bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence Mechanism of Convective Geothermal Systems in Jiaodong Peninsula, China
Authors: Shi Meng , Kang Fengxin , Yin Tao , Gao Song , Sui Haibo , Guo Xu , Yu Xiaojing
Published: April 2022

Previous studies have shown that on the surface, Jiaobei uplift and Weihai uplift have higher heat flow values than Jiaolai depression. However, the mechanism by which the deep heat flow migrates and the exposure of geothermal resources are still unclear. In this study, the geothermal field distribution, thermal conductivity, temperature logging data, and chemical composition of the geothermal fluid in the Jiaodong Peninsula were analyzed. Regarding the thermal field’s characteristics and their controlling factors, a conceptual model of heat flow diversion-accumulation between the uplift and basin areas in the Jiaodong Peninsula is proposed. The lithology of the uplift area is mainly composed of intrusive rocks and metamorphic rocks with high thermal conductivities. The lithology of the basin mainly consists of sandstone with a low thermal conductivity. The bottom of the basin, which has a low thermal conductivity and low permeability, serves as a heat insulation and water insulation roof, which causes the heat flow and the heat-carrying fluids and gases from the deep crust to be refracted and redistributed at the bottom of the basin area. As a result, the bottom of the uplift areas has a higher heat flow. In particular, the axial position in the uplift area has the highest heat flow. In addition, the geothermal resources in the Jiaodong Peninsula are mainly distributed in the V-shaped area where the upper block of the NE- and NW-trending faults intersect, and the scope of the exposure of the geothermal resources is very limited.
Extended Exam Time Has a Minimal Impact on Disparities in Student Outcomes in Introductory Physics
Authors: Tarchinski Nita A. , Rypkema Heather , Finzell Thomas , Popov Yuri O. , McKay Timothy A.
Published: April 2022

Disparities in student outcomes, including gendered performance differences, are widespread in introductory physics and other STEM courses. STEM education researchers have investigated many course and student factors that could contribute to these inequities, including class size, test formats, assignment weightings, and students’ sense of belonging. These inequities are often largest in the timed, multiple-choice, high-stakes exams that characterize so many traditional introductory STEM courses. Time pressure is widely believed to influence student outcomes on these exams, reducing overall performance and perhaps exaggerating widespread group performance disparities. Reducing time pressure for students by providing more test-taking time is a small, structural change that could have large impacts on student performance and could differentially affect students. To explore this possibility, we offered all 596 students in our introductory physics course a 50% extension in test-taking time and collected data on exam performance, student demographics, and the time each student took to complete each exam. We made careful comparisons of student performance to historical data, across demographic groups, and across time usage on the exams using both raw exam scores and a “Better Than Expected” measure that compares student performance in the course under study to their own performance in other courses. While students overall scored slightly higher with extended exam time, we found that extended time did not reduce the well-established disparities in student outcomes categorized by sex, race/ethnicity, or college generation status present in our introductory physics course. These findings both indicate that extending exam time is not a simple fix for disparities in student outcomes and reinforce that systemic changes towards more authentic assessments of STEM knowledge and capabilities are imperative.
Empowerment and Well-Being Through Participatory Action Research and Accessible Gaming: A Case Study With Adults With Intellectual Disability
Authors: Sousa Carla , Neves José Carlos , Damásio Manuel José
Published: April 2022

Although the potential of games to foster learning, representation, empowerment, well-being, and social inclusion is already documented, some groups seem to remain underrepresented. In the field of disability, this potential is still immersed in a set of barriers and hindrances, arising from the lack of accessibility of this medium and the lack of representation of voices in research and development processes. This problem seems to be exponentiated in the field of Intellectual Disability (ID). The present study describes insights from a case study developed with 14 institutionalized adults with severe ID, with two complementary aims: (a) explore the effectiveness of a PAR gaming approach in the empowerment and well-being of adults with ID living in an institutional setting; and (b) explore the feasibility of promoting accessibility in games through PAR. The proposed intervention included the development of games by higher education students for these individuals, with their active participation in all phases – conceptual definition, game design, game development, and playtesting. A total of 38 playtesting sessions and 162 gaming sessions were conducted, where systematic observation grids were filled, and pre and post-process assessments were conducted, targeting variables related to empowerment and well-being. The obtained results sustain this type of action-research design as a feasible strategy to empower people with ID and foster their well-being, through games as a form of expression and not only therapy. It also reflects on accessibility improvement through the presence of underrepresented groups (people with ID particularly) in the media creation processes that can,per se, be considered a form of empowerment. These insights also open a discussion about a potential paradigm shift toward a social model of accessibility aligned with the current views on the field of disability studies. Future studies should replicate this methodology with larger samples and in a context not aligned with the pandemic isolation. Furthermore, PAR must also be explored from a more general perspective, as a strategy to promote accessibility and participation in other media and cultural products as a whole.
Benefits of Surgical Over Medical Treatment for Unilateral Primary Aldosteronism
Authors: Ahmed Sumaiya , Hundemer Gregory L.
Published: April 2022

