bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Changes in the Composition of the Penile Microbiome Are Associated With Circumcision Status, HIV and HSV-2 Status, Sexual Practices, and Female Partner Microbiome Composition
Authors: Mehta Supriya D. , Nandi Debarghya , Agingu Walter , Green Stefan J. , Otieno Fredrick O. , Bhaumik Dulal K. , Bailey Robert C.
Published: July 2022

Background

Penile microbiome composition has been associated with HSV-2 and HIV in men and with bacterial vaginosis (BV) and HSV-2 in female sex partners. This study sought to 1) characterize penile microbiome composition over a 1-year period and 2) identify factors associated with penile microbiome composition over time.

Methods

This prospective study of community-recruited heterosexual couples in Kenya measured penile and vaginal microbiomes via 16S ribosomal RNA gene amplicon sequencing at 4 time points over 1 year (1, 6, and 12 months after baseline). We used longitudinal mixed-effects modeling to assess associated demographic, behavioral, and disease factors and changes in community type, meatal taxa with the highest mean relative abundance, and alpha and beta diversity measures. We estimated group-based trajectories to elucidate compositional trends.

Results

Among 218 men with 740 observations, men had a median age of 26 years, 11.6% were living with HIV, and 46.1% were HSV-2 seropositive. We identified 7 penile community types that varied with circumcision status, female partner vaginal microbiome community state type (CST), condom use, and penile washing. Across varying analytic approaches, 50%–60% of men had stable penile microbiome compositions. Alpha diversity measures were lower for circumcised men and those who reported condom use; they were stable over time but higher if female partners had diverse CSTs or BV. BV was positively associated with the relative abundance of numerous individual penile taxa. The decreased Bray–Curtis similarity was more common for men with HSV-2, and HSV-2 was also associated with a lower relative abundance of Corynebacterium and Staphylococcus.

Conclusions

Over a 1-year period, penile microbiome composition was stable for a substantial proportion of men and was influenced by men’s circumcision status, sexual practices, female partner’s vaginal CST and BV status, and men’s HSV-2 status. In the female genital tract, a diverse CST is often associated with poorer health outcomes. Our results contribute toward understanding whether this framework extends to the penile microbiome and whether diversity and the associated penile microbiome compositions influence susceptibility or resilience to poorer health outcomes in men. Focusing on understanding how these factors influence the penile microbiome may lead to therapeutic avenues for reduced HSV-2 and BV infections in men and their female sex partners.
Time-Dependent Effect of Anthracycline-Based Chemotherapy on Central Arterial Stiffness: A Systematic Review and Meta-Analysis
Authors: Schneider Caroline , González-Jaramillo Nathalia , Marcin Thimo , Campbell Kristin L. , Suter Thomas , Bano Arjola , Wilhelm Matthias , Eser Prisca
Published: July 2022

Background and Aims

Anthracycline-based chemotherapy (ANTH-BC) has been proposed to increase arterial stiffness, however, the time-dependency of these effects remain unclear. This systematic review and meta-analysis aimed to investigate the time-dependent effect of ANTH-BC on markers of central aortic stiffness, namely aortic distensibility (AD) and pulse-wave-velocity (PWV) in cancer patients.

Methods

An extensive literature search without language restrictions was performed to identify all studies presenting longitudinal data on the effect of ANTH-BC on either AD and/or central PWV in cancer patients of all ages. An inverse-variance weighted random-effect model was performed with differences from before to after chemotherapy, as well as for short vs. mid-term effects.

Results

Of 2,130 articles identified, 9 observational studies with a total of 535 patients (mean age 52 ± 11; 73% women) were included, of which four studies measured AD and seven PWV. Short-term (2–4 months), there was a clinically meaningful increase in arterial stiffness, namely an increase in PWV of 2.05 m/s (95% CI 0.68–3.43) and a decrease in AD (albeit non-significant) of −1.49 mmHg-1 (−3.25 to 0.27) but a smaller effect was observed mid-term (6–12 months) for PWV of 0.88 m/s (−0.25 to 2.02) and AD of −0.37 mmHg-1 (−1.13 to 0.39). There was considerable heterogeneity among the studies.

Conclusions

Results from this analysis suggest that in the short-term, ANTH-BC increases arterial stiffness, but that these changes may partly be reversible after therapy termination. Future studies need to elucidate the long-term consequences of ANTH-BC on arterial stiffness, by performing repeated follow-up measurements after ANTH-BC termination.

Systematic Review Registration

[www.crd.york.ac.uk/prospero/], identifier [CRD42019141837].
Vascular Age, Metabolic Panel, Cardiovascular Risk and Inflammaging in Patients With Rheumatoid Arthritis Compared With Patients With Osteoarthritis
Authors: Rodríguez-Vargas Gabriel-Santiago , Santos-Moreno Pedro , Rubio-Rubio Jaime-Andrés , Bautista-Niño Paula-Katherine , Echeverri Darío , Gutiérrez-Castañeda Luz-Dary , Sierra-Matamoros Fabio , Navarrete Stephania , Aparicio Anggie , Saenz Luis , Rojas-Villarraga Adriana
Published: July 2022

Introduction

The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is 1.5–2 times higher than the general population. The fundamental risk factor for CVD is age, related to alterations at the arterial level. The aim of the study was to compare vascular age (VA) in RA patients under a strict treat-to-target (T2T) strategy with Osteoarthritis (OA) patients without strict follow up and to assess the influence of inflammaging (chronic, sterile, low-grade inflammation related to aging) and metabolic markers on VA.

