bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic Characteristics, Coping Skills, and Parental Sense of Competence of Working and Nonworking Mothers
Authors: Shakil Muneeba , Aslam Rubab , Ashraf Farzana , Idris Memoona
Published: April 2021

Demographics of Pakistani working and non-working mothers, coping skills and parental sense of competence was examined in this cross-sectional study. Two hundred (100 non-working & 100 working) mothers aged 20 to 50 years responded to demographic information, Brief Cope Scale (Carver, Scheier, & Weintraub, 1989) and Parental Sense Of Competence Scale (Gibaud-Walston & Wandersman, 1978). Results indicated that working mothers from nuclear family system used more positive coping skills and middle age working mothers were found to have more parental sense of competence than their counterparts. Interestingly, analysis of interactive effect revealed that young working mothers living in nuclear family system had more parental sense of competence than their counterparts. This study highlighted the importance of examining mother’s demographics in their coping and sense of competence in parenting. Findings would assist social psychologists to guide suitable infrastructure to mothers in both roles to improve their coping with higher parental sense of competence.
Understanding the Multiple Role of Mitochondria in Parkinson’s Disease and Related Disorders: Lesson From Genetics and Protein–Interaction Network
Authors: Nicoletti Valentina , Palermo Giovanni , Del Prete Eleonora , Mancuso Michelangelo , Ceravolo Roberto
Published: April 2021

As neurons are highly energy-demanding cell, increasing evidence suggests that mitochondria play a large role in several age-related neurodegenerative diseases. Synaptic damage and mitochondrial dysfunction have been associated with early events in the pathogenesis of major neurodegenerative diseases, including Parkinson’s disease, atypical parkinsonisms, and Huntington disease. Disruption of mitochondrial structure and dynamic is linked to increased levels of reactive oxygen species production, abnormal intracellular calcium levels, and reduced mitochondrial ATP production. However, recent research has uncovered a much more complex involvement of mitochondria in such disorders than has previously been appreciated, and a remarkable number of genes and proteins that contribute to the neurodegeneration cascade interact with mitochondria or affect mitochondrial function. In this review, we aim to summarize and discuss the deep interconnections between mitochondrial dysfunction and basal ganglia disorders, with an emphasis into the molecular triggers to the disease process. Understanding the regulation of mitochondrial pathways may be beneficial in finding pharmacological or non-pharmacological interventions to delay the onset of neurodegenerative diseases.
LncRNA GHET1 Promotes Hypoxia-Induced Glycolysis, Proliferation, and Invasion in Triple-Negative Breast Cancer Through the Hippo/YAP Signaling Pathway
Authors: Wang Yu , Liu Shuwei
Published: April 2021

Objective

This study was to assess the specific impacts and mechanism of lncRNA GHET1 in the development of triple-negative breast cancer (TNBC).

Methods

The lncRNA GHET1 expression in TNBC tissues and adjacent healthy tissues was detected by qRT-PCR, and its expression was then measured at the cellular level, including TNBC cells and human normal breast epithelial cell line MCF10A. On the completion of transfection of negative shRNA or lncRNA GHET1 shRNA, the TNBC cells, HCC1937 and MDA-MB-468, were then cultured in a normoxia or hypoxia environment, respectively. 5-Ethynyl-2′-deoxyuridine (EdU) assay, colony formation assay, and transwell assay were applicable to the determination of cell proliferation, cell viability, and invasion in each group, respectively. Reagent kits were used for testing glucose consumption and lactate production levels. HCC1937 cells with knockdown or overexpression of lncRNA GHET1 were injected into the nude mice, followed by the examination of resulting tumor volume and weight. The distribution and expression of Hippo/YAP signaling pathway-related proteins were probed using western blotting.

Results

Highly expressed lncRNA GHET1 in TNBC tissues and cells and induction of lncRNA GHET1 by hypoxia were proved. Knockdown of lncRNA GHET1 significantly reduced proliferation, viability, and invasion of TNBC cells, and decreased glucose consumption and lactate production levels under the hypoxia condition. Furthermore, lncRNA GHET1 knockdown decreased HIF-1α expression in hypoxia and significantly inhibited tumor development in vivo. Knockdown of lncRNA GHET1 increased the phosphorylation levels of LATS1 and Yes-associated protein (YAP) to retain YAP within the cytoplasm, while the overexpression of lncRNA GHET1 or hypoxia promoted nuclear translocation of YAP and TNBC development.