Primary aldosteronism is the most common and modifiable form of secondary hypertension. Left untreated, primary aldosteronism leads high rates of cardiovascular, metabolic, and kidney disease. Therefore, early diagnosis and targeted therapy are crucial to improve long-term patient outcomes. In the case of unilateral primary aldosteronism, surgical adrenalectomy is the guideline-recommended treatment of choice as compared to alternative medical therapies such as mineralocorticoid receptor antagonist medications. Surgical adrenalectomy is not only highly successful in reversing the biochemical abnormalities inherent to primary aldosteronism, but also in mitigating the long-term risks associated with this disease. Indeed, as opposed to medical treatment alone, surgical adrenalectomy offers the potential for disease cure. Within this review article, we review the existing evidence highlighting the benefits of surgical over medical treatment for unilateral primary aldosteronism.
Quantitative Analysis of System Operating Margin With the High Penetration of Distributed Generators in Distribution Networks
Authors: Zhu Ruijin , Dong Yali , Zhao Wentao , Gong Xuejiao , Tang Bo
Published: April 2022

With the integration of distributed generators (DGs) and multiple types of loads, it is increasingly difficult to cope with the uncertainties of DGs, which brings challenges to the secure operation of distribution networks (DNs). Source and load cannot obtain the power balance locally, which may cause operational problems such as line power overload and node voltage violation. However, the methods for quantitatively analyzing the operating status of DNs have not yet formed a unified standard. For which reason, the concept of operating margin is proposed in this study, to represent the distance from the operating point to the boundary. In this study, to generally evaluate the operating status of DNs, the concept of node power margin is proposed first. Then the evaluation indexes including line power margin (LPM) and node voltage margin (NVM) are introduced. The quantitative calculation method for system operating margin (SOM) is further elaborated, which is supposed to be the evaluation indexes on system level. After that, the analysis process of evaluation methods for SOM is discussed. Finally, case studies are performed on the modified IEEE 33-node system to evaluate the operating margin of DNs and verify the enhancement brought by the energy storage system (ESS) and soft open point (SOP) through the flexible adjustment of power flow. The simulation results show that the distance between the DN and the security boundary is effectively quantified through the proposed method, the value can be easily calculated, and the change can be clearly reflected.
Supported SnS2 Nanosheet Arrays on Ni Foam for Supercapacitors
Authors: Sun Haibin , Liang Shuangshuang , Zheng Wenrui , Liu Congcong , Zhang Chao , Ji Zhichao , Liu Shenghong , Xie Wenhe
Published: April 2022

Layered metal sulfides are regarded as potential candidates for supercapacitive electrode materials due to the unique spatial dimensions for charge transport. Herein, self-supported SnS2 nanosheet arrays on nickel (Ni) foam were successfully fabricated via a facile solvothermal approach. Interestingly, the continuous and high-density SnS2 nanosheet arrays are interconnected to form porous Ni@SnS2 electrode materials, which suppress the self-aggregation of SnS2 and provide outstanding conductivity with 3D-networked Ni framework. The Ni@SnS2 electrode demonstrates a high areal specific capacitance of 1965.56 mF cm−2 at a current density of 1 mA cm−2 and satisfactory cycling stability (78.3% capacity retention after 10,000 cycles). This self-supported porous structure provides a promising way to build advanced electrode material for supercapacitors.
A Low-Carbon Dispatch Strategy for Power Systems Considering Flexible Demand Response and Energy Storage
Authors: Han Haiteng , Wei Tiantian , Wu Chen , Xu Xiuyan , Zang Haixiang , Sun Guoqiang , Wei Zhinong
Published: April 2022

The consumption of traditional fossil energy brings inevitable environmental protection problems, which also makes the low-carbon transition in industrial development imminent. In the process of low-carbon transition, the power industry plays a very important role. However, the large-scale integration of renewable energy resources such as wind power and photovoltaic brings new characteristics to power system dispatch. How to design a dispatch strategy that considers both low-carbon demand and economic cost has become a major concern in power systems. The flexible resources such as demand response (DR) and energy storage (ES) can cooperate with these renewable energy resources, promoting the renewable energy generation and low-carbon process. Thus, a low-carbon dispatch strategy for power systems considering flexible DR and ES is proposed in this article. First, models of DR and ES based on their behavior characteristics are established. Then, a carbon emission index is presented according to China’s Clean Development Mechanism (CDM). Finally, the low-carbon dispatch strategy for power systems is proposed through the combination of the carbon emission index and flexible resource dispatch models. The simulation results show that the proposed dispatch strategy can significantly improve wind power consumption and reduce carbon emission.
Habitat Characteristics Supporting Bird Species Richness in Mid-Field Woodlots
Authors: Dvořáková Lenka , Kuczyński Lechosław , Rivas-Salvador Javier , Reif Jiří
Published: April 2022

