bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in HIV Seronegative Patients: A Case Report and Review of the Literature
Authors: Chen Hongchao , Yuan Qing , Hu Hangbin , Wang Jie , Yu Meihong , Yang Qing , Qu Tingting
Published: June 2022

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum infection is a rare disorder with poor outcome. Although cases of patients with human immunodeficiency virus (HIV) infection have been well documented, little study has reported in the setting of HIV seronegative. In this study, we report a case of HLH secondary to histoplasmosis in an immunocompetent patient in China and review all cases on this situation. The objective was to summary their epidemiology, clinical characteristics, diagnostic approaches, and therapeutic response. A 46-year-old male cooker presented fever, fatigue, anorexia, and weight loss. Bone marrow examination suggest fungus organism and hemophagocytosis, and further, bone marrow culture confirmed Histoplasma capsulatum, as the etiology of HLH. The patient was successfully treated. We reviewed a total of the 13 cases (including our patient) of HLH with histoplasmosis in intact immunology patients. Twelve of the 13 patients are from endemic areas, and nine of the 12 cases are from emerging endemic areas, India and China. Three patients had sojourn history may related to the disease onset. Twelve of the 13 cases fulfilled HLH-2004 criteria. The diagnosis of Histoplasma capsulatum infection was established by histological examination (13 of 13), culture (4 of 13), molecular method (2 of 13), and antigen or serological assays (2 of 13). Amphotericin B, posaconazole, and itraconazole show favorable activity against the fungus, seven patients used specific treatment for HLH. For analysis of outcomes, two of the 13 patients died. Our present case report and literature review show that disseminated Histoplasma capsulatum infection with HLH in the immunocompetent population becomes increasingly common in emerging endemic areas and have high mortality. It is necessary for clinicians to improve the awareness of disease diagnosis due to the atypical population and disease presentation. Timely diagnosis and early use of antifungal agents will lead to favorable prognosis.
Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era
Authors: Moussa Dina G. , Ahmad Paras , Mansour Tamer A. , Siqueira Walter L.
Published: June 2022

Despite significant healthcare advances in the 21st century, the exact etiology of dental caries remains unsolved. The past two decades have witnessed a tremendous growth in our understanding of dental caries amid the advent of revolutionary omics technologies. Accordingly, a consensus has been reached that dental caries is a community-scale metabolic disorder, and its etiology is beyond a single causative organism. This conclusion was based on a variety of microbiome studies following the flow of information along the central dogma of biology from genomic data to the end products of metabolism. These studies were facilitated by the unprecedented growth of the next- generation sequencing tools and omics techniques, such as metagenomics and metatranscriptomics, to estimate the community composition of oral microbiome and its functional potential. Furthermore, the rapidly evolving proteomics and metabolomics platforms, including nuclear magnetic resonance spectroscopy and/or mass spectrometry coupled with chromatography, have enabled precise quantification of the translational outcomes. Although the majority supports ‘conserved functional changes’ as indicators of dysbiosis, it remains unclear how caries dynamics impact the microbiota functions and vice versa, over the course of disease onset and progression. What compounds the situation is the host-microbiota crosstalk. Genome-wide association studies have been undertaken to elucidate the interaction of host genetic variation with the microbiome. However, these studies are challenged by the complex interaction of host genetics and environmental factors. All these complementary approaches need to be orchestrated to capture the key players in this multifactorial disease. Herein, we critically review the milestones in caries research focusing on the state-of-art singular and integrative omics studies, supplemented with a bibliographic network analysis to address the oral microbiome, the host factors, and their interactions. Additionally, we highlight gaps in the dental literature and shed light on critical future research questions and study designs that could unravel the complexities of dental caries, the most globally widespread disease.
Bioinformatics Analysis Highlights Five Differentially Expressed Genes as Prognostic Biomarkers of Cervical Cancer and Novel Option for Anticancer Treatment
Authors: Cui Hongtu , Ma Ruilin , Hu Tao , Xiao Gary Guishan , Wu Chengjun
Published: June 2022

Cervical cancer is one of the most common gynecological malignancies and is related to human papillomavirus (HPV) infection, especially high-risk type HPV16 and HPV18. Aberrantly expressed genes are involved in the development of cervical cancer, which set a genetic basis for patient prognosis. In this study, we identified a set of aberrantly expressed key genes from The Cancer Genome Atlas (TCGA) database, which could be used to accurately predict the survival rate of patients with cervical squamous cell carcinoma (CESC). A total of 3,570 genes that are differentially expressed between normal and cancerous samples were analyzed by the algorithm of weighted gene co-expression network analysis (WGCNA): 1,606 differentially expressed genes (DEGs) were upregulated, while 1,964 DEGs were downregulated. Analysis of these DEGs divided them into 7 modules including 76 hub genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis revealed a significant increase of genes related to cell cycle, DNA replication, p53 signaling pathway, cGMP-PKG signaling pathway, and Fanconi anemia (FA) pathway in CESC. These biological activities are previously reported to associate with cervical cancer or/and HPV infection. Finally, we highlighted 5 key genes (EMEMP2, GIMAP4, DYNC2I2, FGF13-AS1, and GIMAP1) as robust prognostic markers to predict patient’s survival rate (p = 3.706e-05) through univariate and multivariate regression analyses. Thus, our study provides a novel option to set up several biomarkers for cervical cancer prognosis and anticancer drug targets.
Production and Perception of Mandarin Laryngeal Contrast: The Role of Post-plosive F0
Authors: Guo Yuting , Kwon Harim
Published: June 2022

