bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin-8 in Hyperlipidemia and Coronary Heart Disease in Thai Patients Taking Statin Cholesterol-Lowering Medication While Undergoing Coronary Artery Bypass Grafting Treatment
Authors: Dechkhajorn Wilanee , Maneerat Yaowapa , Prasongsukarn Kriengchai , Kanchanaphum Panan , Kumsiri Ratchanok
Published: June 2020

The role of interleukin-8 (IL-8), a pivotal chemokine in atherogenesis and coronary heart disease (CHD) development, is diverse and remains unclear. This cross-sectional study investigates the association of the IL-8 expression in hyperlipidemia (H) and CHD patients who have been treated with statin cholesterol-lowering drugs while undergoing coronary artery bypass grafting treatment. Fifty-five Thai volunteers including 13 normal (N), 24 H, and 18 CHD patients were enrolled for the investigation. All the CHD patients had been treated continuously with statin cholesterol-lowering medications since the disease was diagnosed and were undergoing coronary bypass grafting approximately one month later. Therefore, the CHD group was representative of a pathogenesis improvement in CHD. The IL8 mRNA expression was determined by real-time quantitative PCR in the peripheral blood mononuclear cells from heparinized blood. The plasma IL-8 levels were assessed by enzyme-linked immunosorbent assay. The result shows that the IL8 mRNA expression in the H group tended to increase; however, in the CHD group, there was a significant decrease (p=0.0111) compared to the N group. The IL8 mRNA expression and the plasma levels in the CHD group were significantly lower than those in the H group (p<0.05). A significant negative correlation between the IL8 mRNA (r = −0.499) or plasma IL-8 (r = −0.3875) expression and CHD progression was observed (p<0.05). In conclusion, the transcriptomic and the phenotypic IL-8 expression decreased significantly in the Thai CHD patients who had continuously received statin-group medications compared to the H and N group participants. Therefore, IL-8 should serve as a feasible marker and could be used to evaluate the therapeutic effects of statins and illustrate the pathology of CHD treatment.
Impact of Clinical Factors on Generic and Disease-Specific Quality of Life in COPD and Asthma-COPD Overlap with Exacerbations
Authors: Lázár Zsófia , Horváth Alpár , Tomisa Gábor , Tamási Lilla , Müller Veronika
Published: June 2020

Purpose. The health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) is worsened by frequent exacerbations, and it can be affected by the concomitant presence of bronchial asthma (asthma-COPD overlap (ACO)). The impacts of clinical factors associated with HRQL have not been compared in patients with COPD and ACO experiencing exacerbations. Patients and Methods. Patients with COPD (N =705) and ACO (N =148) belonging to C and D groups according to GOLD 2017 were recruited in stable condition. Demographic and clinical data were collected, spirometry was performed, and patients rated the intensity of respiratory symptoms during the previous week. The COPD Assessment Test (CAT) and the EQ-5D 3 level version (dimensions and visual analogue scale (VAS)) were used to assess disease-specific and generic HRQL, respectively. Fisher’s exact test, χ2 test, ANOVA, and Pearson correlation were used for analysis (mean±SD). Multiple linear regression was applied to identify variables related to CAT and EQ-5D VAS scores. Results. The CAT and EQ-5D VAS scores showed similarly low HRQL in COPD and ACO (20.7±6.7 vs. 21.1±6.3 (p=0.52) and 56.2±17.8 vs. 53.7±18.2 (p=0.11)). There was a weak correlation between CAT and EQ-5D VAS scores (COPD: r=−0.345, p<0.001; ACO: r=−0.245, p=0.003). More patients with COPD had problems related to anxiety/depression in EQ-5D (63.7% vs. 55.4%, p=0.06). Pack-years exerted a negative effect on HRQL measures both in ACO and COPD. Low HRQL in COPD was associated with female gender, dyspnea, cough, gastroesophageal reflux disease, and arrhythmia, while in ACO, it was related to arrhythmia, hypertension, and cough, but less to dyspnea. Conclusions. Patients with COPD and ACO experiencing exacerbations have low quality of life, which is influenced by smoking history, symptoms, and comorbidities. These findings have important implications for the development of therapeutic strategies to improve the health status of patients with these conditions.
Periorbital Silicone Granulomatosis 30 Years after Acupuncture
Authors: Pirakitikulr Nathan , Tran Ann Q. , Garcia Armando L. , Dubovy Sander R. , Lee Wendy W.
Published: June 2020

Silicone-based compounds are commonly used in many medical applications, such as coatings for needles and syringes. Foreign body granulomas are a well-recognized complication of silicone exposure; however, they may be challenging to identify without a clear history. A 61-year-old female patient without prior history of periocular injections, filler, or surgery presented to our oculoplastic clinic with multiple periocular lesions. The patient subsequently underwent excisional biopsy of two prominent lesions, which were identified as granulomas on pathology. Further questioning revealed the cause to be facial acupuncture performed decades prior, and a subsequent targeted exam identified additional lesions at other needling sites. A third lesion was subsequently excised, and there was no recurrence at the last follow-up 3 months postsurgery. Acupuncture is an increasingly common but underrecognized source of silicone exposure and can present up to several decades after exposure as a chronic granulomatous response in a characteristic multifocal pattern.
UPLC-ESI-MS/MS Profile and Antioxidant, Cytotoxic, Antidiabetic, and Antiobesity Activities of the Aqueous Extracts of Three Different Hibiscus Species
Authors: Al-Yousef Hanan M. , Hassan Wafaa H. B. , Abdelaziz Sahar , Amina Musarat , Adel Rasha , El-Sayed May A.
Published: June 2020

