bluuebunny/crossref_metadata_2025 huggingface dataset:
Preadaptation and Naturalization of Nonnative Species: Darwin's Two Fundamental Insights into Species Invasion
Authors: Cadotte Marc W. , Campbell Sara E. , Li Shao-peng , Sodhi Darwin S. , Mandrak Nicholas E.
Published: February 2018

Predicting which nonnative species become invasive is critical for their successful management, and Charles Darwin provided predictions based on species’ relatedness. However, Darwin provided two opposing predictions about the relatedness of introduced nonnatives to indigenous species. First, environmental fit is the dominant factor determining invader success; thus, we should expect that invasive species are closely related to local native residents. Alternatively, if competition is important, we should expect successful invaders are distantly related to the native residents. These opposing expectations are referred to as Darwin's naturalization conundrum. The results of studies that examine nonnative species relatedness to natives are largely inconsistent. This inconsistency arises from the fact that studies occur at different spatial and temporal scales, and at different stages of invasion, and so implicitly examine different mechanisms. Further, while species have evolved ecological differences, the mode and tempo of evolution can affect species’ differences, complicating the predictions from simple hypotheses. We outline unanswered questions and provide guidelines for collecting the data required to test competing hypotheses.
Regulation of the Cell Biology of Antigen Cross-Presentation
Authors: Blander J. Magarian
Published: February 2018

Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide–MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source. Three distinct pathways of vesicular traffic converge to form the ideal cross-presentation compartment, each regulated differently to supply a unique component that enables cross-presentation of a diverse repertoire of peptides. Delivery of centerpiece MHC-I molecules is the critical step regulated by microbe-sensitive Toll-like receptors. Defining the subcellular sources of MHC-I and identifying sites of peptide loading during cross-presentation remain key challenges.
Abnormal mTOR Activation in Autism
Authors: Winden Kellen D. , Ebrahimi-Fakhari Darius , Sahin Mustafa
Published: February 2018

The mechanistic target of rapamycin (mTOR) is an important signaling hub that integrates environmental information regarding energy availability and stimulates anabolic molecular processes and cell growth. Abnormalities in this pathway have been identified in several syndromes in which autism spectrum disorder (ASD) is highly prevalent. Several studies have investigated mTOR signaling in developmental and neuronal processes that, when dysregulated, could contribute to the development of ASD. Although many potential mechanisms still remain to be fully understood, these associations are of great interest because of the clinical availability of mTOR inhibitors. Clinical trials evaluating the efficacy of mTOR inhibitors to improve neurodevelopmental outcomes have been initiated.
Structural Plasticity in Adulthood with Motor Learning and Stroke Rehabilitation
Authors: Sampaio-Baptista Cassandra , Sanders Zeena-Britt , Johansen-Berg Heidi
Published: February 2018

The development of advanced noninvasive techniques to image the human brain has enabled the demonstration of structural plasticity during adulthood in response to motor learning. Understanding the basic mechanisms of structural plasticity in the context of motor learning is essential to improve motor rehabilitation in stroke patients. Here, we review and discuss the emerging evidence for motor-learning-related structural plasticity and the implications for stroke rehabilitation. In the clinical context, a few studies have started to assess the effects of rehabilitation on structural measures to understand recovery poststroke and additionally to predict intervention outcomes. Structural imaging will likely have a role in the future in providing measures that inform patient stratification for optimal outcomes.
Addressing the Challenge of Molecular Change: An Interim Report
Authors: Levine Raphael D.
Published: February 2018

Invited by the editorial committee of the Annual Review of Physical Chemistry to “contribute my autobiography,” I present it here, as I understand the term. It is about my parents, my mentors, my coworkers, and my friends in learning and the scientific problems that we tried to address. Courtesy of the editorial assistance of Annual Reviews, some of the science is in the figure captions and sidebars. I am by no means done: I am currently trying to fuse the quantitative rigor of physical chemistry with systems biology while also dealing with a post–Born-Oppenheimer regime in electronic dynamics and am attempting to instruct molecules to perform advanced logic.
Association of High Cardiovascular Fitness and the Rate of Adaptation to Heat Stress
Authors: Żychowska Małgorzata , Nowak-Zaleska Alicja , Chruściński Grzegorz , Zaleski Ryszard , Mieszkowski Jan , Niespodziński Bartłomiej , Tymański Roman , Kochanowicz Andrzej
Published: February 2018

This study aimed to compare changes in genes expression associated with inflammation and apoptosis in response to heat stress caused by sauna between people with varying cardiorespiratory fitness levels. We hypothesis that high cardiorespiratory level caused higher positive changes after four weeks of sauna bathing. Blood samples were taken at rest before and after the first and last sauna sessions and 48 hours after the last sauna session and used to assay HSP70 (HSPA1A), HSP27 (HSPB1), interleukin 6 (IL6), and interleukin 10 (IL10) genes expression in blood with quantitative real-time qRT-PCR. Overall, small decreases in rest values of HSPA1A and IL6 mRNA, increase in HSPB1 mRNA, and a significant increase in IL10 mRNA were observed after four weeks of exposure to heat stress. Our findings suggest that an adaptive response to heat stress (an anti-inflammatory response) occurs faster in people with higher cardiorespiratory fitness.
Seismic Performance of High‐Ductile Fiber‐Reinforced Concrete Short Columns
Authors: Deng Mingke , Zhang Yangxi
Published: February 2018

