bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSET UTILIZATION OPTIMIZATION, LOCAL GOVERNMENT SUPPORT, ASSET MANAGEMENT PROFESSIONALISM TOWARDS INCREASING VILLAGE ORIGINAL INCOME
Authors: Hendrawati Erna
Published: July 2021

This study aims to examine and analyze the effect of optimizing asset utilization, local government support, asset management professionalism on increasing Village Original Income (PA Desa). The research population is village officials in Menganti District, Gresik Regency, East Java. The questionnaire that can be obtained is 160 respondents. The data analysis techniques are validity test, reliability test, classical assumption test and multiple regression test. The results of the optimization of asset utilization and asset management professionalism affect village original income, while government support does not affect village original income. This can happen because village officials are aware that by optimizing asset utilization and managing assets professionally, they can increase the village's original income even though there is and no support from the government.
LEAD CONCENTRATION IN HUMAN HAIR IN THE ADMINISTRATIVE CENTER OF THE ALTAI REPUBLIC
Authors: Chanchaeva E. A. , Sukhova M. G. , Kurilenko T. K.
Published: July 2021

Background: Liquid and solid fuels are the main source of lead (Pb) in urban settings. Some household items have also been identified as sources of lead. Thus, monitoring of this trace element in humans remains an important public health issue. Aim: To assess concentration of lead in hair of residents of Gorno-Altaisk city - the administrative center of the Altai Republic and to estimate the proportion of the population with high hair concentration of lead. Methods: Hair samples were collected from 122 (50.8 % men) neither smoking nor taking mineral supplements healthy permanent residents of Gorno-Altaisk aged 4-50 years. Fifty-three percent of them lived in the central part of the city. Concentration of led in the hair samples was estimated by atomic absorption method. Differences in average concentrations across genders, age-groups and locations were studied using Mann - Whitney tests. Associations between continuous variables were studied by non-parametric correlation analysis. Results: The average lead hair concentration in Gorno-Altaisk was 3.18 mg/kg which exceeds the values previously reported from other Russian settings (0.5-3.0 mg/kg). Twenty-six percent of residents had hair concentration of lead above the maximum allowed level of 5.0 mg/kg. Hair lead concentration positively correlated with age (r = 0.54), but was not associated with either gender or place of residence. Conclusions: Average concentration of led in human hair in Gorno-Altaisk is high, but it does not exceed the maximum allowed level. More than every fourth resident of the city has hair lead concentration exceeding biologically acceptable level. We found significant associations between hair lead concentrations and age, but not with gender or place of residence.
ECOLOGICAL FACTORS ASSOCIATED WITH FLUCTUATIONS IN THE INCIDENCE OF NEOPLASMS IN CHILDREN
Authors: Pinaev S. K. , Torshin V. I. , Radysh I. V. , Chizhov A. Ya. , Pinaeva O. G.
Published: July 2021

Introduction: Despite the increasing volume of knowledge on oncogenesis, the year-to-year fluctuations in the incidence of neoplasms remain poorly explained. Neoplasms in children
ASSOCIATIONS BETWEEN THE CHARACTERISTICS OF LARGE NATIONAL REGIONS, INDIVIDUAL ALCOHOL CONSUMPTION AND TOBACCO SMOKING: A SYSTEMATIC REVIEW PROTOCOL
Authors: Maksimov Sergey Alekseevich , Tsygankova Daria P. , Danilchenko Yana V. , Shalnova Svetlana A. , Zelenina Anastasia A. , Drapkina Oksana M.
Published: July 2021

Introduction: Tobacco smoking and hazardous alcohol consumption significantly contribute to the burden of diseases worldwide. Characteristics of the environment has been consistently shown to be associated with the patterns of tobacco smoking and alcohol consumption patterns. This evidence has been previously summarized on country- and neighbourhood-level reviews although the evidence on the associations on the regional level is still scarce. Aim: to present a protocol of the systematic review of available evidence on the associations between certain characteristics of large national regions and alcohol consumption and tobacco smoking. Methods: A systematic search of PubMed, Google Scholar, OpenGrey, CrossRef, and eLibrary) will be conducted to identify original studies with no date or language restrictions. Only studies with territorial characteristics as exposure variables and with tobacco smoking and alcohol consumption as the outcomes will be selected. The studies have no restrictions regarding participant characteristics, that is, gender, age, socioeconomic criteria, or health status. Titles, abstracts, and full text of articles retrieved from the search will be screened and read independently by two reviewers for eligibility. Articles selected for inclusion will be critically and independently appraised by two reviewers. The full-text of the selected studies will be assessed in detail, and findings and their illustrations will be extracted and aggregated. Any disagreements between the reviewers that may arise at any stage will be resolved through discussion, or mediated by a third reviewer. Systematic review registration number: PROSPEROCRD42021234874.
Etiology of Epiphora
Authors: Lee Jeong Min , Baek Ji Sun
Published: July 2021