The aqueous extracts of Hibiscus calyphyllus (HcA), Hibiscus micranthus (HmA), and Hibiscus deflersii (HdA) growing in Saudi Arabia did not receive enough attention in phytochemical and biological studies. This inspired the authors to investigate the phytochemicals of these extracts for the first time using UPLC-ESI-MS/MS in negative and positive ionization modes. The analysis afforded the tentative identification of 103 compounds including phenolic compounds, flavonoids, and anthocyanins. Moreover, in vitro evaluations of their cytotoxic, antioxidant, antidiabetic, and antiobesity activities were carried out. The results showed that aqueous extract of Hibiscus calyphyllus had the highest activity as an antioxidant agent (SC50 = 111 ± 1.5 μg/mL) compared with ascorbic acid (SC50 = 14.2 ± 0.5 μg/mL). MTT assay was used to evaluate cytotoxic activity compared to cisplatin. Hibiscus deflersii showed the most potent cytotoxic effect against A-549 (human lung carcinoma) with IC50 = 50 ± 5.1 μg/mL, and Hibiscus micranthus showed a close effect with IC50 = 60.4 ± 1.7 μg/mL. Hibiscus micranthus showed the most potent effect on HCT-116 (human colon carcinoma) with IC50 = 56 ± 1.9 μg/mL compared with cisplatin (IC50 = 7.53 ± 3.8 μg/mL). HcA and HdA extracts showed weak cytotoxic activity against A-549 and HCT-116 cell lines compared to the other extracts. Eventually, Hibiscus deflersii showed astonishing antidiabetic (IC50 = 56 ± 1.9 μg/mL) and antiobesity (IC50 = 95.45 ± 1.9 μg/mL) activities using in vitro α-amylase inhibitory assay (compared with acarbose (IC50 = 34.71 ± 0.7 μg/mL)) and pancreatic lipase inhibitory assay (compared with orlistat (IC50 = 23.8 ± 0.7 μg/mL)), respectively. In conclusion, these findings are regarded as the first vision of the phytochemical constituents and biological activities of different Hibiscus aqueous extracts. Hibiscus deflersii aqueous extract might be a hopeful origin of functional constituents with anticancer (on A-549 cell line), antidiabetic, and antiobesity activities. It might be a natural alternative remedy and nutritional policy for diabetes and obesity treatment without negative side effects. Isolation of the bioactive phytochemicals from the aqueous extracts of aerial parts of Hibiscus calyphyllus, Hibiscus micranthus, and Hibiscus deflersii and estimation of their biological effects are recommended in further studies.
Neurosarcoidosis Presentation as Adipsic Diabetes Insipidus Secondary to a Pituitary Stalk Lesion and Association with Anti-NMDA Receptor Antibodies
Authors: Solis Jose Gabriel , Olascoaga Lugo Arturo , Rodríguez Florido Marco Antonio , Sandoval Bonilla Bayron Alexander , Malagón Rangel Jose
Published: June 2020

Sarcoidosis is a multisystemic inflammatory disease of unknown cause. It is characterized by the presence of noncaseating granuloma on a biopsy specimen. Clinical presentation varies across case report series with myriad of symptoms ranging from fever, respiratory symptoms, and skin lesions, or atypical symptoms like heart block or neurological symptoms. Hence, we report the case of a 22-year-old woman with encephalitis, a pituitary mass, and adipsic diabetes insipidus. The diagnostic approach did not end on the biopsy of the lesion, which reported noncaseating granulomas; on the contrary, it was the beginning of a path to exclude other causes of the central nervous system granulomas that ended with the diagnosis of the isolated central nervous system sarcoidosis. Also, we report the first proven association between anti-NMDA receptor antibodies and sarcoidosis.
Decreased Peripheral Blood ALKBH5 Correlates with Markers of Autoimmune Response in Systemic Lupus Erythematosus
Authors: Luo Qing , Fu Biqi , Zhang Lu , Guo Yang , Huang Zikun , Li Junming
Published: June 2020

Although it has been proved that the epigenetic modification of DNA and histones is involved in the pathogenesis of systemic lupus erythematosus (SLE), there is no study to explore whether the modification of N6-methyladenosine (m6A) in RNA is involved. In this study, the mRNA levels of m6A “writers” (METTL3, MTEEL14, and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results demonstrated that the mRNA levels of METTL3, WTAP, FTO, ALKBH5, and YTHDF2 in peripheral blood from SLE patients were significantly decreased. The levels of ALKBH5 mRNA in SLE patients were associated with anti-dsDNA, antinucleosome, rash, and ulceration. Multivariate logistic regression analysis showed that the level of ALKBH5 mRNA in peripheral blood is a risk factor of SLE (P<0.001). Moreover, our results suggested that there was a positive correlation between m6A“writers” (METTL3 and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in SLE patients. This study suggests that the mRNA level of ALKBH5 in peripheral blood may be involved in the pathogenesis of SLE.
Effect of Water-Decked Blasting on Rock Fragmentation Energy
Authors: Xia Wenjun , Lu Wenbo , Li Ruize , Chen Ming , Lei Zhen
Published: June 2020