Farmland biodiversity has undergone drastic declines due to agricultural intensification during the last decades. To prevent further biodiversity loss, the maintenance and restoration of non-productive habitats is essential. Woodlots, small patches of woody vegetation in agricultural landscapes, are one such habitat that are currently subsidized by the European Union’s Common Agricultural Policy (EU’s CAP). For effective implementation, however, it is necessary to assess what habitat characteristics are the most beneficial for biodiversity. Our study performs such an assessment using birds as model organisms. Specifically, we related characteristics of various woodlots to (I) the species richness of all birds, and (II) the species richness of both forest and farmland birds–groups with different ecological requirements. For this purpose, we counted birds (27 farmland and 26 forest species) and measured habitat characteristics (describing vegetation structure, diversity and nativeness) and spatial characteristics (area, shape and isolation) in 82 mid-field woodlots (0.76–1.25 ha, average 0.46 ha) in the Czech Republic (Central Europe). After accounting for the effects of spatial characteristics, overall bird species richness increased with vegetation height and woody plant species richness. In addition, richness showed a non-linear decrease with the cover of an invasive tree, the Black Locust Robinia pseudoaccacia. Interestingly, forest bird species richness was related to the same habitat characteristics as the overall bird species richness. By contrast, farmland bird species richness was positively related to the diversity of woodlot microhabitats, which reflects mainly enrichment by non-forest sites such as grassland or sparse shrubs. Our results indicate that the ecological performance of habitat characteristics (and not only the woodlot area) is important for the restoration of bird diversity in woodlots, and as such should be taken into consideration by the EU’s CAP subsidy system. Moreover, if woodlot management aims to maximize the overall bird diversity—a common practice in biodiversity conservation—our results show that current practices may favor widespread forest bird species, but not the farmland birds that are more threatened in Europe. To manage the woodlot habitat for farmland birds, we suggest that microhabitat heterogeneity should be maximized.
Integrated Monitoring for the Rock Mass State During Large-Scale Subsoil Development
Authors: Bazaluk Oleg , Rysbekov Kanay , Nurpeisova Marzhan , Lozynskyi Vasyl , Kyrgizbayeva Guldana , Turumbetov Turar
Published: April 2022

The purpose of this study was to develop a methodology for integrated monitoring of the rock mass state, which ensures the industrial and environmental safety of the Central Kazakhstan region. As a result of the research, a methodology for maintaining an integrated system of geodynamic monitoring has been developed. The results of predicting the physical–mechanical properties and stress–strain state of the rock mass are presented. Based on the data obtained, graphical–analytical dependences between the most important quantitative characteristics of the rock properties in the studied deposits are presented. The scientific novelty of the presented research lies in determining the pattern of changes in the structural peculiarities and strength properties of rocks with the depth of their occurrence, which makes it possible to predict the stress–strain state of the rock mass. The authors propose a new method for creating a geodynamic test site. The geodynamic test site created in the fields of Central Kazakhstan is a reliable basis for the organization of long-term monitoring for the earth’s surface deformation processes during large-scale development of the field, which improves the productivity and accuracy of observations. The results obtained can be used to improve the level of industrial safety at mines and minimize environmental risks caused by the subsoil development.
The Spatiotemporal Characteristics and Rationality of Emerging Megacity Urban Expansion: A Case Study of Zhengzhou in Central China
Authors: Cai Enxiang , Bi Qingsheng , Lu Jie , Hou Heping
Published: April 2022

Studies on urban expansion in megacities are essential for managing urban sprawl to promote high-quality development. In this study, we have selected the emerging megacity of Zhengzhou as the research area, used the spatial analysis method to quantify the spatiotemporal characteristics of urban expansion from 1990 to 2020, and evaluated the rationality of urban expansion on the basis of the elasticity index and a comparison with other megacities. Results demonstrated that 1) Zhengzhou experienced great urban expansion from 1990 to 2020 and showed a trend of “steady–fast–slow,” with steady expansion from 1990 to 2000, fast expansion from 2000 to 2010, and slow expansion after 2010; 2) Zhengzhou’s urban expansion has obvious imbalance and spatial disorder, mainly concentrated in the urban central area, and is characterized by sprawl or a leap in space; 3) the occupation of cultivated land by urban expansion in Zhengzhou has gradually decreased, but the occupation of ecological land such as water areas has increased significantly, which may lead to a series of negative ecological effects; 4) Zhengzhou’s urban expansion was inefficient, while the utilization intensity and economic benefits of Zhengzhou’s urban construction land have improved, but relatively lower than those of other megacities in China. The findings have important reference that is significant for promoting the sustainable urban expansion of megacities and achieving sustainable regional development.
Research on the Impact of COVID-19 on Import and Export Strategies
Authors: Tang Wenguang , Hu Jian , Reivan Ortiz Geovanny Genaro , Mabrouk Fatma , Li Jinghuan
Published: April 2022

Due to the spread of COVID-19, the public health crisis is bound to have a huge impact on the world economy and international trade. How to study the import and export strategies under the coronavirus pandemic has become a major issue that many scholars need to solve urgently. Therefore, a two-stage game model is constructed, and the reverse solution method is used to obtain the optimal output of enterprises in importing countries and exporting countries before and after the outbreak of pandemic, as well as the optimal subsidies for enterprises from exporting countries and the optimal import quarantine rate for importing countries. Based on the game between the two countries without the pandemic outbreak, the impact of the pandemic on the output, profits, and social welfare of enterprises in the two countries was compared. Enterprises in exporting countries face double threats from the pandemic and import quarantine fees. The increase in import quarantine fees reduces the social welfare of exporting countries. In order to effectively control the spread of the pandemic, subsidies are an effective means to restore exports to normal. Reasonable collection of import quarantine fees by importing countries can promote bilateral trade, but an excessive collection will be counterproductive. The governments of exporting countries should establish emergency mechanisms and relevant subsidy policies, and enterprises should continuously improve their competitiveness. At the same time, countries should abandon the concept of trade protection and negotiate and cooperate to jointly deal with the pandemic.
Roads Disrupt Frugivory and Seed Removal in Tropical Animal-Dispersed Plants in French Guiana
Authors: Coutant Opale , Boissier Olivier , Ducrettet Manon , Albert-Daviaud Aurélie , Bouiges Axelle , Dracxler Caroline Marques , Feer François , Mendoza Irene , Guilbert Eric , Forget Pierre-Michel
Published: April 2022

