bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal mesothelial cell lines newly derived from human pleural biopsy explants
Authors: Pruett Nathanael , Singh Anand , Shankar Ahjeetha , Schrump David S. , Hoang Chuong D.
Published: July 2020

Mesothelial cells are arranged as a monolayer on covering membranes that invest surfaces of body cavities like the pleura and peritoneum. Primary human mesothelial cell (HMC) cultures are needed for studying mesothelial cell homeostasis and developing disease models, such as wound healing or cancers. Remarkably, there is a paucity of useable HMC lines that are currently available that faithfully recapitulate normal in vivo phenotypic characteristics. Here, we present a strategy to recover HMC from human pleural tissue and to immortalize them for extended in vitro culturing. Human pleural membrane was harvested by minimally invasive surgical techniques. HMC were isolated using a two-step process combining explant cellular outgrowth from biopsy tissue and flow cytometry based on cell surface expression of cadherin-1 and CD71. Cell cultures were generated after lentiviral transfection with human telomerase. The new HMC cultures retain the same phenotypic traits and physiologic features as their in vivo counterparts, yet they can be adapted for short-term or long-term culture in large-scale in vitro experimentation. In particular, we generated a new HMC line harboring a germline mutation in breast cancer type-1-associated protein-1 ( BAP1), a causal tumor suppressor gene, that could be instrumental to malignant mesothelioma research. Patient-specific, normal HMC may serve as novel discovery tools allowing more powerful research models of both normal physiology and disease processes. Our surgically driven approach leads to a limitless resource of novel mesothelial cell cultures.
The rise of electronic nicotine delivery systems and the emergence of electronic-cigarette-driven disease
Authors: McAlinden Kielan Darcy , Eapen Mathew Suji , Lu Wenying , Sharma Pawan , Sohal Sukhwinder Singh
Published: July 2020

In 2019, the United States experienced the emergence of the vaping-associated lung injury (VALI) epidemic. Vaping is now known to result in the development and progression of severe lung disease in the young and healthy. Lack of regulation on electronic cigarettes in the United States has resulted in over 2,000 patients and 68 deaths. We examine the clinical representation of VALI and the delve into the scientific evidence of how deadly exposure to electronic cigarettes can be. E-cigarette vapor is shown to affect numerous cellular processes, cellular metabolism, and cause DNA damage (which has implications for cancer). E-cigarette use is associated with a higher risk of developing crippling lung conditions such as chronic obstructive pulmonary disease (COPD), which would develop several years from now, increasing the already existent smoking-related burden. The role of vaping and virus susceptibility is yet to be determined; however, vaping can increase the virulence and inflammatory potential of several lung pathogens and is also linked to an increased risk of pneumonia. As it has emerged for cigarette smoking, great caution should also be given to vaping in relation to SARS-CoV-2 infection and the COVID-19 pandemic. Sadly, e-cigarettes are continually promoted and perceived as a safer alternative to cigarette smoking. E-cigarettes and their modifiable nature are harmful, as the lungs are not designed for the chronic inhalation of e-cigarette vapor. It is of interest that e-cigarettes have been shown to be of no help with smoking cessation. A true danger lies in vaping, which, if ignored, will lead to disastrous future costs.
Vitamin D deficiency downregulates TASK-1 channels and induces pulmonary vascular dysfunction
Authors: Callejo Maria , Mondejar-Parreño Gema , Morales-Cano Daniel , Barreira Bianca , Esquivel-Ruiz Sergio , Olivencia Miguel Angel , Manaud Grégoire , Perros Frédéric , Duarte Juan , Moreno Laura , Cogolludo Angel , Perez-Vizcaíno Francisco
Published: July 2020

Vitamin D (VitD) receptor regulates the expression of several genes involved in signaling pathways affected in pulmonary hypertension (PH). VitD deficiency is highly prevalent in PH, and low levels are associated with poor prognosis. We investigated if VitD deficiency may predispose to or exacerbate PH. Male Wistar rats were fed with a standard or a VitD-free diet for 5 wk. Next, rats were further divided into controls or PH, which was induced by a single dose of Su-5416 (20 mg/kg) and exposure to hypoxia (10% O2) for 2 wk. VitD deficiency had no effect on pulmonary pressure in normoxic rats, indicating that, by itself, it does not trigger PH. However, it induced several moderate but significant changes characteristic of PH in the pulmonary arteries, such as increased muscularization, endothelial dysfunction, increased survivin, and reduced bone morphogenetic protein ( Bmp) 4, Bmp6, DNA damage-inducible transcript 4, and K+two - pore domain channel subfamily K member 3 ( Kcnk3) expression. Myocytes isolated from pulmonary arteries from VitD-deficient rats had a reduced whole voltage-dependent potassium current density and acid-sensitive (TASK-like) potassium currents. In rats with PH induced by Su-5416 plus hypoxia, VitD-free diet induced a modest increase in pulmonary pressure, worsened endothelial function, increased the hyperreactivity to serotonin, arterial muscularization, decreased total and TASK-1 potassium currents, and further depolarized the pulmonary artery smooth muscle cell membrane. In human pulmonary artery smooth muscle cells from controls and patients with PH, the active form of VitD calcitriol significantly increased KCNK3 mRNA expression. Altogether, these data strongly suggest that the deficit in VitD induces pulmonary vascular dysfunction.
Influence of Titanium Alloy Scaffolds on Enzymatic Defense against Oxidative Stress and Bone Marrow Cell Differentiation
Authors: Rodrigues Lais Morandini , Lima Zutin Elis Andrade , Sartori Elisa Mattias , Mendonça Daniela Baccelli Silveira , Mendonça Gustavo , Carvalho Yasmin Rodarte , Reis de Vasconcellos Luana Marotta
Published: July 2020