Fragmentation energy ratio is an important index to evaluate whether an explosive is used efficiently. This paper discusses the effect of water-decked blasting on fragmentation energy based on theory and numerical simulation, and three blasting tests were performed to measure the actual fragmentation energy at a granite-based field. Results show that at the same charge amount, the maximum borehole pressure of water-decked blasting is much greater than that of normal blasting in theory, which facilitates rock breaking. In numerical simulation, water-decked blasting is more beneficial to the transmission of explosive energy; therefore, the damage distribution is more uniform and the damage level is higher. The specific surface area and fragment size distribution were obtained by three-dimensional laser scanning and image analysis in field tests; therefore, the fragmentation energy could be measured, which showed that the fragmentation energy could be increased by 10% in water-decked blasting. In addition, water-decked blasting can reduce fly rocks and ensure the safety of rock blasting.
Allometric Modelling of the Stem Carbon Content ofRhizophora mucronatain a Tropical Mangrove Ecosystem
Authors: Nilmini Wijeyaratne W. M. Dimuthu , Liyanage Pawani Madhushani
Published: June 2020

Mangrove ecosystems are identified as important blue carbon ecosystems because they play an important role in carbon sequestration among the coastal ecosystems. The present study was conducted to develop an allometric model to determine the stem carbon content ofRhizophora mucronatain a conserved tropical mangrove ecosystem. The stepwise regression with backward elimination was used to identify the best fit model to predict the stem carbon content ofRhizophora mucronata. The allometric equation, LnC = −2.403 + 2.247 Ln DBH, whereC: stem carbon content and DBH: diameter at breast height, was constructed to be evaluated and validated as the most suitable and practically applicable model. The reliability of the model was 76.7%, and the model was significant at 95% level of significance. The model bias values and the model efficiency values for the best fit model suggested that the model is suitable to be used practically. The present study used a nondestructive method of measuring individual tree parameters to develop this allometric equation to predict the stem carbon content and it is considered as an environmentally friendly approach with minimum damage to the tree.
GBDT-Based Fall Detection with Comprehensive Data from Posture Sensor and Human Skeleton Extraction
Authors: Cai Wen-Yu , Guo Jia-Hao , Zhang Mei-Yan , Ruan Zhi-Xiang , Zheng Xue-Chen , Lv Shuai-Shuai
Published: June 2020

Since fall is happening with increasing frequency, it has been a major public health problem in an aging society. There are considerable demands to distinguish fall down events of seniors with the characteristics of accurate detection and real-time alarm. However, some daily activities are erroneously signaled as falls and there are too many false alarms in actual application. In order to resolve this problem, this paper designs and implements a comprehensive fall detection framework on the basis of inertial posture sensors and surveillance cameras. In the proposed system framework, data sources representing behavior characteristics to indicate potential fall are derived from wearable triaxial accelerometers and monitoring videos of surveillance cameras. Moreover, the NB-IoT based communication mode is adopted to transmit wearable sensory data to the Internet for subsequent analysis. Furthermore, a Gradient Boosting Decision Tree (GBDT) classifier-based fall detection algorithm (GBDT-FD in short) with comprehensive data fusion of posture sensor and human video skeleton is proposed to improve detection accuracy. Experimental results verify the good performance of the proposed GBDT-FD algorithm compared to six kinds of existing fall detection algorithms, including SVM-based fall detection, NN-based fall detection, etc. Finally, we implement the proposed integrated systems including wearable posture sensors and monitoring software on the Cloud Server.
Chitosan-S-triazinyl-bis(2-aminomethylpyridine) and Chitosan-S-triazinyl-bis(8-oxyquinoline) Derivatives: New Reagents for Silver Nanoparticle Preparation and Their Effect of Antimicrobial Evaluation
Authors: Al-Rasheed Hessa H. , Dahlous Kholood A. , Sholkamy Essam N. , Osman Sameh M. , Abd-Elkader Omar H. , El-Faham Ayman
Published: June 2020

Herein, we described the modification of chitosan with cyanuric chloride as a mediator for preparation of chitosan-s-triazinyl-bis(2-aminomethylpyridine) and chitosan-s-triazinyl-bis(8-oxyquinoline) derivatives to be used as reagents for preparation of silver nanoparticles under ecofriendly conditions. These two reagents are convenient and effective for reduction of silver ions to silver nanoparticles with particle size less than 10 nm that might be suitable for industrial and medicinal applications. The formation and particle size of AgNPs are characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray analysis (EDX). The antimicrobial activity of the two modified chitosan-s-triazine-AgNPs was evaluated against activities against Gram-positive bacteria (M. luteus ATCC 10240 and MRSA ATCC 43300), Gram-negative bacteria (E. coli ATCC 25922 and P. aeruginosa ATCC 75853), and C. albicans. The results showed that chitosan-s-triazinyl-bis(2-aminomethylpyridine) AgNPs showed high antimicrobial activities against all the tested microorganisms, while their analogous chitosan-s-triazinyl-bis(8-oxyquinoline) AgNPs showed moderate activities.
Clinical Significance of Circulating Tumor Cells in Hormone Receptor–positive Metastatic Breast Cancer Patients who Received Letrozole with or Without Bevacizumab
Authors: Magbanua Mark Jesus M. , Savenkov Oleksandr , Asmus Erik J. , Ballman Karla V. , Scott Janet H. , Park John W. , Dickler Maura , Partridge Ann , Carey Lisa A. , Winer Eric P. , Rugo Hope S.
Published: June 2020

Purpose:

We evaluated the prognostic and predictive value of circulating tumor cells (CTCs) hormone receptor–positive (HR+) metastatic breast cancer (MBC) patients randomized to letrozole alone or letrozole plus bevacizumab in the first-line setting (CALGB 40503).

