bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Oxygenated Acids on Graphene Oxide: The Source of Oxygen-Containing Functional Group
Authors: Zhu Xinghua , Xu Yuanpu , Lu Zhibin , Xue Qunji
Published: September 2021

Graphene oxide is an important member of the graphene family which has a wide range of applications. The chemical method, especially the liquid phase method, is one of the most common and important methods for its preparation. However, the complex solution environment not only gives them rich structure, but also brings great challenges for its large-scale industrial synthesis. In order to better realize its industrial application, it is important to understand its structure, such as the source of oxygen-containing functional groups. Here we studied the contribution of four oxygenated acids to oxygen-containing functional groups in Hummers’ method using first principles. We found that the permanganic acid molecules that exist instantaneously due to energy fluctuations can be the source of oxygen-containing functional group. In addition, Stone-Wales defect have a certain effect on the formation of oxygen-containing functional groups, but this effect is not as good as that of solvation effect. This work provides a guide for exploring the source of oxygen-containing functional groups on graphene oxide.
Non-Targeted Analysis Using Gas Chromatography-Mass Spectrometry for Evaluation of Chemical Composition of E-Vapor Products
Authors: Shah Niti H. , Noe Michael R. , Agnew-Heard Kimberly A. , Pithawalla Yezdi B. , Gardner William P. , Chakraborty Saibal , McCutcheon Nicholas , Grisevich Hannah , Hurst Thomas J. , Morton Michael J. , Melvin Matt S. , Miller IV John H.
Published: September 2021

The Premarket Tobacco Product Applications (PMTA) guidance issued by the Food and Drug Administration for electronic nicotine delivery systems (ENDSs) recommends that in addition to reporting harmful and potentially harmful constituents (HPHCs), manufacturers should evaluate these products for other chemicals that could form during use and over time. Although e-vapor product aerosols are considerably less complex than mainstream smoke from cigarettes and heated tobacco product (HTP) aerosols, there are challenges with performing a comprehensive chemical characterization. Some of these challenges include the complexity of the e-liquid chemical compositions, the variety of flavors used, and the aerosol collection efficiency of volatile and semi-volatile compounds generated from aerosols. In this study, a non-targeted analysis method was developed using gas chromatography-mass spectrometry (GC-MS) that allows evaluation of volatile and semi-volatile compounds in e-liquids and aerosols of e-vapor products. The method employed an automated data analysis workflow using Agilent MassHunter Unknowns Analysis software for mass spectral deconvolution, peak detection, and library searching and reporting. The automated process ensured data integrity and consistency of compound identification with >99% of known compounds being identified using an in-house custom mass spectral library. The custom library was created to aid in compound identifications and includes over 1,100 unique mass spectral entries, of which 600 have been confirmed from reference standard comparisons. The method validation included accuracy, precision, repeatability, limit of detection (LOD), and selectivity. The validation also demonstrated that this semi-quantitative method provides estimated concentrations with an accuracy ranging between 0.5- and 2.0-fold as compared to the actual values. The LOD threshold of 0.7 ppm was established based on instrument sensitivity and accuracy of the compounds identified. To demonstrate the application of this method, we share results from the comprehensive chemical profile of e-liquids and aerosols collected from a marketed e-vapor product. Applying the data processing workflow developed here, 46 compounds were detected in the e-liquid formulation and 55 compounds in the aerosol sample. More than 50% of compounds reported have been confirmed with reference standards. The profiling approach described in this publication is applicable to evaluating volatile and semi-volatile compounds in e-vapor products.
Predisposing and Precipitating Risk Factors for Delirium in Elderly Patients Admitted to a Cardiology Ward: An Observational Cohort Study in 1,042 Patients
Authors: Zipser Carl Moritz , Hildenbrand Florian Freimut , Haubner Bernhard , Deuel Jeremy , Ernst Jutta , Petry Heidi , Schubert Maria , Jordan Katja-Daniela , von Känel Roland , Boettger Soenke
Published: September 2021

Aim: Although the risk factors for delirium in general medicine are well-established, their significance in cardiac diseases remains to be determined. Therefore, we evaluated the predisposing and precipitating risk factors in patients hospitalized with acute and chronic heart disease.

Methods and Results: In this observational cohort study, 1,042 elderly patients (≥65 years) admitted to cardiology wards, 167 with and 875 without delirium, were included. The relevant sociodemographic and cardiac- and medical-related clusters were assessed by simple and multiple regression analyses and prediction models evaluating their association with delirium. The prevalence of delirium was 16.0%. The delirious patients were older (mean 80 vs. 76 years; p < 0.001) and more often institutionalized prior to admission (3.6 vs. 1.4%, p = 0.05), hospitalized twice as long (12 ± 10 days vs. 7 ± 7 days; p < 0.001), and discharged more often to nursing homes (4.8 vs. 0.6%, p < 0.001) or deceased (OR, 2.99; 95% CI, 1.53–5.85; p = 0.003). The most relevant risk factor was dementia (OR, 18.11; 95% CI, 5.77–56.83; p < 0.001), followed by history of stroke (OR, 6.61; 95% CI 1.35–32.44; p = 0.020), and pressure ulcers (OR, 3.62; 95% CI, 1.06–12.35; p = 0.040). The predicted probability for developing delirium was highest in patients with reduced mobility and institutionalization prior to admission (PP = 31.2%, p = 0.001). Of the cardiac diseases, only valvular heart disease (OR, 1.57; 95% CI, 1.01–2.44; p = 0.044) significantly predicted delirium. The patients undergoing cardiac interventions did not have higher rates of delirium (OR, 1.39; 95% CI 0.91–2.12; p = 0.124).