Ecological interactions are being affected at unprecedented rates by human activities in tropical forests. Yet, the continuity of ecological functions provided by animals, such as seed dispersal, is crucial for forest regeneration and species resilience to anthropogenic pressures. The construction of new roads in tropical forests is one of the main boosters of habitat destruction as it facilitates human access to previously isolated areas and increases defaunation and loss of ecological functions. It, therefore, becomes increasingly urgent to rapidly assess how recently opened roads and associated anthropogenic activities affect ecological processes in natural habitats, so that appropriate management measures to conserve diversity can be taken. In this study, we aimed to evaluate the effects of anthropogenic pressures on the health status of a mature rainforest crossed by a newly opened road in French Guiana. For this, we combined different methods to conduct a rapid assessment of the forest’s health status. Firstly, we evaluated the activity of frugivores using camera traps deployed in four forest patches located near (<1 km) ecological corridors preserved as canopy bridges over the road during the fruiting periods of four animal-dispersed tree species. Secondly, we analyzed the fate of seeds enclosed in animal-dispersed tropical fruits by calculating the proportions of fruits consumed and seeds removed (either dispersed or predated) by frugivores. Results show that the proportion of fruits opened and consumed was lower in the forest areas located near the road than in the control forest, and this difference was more significant for plant species strictly dependent on large-bodied primates for seed dispersal than for species relying on both primates and birds. Camera traps showed the presence of small primates and kinkajous feeding on Virola fruits in the forest impacted by the road, where large primates were absent. It is thus likely that smaller frugivores exert a compensatory effect that maintains ecological functions near the road. Despite efforts made to preserve forest continuity through ecological corridors, anthropogenic pressures associated with road proximity are affecting wildlife and disrupting associated ecological functions crucial for plant regeneration, contributing to further forest degradation.
Identification of Potential Diagnoses Based on Immune Infiltration and Autophagy Characteristics in Major Depressive Disorder
Authors: Sun Ye , Li Jinying , Wang Lin , Cong Ting , Zhai Xiuli , Li Liya , Wu Haikuo , Li Shouxin , Xiao Zhaoyang
Published: April 2022

Background: Major depressive disorder (MDD) is a serious mental illness characterized by mood changes and high suicide rates. However, no studies are available to support a blood test method for MDD diagnosis. The objective of this research was to identify potential peripheral blood biomarkers for MDD and characterize the novel pathophysiology.

Methods: We accessed whole blood microarray sequencing data for MDD and control samples from public databases. Biological functions were analysed by GO and KEGG pathway enrichment analyses using the clusterprofile R package. Infiltrated immune cell (IIC) proportions were identified using the CIBERSORT algorithm. Clustering was performed using the ConsensusClusterPlus R package. Protein–protein interactions (PPI) were assessed by constructing a PPI network using STRING and visualized using Cytoscape software. Rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks to induce stress behaviour. Stress behaviour was evaluated by open field experiments and forced swimming tests. Flow cytometry was used to analyse the proportion of CD8+ T cells. The expression of the corresponding key genes was detected by qRT–PCR.

Results: We divided MDD patients into CD8H and CD8L clusters. The functional enrichment of marker genes in the CD8H cluster indicated that autophagy-related terms and pathways were significantly enriched. Furthermore, we obtained 110 autophagy-related marker genes (ARMGs) in the CD8H cluster through intersection analysis. GO and KEGG analyses further showed that these ARMGs may regulate a variety of autophagy processes and be involved in the onset and advancement of MDD. Finally, 10 key ARMGs were identified through PPI analysis: RAB1A, GNAI3, VAMP7, RAB33B, MYC, LAMP2, RAB11A, HIF1A, KIF5B, and PTEN. In the CUMS model, flow cytometric analysis confirmed the above findings. qRT–PCR revealed significant decreases in the mRNA levels of Gnai3, Rab33b, Lamp2, and Kif5b in the CUMS groups.

Conclusion: In this study, MDD was divided into two subtypes. We combined immune infiltrating CD8+ T cells with autophagy-related genes and screened a total of 10 ARMG genes. In particular, RAB1A, GNAI3, RAB33B, LAMP2, and KIF5B were first reported in MDD. These genes may offer new hope for the clinical diagnosis of MDD.
Construction of a Comprehensive Diagnostic Scoring Model for Prostate Cancer Based on a Novel Six-Gene Panel
Authors: Liu Yunfeng , Qiu Simei , Sun Dongshan , Xiong Ting , Xiang Qiuling , Li Quhuan
Published: April 2022

