bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Hypercholesterolemia May Involve in Preterm Birth
Authors: Chen Jingfei , Hua Lan , Luo Fei , Chen Jianlin
Published: July 2022

Maternal hypercholesterolemia during pregnancy is associated with an increased risk of preterm birth which is defined as <37 weeks of complete gestation. However, the underlying mechanism for the association between hypercholesterolemia and preterm birth is not fully understood. Macrophage, as one of the largest cell types in the placenta, plays a very critical role in mediating inflammation and triggers labor initiation. Here, we hypothesize that macrophages can uptake maternal excessive cholesterol leading to its accumulation, resulting in a breach of the immune tolerance and precipitating labor.
Chinese Herbal Medicine Reduces the Risk of Heart Failure in Hypertensive Patients: A Nationwide, Retrospective, Cohort Study
Authors: Liu Chun-Ting , Hung I-Ling , Hsu Chung Y. , Hu Kai-Chieh , Chen Yung-Hsiang , Tsai Ming-Yen
Published: July 2022

Background

Hypertension (HTN) is the leading preventable risk factor for cardiovascular disease worldwide. Patients with HTN are at higher risk for heart failure (HF). The currently available therapeutic approaches for HTN do not always optimally control blood pressure or are not suitable for hypertensive patients who have a higher number of comorbidities. This study aimed to determine whether Chinese herbal medicine (CMH)-based interventions could reduce the risk of HF in hypertensive patients.

Methods

This retrospective study randomly selected 2 million enrollees from the National Health Insurance Research Database and identified 507,608 patients who were newly diagnosed with HTN in 2000–2017. After 1:1 frequency-matching by age, sex, index year, income, urbanization, duration of HTN, comorbidities and antihypertensive medications, we selected 8,912 eligible patients in each group. During 16 years of follow-up, 380 CHM users and 426 CHM non-users developed HF, representing incidence rates of 6.29 and 7.43 per 1,000 person-years, respectively.

Results

CHM users had significantly lower HF risk compared with CHM non-users (adjusted HR = 0.85, 95% CI 0.74–0.98). The markedly predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR = 0.65). The frequently prescribed formula, Jia-Wei-Xiao-Yao-San, and the single herbs Ge Gen, Huang Qi, Du Zhong, Huang Qin, and Chuan Xiong were significantly associated with lower risk of HF.

Conclusions

This population-based study revealed decreased HF risk in hypertensive patients with CHM use. These findings may provide a reference for HF prevention strategies and support the integration of CHM into clinical intervention programs that provide a favorable prognosis for hypertensive patients.
Case Report: Steroid-Responsive Takotsubo Cardiomyopathy Associated With Cytokine Storm and Obstructive Shock
Authors: Gudenkauf Brent , Goetsch Michael R. , Vakil Rachit M. , Cingolani Oscar , Adamo Luigi
Published: July 2022

A growing body of evidence suggests that inflammation may play a key role in the development of Takotsubo stress cardiomyopathy. Here, we report the case of a 63-year-old woman who presented with chest pain and was diagnosed with this cardiomyopathy. After an initial improvement, the patient experienced a systemic inflammatory response of unclear origin and deteriorated rapidly into obstructive shock. Her presentation was considered consistent with cytokine storm. She was, therefore, treated with steroids with rapid improvement in her clinical picture. She relapsed after the taper. Endomyocardial biopsy soon after initiation of pulse dose steroids showed macrophage and lymphocytic infiltration. This case highlights the potential intimate connection between systemic inflammatory response and Takotsubo stress cardiomyopathy and contributes to the evolving understanding of inflammation in the pathogenesis of this disease.
Smartwatch-Based Blood Pressure Measurement Demonstrates Insufficient Accuracy
Authors: Falter Maarten , Scherrenberg Martijn , Driesen Karen , Pieters Zoë , Kaihara Toshiki , Xu Linqi , Caiani Enrico Gianluca , Castiglioni Paolo , Faini Andrea , Parati Gianfranco , Dendale Paul
Published: July 2022

Background

Novel smartwatch-based cuffless blood pressure (BP) measuring devices are coming to market and receive FDA and CE labels. These devices are often insufficiently validated for clinical use. This study aims to investigate a recently CE-cleared smartwatch using cuffless BP measurement in a population with normotensive and hypertensive individuals scheduled for 24-h BP measurement.

Methods

Patients that were scheduled for 24-h ambulatory blood pressure monitoring (ABPM) were recruited and received an additional Samsung Galaxy Watch Active 2 smartwatch for simultaneous BP measurement on their opposite arm. After calibration, patients were asked to measure as much as possible in a 24-h period. Manual activation of the smartwatch is necessary to measure the BP. Accuracy was calculated using sensitivity, specificity, positive and negative predictive values and ROC curves. Bland-Altman method and Taffé methods were used for bias and precision assessment. BP variability was calculated using average real variability, standard deviation and coefficient of variation.

Results

Forty patients were included. Bland-Altman and Taffé methods demonstrated a proportional bias, in which low systolic BPs are overestimated, and high BPs are underestimated. Diastolic BPs were all overestimated, with increasing bias toward lower BPs. Sensitivity and specificity for detecting systolic and/or diastolic hypertension were 83 and 41%, respectively. ROC curves demonstrate an area under the curve (AUC) of 0.78 for systolic hypertension and of 0.93 for diastolic hypertension. BP variability was systematically higher in the ABPM measurements compared to the smartwatch measurements.