Conclusion: In patients admitted to a cardiology ward, age-related functional and cognitive impairment, history of stroke, and pressure ulcers were the most relevant risk factors for delirium. With regards to specific cardiological factors, only valvular heart disease was associated with risk for delirium. Knowing these factors can help cardiologists to facilitate the early detection and management of delirium.
Relationship Between Immunoinflammation and Coronary Physiology Evaluated by Quantitative Flow Ratio in Patients With Coronary Artery Disease
Authors: Liu Chengzhe , Yu Zhiyao , Chen Huaqiang , Wang Jun , Liu Wei , Zhou Liping , Wang Yueyi , Chen Hu , Zhou Huixin , Liu Zhihao , Han Jiapeng , Jiang Hong , Yu Lilei
Published: September 2021

Background: The association between coronary physiology and immunoinflammation has not been investigated. We performed a retrospective study using quantitative flow ratio (QFR) to evaluate the interaction between immunoinflammatory biomarkers and coronary physiology.

Methods: A total of 172 patients with CAD who underwent coronary arteriography (CAG) and QFR were continuously enrolled from May 2020 to February 2021. As a quantitative indicator of coronary physiology, QFR can reflect the functional severity of coronary artery stenosis. The target vessel measured by QFR was defined as that with the most severe lesions. Significant coronary anatomical stenosis was defined as 70% stenosis in the target vessel.

Results: Compared with the QFR > 0.8 group, interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased and CD3+ and CD4+ T lymphocyte counts were decreased in the QFR ≤ 0.8 group. In addition, patients with DS ≤ 70% had higher IL-6, IL-10, and TNF-α levels and decreased CD3+ and CD4+ T lymphocyte counts than those with DS > 70%. Logistic regression analysis indicated IL-6 to be an independent predictor of significant coronary functional and anatomic stenosis (odds ratio, 1.125; 95% CI, 1.059–1.196; P < 0.001). Receiver operating characteristic (ROC) analyses showed that IL-6 > 6.36 was predictive of QFR ≤ 0.8 of the target vessel. The combination of IL-6, IL-10 and CD4 improved the value for predicting QFR ≤ 0.8 of the target vessel (AUC, 0.737; 95% CI, 0.661–0.810).

Conclusion: Among immunoinflammatory biomarkers, IL-6 was independently associated with a higher risk of QFR ≤ 0.8 of the target vessel. The combination of immunoinflammatory biomarkers was highly predictive of significant coronary functional and anatomic stenosis.
Sevelamer Attenuates Bioprosthetic Heart Valve Calcification
Authors: Meng Zhen , Li Zhe , Zhang Erli , Zhang Li , Liu Qingrong , Wu Yongjian
Published: September 2021

Objective: Sevelamer hydrochloride is a phosphate binder used to treat hyperphosphatemia in chronic kidney disease (CKD) patients that can reduce valvular and vascular calcification. The aim of this study was to examine the effects of sevelamer treatment on calcification in bioprosthetic heart valves (BHVs).

Methods: Wister rats were randomly divided into three groups according to sevelamer intake and implantation (sham–sham operation; implant–implantation and normal diet, implant+S implantation, and sevelamer diet). Two kinds of BHVs—bovine pericardium treated with glutaraldehyde (GLUT) or non-GLUT techniques—were implanted in rat dorsal subcutis at 4 weeks. After implantation, sevelamer was administered to the implant+S group. The animals were executed at days 0 (immediately after implantation), 7, 14, 28, and 56. Calcium levels were determined by atomic absorption spectroscopy and von Kossa staining. Serum biochemistry analysis, Western blotting, real-time quantitative polymerase chain reaction, alkaline phosphatase activity measurement, histopathologic analysis, immunohistochemistry, and enzyme-linked immunosorbent assay were conducted to identify the anti-calcification mechanism of sevelamer.

Results: Non-GLUT crosslinking attenuates BHV calcification. Serum phosphate and calcium remained unreactive to sevelamer after a 14-day treatment. However, the mean calcium level in the implant+S group was significantly decreased after 56 days. In addition, the PTH level, inflammatory cell infiltration, system and local inflammation, and expression of Bmp2, Runx2, Alp, IL-1β, IL-6, and TNF-α were significantly reduced in the implant+S group.