Materials and Methods

This was an analytical cross-sectional study. Patients with RA (under a strict a T2T strategy) and OA patients without strict clinical follow-up were included. Patients with a history of uncontrolled hypertension, CVD, and/or current smoking were excluded. Sociodemographic, physical activity, and toxic exposure data were obtained. Waist-hip ratio and body mass index (BMI) were measured. DAS-28 (RA) and inflammatory markers, lipid profile, and glycaemia were analyzed. Pulse wave velocity (PWV) was measured (oscillometric method, Arteriograph-TensioMed®). VA was calculated based on PWV. Eleven components of inflammaging [six interleukins, three metalloproteinases (MMP), and two tissue inhibitors of metalloproteinases (TIMP)] were evaluated (Luminex® system). Univariate and bivariate analyzes (Mann Whitney U and chi-square) and correlations (Spearmans Rho) were done to compare the two groups.

Results

A total of 106 patients (74% women) were included, 52/RA and 54/OA. The mean age was 57 (Interquartile range - IQR 9 years). The BMI, waist circumference, and weight were higher in patients with OA (p < 0.001). RA patients had low disease activity (DAS-28-CRP). There were no differences in VA, inflammaging nor in PWV between the two groups. VA had a positive, but weak correlation, with age and LDL. In group of RA, VA was higher in those who did not receive methotrexate (p = 0.013). LDL levels correlated with MMP1, TIMP1, and TIMP2.

Conclusions

When comparing RA patients with low levels of disease activity with OA patients with poor metabolic control, there are no differences in VA. Furthermore, methotrexate also influences VA in RA patients. This shows that implemented therapies may have an impact on not only the inflammatory state of the joint but also CVD risk.
MiR-208b/miR-21 Promotes the Progression of Cardiac Fibrosis Through the Activation of the TGF-β1/Smad-3 Signaling Pathway: An in vitro and in vivo Study
Authors: Zhang Yifan , Yuan Bo , Xu Yue , Zhou Na , Zhang Ruiqi , Lu Lan , Feng Zhanbin
Published: July 2022

Background

Regulatory molecule microRNAs (miRNAs) have been implicated in myocardial fibrosis. However, the specific mechanism by which they lead to myocardial fibrosis remains unclear. This study aimed to explore the roles of miR-208b, miR-21 and transforming growth factor-β1 (TGF-β1)/Smad-3 signaling pathway components in cardiac fibrosis development.

Materials and Methods

Thirty-six consecutive acute myocardial infarction (AMI) patients were included in this study. Plasma was collected on admission and at 24 h, 48 h and 6 d. The levels of plasma miR-208b, miR-21, TGF-β1, and Smad-3 were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and cardiac calcium protein T (cTnT) and creatine kinase isoenzyme (CK-MB) were detected by electrochemiluminescence analysis. H9C2 cells were exposed to hypoxia and divided into 4 groups (hypoxia treatment for 6 h, 24 h, 48 h, and 72 h). These stimulated cells were then transfected with miRNA inhibitors and mimics for gene overexpression and inhibition. RT-qPCR was used to detect the expression of miR-208b, miR-21, TGF-β1, and Smad-3, and western blot analysis was used to detect TGF-β1 and Smad-3 protein expression.

Results

The plasma analysis showed cTnT and CK-MB expression peaked at 24 h after symptom onset; miR-208b, miR-21, TGF-β1, and Smad-3 levels showed no peak and increased gradually with time. Cell experiments revealed that miR-208b and TGF-β1 were upregulated along with increased hypoxia exposure; miR-21 expression peaked at 24 h and 72 h, with the highest peak at 72 h, and Smad-3 expression peaked at 6 h and 72 h, with the highest peak at 72 h. miR-208b and miR-21 expressions were positively correlated with TGF-β/Smad-3 expression. TGF-β1/Smad-3 mRNA and protein levels were elevated in the miR-208b and miR-21 overexpression groups and reduced in the miR-208b and miR-21 inhibition groups.

Conclusion

MiR-208b and miR-21 promote cardiac fibrosis progression through TGF-β1/Smad-3 signaling pathway activation.
Short-Term Prognostic Efficacy of mGPS and LCS in Patients With Acute Heart Failure
Authors: Wang Jing , Xie Ling , Lyu Ping , Zhou Feng , Cai Hong-Li , Qi Rong-Xing , Zhang Qing
Published: July 2022

Aim

Systemic inflammation plays an important role in the occurrence and development of acute heart failure. The modified Glasgow Prognostic Score (mGPS) and “lymphocyte C-reactive protein score” (LCS) are used to assess the inflammation levels in cancer patients. The purpose of this study was to assess the prognostic value of these two inflammation-related scoring systems in patients with acute heart failure.

Methods

Two hundred and fifty patients with acute heart failure were enrolled in this study. The mGPS and LCS scores were recorded after admission. All patients were divided into 2 groups: the death group and the survival group according to the 3-month follow-up results. The predictive values of mGPS and LCS were assessed using receiver-operating characteristic (ROC) analyses. Univariate and multivariate logistic analyses were used to evaluate the relationships between variables and endpoint.