This study examines the relation between plosive aspiration and post-plosive f0 (fundamental frequency) in the production and perception of the laryngeal contrast in Mandarin. Production data from 25 Mandarin speakers showed that, in word onsets, VOTs (voice onset time) of aspirated and unaspirated plosives were different, as expected. At the same time, the speakers produced different post-plosive f0 between aspirated and unaspirated plosives, but the difference varied according to the lexical tones – post-aspirated f0 was higher than post-unaspirated f0 in high-initial tones (i.e., lexical tones with high onset f0), but the pattern was the opposite and less robust in low-initial tones. In the perception of the same participants, VOT was the primary cue to aspiration but, when VOT was ambiguous, high post-plosive f0 yielded more aspirated responses in general. We claim that the asymmetry in f0 perturbation between high-initial and low-initial tones in production arises from different laryngeal maneuvers for different tonal targets. In low-initial tones, in which the vocal folds are slack and the glottal opening is wider, aspirated plosives have a lower subglottal air pressure than unaspirated plosives at the voicing onset, resulting in lower post-aspirated f0 than post-unaspirated f0. But in high-initial tones, the vocal folds are tense, which requires a higher trans-glottal pressure threshold to initiate phonation at the onset of voicing. As a result, the subglottal pressure does not decrease as much. Instead, the faster airflow in aspirated than unaspirated plosives gives rise to the pattern that post-aspirated f0 is higher than post-unaspirated f0. Regardless of this variation in production, our perception data suggest that Mandarin listeners generalize the f0 perturbation patterns from high-initial tones and associate high post-plosive f0 with aspirated plosives even in low-initial tone contexts. We cautiously claim that the observed perceptual pattern is consistent with the robustly represented production pattern, as high-initial tones are more prevalent and salient in the language and exhibit stronger f0 perturbation in the speakers' productions.
Cardiovascular Outcomes in the Patients With Colorectal Cancer: A Multi-Registry-Based Cohort Study of 197,699 Cases in the Real World
Authors: Zhang Shilong , Wang Yan , Zhang Pengfei , Ai Luoyan , Liu Tianshu
Published: June 2022

Purpose

We aimed to investigate the mortality patterns and quantitatively assess the risks of cardiovascular death (CVD) in patients with colorectal cancer (CRC). We also established a competing-risk model to predict the probability of CVD for patients with CRC.

Patients and Methods

Patients with CRC who diagnosed between 2007 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the present study. The cumulative incidence function (CIF) was used for CVD and other causes of death, and Gray’s test was used to determine the subgroup difference in CIF. The Fine-Gray proportional subdistribution hazards model was used for identifying independent risk factors for CVD. A novel competing-risk model was established to evaluate the probability of CVD for patients with CRC. The performance of the nomogram was measured by concordance index (C-index), calibration curve, decision curve analysis (DCA), and risk stratification.

Results

After a median follow-up of 37.00 months, 79,455 deaths occurred, of whom 56,185 (70.71%) succumbed to CRC and 23,270 (29.29%) patients died due to non-CRC, among which CVD accounted for 9,702 (41.69%), being the major cause of non-cancer deaths. The 1-, 3-, and 5-year cumulative rates for CVD were 12.20, 24.25, and 30.51%, respectively. In multivariate analysis, age, race, marital status, tumor size, tumor stage, advanced stage, surgery, and chemotherapy were independent risk factors of CVD among patients with CRC. The nomogram was well calibrated and had good discriminative ability, with a c-index of 0.719 (95% CI, 0.738–0.742) in the training cohort and 0.719 (95% CI, 0.622–0.668) in the validation cohort. DCA demonstrated that nomogram produced more benefit within wide ranges of threshold probabilities for 1-, 3-, and 5-year CVD, respectively.