Accumulating evidence indicates that the N6-methyladenosine (m6A) modification plays a critical role in human cancers. Given the current understanding of m6A modification, this process is believed to be dynamically regulated by m6A regulators. Although the discovery of m6A regulators has greatly enhanced our understanding of the mechanism underlying m6A modification in cancers, the function and role of m6A in the context of prostate cancer (PCa) remain unclear. Here, we aimed to establish a comprehensive diagnostic scoring model that can act as a complement to prostate-specific antigen (PSA) screening. To achieve this, we first drew the landscape of m6A regulators and constructed a LASSO-Cox model using three risk genes (METTL14, HNRNP2AB1, and YTHDF2). Particularly, METTL14 expression was found to be significantly related to overall survival, tumor T stage, relapse rate, and tumor microenvironment of PCa patients, showing that it has important prognostic value. Furthermore, for the sake of improving the predictive ability, we presented a comprehensive diagnostic scoring model based on a novel 6-gene panel by combining with genes found in our previous study, and its application potential was further validated by the whole TCGA and ICGC cohorts. Our study provides additional clues and insights regarding the treatment and diagnosis of PCa patients.
Detection of Parent-of-Origin Effects for the Variants Associated With Behavioral Disinhibition in the MCTFR Data
Authors: Kong Yi-Fan , Li Meng-Kai , Yuan Yu-Xin , Yang Zi-Ying , Yu Wen-Yi , Zhao Pei-Zhen , Zhou Ji-Yuan
Published: April 2022

Behavioral disinhibition is one of the important characteristics of many mental diseases. It has been reported in literature that serious behavioral disinhibition will affect people’s health and greatly reduce people’s quality of life. Meanwhile, behavioral disinhibition can easily lead to illegal drug abuse and violent crimes, etc., which will bring great harm to the society. At present, large-scale genome-wide association analysis has identified many loci associated with behavioral disinhibition. However, these studies have not incorporated the parent-of-origin effects (POE) into analysis, which may ignore or underestimate the genetic effects of loci on behavioral disinhibition. Therefore, in this article, we analyzed the five phenotypes related to behavioral disinhibition in the Minnesota Center for Twin and Family Research data (nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance use related behavioral disinhibition), to further explore the POE of variants on behavioral disinhibition. We applied a linear mixed model to test for the POE at a genome-wide scale on five transformed phenotypes, and found nine SNPs with statistically significant POE at the significance level of 5 × 10−8. Among them, SNPs rs4141854, rs9394515, and rs4711553 have been reported to be associated with two neurological disorders (restless legs syndrome and Tourette’s syndrome) which are related to behavioral disinhibition; SNPs rs12960235 and rs715351 have been found to be associated with head and neck squamous cell carcinoma, skin cancer and type I diabetes, while both SNPs have not been identified to be related to behavioral disinhibition in literature; SNPs rs704833, rs6837925, rs1863548, and rs11067062 are novel loci identified in this article, and their function annotations have not been reported in literature. Follow-up study in molecular genetics is needed to verify whether they are surely related to behavioral disinhibition.
Molecular Mechanisms of Isolated Polycystic Liver Diseases
Authors: Yu Ziqi , Shen Xiang , Hu Chong , Zeng Jun , Wang Aiyao , Chen Jianyong
Published: April 2022

Polycystic liver disease (PLD) is a rare autosomal dominant disorder including two genetically and clinically distinct forms: autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (PCLD). The main manifestation of ADPKD is kidney cysts, while PCLD has predominantly liver presentations with mild or absent kidney cysts. Over the past decade, PRKCSH, SEC63, ALG8, and LRP5 have been candidate genes of PCLD. Recently, more candidate genes such as GANAB, SEC61B, and ALR9 were also reported in PCLD patients. This review focused on all candidate genes of PCLD, including the newly established novel candidate genes. In addition, we also discussed some other genes which might also contribute to the disease.
Description of the Molecular and Phenotypic Spectrum of Lesch-Nyhan Disease in Eight Chinese Patients
Authors: Li Lu , Qiao Xiaohui , Liu Fei , Wang Jingjing , Shen Huijun , Fu Haidong , Mao Jian-Hua
Published: April 2022

Background: Lesch-Nyhan disease (LND) is a rare disorder involving pathogenic variants in the HPRT1 gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) that result in hyperuricemia, intellectual disability, dystonic movement disorder, and compulsive self-mutilation. The purpose of the present study was to characterize the genetic basis of LND and describe its phenotypic heterogeneity by identifying the variation in the HPRT1 gene in a cohort of Chinese LND patients.

Results: The median age at diagnosis was 31 mo (interquartile range (IQR): 7–76 mo), and the initial manifestations were mainly head control weakness and motor development delay. The median age of self-mutilation behavior onset was 19 mo (IQR: 17–24 mo), and all patients were required to travel in a wheelchair and fall into the predicament of compulsive self-harm behavior. There were two patients whose blood uric acid levels were normal for their high urinary acid excretion fraction without taking uric acid-lowering drugs. Seven different pathogenic variants of the HPRT1 gene were identified among eight independent pedigrees, including four novel mutations [c.299 (exon 3) T > A; loss (exon: 6) 84 bp; c.277_281delATTGC; c.468_470delGAT]. The pathogenic variant sites were mainly concentrated in exon 3, and truncating mutations (including frameshift mutations and nonsense mutations) were the most common genetic variant types (5/7, 71.4%).