Purpose: This study aimed to analyze the common causes of epiphora in Korean patients and their response to subsequent management.Methods: We retrospectively analyzed the medical records of 180 patients who visited Kim’s Eye Hospital for epiphora between December 2017 and January 2019. This study included 320 eyes of 180 patients.Results: In the 320 eyes of 180 patients, the most common etiology of epiphora was reflex tearing due to dry eye syndrome, which occurred in 167 eyes (52.19%). The other etiologies of epiphora included anatomical abnormality (68 eyes, 21.25%), multifactorial (60 eyes, 18.75%), functional epiphora (14 eyes, 4.38%), ocular surface disease (seven eyes, 2.19%), and eyelid abnormality (four eyes, 1.25%).Conclusions: The most common etiology of epiphora in Korean patients was reflex tearing due to dry eye syndrome, followed by lacrimal passage abnormality, multifactorial, functional epiphora, anterior segment disease, and eyelid malposition. Most patients with reflex tearing reported improvement in their symptoms after lubrication.
PERBEDAAN INSIDENSI DIABETES MELITUS TIPE 2 DAN HBA1C PADA POPULASI TERPAPAR-TIDAK TERPAPAR EMISI PABRIK SEMEN PADANG
Authors: Adelin Prima , Yaswir Rismawati , Rofinda Zelly Dia , Machmud Rizanda , Yetti Husna
Published: July 2021

Background: Cement factory emission disrupt blood glucose control through insulin resistance mechanism, thus increasing incidence of type 2 diabetes mellitus (DM type 2). Aim: Aim of this study is to determine incidence’s differences of DM type 2 and mean HbA1c patients with DM type 2 within population exposed and unexposed cement Padang factory emission. Method: This was a cross sectional analytic study with cluster sampling that conducted on June-December 2015 with 129 and 125 participant from exposed and unexposed areas. Age of participants are 20-79 years old. Incidence is total new cases per total sample in exposed or unexposed area. HbA1c were measured with immunoturbidimetry method. Data were analyzed by chi-squared test to asses differences of two proportions and t test to asses differences of two averages. Results: The incidence DM type 2 are 3,9% and 7,2% respectively in exposed and unexposed areas, without significant difference (p>0,05). The mean HbA1c patients DM type 2 are 10,0(2,4)% and 8,8(1,6)% in exposed and unexposed areas, without significant difference (p>0,05). Conclusions: There were no significant differences incidence of DM type 2 and  mean HbA1c patients DM type 2 in the populations exposed and unexposed cement Padang factory emission. Cohort studies is required to see the effects of cement factory emission
Lupus Eritematosus Sistemik pada Pria
Authors: Andrean Harry , Raveinal Raveinal
Published: July 2021

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by presence of nucleus autoantibody and affected multiple organ. Systemic lupus erythematosus is more common in women than men with ratio 2:1 to 15:1. Men with SLE often have a more aggressive clinical course, lead to a poorer prognosis compared with women with SLE. Case Report: A man, 29 years old came to hospital with main complain joint pain increased since 1 week ago, accompanied with red spot on face, trunk, hands, foot, and back, hair loss, swollen leg, mouth ulcer, and fatique. Malar rash and discoid rash were identified from physical examination. From laboratorium, ANA profile was positive for RNP/Sm, Sm, dsDNA, and histone. Skin biopsy showed a lupus discoid. Conclusion: The patient was treated with pulse-dose methylprednisolone for 3 days and showed a good response clinically.
Elder Mistreatment: a Clinical, Social, and Legal Concern
Authors: Este Muhammad Rasyid
Published: July 2021

Elder mistreatment is all activities carried out by other people towards the elderly which are classified as dangerous and causing harm, such as physical, verbal, financial or material abuse and or neglect, and violation of human rights. The incidence ranges from 3.2% to 27.5% of the elderly population, where this population is predicted to be 1.2 billion people by 2025. The main risk factors are under-reporting, individual factors, relationship factors, community factors and social factors. The diagnosis includes anamnesis of the patient, family or caregiver. Detection begins by confirming any cognitive impairment, using the Mini-Cog or Mini Mental State Examination (MMSE) form. Followed by screening, which can be done using the Elder Abuse Suspicion Index (EASI) instrument, then a physical examination looks for evidence of acts of abuse or neglect. Intervention is carried out by providing medical treatment for physical injuries, temporary protection, keeping the perpetrator away from the victim, and education on patterns of mistreatment that can involve social services and law enforcement. Management includes a complete and focused examination of mistreatment, preparing a safety plan, which is providing plans to improve patient protection, as well as education on treatment goals. Patient management should use a multidisciplinary team consisting of doctors, nurses, social workers, legal representatives and administrative officers. Complete data and clear laws and regulations regarding mistreatment are needed, such as in America and Britain where absolute mistreatment is legally reported.
Effects of Choice of Medical Imaging Modalities on a Non-invasive Diagnostic and Monitoring Computational Framework for Patients With Complex Valvular, Vascular, and Ventricular Diseases Who Undergo Transcatheter Aortic Valve Replacement
Authors: Baiocchi Melissa , Barsoum Shirley , Khodaei Seyedvahid , de la Torre Hernandez Jose M. , Valentino Sydney E. , Dunford Emily C. , MacDonald Maureen J. , Keshavarz-Motamed Zahra
Published: July 2021