Conclusion: Sevelamer treatment significantly attenuated the calcification of BHVs and had anti-inflammation effects that were independent from serum calcium and phosphate regulation. Thus, sevelamer treatment might be helpful to improve the longevity of BHVs.
Left Ventricular Hypertrophy in Diabetic Cardiomyopathy: A Target for Intervention
Authors: Mohan Mohapradeep , Dihoum Adel , Mordi Ify R. , Choy Anna-Maria , Rena Graham , Lang Chim C.
Published: September 2021

Heart failure is an important manifestation of diabetic heart disease. Before the development of symptomatic heart failure, as much as 50% of patients with type 2 diabetes mellitus (T2DM) develop asymptomatic left ventricular dysfunction including left ventricular hypertrophy (LVH). Left ventricular hypertrophy (LVH) is highly prevalent in patients with T2DM and is a strong predictor of adverse cardiovascular outcomes including heart failure. Importantly regression of LVH with antihypertensive treatment especially renin angiotensin system blockers reduces cardiovascular morbidity and mortality. However, this approach is only partially effective since LVH persists in 20% of patients with hypertension who attain target blood pressure, implicating the role of other potential mechanisms in the development of LVH. Moreover, the pathophysiology of LVH in T2DM remains unclear and is not fully explained by the hyperglycemia-associated cellular alterations. There is a growing body of evidence that supports the role of inflammation, oxidative stress, AMP-activated kinase (AMPK) and insulin resistance in mediating the development of LVH. The recognition of asymptomatic LVH may offer an opportune target for intervention with cardio-protective therapy in these at-risk patients. In this article, we provide a review of some of the key clinical studies that evaluated the effects of allopurinol, SGLT2 inhibitor and metformin in regressing LVH in patients with and without T2DM.
Transcatheter Aortic Valve Implantation: All Transfemoral? Update on Peripheral Vascular Access and Closure
Authors: Perrin Nils , Bonnet Guillaume , Leroux Lionel , Ibrahim Réda , Modine Thomas , Ben Ali Walid
Published: September 2021

Transfemoral access remains the most widely used peripheral vascular approach for transcatheter aortic valve implantation (TAVI). Despite technical improvement and reduction in delivery sheath diameters of all TAVI platforms, 10–20% of patients remain not eligible to transfemoral TAVI due to peripheral artery disease. In this review, we aim at presenting an update of recent data concerning transfemoral access and percutaneous closure devices. Moreover, we will review peripheral non-transfemoral alternative as well as caval-aortic accesses and discuss the important features to assess with pre-procedural imaging modalities before TAVI.
Continued Discontinuation of TKI Treatment in Medullary Thyroid Carcinoma – Lessons From Individual Cases With Long-Term Follow-Up
Authors: Brandenburg Tim , Tiedje Vera , Muchalla Philipp , Theurer Sarah , Weber Frank , Schmid Kurt Werner , Dralle Henning , Führer Dagmar
Published: September 2021

Background

The tyrosine kinase inhibitors (TKI) vandetanib and cabozantinib are approved as targeted therapies in advanced medullary thyroid carcinoma (MTC) with symptoms or high tumour burden. Only recently, toxicity in long-time TKI usage was analysed. However, little is known about the impact of TKI discontinuation on MTC disease course after longer-term therapy. Here, we report our experience in a series of 7 MTC patients with vandetanib treatment of up to 87 months followed by discontinuation for concerns of toxicity or due to side-effects. The discontinuation of TKI therapy is a relevant clinical scenario. To our knowledge we present the largest single center series on an important aspect of TKI management.

Methods

Retrospective analysis of MTC patients with continued discontinuation of vandetanib treatment in a tertiary referral endocrine tumour centre. Analysis included a review of patients’ records for TKI indication, and treatment response as well indications for continued TKI discontinuation and follow-up by clinical assessment, calcitonin and CEA doubling times as well as imaging (ultrasound, CT).

Results

Seven MTC patients [6 sporadic MTC, 1 Multiple Endocrine Neplasie Type 2a (MEN2a)] with previous vandetanib treatment (median: 41 months; range 7-87 months) and continued TKI discontinuation were identified out of 161 analysed MTC files. TKI treatment was initiated due to high tumour burden and symptoms or RECIST (Response Evaluation Criteria In Solid Tumors) progression in all patients. Two patients (29%) remained stable after discontinuation of vandetanib until now (follow-up of 47 and 61 months). Both patients had been on TKI therapy for 73 and 58 months. Five patients (71%) developed progressive disease after TKI discontinuation. In 2 patients, vandetanib was restarted after 45 and 52 months resulting again in disease control. One patient was enrolled in a new RET kinase inhibitor trial after 45 months of vandetanib discontinuation. Two patients declined restart of treatment due to mental health issues leading to discontinuation of vandetanib in the first place (after 7 and 38 months of treatment) and both patients died of rapidly progressive disease. At time points of tumour progression, calcitonin-doubling time (CDT) was < 2 years in all patients.

Conclusion

This case series suggests that discontinuation of long-term vandetanib treatment with documented stable disease does not automatically result in rapid disease progression but may be followed by prolonged “TKI free” stable disease in individual patients. Analysis of calcitonin and CDT during discontinuation is indicated as it will unmask tumour progression earlier than imaging. Restart with the same TKI is possible in case of progression.
Long-Term Global Solar Radiation Prediction in 25 Cities in Morocco Using the FFNN-BP Method
Authors: Belmahdi Brahim , Louzazni Mohamed , Akour Mohamed , Cotfas Daniel Tudor , Cotfas Petru Adrian , El Bouardi Abdelmajid
Published: September 2021