Conclusion: The present study described the phenotypic and molecular spectrum of LND in eight Chinese families, including four novel mutations, which expands our understanding of LND.
Ataxin-3, The Spinocerebellar Ataxia Type 3 Neurodegenerative Disorder Protein, Affects Mast Cell Functions
Authors: Sowa Anna S. , Haas Eva , Hübener-Schmid Jeannette , Lorentz Axel
Published: April 2022

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease, is a progressive neurodegenerative disorder characterized by loss of neuronal matter due to the expansion of the CAG repeat in theATXN3/MJD1gene and subsequent ataxin-3 protein. Although the underlying pathogenic protein expansion has been known for more than 20 years, the complexity of its effects is still under exploration. The ataxin-3 protein in its expanded form is known to aggregate and disrupt cellular processes in neuronal tissue but the role of the protein on populations of immune cells is unknown. Recently, mast cells have emerged as potential key players in neuroinflammation and neurodegeneration. Here, we examined the mast cell-related effects of ataxin-3 expansion in the brain tissues of 304Q ataxin-3 knock-in mice and SCA3 patients. We also established cultures of mast cells from the 304Q knock-in mice and examined the effects of 304Q ataxin-3 knock-in on the immune responses of these cells and on markers involved in mast cell growth, development and function. Specifically, our results point to a role for expanded ataxin-3 in suppression of mast cell marker CD117/c-Kit, pro-inflammatory cytokine TNF-α and NF-κB inhibitor IκBα along with an increased expression of the granulocyte-attracting chemokine CXCL1. These results are the beginning of a more holistic understanding of ataxin-3 and could point to the development of novel therapeutic targets which act on inflammation to mitigate symptoms of SCA3.
Impact of Consolidative Unrelated Cord Blood Transplantation on Clinical Outcomes of Patients With Relapsed/Refractory Acute B Lymphoblastic Leukemia Entering Remission Following CD19 Chimeric Antigen Receptor T Cells
Authors: Xu Qianwen , Xue Lei , An Furun , Xu Hui , Wang Li , Geng Liangquan , Zhang Xuhan , Song Kaidi , Yao Wen , Wan Xiang , Tong Juan , Liu Huilan , Liu Xin , Zhu Xiaoyu , Zhai Zhimin , Sun Zimin , Wang Xingbing
Published: April 2022

Background

While chimeric antigen receptor (CAR)-T cell therapy is becoming widely used in hematological malignancies with remarkable remission rate, their high recurrence remains an obstacle to overcome. The role of consolidative transplantation following CAR-T cell-mediated remission remains controversial. We conducted a retrospective study to explore whether bridging to unrelated cord blood transplantation (UCBT) could improve the prognosis of patients entering remission after CAR-T therapy with different characteristics through subgroup analyses.

Methods

We reviewed 53 patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) successfully infused with CD19 CAR-T cells and achieved complete remission (CR). In this study, 25 patients received consolidative UCBT (UCBT group) and 28 patients did not accept any intervention until relapse (non-UCBT group). Subgroup analysis on prognosis was then performed according to gender, age, number of previous relapses, tumor burden, presence of poor prognostic markers, and structure of CAR.

Results

Compared with the non-UCBT group, patients who underwent consolidative UCBT had better median event-free survival (EFS; 12.3 months vs. 6.2 months; P = 0.035) and relapse-free survival (RFS; 22.3 months vs. 7.2 months; P = 0.046), while no significant difference was found in overall survival (OS; 30.8 months vs. 15.3 months; P = 0.118). Subsequent multivariate analysis revealed that bridging to UCBT was a protective factor for RFS (P = 0.048) but had no significant effect on EFS (P = 0.205) or OS (P = 0.541). In the subgroup analysis, UCBT has an added benefit in patients with specific characteristics. Patients who experienced ≥2 relapses or with sustained non-remission (NR) showed better RFS (P = 0.025) after UCBT. Better EFS was seen in patients with poor prognostic markers (P = 0.027). In the subgroup with pre-infusion minimal residual disease (MRD) ≥5% or with extramedullary disease (EMD), UCBT significantly prolonged EFS (P = 0.009), RFS (P = 0.017), and OS (P = 0.026). Patients with occurrence of acute graft-versus-host disease (aGVHD) appeared to have a longer duration of remission (P = 0.007).