Studies have been directed towards the production of new titanium alloys, aiming for the replacement of Ti-6 Aluminium-4 Vanadium (TiAlV) alloy in the future. Many mechanisms related to biocompatibility and chemical characteristics have been studied in the field of implantology, but enzymatic defenses against oxidative stress remain underexplored. Bone marrow stromal cells have been explored as source of cells, which have the potential to differentiate into osteoblasts and therefore could be used as cells-based therapy. The objective of this study was to evaluate the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in porous scaffolds of Ti-6 Aluminium-4 Vanadium (TiAlV), Ti-35 Niobium (TiNb), and Ti-35 Niobium-7 Zirconium-5 Tantalum (TiNbZrTa) on mouse bone marrow stromal cells. Porous titanium alloy scaffolds were prepared by powder metallurgy. After 24 hours, cells plated on the scaffolds were analyzed by scanning electron microscopy (SEM). The antioxidant enzyme activity was measured 72 hours after cell plating. Quantitative real time PCR (qRT-PCR) was performed after 3, 7, and 14 days, and Runx2 (Runt-related transcription factor2) expression was evaluated. The SEM images showed the presence of interconnected pores and growth, adhesion, and cell spreading in the 3 scaffolds. Although differences were noted for SOD and CAT activity for all scaffolds analyzed, no statistical differences were observed (p>0.05). The osteogenic gene Runx2 presented high expression levels for TiNbZrTa at day 7, compared to the control group (TiAlV day 3). At day 14, all scaffolds had more than 2-fold induction for Runx2 mRNA levels, with statistically significant differences compared to the control group. Even though we were not able to confirm statistically significant differences to justify the replacement of TiAlV regarding antioxidant enzymes, TiNbZrTa was able to induce faster bone formation at early time points, making it a good choice for biomedical and tissue bioengineering applications.
A PSD Maps Estimation Algorithm for Underlay Cognitive Radio Networks Based on the Convolutional Neural Network
Authors: Han Xu , Xue Lei , Xu Ying
Published: July 2020

In the underlay cognitive radio networks (CRNs), the power spectral density (PSD) maps play a foundational role in detecting the idle radio resources. However, it is hard to get a high-accurate PSD map estimation result because of the complicated radio environment. For this reason, we propose a novel convolutional neural network- (CNN-) based PSD map estimation algorithm named map reconstruction CNN (MRCNN). Using the CNN to estimate PSD maps for underlay CRNs has not been reported until now. First, on the basis of the proposed color mapping process, we transform the PSD map estimation task to the image reconstruction task. Then, we train the MRCNN to learn the radio environment characteristics from the training data, rather than making direct biased or imprecise wireless environment hypotheses as in the conventional methods. We utilize the extracted knowledge in the training process to reconstruct the PSD map images. As demonstrated in the simulations, the proposed MRCNN method has a better PSD map estimation performance than the conventional methods.
Inhibition of Digestive Enzyme and Stimulation of Human Liver Cells (HepG2) Glucose Uptake by Date Seeds Extract
Authors: Shakoor Hira , Abdelfattah Fatima , Albadi Khaula , Adib Mentalla , Kizhakkayil Jaleel , Platat Carine
Published: July 2020

Type 2 diabetes mellitus is increasing worldwide, and the United Arab Emirates is presenting one of the world’s highest prevalence rates. Dietary polyphenols exert an antidiabetic effect by modulating carbohydrates digestion and cellular glucose uptake. Due to their particularly high content in polyphenols, date seeds represent a potential antidiabetic agent. This study aims to determine if date seed polyphenols inhibit the activity of the enzymes (α‐amylase and α‐glucosidase), responsible for the digestion of carbohydrates and modulating the glucose uptake by human liver cells. In vitro activity of the intestinal α‐glucosidase, pancreatic α‐amylase, the glucose uptake by HepG2 cells, and the expression of GLUT4 and AMPK analyzed by western blotting (with and without date seeds extract). Our result showed that the maximum enzymes inhibition was obtained with 400 μg/mL and 900 μg/mL DSE for α‐amylase and α‐glucosidase, respectively. The HepG2 cell viability significantly decreased up to 80% at 4000 μg/mL DSE. The expression of GLUT4 was higher at 100 μg/mL DSE (with insulin and without insulin). However, the expressions of P‐AMPK and AMPK were increased by DSE, mainly in a non‐insulin‐dependent manner. Therefore, DSE, by inhibiting carbohydrate digestion and stimulating glucose uptake by HepG2, can potentially demonstrate the therapeutic potential for diabetes management.
Immediate Placement and Restoration of a New Tapered Implant System in the Aesthetic Region: A Report of Three Cases
Authors: Meijndert Caroliene M. , Raghoebar Gerry M. , Vissink Arjan , Meijer Henny J. A.
Published: July 2020