Results

The levels of mGPS and LCS in the death group were significantly higher than those in the survival group (P < 0.05). The areas under the ROC curve of the mGPS and LCS for predicting death were 0.695 (95%CI: 0.567~0.823) and 0.736 (95%CI: 0.616~0.856), respectively. Multivariate analysis demonstrated that both LCS, LVEF and serum direct bilirubin were independent predictors of all-cause death, excluding mGPS.

Conclusions

Compared with mGPS, LCS is independently associated with short-term outcomes in patients with acute heart failure. LCS was a clinically promising and feasible prognostic scoring system for patients with acute heart failure.
The Volcanic Landscapes of the Ancient Hunter-Gatherers of the Atacama Desert Through Their Lithic Remains
Authors: Loyola Rodrigo , Figueroa Valentina , Núñez Lautaro , Vasquez Marco , Espíndola Christian , Valenzuela Millarca , Prieto Manuel
Published: July 2022

Since ancient times Andean societies have formed an intimate relationship with volcanoes, the beginnings of which can be traced right back to the initial peopling of the region. By studying rocks used for stone tools and other everyday artifacts, we explore the volcanic landscapes of early hunter-gatherer groups (11,500–9,500 cal BP) of the highlands of the Atacama Desert (22–24°S/67–68°W). Petrological classification of the lithic assemblages of three Early Holocene archaeological sites showed the procurement of a great diversity of volcanic and subvolcanic rocks, including pumice, granitic rocks, micro-diorites, a large variety of tuffs and andesites, dacites, cherts, basalts, obsidians, among others. Field surveys enabled us to detect many of their sources related to volcanic features such as craters, maars, caldera-domes, lava flows, probable hydrothermal deposits, and ignimbrites. In these places, we also document large quarry-workshops and campsites from different periods, indicating intense and repeated human occupation over time. By comparing the artifacts with geological samples collected in the field, it was possible to assign the source of origin of a large part of the archaeological assemblages. Our data suggest that the volcanic features of the Atacama highlands were integrated into the mobility and interaction networks of ancient hunter-gatherer groups at an early date.
Rapid Model Development for GSFLOW With Python and pyGSFLOW
Authors: Larsen Joshua D. , Alzraiee Ayman H. , Martin Donald , Niswonger Richard G.
Published: July 2022

Following the advancement of high-performance computing and sensor technology and the increased availability of larger climate and land-use data sets, hydrologic models have become more sophisticated. Instead of simple boundary conditions, these data sets are incorporated with the aim of providing more accurate insights into hydrologic processes. Integrated surface-water and groundwater models are developed to represent the most important processes that affect the distribution of water in hydrologic systems. GSFLOW is an integrated hydrologic modeling software that couples surface-water processes from PRMS and groundwater processes from MODFLOW and simulates feedbacks between both components of the hydrologic system. Development of GSFLOW models has previously required multiple tools to separately create surface-water and groundwater input files. The use of these multiple tools, custom workflows, and manual processing complicates reproducibility and confidence in model results. Based on a need for rapid, reproduceable, and robust methods, we present two example problems that showcase the latest updates to pyGSFLOW. The software package, pyGSFLOW, is an end-to-end data processing tool made from open-source Python libraries that enables the user to edit, write input files, run models, and postprocess model output. The first example showcases pyGSFLOW’s capabilities by developing a streamflow network in the Russian River watershed with an area of 3,850 km2 located on the coast of northern California. A second example examines the effects of model discretization on hydrologic prediction for the Sagehen Creek watershed with an area of 28 km2, near Lake Tahoe, California, in the northern Sierra Nevada.
Effects of a 12-Week Interventional Exercise Programme on Muscle Strength, Mobility and Fitness in Patients With Diabetic Foot in Remission: Results From BIONEDIAN Randomised Controlled Trial
Authors: Vrátná Eliška , Husáková Jitka , Jarošíková Radka , Dubský Michal , Wosková Veronika , Bém Robert , Jirkovská Alexandra , Králová Kateřina , Pyšková Bára , Lánská Věra , Fejfarová Vladimíra
Published: July 2022

Objectives

Diabetic foot syndrome (DFS) is a serious late diabetic complication characterised by limited joint mobility and other biomechanical and muscle abnormalities.

Aim

To evaluate the effect of an interventional exercise programme on anthropometric parameters, muscle strength, mobility and fitness in patients with diabetic foot in remission.

Data Sources and Study Selection

Thirty-eight patients with type 2 diabetes and DFS without active lesions (mean age 65 ± 6.9 years, BMI 32 ± 4.7 kg.m-2, waist-hip ratio (WHR)1.02 ± 0.06) were enrolled in our randomised controlled trial. All subjects were randomised into two groups: an intervention group (I; n=19) and a control group (C; n=19). The 12-week exercise intervention focused on ankle and small-joint mobility in the foot, strengthening and stretching of the lower extremity muscles, and improvements in fitness. Changes (Δ=final minus initial results) in physical activity were assessed using the International Physical Activity Questionnaire (IPAQ), with joint mobility detected by goniometry, muscle strength by dynamometry, and fitness using the Senior Fitness Test (SFT).