Conclusion

Consolidative UCBT can, to some extent, improve clinical outcomes of patients with R/R B-ALL entering remission following CD19 CAR-T therapy, especially in patients with more recurrences before treatment, patients with poor prognostic markers, and patients with a higher tumor burden. The occurrence of aGVHD after UCBT was associated with better RFS.
cGAS Restricts PRRSV Replication by Sensing the mtDNA to Increase the cGAMP Activity
Authors: Liu Xiao-Na , Li Li-Wei , Gao Fei , Jiang Yi-Feng , Yuan Wan-Zhe , Li Guo-Xin , Yu Ling-Xue , Zhou Yan-Jun , Tong Guang-Zhi , Zhao Kuan
Published: April 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that causes great economic losses globally to the swine industry. Innate immune RNA receptors mainly sense it during infection. As a DNA sensor, cyclic GMP-AMP synthase (cGAS) plays an important role in sensing cytosolic DNA and activating innate immunity to induce IFN-I and establish an antiviral cellular state. In contrast, the role of innate immune DNA sensors during PRRSV infection has not been elucidated. In this study, we found that cGAS facilitates the production of IFN-β during PRRSV infection. Western blot and virus titer assays suggested that cGAS overexpression suppressed the replication of multiple PRRSV strains, while knockout of cGAS increased viral titer and nucleocapsid protein expression. Besides, our results indicated that the mitochondria were damaged during PRRSV infection and leaked mitochondrial DNA (mtDNA) into the cytoplasm. The mtDNA in the cytoplasm co-localizes with the cGAS, and the cGAMP activity was increased when the cGAS was overexpressed during PRRSV infection. Furthermore, the cGAMP also possesses an anti-PRRSV effect. These results indicate for the first time that cGAS restricts PRRSV replication by sensing the mtDNA in the cytoplasm to increase cGAMP activity, which not only explains the molecular mechanism by which cGAS inhibits PRRSV replication but also provides research ideas for studying the role of the cGAS-STING signaling pathway in the process of RNA virus infection.
Coral Symbiosis Carbon Flow: A Numerical Model Study Spanning Cellular to Ecosystem Levels
Authors: Xu Yi , Zhang Jing , Huang Hui , Yuan Xiangcheng , Zhang Junxiao , Ge Jianzhong
Published: April 2022

Corals rely on a symbiotic relationship with algae (zooxanthellae), which reside in the host tissue and play a critical role for host metabolism through photosynthesis, respiration, carbon translocation, and calcification. These processes affect coral reefs on different scales from cellular to organismal and ecosystem levels. A process-based dynamic model was developed and coupled with a one-dimensional (1-D) biogeochemical model to describe coral photosynthesis, respiration, and carbon translocation at the cellular level, calcification and ion transport in different coral polyp components (i.e., coelenteron, calcifying fluid) at the organismal level; and the exchange of material between corals and the ambient seawater at the ecosystem level. Major processes controlling the carbon budget in internal symbiosis were identified. For the symbiont, photosynthesis is the primary carbon source and translocation to the host is the major sink. For the host, most of the carbon translocated from the symbiont is lost through mucus leakage. In the host dissolved inorganic carbon (DIC) pool, most of the carbon is obtained from the surrounding seawater through uptake; photosynthesis and calcification are the major sinks of DIC. Based on a series of scenario studies, the model produced increase of photosynthesis rate with decline of calcification rate under higher air pCO2 and associated carbonate chemistry variabilities in different polyp components. The model results support the hypothesis that elevated pCO2 stimulates photosynthesis, resulting in a reduced supply of DIC to calcification. Such coupled models allow the exploration of process-based mechanisms, complementing laboratory and field studies.
Multi-Tube Helmholtz Resonator Based Triboelectric Nanogenerator for Broadband Acoustic Energy Harvesting
Authors: Zhang Qiqi , Xi Ziyue , Wang Yawei , Liu Ling , Yu Hongyong , Wang Hao , Xu Minyi
Published: April 2022

Acoustic energy, especially broadband low-frequency sound energy is part of the environmental mechanical energy acquisition cannot be ignored. Herein, a multi-tube parallel Helmholtz resonator-based triboelectric nanogenerator (MH-TENG) is investigated to reap sound energy in low-frequency noise environments. The designed MH-TENG consists of a modified Helmholtz resonator and a thin-film TENG transducer. The core materials of the TENG transducer are aluminum, FEP film, and carbon. To further clarify the influence of the modified Helmholtz resonator on the conversion performance of MH-TENG, the acoustic characteristics of the improved resonators are systematically studied. A series of experiments show that the multi-tube parallel Helmholtz resonator structure has a better sound wave collection effect. Meanwhile, the flexible film TENG can reduce the optimal output frequency of the device. The power generation performance and the bandwidth of the MH-TENG are significantly improved by adopting a multi-tube Helmholtz resonator. Within the frequency bandwidth range of 230 Hz, MH-TENG can effectively improve the efficiency of acoustic energy harvesting. 110 LEDs and an electronic thermometer can be powered by the sound-driven MH-TENG. In addition, the MH-TENG has a good capacitor charging performance, which is conducive to its application in ambient sound energy harvesting.
CMOS MEMS Design and Fabrication Platform
Authors: Tseng Sheng-Hsiang
Published: April 2022

This article mainly describes the technology related to the CMOS MEMS process platform provided by the Taiwan Semiconductor Research Institute (TSRI), including the process flow, design verification, back-end dicing, and packaging of the CMOS MEMS integrated sensing single chip. The front-end CMOS processes can be a standard 0.35 or 0.18 µm CMOS process, or even a BCD high-voltage process. Some academic designs also utilize this platform for in-house post-CMOS process. Finally, the article also explains in detail the CMOS MEMS design flowchart and implementation method provided by TSRI.
Number of Births and Risk of Diabetes in China's Older Women
Authors: Gu Ying-wen , Zhang Shuo , Wang Jia-hao , Yang Hua-lei , Zhang Si-qing , Yao Yi-dan , Wu Yuan-yang , Xie Lin , Li Zhi-yun , Cao Jin-yan
Published: April 2022