This study mainly aims to investigate the effectiveness of high‐ductile fiber‐reinforced concrete (HDC) as a means to enhance the seismic performance of short columns. Six HDC short columns and one reinforced concrete (RC) short column were designed and tested under lateral cyclic loading. The influence of the material type (concrete or HDC), axial load, stirrup ratio, and shear span ratio on crack patterns, hysteresis behavior, shear strength, deformation capacity, energy dissipation, and stiffness degradation was presented and discussed, respectively. The test results show that the RC short column failed in brittle shear with poor energy dissipation, while using HDC to replace concrete can effectively improve the seismic behavior of the short columns. Compared with the RC short column, the shear strength of HDC specimens was improved by 12.6–30.2%, and the drift ratio and the energy dissipation increases were 56.9–88.5% and 237.7–336.7%, respectively, at the ultimate displacement. Additionally, the prediction model of the shear strength for RC columns based on GB50010‐2010 (Chinese code) can be safely adopted to evaluate the shear strength of HDC short columns.
Colonic Mucosal Ulceration and Gastrointestinal Bleeding Associated with Sevelamer Crystal Deposition in a Patient with End Stage Renal Disease
Authors: Nambiar Sudheer , Pillai Unnikrishnan Kunjan , Devasahayam Joe , Oliver Tony , Karippot Asha
Published: February 2018

End stage renal disease (ESRD) population account for 1.9 per patient year of hospital admissions annually. ESRD population are at increased risk of bleeding secondary to use of anticoagulation during hemodialysis and uremia induced platelet dysfunction. Gastrointestinal bleeding accounts for 3–7% of all deaths in ESRD population. Lower gastrointestinal bleeding refers to blood loss from a site in the gastrointestinal tract distal to the ligament of Treitz. It is usually suspected when a patient complains of hematochezia. It is different from patients presenting with hematemesis that suggests bleeding from upper gastrointestinal tract. Common causes of lower gastrointestinal bleed include diverticulosis, ischemia, hemorrhoids, neoplasia, angiodysplasia, and inflammatory bowel disease. ESRD patients are known to retain phosphate alone or in combination with calcium which has been associated with high mortality. Sevelamer is a phosphate binder used widely in ESRD population. The known side effects of sevelamer include metabolic acidosis, vomiting, nausea, diarrhea, dyspepsia, abdominal pain, constipation, flatulence, fecal impaction, and skin rash. We are reporting a unique case of a 56-year-old female with end stage renal disease on sevelamer hydrochloride who presented with gastrointestinal bleeding and underwent a right hemicolectomy found to have sevelamer-induced mucosal ulceration and crystal deposition in the colonic mucosa. This case report highlights the fact that, with widespread use of this medication in the patients with chronic kidney diseases, physicians should be aware of this underrecognized entity in the differential diagnosis of gastrointestinal bleed in ESRD patients.
Diagenetic Self-Organization and Stochastic Resonance in a Model of Limestone-Marl Sequences
Authors: L’Heureux Ivan
Published: February 2018

Banded patterns in limestone-marl sequences (“rhythmites”) form widespread sediments typical of shallow marine environments. They are characterized by alternations of limestone-rich layers and softer calcareous-clayey material (marl) extending over hundreds of meters with a thickness of a few tens of meters. The banded sequences are usually thought to result from systematic variations in the external environment, but the pattern may be distorted by diagenetic nonlinear processes. Here, we present a reactive-transport model for the formation of banded patterns in such a system. The model exhibits interesting features typical of nonlinear dynamical systems: (i) the existence of self-organized oscillating patterns between a calcite-rich mode (“limestone”) and a calcite-poor one (“marl”) for fixed environmental conditions and (ii) bistability between these two modes. We then illustrate the phenomena of stochastic resonance, whereby the multistable system is driven by a small external periodic signal (the 100,000 years’ Milankovitch cycle comes to mind) that is too weak to generate oscillations between the states on its own. In the presence of random fluctuations, however, the system generates transitions between the calcite-rich and calcite-poor states in statistical synchrony with the external forcing. The signal-to-noise ratio exhibits many maxima as the noise strength is varied. Hence, this amplification effect is maximized for specific values of the noise strength.
Granulomatosis with Polyangiitis Localized in the Greater Omentum
Authors: Komine Ryuji , Kobayashi Takashi , Uehara Hiro , Minamimura Keisuke , Mori Kazuhiko , Hirata Toru , Shimizu Atsushi , Mori Masaya
Published: February 2018