Data extraction

Due to reulceration, 15.8% of patients from group I (3/19) and 15.8% of patients from group C were excluded. Based on the IPAQ, group I was more active when it came to heavy (p=0.03) and moderate physical activity (p=0.06) after intervention compared to group C. Group I improved significantly in larger-joint flexibility (p=0.012) compared to controls. In group I, dynamometric parameters increased significantly in both lower limbs (left leg; p=0.013, right leg; p=0.043) compared to group C. We observed a positive trend in the improvement of fitness in group I compared to group C. We also confirmed positive correlations between heavy physical activity and selected parameters of flexibility (r=0.47; p=0.007), SFT (r=0.453; p=0.011) and dynamometry (r=0.58; p<0.0025). Anthropometric parameters, such as BMI and WHR, were not significantly influenced by the intervention programme.

Conclusion

Our 12-week interventional exercise programme proved relatively safe, resulting in improved body flexibility and increased muscle strength in DF patients in remission.
Bone Microarchitecture in Obese Postmenopausal Chinese Women: The Chinese Vertebral Osteoporosis Study (ChiVOS)
Authors: Qi Wenting , Jiang Yan , Liu Wei , Chi Yue , Jiajue Ruizhi , Pang Qianqian , Wang Ou , Li Mei , Xing Xiaoping , Yu Wei , Xia Weibo
Published: July 2022

Background

Obesity is associated with improved bone mass and microarchitecture in Caucasian individuals, but evidence in obese Asian individuals is lacking.

Objective

To analyze the areal bone mineral density (aBMD) and bone microarchitecture in normal-weight, overweight, and obese postmenopausal Chinese women.

Methods

A total of 243 postmenopausal women from the Chinese Vertebral Osteoporosis Study (ChiVOS) were included and were divided into three groups (OB, obese group; OW, overweight group; NW, normal weight group) by BMI level. aBMD, trabecular bone score (TBS), and appendicular lean mass (ALM) were measured by dual‐energy X‐ray absorptiometry (DXA). Bone microarchitecture was measured by HR-pQCT at the distal radius and tibia. X-ray was performed to confirm vertebral fractures (VFs). Multiple linear regression was used to evaluate the correlations between bone parameters and ALM after adjusting for confounding variables.

Results

The prevalence of VFs and clinical fractures were similar among the groups. Participants in the OB group showed a lower level of osteocalcin with comparable levels of other bone turnover markers (BTMs). The aBMD at several skeletal sites was higher in the OB group than in the NW group after adjusting for age (p<0.01 for all comparisons). At the radius, the OB group had a higher Ct.Ar, Tb.vBMD, Tb.BV/TV, Tb.N, Tb.Th, and Ct.Th than the NW group after adjusting for covariates (p<0.05 for all). Differences of a similar magnitude were found at the distal tibia. There was a trend of decreasing trend in Tb.Sp, Tb.1/N/SD, and Ct.Po among groups at both sites. However, the bone microarchitecture did not differ between participants with severe obesity (BMI≥35.0kg/m2) and those with 30.0≤BMI<35 kg/m2. Multiple linear regression revealed that the associations between ALM and most of the bone microarchitecture parameters at both sites were much stronger than the association between body weight and bone parameters.

Conclusion

We have observed significant improvements in aBMD, bone geometry, and bone microarchitecture in obese postmenopausal Chinese women. Except for a lower level of osteocalcin in the OB group, no significant differences in BTMs were found among the groups. Compared with body weight, ALM may explain greater variance in the improvement of bone microarchitecture parameters.
MicroRNA-21: A Critical Pathogenic Factor of Diabetic Nephropathy
Authors: Liu Shuijiao , Wu Weizhou , Liao Jian , Tang Fuqin , Gao Ge , Peng Jing , Fu Xiujing , Zhan Yuqin , Chen Zhihui , Xu Weifang , Zhao Shankun
Published: July 2022

Diabetic nephropathy (DN), one of the most common and intractable microvascular complications of diabetes, is the main cause of terminal renal disease globally. MicroRNA-21 (miR-21) is a kind of miRNA early identified in human circulation and tissues. Mounting studies have demonstrated that miR-21 plays an important role in the development and progression of DN. This collaborative review aimed to present a first attempt to capture the current evidence on the relationship between miR-21 and DN. After a systematic search, 29 relevant studies were included for comprehensively and thoroughly reviewing. All these eligible studies reported that miR-21 was up-regulated in DN, whether in serum or renal tissues of human or animal models. MiR-21 exhibited its pathogenic roles in DN by forming a complex network with targeted genes (e.g. MMP-9, Smad7, TIMP3, Cdk6, FOXO1, IMP3, and MMP2) and the signaling cascades (e.g. Akt/TORC1 signaling axis, TGF-β/NF-κB signaling pathways, TGF-β/SMAD pathway, CADM1/STAT3 signaling, and AGE-RAGE regulatory cascade), which resulted in epithelial-to-mesenchymal transition, extracellular matrix deposition, cytoskeletal remodeling, inflammation, and fibrosis. This review highlights that miR-21 is a pivotal pathogenic factor in the development of DN. It may serve as an attractive potential diagnostic, prognostic, and predictive biomarker for DN in clinical practice after further confirmation of the clinicopathological features and molecular mechanisms of miR-21-mediated DN.
Measurement Error Estimation for Distributed Smart Meters Through a Modified BP Neural Network
Authors: Xia Tian , Liu Cencen , Lei Ming , Xia Shuibin , Li Ding , Ming Dongyue
Published: July 2022