Objective. To assess the clinical, radiographic, aesthetic, and patient-centred outcomes of a new implant system applied for an immediate implant placement and restoration approach in single tooth replacement of anterior maxillary teeth. Material and Method. Three cases were treated with a bone level tapered implant. All patients were treated with the same strategy involving flapless extraction and implant placement with simultaneous augmentation. Implants were provisionally restored with a screw-retained restoration at the day of surgery. Definitive restoration was fabricated after 3 months. Follow-up was one year after definitive restoration. Results. At the 1-year follow-up, the implants were stable and no complications had occurred. Peri-implant bone levels had increased with a mean value of 0.24±0.30 mm between definitive restoration placement and 1 year of follow-up. Clinical outcome scores showed healthy soft tissues. Mean Pink and White Esthetic scores were rated 7.0 and 7.3, respectively. Mean patient satisfaction had improved from 55.7 (pretreatment) to 90.0 (1-year follow-up) on a 0-100 VAS scale. Conclusion. Immediate implant placement and restoration with the new tapered bone level implant system are accompanied by good initial clinical and radiographic results as well as high patient satisfaction.
Preclinical Evidence of Curcuma longa and Its Noncurcuminoid Constituents against Hepatobiliary Diseases: A Review
Authors: An Soyeon , Jang Eungyeong , Lee Jang-Hoon
Published: July 2020

Hepatobiliary disease currently serves as an important public health issue due to the fact that it is one of the major causes of death among economically active individuals and can easily progress to chronic diseases. Despite the development of vaccines and numerous drugs, a definite treatment remains lacking owing to different stages of the disease itself, its intricate pathogenesis, an effect uncertainty for long‐term use, resistance, and side effects. Curcuma longa (C. longa), which belongs to the family Zingiberaceae and the genus Curcuma, has long been used not only as spice for curry or dye but also as a constituent of herbal formula for the treatment of different diseases due to its bioactive activities. Recently, many studies on the experimental results of C. longa have been published relative to hepatobiliary diseases such as fatty liver, hepatitis, cirrhosis, and tumors. Therefore, in this review, we aimed to summarize the pharmacological effects and underlying molecular mechanisms of C. longa and its four compounds, β‐elemene, germacrone, ar‐turmerone, and bisacurone, against hepatobiliary diseases. C. longa exhibited antioxidant, hepatoprotective, antisteatotic, anti‐inflammatory, antifibrotic, antitumor, and cholagogic effects by regulating apoptosis, CYP2E1, Nrf, lipid metabolism‐related factors, TGF‐β, NF‐κB, CYP7A1, and so on. In particular, β‐elemene could be an attractive compound owing to its remarkable hepatoprotective, anti‐inflammatory, antifibrotic, and antitumor activities. Altogether, the present review provides a preclinical basis for the efficacy of C. longa as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases, despite the need for further studies to establish the extraction conditions and separation of active constituents with high bioavailability, and warrants further evaluation in clinical trials.
An Experimental Study on the Compressive Dynamic Performance of Polypropylene Fiber Reinforced Concrete for Retaining Structure under Automobile Collision Magnitude
Authors: Li Furong , Chen Guoxing , Xu Guizhong , Wu Yongyi
Published: July 2020

In order to examine the compressive dynamic performance of polypropylene fiber reinforced concrete to be used for the retaining structure under the automobile collision magnitude, an experimental study was carried out by using hydraulic servo on concrete specimens with 4 different polypropylene fiber contents under 6 loading strain rates. The failure modes and stress‐strain curves of concrete under different loading conditions were obtained. Then, by comparatively analyzing the mechanical characteristic parameters of polypropylene fiber reinforced concrete under different loading conditions, the following conclusions are drawn: with the increase of the polypropylene fiber content, the integrity of concrete upon compressive failure is gradually improved. When the polypropylene fiber content is relatively high, the static and dynamic failure modes are basically similar. With the increase of the loading strain rate, the peak compressive stress and elastic modulus of the polypropylene fiber reinforced concrete gradually increase. The increase in the polypropylene fiber content gradually intensifies the effect of loading strain rate on the peak compressive stress dynamic improvement coefficient. The peak strain of polypropylene fiber reinforced concrete is gradually increased with the increase of polypropylene fiber content, while the effect of the loading strain rate on the peak strain shows an obvious discreteness characteristic. Meanwhile, we proposed a relationship equation for describing the peak compressive stress dynamic improvement coefficient based on the coupling effect of the polypropylene fiber content and loading strain rate and further discussed the underlying stress mechanism in detail. Our research findings are of important research significance for the application and promotion of polypropylene fiber reinforced concrete in the engineering practice of retaining structures.
Φ,Ψ-Weak Contractions in Neutrosophic Cone Metric Spaces via Fixed Point Theorems
Authors: Al-Omeri Wadei F. , Jafari Saeid , Smarandache Florentin
Published: July 2020

In this manuscript, we obtain common fixed point theorems in the neutrosophic cone metric space. Also, notion of Φ,Ψ-weak contraction is defined in the neutrosophic cone metric space by using the idea of altering distance function. Finally, we review many examples of cone metric spaces to verify some properties.
A Systematic Review of the Various Effect of Arsenic on Glutathione Synthesis In Vitro and In Vivo
Authors: Ran Shanshan , Liu Jiaqing , Li Shugang
Published: July 2020

