute at random over the whole hemisphere outside the tropics, irrespective of their original launching site. Early results of Eulerian and Lagrangian averages of the Eole wind data are given for describing the mean 200-mb zonal and meridional circulations. The effect of the small scale eddies of two-dimensional turbulence has been studied with respect to the relative eddy diffusion of pairs of balloons and the relative dispersion of triangular clusters. New estimates of the rms divergence of the 200-mb flow are given, together with their scale dependence which was found to be a logarithmic law.