Granulomatosis with polyangiitis (GPA) is known as anti-neutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis and typically manifests as pulmonary-renal syndrome, but the disease is not limited to pulmonary or renal systems. The inflammation can involve whole body organs. In addition, the ANCA titer does not always become positive. Here, we describe the case of a 91-year-old man who presented with umbilical pain and fever of unknown origin. Only the increased computed tomography value of the greater omentum suggested intra-abdominal inflammation; however, serological examinations, including the ANCA level, could not reveal the focus or cause of symptoms. Finally, the histopathological examination of specimens surgically excised from the greater omentum demonstrated GPA limited to the greater omentum. This report reminds physicians to consider GPA in the differential diagnosis of acute abdominal pain or fever of unknown origin.
Flavonoids Effects on Hepatocellular Carcinoma in Murine Models: A Systematic Review
Authors: García Estefanny Ruiz , Gutierrez Eliana Alviárez , Melo Fabiana Cristina Silveira Alves de , Novaes Rômulo Dias , Gonçalves Reggiani Vilela
Published: February 2018

The hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. It occurs primarily as manifestation of other pathological processes, such as viral hepatitis, cirrhosis, and toxin exposure that affect directly the cellular process. Studies were selected from PubMed and Scopus databases according to the PRISMA statement. The research filters were constructed using three parameters: flavonoids, hepatocellular carcinoma, and animal model. The bias analysis of the 34 selected works was done using the ARRIVE guidelines. The most widely used flavonoid in the studies was epigallocatechin gallate extracted from green tea. In general, the treatment with different flavonoids presented inhibition of tumor growth and antiangiogenic, antimetastatic, antioxidant, and anti‐inflammatory activities. The bias analysis evidenced the absence of methodological processes in all studies, such as the age or weight of the animals, the method of flavonoids’ extraction, or the experimental designs, analytical methods, and outcome measures. It has been known that flavonoids have a protective effect against HCC. However, the absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impaired the internal validity of the individual studies, making it difficult to determine the effectiveness of plant‐derived products in the treatment of HCC.
Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers
Authors: Kou Chung-Ting Jimmy , Kandpal Raj P.
Published: February 2018

Eph receptors constitute the largest family of receptor tyrosine kinases, which are activated by ephrin ligands that either are anchored to the membrane or contain a transmembrane domain. These molecules play important roles in the development of multicellular organisms, and the physiological functions of these receptor-ligand pairs have been extensively documented in axon guidance, neuronal development, vascular patterning, and inflammation during tissue injury. The recognition that aberrant regulation and expression of these molecules lead to alterations in proliferative, migratory, and invasive potential of a variety of human cancers has made them potential targets for cancer therapeutics. We present here the involvement of Eph receptors and ephrin ligands in lung carcinoma, breast carcinoma, prostate carcinoma, colorectal carcinoma, glioblastoma, and medulloblastoma. The aberrations in their abundances are described in the context of multiple signaling pathways, and differential expression is suggested as the mechanism underlying tumorigenesis.
Energy Transfer Using Gradient Index Metamaterial
Authors: Ganapathy Boopalan , Chittur Krishnaswamy Subramaniam
Published: February 2018

The gradient refractive index structure in this paper is used to increase the quantum of energy transfer. This is done by improving the directive gain of the pyramidal horn antenna at a frequency of 10 GHz. A three-dimensional array of closed square rings is placed in front of the horn antenna aperture to form a gradient refractive index structure. This structure increases the directive gain by 1.6 dB as compared to that of the conventional horn antenna. The structure nearly doubles the wireless power transfer quantum between the transmitter and the receiver when placed at both ends. The increase in the directivity is achieved by converting the spherical wave emanating from the horn to a plane wave once it passes through the structure. This transformation is realized by the gradient refractive index structure being placed perpendicular to the direction of propagation. The gradient refractive index is constructed by changing the dimensions of a closed square ring placed in the unit cell of the array. The change in the refractive index gives rise to an improvement of the half power beam width and side lobe level compared to that of the normal horn. The design and simulation were done using CST Studio software.
Effects of Xin‐Ji‐Er‐Kang on Anticardiovascular Remodeling in L‐NAME Induced Hypertensive Mice and Its Potential Mechanisms
Authors: Wang Li , Cai Guo-wei , Ding Ling , Hu Juan , Zhang Yong-xue , Huang Guang-yao , Cheng Pan , Gao Shan
Published: February 2018