This article presents different combinations of input parameters based on an intelligent technique, using neural networks to predict daily global solar radiation (GSR) for twenty-five Moroccan cities. The collected measured data are available for 365 days and 25 stations around Morocco. Different input parameters are used, such as clearness index KT, day number, the length of the day, minimal temperature Tmin, maximal temperature Tmax, average temperature Taverage, difference temperature ΔT, ratio temperature T-Ratio, average relative humidity RH, solar radiation at the top outside atmosphere TOA, average wind speed Ws, altitude, longitude, latitude, and solar declination. A different combination was employed to predict daily GSR for the considered locations in order to find the most adequate input parameter that can be used in the prediction procedure. Several statistical metrics are applied to evaluate the performance of the obtained results, such as coefficients of determination (R2), mean absolute percentage error (MAPE), root mean square error (RMSE), normalized root mean square error (NRMSE), mean bias error (MBE), test statistic (TS), linear regression coefficients (the slope “a” and the constant “b”), and standard deviation (σ). It is found that the usage of input parameters gives highly accurate results in the artificial neural network (FFNN-BP) model, obtaining the lowest value of the statistical metrics. The results showed the best input of 25 locations, 12 inputs for Er-Rachidia, Marrakech, Medilt, Taza, Oujda, Nador, Tetouan, Tanger, Al-Auin, Dakhla, Settat, and Safi, seven inputs for Fes, Ifrane, Beni-Mellal, and Meknes, six inputs for Agadir and Rabat, five inputs for Sidi Ifni, Essaouira, Casablanca and Kenitra, four inputs for Ouarzazate, Lareche, and Al-Hoceima. In terms of accuracy, R2 of the selected best inputs parameters varies between 0.9860% and 0.9920%, the range value of MBE (%) being from −0.1076% to −0.5931%, the RMSE between 0.1990 and 0.4580%, the range value of the NRMSE between 0.0355 and 0.8938, and the lowest value MAPE between 0.0019 and 0.0060%. This technique could be used to predict other parameters for locations where measurement instrumentation is unavailable or costly to obtain.
Coordinated Frequency Regulation of Smart Grid by Demand Side Response and Variable Speed Wind Turbines
Authors: Zhu Qi , Wang Yingjie , Song Jiuxu , Jiang L. , Li Yingliang
Published: September 2021

Frequency stability of the power system is impacted by the increasing penetration of wind power because the wind power is intermittent. Meanwhile, sometimes the demand side loads increase quickly to require more power than total power produced. So balancing the active power in the power system to maintain the frequency is the main challenge of the high penetration of wind power to the smart grid. This paper proposes coordination rotor speed control (RSC), pitch angle control (PAC) and inertial control (IC) to control wind turbines, together with demand side response (DSR) participating in frequency regulation to balance active power in the power system. Firstly, the model of a single area load frequency control (LFC) system is obtained, which includes variable-speed wind turbines (VSWT) and DSR containing aggregated air conditioners and plug-in electric vehicles (PEVs). Then the RSC, PAC and IC, which controls wind turbines participating in frequency regulation in the power system, are introduced, respectively. Finally, the coordination of these three methods for wind turbines in different wind speeds is proposed. Case studies are carried out for the single area LFC system with a wind farm and DSR supported grid frequency. Coordination RSC and PAC combined IC are used to control wind turbines with DSR to balance active power in the power system. The proposed method used in the power system with high penetration of wind power and fluctuation of demand load is tested, respectively. Coordinated RSC or PAC with DSR can increase penetration of wind power and reduce peak load.
Experimental Study on the Riverbed Coarsening Process and Changes in the Flow Structure and Resistance in the Gravel Riverbed Downstream of Dams
Authors: Zhou Yinjun , Lu Jinyou , Jin Zhongwu , Li Yuan , Gao Yu , Liu Yujiao , Chen Peng
Published: September 2021

Following the construction of a reservoir, sediment is intercepted, which greatly reduces the sediment concentration in the discharged flow. This reduction causes riverbed scouring and flow structure adjustments downstream, thereby impacting the river habitat. This study used the generalized flume test with different bed sand compositions and discharge rates to simulate the scouring adjustment process of a sand pebble riverbed channel downstream of a reservoir. The results show that the bed sediment composition affects the water surface gradient, scour depth, turbulence intensity, and sand resistance directly after final scouring. Coarse-grained bed sediment demonstrated the greatest final turbulence intensity and sand resistance, while bed sediments with reduced coarseness exhibited a greater scouring degree; the resistance for sand grains of moderate coarseness showed the greatest change. Sand resistance was exponentially and positively correlated with the median grain size and the fractal dimension of bed sediment mass. The mass fractal dimension expression was suitable for the analysis of bed sand grain-size distribution; it contributed to the calculation of grain resistance with fewer hydraulic parameters. The relationship between the mass fractal dimension and the adjusted grain resistance was also established, which can aid the calculation of the resistance changes in sandy gravel-bed river reaches downstream of reservoirs, enabling the prediction of their effects on aquatic habitats.
The Heterogeneous Impacts of Human Capital on Green Total Factor Productivity: Regional Diversity Perspective
Authors: Xiao Hang , You Jialu
Published: September 2021