Conclusion

This study demonstrates that the BP measurements by the Samsung Galaxy Watch Active 2 show a systematic bias toward a calibration point, overestimating low BPs and underestimating high BPs, when investigated in both normotensive and hypertensive patients. Standards for traditional non-invasive sphygmomanometers are not met, but these standards are not fully applicable to cuffless devices, emphasizing the urgent need for new standards for cuffless devices. The smartwatch-based BP measurement is not yet ready for clinical usage. Future studies are needed to further validate wearable devices, and also to demonstrate new possibilities of non-invasive, high-frequency BP monitoring.
An Exceptionally Preserved Terrestrial Record of LIP Effects on Plants in the Carnian (Upper Triassic) Amber-Bearing Section of the Dolomites, Italy
Authors: Roghi Guido , Gianolla Piero , Kustatscher Evelyn , Schmidt Alexander R. , Seyfullah Leyla J.
Published: July 2022

The Carnian Pluvial Episode (CPE) has been recognized as a time of plant radiations and originations, likely related to observed swift changes from xerophytic to more hygrophytic floras. This suggests that the increasing humidity causally resulting from LIP volcanism was the trigger for these changes in the terrestrial realm. Understanding the cause and effects of the CPE on the plant realm, requires study of well-preserved floras that are precisely aligned with the CPE. We therefore focus on the best age-constrained section within the CPE for the terrestrial to marginal marine environment to understand the floristic composition at the early CPE. This is found in the Dolomites, Italy, and is remarkable for the preservation of the oldest fossiliferous amber found in the rock record. An integrated study of palynomorphs and macro-remains related to the conifer families of the fossil resin bearing level brings together the floral components from this section. This observed mixture of different taxa of extinct and modern conifer families underlines firmly the effects of the LIP-induced CPE on the evolution and radiation of conifers.
Multi-Scale Pore Structure Characterization of Silurian Marine Shale and Its Coupling Relationship With Material Composition: A Case Study in the Northern Guizhou Area
Authors: Du Wei , Lin Ruiqin , Shi Fulun , Luo Nina , Wang Yisong , Fan Qingqing , Cai Junying , Zhang Ziya , Liu Li , Yin Wei , Zhao Fuping , Sun Zhao , Chen Yi
Published: July 2022

Investigation of pore structure is vital for shale reservoir evaluation and also “sweet spot” prediction. As the strong heterogeneity in pore types, morphology, and size distributions of organic matter-rich shales, it is essential to combine different approaches to comprehensively characterize them.Field emission-scanning electron microscopy (FE-SEM), low-pressure gas (CO2 and N2) adsorption, and high-pressure mercury intrusion (HPMI) were employed to systematically investigate the pore structure of the lower Longmaxi shale reservoirs in the northern Guizhou area. The results show that the shales can be divided into four lithofacies based on mineral composition, namely, siliceous shale (SS), clay shale (CS), carbonate shale (CAS), and mixed shale (MS), among which siliceous shale is the primary lithofacies of the Longmaxi shale. Numerous organic matter (OM)-hosted pores, clay interlayer pores, interparticle pores, and intraparticle pores were identified within shale reservoirs. The specific surface area ranges from 11.3 to 27.4 m2/g, with an average of 18.1 m2/g. It exhibits a strong positive correlation with TOC contents, suggesting that organic matter is the major contributor to the specific surface areas. A wide range of pore size distribution was measured by integration of gas adsorption and HPMI. It is shown that the pore size is primarily distributed within ∼100 nm, corresponding to micropores, mesopores, and part of macropores. The total pore volume, which is mostly derived from the contribution of micropores and mesopores, remains within a range of 0.11 to 0.025 ml/g, with an average of 0.018 ml/g. Furthermore, the volume of micropores and mesopores is mainly controlled by organic matter contents. The dissolution pore contributes most to the macropore space within shale reservoirs, based on the positive correlation with macropore volume and easily dissolved minerals, including carbonate and feldspar. Also, the total pores volume is mainly dominated by organic matter and carbonate contents. This is possibly attributed to the easily dissolved and rigid features of carbonate, which can protect the primary interparticle pores due to its high compression resistance and is conducive to forming abundant dissolution pores. OM-rich carbonate-bearing mixed shale may be the most favorable lithofacies for gas storage in the northern Guizhou area.
Unilateral Surgery for Medullary Thyroid Carcinoma: Seeking for Clinical Practice Guidelines
Authors: Zhang Daqi , Colombo Carla , Sun Hui , Kim Hoon Yub , Pino Antonella , De Leo Simone , Gazzano Giacomo , Persani Luca , Dionigi Gianlorenzo , Fugazzola Laura
Published: July 2022

Optimized preoperative diagnostic tools with calcitonin tests, ultrasound features, functional imaging modalities, and genetic testing to detect hereditary forms have led to an increased rate of earlier diagnosis and surgery for medullary thyroid cancer (MTC). This helps to adapt the primary surgery to the tumor stage and avoid surgical overtreatment for localized tumor growth, i.e., deviating from the regularly recommended thyroidectomy with bilateral central lymph node dissection in favor of a limited unilateral approach. To limit primary surgical therapy, it is crucial that the MTC is clinically unifocal, sporadic, and confined to the thyroid, and that calcitonin levels indicate biochemical recovery after surgery. The main requirement for such a limited approach is the availability of frozen section studies that reliably indicate (i) R0 resection of the MTC, (ii) absence of infiltration of the organ capsule, (iii) lack of desmoplasia (i.e., evidence of the metastatic potential of the MTC), (iiii) absence of contralateral disease or precancerous lesions. Informed consent is mandatory from the patient, who has been fully informed of the advantages, disadvantages, and potential risks of not undergoing the “classic” surgical procedure. The aim of this article is to review the guidelines for the management of early-stage MTC.
Finite Element Analysis of Osteoporotic and Osteoblastic Vertebrae and Its Association With the Proton Density Fat Fraction From Chemical Shift Encoding-Based Water-Fat MRI – A Preliminary Study
Authors: Greve Tobias , Rayudu Nithin Manohar , Dieckmeyer Michael , Boehm Christof , Ruschke Stefan , Burian Egon , Kloth Christopher , Kirschke Jan S. , Karampinos Dimitrios C. , Baum Thomas , Subburaj Karupppasamy , Sollmann Nico
Published: July 2022