Experimental Design:

Blood samples were collected at pretreatment and three additional time points during therapy. The presence of ≥5 CTCs per 7.5 mL of blood was considered CTC positive. Association of CTCs with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models.

Results:

Of 343 patients treated, 294 had CTC data and were included in this analysis. Median follow-up was 39 months. In multivariable analysis, CTC-positive patients at baseline (31%) had significantly reduced PFS [HR, 1.49; 95% confidence interval (CI), 1.12–1.97] and OS (HR, 2.08; 95% CI, 1.49–2.93) compared with CTC negative. Failure to clear CTCs during treatment was associated with significantly increased risk of progression (HR, 2.2; 95% CI, 1.58–3.07) and death (HR, 3.4; 95% CI, 2.36–4.88). CTC-positive patients who received only letrozole had the worse PFS (HR, 2.3; 95% CI, 1.54–3.47) and OS (HR, 2.6; 95% CI, 1.59–4.40). Median PFS in CTC-positive patients was significantly longer (18.0 vs. 7.0 months) in letrozole plus bevacizumab versus letrozole arm (P = 0.0009). Restricted mean survival time analysis further revealed that addition of bevacizumab was associated with PFS benefit in both CTC-positive and CTC-negative patients, but OS benefit was only observed in CTC-positive patients.

Conclusions:

CTCs were highly prognostic for the addition of bevacizumab to first-line letrozole in patients with HR+ MBC in CALGB 40503. Further research to determine the potential predictive value of CTCs in this setting is warranted.
Elevated V–ATPase Activity Following PTEN Loss Is Required for Enhanced Oncogenic Signaling in Breast Cancer
Authors: Mohammad Amro H. , Kim Sung-Hoon , Bertos Nicholas , El-Assaad Wissal , Nandi Ipshita , Smith Harvey , Yang Jieyi , Chen Owen J. , Gamache Isabelle , Rao Trisha , Gagnon Bruno , Gruosso Tina , Tremblay Michel L. , Sonenberg Nahum , Guiot Marie-Christine , Muller William , Park Morag , Teodoro Jose G.
Published: June 2020

PTEN loss-of-function contributes to hyperactivation of the PI3K pathway and to drug resistance in breast cancer. Unchecked PI3K pathway signaling increases activation of the mechanistic target of rapamycin complex 1 (mTORC1), which promotes tumorigenicity. Several studies have suggested that vacuolar (H+)–ATPase (V–ATPase) complex activity is regulated by PI3K signaling. In this study, we showed that loss of PTEN elevated V–ATPase activity. Enhanced V–ATPase activity was mediated by increased expression of the ATPase H+ transporting accessory protein 2 (ATP6AP2), also known as the prorenin receptor (PRR). PRR is cleaved into a secreted extracellular fragment (sPRR) and an intracellular fragment (M8.9) that remains associated with the V–ATPase complex. Reduced PTEN expression increased V–ATPase complex activity in a PRR-dependent manner. Breast cancer cell lines with reduced PTEN expression demonstrated increased PRR expression. Similarly, PRR expression became elevated upon PTEN deletion in a mouse model of breast cancer. Interestingly, concentration of sPRR was elevated in the plasma of patients with breast cancer and correlated with tumor burden in HER2-enriched cancers. Moreover, PRR was essential for proper HER2 receptor expression, localization, and signaling. PRR knockdown attenuated HER2 signaling and resulted in reduced Akt and ERK 1/2 phosphorylation, and in lower mTORC1 activity. Overall, our study demonstrates a mechanism by which PTEN loss in breast cancer can potentiate multiple signaling pathways through upregulation of the V–ATPase complex.

Implications:

Our study contributed to the understanding of the role of the V–ATPase complex in breast cancer cell tumorigenesis and provided a potential biomarker in breast cancer.
MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction
Authors: Morales-Roselló José , García-Giménez José Luis , Martinez Priego Llucia , González-Rodríguez Daymé , Mena-Mollá Salvador , Maquieira Catalá Angel , Loscalzo Gabriela , Buongiorno Silvia , Jakaite Vaidile , Cañada Martínez Antonio José , Perales Marín Alfredo
Published: June 2020

Objective: It was the aim of this study to describe a micro­RNA (miRNA) profile characteristic of late-onset fetal growth restriction (FGR) and to investigate the pathways involved in their biochemical action. Methods: In this prospective study, 25 fetuses (16 normal and 9 with FGR [estimated fetal weight <10th centile plus cerebroplacental ratio <0.6765 multiples of the median]) were evaluated with Doppler ultrasound after 36 weeks. Afterwards, for every fetus, plasma from umbilical vein blood was collected at birth, miRNA was extracted, and full miRNA sequencing was performed. Subsequently, comparisons were done in order to obtain those miRNAs that were differentially expressed. Results: The FGR fetuses expressed upregulation of two miRNAs: miR-25-3p and, especially, miR-148b-3p, a miRNA directly involved in Schwann cell migration, neuronal plasticity, and energy metabolism (p = 0.0072, p = 0.0013). Conclusions: FGR fetuses express a different miRNA profile, which includes overexpression of miR-25-3p and miR-148b-3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose miRNAs as a valid tool in the diagnosis and management of FGR.
High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)
Authors: Strand Keith A. , Lu Sizhao , Mutryn Marie F. , Li Linfeng , Zhou Qiong , Enyart Blake T. , Jolly Austin J. , Dubner Allison M. , Moulton Karen S. , Nemenoff Raphael A. , Koch Keith A. , LaBarbera Daniel V. , Weiser-Evans Mary C.M.
Published: June 2020

Objective:

Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease.