Conclusion

This study was the first to analyze the CIF and risk factors for CVD among CRC based on a competing-risk model. We have also built the first 1-, 3-, and 5-year competing nomogram for predicting CVD. This nomogram had excellent performance and could help clinicians to provide individualized management in clinical practice.
An Updated Meta-Analysis of DOACs vs. VKAs in Atrial Fibrillation Patients With Bioprosthetic Heart Valve
Authors: Cao Yalin , Zheng Yuxiang , Li Siyuan , Liu Fuwei , Xue Zhengbiao , Yin Kang , Luo Jun
Published: June 2022

Background

Current guidelines recommend the utilization of direct-acting oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (AF). However, the optimal anticoagulation strategy for AF patients with bioprosthetic heart valves (BPHV) remains controversial. Therefore, we conducted this meta-analysis to explore the effect of DOACs versus vitamin K antagonists (VKAs) in this population.

Methods

We systematically searched the PubMed and Embase databases until November 2021 for studies reporting the effect of DOACs versus VKAs in AF patients with BPHV. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using the random-effects model with an inverse variance method.

Results

We selected four randomized clinical trials and seven observational studies (2236 DOAC- and 6403 VKAs-users). Regarding the effectiveness outcomes, there were no significant differences between DOACs and VKAs in stroke or systemic embolism (RR = 0.74, 95%CI: 0.50–1.08), ischemic stroke (RR = 1.08, 95%CI: 0.76–1.55), all-cause death (RR = 0.98, 95%CI: 0.86–1.12), and cardiovascular death (RR = 0.85, 95%CI: 0.40–1.80). In terms of the safety outcomes, DOACs was associated with lower risks of major bleeding (RR = 0.70, 95%CI: 0.59–0.82) and intracranial bleeding (RR = 0.42, 95%CI: 0.26–0.70), but the risks of any bleeding (RR = 0.85, 95%CI: 0.65–1.13) and gastrointestinal bleeding (RR = 0.92, 95%CI: 0.73–1.17) are not significantly different when compared with VKAs. The subgroup analysis with follow-up as a covariate revealed that the DOACs had lower risks of SSE (RR = 0.59, 95%CI: 0.37–0.94) and major bleeding (RR = 0.69, 95%CI: 0.58–0.81) in patients with a mean follow-up of more than 24 months, but no statistical differences were found in patients with the follow-up less than 24 months (SSE: RR = 1.10, 95%CI: 0.92–1.32; major bleeding: RR = 0.91, 95%CI: 0.42–2.01).

Conclusions

In AF with BPHV, patients on DOACs experienced a reduced risk of major bleeding and intracranial bleeding compared with VKAs, while the risks of stroke, cardiovascular death, and all-cause mortality were similar.
Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease
Authors: Lin Jianguo , Duan Jinlong , Wang Qingqing , Xu Siyu , Zhou Simin , Yao Kuiwu
Published: June 2022

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) and mitophagy, are critical to mitochondrial function. Fusion allows organelles to share metabolites, proteins, and mitochondrial DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria to ensure that they are passed on to their offspring during mitosis. Mitophagy is a process of selective removal of excess or damaged mitochondria that helps improve energy metabolism. Cardiometabolic disease is characterized by mitochondrial dysfunction, high production of reactive oxygen species, increased inflammatory response, and low levels of ATP. Cardiometabolic disease is closely related to mitochondrial dynamics and mitophagy. This paper reviewed the mechanisms of mitochondrial dynamics and mitophagy (focus on MFN1, MFN2, OPA1, DRP1, and PINK1 proteins) and their roles in diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, and obesity.
Sedimentology and Geochemistry of the Upper Permian Linghao Formation Marine Shale, Central Nanpanjiang Basin, SW China
Authors: Gu Yifan , Hu Dongfeng , Wei Zhihong , Liu Ruobing , Hao Jingyu , Han Jing , Fan Zhiwei , Jiang Yuqiang , Wang Yansong , Xu Qidi
Published: June 2022

The Upper Permian Linghao Formation marine shale and contemporaneous transitional shale are the most potential shale gas targets in the Nanpanjiang basin, which is characterized by considerable TOC content, wide distribution, and considerable shale thickness. On the basis of division in Linghao Formation, petrographic, mineralogical, and high-resolution geochemical analyses were integrated to reveal the sedimentary environment including paleoproductivity, paleoredox conditions, detrital influx, paleoclimate, and the paleosalinity. There are two organic-rich shale intervals in Linghao Formation, which are Ling 1 member and the lower Ling 3 member. The lower Ling 1 is dominated by deep-water shelf facies, which are characterized by high TOC value (0.93%–6.36%, avg. 2.43%), high detrital influx proxies (Zr, 746–1508 ppm, avg. 1093 ppm; Ti, 19278–128730 ppm, avg. 16091 ppm), relatively warm–humid paleoclimate condition (CIA*, 75.94-91.90, avg. 82.26), low paleosalinity proxies (Sr/Ba, 0.13-0.34, avg. 0.22), and high paleoproductivity (P/Al (10−2), 1.06-2.06, avg. 1.63; Mn/Ca (10−3), 27.37-291.69, avg. 128.07). Detrital influx including gravity flow plays a critical role in the enrichment of organic matter. The sedimentary environment of upper Ling 1 and lower Ling 3 is the same as that of lower Ling 1. Unlike lower Ling 1, these intervals are characterized by low detrital influx proxies, moderate weathering, and relatively high paleosalinity proxies. The volcanic ash of Emei volcanism and felsic volcanism in South China plays a critical role in the enrichment of organic matter in upper Ling 1 and lower Ling 3, respectively. The sedimentary models for Linghao Formation organic-rich shale can reveal factors controlling the enrichment of organic matter.
SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell via Balancing ERα and PR Signals
Authors: Lin Yi-Kong , Li Yun-Yun , Li Yue , Li Da-Jin , Wang Xiao-Lin , Wang Li , Yu Min , Zhu Yi-Zhun , Cheng Jia-Jing , Du Mei-Rong
Published: June 2022