Purpose

Osteoporosis is prevalent and entails alterations of vertebral bone and marrow. Yet, the spine is also a common site of metastatic spread. Parameters that can be non-invasively measured and could capture these alterations are the volumetric bone mineral density (vBMD), proton density fat fraction (PDFF) as an estimate of relative fat content, and failure displacement and load from finite element analysis (FEA) for assessment of bone strength. This study’s purpose was to investigate if osteoporotic and osteoblastic metastatic changes in lumbar vertebrae can be differentiated based on the abovementioned parameters (vBMD, PDFF, and measures from FEA), and how these parameters correlate with each other.

Materials and Methods

Seven patients (3 females, median age: 77.5 years) who received 3-Tesla magnetic resonance imaging (MRI) and multi-detector computed tomography (CT) of the lumbar spine and were diagnosed with either osteoporosis (4 patients) or diffuse osteoblastic metastases (3 patients) were included. Chemical shift encoding-based water-fat MRI (CSE-MRI) was used to extract the PDFF, while vBMD was extracted after automated vertebral body segmentation using CT. Segmentation masks were used for FEA-based failure displacement and failure load calculations. Failure displacement, failure load, and PDFF were compared between patients with osteoporotic vertebrae versus patients with osteoblastic metastases, considering non-fractured vertebrae (L1-L4). Associations between those parameters were assessed using Spearman correlation.

Results

Median vBMD was 59.3 mg/cm3 in osteoporotic patients. Median PDFF was lower in the metastatic compared to the osteoporotic patients (11.9% vs. 43.8%, p=0.032). Median failure displacement and failure load were significantly higher in metastatic compared to osteoporotic patients (0.874 mm vs. 0.348 mm, 29,589 N vs. 3,095 N, p=0.034 each). A strong correlation was noted between PDFF and failure displacement (rho -0.679, p=0.094). A very strong correlation was noted between PDFF and failure load (rho -0.893, p=0.007).

Conclusion

PDFF as well as failure displacement and load allowed to distinguish osteoporotic from diffuse osteoblastic vertebrae. Our findings further show strong associations between PDFF and failure displacement and load, thus may indicate complimentary pathophysiological associations derived from two non-invasive techniques (CSE-MRI and CT) that inherently measure different properties of vertebral bone and marrow.
Bioinformatics Analysis Identifies Potential Ferroptosis Key Gene in Type 2 Diabetic Islet Dysfunction
Authors: Ye Haowen , Wang Ruxin , Wei Jinjing , Wang Ying , Zhang Xiaofang , Wang Lihong
Published: July 2022

Background

Islet β cells dysfunction (IBCD) is a cortical component in pathogenesis of type 2 diabetic mellitus (T2DM). However, the relationship of ferroptosis and IBCD remains unknown. This study was aimed to screen potential ferroptosis key genes to reveal latent physiological and pathological process of IBCD in T2DM.

Methods

Firstly, T2DM key genes were screened by combining with differentially expressed genes (DEGs) analysis and WGCNA. Then, ferroptosis-related genes (FRGs) in IBCD of T2DM were identified by taking the intersection between T2DM key genes and FRGs. Finally, T2DM-FRGs were validated in another T2DM dataset as well as islet single-cell RNA sequencing dataset and the miRNA regulated T2DM-FRG was predicted by using four miRNA databases.

Results

89 T2DM key genes were identified between DEGs and WGCNA. Then, 3 T2DM-FRGs were screened by taking the intersection of T2DM key genes and FRGs, namely ITGA6, MGST1 and ENO2. At last, MGST1 were validated as the T2DM-FRG in another T2DM islet issues dataset and islet single-cell RNA sequencing dataset.

Conclusion

MGST1 may be the potential ferroptosis key gene of IBCD in T2DM.
Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials
Authors: Hu Weiting , Song Rui , Cheng Rui , Liu Caihong , Guo Rui , Tang Wei , Zhang Jie , Zhao Qian , Li Xing , Liu Jing
Published: July 2022