Approach and Results:

To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation.

Conclusions:

Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.
Comparison of Outcome Adjudication by Investigators and by a Central End Point Committee in Heart Failure Trials
Authors: Tyl Benoît , Lopez Sendon José , Borer Jeffrey S. , Lopez De Sa Esteban , Lerebours Guy , Varin Claire , De Montigny Aurélie , Pannaux Matthieu , Komajda Michel
Published: June 2020

Background:

The usefulness of adjudication by central end point committees (CECs) is poorly assessed in heart failure (HF) trials. We aimed to assess its impact on the outcome of the SHIFT trial (Systolic HF Treatment With the If Inhibitor Ivabradine Trial).

Methods:

SHIFT was a randomized placebo-controlled trial investigating the effect of ivabradine in 6505 HF patients with reduced ejection fraction. Prespecified end points, reported by investigators (all cardiologists) using specific case report form pages, included all-cause and specific causes of deaths and hospitalizations. The primary end point was a composite of cardiovascular deaths or hospitalizations for worsening HF. We compared the adjudication of prespecified end points made by investigators and by the CEC.

Results:

Investigators identified 7529 prespecified end points, 6793 of which were confirmed by the CEC: 98.1% of cardiovascular deaths, 88.6% of all hospitalizations, and 84.4% of hospitalizations for worsening HF. These differences had no meaningful impact on the study results; hazard ratio for the primary composite end point: investigators, 0.83 (95% CI, 0.76–0.91) versus CEC, 0.82 (95% CI, 0.75–0.90), with similar results for each component of the primary end point (hazard ratio of 0.92 versus 0.91 for cardiovascular death and 0.78 versus 0.74 for hospitalization for worsening HF).

Conclusions:

Central adjudication by a CEC in the SHIFT study confirmed most of cardiovascular deaths and worsening HF hospitalizations assessed by cardiologists and did not result in a significant change of the final result as compared to investigator judgment. In this context, the benefits of CEC in blinded HF trials should be reconsidered.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02441218. URL:
http://www.isrctn.com/ISRCTN70429960
; Unique identifier: ISRCTN70429960.
Elevated Angiotensin 1–7/Angiotensin II Ratio Predicts Favorable Outcomes in Patients With Heart Failure
Authors: Wang Kaiming , Basu Ratnadeep , Poglitsch Marko , Bakal Jeffrey A. , Oudit Gavin Y.
Published: June 2020

Background:

ACE2 (angiotensin-converting enzyme 2) and Ang 1–7 (angiotensin 1–7) are endogenous negative regulators of the renin-angiotensin system exerting cardioprotective effects in models of heart failure. Recombinant human ACE2 markedly increased plasma Ang 1–7 and lowered Ang II levels in phase II clinical trials. We hypothesize that the dynamic state of this renin-angiotensin system protective arm could influence long-term outcomes in patients with heart failure.

Methods:

One hundred ten patients with heart failure were prospectively enrolled from our outpatient clinic and the emergency department. Comprehensive circulating and equilibrium levels of plasma angiotensin peptide profiles were assessed using novel liquid chromatography-mass spectrometry/mass spectroscopy techniques. Plasma aldosterone, B-type natriuretic peptide, active renin concentration, and clinical profiles were captured at baseline. During a median follow-up of 5.1 years (interquartile range, 4.7–5.7 years), composite clinical outcomes were assessed using all-cause in-patient hospitalizations and mortality.

Results:

Circulating and equilibrium angiotensin peptide levels strongly correlated in our patient cohort. Adjusting for covariates, elevated equilibrium (hazard ratio, 0.38 [95% CI, 0.18–0.81]
P
=0.012), and circulating (hazard ratio, 0.38 [95% CI, 0.18–0.80]
P
=0.011) Ang 1–7/Ang II ratios were associated with improved survival. Lower hospitalization duration was also associated with elevated equilibrium (
P
<0.001) and circulating (
P
=0.023) Ang 1–7/Ang II ratios. Importantly, individual Ang 1–7 and Ang II peptide levels failed to predict all-cause mortality or hospitalization duration in our patient cohort.

Conclusions:

We extensively profiled plasma angiotensin peptides in patients with heart failure and identified elevated Ang 1–7/Ang II ratio, as an independent and incremental predictor of beneficial outcomes, higher survival rate, and decreased hospitalization duration. These findings provide important clinical evidence supporting strategies aiming to promote the beneficial Ang 1–7/Mas axis concurrent with renin-angiotensin system blockade therapies inhibiting the detrimental Ang II/AT
1
receptor axis.
An Introduction to Nicos Hadjinicolaou's “Art Centers and Peripheral Art” (1982)
Authors: Smith Terry
Published: June 2020

Change in the history of art has many causes, but one often overlooked by art historical institutions is the complex, unequal set of relationships that subsist between art centers and peripheries. These take many forms, from powerful penetration of peripheral art by the subjects, styles and modes of the relevant center, through accommodation to this penetration to various degrees and kinds of resistance to it. Mapping these relationships should be a major task for art historians, especially those committed to tracing the reception of works of art and the dissemination of ideas about art. This lecture, delivered by Nicos Hadjinicolaou in 1982, outlines a “political art geography” approach to these challenges, and demonstrates it by exploring four settings: the commissioning of paintings commemorating key battles during the Greek War of Independence; the changes in Diego Rivera's style on his return to Mexico from Paris in the 1920s; the impact on certain Mexican artists in the 1960s of “hard edge” painting from the United States; and the differences between Socialist Realism in Moscow and in the Soviet Republics of Asia during the mid-twentieth century. The lecture is here translated into English for the first time and is introduced by Terry Smith, who relates it to its author's long-term art historical quest, as previously pursued in his book Art History and Class Struggle (1973).
Józef Nowacki as a Theoretician of Normativism in Poland
Authors: Tkacz Sławomir
Published: June 2020