Background. Xin‐Ji‐Er‐Kang (XJEK) shows protective effects on the myocardial ischemic diseases in our previous reports. We hypothesized that XJEK may exert preventing effects on L‐NAME induced hypertensive mice by ameliorating oxidative stress (OS) and endothelial dysfunction (ED). Methods. After treatment with XJEK for four weeks, cardiac function and cardiovascular pathology changes were evaluated. Then, endothelial‐dependent vascular relaxation and serum NO, eNOS, AMDA, SOD, MDA content, and cardiac tissue eNOS expression were detected. Results. The hypertensive mice displayed distinct cardiovascular remodeling including increased HW/BW index (4.7 ± 0.33 versus 5.2 ± 0.34), cross‐section area, and collagen deposition. In addition, ED was found manifested by decreased serum NO (20.54 ± 8.05 versus 6.29 ± 2.33), eNOS (28.34 ± 2.36 versus 20.37 ± 2.30), content, and decreased eNOS expression in cardiac tissue and damaged endothelium‐dependent diastolic function. Moreover, OS was detected confirmed by decreased SOD activity and increased MDA content in serum. However, treatment with XJEK for 4 wk could reverse cardiovascular remodeling (HW/BW index normalized from 5.2 ± 0.34 to 4.59 ± 0.25), ameliorate and preserve endothelial function (NO: 16.67 ± 7.24 versus 6.29 ± 2.33; eNOS: 16.67 ± 7.24 versus 6.29 ± 2.33), and suppress OS. Conclusion. XJEK has protective effects against cardiovascular remodeling in L‐NAME induced hypertensive mice.
Metabolomic Profiling of Human Spermatozoa in Idiopathic Asthenozoospermia Patients Using Gas Chromatography-Mass Spectrometry
Authors: Zhao Kai , Zhang Jianzhong , Xu Zhen , Xu Yue , Xu Aiming , Chen Wei , Miao Chenkui , Liu Shouyong , Wang Zengjun , Jia Ruipeng
Published: February 2018

The purpose of this study was to describe the first metabolic profile of human sperm cells through the application of an untargeted platform based on gas chromatography-mass spectrometry (GC-MS). Sperm cell samples from patients diagnosed with idiopathic asthenozoospermia (n=30) and healthy subjects (n=30) were analyzed using a nontargeted metabolomics method based on GC-MS spectroscopy. The mass spectrometric data were collected using multivariate and univariate analyses to identify metabolites related to idiopathic asthenozoospermia. By using metabolomic strategies, we identified 33 metabolites, 27 of which were decreased in the idiopathic asthenozoospermia group compared with the normozoospermic group and six were increased in idiopathic asthenozoospermia. With respect to human sperm cells, some of these metabolites are reported here for the first time. Pathways for nucleoside, amino acid and energy metabolism, and the Krebs cycle were disturbed and were associated with idiopathic asthenozoospermia. The metabolic profiling provides an important first step in studying the pathophysiological mechanisms involved in IAS, and the identified metabolites may become potential biomarkers for its diagnosis and treatment.
Anti‐Inflammatory Effect of Feiyangchangweiyan Capsule on Rat Pelvic Inflammatory Disease through JNK/NF‐κB Pathway
Authors: Li Yao , Liu Yang , Yang Qian , Shi Zhihui , Xie Yanhua , Wang Siwang
Published: February 2018

Objectives. In this study, we aimed to illustrate the preventive effect and possible mechanisms of Feiyangchangweiyan capsule (FYCWYC) on rat pelvic inflammatory disease (PID) model. Methods. To construct the rat PID model, upper genital tract was infected by multipathogen, and then drugs were orally administered for 8 days. The histological examination, immunohistochemical analysis, and ELISA were carried out. Furthermore, Western blotting was used to analyze the expression of Akt, MAPKs, NF‐κB p65, and IκB‐α in uterus. Results. As the results showed, infiltrations of neutrophils and lymphocytes in uterus were significantly suppressed, and IL‐1β, IL‐6, CXCL‐1, and TNF‐α were also reduced in a dose‐dependent manner. We also found that FYCWYC inhibited apoptosis induced by infection. Furthermore, FYCWYC could block the infection‐induced nuclear translocation of NF‐κB. We found that FYCWYC treatment only decreased the phosphorylation of JNK induced by infection and had no effects on Akt and P38. Additional, the effects of SP600125, an inhibitor of phospho‐JNK, were similar to the results of FYCWYC. Conclusions. Taken together, our results demonstrated that FYCWYC had anti‐inflammatory effect in pathogen‐induced PID model, and the mechanism might be through inhibiting NF‐κB nuclear translocation which is mediated by JNK.
Bedside Endoscopic Retrograde Cholangiopancreatography Using Portable X-Ray in Acute Severe Cholangitis
Authors: Shah Rushikesh , Qayed Emad
Published: February 2018

Patients with acute cholangitis require emergent biliary decompression. Those who are hemodynamically unstable on vasopressor support and mechanical ventilation are too critically ill to move outside of the intensive care unit. This prohibits performing Endoscopic Retrograde Cholangiopancreatography (ERCP) in the endoscopy unit. Fluoroscopic guidance is required to confirm deep biliary cannulation during ERCP. There are a few reported cases of bedside ERCP using portable C-arm fluoroscopy unit or ultrasound guided cannulation. We present a unique case of life-saving emergent bedside ERCP in a severely ill patient with cholangitis and septic shock, using simple portable X-ray to confirm biliary cannulation.
Targeting Tumor Vasculature with TNF Leads Effector T Cells to the Tumor and Enhances Therapeutic Efficacy of Immune Checkpoint Blockers in Combination with Adoptive Cell Therapy
Authors: Elia Angela Rita , Grioni Matteo , Basso Veronica , Curnis Flavio , Freschi Massimo , Corti Angelo , Mondino Anna , Bellone Matteo
Published: February 2018

Purpose: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTL). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intratumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors.