The association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of various kinds of thyroid disorders remains uncertain. We aimed to evaluate the relationship between the use of GLP-1 receptor agonists and the occurrence of 6 kinds of thyroid disorders. We searched PubMed (MEDLINE), EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science from database inception to 31 October 2021 to identify eligible randomized controlled trials (RCTs). We performed meta-analysis using a random-effects model to calculate risk ratios (RRs) and 95% confidence intervals (CIs). A total of 45 trials were included in the meta-analysis. Compared with placebo or other interventions, GLP-1 receptor agonists’ use showed an association with an increased risk of overall thyroid disorders (RR 1.28, 95% CI 1.03-1.60). However, GLP-1 receptor agonists had no significant effects on the occurrence of thyroid cancer (RR 1.30, 95% CI 0.86-1.97), hyperthyroidism (RR 1.19, 95% CI 0.61-2.35), hypothyroidism (RR 1.22, 95% CI 0.80-1.87), thyroiditis (RR 1.83, 95% CI 0.51-6.57), thyroid mass (RR 1.17, 95% CI 0.43-3.20), and goiter (RR 1.17, 95% CI 0.74-1.86). Subgroup analyses and meta-regression analyses showed that underlying diseases, type of control, and trial durations were not related to the effect of GLP-1 receptor agonists on overall thyroid disorders (all P subgroup > 0.05). In conclusion, GLP-1 receptor agonists did not increase or decrease the risk of thyroid cancer, hyperthyroidism, hypothyroidism, thyroiditis, thyroid mass and goiter. However, due to the low incidence of these diseases, these findings need to be examined further.

Systematic Review Registration

PROSPERO https://www.crd.york.ac.uk/prospero/, identifier: CRD42021289121.
Predictive Role of NEK6 in Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma
Authors: Yang Zhi-Min , Liao Bing , Yang Si-Si , Su Tong , Zhang Jing , Wang Wei-Ming
Published: July 2022

Head and neck squamous cell carcinoma (HNSCC), as one of the common malignant tumors, seriously threatens human health. NEK6 (Never in Mitosis A (NIMA) related kinases 6), as a cyclin, promotes cancer cell proliferation and cancer progression. However, the prognostic value of NEK6 and its correlation with immune cell infiltration in HNSCC remain unclear. In this study, we comprehensively elucidated the prognostic role and potential function of NEK6 expression in HNSCC. The expression of NEK6 was significantly up-regulated by immunohistochemistry in HNSCC. Upregulation of NEK6 expression in gene expression studies predicts poor prognosis in HNSCC patients. The results of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set variation analysis indicated that NEK6 is mainly involved in extracellular matrix metabolism and EMT processes. The expression of NEK6 increased with the level of immune cell infiltration and the expression of various immune checkpoints. In conclusion, NEK6 may serve as a candidate prognostic predictor and may predict the response of HNSCC patients to immunotherapy.
Alterations of Cytokine Profiles in Patients With Recurrent Implantation Failure
Authors: Guo Ling , Guo Anliang , Yang Fang , Li Li , Yan Junhao , Deng Xiaohui , Dai Caifeng , Li Yan
Published: July 2022

Serum cytokine profile and T helper (Th)1/Th2 cell balance are related to the success of embryo implantation, although not yet firmly linked to recurrent implantation failure (RIF), a repeated failure to achieve clinical pregnancy following multiple high-quality embryo transfer. In this prospective study, comprehensive bioinfomatic analysis and logistic regression analysis were used to compare the serum cytokine profiles of 41 RIF patients with those of 29 subjects with first-cycle successful pregnancy in the mid-luteal phase and to assess the alterations of cytokine profiles in patients with clinical pregnancy at five weeks post-transplantation. We found several elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and increased Th1/Th2 cytokine ratios in RIF patients compared to control subjects. Specifically, the receiver operating characteristic (ROC) curve generated using multiple indicators provides a high predictive value for diagnosing RIF (area under the curve [AUC] = 0.94, 95% confidence interval [CI] 0.87-1.00,P< 0.0001), with a sensitivity of 96.55% and a specificity of 87.50%. Meanwhile, at five weeks post-transplantation, patients in both groups diagnosed with clinical pregnancy exhibited increased levels of several cytokines compared with pre-pregnancy levels, and a gradual shift in Th1/Th2 balance toward Th2. These findings suggest that inflammatory serum cytokines and the predominance of Th1 cells likely contribute to RIF and possibly reflect the immune environment at the maternal-fetal interface, suggesting their value as outcome indicators in assisted reproductive therapy.
Particle Swarm-Assisted Artificial Neural Networks for Making Liquefied Natural Gas Processes Feasible Under Varying Feed Conditions
Authors: Ahmad Ashfaq , Qadeer Kinza , Naquash Ahmad , Riaz Fahid , Hasan Mudassir , Qyyum Muhammad Abdul , Lee Moonyong
Published: July 2022

Natural gas (NG) has been widely recognized as a cleaner fuel compared to other fossil fuels. Reserves of NG are typically located in remote areas, and their conditions and compositions vary geographically. The NG from such areas is transported in the form of liquefied natural gas (LNG). Liquefying NG is highly complex. Generally, the process is designed to be carried out under fixed natural gas (NG) conditions; hence, it may not perform well under variable NG conditions. Considering this issue, the use of an artificial intelligence approach, rather than the conventional optimization one, was investigated to make the LNG process feasible under variable NG conditions. This study is the first in this research area to train an artificial neural network (ANN) using the particle swarm optimization (PSO) algorithm as a learning method. The developed PSO-ANN model was used to predict the decision variables of a single mixed refrigerant (SMR) LNG process for its feasible design under varying NG conditions. The correctness of the predicted set of decision variables (NG conditions) was verified by inputting them into Aspen HYSYS. The output of the SMR-LNG process was the overall power at a constrained minimum internal temperature approach (MITA) value, i.e., 1.0 ≤ MITA ≤3.0. The prediction results of the PSO-ANN model were compared with those of the classical ANN backpropagation learning method. The success rate of the proposed PSO-ANN model was 80%. Furthermore, the proposed model can make the LNG process feasible for a diverse range of temperature and pressure values. A feasible process with a better MITA value can also be achieved by tuning the model parameters.
Development of Community-Based Peer-to-Peer Energy Trading Mechanism Using Z-Bus Network Cost Allocation
Authors: Noorfatima Nadya , Choi Yunjeong , Lee Semi , Jung Jaesung
Published: July 2022