Smart meters generally suffer degradation of metering accuracy and performance due to aging, faults, and other factors, which, however, are difficult to detect. This study proposes a measurement error estimation method for distributed smart meters based on a modified BP neural network. First, the relationship model between the metering correction coefficient, network loss, and energy consumption measurement value for the distributed system is established. Then, a modified BP neural network for the parameter estimation method is proposed, in which the internal activation function, iterative step size, and other parameters are comprehensively designed. Finally, the parameters of the distributed smart meter measurement error are solved through training and learning. The case study verifies the effectiveness of the proposed method, and this study lays a theoretical foundation for accurate prediction of the measurement error for distributed smart meters.
Early Warning of Telecom Customer Churn Based on Multialgorithm Model Optimization
Authors: Xu Jingxiu , Li Xueguang , He Zhonglin , Zhou Jing
Published: July 2022

Background: China telecom is the largest integrated information service provider in China, its business volume all over the world. It is interesting to note that China Unicom and other telecom companies have carried out similar businesses one after another. How to prevent the loss of existing customers in the fierce competition is an important issue for telecom companies to think about.

Methods: This work aims to build a variety of algorithm models for target optimization and use them to predict whether telecom companies will lose customers, respond to the early warning of customer churn, and then implement active retention measures. Data characteristics affect the final loss prediction effect. In this study, the weight contribution rate of each characteristic variable is obtained by calculating the evidence weight and then the characteristic variable information value so as to optimize the prediction accuracy of the algorithm model. Through calculation, we noted the weight contribution rate of five characteristic variables to be the highest. Including total day charge, total day minutes customer service calls, international plan, and number of voicemail messages, linear regression, decision tree, Bayesian, artificial neural network, and support vector machine are used to predict customer churn on the customer dataset published by telecom companies. The experimental results are used to test the performance of the algorithm model.

Results: It is found that the characteristic variables calculated after optimization are put into multialgorithm models to predict the churn of telecom customers. Finally, it is found that it is better for the optimized characteristic variables to use the decision tree algorithm model to predict the loss of telecom customers.
Solar-Driven Carbon Dioxide Reduction: A Fair Evaluation of Photovoltaic-Biased Photoelectrocatalysis and Photovoltaic-Powered Electrocatalysis
Authors: Zhang Ying , Ye Conglin , Duan Jingjing , Feng Hao , Liu Dong , Li Qiang
Published: July 2022

The salient question addressed in this work is whether and how photovoltaic-biased photoelectrocatalysis (PV-PEC) can fairly and practically be as competitive as photovoltaic-powered electrocatalysis (PV-EC) for solar-driven carbon dioxide reduction (CO2RR). It was argued that to fairly evaluate PV-PEC and PV-EC CO2RR approaches in terms of techno-economy, the two devices should be driven by the same PV cell and produce the same group of products for the same series of Faradaic efficiency for each product. For this condition, PV-PEC CO2RR was shown to surprisingly have higher solar-to-chemical (STC) energy conversion efficiency than PV-EC. Results show that the STC efficiency of 8%, double the state-of-the-art efficiency, is achievable for PV-PEC CO2RR that employs low-cost perovskite PV cell and silicon PEC photocathode. This non-trivial performance was achieved by leveraging novel design of light management. In particular, the proposed reflective-spectrum-splitting light management configuration enables the use of high-efficiency opaque perovskite PV cell, which significantly boosts the efficiency of PV-PEC CO2RR. Furthermore, the framework generalized in this work is also applicable to other solar-driven catalytic processes with various different products such as productions of H2O2 by water oxidation and ammonia by nitrogen fixation.
Advances in Research Into and Applications of Heterotrophic Nitrifying and Aerobic Denitrifying Microorganisms
Authors: Fu Weilai , Song Guolong , Wang Yunshuang , Wang Qiang , Duan Peifeng , Liu Chao , Zhang Xian , Rao Zhiming
Published: July 2022

With the increasing use of animal and plant proteins, pollution due to nitrogen sources is attracting increasing attention. In particular, the amount of nitrogen-containing sewage discharged into the environment has increased significantly, causing eutrophication of water bodies and environmental degradation of water quality. Traditionally, nitrifying bacteria perform ammonia nitrification under aerobic conditions, while denitrifying bacteria perform nitrate/nitrite denitrification under anaerobic conditions. However, heterotrophic nitrifying and aerobic denitrifying microorganisms (HNADs) perform ammonia nitrification and nitrate/nitrite denitrification under the same aerobic conditions using an organic carbon source, which is a much simpler and more efficient process. In this review, the distribution and evolutionary relationships of novel HNADs strains are presented, and the influencing factors, metabolic pathways, key enzymes, and practical applications of HNADs are reviewed.
Progress and Perspectives of Geotechnical Anchor Bolts on Slope Engineering in China
Authors: Du Yan , Li Heng , Chicas Santos D. , Huo Leichen
Published: July 2022