Background

Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation.

Methods

The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis.

Results

Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression.

Conclusion

Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.
Early Initiation of Intermittently Scanned Continuous Glucose Monitoring in a Pediatric Population With Type 1 Diabetes: A Real World Study
Authors: Franceschi Roberto , Cauvin Vittoria , Stefani Lorenza , Berchielli Federica , Soffiati Massimo , Maines Evelina
Published: June 2022

Background

Use of Continuous Glucose Monitoring (CGM) systems early in the course of diabetes has the potential to help glycemic management and to improve quality of life (QoL). No previous research has examined these outcomes in children-adolescents with type 1 diabetes (T1D) who use intermittently scanned CGM (isCGM) starting within the first month after diagnosis.

Aim

To evaluate the impact of isCGM early after T1D diagnosis, on metabolic control and QoL, comparing a group who started the use of the device within one month from the onset with another one who started at least one year later.

Subjects and Methods

Patients who used isCGM within 1 month from T1D diagnosis were enrolled in group A; those who didn’t have the device during the first year were considered as control group (group B). HbA1c and total daily insulin were evaluated at 3 (T1), 6 (T2) and 12 (T3) months post-baseline (T0, diabetes onset), QoL after 1 year. In group A, isCGM glucose metrics were also recorded.

Results

85 patients were enrolled in group A and 67 patients in group B. In group A isCGM was well accepted during follow up: no patient dropped out; percentage of time with active sensor was in mean > 87%; number of scans/day remained stable. QoL was higher in group A than in group B both in children-adolescents (p<0.0001) and in parents (p 0.003). Group A presented lower HbA1c during the first year after diagnosis (p<0.001), and this data correlated with glucose management indicator (GMI), time in range (TIR) and mean glucose. The honeymoon period lasted more in group A than in B (p 0.028). Furthermore, the mean hypoglycemia duration decreased during follow-up (p 0.001) in group A.

Conclusions

Early use of isCGM, starting within the first month after diagnosis, improves metabolic control and QoL in pediatric patients with T1D.
Effects of Bariatric Endoscopy on Non-Alcoholic Fatty Liver Disease: A Comprehensive Systematic Review and Meta-Analysis
Authors: Ren Mengting , Zhou Xinxin , Zhang Yunyun , Mo Feifei , Yang Jinpu , Yu Mosang , Ji Feng
Published: June 2022

Background and objective

Endoscopic bariatric and metabolic therapies (EBMTs) are emerging minimally invasive therapeutic options for obesity and its related complications, including non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the effects of EBMTs on NALFD in patients with obesity.

Methods

Four databases were searched until Nov 2021. Randomized controlled trials (RCTs) and observational studies reporting liver-related outcomes following Food and Drug Administration (FDA)-approved and non-FDA-approved EBMTs were included. Liver parameters, metabolic parameters, and weight loss were evaluated. Risk of bias was assessed using the “risk of bias” tool in the Cochrane Collaboration for RCTs and the Methodological Index for Non-Randomized Studies criteria for observational studies.

Results

Thirty-three studies with 1710 individuals were included. Regarding the effects of EBMTs on liver fibrosis, a significant decline of NAFLD Fibrosis Score, but not transient elastography-detected liver stiffness or Fibrosis-4 Index, was observed. EBMTs significantly improved liver steatosis (control attenuation parameter and Hepatic Steatosis Index), NAFLD Activity Score, and Homeostasis Model Assessment of Insulin Resistance. EBMTs reduced serum levels of alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transpeptidase considerably. Moreover, EBMTs had reducing effects on the serum levels of triglycerides and total cholesterol as well as body weight.