The present paper aims to present an outline of the views of the Polish legal theorist Józef Nowacki (1923–2005). The claim put forward is that Nowacki was the chief representative of Hans Kelsen’s normativism in Polish legal theory. The paper begins with a short historical sketch presenting the reception of Hans Kelsen’s views in Polish jurisprudence, noting that in the post-war period the communist authorities believed that normativism was at odds with the then prevailing system of actually existing socialism. Drawing inspiration from German-speaking authors, Nowacki rejected the ideology prevailing in Poland at that time and became a staunch advocate of the normativist stance, in particular with regard to the theory of the legal system. The second part of the paper discusses Nowacki’s views regarding the concept of the rule of law, and the third and last part presents Nowacki’s critique of the case-law of the Polish Constitutional Court.
L’iconographie et le statut de femmes sur les bas-reliefs sassanides (224-651 apr. J.-C.)
Authors: Sangari Esmaeil
Published: June 2020

So far, more than forty Sasanian bas-reliefs have been discovered in numerous archaeological sites. Among them, eleven bas-reliefs in seven archaeological sites represent women on them. In this article, the eleven bas-reliefs and the women’s images and their characteristics in different scenes have been analyzed and studied. It can be concluded that women on these bas-reliefs have been represented in the social-cultural fields, such as in the royal family or as goddesses, musicians, etc. Most of the female characters on the bas-reliefs belong to the upper classes of the Iranian society.
A Matter of Metals: Finno-Ugric and Northern Iranian
Authors: Ognibene Paolo
Published: June 2020

Vsevolod Miller in the third part of his Ossetic Studies considered the names of the metals both in Iron and Digoron, with particular reference to those of Finno-Ugric origin, in order to determine the way followed by the Alans to reach the Northern Caucasus in the first century A.D. In this paper Miller's theory is examined in the light of the historical linguistic data currently available.
Mission, Reunion and the Anglican Communion: The ‘Appeal to All Christian People’ and approaches to ecclesial unity at the 1920 Lambeth Conference
Authors: Methuen Charlotte
Published: June 2020

This article explores the understanding of unity articulated in the ‘Appeal to all Christian People’ issued by the 1920 Lambeth Conference of Anglican bishops. It first examines the expression of the Appeal’s vision in terms of organic unity and mutual recognition, the way that this developed through the drafting process and how this vision related to later Anglican approaches to unity. It then explores the relationship of the Appeal to the Lambeth Quadrilateral of 1888, particularly with respect to the episcopate, arguing that the Appeal took an ambiguous approach to episcopacy which was in tension with the language of mutual recognition. Finally, acknowledging that the overarching theme of the 1920 Lambeth Conference was ‘fellowship’, the article considers the Appeal’s vision of unity in the context of the approach to unity taken by the 1920 Lambeth Conference more widely, including the Conference’s other ecumenical resolutions, and its resolutions on mission and the Anglican Communion and the bishops’ Encyclical Letter, particularly its approach to international relations. The article concludes that, while the vision of organic unity that was articulated in the Appeal was reflected in the conference’s resolutions on mission, in other aspects of its work the 1920 Lambeth Conference tended to take a federal approach to unity and fellowship and was thus not fully consistent.
Special Issue: UNCITRAL and Investment Arbitration Reform: Matching Concerns and Solutions
Authors: Langford Malcolm , Potestà Michele , Kaufmann-Kohler Gabrielle , Behn Daniel
Published: June 2020

The ongoing ‘legitimacy crisis’ in investor-State dispute settlement (ISDS) has triggered a comprehensive attempt at multilateral reform. In 2017, Working Group III at the United Nations Commission on International Trade Law (UNCITRAL) was entrusted with a broad, open-ended and problem-driven mandate. The reform process aims to tackle particular concerns with ISDS: excessive costs and lengthy proceedings, inconsistent and incorrect decisions, and a lack of arbitral diversity and independence. The exclusion of substantive treaty reform has met critique but states are considering a wide range of procedural options from incremental reform to a multilateral court, appellate mechanism, and ISDS alternatives. In this article, we introduce the reform process and the seven articles that follow in this Special Issue of the Journal on World and Investment and Trade. In these contributions, ISDS Academic Forum members analyse the basis for each concern and the potential contribution of leading reform models.
Empirical Perspectives on Investment Arbitration: What Do We Know? Does It Matter?
Authors: Behn Daniel , Langford Malcolm , Létourneau-Tremblay Laura
Published: June 2020

Due to the problem-centric nature of its mandate, empirical research has been relatively central in the United Nations Commission on International Trade Law (UNCITRAL) investment arbitration reform process. In this article, the authors seek to provide a state-of-the-art summary and assessment of empirical studies on the six identified concerns of states: legal cost, duration of proceedings, consistency, correctness, diversity and independence. The article asks: (1) What do we know? and (2) Does it matter? The survey of evidence reveals an emerging base of quantitative, qualitative and computational evidence for justifying some but not all concerns and understanding their causes. However, there are challenges in accessing all relevant data, modelling outcomes and evaluating whether there was normatively a problem. The article concludes by indicating that some concerns are clearly justified, others not, and others fall within an unknown category.
Makosa Ya Kisarufi Katika Makala Andishi Za Habari: Uchunguzi Kifani Wa BBC Swahili Na DW Kiswahili
Authors: Mushumbwa Alcheraus R
Published: June 2020