Experimental Design: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with autochthonous prostate cancer and C57BL/6 mice with orthotopic B16 melanoma were treated with NGR-TNF, adoptive T-cell therapy (ACT), and ICB, and monitored for immune surveillance and disease progression.

Results: The combination of ACT, NGR-TNF, and ICB was the most effective in delaying disease progression, and in improving overall survival of mice bearing ICB-resistant prostate cancer or melanoma. Mechanistically, the therapeutic effects were associated with potent tumor infiltration, especially by endogenous but also by adoptively transferred PD-1+, granzyme B+, and interferon-γ+ CTLs. The therapeutic effects were also associated with favorable T-effector/regulatory T cell ratios.

Conclusions: Targeting the tumor vasculature with low-dose TNF in association with ACT may represent a novel strategy for enhancing T-cell infiltration in tumors and overcoming resistance to immune checkpoint blockers. Clin Cancer Res; 24(9); 2171–81. ©2018 AACR.
Combinations of Bevacizumab and Erlotinib Show Activity in Colorectal Cancer Independent of RAS Status
Authors: Mésange Paul , Bouygues Anaïs , Ferrand Nathalie , Sabbah Michèle , Escargueil Alexandre E. , Savina Ariel , Chibaudel Benoist , Tournigand Christophe , André Thierry , de Gramont Aimery , Larsen Annette K.
Published: February 2018

Purpose: There is extensive cross-talk between VEGF- and EGFR-pathway signaling in colorectal cancer. However, combinations of VEGF- and EGFR-targeted monoclonal antibodies (mAb) show disappointing activity, in particular for patients with mutant RAS. Previous results show that tyrosine kinase inhibitors (TKI) can be active in colorectal cancer models resistant to mAbs. This prompted us to examine whether the activity of bevacizumab can be increased by combination with erlotinib.

Experimental Design: The antitumor activity of bevacizumab, erlotinib, and their combination was determined in colorectal cancer models with different RAS status and bevacizumab sensitivity. EGFR/VEGF pathway activation was characterized by immunohistochemistry, Western blot, and ELISA assays. The influence of cetuximab and erlotinib on EGF-mediated migration and the EGFR–EGF ligand feedback loop was established in colorectal cancer cell lines with different RAS status.

Results: The addition of erlotinib increased bevacizumab activity in all models independent of RAS status. Bevacizumab exposure was accompanied by marked EGFR activation in tumor cells as well as in tumor-associated endothelial cells (TECs) and resulted in strong accumulation of intracellular EGFR, which could be attenuated by erlotinib. In cellular models, erlotinib was able to attenuate EGF-mediated functions in all cell lines independent of RAS status while cetuximab only showed activity in RAS wild-type cells.

Conclusions: These results should provide a molecular framework to better understand the increased activity of the bevacizumab–erlotinib combination, compared with bevacizumab alone, in the GERCOR DREAM phase III clinical trial. Differential activity of mAbs and TKIs targeting the same signaling pathway is likely applicable for other tumor types. Clin Cancer Res; 24(11); 2548–58. ©2018 AACR.
Association between Rheumatoid Arthritis and Pulmonary Hypertension: Data from the French Pulmonary Hypertension Registry
Authors: Montani David , Henry Julien , O’Connell Caroline , Jaïs Xavier , Cottin Vincent , Launay David , Habib Gilbert , Bourdin Arnaud , Jevnikar Mitja , Savale Laurent , Rottat Laurence , Simonneau Gérald , Sitbon Olivier , Humbert Marc , Allanore Yannick
Published: February 2018

Background: Precapillary pulmonary hypertension (PH), and particularly pulmonary arterial hypertension (PAH), is a life-threatening complication of connective tissue diseases (systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease). The relationship between PH and rheumatoid arthritis (RA) has not been clearly established. Objectives: The aim of the study was to evaluate the relationship between precapillary PH and RA. Methods: We identified patients with PH and suspected RA included in the French PH Registry between 1 May 2004 and 31 December 2012 and evaluated the prevalence of confirmed RA in this population. RA phenotypes, clinical, functional, and hemodynamic data, and patient outcomes were recorded. Results: RA was confirmed in 20 patients (70% female; mean age 52 years) with precapillary PH, including 10 patients with PAH, 6 with severe PH due to lung disease, and 4 with chronic thromboembolic PH. The prevalence of RA was 0.35% (95% CI: 0.23–0.54) in the French PH Registry and 0.58% (95% CI: 0.30–1.11) in idiopathic PAH, comparable to that in the general population. The RA phenotype was characterized by the presence of specific RA autoantibodies and joint erosions in 75% of the patients. The outcomes of PH in the RA patients were unremarkable compared to those in other patients from the registry, and RA therapies had no major impact on the cardiopulmonary parameters. Conclusion: When precapillary PH occurs in RA patients, all PH subsets may be identified. The RA prevalence in the French PH Registry is similar to that in the general population, which does not support a specific association or an indication for PH screening in RA patients.
ABC4 Consensus: Assessment by a German Group of Experts
Authors: Harbeck Nadia , Lüftner Diana , Marschner Norbert , Untch Michael , Augustin Doris , Briest Susanne , Ettl Johannes , Haidinger Renate , Müller Lothar , Müller Volkmar , Ruckhäberle Eugen , Wuerstlein Rachel , Thomssen Christoph
Published: February 2018