Community-based peer-to-peer (P2P) energy trading is applied to manage local market transactions to maximize the social welfare of the community. However, the increasing number of distributed energy resources in distribution systems affects the performance of community-operators in P2P energy trading. Hence, this study develops a community-based P2P energy trading mechanism to ensure fair profit allocation and reduce computation cost, even with numerous participants. To achieve this, the P2P participants were aggregated into smaller groups using the K-means clustering method, allowing the community manager to perform market transactions in a hierarchical manner. In the hierarchical P2P market, social welfare maximization is performed in the higher layer and profit distribution in the lower layer. Furthermore, the Z-bus network cost allocation method was applied to determine the network usage cost and was thus considered as a parameter to ensure fair profit allocation based on the Shapley value. The proposed method was simulated in South Korean P2P energy trading at various market scales. The results showed an improvement in the proposed method compared with conventional single-layer community-based P2P energy trading.
Wage Gaps in Energy Industry: The Role of Sector
Authors: Li Mingming , Tu Chunlu , Zhang Fumei
Published: July 2022

Although wage gaps brought about by differences between sectors has been widely discussed, its specificality in the energy industry has received little attention. Due to the nature of the Chinese energy sector as a monopoly and to the influence of the Soviet Union, the wages of public sector employees in the energy industry in China are much less influenced by market mechanisms and are much higher than those in the private sector. This paper is the first article to explore the impact of the public sector on wage gaps in the energy industry using the China Urban Household Survey for 2004, 2008, and 2013. The cross-sectional regression results show a significant and continuous wage premium exists between sectors, although the size of the premium declined slightly over time. The Blinder-Oaxaca decomposition finds unexplainable part and discrimination dominates the wage gaps. The quantile regression results show that education and work experience have significant effects on low- and middle-wage groups. The heterogeneity analysis considers two sub-industries and finds that the wage gaps between the two sectors are much higher in the extractive segment of the energy industry than in the production and supply sector of the industry. The results of the study reveal that market-oriented reforms in China are not yet complete, because the obvious premium on wages in the public sector means they are not determined by market mechanisms. Finally, the paper provides policy recommendations from three perspectives: further market-oriented reform, elimination of discrimination, and education and vocational training.
A Preliminary European-Scale Assessment of Microplastics in Urban Wastewater
Authors: Obermaier Nathan , Pistocchi Alberto
Published: July 2022

Microplastics (MP) are not well defined from an analytical point of view and their measurement in the environment is still challenging. At the same time, their increasingly widespread presence is raising concerns for human health and ecosystems. In this contribution, we present a preliminary European-scale assessment of the environmental input of MP through urban wastewater and urban runoff. We quantify the emissions associated with urban wastewater based on the range of observed concentrations in wastewater treatment plants (WWTPs) effluents, and the emissions from tire wear particles (TWP) by assuming that a percentage of the particles generated on roads eventually reaches surface waters. In spite of the large uncertainties entailed in the calculation, it is apparent that TWP dominate the input of total plastic loads into European surface waters. The management of urban runoff, road runoff, and combined sewer overflows (CSO) is essential to control the emissions of MP from urban areas. On the other hand, WWTPs retain the majority of MP in the sewage sludge. The spreading of sewage sludge onto soil therefore represents a potential pathway of MP from urban wastewater into the environment.
Spatio-Temporal Evolution of Sandy Land and its Impact on Soil Wind Erosion in the Kubuqi Desert in Recent 30 Years
Authors: Dang Xiaohong , Na Ya , Chi Wenfeng , Zhao Jiangjia , Zhao Yuanyuan , Wang Yue , Wu Xiaoguang , Wang Yuetian
Published: July 2022

Continuous remote-sensing monitoring of sand in desert areas and the exploration of the spatio–temporal evolution characteristics of soil–wind erosion has an important scientific value for desertification prevention and ecological restoration. In this study, the Kubuqi Desert was selected as the study area, and the Landsat series satellite remote sensing data, supplemented by satellite remote sensing data such as GE images, SPOT-5, ZY-3, GF-1/2/6, etc., integrated object-oriented, decision tree, and auxiliary human–computer interaction interpretation methods, developed the Kubuqi Desert area dataset from 1990 to 2020, and established a soil erosion intensity database of the past 30 years based on the soil–wind erosion correction equation. The results show that the application of the training samples obtained by a high-score collaborative ground sampling to land use/cover classification in desert areas can effectively improve the efficiency of remote-sensing mapping of sand changes and the accuracy of change information identification, and the overall accuracy of the classification results is 95%. In general, the sandy area of the Kubuqi Desert area has decreased year by year, during which the mobile sand in the hinterland of the desert has expanded in a scattered distribution. The overall soil–wind erosion intensity showed a downward trend, especially since 2000; the ecological improvement trend after the implementation of desertification control projects is obvious. Changes in the sand type contributed the most to the reduction of soil–wind erosion intensity (contribution 81.14%), ecological restoration played a key role in reducing the soil–wind erosion intensity (contribution 14.42%), and the increase of forest and grass vegetation covers and agricultural oases played a positive role in solidifying the soil- and wind-proof sand fixation. The pattern of sandy land changes in desert areas is closely related to the national ecological civilization construction policy and the impact of climate change.
Whole-Genome Sequencing and Genomic Variant Analysis of Kazakh Individuals
Authors: Kairov Ulykbek , Molkenov Askhat , Sharip Aigul , Rakhimova Saule , Seidualy Madina , Rhie Arang , Kozhamkulov Ulan , Zhabagin Maxat , Kim Jong-Il , Lee Joseph H. , Terwilliger Joseph D. , Seo Jeong-Sun , Zhumadilov Zhaxybay , Akilzhanova Ainur
Published: July 2022