Conclusions

Our meta-analysis suggested that EBMTs could ameliorate NAFLD based on the evidence of improved liver steatosis, liver function, and insulin resistance. Large-scale, prospective, long-term studies are warranted to clarify the role of EBMTs in patients with different stages of NAFLD.
Research on Optimal Energy Flow Calculation of an Electro-Thermal Coupled System via an Interior-Point Approach
Authors: Li Zhaoying , Zhao Yan , Xu Jian , Shao Qianzhi
Published: June 2022

With the contradiction between energy consumption and ecological protection becoming increasingly prominent, it has become a serious issue to study an energy system with high efficiency, low pollution, and strong controllability. The application of the backpressure unit and the peak-shaving electric boiler makes the power grid and the heat grid connected and becomes an electro-thermal coupling system, which can be studied as a representative of the integrated energy system. In this study, to make full use of energy, a power system model considering a large number of distributed energy injections and a multi-source thermal system model are constructed. After the energy flow is solved, the optimization method of the electrothermal coupled system is studied to minimize the fuel consumption and obtain the minimum operating cost. In addition, a more comprehensive algorithm is proposed in this study, and the actual model is used in the fourth section of the article to verify that the algorithm can be practically applied.
Lessons Learnt From the Residential Zero Carbon District Demonstration Project, Governance Practice, Customer Response, and Zero-energy House Operation in Japan
Authors: Li Yanxue , Zhang Xiaoyi , Gao Weijun , Qiao Jiuli
Published: June 2022

The building sector is undergoing a low-carbon transition featuring applications of energy-efficient technologies and management innovations. Herein, we contribute to the study of the residential zero-carbon district demonstration project in Japan, introducing smart practices and examining occupants’ awareness. We proposed a questionnaire survey covering more than 400 smart zero-energy house owners that looks beyond the technologies for smart energy management and recognizes how the residential consumers engaged and perceive delivered energy saving and cost reduction issues, and their usage frequency of home energy management system information-based services is also examined considering the impact of the variables of household income and occupants’ age. Overall, the respondents’ energy and cost-saving awareness vary widely, and the results provide the effectiveness of the visual-based service in engaging end-users in the responsive energy management system. In the context of the detailed operational performances of real zero-energy houses, we find evidence that automatic control has reshaped the characteristics of intraday energy balance and gives consumers greater control over their own energy bills. The findings clearly show the detailed role of integrated energy-efficient technologies over typical periods; the grid-connected photovoltaic system plays a significant role in the realization of net annual zero electricity balance, and micro-cogeneration’s contribution to zero-energy houses’ energy self-sufficiency largely depends on the building heating load.
Reliability Improvement of the Smart Distribution Grid Incorporating EVs and BESS via Optimal Charging and Discharging Process Scheduling
Authors: Jozi Fatemeh , Abdali Ali , Mazlumi Kazem , Hosseini Seyed Hadi
Published: June 2022

The use of large-scale electric vehicles (EVs), along with technological advances in battery energy storage systems (BESS), offers numerous technical and economic benefits to the smart distribution system. Parking lots not only provide EV owners with the opportunity to charge their BESS but also contribute power to the grid via vehicle-to-grid (V2G) technology, which significantly improves the reliability of distribution systems. In addition, parking lots equipped with V2G capability can participate in the electricity market as a producer. In this study, the reliability of a smart radial distribution system in the presence of EVs is investigated. It should always be borne in mind that parking lots can improve system reliability if the charging and discharging strategies are optimally and correctly scheduled. On the contrary, the parking lot participates in sending power to the grid in a situation where the profit is appropriate. Accordingly, in this study, first, five optimal strategies for scheduling the process of EV charging and discharging in a parking lot equipped with V2G capability are proposed to maximize parking profits. The proposed strategies include constraints on the amount of power exchange between the parking lot and the distribution system and the random and stochastic nature of quantities, such as when EVs enter and exit the parking lot and their BESS charge amounts when entering the parking lot. The results demonstrate that using the proposed optimal charging and discharging strategies scheduling increases the parking profit by 31% and also improves the reliability of the understudy distribution system by 9%.
Single-Well Dynamic Permeability Splitting Algorithm and Classification Evaluation: A Case Study of a Super-Thick Carbonate Reservoir in the Middle East
Authors: Cao Peng , Wang Yongjun , Qiao Zhanfeng , Zhu Guangya , Su Haiyang , Shao Guanming , Gong Jie , Deng Haiyang
Published: June 2022