Due to the high individual differences in the anatomy and pathophysiology of patients, planning individualized treatment requires patient-specific diagnosis. Indeed, hemodynamic quantification can be immensely valuable for accurate diagnosis, however, we still lack precise diagnostic methods for numerous cardiovascular diseases including complex (and mixed) valvular, vascular, and ventricular interactions (C3VI) which is a complicated situation made even more challenging in the face of other cardiovascular pathologies. Transcatheter aortic valve replacement (TAVR) is a new less invasive intervention and is a growing alternative for patients with aortic stenosis. In a recent paper, we developed a non-invasive and Doppler-based diagnostic and monitoring computational mechanics framework for C3VI, called C3VI-DE that uses input parameters measured reliably using Doppler echocardiography. In the present work, we have developed another computational-mechanics framework for C3VI (called C3VI-CT). C3VI-CT uses the same lumped-parameter model core as C3VI-DE but its input parameters are measured using computed tomography and a sphygmomanometer. Both frameworks can quantify: (1) global hemodynamics (metrics of cardiac function); (2) local hemodynamics (metrics of circulatory function). We compared accuracy of the results obtained using C3VI-DE and C3VI-CT against catheterization data (gold standard) using a C3VI dataset (N = 49) for patients with C3VI who undergo TAVR in both pre and post-TAVR with a high variability. Because of the dataset variability and the broad range of diseases that it covers, it enables determining which framework can yield the most accurate results. In contrast with C3VI-CT, C3VI-DE tracks both the cardiac and vascular status and is in great agreement with cardiac catheter data.
Propositions for a Resilient, Post-COVID-19 Future for the AEC Industry
Authors: Nassereddine Hala , Seo Kyung Wook , Rybkowski Zofia K. , Schranz Christian , Urban Harald
Published: July 2021

The coronavirus outbreak has challenged and continues to challenge every aspect of the supply chain within the AEC industry, forcing stakeholders to cope with increasing uncertainties and continuous change. The notion of resilience is especially salient now. While the need for the AEC industry to focus on resilience has been highlighted in recent articles, there is a need for a comprehensive discussion on what resilience means for the AEC industry and how companies can create built-in resilience. This paper takes the form of a high-level overview of where the industry is headed and aims to establish eleven propositions for a resilient, post-COVID-19 future, for practitioners working in the design and construction industry. Moreover, this paper proposes a ‘decentralization of workforce and integration of data’ model in which the established propositions are manifested to support a resilient AEC industry.
HIV-1 Hijacking of Host ATPases and GTPases That Control Protein Trafficking
Authors: Tavares Lucas A. , Januário Yunan C. , daSilva Luis L. P.
Published: July 2021

The human immunodeficiency virus (HIV-1) modifies the host cell environment to ensure efficient and sustained viral replication. Key to these processes is the capacity of the virus to hijack ATPases, GTPases and the associated proteins that control intracellular protein trafficking. The functions of these energy-harnessing enzymes can be seized by HIV-1 to allow the intracellular transport of viral components within the host cell or to change the subcellular distribution of antiviral factors, leading to immune evasion. Here, we summarize how energy-related proteins deviate from their normal functions in host protein trafficking to aid the virus in different phases of its replicative cycle. Recent discoveries regarding the interplay among HIV-1 and host ATPases and GTPases may shed light on potential targets for pharmacological intervention.
Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma
Authors: Fu Yuyin , Peng Yujia , Zhao Shengyan , Mou Jun , Zeng Lishi , Jiang Xiaohua , Yang Chengli , Huang Cheng , Li Yuyan , Lu Yin , Wu Mengdan , Yang Yanfang , Kong Ting , Lai Qinhuai , Wu Yangping , Yao Yuqin , Wang Yuxi , Gou Lantu , Yang Jinliang
Published: July 2021

Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. However, the overall response rate to immune checkpoint inhibitor therapy for many cancers is only between 20 and 40%, and even less for colorectal cancer (CRC) patients. Thus, there is an urgent need to develop an efficient immunotherapeutic strategy for CRC. Here, we developed a novel CRC combination therapy consisting of a multiple receptor tyrosine kinase inhibitor (Foretinib) and anti-PD-1 antibody. The combination therapy significantly inhibited tumor growth in mice, led to improved tumor regression without relapse (83% for CT26 tumors and 50% for MC38 tumors) and prolonged overall survival. Mechanistically, Foretinib caused increased levels of PD-L1 via activating the JAK2-STAT1 pathway, which could improve the effectiveness of the immune checkpoint inhibitor. Moreover, the combination therapy remodeled the tumor microenvironment and enhanced anti-tumor immunity by further increasing the infiltration and improving the function of T cells, decreasing the percentage of tumor-associated macrophages (TAMs) and inhibiting their polarization toward the M2 phenotype. Furthermore, the combination therapy inhibited the metastasis of CT26-Luc tumors to the lung in BALB/c mouse by reducing proportions of regulatory T-cells, TAMs and M2 phenotype TAMs in their lungs. This study suggests that a novel combination therapy utilizing both Foretinib and anti-PD-1 antibody could be an effective combination strategy for CRC immunotherapy.
Distilling Professional Opinion to Gauge Vulnerability of Guam Avifauna to Brown Treesnake Predation
Authors: McElderry Robert M. , Paxton Eben H. , Nguyen Andre V. , Siers Shane R.
Published: July 2021