The Advanced Breast Cancer Fourth Consensus (ABC4) on diagnosis and treatment of advanced breast cancer (ABC) again took place in Lisbon, on November 2-4, 2017, and was chaired by Fatima Cardoso, MD, PhD. This year's contents focused very much on new developments in the treatment of ABC. For example, the significance of inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) in hormone receptor (HR)-positive ABC, of dual antibody blockade in human epidermal growth factor receptor 2 (HER2)-positive ABC, and of poly(ADP-ribose) polymerase (PARP) inhibition in triple-negative ABC, as well as the potential therapeutic consequences, were discussed. Other key issues were BRCA-associated breast cancer, treatment of brain metastases, and personalized therapy decision-making using molecular testing (so-called ‘precision medicine'). As in past years, an important objective of the ABC conference was cooperation with representatives of patient organizations from around the world. This cooperation was further intensified during the ABC4. Following the main conference, the ‘Global Alliance' was founded, with the goal of publicizing and coordinating measures necessary worldwide from the patient advocates' standpoint. - The ABC consensus inevitably cannot accommodate country-specific needs, due to the truly global expert panel. Therefore, a working group of German breast cancer experts commented - as in the past years - on the on-site voting results by the ABC panelists upon which the final ABC4 consensus will be based, with particular consideration of the German guidelines on diagnosis and treatment of breast cancer for everyday treatment in Germany.
Inhibition of Autophagy Attenuated Ethylene Glycol Induced Crystals Deposition and Renal Injury in a Rat Model of Nephrolithiasis
Authors: Liu Yunlong , Liu Quan , Wang Xiang , He Ziqi , Li Derong , Guan Xiaofeng , Tao Zhiwei , Deng Yaoliang
Published: February 2018

Background/Aims: Nephrolithiasis is a common and frequently occurring disease, its exact pathogenesis is remains unclear. Emerging data suggest that autophagy plays a vital role in the pathophysiological processes of kidney diseases. Therefore, this study was designed to investigate the potential role of autophagy in the formation of calcium oxalate (CaOx) kidney stones in rat model. Methods: Thirty-two rats were randomly divided into four groups (eight rats/group): untreated control group, stone model group, rapamycin-treated group, chloroquine-treated group. Rat models of CaOx nephrolithiasis was administration of 0.75% ethylene glycol (EG) in their drinking water for 4 weeks. Western blot and transmission electron microscope (TEM) were used to detect the expression of autophagy related protein LC3-II, BECN1 and p62 and autophagic vacuoles respectively. Renal function was evaluated by measuring the levels of serum CRE and BUN. Renal tubular injury markers NGAL and Kim-1 was determined by ELISA kits. Von Kossa staining was used to assess crystal deposits and histological tissue injury. TUNEL staining was employed to assess apoptosis of the renal tubular cell. Results: Compare with the controls, the expression of autophagy related protein LC3-II, BECN1 and number of autophagic vacuoles were increased significantly, whereas the p62 protein level was decreased in the stone model group. The levels of apoptosis, serum CRE and BUN, NGAL and Kim-1 in the stone model group were increased compared with the control group and crystals deposition and renal injury were increased significantly. However, the levels of autophagy, kidney injury and crystal deposition were decreased by chloroquine but increased by rapamycin. Conclusion: These findings suggested that rats were administration of ethylene glycol could lead to the formation of CaOx nephrolithiasis and autophagy activation. Inhibiting autophagy could be an effective therapeutic approach for decreasing the formation of nephrolithiasis.
Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury
Authors: Hu Bo , Tong Fei , Xu Long , Shen Zhiwei , Yan Lijian , Xu Guangtao , Shen Ruilin
Published: February 2018

Background/Aims: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). Methods: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.
Mdia1 is Crucial for Advanced Glycation End Product-Induced Endothelial Hyperpermeability
Authors: Zhou Xiaoyan , Weng Jie , Xu Jing , Xu Qiulin , Wang Weiju , Zhang Weijin , Huang Qiaobing , Guo Xiaohua
Published: February 2018