The permeability interpretation accuracy of single wells in the Middle East super-thick carbonate reservoir can hardly meet the actual demand of water injection development. Therefore, this study develops an iterative split algorithm to calculate single-well segmental dynamic permeability and SPI (specific production index) based on the dynamic and static well test, PLT (production log test), production test, and logging interpretation data. Moreover, the dynamic permeability classification evaluation index was optimized. The detailed steps are as follows: 1) The liquid supply of a single well is split according to tp PLT. 2) For some production intervals, the log interpretation data are applied to carry out the second iteration splitting of formation coefficient and fluid supply. 3) The proportion of liquid supply in the stratification section is calculated based on the calculation results of steps 1 and step 2. 4) The total formation coefficient of well test interpretation is divided based on the calculation results of step 3. 5) The dynamic permeability and SPI are calculated. The research results show that the dynamic permeability and SPI of a single well are accurate to the scale of one meter from the several original meters to tens of meters, which can better meet the needs of water injection development. In addition, SPI can be used as an essential index for permeability classification evaluation. Taking the Halfaya Oilfield and the Mishrif format reservoir as examples, the low penetration rate of the MB1-2 high penetration rate is 200md and the lower specific production index limit is 0.35 bbl/(d·m·psi), respectively. The dynamic foundation of the high-permeability layer is identified. This method offers a new idea for the title of high-permeability streaks. Moreover, this method can provide the scientific basis for correcting the permeability attribute model, water injection plan optimization, single-well completion cementing scheme, and water coning control, which can be popularized and applied in the same reservoirs.
Spatio-Temporal Evolution and Quality Analysis of Construction Land in Urban Agglomerations in Central China
Authors: Ning Qimeng , Ouyang Xiao , Liu Shaobo
Published: June 2022

Understanding the pattern and quality of construction land expansion in urban agglomerations is important for new urbanization and high-quality development of land spaces. Taking urban agglomeration in the middle reaches of the Yangtze River as the research object, this study analyzes the spatio-temporal pattern and quality level of construction land expansion at various scales using remote sensing images, the expansion intensity index, the coordination degree model, and the Tapio elastic decoupling model. The results show that from 2000 to 2020, (1) the construction land scale of urban agglomeration in the study area had expanded, with significant stage characteristics and spatial differentiation patterns. (2) The overall relationship between the construction land and the population in urban agglomerations was found to be uncoordinated, but the coordination degree had been improved. The optimization of human–land coordination was faster at the metropolitan scale than at the overall level and the sub-urban agglomerations. (3) The decoupling relationship between the overall construction land and the economy in urban agglomerations was weak and had improved. The coupling/decoupling relationship was found to be better at the metropolitan scale than at the overall level and sub-urban agglomerations.
Integrated Analysis of miRNAs and Gene Expression Profiles Reveals Potential Biomarkers for Osteoarthritis
Authors: Li Zhen , Chen Zhenyue , Wang Xiaotan , Li Zehui , Sun He , Wei Jinqiang , Zeng Xianzhong , Cao Xuewei , Wan Chao
Published: June 2022

Purpose: Currently, the early diagnosis and treatment of osteoarthritis (OA) remain a challenge. In the present study, we attempted to explore potential biomarkers for the diagnosis and treatment of OA.

Methods: The differentially expressed genes (DEGs) were identified based on three mRNA datasets of synovial tissues for OA patients and normal controls downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used for evaluating gene function related categories. Then, miRNA sequencing was performed for differentially expressed miRNAs’ identification. Finally, weighted gene co-expression network analysis (WGCNA) was performed for genes detected by the three mRNA datasets and a competing endogenous RNA (ceRNA) network with DEGs and differentially expressed microRNAs (miRNAs) was constructed for central genes identification. In addition, the relationship between central gene expression and immune infiltration was analyzed, and the candidate agents for OA were predicted based on the Connectivity Map database. Quantitative RT-PCR (qRT-PCR), Western blotting analysis, and immunofluorescent staining were performed to validate the expression levels of differentially expressed miRNAs and differentially expressed target genes in normal and OA tissues and chondrocytes. MiRNA–mRNA network was also validated in chondrocytes in vitro.

Results: A total of 259 DEGs and 26 differentially expressed miRNAs were identified, among which 94 miRNA–mRNA interactions were predicted. The brown module in WGCNA was most closely correlated with the clinical traits of OA. After overlapping the brown module genes with miRNA–mRNA pairs, 27 miRNA–mRNA pairs were obtained. A ceRNA network was constructed with 5505 lncRNA–miRNA–mRNA interactions. B-cell translocation gene 2(BTG2), Abelson-related gene (ABL2), and vascular endothelial growth factor A (VEGFA) were identified to be the central genes with good predictive performance, which were significantly correlated with immune cell infiltration in OA, reflected by declined activated dendritic cells (aDCs), and elevated contents of B cells, macrophages, neutrophils, and T helper cells. Anisomycin, MG-132, thapsigargin, and lycorine were predicted to be the potential candidate agents for OA intervention. In vitro, the expression levels of differentially expressed miRNAs and biomarkers identified in the present study were consistent with the results obtained in normal or OA knee cartilage tissues and chondrocytes. Furthermore, BTG2 was identified to be negatively regulated by miR-125a-5p.

Conclusion: BTG2, ABL2, and VEGFA can be regarded as potential predictive and treatment biomarkers for OA, which might guide the clinical therapy of OA.
A Novel Extracellular Matrix Gene-Based Prognostic Model to Predict Overall Survive in Patients With Glioblastoma
Authors: Qian Chen , Xiufu Wu , Jianxun Tang , Zihao Chen , Wenjie Shi , Jingfeng Tang , Kahlert Ulf D. , Renfei Du
Published: June 2022

Background: Glioblastoma (GBM), one of the most prevalent brain tumor types, is correlated with an extremely poor prognosis. The extracellular matrix (ECM) genes could activate many crucial pathways that facilitate tumor development. This study aims to provide online models to predict GBM survival by ECM genes.