Background. Arsenic is a toxic metalloid widely present in nature, and arsenic poisoning in drinking water is a serious global public problem. Glutathione is an important reducing agent that inhibits arsenic‐induced oxidative stress and participates in arsenic methylation metabolism. Therefore, glutathione plays an important role in regulating arsenic toxicity. In recent years, a large number of studies have shown that arsenic can regulate glutathione synthesis in many ways, but there are many contradictions in the research results. At present, the mechanism of the effect of arsenic on glutathione synthesis has not been elucidated. Objective. We will conduct a meta‐analysis to illustrate the effects of arsenic on GSH synthesis precursors Glu, Cys, Gly, and rate‐limiting enzyme γ‐GCS in mammalian models, as well as the regulation of p38/Nrf2 of γ‐GCS subunit GCLC, and further explore the molecular mechanism of arsenic affecting glutathione synthesis. Results. This meta‐analysis included 30 studies in vivo and 58 studies in vitro, among which in vivo studies showed that arsenic exposure could reduce the contents of GSH (SMD = −2.86, 95% CI (‐4.45, ‐1.27)), Glu (SMD = −1.11, 95% CI (‐2.20,‐0.02)), and Cys (SMD = −1.48, 95% CI (‐2.63, ‐0.33)), with no statistically significant difference in p38/Nrf2, GCLC, and GCLM. In vitro studies showed that arsenic exposure increased intracellular GSH content (SMD = 1.87, 95% CI (0.18, 3.56)) and promoted the expression of p‐p38 (SMD = 4.19, 95% CI (2.34, 6.05)), Nrf2 (SMD = 4.60, 95% CI (2.34, 6.86)), and GCLC (SMD = 1.32, 95% CI (0.23, 2.41)); the p38 inhibitor inhibited the expression of Nrf2 (SMD = −1.27, 95% CI (‐2.46, ‐0.09)) and GCLC (SMD = −5.37, 95% CI (‐5.37, ‐2.20)); siNrf2 inhibited the expression of GCLC, and BSO inhibited the synthesis of GSH. There is a dose‐dependent relationship between the effects of exposure on GSH in vitro. Conclusions. These indicate the difference between in vivo and in vitro studies of the effect of arsenic on glutathione synthesis. In vivo studies have shown that arsenic exposure can reduce glutamate and cysteine levels and inhibit glutathione synthesis, while in vitro studies have shown that chronic low‐dose arsenic exposure can activate the p38/Nrf2 pathway, upregulate GCLC expression, and promote glutathione synthesis.
Copy Number Loss of 17q22 Is Associated with Enzalutamide Resistance and Poor Prognosis in Metastatic Castration-Resistant Prostate Cancer
Authors: Guan Xiangnan , Sun Duanchen , Lu Eric , Urrutia Joshua A. , Reiter Robert Evan , Rettig Matthew , Evans Christopher P. , Lara Primo , Gleave Martin , Beer Tomasz M. , Thomas George V. , Huang Jiaoti , Aggarwal Rahul R. , Quigley David A. , Foye Adam , Chen William S. , Youngren Jack , Weinstein Alana S. , Stuart Joshua M. , Feng Felix Y. , Small Eric J. , Xia Zheng , Alumkal Joshi J.
Published: July 2020

Purpose:

The purpose of this study was to measure genomic changes that emerge with enzalutamide treatment using analyses of whole-genome sequencing and RNA sequencing.

Experimental Design:

One hundred and one tumors from men with metastatic castration-resistant prostate cancer (mCRPC) who had not been treated with enzalutamide (n = 64) or who had enzalutamide-resistant mCRPC (n = 37) underwent whole genome sequencing. Ninety-nine of these tumors also underwent RNA sequencing. We analyzed the genomes and transcriptomes of these mCRPC tumors.

Results:

Copy number loss was more common than gain in enzalutamide-resistant tumors. Specially, we identified 124 protein-coding genes that were more commonly lost in enzalutamide-resistant samples. These 124 genes included eight putative tumor suppressors located at nine distinct genomic regions. We demonstrated that focal deletion of the 17q22 locus that includes RNF43 and SRSF1 was not present in any patient with enzalutamide-naïve mCRPC but was present in 16% (6/37) of patients with enzalutamide-resistant mCRPC. 17q22 loss was associated with lower RNF43 and SRSF1 expression and poor overall survival from time of biopsy [median overall survival of 19.3 months in 17q22 intact vs. 8.9 months in 17q22 loss, HR, 3.44 95% confidence interval (CI), 1.338–8.867, log-rank P = 0.006]. Finally, 17q22 loss was linked with activation of several targetable factors, including CDK1/2, Akt, and PLK1, demonstrating the potential therapeutic relevance of 17q22 loss in mCRPC.