Kazakhstan, the ninth-largest country in the world, is located along the Great Silk Road and connects Europe with Asia. Historically, its territory has been inhabited by nomadic tribes, and modern-day Kazakhstan is a multiethnic country with a dominant Kazakh population. We sequenced and analyzed the genomes of five ethnic Kazakhs at high coverage using the Illumina HiSeq2000 next-generation sequencing platform. The five Kazakhs yielded a total number of base pairs ranging from 87,308,581,400 to 107,526,741,301. On average, 99.06% were properly mapped. Based on the Het/Hom and Ti/Tv ratios, the quality of the genomic data ranged from 1.35 to 1.49 and from 2.07 to 2.08, respectively. Genetic variants were identified and annotated. Functional analysis of the genetic variants identified several variants that were associated with higher risks of metabolic and neurogenerative diseases. The present study showed high levels of genetic admixture of Kazakhs that were comparable to those of other Central Asians. These whole-genome sequence data of healthy Kazakhs could contribute significantly to biomedical studies of common diseases as their findings could allow better insight into the genotype–phenotype relations at the population level.
Functions and Interactions of Mammalian KDM5 Demethylases
Authors: Pavlenko Egor , Ruengeler Till , Engel Paulina , Poepsel Simon
Published: July 2022

Mammalian histone demethylases of the KDM5 family are mediators of gene expression dynamics during developmental, cellular differentiation, and other nuclear processes. They belong to the large group of JmjC domain containing, 2-oxoglutarate (2-OG) dependent oxygenases and target methylated lysine 4 of histone H3 (H3K4me1/2/3), an epigenetic mark associated with active transcription. In recent years, KDM5 demethylases have gained increasing attention due to their misregulation in many cancer entities and are intensively explored as therapeutic targets. Despite these implications, the molecular basis of KDM5 function has so far remained only poorly understood. Little is known about mechanisms of nucleosome recognition, the recruitment to genomic targets, as well as the local regulation of demethylase activity. Experimental evidence suggests close physical and functional interactions with epigenetic regulators such as histone deacetylase (HDAC) containing complexes, as well as the retinoblastoma protein (RB). To understand the regulation of KDM5 proteins in the context of chromatin, these interactions have to be taken into account. Here, we review the current state of knowledge on KDM5 function, with a particular emphasis on molecular interactions and their potential implications. We will discuss and outline open questions that need to be addressed to better understand histone demethylation and potential demethylation-independent functions of KDM5s. Addressing these questions will increase our understanding of histone demethylation and allow us to develop strategies to target individual KDM5 enzymes in specific biological and disease contexts.
Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos
Authors: Wei Jingwei , Brophy Brigid , Cole Sally-Ann , Moormann Jannis , Boch Jens , Laible Gӧtz
Published: July 2022

Genome editing provides opportunities to improve current cattle breeding strategies through targeted introduction of natural sequence variants, accelerating genetic gain. This can be achieved by harnessing homology-directed repair mechanisms following editor-induced cleavage of the genome in the presence of a repair template. Introducing the genome editors into zygotes and editing in embryos has the advantage of uncompromised development into live animals and alignment with contemporary embryo-based improvement practices. In our study, we investigated the potential to introduce sequence variants, known from the pre-melanosomal protein 17 (PMEL) and prolactin receptor (PRLR) genes, and produce non-mosaic, edited embryos, completely converted into the precision genotype. Injection of gRNA/Cas9 editors into bovine zygotes to introduce a 3 bp deletion variant into the PMEL gene produced up to 11% fully converted embryos. The conversion rate was increased to up to 48% with the use of TALEN but only when delivered by plasmid. Testing three gRNA/Cas9 editors in the context of several known PRLR sequence variants, different repair template designs and delivery as DNA, RNA or ribonucleoprotein achieved full conversion rates up to 8%. Furthermore, we developed a biopsy-based screening strategy for non-mosaic embryos which has the potential for exclusively producing non-mosaic animals with intended precision edits.
Early Expression of Functional Markers on CD4+ T Cells Predicts Outcomes in ICU Patients With Sepsis
Authors: Chen Jianwei , Wang Hao , Guo Ran , Li Haolong , Cui Na
Published: July 2022

Objective

There is evidence that metabolic disorder, dysfunction and abnormal apoptosis of immune cells are closely related to immunosuppression in sepsis. Single monitoring of exhaustion receptors does not reflect well the immune status of septic patients; therefore, we monitored immune status in relation to metabolism, function and apoptosis of immune cells to find good prognostic indicators for sepsis.

Design

A single-center prospective observational study.

Setting

Teaching hospital including an academic tertiary care center.

Patients

81 patients with sepsis and 22 without sepsis admitted to the ICU.