Methods: The associations of ECM genes with the prognosis of GBM were analyzed, and the significant prognosis-related genes were used to develop the ECM index in the CGGA dataset. Furthermore, the ECM index was then validated on three datasets, namely, GSE16011, TCGA-GBM, and GSE83300. The prognosis difference, differentially expressed genes, and potential drugs were obtained. Multiple machine learning methods were selected to construct the model to predict the survival status of GBM patients at 6, 12, 18, 24, 30, and 36 months after diagnosis.

Results: Five ECM gene signatures (AEBP1, F3, FLNC, IGFBP2, and LDHA) were recognized to be associated with the prognosis. GBM patients were divided into high– and low–ECM index groups with significantly different overall survival rates in four datasets. High–ECM index patients exhibited a worse prognosis than low–ECM index patients. Four small molecules (podophyllotoxin, lasalocid, MG-262, and nystatin) that might reduce GBM development were predicted by the Cmap dataset. In the independent dataset (GSE83300), the maximum values of prediction accuracy at 6, 12, 18, 24, 30, and 36 months were 0.878, 0.769, 0.748, 0.720, 0.705, and 0.868, respectively. These machine learning models were provided on a publicly accessible, open-source website (https://ospg.shinyapps.io/OSPG/).

Conclusion: In summary, our findings indicated that ECM genes were prognostic indicators for patient survival. This study provided an online server for the prediction of survival curves of GBM patients.
The Great Majority of Homologous Recombination Repair-Deficient Tumors Are Accounted for by Established Causes
Authors: Štancl Paula , Hamel Nancy , Sigel Keith M. , Foulkes William D. , Karlić Rosa , Polak Paz
Published: June 2022

Background: Gene-agnostic genomic biomarkers were recently developed to identify homologous recombination deficiency (HRD) tumors that are likely to respond to treatment with PARP inhibitors. Two machine-learning algorithms that predict HRD status, CHORD, and HRDetect, utilize various HRD-associated features extracted from whole-genome sequencing (WGS) data and show high sensitivity in detecting patients with BRCA1/2 bi-allelic inactivation in all cancer types. When using only DNA mutation data for the detection of potential causes of HRD, both HRDetect and CHORD find that 30–40% of cases that have been classified as HRD are due to unknown causes. Here, we examined the impact of tumor-specific thresholds and measurement of promoter methylation of BRCA1 and RAD51C on unexplained proportions of HRD cases across various tumor types.

Methods: We gathered published CHORD and HRDetect probability scores for 828 samples from breast, ovarian, and pancreatic cancer from previous studies, as well as evidence of their biallelic inactivation (by either DNA alterations or promoter methylation) in HR-related genes. ROC curve analysis evaluated the performance of each classifier in specific cancer. Tenfold nested cross-validation was used to find the optimal threshold values of HRDetect and CHORD for classifying HR-deficient samples within each cancer type.

Results: With the universal threshold, HRDetect has higher sensitivity in the detection of biallelic inactivation in BRCA1/2 than CHORD and resulted in a higher proportion of unexplained cases. When promoter methylation was excluded, in ovarian carcinoma, the proportion of unexplained cases increased from 26.8 to 48.8% for HRDetect and from 14.7 to 41.2% for CHORD. A similar increase was observed in breast cancer. Applying cancer-type-specific thresholds led to similar sensitivity and specificity for both methods. The cancer-type-specific thresholds for HRDetect reduced the number of unexplained cases from 21 to 12.3% without reducing the 96% sensitivity to known events. For CHORD, unexplained cases were reduced from 10 to 9% while sensitivity increased from 85.3 to 93.9%.

Conclusion: These results suggest that WGS-based HRD classifiers should be adjusted for tumor types. When applied, only ∼10% of breast, ovarian, and pancreas cancer cases are not explained by known events in our dataset.
Selection Signatures in South African Nguni and Bonsmara Cattle Populations Reveal Genes Relating to Environmental Adaptation
Authors: Kooverjee Bhaveni B. , Soma Pranisha , Van Der Nest Magrieta A. , Scholtz Michiel M. , Neser Frederick W. C.
Published: June 2022