Geotechnical anchoring technology is an important tool for disaster prevention and mitigation in slope engineering. Anchor bolts which are commonly used in slope engineering can be divided into prestressed anchors and non-prestressed anchors. Due to the superiority of anchor support technology, research on various aspects of anchor bolts, such as mechanical mechanism, anchorage effect, and the development of new-type anchor bolts, has been a significant research topic for scholars. This mini-review sums up the diverse past and current literature on anchor support technology of slope engineering in China. It focuses on the characteristics, applications, research methods, and practical cases of anchor bolts and briefly describes the history of slope anchor bolt development in China in the past 3 decades. Nowadays, the demand for engineering construction processes is increasing, and engineering geological conditions are becoming more complex, which promotes the development of anchor support technology. At the international level, achieving carbon neutrality is both an international trend and a general objective. Against the background of global commitment to carbon neutrality, the potential future perspectives for the developments of anchor support technology have been prospected in light of actual engineering needs.
How Can the Financing Constraints of SMEs Be Eased in China?-Effect Analysis, Heterogeneity Test and Mechanism Identification Based on Digital Inclusive Finance
Authors: Li Jianwei , Wei Renyi , Guo Yuanyuan
Published: July 2022

Due to the impact of COVID-19 and other factors, SMEs are increasingly facing the contradiction of financing constraints. In order to explore feasible ways to ease the financing constraints of SMEs, we further incorporate digital inclusive finance into the analytical framework of financing constraints of SMEs, and test the causal relationship between them by using models such as two-way fixed effects model and moderated intermediary effect model. We find that digital inclusive finance can effectively alleviate financing constraints of SMEs, and this phenomenon is particularly significant in private enterprises and family enterprises. In addition, the mitigation effect of digital financial inclusion is more like icing on the cake, and it cannot provide practical assistance to small and medium-sized enterprises with poor business conditions. Further research also finds that commercial credit seems to be an effective channel for digital financial inclusion to alleviate financing constraints of SMEs, but corporate leverage also plays an important role in this process, playing a negative moderating role. In general, our study strengthens the effectiveness of digital inclusive finance in alleviating financing constraints of SMEs, at the same time, confirming the existence of commercial credit channels and the moderating effect of enterprises’ lever ratio and providing a feasible direction for alleviating financing constraints of enterprises.
Large-Scale Wildfire Mitigation Through Deep Reinforcement Learning
Authors: Altamimi Abdulelah , Lagoa Constantino , Borges José G. , McDill Marc E. , Andriotis C. P. , Papakonstantinou K. G.
Published: July 2022

Forest management can be seen as a sequential decision-making problem to determine an optimal scheduling policy, e.g., harvest, thinning, or do-nothing, that can mitigate the risks of wildfire. Markov Decision Processes (MDPs) offer an efficient mathematical framework for optimizing forest management policies. However, computing optimal MDP solutions is computationally challenging for large-scale forests due to the curse of dimensionality, as the total number of forest states grows exponentially with the numbers of stands into which it is discretized. In this work, we propose a Deep Reinforcement Learning (DRL) approach to improve forest management plans that track the forest dynamics in a large area. The approach emphasizes on prevention and mitigation of wildfire risks by determining highly efficient management policies. A large-scale forest model is designed using a spatial MDP that divides the square-matrix forest into equal stands. The model considers the probability of wildfire dependent on the forest timber volume, the flammability, and the directional distribution of the wind using data that reflects the inventory of a typical eucalypt (Eucalyptus globulus Labill) plantation in Portugal. In this spatial MDP, the agent (decision-maker) takes an action at one stand at each step. We use an off-policy actor-critic with experience replay reinforcement learning approach to approximate the MDP optimal policy. In three different case studies, the approach shows good scalability for providing large-scale forest management plans. The results of the expected return value and the computed DRL policy are found identical to the exact optimum MDP solution, when this exact solution is available, i.e., for low dimensional models. DRL is also found to outperform a genetic algorithm (GA) solutions which were used as benchmarks for large-scale model policy.
Identification of BST2 Contributing to the Development of Glioblastoma Based on Bioinformatics Analysis
Authors: Kong Yang , Xue Zhiwei , Wang Haiying , Cui Guangqiang , Chen Anjing , Liu Jie , Wang Jian , Li Xingang , Huang Bin
Published: July 2022

Rigorous molecular analysis of the immune cell environment and immune response of human tumors has led to immune checkpoint inhibitors as one of the most promising strategies for the treatment of human cancer. However, in human glioblastoma multiforme (GBM) which develops in part by attracting immune cell types intrinsic to the human brain (microglia), standard immunotherapy has yielded inconsistent results in experimental models and patients. Here, we analyzed publicly available expression datasets to identify molecules possibly associated with immune response originating from or influencing the tumor microenvironment in primary tumor samples. Using three glioma datasets (GSE16011, Rembrandt-glioma and TCGA-glioma), we first analyzed the data to distinguish between GBMs of high and low tumor cell purity, a reflection of the cellular composition of the tumor microenvironment, and second, to identify differentially expressed genes (DEGs) between these two groups using GSEA and other analyses. Tumor purity was negatively correlated with patient prognosis. The interferon gamma-related gene BST2 emerged as a DEG that was highly expressed in GBM and negatively correlated with tumor purity. BST2high tumors also tended to harbor PTEN mutations (31 vs. 9%, BST2high versus BST2low) while BST2low tumors more often had sustained TP53 mutations (8 versus 36%, BST2high versus BST2low). Prognosis of patients with BST2high tumors was also poor relative to patients with BST2low tumors. Further molecular in silico analysis demonstrated that high expression of BST2 was negatively correlated with CD8+ T cells but positively correlated with macrophages with an M2 phenotype. Further functional analysis demonstrated that BST2 was associated with multiple immune checkpoints and cytokines, and may promote tumorigenesis and progression through interferon gamma, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling and the TNF-α signaling via NF-kB pathway. Finally, a series of experiments confirmed that the expression of BST2 can be significantly increased by IFN induction, and knockdown of BST2 can significantly inhibit the growth and invasion of GBM cells, and may affect the phenotype of tumor-associated macrophages. In conclusion, BST2 may promote the progression of GBM and may be a target for treatment.
Spatial Transcriptomics for Tumor Heterogeneity Analysis
Authors: Li Qiongyu , Zhang Xinya , Ke Rongqin
Published: July 2022