The avifauna of Guam was devastated by the introduction of the Brown Treesnake, and the restoration of native birds would need to address the problem with eradication or suppression of BTS. With eradication of the snake unlikely in the near term, and suppression capabilities limited to specific finite areas, key information for reintroductions is how low BTS abundance will likely need to be for each bird species to be re-established based on their vulnerability to BTS predation. Here, we estimate vulnerability, which can no longer be measured directly, so biologists who are familiar with one or more of seven Guam birds were surveyed to obtain their knowledge and produce quantitative vulnerability estimates. As is typical of birds adapted to islands devoid of predators, respondents judged that our focal species exhibit few predator avoidance and tolerance traits, leaving body size as the prime determinant of vulnerability. Respondent opinion also holds that any behavior that reduces the likelihood of an encounter by BTS, e.g., roosting/nesting in palm crowns, cavity nesting, and in particular urban dwelling, substantially reduces vulnerability. Our results can help inform species-specific decisions about when it may be safe to consider the release of birds on Guam depending on the relative vulnerability of each species to predation by BTS.
White Blood Cell Counts to High-Density Lipoprotein Cholesterol Ratio, as a Novel Predictor of Long-Term Adverse Outcomes in Patients After Percutaneous Coronary Intervention: A Retrospective Cohort Study
Authors: Wu Ting-Ting , Zheng Ying-Ying , Xiu Wen-Juan , Wang Wan-Rong , Xun Yi-Li , Ma Yan-Yan , Kadir Patigvl , Pan Ying , Ma Yi-Tong , Xie Xiang
Published: July 2021

Background: White blood cell (WBC) counts and high-density lipoprotein cholesterol (HDL-C) are widely available in clinical practice. However, the predictive value for cardiovascular disease (CVD) is uncertain. In the present study, we firstly assessed the prognostic value of WBC to HDL-C ratio (WHR) in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).

Methods: Six thousand and fifty patients with CAD after PCI from a retrospective cohort study (identifier: ChiCTR-INR-16010153) were evaluated initially. Three hundred and seventy-one patients were excluded due to HDL cholesterol data not available, malignancy, dementia, psoriasis or eczema, systemic connective tissue disorders, multiple sclerosis, chronic liver disease, and chronic obstructive pulmonary disorder. Finally, 5,679 patients were included in the study. The primary outcome was long-term mortality. Secondary endpoints were mainly major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a combination of stroke, cardiac death, stent thrombosis, recurrent myocardial infarction, and target vessel revascularization. The mean follow-up time of this study was 35.9 ± 22.5 months. We defined the best cutoff value of MHR according to the receiver operating curve (ROC), and then patients were divided into high and low WHR groups according to the cutoff value. We analyzed the data in both an acute coronary syndrome group (ACS) and a stable CAD subgroup, respectively.

Results: Overall, there were 293 cases of long-term mortality during the follow-up period. According to the cutoff value (WHR = 8.25), 1,901 ACS patients were divided into high WHR group (n = 724) and low WHR group (n = 1,177). Compared to low WHR group, the incidence of all-cause mortality (ACM, 5.5 vs. 3.6%, p = 0.048) and cardiac death (4.7vs. 2.9%, p = 0.042) were significantly higher in the high WHR group. In stable CAD group, we also found the incidence of ACM and cardiac death were significantly higher in the high group compared to that in the low group. We did not find significant difference between the high and the low WHR group in the incidence of MACCEs. The multivariate Cox proportional hazards model showed that increased WHR level was independently correlated with the mortality. In the high WHR group, the risk of ACM increased two times in ACS [adjusted HR = 2.036 (1.258–3.296), p = 0.004] and 1.5 times in stable CAD [adjusted HR = 1.586 (1.178–2.136), p = 0.002].

Conclusion: The present study indicated that an increased WBC count to HDL-C ratio was independently associated with long-term mortality in CAD patients who underwent PCI.
Clinical Outcomes in Patients With Left Bundle Branch Area Pacing vs. Right Ventricular Pacing for Atrioventricular Block
Authors: Li Xiaofei , Zhang Junmeng , Qiu Chunguang , Wang Zhao , Li Hui , Pang Kunjing , Yao Yan , Liu Zhimin , Xie Ruiqin , Chen Yangxin , Wu Yongquan , Fan Xiaohan
Published: July 2021

Background: Left bundle branch area pacing (LBBAP) is a novel pacing modality with stable pacing parameters and a narrow-paced QRS duration. We compared heart failure (HF) hospitalization events and echocardiographic measures between LBBAP and right ventricular pacing (RVP) in patients with atrioventricular block (AVB).

Methods and Results: This multicenter observational study prospectively recruited consecutive AVB patients requiring ventricular pacing in five centers if they received LBBAP or RVP and had left ventricular ejection fraction (LVEF) >50%. Data on electrocardiogram, pacing parameters, echocardiographic measurements, device complications, and clinical outcomes were collected at baseline and during follow-up. The primary outcome was first episode hospitalization for HF or upgrade to biventricular pacing. LBBAP was successful in 235 of 246 patients (95.5%), while 120 patients received RVP. During a mean of 11.4 ± 2.7 months of follow-up, the ventricular pacing burden was comparable (83.9 ± 35.1 vs. 85.7 ± 30.0%), while the mean LVEF differed significantly (62.6 ± 4.6 vs. 57.8 ± 11.4%) between the LBBAP and RVP groups. Patients with LBBAP had significantly lower occurrences of HF hospitalization and upgrading to biventricular pacing than patients with RVP (2.6 vs. 10.8%, P <0.001), and differences in primary outcome between LBBAP and RVP were mainly observed in patients with ventricular pacing >40% or with baseline LVEF <60%. The primary outcome was independently associated with LBBAP (adjusted HR 0.14, 95% CI: 0.04–0.55), previous myocardial infarction (adjusted HR 6.82, 95% CI: 1.23–37.5), and baseline LVEF (adjusted HR 0.91, 95% CI: 0.86–0.96).