That human capital improves the efficiency of Green Total Factor Productivity has been established in research fields, but the heterogeneous effects of human capital on GTFP and its sustainable mechanisms are unclear. This study examines the effects of human capital accumulation, fiscal spending on education, and innovation on GTFP efficiency under spatial and temporal diversity. Employing panel data from 30 provinces from 2001 to 2018 in China, we analyzed the dynamic and static efficiency of GTFP in different regions by three-stage data envelopment analysis (DEA). The heterogeneous effects of human capital on GTFP were explored through Tobit regression. Results reveal that the average value of GTFP efficiency is an inverted U-shape and the presence of significant t geography differences. Human capital accumulation and fiscal spending on education have positive effects on GTFP efficiency; however, innovation negatively affects it. At the same time, marketization growth decreases the positive influence of human capital and education on GTFP efficiency. While, this effect was not observed regarding innovation, the implication of these results concerning the human capital heterogeneous effects of GTFP efficiency in a different geographic context. Establishing a fair and transparent system can reduce the endowments gap and effectively promote GTFP efficiency in developing countries.
Future Representation of Species’ Climatic Niches in Protected Areas: A Case Study With Austrian Endemics
Authors: Semenchuk Philipp , Moser Dietmar , Essl Franz , Schindler Stefan , Wessely Johannes , Gattringer Andreas , Dullinger Stefan
Published: September 2021

Climate driven species’ range shifts may interfere with existing protected area (PA) networks, resulting in a mismatch between places where species are currently protected and places where they can thrive in the future. Here, we assess the climate-smartness of the Austrian PA network by focusing on endemic species’ climatic niches and their future representation within PAs. We calculated endemic species’ climatic niches and climate space available in PAs within their dispersal reach under current and future climates, with the latter represented by three climate change scenarios and three time-steps (2030, 2050, and 2080). Niches were derived from the area of occupancy of species and the extent of PAs, respectively, and calculated as bivariate density kernels on gradients of mean annual temperature and annual precipitation. We then computed climatic representation of species’ niches in PAs as the proportion of the species’ kernel covered by the PA kernel. We found that under both a medium (RCP 4.5) and severe (RCP 8.5) climate change scenario, representation of endemic species’ climatic niches by PAs will decrease to a sixth for animals and to a third for plants, on average, toward the end of the century. Twenty to thirty percent of Austrian endemic species will then have no representation of their climatic niches in PAs anymore. Species with larger geographical and wider elevational ranges will lose less climatic niche representation. The declining representation of climatic niches in PAs implies that, even if PAs may secure the persistence of a part of these endemics, only a small portion of intraspecific diversity of many species may be represented in PAs in the future. We discuss our findings in the context of the varied elevational gradients found in Austria and suggest that the most promising strategies for safeguarding endemic species’ evolutionary potential are to limit the magnitude of climate change and to reduce other pressures that additionally threaten their survival.
Tetracycline Exposure Alters Key Gut Microbiota in Africanized Honey Bees (Apis mellifera scutellata x spp.)
Authors: Soares Kilmer Oliveira , Oliveira Celso José Bruno de , Rodrigues Adriana Evangelista , Vasconcelos Priscylla Carvalho , Silva Núbia Michelle Vieira da , Cunha Filho Octavio Gomes da , Madden Christopher , Hale Vanessa L.
Published: September 2021

Honey bees play a critical role in ecosystem health, biodiversity maintenance, and crop yield. Antimicrobials, such as tetracyclines, are used widely in agriculture, medicine, and in bee keeping, and bees can be directly or indirectly exposed to tetracycline residues in the environment. In European honey bees, tetracycline exposure has been linked with shifts in the gut microbiota that negatively impact bee health. However, the effects of antimicrobials on Africanized honey bee gut microbiota have not been examined. The aim of this study was to investigate the effects of tetracycline exposure on the gut microbial community of Africanized honey bees (Apis mellifera scutellatax spp.), which are important pollinators in South, Central, and North America. Bees (n= 1,000) were collected from hives in Areia-PB, Northeastern Brazil, placed into plastic chambers and kept under controlled temperature and humidity conditions. The control group (CON) was fed daily with syrup (10 g) consisting of a 1:1 solution of demerara sugar and water, plus a solid protein diet (10 g) composed of 60% soy extract and 40% sugar syrup. The tetracycline group (TET) was fed identically but with the addition of tetracycline hydrochloride (450 μg/g) to the sugar syrup. Bees were sampled from each group before (day 0), and after tetracycline exposure (days 3, 6, and 9). Abdominal contents dissected out of each bee underwent DNA extraction and 16S rRNA sequencing (V3-V4) on an Illumina MiSeq. Sequences were filtered and processed through QIIME2 and DADA2. Microbial community composition and diversity and differentially abundant taxa were evaluated by treatment and time. Bee gut microbial composition (Jaccard) and diversity (Shannon) differed significantly and increasingly over time and between CON and TET groups. Tetracycline exposure was associated with decreased relative abundances ofBombellaandFructobacillus, along with decreases in key core microbiota such asSnodgrassella,Gilliamella, Rhizobiaceae, andApibacter.These microbes are critical for nutrient metabolism and pathogen defense, and it is possible that decreased abundances of these microbes could negatively affect bee health. Considering the global ecological and economic importance of honey bees as pollinators, it is critical to understand the effects of agrochemicals including antimicrobials on honey bees.
Spatiotemporal Variations of Freezing and Thawing Indices During the Past Four Decades in Tibet
Authors: Liao Ying , Li Yiying , Fan Jihui , Galoie Majid , Motamedi Artemis
Published: September 2021