The molecular heterogeneity of cancer is one of the major causes of drug resistance that leads to treatment failure. Thus, better understanding the heterogeneity of cancer will contribute to more precise diagnosis and improved patient outcomes. Although single-cell sequencing has become an important tool for investigating tumor heterogeneity recently, it lacks the spatial information of analyzed cells. In this regard, spatial transcriptomics holds great promise in deciphering the complex heterogeneity of cancer by providing localization-indexed gene expression information. This study reviews the applications of spatial transcriptomics in the study of tumor heterogeneity, discovery of novel spatial-dependent mechanisms, tumor immune microenvironment, and matrix microenvironment, as well as the pathological classification and prognosis of cancer. Finally, future challenges and opportunities for spatial transcriptomics technology’s applications in cancer are also discussed.
Genetically Predicted Circulating Levels of Cytokines and the Risk of Cancer
Authors: Song Jie , Li Aole , Qian Yu , Liu Bin , Lv Linshuoshuo , Ye Ding , Sun Xiaohui , Mao Yingying
Published: July 2022

Background

Inflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach.

Method

We used genetic variants associated with circulating levels of cytokines from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns as instrumental variables. Summary level data of 20 site-specific cancer were obtained from the UK BioBank including up to 456,348 participants of European ancestry. We performed two-sample MR analyses using inverse-variance weighted (IVW) method as the main method, followed by weighted-median and likelihood-based methods as sensitivity analysis. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test.

Results

224 genetic variants associated with 27 circulating cytokines achieving genome-wide significance (P<5×10-8) were used as IVs. After Bonferroni correction, genetically predicted high levels of interleukin-18 (IL-18) were associated with a decreased risk of acute myeloid leukemia (odds ratio (OR) per 1 standard deviation (SD) increase = 0.55, 95% confidence interval (CI):0.43-0.69,P=5.39×10-7), and circulating levels of IL-17 were associated with altered stomach cancer risk (OR per 1 SD increase = 0.15, 95% CI: 0.07-0.36,P=1.25×10-5) by IVW. Results were stable across sensitivity analyses, and MR-Egger regression did not suggest the presence of directional pleiotropy. Additionally, we found suggestive evidence for 48 cytokine-cancer associations including tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and cutaneous T-cell attracting chemokine (CTACK) with the risk of several types of cancer (9.26×10-5≤P<0.05).

Conclusions

By using a genetic epidemiological approach, our study systematically evaluated the role of circulating cytokines on the risk of cancer, and provided clues for potential therapeutic targets. However, the exact underlying biological mechanism warrants further investigation.
Function of CTLGA9 Amino Acid Residue Leucine-6 in Modulating Cry Toxicity
Authors: Alam Intikhab , Batool Khadija , Idris Aisha Lawan , Tan Weilong , Guan Xiong , Zhang Lingling
Published: July 2022

Aedes aegypti is a crucial vector for many arboviral diseases that cause millions of deaths worldwide and thus is of major public health concern. Crystal (Cry) proteins, which are toxins produced by Bacillus thuringiensis, are structurally organized into three-domains, of which domain II is the most variable in terms of binding towards various toxin receptors. The binding of Cry11Aa to putative receptor such as aminopeptidase-N (APN) is explicitly inhibited by midgut C-type lectins (CTLs). The similarity between the domain II fold of Cry11Aa toxin and the carbohydrate recognition domain in the CTLs is a possible structural basis for the involvement of Cry domain II in the recognition of carbohydrates on toxin receptors. In this study, a site-directed point mutation was introduced into the A. aegypti CTLGA9 gene on the basis of molecular docking findings, leading to substitution of the Leucine-6 (Leu-6) residue in the protein with alanine. Subsequently, functional monitoring of the mutated protein was carried out. Unlike the amino acid residues of wild-type CTLGA9, none of the residues of mutant (m) CTLGA9 were competed with Cry11Aa for binding to the APN receptor interface. Additionally, ligand blot analysis showed that both wild-type and mutant CTLGA9 had similar abilities to bind to APN and Cry11Aa. Furthermore, in the competitive ELISA in which labeled mutant CTLGA9 (10 nM) was mixed with increasing concentrations of unlabeled Cry11Aa (0–500 nM), the mutant showed no competition with Cry11Aa for binding to APN., By contrast, in the positive control sample of labeled wild type CTLGA9 mixed with same concentrations of Cry11Aa competition between the two ligands for binding to the APN was evident. These results suggest that Leucine-6 may be the key site involved in the competitive receptor binding between CTLGA9 and Cry11Aa. Moreover, according to the bioassay results, mutant CTLGA9 could in fact enhance the toxicity of Cry11Aa. Our novel findings provide further insights into the mechanism of Cry toxicity as well as a theoretical basis for enhancing the mosquitocidal activity of these toxin through molecular modification strategies.
Radiotheranostic Agents in Hematological Malignancies
Authors: Caers Jo , Duray Elodie , Vrancken Louise , Marcion Guillaume , Bocuzzi Valentina , De Veirman Kim , Krasniqi Ahmet , Lejeune Margaux , Withofs Nadia , Devoogdt Nick , Dumoulin Mireille , Karlström Amelie Eriksson , D’Huyvetter Matthias
Published: July 2022