Background/Aims: Disruption of endothelial barrier integrity in response to advanced glycation end products (AEGs) stimulation contributes to vasculopathy associated with diabetes mellitus. Mammalian diaphanous-related formin (mDia1) has been reported to bind to the cytoplasmic domain of the receptor for advanced glycation end products (RAGE), which induces a series of cellular processes. This study directly evaluated the participation of mDia1 in AGE-induced hyperpermeability and revealed the precise intracellular signal transductions of this pathological process. Methods: Human umbilical vein endothelial cells (HUVECs) were used in the in vitro studies. Trans-endothelial electric resistance and permeability coefficient for dextran (Pd) were measured to analyze cell permeability. Western blotting, immunofluorescence staining and flow cytometry assay were performed to investigate the underlying mechanism. Dextran flux across the mesentery in mice was monitored to investigate in vivo microvascular permeability. Results: we found that AGEs evoked Nox4 membrane translocation, reactive oxygen species production, phosphorylation of Src and VE-cadherin, dissociation of adherens junctions and eventual endothelial hyperpermeability through RAGE-mDia1 binding. Cells overexpressing mDia1 by recombinant adenovirus infection showed stronger cellular responses induced by AGEs. Down-regulation of mDia1 by infection with an adenovirus encoding siRNA or blockade of RAGE-mDia1 binding by transfection with RAGE mutant plasmids into HUVECs abolished these AGE-induced effects. Furthermore, knockdown of mDia1 using an adenovirus or genetical knockout of RAGE in C57 mice rescued AGE-evoked microvascular hyperpermeability. Conclusion: Our study revealed that mDia1 plays a critical role in AGE-induced microvascular hyperpermeability through binding to RAGE.
Socioeconomic status in childhood and obesity in adults: a population-based study
Authors: Wagner Katia Jakovljevic Pudla , Bastos João Luiz Dornelles , Navarro Albert , Gonzalez-Chica David Alejandro , Boing Antonio Fernando
Published: February 2018

OBJECTIVE: To test whether there is an association between socioeconomic status in childhood and measures of body mass index, waist circumference and the presence of overall and abdominal obesity in adult life. METHODS: A cross-sectional analysis of a population-based cohort study, including a sample of adults (22–63 years old) living in Florianópolis, Southern Brazil. The socioeconomic status in childhood was analyzed through the education level of the participant’s parents. Height, weight and waist circumference were measured by previously trained interviewers. Linear and logistic regressions with adjustment for confounding factors and stratification of data according to gender were used. RESULTS: Of the 1,222 adults evaluated, 20.4% (95%CI 18.1–22.8) presented overall obesity and 24.8% (95%CI 22.4–27.4), abdominal obesity. The body mass index and waist circumference averages among women were, respectively, 1.2 kg/m2 (95%CI -2.3– -0.04) and 2.8 cm (95%CI -5.3– -0.2) lower among those with higher socioeconomic status in childhood. Among men, waist circumference was 3.9 cm (95%CI 1.0–6.8) higher in individuals with higher socioeconomic status in childhood. Regarding obesity, women of higher socioeconomic status in childhood had lower odds of abdominal obesity (OR = 0.56, 95%CI 0.34–0.90), and no such association was observed among men. CONCLUSIONS: The socioeconomic status in childhood influences body mass index, waist circumference and obesity in adults, with a difference in the direction of association according to gender. The higher socioeconomic status among men and the lower socioeconomic status among women were associated with higher adiposity indicators.
Leprosy and gender in Brazil: trends in an endemic area of the Northeast region, 2001–2014
Authors: Souza Eliana Amorim de , Ferreira Anderson Fuentes , Boigny Reagan Nzundu , Alencar Carlos Henrique , Heukelbach Jorg , Martins-Melo Francisco Rogerlândio , Barbosa Jaqueline Caracas , Ramos Junior Alberto Novaes
Published: February 2018

OBJECTIVE: To analyze, stratifield by gender, trends of the new case leprosy detection rates in the general population and in children; of grade 2 disability, and of proportion of multibacillary cases, in the state of Bahia, Brazil from 2001 to 2014. METHODS: A time series study based on leprosy data from the National Information System for Notifiable Diseases. The time trend analysis included Poisson regression models by infection points (Joinpoint) stratified by gender. RESULTS: There was a total of 40,054 new leprosy cases with a downward trend of the overall detection rate (Average Annual Percent Change [AAPC = -0.4, 95%CI -2.8–1.9] and a nonsignificant increase in children under 15 years (AAPC = 0.2, 95%CI -3.9–4.5). The proportion of grade 2 disability among new cases increased significantly (AAPC = 4.0, 95%CI 1.3–6.8), as well as the proportion of multibacillary cases (AAPC = 2.2, 95%CI 0.1–4.3). Stratification by gender showed a downward trend of detection rates in females and no significant change in males; in females, there was a more pronounced upward trend of the proportion of multibacillary and grade 2 disability cases. CONCLUSIONS: Leprosy is still highly endemic in the state of Bahia, with active transmission, late diagnosis, and a probable hidden endemic. There are different gender patterns, indicating the importance of early diagnosis and prompt treatment, specifically in males without neglecting the situation among females.
Age-related Differences in Prestimulus Subsequent Memory Effects Assessed with Event-related Potentials
Authors: Koen Joshua D. , Horne Erin D. , Hauck Nedra , Rugg Michael D.
Published: February 2018