Conclusions:

Copy number loss is common in enzalutamide-resistant tumors. Focal deletion of chromosome 17q22 defines a previously unappreciated molecular subset of enzalutamide-resistant mCRPC associated with poor clinical outcome.
Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities
Authors: Kelly Marcus R. , Kostyrko Kaja , Han Kyuho , Mooney Nancie A. , Jeng Edwin E. , Spees Kaitlyn , Dinh Phuong T. , Abbott Keene L. , Gwinn Dana M. , Sweet-Cordero E. Alejandro , Bassik Michael C. , Jackson Peter K.
Published: July 2020

Activating mutations in RAS GTPases drive many cancers, but limited understanding of less-studied RAS interactors, and of the specific roles of different RAS interactor paralogs, continues to limit target discovery. We developed a multistage discovery and screening process to systematically identify genes conferring RAS-related susceptibilities in lung adenocarcinoma. Using affinity purification mass spectrometry, we generated a protein–protein interaction map of RAS interactors and pathway components containing hundreds of interactions. From this network, we constructed a CRISPR dual knockout library targeting 119 RAS-related genes that we screened for KRAS-dependent genetic interactions (GI). This approach identified new RAS effectors, including the adhesion controller RADIL and the endocytosis regulator RIN1, and >250 synthetic lethal GIs, including a potent KRAS-dependent interaction between RAP1GDS1 and RHOA. Many GIs link specific paralogs within and between gene families. These findings illustrate the power of multiomic approaches to uncover synthetic lethal combinations specific for hitherto untreatable cancer genotypes.

Significance:

We establish a deep network of protein–protein and genetic interactions in the RAS pathway. Many interactions validated here demonstrate important specificities and redundancies among paralogous RAS regulators and effectors. By comparing synthetic lethal interactions across KRAS-dependent and KRAS-independent cell lines, we identify several new combination therapy targets for RAS-driven cancers.

This article is highlighted in the In This Issue feature, p. 1775
Trimester-Specific Thyroid Function in Pregnant Women with Different Iodine Statuses
Authors: Guo Wenxing , Wang Wei , Jin Ya , Chen Wen , Chen Lu , Lin Laixiang , Cheng Yuangui , Cui Tingkai , Chen Yanting , Pan Ziyun , Shen Jun , Tan Long , Gao Min , Zhang Yixin , Zhang Wanqi
Published: July 2020

Objectives: To explore trimester-specific thyroid function changes under different iodine statuses throughout pregnancy. Methods: A cross-sectional study was conducted to assess the pregnancy iodine status, and 2,378 healthy pregnant women covering all 3 trimesters were recruited. Urinary iodine concentration (UIC) was measured by collecting spot urine samples. Blood samples were collected to evaluate thyroid function. Thyroid B-ultrasonography was conducted to measure the thyroid volume (Tvol). Results: The median UIC was 168 μg/L (111–263 μg/L). The UIC, free triiodothyronine (FT3), and free thyroxine (FT4) were significantly decreased as the pregnancy progressed (p < 0.001, p for trend <0.001), while Tvol increased (p < 0.001, p for trend <0.001). Thyrotropin (TSH) was significantly different between the 3 trimesters and showed an upward trend (p < 0.001), but the p for trend was not significant (p for trend = 0.88). After stratification by UIC, there were no significant differences in serum TSH, FT4, or FT3 level between UIC groups. Tvol was significantly higher in the UIC ≥500 μg/L group in the first trimester (β: 2.41, 95% CI: 1.09–3.72, p <0.001), as well as in the 250 ≤ UIC < 500 μg/L group (β: 1.65, 95% CI: 0.61–2.70, p < 0.001) and UIC ≥500 μg/L group (β: 3.35, 95% CI: 1.96–4.74, p < 0.001) in the third trimester. Conclusions: No difference was observed in TSH, FT3, or FT4 among the different iodine status groups throughout pregnancy. Tvol increased as the pregnancy progressed, and it was especially higher in the UIC ≥500 μg/L group in the first and third trimesters.
Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder
Authors: Massardo Teresa , Quintana Juan Carlos , Jaimovich Rodrigo , Sáez Claudia G. , Risco Luis , Liberman Claudio , Araya Aída Verónica , Galleguillos Tamara , Castro-Mora Gabriel , Pereira Jaime
Published: July 2020

Background: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. Purpose: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. Patients and Methods: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. Results: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. Conclusion: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.
Endocrine-Resistant Breast Cancer: Mechanisms and Treatment
Authors: Hartkopf Andreas D. , Grischke Eva-Maria , Brucker Sara Y.
Published: July 2020

Background: Endocrine treatment is one of the most effective therapies for estrogen receptor-positive breast cancer. However, most tumors will develop resistance to endocrine therapy as the cancer progresses. This review focuses on the mechanisms and markers of endocrine-resistant breast cancer. In addition, current and future strategies to overcome endocrine resistance are discussed. Summary: Several molecular mechanisms of endocrine resistance have been identified, including alterations in the ESR1 gene or in the PIK3CA/mTOR pathway. Meanwhile, CDK4/6, mTOR, and PI3K inhibition have shown to improve the efficacy of endocrine treatment and new promising approaches are being developed. Key Message: Overcoming primary or acquired resistance to endocrine treatment remains a major challenge. Since the molecular mechanisms of endocrine resistance are manifold, optimal combination and sequencing strategies will have to be developed in the future.
Serum Exosomal Gamma-Glutamyltransferase Activity Increased in Patients with Renal Cell Carcinoma with Advanced Clinicopathological Features
Authors: Horie Kengo , Kawakami Kyojiro , Fujita Yasunori , Matsuda Yoko , Arai Tomio , Suzui Natsuko , Miyazaki Tatsuhiko , Koie Takuya , Mizutani Kosuke , Ito Masafumi
Published: July 2020