Radioimmunotherapy (RIT) is a cancer treatment that combines radiation therapy with tumor-directed monoclonal antibodies (Abs). Although RIT had been introduced for the treatment of CD20 positive non-Hodgkin lymphoma decades ago, it never found a broad clinical application. In recent years, researchers have developed theranostic agents based on Ab fragments or small Ab mimetics such as peptides, affibodies or single-chain Abs with improved tumor-targeting capacities. Theranostics combine diagnostic and therapeutic capabilities into a single pharmaceutical agent; this dual application can be easily achieved after conjugation to radionuclides. The past decade has seen a trend to increased specificity, fastened pharmacokinetics, and personalized medicine. In this review, we discuss the different strategies introduced for the noninvasive detection and treatment of hematological malignancies by radiopharmaceuticals. We also discuss the future applications of these radiotheranostic agents.
Use of Tumor Necrosis Factor-α Antagonists Is Associated With Attenuated IgG Antibody Response Against SARS-CoV-2 in Vaccinated Patients With Inflammatory Bowel Disease
Authors: Otten Antonius T. , Bourgonje Arno R. , Horinga Petra P. , van der Meulen Hedwig H. , Festen Eleonora A. M. , van Dullemen Hendrik M. , Weersma Rinse K. , van Leer-Buter Coretta C. , Dijkstra Gerard , Visschedijk Marijn C.
Published: July 2022

Introduction

Patients with Inflammatory Bowel Disease (IBD) frequently receive immunomodulating treatment, which may render them at increased risk of an attenuated immune response upon vaccination. In this study, we assessed the effects of different types of commonly prescribed immunosuppressive medications on the serological response after vaccination against SARS-CoV-2 in patients with IBD.

Methods

In this prospective observational cohort study, IgG antibody titers against SARS-CoV-2 were measured 2-10 weeks after completion of standard vaccination regimens in patients with IBD. Clinical characteristics, previous history of SARS-CoV-2 infection, type of vaccine (mRNA- or vector-based) and medication use were recorded at the time of sampling. Subsequently, a chemiluminescent microparticle immunoassay was used for the quantitative determination of IgG antibodies against the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2.

Results

Three hundred and twelve (312) patients with IBD were included (172 Crohn’s disease [CD] and 140 ulcerative colitis [UC]). Seroconversion (defined as titer of >50 AU/ml) was achieved in 98.3% of patients. Antibody concentrations were significantly lower in patients treated with TNF-α-antagonists vs. non-users of TNF-α-antagonists (geometric mean [95% confidence interval]: 2204 [1655-2935] vs. 5002 [4089-6116] AU/ml, P<0.001). In multivariable models, use of TNF-α-antagonists (P<0.001), vector vaccines (P<0.001), age (>50 years) (P<0.01) and CD (P<0.05) were independently associated with lower anti-SARS-CoV-2 antibody titers. In patients who received mRNA vaccines, users of thiopurines (either prescribed as monotherapy or in combination with biologicals) demonstrated significantly lower antibody titers compared to thiopurine non-users (P<0.05).

Conclusion

Despite reassuring findings that most patients with IBD have detectable antibodies after anti-SARS-CoV-2 vaccination, TNF-α-antagonists were found to be strongly associated with an attenuated IgG antibody response after vaccination against SARS-CoV-2, independent of vaccine type, the time elapsed after vaccination and blood sampling, prior SARS-CoV-2 infection and patient age. Patients treated with thiopurines and receiving mRNA-based vaccines demonstrated lower anti-SARS-CoV-2 antibody titers compared with non-users.
Single-cell RNA Sequencing Analysis Reveals New Immune Disorder Complexities in Hypersplenism
Authors: Zhao Hai-chao , Chen Chang-zhou , Song Huang-qin , Wang Xiao-xiao , Zhang Lei , Zhao Hao-liang , He Jie-feng
Published: July 2022

Hypersplenism (HS) is a concomitant symptom of liver or blood disease. Not only does the treatment of HS face challenges, but the transcriptome of individual cells is also unknown. Here, the transcriptional profiles of 43,037 cells from four HS tissues and one control tissue were generated by the single-cell RNA sequencing and nine major cell types, including T-cells, B-cells, NK cells, hematopoietic stem cells, neutrophil cells, mast cells, endothelial cells, erythrocytes, and dendritic cells were identified. Strikingly, the main features were the lack of CCL5+ B-cells in HS and the presence of SESN1+ B cells in HS with hepatocellular carcinoma (HS-HCC). In cell-cell interaction analysis, CD74-COPA and CD94-HLA-E in HS were found to be up-regulated. We further explored HS-specifically enriched genes (such as FKBP5, ADAR, and RPS4Y1) and found that FKBP5 was highly expressed in HCC-HS, leading to immunosuppression. Taken together, this research provides new insights into the genetic characteristics of HS via comprehensive single-cell transcriptome analysis.