Interventions

Patients were divided according to Sequential Organ Failure Assessment (SOFA) score: mild sepsis 2–5 points and severe sepsis ≥6 points. SOFA score was recalculated daily. If it changed by ≥2 points within 2 days, T-cell metabolism, function and apoptotic makers [mammalian target of rapamycin (mTOR), T-bet, interferon (IFN)-γ, granzyme B, and programmed cell death (PD)-1] were continuously monitored on days 1, 3 and 5 after admission.

Measurements and Main Results

The overall status of immune cells was compared among patients with different severity of sepsis. Patients with severe sepsis, compared with mild and no sepsis, had lower lymphocyte counts, higher expression of receptors associated with cell metabolism, activation and apoptosis, and lower expression of functional receptors. Multivariate regression analysis revealed that frequency of CD4+ T cells expressing mTOR, IFN-γ and PD-1 at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that frequency of CD4+ T cells expressing mTOR, IFN-γ and PD-1 predicted 28-day mortality, with cutoffs of 30.57%, 12.81% and 22.46%, respectively. The expression of related receptors on CD8+ T cells showed similar trend to that on CD4+ T cells, but no significant difference was found.

Conclusions

Abnormally increased expression of metabolic and apoptotic receptors on CD4+ T cells and decreased expression of functional factors are associated with poor prognosis in ICU patients with sepsis. Poor prognosis can be identified by early detection of expression of mammalian target of rapamycin (mTOR), IFN-γ and PD-1 on CD4+ T cells.
Pathogen Filtration: An Untapped Ecosystem Service
Authors: Klohmann C. A. , Padilla-Gamiño J. L.
Published: July 2022

Marine pathogens present serious challenges to aquaculture, fisheries productivity, and marine conservation requiring novel solutions to identify, control, and mitigate their effects. Several ecological habitats, such as mangroves and wetlands can recycle waste and serve as aquatic filtration systems. While nutrient cycling and other ecosystem services of these habitats have been well-studied, their potential to remove pathogens and mechanisms of filtration remain largely unstudied. Here, we review how mangroves, shellfish beds, seagrasses, and constructed wetlands can reduce pathogen pressure in coastal ecosystems. Mangroves may inhibit bacterial growth through phytochemicals in their leaves and remove viruses through desalination in their roots. Some bivalves remove pathogens by excreting pathogens through their pseudofeces and others concentrate pathogens within their tissues. Seagrasses slow flow rates, increase sedimentation rates and may reduce pathogens through allelopathy. Constructed wetlands decrease pathogens through a combination of mechanical, biological, and chemical filtration mechanisms. Protecting and restoring coastal ecosystems is key to maintaining pathogen filtration capacity, benefiting conservation efforts of threatened host populations, and mitigating large disease outbreaks.
CYP2C19 Gene Profiling as a Tool for Personalized Stress Ulcer Prophylaxis With Proton Pump Inhibitors in Critically Ill Patients - Recommendations Proposal
Authors: Bořilová Linhartová Petra , Zendulka Ondřej , Janošek Jaroslav , Mlčůchová Natálie , Cvanová Michaela , Daněk Zdeněk , Kroupa Radek , Bartošová Ladislava , Lipový Břetislav
Published: July 2022

To this date, there are no recommendations for personalized stress ulcer prophylaxis (SUP) in critical care that would take the patient's individual genetic predispositions into account. Of drugs used for this purpose, proton pump inhibitors (PPIs) are the first-choice drugs in intensive care unit patients. The degradation of proton pump inhibitors is mediated by cytochrome P450 (CYP) enzymes; in particular, CYP2C19 and, to a lesser extent, CYP3A4 are involved. Expression and metabolic activity of, namely in, CYP2C19 is significantly affected by single nucleotide polymorphisms, the drug metabolization rate varies greatly from ultrarapid to poor and likely influences the optimal dosage. As these CYP2C19 predictive phenotypes via CYP2C19 haplogenotypes (rs12248560/rs4244285) can be relatively easily determined using the current standard equipment of hospital laboratories, we prepared a set of recommendations for personalized PPI-based stress ulcer prophylaxis taking into account the patient's CYP2C19 predictive phenotype determined in this way. These recommendations are valid, in particular, for European, American and African populations, because these populations have the high representations of the CYP2C19*17 allele associated with the overexpression of the CYP2C19 gene and ultrarapid degradation of PPIs. We propose the CYP2C19 gene profiling as a tool for personalized SUP with PPI in critically ill patients.
Efficacy and Safety of 5% Minoxidil Alone, Minoxidil Plus Oral Spironolactone, and Minoxidil Plus Microneedling on Female Pattern Hair Loss: A Prospective, Single-Center, Parallel-Group, Evaluator Blinded, Randomized Trial
Authors: Liang Xuelei , Chang Yuan , Wu Haixuan , Liu Yi , Zhao Jian , Wang Leyi , Zhuo Fenglin
Published: July 2022

Background

The efficacy of topical minoxidil (MX) alone on female pattern hair loss (FPHL) is limited. Combination therapy based on topical MX is currently expected to provide better outcomes.

Objectives

This study aimed to assess whether the combined therapies including MX plus oral spironolactone (SPT) and MX plus microneedling (MN) have advantages in efficacy and safety over topical MX alone on mild-to-moderate FPHL with normal hormone levels in the blood and regular menstrual cycle.