Ikisiri

Tafiti juu ya matumizi ya lugha katika vyombo vya habari zimethibitisha kuwapo kwa makosa kadhaa ya lugha katika utoaji wa habari. Makala haya, yanamakinikia makosa ya kisarufi katika matini andishi za habari za BBC Swahili na DW Kiswahili. Sampuli ya makala kumi kutoka kila tovuti ya chombo husika zilichanganuliwa kulingana na nadharia ya Corder (1967). Makosa ya udondoshaji, uchopekaji, upatanisho wa kisarufi, umoja na wingi, mpangilio wa vipashio na mantiki yalithibitika. Sababu za kufanyika kwa makosa hayo ni pamoja na: kutomudu sarufi ya Kiswahili, kukosa umakini katika uandishi na uhariri, athari za lugha mama, lugha za kigeni, lugha ya mazungumzo, na uteuzi mbaya wa msamiati. Vilevile, ilibainika kuwa makosa hayo yana athari hasi kwa wazungumzaji wa lugha pamoja na lugha yenyewe. Hata hiyo, tafiti zaidi zinapaswa kufanywa juu ya mazingira yachocheayo uvumilivu wa makosa ya lugha katika utangazaji wa habari kwa Kiswahili.
Areas of endemism on Brazilian mountaintops revealed by taxonomically verified records of Microlicieae (Melastomataceae)

Authors: PACIFICO RICARDO , ALMEDA FRANK , FROTA AUGUSTO , FIDANZA KARINA
Published: June 2020

In this study we describe areas of endemism from Brazilian mountaintops associated with campo rupestre vegetation based on taxonomically verified records of Microlicieae (Melastomataceae). To test the relevance of taxonomically vetted data, we compared these areas with those recovered using records downloaded from the Global Biodiversity Information Facility (GBIF) website. A total of 12 areas of endemism are recognized and described, of which only eight (66%) were retrieved using GBIF data. With 1º and 0.5º cells, analyses of GBIF data didn’t detect both individual and consensus areas of endemism with Endemicity scores as high as analyses of taxonomically verified data. Records based on misidentified specimens and/or incorrect coordinates affected the detection of areas of endemism using GBIF data. Our results show that taxonomically verified data may improve the efficiency of areas of endemism identification. Besides, the results suggest that the recovery of stable and continuous areas of endemism may be improved by using larger cells and adopting the loose criterion rule to merge individual areas of endemism into consensus areas. Biogeographically, the results indicate that the evolutionary histories of Chapada Diamantina, Southern Espinhaço and Brazilian Central Plateau were related to the radiation of Microlicieae, especially the genera Lavoisiera, Microlicia, and Trembleya. The expansion of areas of endemism in the Cadeia do Espinhaço was probably accelerated by climatic instability and glaciation cycles from Pliocene to Pleistocene.
A new status and combination in a Madagascan Kalanchoe, K. brevicalyx (Crassulaceae subfam. Kalanchooideae)

Authors: SMITH GIDEON F. , FIGUEIREDO ESTRELA
Published: June 2020

The proposed name at new rank ‘Kalanchoe brevicalyx’ (Raymond-Hamet & Perrier de la Bâthie 1915: 88) L.Allorge (in Boiteau & Allorge-Boiteau 1995: 133) (Crassulaceae subfam. Kalanchooideae) was not validly published as a full and direct reference to the place of valid publication of the basionym, K. pinnata var. brevicalyx Raymond-Hamet & Perrier de la Bâthie (1915: 88), with page or plate reference and date, was not clearly indicated (Turland et al. 2018: Art. 41.5). We here validly publish the new combination and status.
A new spider fly (Diptera: Acroceridae: Ogcodinae: Ogcodes Latreille) from Chiloé Island’s evergreen forest and new distributional records for other spider flies in Chile
Authors: BARAHONA-SEGOVIA RODRIGO M. , GUZMÁN VICENTE VALDÉS , BARCELÓ MATÍAS , PAÑINAO-MONSÁLVEZ LAURA
Published: June 2020

Ogcodes Latreille is the largest genus of Acroceridae. They exhibit a cosmopolitan distribution and parasitize several spider families. Eleven Neotropical species are currently recognized in the genus, with five of them occurring in Chile, though distribution data is limited in this group of rarely collected flies. In this work, we describe a new species, Ogcodes kunkunche sp. nov. Barahona-Segovia from the evergreen forest of Chiloé Island, provide an identification key to the Chilean species of Ogcodes, and include novel distributional data for other species of spider flies (Acrocerinae and Ogcodinae). Based in our results, we suggest that O. kunkunche sp. nov. must be incorporated in the porteri group, due to wing vein reduction. Morphological aspects within Ogcodes, and their evolutionary implications are discussed.
Taxonomy of the genus Cyrtopholis Simon, 1892 (Araneae, Mygalomorphae, Theraphosidae): Cuban species described by Pelegrín Franganillo Balboa
Authors: FABIANO-DA-SILVA WILLIAN , GUADANUCCI JOSÉ PAULO LEITE , GARCIA GIRALDO ALAYÓN , LUCAS SYLVIA MARLENE , DASILVA MARCIO BERNARDINO
Published: June 2020