Climate change is a major influencing factor in beef production. The greenhouse gases produced from livestock production systems contribute to the overall greenhouse gas emissions. The aim of this study was to identify selection signatures within and between Nguni and Bonsmara cattle in relation to production and adaptation. For this purpose, genomic 150 K single nucleotide polymorphism data from Nguni (n = 231) and Bonsmara (n = 252) cattle in South Africa were used. Extended haplotype homozygosity (EHH) based analysis was executed within each population using integrated haplotype score (iHS). The R package rehh was used for detecting selection signatures across the two populations with cross population EHH (XP-EHH). Total of 121 regions of selection signatures were detected (p < 0.0001) in the Bonsmara and Nguni populations. Several genes relating to DNA methylation, heat stress, feed efficiency and nitrogen metabolism were detected within and between each population. These regions also included QTLs associated with residual feed intake, residual gain, carcass weight, stature and body weight in the Bonsmara, while QTLs associated with conception rate, shear force, tenderness score, juiciness, temperament, heat tolerance, feed efficiency and age at puberty were identified in Nguni. Based on the results of the study it is recommended that the Nguni and Bonsmara be utilized in crossbreeding programs as they have beneficial traits that may allow them to perform better in the presence of climate change. Results of this study coincide with Nguni and Bonsmara breed characteristics and performance, and furthermore support informative crossbreeding programs to enhance livestock productivity in South Africa.
Identification of an Immune-Related Prognostic Risk Model in Glioblastoma
Authors: Lin Zhiying , Wang Rongsheng , Huang Cuilan , He Huiwei , Ouyang Chenghong , Li Hainan , Zhong Zhiru , Guo Jinghua , Chen Xiaohong , Yang Chunli , Yang Xiaogang
Published: June 2022

Background: Glioblastoma (GBM) is the most common and malignant type of brain tumor. A large number of studies have shown that the immunotherapy of tumors is effective, but the immunotherapy effect of GBM is not poor. Thus, further research on the immune-related hub genes of GBM is extremely important.

Methods: The GBM highly correlated gene clusters were screened out by differential expression, mutation analysis, and weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and proportional hazards model (COX) regressions were implemented to construct prognostic risk models. Survival, receiver operating characteristic (ROC) curve, and compound difference analyses of tumor mutation burden were used to further verify the prognostic risk model. Then, we predicted GBM patient responses to immunotherapy using the ESTIMATE algorithm, GSEA, and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm.

Results: A total of 834 immune-related differentially expressed genes (DEGs) were identified. The five hub genes (STAT3, SEMA4F, GREM2, MDK, and SREBF1) were identified as the prognostic risk model (PRM) screened out by WGCNA and LASSO analysis of DEGs. In addition, the PRM has a significant positive correlation with immune cell infiltration of the tumor microenvironment (TME) and expression of critical immune checkpoints, indicating that the poor prognosis of patients is due to TIDE.

Conclusion: We constructed the PRM composed of five hub genes, which provided a new strategy for developing tumor immunotherapy.
Dysregulated Hypothalamic–Pituitary–Adrenal Axis Is Associated With Increased Inflammation and Worse Outcomes After Ischemic Stroke in Diabetic Mice
Authors: Kim Sehee , Park Eun S. , Chen Peng R. , Kim Eunhee
Published: June 2022

Diabetic patients have larger infarcts, worse neurological deficits, and higher mortality rate after an ischemic stroke. Evidence shows that in diabetes, the hypothalamic–pituitary–adrenal (HPA) axis was dysregulated and levels of cortisol increased. Based on the role of the HPA axis in immunity, we hypothesized that diabetes-dysregulated stress response exacerbates stroke outcomes via regulation of inflammation. To test this hypothesis, we assessed the regulation of the HPA axis in diabetic mice before and after stroke and determined its relevance in the regulation of post-stroke injury and inflammation. Diabetes was induced in C57BL/6 mice by feeding a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then the mice were subjected to 30 min of middle cerebral artery occlusion (MCAO). Infarct volume and neurological scores were measured in the ischemic mice. The inflammatory cytokine and chemokine levels were also determined in the ischemic brain. To assess the effect of diabetes on the stroke-modulated HPA axis, we measured the expression of components in the HPA axis including corticotropin-releasing hormone (CRH) in the hypothalamus, proopiomelanocortin (POMC) in the pituitary, and plasma adrenocorticotropic hormone (ACTH) and corticosterone. Diabetic mice had larger infarcts and worse neurological scores after stroke. The exacerbated stroke outcomes in diabetic mice were accompanied by the upregulated expression of inflammatory factors (including IL-1β, TNF-α, IL-6, CCR2, and MCP-1) in the ischemic brain. We also confirmed increased levels of hypothalamic CRH, pituitary POMC, and plasma corticosterone in diabetic mice before and after stroke, suggesting the hyper-activated HPA axis in diabetic conditions. Finally, we confirmed that post-stroke treatment of metyrapone (an inhibitor of glucocorticoid synthesis) reduced IL-6 expression and the infarct size in the ischemic brain of diabetic mice. These results elucidate the mechanisms in which the HPA axis in diabetes exacerbates ischemic stroke. Maintaining an optimal level of the stress response by regulating the HPA axis may be an effective approach to improving stroke outcomes in patients with diabetes.