Freezing and thawing indices (FI and TI) are commonly used as indicators for climate change assessment and permafrost extent estimation in cold regions. In this study, based on the meteorological daily data (1978–2017) among 34 meteorological stations in Tibet, the temperature in space has been interpolated and FI and TI have been calculated. Finally, spatiotemporal variations have been analyzed and the permafrost area has been estimated. The results showed the mean annual of FI and TI in Tibet are 1241.36 and 1290.22°C⋅day, respectively. A significant downward trend in freezing index (FI) and an upward trend in thawing index (TI) have been reported in the time series, in against, analyzing the spatial distribution showed there is an increasing trend from southeast to northwest for FI while TI was decreased gradually in the same region in Tibet. This research indicates that altitude has a significant influence on the change of FI and TI. With the increase of altitude, FI decreased and TI increased more significantly. The permafrost area was estimated at about 0.59 × 106 km2 in Tibet.
Genotoxic Potential of Nanoparticles: Structural and Functional Modifications in DNA
Authors: Shukla Ritesh K , Badiye Ashish , Vajpayee Kamayani , Kapoor Neeti
Published: September 2021

The rapid advancement of nanotechnology enhances the production of different nanoparticles that meet the demand of various fields like biomedical sciences, industrial, material sciences and biotechnology, etc. This technological development increases the chances of nanoparticles exposure to human beings, which can threaten their health. It is well known that various cellular processes (transcription, translation, and replication during cell proliferation, cell cycle, cell differentiation) in which genetic materials (DNA and RNA) are involved play a vital role to maintain any structural and functional modification into it. When nanoparticles come into the vicinity of the cellular system, chances of uptake become high due to their small size. This cellular uptake of nanoparticles enhances its interaction with DNA, leading to structural and functional modification (DNA damage/repair, DNA methylation) into the DNA. These modifications exhibit adverse effects on the cellular system, consequently showing its inadvertent effect on human health. Therefore, in the present study, an attempt has been made to elucidate the genotoxic mechanism of nanoparticles in the context of structural and functional modifications of DNA.
The Global Impact of COVID-19 on the Care of People With Endometriosis
Authors: Demetriou Lysia , Cox Emma , Lunde Claire E. , Becker Christian M. , Invitti Adriana L. , Martínez-Burgo Beatriz , Kvaskoff Marina , Garbutt Kurtis , Evans Emma , Fox Elaine , Zondervan Krina T. , Vincent Katy
Published: September 2021

Endometriosis is a chronic condition affecting ~10% of women globally. Little is known about the impact of the coronavirus disease 2019 (COVID-19) pandemic on their care. This brief report is aimed to explore the impact of COVID-19 on the care of people with endometriosis around the world, their priorities in relation to their clinical care during and coming out of the pandemic, and whether they believed that endometriosis makes them more vulnerable to COVID-19. An internet-based survey collected data in five languages between May 11, 2020, and June 8, 2020. Only participants with a surgical or radiological diagnosis of endometriosis aged 18 years or over were included. A total of 6,729 eligible respondents completed the survey with 80.7% [95% CI (79.7, 81.6)] reporting a negative impact on their care. This included difficulties obtaining medication (20.3%), cancelled/postponed gynaecology appointments (50.0%), and cancelled/postponed procedures (37.2%). More than half worried that their endometrioses make them more vulnerable to COVID-19 [54.2%; 95% CI (53.0, 55.4)]. The top three priorities were remarkably consistent around the world: contact with gynaecologists, knowing when procedures would be performed, and support with mental health (20.3% prioritising this aspect during the pandemic and 13.0% as restrictions begin to ease). This study shows the substantial impact the COVID-19 pandemic has had on people with endometriosis and describes how they would like care prioritised moving forwards. The findings regarding significant support needs for mental health add further weight to the growing recognition of attending to such issues as part of good patient-centred care.
COVID-19 Among Patients With Inflammatory Rheumatic Diseases
Authors: Esatoglu Sinem Nihal , Tascilar Koray , Babaoğlu Hakan , Bes Cemal , Yurttas Berna , Akar Servet , Pehlivan Ozlem , Akleylek Cansu , Tecer Duygu , Seyahi Emire , Yuce-Inel Tuba , Alpay-Kanitez Nilufer , Bodakci Erdal , Tekgoz Emre , Colak Seda , Bolek Ertugrul Cagri , Koca Suleyman Serdar , Kalyoncu Umut , Icacan Ozan Cemal , Ugurlu Serdal , Oz Hande Ece , Hamuryudan Vedat , Hatemi Gulen ,   the Turkish Society for Rheumatology COVID-19 Registry Investigators
Published: September 2021

Background

The course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses.

Objective

In this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs.

Methods

Between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome.

Results

165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive.