Conclusion: Permanent LBBAP might reduce the risk of HF hospitalization or upgrade to biventricular pacing compared with RVP in AVB patients requiring a high burden of ventricular pacing.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03851315; URL: http://www.chictr.org.cn; Unique Identifier: ChiCTR2100043296.
Earthquake Early Warning System for Structural Drift Prediction Using Machine Learning and Linear Regressors
Authors: Iaccarino Antonio Giovanni , Gueguen Philippe , Picozzi Matteo , Ghimire Subash
Published: July 2021

In this work, we explored the feasibility of predicting the structural drift from the first seconds of P-wave signals for On-site Earthquake Early Warning (EEW) applications. To this purpose, we investigated the performance of both linear least square regression (LSR) and four non-linear machine learning (ML) models: Random Forest, Gradient Boosting, Support Vector Machines and K-Nearest Neighbors. Furthermore, we also explore the applicability of the models calibrated for a region to another one. The LSR and ML models are calibrated and validated using a dataset of ∼6,000 waveforms recorded within 34 Japanese structures with three different type of construction (steel, reinforced concrete, and steel-reinforced concrete), and a smaller one of data recorded at US buildings (69 buildings, 240 waveforms). As EEW information, we considered three P-wave parameters (the peak displacement, Pd, the integral of squared velocity, IV2, and displacement, ID2) using three time-windows (i.e., 1, 2, and 3 s), for a total of nine features to predict the drift ratio as structural response. The Japanese dataset is used to calibrate the LSR and ML models and to study their capability to predict the structural drift. We explored different subsets of the Japanese dataset (i.e., one building, one single type of construction, the entire dataset. We found that the variability of both ground motion and buildings response can affect the drift predictions robustness. In particular, the predictions accuracy worsens with the complexity of the dataset in terms of building and event variability. Our results show that ML techniques perform always better than LSR models, likely due to the complex connections between features and the natural non-linearity of the data. Furthermore, we show that by implementing a residuals analysis, the main sources of drift variability can be identified. Finally, the models trained on the Japanese dataset are applied the US dataset. In our application, we found that the exporting EEW models worsen the prediction variability, but also that by including correction terms as function of the magnitude can strongly mitigate such problem. In other words, our results show that the drift for US buildings can be predicted by minor tweaks to models.
Mitochondrial DNA 4977 bp Deletion in Peripheral Blood Is Associated With Polycystic Ovary Syndrome
Authors: Ye Mujin , Hu Bin , Shi Weihui , Guo Fei , Xu Chenming , Li Shuyuan
Published: July 2021

Background

Polycystic ovary syndrome (PCOS) is a common endocrine disorder worldwide. We aimed to examine the associations of two mitochondrial DNA (mtDNA) biomarkers in the peripheral blood, mtDNA copy number (CN), and mtDNA4977 deletion rate (DR), with PCOS in a clinical setting.

Methods

We performed a study involving 263 women with PCOS and 326 age-matched controls between June 2015 and June 2019. The mtDNA CN and mtDNA4977 DR were measured using multiplex probe-based qPCR. The associations of the mtDNA CN and mtDNA4977 DR with the risk of PCOS were estimated using logistic regression.

Results

Analysis of the associations between mtDNA biomarkers and PCOS indicate that the mtDNA CN (P = 0.003) and mtDNA4977 DR (P < 0.001) in PCOS patients were significantly higher than those in the controls. After adjusting for the body mass index, luteinizing hormone/follicle-stimulating hormone ratio, and testosterone level, only higher mtDNA4977 DR was associated with PCOS (odds ratio 1.053, 95% confidence interval 1.024 to 1.083; P < 0.001). The linear dose-response trends of the mtDNA4977 DR were also supported by the quartile analysis.

Conclusion

Multivariable models suggest that mtDNA4977 DR levels are strongly associated with PCOS and represent an independent risk factor for PCOS. Further investigation of the utility of mtDNA as a biomarker for PCOS is warranted.
Optimizing the RMC Code Using the Decay Chain Method for Large-Scale Decay Calculations
Authors: Li Hao , Yu Ganglin , Huang Shanfang , Wang Kan
Published: July 2021