As an important life event in individuals' life, childbirth will affect the health of women to different degrees. More and more attention has been paid to whether the number of births will affect the incident diabetes in elderly women, but there are few related studies. Based on the data of the Chinese Longitudinal Healthy Longevity Survey in 2018, 6,159 older women are selected as the study population. Logistic regression analyses are used to estimate the relationship between the number of births and diabetes risk. For each additional birth, the odds ratio of maternal diabetes will decrease by 6.9% and the result is significant at the 1% level, especially among mothers having four children or less. The conclusion is equally applicable in the sample of fathers and urban mothers, but the increase in the number of births will increase the risk of diabetes in rural mothers, although this result is not statistically significant. Later age at first birth, later age at last birth, the longer childbearing period, and birth interval will significantly reduce the risk of diabetes.
Blue Light Induces RPE Cell Necroptosis, Which Can Be Inhibited by Minocycline
Authors: Song Weilin , Zhu Ruilin , Gao Wenna , Xing Chen , Yang Liu
Published: April 2022

Purpose:

Damage to and death of the retinal pigment epithelium (RPE) are closely related to retinal degeneration. Blue light is a high-energy light that causes RPE damage and triggers inflammatory responses. This study investigates whether blue light induces RPE necroptosis, explores pharmacologic therapy and specific mechanisms, and provides hints for research on retinal degeneration.

Methods

The human RPE cell line ARPE-19 was cultured and subjected to blue light insult in vitro. Annexin V/PI was used to evaluate RPE survival. Minocycline was applied to inhibit the death of RPE. Proteomic measurement was used to analyze protein expression. Inhibitors of necroptosis and apoptosis were applied to assess the death mode. Immunofluorescence of protein markers was detected to analyze the mechanism of cell death. Subcellular structural changes were detected by transmission electron microscopy. Reactive oxygen species (ROS) was tested by DCFH-DA. Mitochondrial membrane potential (Δψm) was detected by JC-1. BALB/c mice received bule light exposure, and RPE flatmounts were stained for verification in vivo.

Results

Blue light illumination induced RPE death, and minocycline significantly diminished RPE death. Proteomic measurement showed that minocycline effectively mitigated protein hydrolysis and protein synthesis disorders. Necroptosis inhibitors (Nec-1s, GSK-872) increased the survival of RPE cells, but apoptosis inhibitors (Z-VAD-FMK) did not. After blue light illumination, high-mobility group box-1 (HMGB1) was released from the nucleus, receptor-interacting protein kinase 3 (RIPK3) aggregated, and mixed-lineage kinase domain-like protein (MLKL) increased in the RPE. The application of minocycline alleviated the above phenomena. After blue light illumination, RPE cells exhibited necrotic characteristics accompanied by destruction of cell membranes and vacuole formation, but nuclear membranes remained intact. Minocycline improved the morphology of RPE. Blue light increased ROS and decreased Δψm of RPE, minocycline did not reduce ROS but kept Δψm stable. In vivo, HMGB1 release and RIPK3 aggregation appeared in the RPE of BALB/c mice after blue light illumination, and minocycline alleviated this effect.

Conclusions

Blue light exposure causes RPE necroptosis. Minocycline reduces the death of RPE by keeping Δψm stable, inhibiting necroptosis, and preventing HMGB1 release. These results provide new ideas for the pathogenesis and treatment of retinal degeneration.
Identification of Prognostic Factors in Patients With Streptococcus Bloodstream Infection
Authors: Duan Xiaoguang , Zhang Ruifang , Zhang Xiaojuan , Ding Xianfei , Sun Tongwen
Published: April 2022

Aim

The purpose of this study was to explore prognostic factors of bloodstream infections (BSIs), a common severe infection and a major cause of mortality worldwide, so as to construct a prognosis model of patients with BSI.

Materials and Methods

Clinical and biochemical test data were obtained retrospectively from the medical records of 562 patients with BSI who had been treated at a single center; the end point was 60 days of all-cause death. The chi-square test was used to compare the mortality of patients grouped by the types of antibiotic treatment. The logistic regression analysis was adopted to identify prognostic factors; the Kaplan–Meier survival curve and log-rank test were conducted to compare the survival rate of patients with different prognostic factors; the receiver operating characteristic (ROC) curve was used to estimate the predictive value of different prognostic factors.

Results

Of the 562 patients, 455 survived (80.96%), and 107 died (19.04%). The mortality rate of patients treated with a combination of antibiotics (25.40%) was higher than that treated with a single antibiotic (15.82%). Univariate analysis identified 19 prognostic factors for patients with BSI, including gender, age, diabetes, malignant tumor (non-blood system), total hospitalization time, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, total bilirubin, direct bilirubin, creatinine, ratio of granulocytes, fibrinogen, D-dimer, platelet, C-reactive protein, shock, and respiratory failure (P < 0.05). Multivariate analysis indicated that albumin (odds ratio [OR] = 0.94, 95% confidence interval [CI]: 0.89–0.99), fibrinogen (OR = 0.61, 95%CI: 0.46–0.82), shock (OR = 16.61, 95%CI: 7.00–39.41), and respiratory failure (OR = 47.53, 95%CI: 19.93–133.64) were independent factors. The combination of four indicators demonstrated a favorable predictive value for the 60-day outcome of patients with BSI, with an area under the ROC of 0.96 (95%CI: 0.94–0.99), sensitivity of 90.65%, specificity of 94.95%, and accuracy of 94.13%.

Conclusions

Shock, respiratory failure, albumin, and fibrinogen are potential independent prognostic factors for 60-day mortality.