Background: There has been no clinically useful diagnostic or prognostic biomarker for renal cell carcinoma (RCC). Serum γ-glutamyltransferase (GGT) activity has been reported to be a prognostic marker for several types of cancer including RCC. Exosomes or small extracellular vesicles present in body fluids have potential as a biomarker. We have recently demonstrated that GGT activity on exosomes isolated from serum is useful for the differential diagnosis of prostate cancer and benign prostate hyperplasia. In this study, we aimed to examine if serum exosomal GGT activity could be a marker for RCC. Methods: We examined GGT1 expression and GGT activity in cell lysates and exosomes from culture medium of HK-2 proximal tubule epithelial and RCC cell lines. GGT activity was measured using a fluorescent probe for GGT, γ-glutamyl hydroxymethyl rhodamine green. Serum and serum exosomal GGT activities were measured in patients with RCC. GGT1 expression in RCC tissues was evaluated by immunohistochemical staining. Results: GGT1 levels in exosomes from KMRC-1, OS-RC-2 and 786-O cells were elevated compared with those from HK-2 cells. In exosomes, GGT1 expression correlated with GGT activity determined using a fluorescent probe for GGT. In RCC patients, serum exosomal GGT activity was elevated in those with advanced stages (III/IV vs. I/II, p = 0.037) and those with microvascular invasion (with vs. without, p = 0.034). Immunohistochemical analysis showed that membranous GGT1 expression was increased in RCC with microvascular invasion. Notably, preoperative serum exosomal GGT activity could predict the likelihood of having microvascular invasion diagnosed by pathological examination of surgically resected specimens. Conclusions: Our results suggest that serum exosomal GGT activity could be a clinically useful marker for advanced clinicopathological features of RCC patients, and its combined use with conventional diagnostic modalities may improve the diagnosis and treatment of patients.
Gamma Knife Radiosurgery for Treatment of Brain Metastases during the COVID-19 Outbreak
Authors: Crisà Francesco Maria , Leocata Filippo , Arienti Virginia Maria , Picano Marco , Berta Luca , Mainardi Hae Song , Monti Angelo Filippo , Musca Francesco , Colombo Silvia , Palazzi Mauro , La Camera Alessandro
Published: July 2020

Introduction: The WHO declared 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a public health emergency of international concern. The National and Regional Health System has been reorganized, and many oncological patients died during this period or had to interrupt their therapies. This study summarizes a single-centre experience, during the COVID-19 period in Italy, in the treatment of brain metastases with Gamma Knife stereotactic radiosurgery (GKRS). Methods: We retrospectively analysed our series of patients with brain metastases who underwent GKRS at the Niguarda Hospital from February 24 to April 24, 2020. Results: We treated 30 patients with 66 brain metastases. A total of 22 patients came from home and 8 patients were admitted to the emergency room for urgent neurological symptoms. Duration of stay was limited to 0–1 day in 17 patients. We chose to treat a cluster of 9 patients, whose greater lesion exceeded 10 cm3, with 2-stage modality GKRS to minimize tumour recurrence and radiation necrosis. Conclusion: Due to the COVID-19 pandemic, the whole world is at a critical crossroads about the use of health care resources. During the COVID-19 outbreak, the deferral of diagnostic and therapeutic procedures and a work backlog in every medical specialty are the natural consequences of reservation of resources for COVID-19 patients. GKRS improved symptoms and reduced the need for open surgeries, allowing many patients to continue their therapeutic path and sparing beds in ICUs. Neurosurgeons have to take into account the availability of stereotactic radiosurgery to reduce hospital stay, conciliating safety for patients and operators with the request for health care coming from the oncological patients and their families.
Extracellular Superoxide Dismutase Is Associated With Left Ventricular Geometry and Heart Failure in Patients With Cardiovascular Disease
Authors: Li Xiuwen , Lin Yingying , Wang Shaohua , Zhou Shiyi , Ju Jingmeng , Wang Xiaohui , Chen Yangxin , Xia Min
Published: July 2020

Background

Extracellular superoxide dismutase (Ec‐SOD) is a major scavenger of reactive oxygen species. However, its relationships with abnormal left ventricular (LV) geometry patterns and heart failure (HF) are still unknown in patients with cardiovascular disease.

Methods and Results

A cross‐sectional study was carried out to evaluate the association of serum Ec‐SOD activity with LV geometry, as well as HF in 1047 patients with cardiovascular disease. All participants underwent standard echocardiography examination and measurement of serum Ec‐SOD activity. Overall, we found a significantly decreased trend of serum Ec‐SOD activity from subjects with normal geometry (147.96±15.94 U/mL), subjects with abnormal LV geometry without HF (140.19±20.12 U/mL), and subjects with abnormal LV geometry and overt HF (129.32±17.92 U/mL) after adjustment for potential confounders (
P
for trend <0.001). The downward trends remained significant in the concentric hypertrophy and eccentric hypertrophy groups after stratification by different LV geometry patterns. Multinomial logistic regression analysis showed that each 10 U/mL increase in serum Ec‐SOD activity was associated with a 16.5% decrease in the odds of concentric remodeling without HF (odds ratio [OR], 0.835; 95% CI, 0.736–0.948), a 40.4% decrease in the odds of concentric hypertrophy with HF (OR, 0.596; 95% CI, 0.486–0.730), a 16.1% decrease in the odds of eccentric hypertrophy without HF (OR, 0.839; 95% CI, 0.729–0.965) and a 34.0% decrease in the odds of eccentric hypertrophy with HF (OR, 0.660; 95% CI, 0.565–0.772).