Decay calculations play an important role in reactor physics simulations. In particular, the isotopic decay of the burned fuel during refueling is important for predicting the startup reactivity of the following burn-up cycle. In addition, there is a growing interest in high-fidelity simulations where the mesh in the burn-up region can involve millions of regions. However, existing models repeatedly solve the same Bateman equations for each region, which is a waste of calculational resources. RMC is a Monte Carlo neutron transport code developed for advanced reactor physics analysis including criticality calculations and burn-up calculations. This paper presents a decay calculation method named the Decay Chain Method (DCM) to optimize the RMC code for large-scale decay calculations. Unlike traditional methods, the Decay Chain Method solves the Bateman equations one decay chain at a time rather than one region at a time. The decay calculation in the burn-up mode then treats the decay steps as zero power burn-up steps with some optimized calculational methods to further reduce the calculational time. These methods were evaluated for a single pin example and for a Virtual Environment for Reactor Applications (VERA) full-core example. The calculations for the single pin example verify the accuracy of the decay step treatment in the burn-up mode and show the improved efficiency. The single pin is divided into 1–1,000,000 decay regions to study the efficiency differences between the Transmutation Trajectory Analysis (TTA) and DCM methods. Both methods have a linear complexity with respect to the number of regions but DCM costs just one-sixtieth of the TTA time. In the simplified VERA full core example, the DCM method reduces the decay calculation time to 0.32 min from 75.26 min while the accuracy remains unchanged.
Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus
Authors: Wang Huanhuan , Zhao Qin , Zhang Yuyu , Zhang Qihe , Zheng Zhuangzhuang , Liu Shiyu , Liu Zijing , Meng Lingbin , Xin Ying , Jiang Xin
Published: July 2021

Head and neck cancer (HNC) is the sixth most common malignancy worldwide; head and neck squamous cell carcinoma (HNSCC) account for the most cases of HNC. Past smoking and alcohol consumption are common risk factors of HNSCC; however, an increasing number of cases associated with human papillomavirus (HPV) infection have been reported in recent years. The treatment of HNSCC is integrated and multimodal including traditional surgery, radiotherapy, chemotherapy, and targeted therapy. Since pembrolizumab was approved in 2016, an increasing number of studies have focused on immunotherapy. However, not all of HNSCC patients have a better outcome on immunotherapy. Immunotherapy has been reported to be more effective in HPV-positive patients, but its molecular mechanism is still unclear. Some researchers have proposed that the high proportion of infiltrating immune cells in HPV-positive tumors and the difference in immune checkpoint expression level may be the reasons for their better response. As a result, a series of individualized immunotherapy trials have also been conducted in HPV-positive patients. This paper summarizes the current status of HNSCC immunotherapy, individualized immunotherapy in HPV-positive patients, and immune differences in HPV-positive tumors to provide new insights into HNSCC immunotherapy and try to identify patients who may benefit from immunotherapy.
Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling
Authors: Chen Pei-Yu , Wei Wen-Fei , Wu Hong-Zhen , Fan Liang-Sheng , Wang Wei
Published: July 2021

Cancer-associated fibroblasts (CAFs) are important, highly heterogeneous components of the tumor extracellular matrix that have different origins and express a diverse set of biomarkers. Different subtypes of CAFs participate in the immune regulation of the tumor microenvironment (TME). In addition to their role in supporting stromal cells, CAFs have multiple immunosuppressive functions, via membrane and secretory patterns, against anti-tumor immunity. The inhibition of CAFs function and anti-TME therapy targeting CAFs provides new adjuvant means for immunotherapy. In this review, we outline the emerging understanding of CAFs with a particular emphasis on their origin and heterogeneity, different mechanisms of their regulation, as well as their direct or indirect effect on immune cells that leads to immunosuppression.
The Influence of Corticosteroids, Immunosuppressants and Biologics on Patients With Inflammatory Bowel Diseases, Psoriasis and Rheumatic Diseases in the Era of COVID-19: A Review of Current Evidence
Authors: Zhang Mengyuan , Bai Xiaoyin , Cao Wei , Ji Junyi , Wang Luo , Yang Yang , Yang Hong
Published: July 2021

Patients with inflammatory bowel disease, psoriasis or other rheumatic diseases treated with corticosteroids, immunomodulators and biologics might face additional risk during COVID-19 epidemic due to their immunocompromised status. However, there was still no unanimous opinion on the use of these therapy during COVID-19 epidemic. Current studies suggested that systemic corticosteroids might increase the risk of hospitalization, as well as risks of ventilation, ICU, and death among patients with immune-mediated inflammatory diseases. Anti-TNF agent was associated with lower rate of hospitalization, as well as lower risks of ventilation, ICU, and death. No significant changes in rates of hospitalization, ventilation, ICU and mortality were observed in patients treated with immunomodulators or biologics apart from anti-TNF agents. The underlying mechanism of these results might be related to pathway of antiviral immune response and cytokine storm induced by SARS-COV-2 infection. Decision on the use of corticosteroids, immunomodulators and biologics should be made after weighing the benefits and potential risks based on individual patients.
Immune Myocarditis Overlapping With Myasthenia Gravis Due to Anti-PD-1 Treatment for a Chordoma Patient: A Case Report and Literature Review
Authors: Liang Shujing , Yang Jingxian , Lin Yun , Li Tong , Zhao Wenrong , Zhao Jun , Dong Chunyan
Published: July 2021