Conclusions

Among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome.
TIGIT Induces (CD3+) T Cell Dysfunction in Colorectal Cancer by Inhibiting Glucose Metabolism
Authors: Shao Qi , Wang Lei , Yuan Maoling , Jin Xiaohong , Chen Zhiming , Wu Changping
Published: September 2021

T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immunosuppressive receptor expressed on the surface of immune cells, suppressing immune responses by activating the intracellular negative regulatory signals. TIGIT plays an important role in the pathogenesis of various tumors, but its immune escape in colorectal cancer remains unclear. We found that the proportion of CD3+TIGIT+ T cells was increased in peripheral blood and cancer tissue in colorectal cancer patients when compared with the healthy donors. These cells exhibited functional defects, low proliferative activity, impaired cytokine production and reduced glucose metabolism. A strong association was also observed between the elevated TIGIT expression and poor prognosis in this cohort. In the in vitro co-culture assays of T cells and tumor cells, the suppressed glucose metabolic activity of T cells was reversed by TIGIT blockade. In addition, this blockade induced the apoptosis and reduced G2/M transit in tumor cells. The antitumor efficacy of TIGIT Ab therapy was further demonstrated in a human colorectal xenograft mice model while co-blockers of TIGIT and PD-1 exhibited synergistic suppressing effects on tumor growth. These results suggest that while TIGIT induces CD3+ T cell dysfunction in colorectal cancer, co-targeting TIGIT and PD-1 can lead to an effective antitumor response and may serve as a novel therapeutic strategy for colorectal patients.
Pathogenic Roles of CXCL10 in Experimental Autoimmune Prostatitis by Modulating Macrophage Chemotaxis and Cytokine Secretion
Authors: Hua Xiaoliang , Ge Shengdong , Zhang Meng , Mo Fan , Zhang Ligang , Zhang Jiong , Yang Cheng , Tai Sheng , Chen Xianguo , Zhang Li , Liang Chaozhao
Published: September 2021

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is an inflammatory immune disease characterized by intraprostatic leukocyte infiltration and pelvic or perineal pain. Macrophages play vital roles in the pathogenesis of CP/CPPS. However, the mechanisms controlling the activation and chemotaxis of macrophages in CP/CPPS remain unclear. This study aimed to investigate the roles of the CXCL10/CXCR3 pathway in the activation and chemotaxis of macrophages in CP/CPPS patients. The serums of CP/CPPS patients and healthy volunteers were collected and measured. Results showed that CXCL10 expression was significantly elevated and correlated with the severity of CP/CPPS patients. The experimental autoimmune prostatitis (EAP) model was generated, and adeno-associated virus and CXCR3 inhibitors were used to treat EAP mice. Immunofluorescence, flow cytometry, and Western blotting were used to analyze the functional phenotype and regulation mechanism of macrophages. Results showed that CXCL10 deficiency ameliorates EAP severity by inhibiting infiltration of macrophages to prostate. Moreover, CXCL10 could induce macrophage migrations and secretions of proinflammatory mediators via CXCR3, which consequently activated the downstream Erk1/2 and p38 MAPK signaling pathways. We also showed that prostatic stromal cell is a potential source of CXCL10. Our results indicated CXCL10 as an important mediator involved in inflammatory infiltration and pain symptoms of prostatitis by promoting the migration of macrophages and secretion of inflammatory mediators via CXCR3-mediated ERK and p38 MAPK activation.
Viral Status and Efficacy of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis
Authors: Ding Ziniu , Dong Zhaoru , Chen Zhiqiang , Hong Jianguo , Yan Lunjie , Li Haichao , Yao Shengyu , Yan Yuchuan , Yang Yafei , Yang Chuncheng , Li Tao
Published: September 2021

Background and Aim

Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to investigate the effects of viral etiology on response to ICIs in HCC and depict the tumor immune microenvironment (TIME) of virally infected and uninfected HCC.

Methods

A systematic search was conducted in PubMed, Web of Science, Embase, and the Cochrane central register of controlled trials up to August 2021. Clinical trials reporting the efficacy of ICIs in HCC were eligible. Baseline characteristics including first author, year of publication, National Clinical Trials (NCT) registry number, study region, sample sizes, interventions, line of treatment, and viral status were extracted. Meta-analysis was conducted to generate combined odds ratios (ORs) with 95% confidence intervals (CI) based on random or fixed effect model, depending on heterogeneity. Tumor immune microenvironment was depicted using ESTIMATE and CIBERSORT algorithm.

Results

Eight studies involving 1,520 patients were included. Combined data suggested that there was no significant difference of objective response rate (ORR) between virally infected HCC and non-viral HCC patients [OR = 1.03 (95% CI, 0.77–1.37; I2 = 30.9%, pH = 0.152)]. Similarly, difference was not observed on ORR between HBV-HCC and HCV-HCC patients [OR = 0.74 (95% CI, 0.52–1.06; I2 = 7.4%, pH = 0.374)]. The infiltration of immune cells in the tumor microenvironment did not differ by etiology except for M0 macrophages, M2 macrophages, regulatory T cells, naive B cells, follicular helper T cells, activated dendritic cells, activated mast cells, and plasma cells. Despite differences in infiltration observed in specific cell types, the immune score and stromal score were generally comparable among etiology groups.