Conclusions

Serum Ec‐SOD activity was independently associated with abnormal LV geometry patterns with and without overt HF. Our results indicate that Ec‐SOD might be a potential link between LV structure remodeling and the development of subsequent HF in patients with cardiovascular disease.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier NCT03351907.
The Ugly Psyche: Arendt and the Right to Opacity
Authors: O’Byrne Anne
Published: July 2020

Arendt was famously dismissive of the work of psychologists, claiming that they did nothing more than reveal the pervasive ugliness and monotony of the psyche. If we want to know who people are, she argued, we should observe what they do and say rather than delving into the turmoil of their inner lives; if we want to understand humanity, we would be better off reading Oedipus Rex than hearing about someone’s Oedipus complex. The rejection has a certain coherence in the context of her understanding of public life as the realm of appearance and opinion, but examining it through the specific question of ugliness complicates that understanding. While beauty invites us to contemplate the world and admire it, ugliness repels our attention and sows the seed of a worry that the world might not want to be known. Working with Eichmann in Jerusalem, The Life of the Mind: Thinking, the Kant lectures and a striking Denktagebuch entry in which she reacts with revulsion to Matisse’s Heads of Jeannette, I argue that Arendt’s response to the ugly psyche requires a re-examination of the sensus communis. If the psyche does not want to be known, and if not all points of view are open to imaginative occupation, the ideal and practice of enlarged mentality must reckon with a right to opacity.
Towards an Arendtian Conception of Justice
Authors: Sari Yasemin
Published: July 2020

This article argues that Arendt’s rich account of the political necessarily involves an implicit, but never fully worked out, phenomenological articulation of justice in her work. Arendt’s unique articulation of the role of judgment in political action provides us with the outline of an Arendtian principle of justice that relieves the tension between idealist and realist theories of justice. Building on this role of judgment, I aim to emphasize the phenomenological premise of identifying the conditions for the possibility of the political in empirico-historical events rooted in her ideas of plurality and freedom. By showing that, for Arendt, justice is a phenomenon like power and equality, we can make progress on an implicit account of justice in her work. Taking seriously Arendt’s articulation of freedom-manifesting and principled political action, I will show that a principle of justice guides political action based on political judgment that is affectively oriented to the world.
Péter Pázmány: Cardinal, Archbishop of Esztergom, Primate of Hungary
Authors: Shore Paul , Tusor Péter
Published: July 2020

Péter Pázmány (1570–1636) was one of the most significant personalities in early modern Hungarian history. Born a Protestant, Pázmány converted to Catholicism while a student and then became a Jesuit. Despite the Society’s requirement of vows from its members that excluded the possibility of holding high ecclesiastical office, Pázmány became provost of Turóc (a small church benefice in northern Hungary) and shortly thereafter archbishop of Esztergom and primate of Hungary. His tenure was marked by ecclesiastical reform and multiple educational projects of which the most notable was the founding of a university in Nagyszombat (Trnava). He was also the author of influential devotional and polemical works in the Hungarian vernacular. Pázmány’s legacy as a preserver and promoter of a “civilization” and a creed both Christian and European and of a culture distinctly Hungarian endures, as does his reputation as a master and shaper of Hungarian prose.
A Failed Politician, a Disputed Jesuit: Cardinal Johann Eberhard Nithard (1607–81)
Authors: Salmerón Miguel Córdoba
Published: July 2020

One of the most controversial Jesuit cardinals was Johann Eberhard Nithard, not only because of the intriguing circumstances of his promotion, but also because he was a favorite of Queen Mariana of Austria, regent of Spain and mother of King Charles ii. The aim of this essay is to examine a series of events in Nithard’s life, focusing in particular on the details surrounding his consecration as bishop and creation as cardinal. This task is performed through an analysis of various sources, many of which—including the Jesuit ones—have been responsible for forging Nithard’s black legend, which resulted in his eventual expulsion from Spain and in distorted narratives of historians of Nithard’s role in the church and state politics in the seventeenth century.
A new outstanding species and a new section of Dalea (Fabaceae: Papilionoideae) from central Mexico

Authors: CASTILLÓN EDUARDO ESTRADA , MARTÍNEZ-RAMÍREZ JULIO , MARES-GUERRERO ANDRÉS ALEJANDRO , OCAMPO GILBERTO
Published: July 2020