Cyrtopholis Simon 1892 is a spider genus from the Caribbean islands characterized by the presence of stridulatory setae on trochanter of palps and legs I. Franganillo Balboa described eight species of Cyrtopholis Simon 1892 from Cuba between 1926–1936. The type-material is deposited in the Instituto de Ecología y Sistematica do Ministerio de Ciencias, Tecnologia e Meio Ambiente, La Habana, Cuba. Four species are redescribed here: Cyrtopholis plumosa Franganillo, 1931, Cyrtopholis major Franganillo, 1926, Cyrtopholis unispina Franganillo, 1926 and Cyrtopholis gibbosa Franganillo, 1936. Cyrtopholis ischnoculoformis Franganillo, 1926 is based on a juvenile specimen without stridulatory setae, and it is therefore considered here as species inquirenda. The type-material of two other species were not located: Cyrtopholis anacanta Franganillo, 1935 and Cyrtopholis obsoleta (Franganillo, 1935), and are considered to be lost. These two species are here considered as species inquirenda, since the original descriptions do not permit identification. Cyrtopholis respina Franganillo 1935 is considered a nomen dubium, due to the lack of a formal description and a doubtful citation.
Cataloguing Prof. Eudóxia M. Froehlich’s wet collection of land planarians (Platyhelminthes, Geoplanidae): a bounty of type specimens of 78 species
Authors: RANELLI BEATRIZ ELIAS , DE FREITAS PEDRO M. , CARBAYO FERNANDO
Published: June 2020

Zoologist Prof. Eudóxia Maria Froehlich (1929*–2015†) kept an uncatalogued personal collection of land planarians in wet medium. We catalogued their contents. Glass jars contained a variable number of small vials, each with one or several labeled specimens. We transcribed the species names and field data, when available, written on card labels to a table. A total of 1772 vials in 80 jars, contained over 2700 specimens. Subsequently, we cross checked field data with that of the type specimens. As a result, we identified, with different degrees of certainty, type specimens of 78 species. These types compose a very significant potential source of additional morphological details of the species to conform with current standards in the taxonomy of the group.
Taxonomy of ‘Euconnus complex’. Part XXI. Status of subgenus Microconnus Franz (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: June 2020

Microconnus Franz, previously treated as a subgenus of Euconnus Thomson, is placed as a subgenus of Napoconnus Franz. Morphological structures of all species included in Microconnus are reviewed and illustrated, and Euconnus canaimanus Franz, Euconnus conulus Franz, and Euconnus janauari O’Keefe are placed as members of Napoconnus (Microconnus), while Euconnus (Microconnus) fulgurans Franz is placed in Euconnus (incertae sedis) (near Napochus Thomson). Emended diagnosis of Napoconnus and a key to identify its subgenera are given.
Heteragrion itacolomii sp. nov. (Odonata: Zygoptera: Heteragrionidae) from Itacolomi State Park, Ouro Preto, Minas Gerais, Brazil
Authors: ÁVILA JÚNIOR WALTER F. , LENCIONI FREDERICO A. A. , CARNEIRO MARCO ANTÔNIO A.
Published: June 2020

Heteragrion itacolomii sp. nov. (♂ holotype: Brazil, Minas Gerais, Ouro Preto, Parque Estadual do Itacolomi, Trilha da Lagoa, 1350m, 23-xii-2018, 20º25’57”S, 43º30’27”W; and ♀ allotype, same data as holotype, but collected in tandem 20-iii-2019, deposited in ABMM – CCT/UFMG collection) is described and illustrated. The new species is similar to H. tiradentense Machado & Bedê, 2006, H. muryense Costa & Santos, 2000 and H. mantiqueirae Machado, 2006, based on coloration of the thorax and has cerci similar to those of H. freddiemercuryi Lencioni, 2013. It belongs to Group A and differs from other congeners by the morphology of the ventral expansion and the medial process of the cerci in males. Information about the intersternite of the single female specimen is also provided.
Two new species of the whip-spider genus Heterophrynus (Arachnida: Amblypygi) with complementary information of four species
Authors: CHIRIVI-JOYA DANIEL , MORENO-GONZÁLEZ JAIRO A. , FAGUA GIOVANNY
Published: June 2020

The family Phrynidae has been mainly recorded from America, including the Antilles, and Heterophrynus is one of its genera endemic of South America and is mainly associated with Amazonian ecosystems. Currently, the genus has 16 valid species, but many original descriptions are ambiguous or incomplete. The more complete work about this genus only includes seven of the currently valid species, and in some cases, some characters useful for the species identification, were not described. This situation hampers the species recognition and the comparison among species to propose diagnosis accurate. Using characters from the male and female genitalia to improve the diagnosis, we present complementary descriptions for four species of Heterophrynus and describe two new species. We present details of morphologic variation, compare the pedipalp spines among the species, present actualized distributions, and for first time, we present a complete illustration of the male genital of eight species using SEM pictures.
Two new Idiocera Dale from the Mediterranean (Diptera: Limoniidae)
Authors: STARÝ JAROSLAV
Published: June 2020

Two new species of Idiocera (Idiocera) Dale, 1842 are described, viz. I. (I.) falcistylus sp. n. (Spain) and I. (I.) cretopunctata sp. n. (Greece: Crete), and their wings and male terminalia are illustrated. A key to the European species of the subgenus is appended.