Prestimulus subsequent memory effects (preSMEs)—differences in neural activity elicited by a task cue at encoding that are predictive of later memory performance—are thought to reflect differential engagement of preparatory processes that benefit episodic memory encoding. We investigated age differences in preSMEs indexed by differences in ERP amplitude just before the onset of a study item. Young and older adults incidentally encoded words for a subsequent memory test. Each study word was preceded by a task cue that signaled a judgment to perform on the word. Words were presented for either a short (300 msec) or long (1000 msec) duration with the aim of placing differential benefits on engaging preparatory processes initiated by the task cue. ERPs associated with subsequent successful and unsuccessful recollection, operationalized here by source memory accuracy, were estimated time-locked to the onset of the task cue. In a late time window (1000–2000 msec after onset of the cue), young adults demonstrated frontally distributed preSMEs for both the short and long study durations, albeit with opposite polarities in the two conditions. This finding suggests that preSMEs in young adults are sensitive to perceived task demands. Although older adults showed no evidence of preSMEs in the same late time window, significant preSMEs were observed in an earlier time window (500–1000 msec) that was invariant with study duration. These results are broadly consistent with the proposal that older adults differ from their younger counterparts in how they engage preparatory processes during memory encoding.
An uncommon habitat for a common salamander: Isthmura bellii in arid tropical scrub
Authors: Domínguez-Vega Hublester , Zuria Iriana , Fernández-Badillo Leonardo
Published: February 2018

Salamanders are usually seen as typical inhabitants of temperate and humid habitats. Among Plethodontids, Isthmura bellii has the broadest altitudinal range of any salamander in the world and it is considered a habitat generalist. Nonetheless, even for this species, dry environments are thought unsuitable. We report the first records of I. bellii in arid tropical scrub from two localities within central Mexico. We analyze the environmental differentiation of these new localities in relation to the known distribution range of the genus. Our study shows that among the new localities, there is at least one site where I. bellii appears to have established in arid tropical scrub. An environmental model reveals that these new localities present different conditions than most of the records of Isthmura spp.
Chasing the phantom: biogeography and conservation of Vipera latastei-monticola in the Maghreb (North Africa)
Authors: Freitas Inês , Fahd Soumia , Velo-Antón Guillermo , Martínez-Freiría Fernando
Published: February 2018

The Maghreb region (North Africa) constitutes a major component of the Mediterranean Basin biodiversity hotspot. During the last centuries, a consistent human population growth has led to an unprecedented rate of habitat transformation and loss in the region and thus, threatening its biodiversity. The Western Mediterranean viper Vipera latastei-monticola inhabits humid and subhumid areas in the main mountain ranges of the Maghreb, facing such threatening factors; however, its elusive character and rarity hindered data collection for distinct biological purposes. Here, we study the biogeographical patterns and conservation status of the Maghrebian V. latastei-monticola resulting from recent sampling campaigns in Morocco and Tunisia. We update species distribution, and integrate phylogeographic and ecological niche modelling analyses at both species and lineage level to identify suitable areas, and to evaluate the impact of anthropogenic transformation and level of protection of their suitable space. We identified four highly divergent mitochondrial lineages, including a new lineage endemic to the Western High Atlas, with allopatric distributions and restricted to mountain ranges, supporting the role of mountains as past climatic refugia. Despite the remoteness of suitable areas, we report widespread habitat degradation and identify the low effectiveness of the current protected areas system in preserving the species and lineages range. Our study shows the urgent need to apply management actions for the long-term conservation of this vulnerable species and suggests a revaluation of the specific status of V. monticola, as these populations likely represent an ecotype of V. latastei.
Identification of type materials of the species of Protypotherium Ameghino, 1885 and Patriarchus Ameghino, 1889 (Notoungulata: Interatheriidae) erected by Florentino Ameghino
Authors: FERNÁNDEZ MERCEDES , FERNICOLA JUAN CARLOS , CERDEÑO ESPERANZA , REGUERO MARCELO A.
Published: February 2018

The first collections of Interatheriinae (Interatheriidae, Notoungulata) were created by the brothers Florentino and Carlos Ameghino, based on fossil specimens collected from diverse outcrops of Argentina and housed at different national institutions. In order to perform a systematic study of the subfamily, it is essential to revise as much specimens as possible, but first of all those that were used to establish the respective species, that is, the type material. Florentino Ameghino never referred to the collection number of the type specimens of the species he erected in any of his publications; this fact added to the occasional absence of illustrations and adequate descriptions, all of which make their identification a complex task. Thus, when studying the species erected by Florentino Ameghino within Protypotherium and Patriarchus, we recognised a lack of correspondence between some specimens that appeared labelled as types in the collections and the original descriptions of these species. In this contribution, we identify the type specimens of the eleven species of Protypotherium and eight of Patriarchus founded by Florentino Ameghino, housed in the Museo Argentino de Ciencias Naturales “Bernardino Rivadavia” (Buenos Aires, Argentina) and the Zoological Museum of the University of Copenhagen (Denmark). Three case studies are presented: a) specimens correctly identified; b) specimens erroneously catalogued as type material; and c) specimens not established as types in Ameghino’s catalogue, but herein recognised as such. Lectotype and paralectotype of P. antiquum are herein designated.