We describe and illustrate Dalea rubriflora A.E. Estrada, J. Martínez-Ramírez, A. Mares & Ocampo as a new species from central Mexico. According to the morphology of its flower, this new species is included in a new section within subgenus Parosela because the shape of its keel, the innermost petals (which make the flower valvate) coherent along their external (dorsal) outer margins. However, this new species and new section have striking differences with the rest of the previously described taxa of subgenus Parosela, highlighting 1) the persistent red color of the flowers, not found in any section and species of Dalea, 2) the stamens are joined in a very long staminal column which are protruded from the keel petals for almost a third of its length, and 3) the blades of the epistemonous petals are not auriculated, instead, are truncated in the keel and absent in the wings. These main features, associated with more particular characteristics of other sections, allow us to recognize Rubriflorae as a new section and Dalea rubriflora as a new species into the subgenus Parosela.
First zoeal stage of the snapping shrimps Alpheus formosus Gibbes, 1850 and Alpheus malleator Dana, 1852 (Caridea: Alpheidae), with new characters to the genus
Authors: PASINATTO KARMINE , MANTELATTO FERNANDO L. , TEROSSI MARIANA
Published: July 2020

The first zoeae of Alpheus formosus Gibbes, 1850 and Alpheus malleator Dana, 1852 are described and illustrated for the first time, based on laboratory-hatched larvae from parental females sampled in Vitória Island, Ubatuba, Brazil. Both species shared many characters with other species of genus Alpheus Fabricius, 1798, but they also have some exclusive characters as 10 setae on the basis of the maxilla, first maxilliped with endopod 2-segmented and exopod 4-segmented, second maxilliped with exopod 4-segmented, presence of bud only of the first pereopod, presence of anal spine and simple dorsal setae on the pleon. The zoea I of both species, nevertheless, can be separated by segmentation in the exopod of the antenna (8 in A. formosus, 6 in A. malleator); segmentation in the endopod and exopod of the third maxilliped (5 in A. formosus and 4 in A. malleator); peduncle of antennule 3-segmented in A. formosus (unsegmented or 2-segmented in other species) and presence of a medial tubercle in the proximal segment in the exopod of the antenna of A. malleator (absent in A. formosus, not reported in all other species). In this study three new characters are proposed to be analyzed in zoea of the genus Alpheus: presence of anal spine in both species (absent in Alpheus saxidomus Holthuis, 1980, but not reported in other species) and for the first time reported, presence of a tubercle in the exopod of the antenna (present only in A. malleator) and presence of simple dorsal setae on the pleon (both species), here analyzed under light and scanning electron microscopy.
Three new cave species of the subgenus Tachycines (Gymnaeta) (Orthoptera: Rhaphidophoridae: Aemodogryllinae) from northern Guizhou, China
Authors: FENG XUELI , HUANG SHIHUI , LUO CHANGQING
Published: July 2020

Some species of the subgenus Tachycines (Gymnaeta) are cavernicolous. In this paper, three new species of this subgenus, namely Tachycines (Gymnaeta) zaoshu sp. nov., Tachycines (Gymnaeta) shuangcha sp. nov., and Tachycines (Gymnaeta) tongrenus sp. nov., from karst caves in Guizhou Province, China are described. The results of this study expand our knowledge of the geographical distribution of the cave species of the subgenus Tachycines (Gymnaeta) in China. The morphological photographs of the three new cave species are provided.
Depression Classification Model Based on Emotionally Related Eye-Movement Data and Kernel Extreme Learning Machine
Authors: Lu Shengfu , Liu Sa , Li Mi , Shi Xin , Li Richeng
Published: July 2020

The paper constructed a depression classification model based on emotionally related eye-movement data and kernel extreme learn machine (ELM). In order to improve the classification ability of the model, we use particle swarm optimization (PSO) to optimize the model parameters (regularization
coefficient C and the parameter σ in the kernel function). At the same time, in order to avoid to be caught in the local optimum and improve PSO's searching ability, we use improved chaotic PSO optimization algorithm and Gauss mutation strategy to increase PSO's particle
diversity. The classification results show that the accuracy, sensitivity and specificity of classification models without parameter optimization and Gauss mutation strategy are 80.23%, 80.31% and 79.43%, respectively, while those results of classification model using improved chaotic projection
model and Gauss mutation strategy are improved to 88.55%, 87.71% and 89.42%, respectively. Compared with other classification methods of depression, the proposed classification method has better performance on depression recognition.
Determining the Correct Number of Clusters in the CT Image Segmentation
Authors: Li Qi , Yue Shihong , Ding Mingliang , Li Jia , Wang Zeying
Published: July 2020

Clustering algorithm plays an essential role in CT image segmentation, and cluster validity index is an essential component in clustering analysis. There are a lot of validity indices used for assessing clustering results, that is, determine the optimal cluster number. But the existing
validity indices are often ineffective for the datasets with irregular-shaped clusters and corrupted by noise. This study aims to define a novel validity index which cannot be affected by the shapes of clusters and corrupted by noise of the investigated datasets. Chain-based distance different
from original Euclidean distance is defined first, then by a multidimensional scaling (MDS) transformation, all points are mapped into a new data space. After evaluation of compactness and separation twice in datasets, a novel validity index is proposed. A lot of synthetic datasets and several
typical CT images were used for validating the proposed validity index. Experimental results validate the proposed index and this index is applicable to the datasets with arbitrary-shaped clusters and corrupted by noise, which is helpful in clustering analysis and computer-aided detection
system.