Immunotherapy begins to be widely used due to the increasing exploration and gratifying effects in multiple cancers. Chordoma, as a rare bone malignant tumor, often recurs and metastasizes after undergoing surgery and radiotherapy. Therefore, immunotherapy can be explored as an emerging, potentially effective treatment to improve the survival rate and clinical benefit of patients. However, a variety of immune-related adverse events (irAEs) cannot be avoided completely. And the immunotherapy-induced myocarditis, as a rare but fatal irAE, has been increasingly reported. Understanding the mechanism involved in irAEs can inform best practices for side effects management. Here, we firstly reported a case of immune myocarditis and subsequent myasthenia gravis (MG) following anti-PD-1 treatment for chordoma.
An Unbiased Machine Learning Exploration Reveals Gene Sets Predictive of Allograft Tolerance After Kidney Transplantation
Authors: Fu Qiang , Agarwal Divyansh , Deng Kevin , Matheson Rudy , Yang Hongji , Wei Liang , Ran Qing , Deng Shaoping , Markmann James F.
Published: July 2021

Efforts at finding potential biomarkers of tolerance after kidney transplantation have been hindered by limited sample size, as well as the complicated mechanisms underlying tolerance and the potential risk of rejection after immunosuppressant withdrawal. In this work, three different publicly available genome-wide expression data sets of peripheral blood lymphocyte (PBL) from 63 tolerant patients were used to compare 14 different machine learning models for their ability to predict spontaneous kidney graft tolerance. We found that the Best Subset Selection (BSS) regression approach was the most powerful with a sensitivity of 91.7% and a specificity of 93.8% in the test group, and a specificity of 86.1% and a sensitivity of 80% in the validation group. A feature set with five genes (HLA-DOA, TCL1A, EBF1, CD79B, and PNOC) was identified using the BSS model. EBF1 downregulation was also an independent factor predictive of graft rejection and graft loss. An AUC value of 84.4% was achieved using the two-gene signature (EBF1 and HLA-DOA) as an input to our classifier. Overall, our systematic machine learning exploration suggests novel biological targets that might affect tolerance to renal allografts, and provides clinical insights that can potentially guide patient selection for immunosuppressant withdrawal.
Toxoplasma gondii Infection Inhibits Histone Crotonylation to Regulate Immune Response of Porcine Alveolar Macrophages
Authors: Yang Jing , He Zhengming , Chen Chengjie , Li Senyang , Qian Jiahui , Zhao Junlong , Fang Rui
Published: July 2021

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can infect almost all warm-blooded animals, causing serious public health problems. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification (PTM), which is first identified on histones and has been proved relevant to procreation regulation, transcription activation, and cell signaling pathway. However, the biological functions of histone crotonylation have not yet been reported in macrophages infected with T. gondii. As a result, a total of 1,286 Kcr sites distributed in 414 proteins were identified and quantified, demonstrating the existence of crotonylation in porcine alveolar macrophages. According to our results, identified histones were overall downregulated. HDAC2, a histone decrotonylase, was found to be significantly increased, which might be the executor of histone Kcr after parasite infection. In addition, T. gondii infection inhibited the crotonylation of H2B on K12, contributing on the suppression of epigenetic regulation and NF-κB activation. Nevertheless, the reduction of histone crotonylation induced by parasite infection could promote macrophage proliferation via activating PI3K/Akt signaling pathway. The present findings point to a comprehensive understanding of the biological functions of histone crotonylation in porcine alveolar macrophages, thereby providing a certain research basis for the mechanism research on the immune response of host cells against T. gondii infection.
Vaccination Against Diphtheria and Tetanus as a Way to Activate Adaptive Immunity in Children with Solid Tumors
Authors: Kostinov Mikhail Petrovich , Akhmatova Nelli Kimovna , Karpocheva Svetlana Victorovna , Vlasenko Anna Egorovna , Polishchuk Valentina Borisovna , Kostinov Anton Mikhailovich
Published: July 2021

Early studies on vaccination of children with oncological diseases were only dedicated to the assessment of safety and immunogenicity of the drug. Mechanisms of the post-vaccination immune response were not investigated. This study involved 41 patients aged 7-15 years who were treated for solid tumors two or more years ago. Of these, 26 were vaccinated against diphtheria and tetanus with ADS-m toxoid. Fifteen children (i.e., controls) were not vaccinated. The vaccination tolerability and clinical characteristics of the underlying disease remission ware assessed. Lymphocyte subpopulations were investigated over time by flow cytometry at 1, 6, and 12 months. IgG anti-diphtheria and anti-tetanus toxoids levels were assessed by ELISA. Within the first day of the post-vaccination period, two (7.7%) children demonstrated moderate local reactions and increased body temperature (up to 38.0°C). Relapse and metastasis were not mentioned within a year after immunization. An increase in concentration of IgG antibodies, maintained for 12 months, were noted [2.1 (1.3-3.4) IU/ml against diphtheria (p <0.001), 6.4 (2.3-9.7) IU/ml against tetanus (p <0.001)]. In contrast to healthy children, those with a history of cancer demonstrated a decrease in the relative number of mature T lymphocytes, as well as in absolute number of cytotoxic T cells and B lymphocytes. In a month after the revaccination, a significant increase in absolute (p = 0.04) and relative (p = 0.007) numbers of T lymphocytes and T helpers was revealed. In a year, these values decreased to baseline levels. As for helpers, they decreased below baseline and control values (p = 0.004). In a year after the vaccination, there was a significant (p = 0.05) increase in lymphocyte level with a decrease in the number of NK cells and B cells as compared with controls. Revaccination against diphtheria and tetanus promoted proliferation of a total lymphocytic cell pool along with restoration of the T lymphocyte subpopulation in children with a history of solid tumors. The ADS-m toxoid has a certain nonspecific immunomodulatory effect. These findings are important, also in the midst of the coronavirus pandemic.
Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia
Authors: Nelde Annika , Maringer Yacine , Bilich Tatjana , Salih Helmut R. , Roerden Malte , Heitmann Jonas S. , Marcu Ana , Bauer Jens , Neidert Marian C. , Denzlinger Claudio , Illerhaus Gerald , Aulitzky Walter Erich , Rammensee Hans-Georg , Walz Juliane S.
Published: July 2021