Methods

A prospective, single-center, parallel-group, evaluator blinded, randomized trial including 120 non-menopause women with proven FPHL (Sinclair class II-III) was performed in China. Patients were randomly assigned to three groups, namely, the MX group (5% topical MX alone, once daily), the MX + SPT group (MX plus SPT 80–100 mg daily), and the MX+MN group (MX plus MN every 2 weeks, 12 sessions). The change from the baseline to week 24 was assessed in hair growth (hair density and diameter under dermoscope), scalp tissue structure (epidermal thickness, dermis thickness, and average hair follicle diameter under ultrasound biomicroscopy), physician's global assessment (using a 7-point global-assessment scale and Sinclair's stage change), patient evaluation (Women's Androgenetic Alopecia Quality of Life Questionnaire and Sinclair's hair-shedding score) and side effects.

Results

In total, 115 participants completed the trial. At week 24, the hair density increased most in MX + MN group and increased least in MX group (p < 0.001 for MX + MN group vs. MX + SPT group; p = 0.009 for MX + SPT group vs. MX group). The hair shaft diameter significantly increased in all groups (p < 0.001, respectively), but there were no significant differences among the three groups (p = 0.905). The epidermal thickness and average hair follicle diameter only increased in MX + MN group. Dermis thickness increased in all groups, but there were no significant differences among the three groups. Both physician's and patient assessments showed improvement in all three groups. Scalp pruritus was the most common side effect. The MX + SPT group had the most reported adverse effects.

Limitations

The main limitations of this study are the relatively small sample size, the exclusion of severe FPHL patients, and the potential bias from unblinded treatments among the 3 groups.

Conclusion

Topical MX combined with MN is a better choice than either MX plus oral SPT or MX alone for the treatment of mild-to-moderate FPHL patients.
Influence of Socio-Demographic Factors in Patients With Cutaneous Lupus Erythematosus
Authors: Walker Amanda M. , Lu Grace , Clifton Shari C. , Ogunsanya Motolani E. , Chong Benjamin F.
Published: July 2022

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disease with potential for systemic involvement, disfigurement, and significant disease burden. The relationships of demographics and socioeconomic status with patients with CLE are emerging topics with important clinical implications. The primary objective of our study is to perform a literature review of studies that have investigated demographic and socioeconomic factors amongst patients with CLE and determine whether these factors influence diagnosis frequency, disease severity and outcomes or health related quality of life. We searched multiple databases to identify literature addressing CLE and concepts such as race, ethnicity, gender, income, education level and geographic location. Information regarding primary research objective was extracted from all full text articles, and a summary of findings was prepared. We found that race and ethnicity can influence CLE diagnosis frequency and disease outcomes. Chronic cutaneous lupus (CCLE) occurs more frequently in Black patients, often with higher overall disease damage. Differences between genders exist in CLE in terms of health-related quality of life, as female gender was a risk factor for worse quality of life in several studies. Lower income, low educational attainment, and lack of health insurance all contribute to poorer overall outcomes in CLE patients. This review will help inform physicians about populations at risk for potentially worse outcomes to guide treatment decisions for patients with CLE and provide important information to design interventions that address modifiable social determinants of health in this population.
Remote Patient Management May Reduce All-Cause Mortality in Patients With Heart-Failure and Renal Impairment
Authors: Naik Marcel G. , Budde Klemens , Koehler Kerstin , Vettorazzi Eik , Pigorsch Mareen , Arkossy Otto , Stuard Stefano , Duettmann Wiebke , Koehler Friedrich , Winkler Sebastian
Published: July 2022

Background

Remote patient management (RPM) in heart failure (HF) patients has been investigated in several prospective randomized trials. The Telemedical Interventional Management in Heart Failure II (TIM-HF2)-trial showed reduced all-cause mortality and hospitalizations in heart failure (HF) patients using remote patient management (RPM) vs. usual care (UC). We report the trial's results for prespecified eGFR-subgroups.

Methods

TIM-HF2 was a prospective, randomized, controlled, parallel-group, unmasked (with randomization concealment), multicenter trial. A total of 1,538 patients with stable HF were enrolled in Germany from 2013 to 2017 and randomized to RPM (+UC) or UC. Using CKD-EPI-formula at baseline, prespecified subgroups were defined. In RPM, patients transmitted their vital parameters daily. The telemedical center reviewed and co-operated with the patient's General Practitioner (GP) and cardiologist. In UC, patients were treated by their GPs or cardiologist applying the current guidelines for HF management and treatment. The primary endpoint was the percentage of days lost due to unplanned cardiovascular hospitalizations or death, secondary outcomes included hospitalizations, all-cause, and cardiovascular mortality.

Results

Our sub analysis showed no difference between RPM and UC in both eGFR-subgroups for the primary endpoint (<60 ml/min/1.73 m2: 40.9% vs. 43.6%, p = 0.1, ≥60 ml/min/1.73 m2 26.5 vs. 29.3%, p = 0.36). In patients with eGFR < 60 ml/min/1.73 m2, 1-year-survival was higher in RPM than UC (89.4 vs. 84.6%, p = 0.02) with an incident rate ratio (IRR) 0.67 (p = 0.03). In the recurrent event analysis, HF hospitalizations and all-cause death were lower in RPM than UC in both eGFR-subgroups (<60 ml/min/1.73 m2: IRR 0.70, p = 0.02; ≥60 ml/min/1.73 m2: IRR 0.64, p = 0.04). In a cox regression analysis, age, NT-pro BNP, eGFR, and BMI were associated with all-cause mortality.

Conclusion

RPM may reduce all-cause mortality and HF hospitalizations in patients with HF and eGFR < 60 ml/min/1.73 m2. HF hospitalizations and all-cause death were lower in RPM in both eGFR-subgroups in the recurrent event analysis. Further studies are needed to investigate and confirm this finding.