Conclusion

Viral etiology may not be considered as the selection criteria for patients receiving ICIs in HCC, and viral status has little impact on TIME remodeling during HCC tumorigenesis.
PlGF Reduction Compromises Angiogenesis in Diabetic Foot Disease Through Macrophages
Authors: Zhu Lingyan , Qian Jieqi , Jiang Yinan , Yang Tianlun , Duan Qiong , Xiao Xiangwei
Published: September 2021

Diabetic foot disease (DFD) is a common and serious complication for diabetes and is characterized with impaired angiogenesis. In addition to the well-defined role of vascular endothelial growth factor (VEGF) -A and its defect in the pathogenesis of DFD, another VEGF family member, placental growth factor (PlGF), was also recently found to alter expression pattern in the DFD patients with undetermined mechanisms. This question was thus addressed in the current study. We detected attenuated PlGF upregulation in a mouse DFD model. In addition, the major cell types at the wound to express the unique PlGF receptor, VEGF receptor 1 (VEGFR1), were macrophages and endothelial cells. To assess how PlGF regulates DFD-associated angiogenesis, we injected recombinant PlGF and depleted VEGF1R specifically in macrophages by local injection of an adeno-associated virus (AAV) carrying siRNA for VEGFR1 under a macrophage-specific CD68 promoter. We found that the angiogenesis and recovery of the DFD were both improved by PlGF injection. The PlGF-induced improvement in angiogenesis and the recovery of skin injury were largely attenuated by macrophage-specific depletion of VEGF1R, likely resulting from reduced macrophage number and reduced M2 polarization. Together, our data suggest that reduced PlGF compromises angiogenesis in DFD at least partially through macrophages.
Interferon-λ Improves the Efficacy of Intranasally or Rectally Administered Influenza Subunit Vaccines by a Thymic Stromal Lymphopoietin-Dependent Mechanism
Authors: Ye Liang , Schnepf Daniel , Ohnemus Annette , Ong Li Ching , Gad Hans Henrik , Hartmann Rune , Lycke Nils , Staeheli Peter
Published: September 2021

Previous work showed that interferon-λ (IFN-λ) can trigger the synthesis of thymic stromal lymphopoietin (TSLP) by specialized epithelial cells in the upper airways of mice, thereby improving the performance of intranasally administered influenza vaccines. Here we demonstrate that protein-only influenza vaccines containing either IFN-λ or TSLP boosted antigen-specific IgG1 and IgA responses and enhanced the resistance of mice to influenza virus challenge, irrespective of whether the vaccines were appliedviathe intranasal or the rectal route. TSLP receptor deficiency negatively influenced vaccine-induced antiviral immunity by impairing the migration of dendritic cells from the airways to the draining lymph nodes of immunized mice, thereby restraining follicular helper T cell and germinal center B cell responses. As previously observed during intranasal vaccination, the adjuvant effect of IFN-λ on a rectally administered influenza vaccine was no longer observed when TSLP receptor-deficient mice were used for immunization, highlighting the central role of the IFN-λ/TSLP axis for vaccine-induced antiviral immunity in the mucosa.
Application of Shape Analyses to Recording Structures of Marine Organisms for Stock Discrimination and Taxonomic Purposes
Authors: Lishchenko Fedor , Jones Jessica Briony
Published: September 2021

Morphometric analysis of biogenic recording structures within marine organisms has applications in stock assessment, taxonomics, and ecomorphological studies, with shape variation markedly influenced by both genetics and the surrounding environment. Geometric morphometrics (GM) is an alternative approach to the “traditional” method of collecting linear measurements and applying multivariate statistical methods to these data. Landmark- and outline-based GM methods are suggested to have several advantages over the “traditional” method. Due to the increasing popularity of GM methods in the modern literature, this chapter first compares different morphometric techniques, and then reviews the methods applied to recording structures, with a focus on GM outline-based analyses. It is clear that outline methods have become a popular method of analysis for structures such as otoliths, particularly for the purpose of distinguishing between population components. However, for other structures such as beaks this technique is only in its early stages of application and is more difficult to apply but shows great promise for future studies. The advantages of using a holistic approach, incorporating several techniques including outline analysis for stock identification purposes is discussed.
Atypical Diagenesis and Geochemistry of Redox-Sensitive Elements in Hydrothermal Sediments of the Southern Okinawa Trough
Authors: Li Li , Dang Duc Huy , Wang Xiaojing , Liu Jihua , Wu Yonghua , Zhu Aimei , Shi Xuefa
Published: September 2021

Early diagenesis processes and the geochemistry of redox-sensitive elements (RSEs) in four sediment cores in an active hydrothermal field in the southern Okinawa Trough (OT) was investigated. Dissolved Fe, Mn, ΣHS–, and several other RSEs (Mo, U, and V) in pore water were measured. We also studied metal distribution in sediments using sequential extraction methods. Very high dissolved Fe concentrations (∼140 μmol L–1) but insignificant dissolved Mn were observed in surficial pore waters in the station adjacent to the hydrothermal vent, where highly reactive Fe, Mo, U in the sediments were also measured. Such an atypical diagenetic sequence found in those cores could be driven by the overwhelmingly high reactive Fe fraction (mostly Fe oxides) delivered from the vents. Consequently, significant upward benthic fluxes of Fe and Mo were estimated for the studied stations. In addition, we performed a principal component analysis (PCA), together with relative ratios of carbonate-related elements (Sr, Ca, Mg), to identify particles’ origins in the hydrothermal field; two endmembers being the hydrothermal source and hydrogenous processes. This comprehensive study on a unique set of samples collected by advanced technology provided valuable data to demonstrate distinctive geochemical features that occur in hydrothermal sediments.