Antigen-specific immunotherapies, in particular peptide vaccines, depend on the recognition of naturally presented antigens derived from mutated and unmutated gene products on human leukocyte antigens, and represent a promising low-side-effect concept for cancer treatment. So far, the broad application of peptide vaccines in cancer patients is hampered by challenges of time- and cost-intensive personalized vaccine design, and the lack of neoepitopes from tumor-specific mutations, especially in low-mutational burden malignancies. In this study, we developed an immunopeptidome-guided workflow for the design of tumor-associated off-the-shelf peptide warehouses for broadly applicable personalized therapeutics. Comparative mass spectrometry-based immunopeptidome analyses of primary chronic lymphocytic leukemia (CLL) samples, as representative example of low-mutational burden tumor entities, and a dataset of benign tissue samples enabled the identification of high-frequent non-mutated CLL-associated antigens. These antigens were further shown to be recognized by pre-existing andde novoinduced T cells in CLL patients and healthy volunteers, and were evaluated as pre-manufactured warehouse for the construction of personalized multi-peptide vaccines in a first clinical trial for CLL (NCT04688385). This workflow for the design of peptide warehouses is easily transferable to other tumor entities and can provide the foundation for the development of broad personalized T cell-based immunotherapy approaches.
Modeling Fine-Scale Cetaceans’ Distributions in Oceanic Islands: Madeira Archipelago as a Case Study
Authors: Fernandez Marc , Alves Filipe , Ferreira Rita , Fischer Jan-Christopher , Thake Paula , Nunes Nuno , Caldeira Rui , Dinis Ana
Published: July 2021

Species distributional estimates are an essential tool to improve and implement effective conservation and management measures. Nevertheless, obtaining accurate distributional estimates remains a challenge in many cases, especially when looking at the marine environment, mainly due to the species mobility and habitat dynamism. Ecosystems surrounding oceanic islands are highly dynamic and constitute a key actor on pelagic habitats, congregating biodiversity in their vicinity. The main objective of this study was to obtain accurate fine-scale spatio-temporal distributional estimates of cetaceans in oceanic islands, such as the Madeira archipelago, using a long-term opportunistically collected dataset. Ecological Niche Models (ENM) were built using cetacean occurrence data collected on-board commercial whale watching activities and environmental data from 2003 to 2018 for 10 species with a diverse range of habitat associations. Models were built using two different datasets of environmental variables with different temporal and spatial resolutions for comparison purposes. State-of-the-art techniques were used to iterate, build and evaluate the MAXENT models constructed. Models built using the long-term opportunistic dataset successfully described distribution patterns throughout the study area for the species considered. Final models were used to produce spatial grids of species average and standard deviation suitability monthly estimates. Results provide the first fine-scale (both in the temporal and spatial dimension) cetacean distributional estimates for the Madeira archipelago and reveal seasonal/annual distributional patterns, thus providing novel insights on species ecology and quantitative data to implement better dynamic management actions.
Review of Research on the Rare-Earth Doped Piezoelectric Materials
Authors: Chen Yan , Zhang Donglai , Peng Zhong , Yuan Maodan , Ji Xuanrong
Published: July 2021

The piezoelectric materials, such as ceramics, crystals, and films, have wide applications in the mechanical industry, medical imaging, electronic information, and ultrasonic devices, etc. Generally, adding oxide dopants, or introducing new solid solutions to form the morphotropic phase boundary of the piezoelectric materials were common strategies to enhance the electric properties. In recent decades, rare-earth elements doped piezoelectric materials have attracted much attention due to their multifunctional performances combining piezoelectric and photoluminescence properties, which has potential applications in ultrasonics, electronics, automatic control, machinery and optoelectronic fields. An overview of the recent investigations and perspectives on rare-earth doped piezoelectric ceramics, single crystals, and films were presented.
ECCO2R in 12 COVID-19 ARDS Patients With Extremely Low Compliance and Refractory Hypercapnia
Authors: Ding Xin , Chen Huan , Zhao Hua , Zhang Hongmin , He Huaiwu , Cheng Wei , Wang Chunyao , Jiang Wei , Ma Jie , Qin Yan , Liu Zhengyin , Wang Jinglan , Yan Xiaowei , Li Taisheng , Zhou Xiang , Long Yun , Zhang Shuyang
Published: July 2021

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed.

Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected.

Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons.

Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance.

Clinical Trial Registration:https://www.clinicaltrials.gov/, identifier NCT04340414.