Conclusion

LncRNA GHET1 expression can be induced by hypoxia, which leads to excessive activation of the Hippo/YAP signaling pathway, thus promoting TNBC progression.
Seven Glycolysis-Related Genes Predict the Prognosis of Patients With Pancreatic Cancer
Authors: Nie Han , Luo Cancan , Liao Kaili , Xu Jiasheng , Cheng Xue-Xin , Wang Xiaozhong
Published: April 2021

Objectives

To identify the key glycolysis-related genes (GRGs) in the occurrence and development of pancreatic ductal carcinoma (PDAC), and to construct a glycolysis-related gene model for predicting the prognosis of PDAC patients.

Methodology

Pancreatic ductal carcinoma (PDAC) data and that of normal individuals were downloaded from the TCGA database and Genotype-Tissue Expression database, respectively. GSEA analysis of glycolysis-related pathways was then performed on PDAC data to identify significantly enriched GRGs. The genes were combined with other patient’s clinical information and used to construct a glycolysis-related gene model using cox regression analysis. The model was further evaluated using data from the validation group. Mutations in the model genes were subsequently identified using the cBioPortal. In the same line, the expression levels of glycolysis related model genes in PDAC were analyzed and verified using immunohistochemical images. Model prediction for PDAC patients with different clinical characteristics was then done and the relationship between gene expression level, clinical stage and prognosis further discussed. Finally, a nomogram map of the predictive model was constructed to evaluate the prognosis of patients with PDAC.

Results

GSEA results of the training set revealed that genes in the training set were significantly related to glycolysis pathway and iconic glycolysis pathway. There were 108 differentially expressed GRGs. Among them, 29 GRGs were closely related to prognosis based on clinical survival time. Risk regression analysis further revealed that there were seven significantly expressed glycolysis related genes. The genes were subsequently used to construct a predictive model. The model had an AUC value of more than 0.85. It was also significantly correlated with survival time. Further expression analysis revealed that CDK1, DSC2, ERO1A, MET, PYGL, and SLC35A3 were highly expressed in PDAC and CHST12 was highly expressed in normal pancreatic tissues. These results were confirmed using immunohistochemistry images of normal and diseases cells. The model could effectively evaluate the prognosis of PDAC patients with different clinical characteristics.

Conclusion

The constructed glycolysis-related gene model effectively predicts the occurrence and development of PDAC. As such, it can be used as a prognostic marker to diagnose patients with PDAC.
The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning
Authors: Kiyomitsu Tomomi , Boerner Susan
Published: April 2021

The nuclear mitotic apparatus (NuMA) protein is well conserved in vertebrates, and dynamically changes its subcellular localization from the interphase nucleus to the mitotic/meiotic spindle poles and the mitotic cell cortex. At these locations, NuMA acts as a key structural hub in nuclear formation, spindle assembly, and mitotic spindle positioning, respectively. To achieve its variable functions, NuMA interacts with multiple factors, including DNA, microtubules, the plasma membrane, importins, and cytoplasmic dynein. The binding of NuMA to dynein via its N-terminal domain drives spindle pole focusing and spindle positioning, while multiple interactions through its C-terminal region define its subcellular localizations and functions. In addition, NuMA can self-assemble into high-ordered structures which likely contribute to spindle positioning and nuclear formation. In this review, we summarize recent advances in NuMA’s domains, functions and regulations, with a focus on human NuMA, to understand how and why vertebrate NuMA participates in these functions in comparison with invertebrate NuMA-related proteins.
Subinhibitory Concentrations of Biogenic Silver Nanoparticles Affect Motility and Biofilm Formation in Pseudomonas aeruginosa
Authors: Saeki Erika Kushikawa , Yamada Amanda Yaeko , de Araujo Larissa Amianti , Anversa Laís , Garcia Doroti de Oliveira , de Souza Renan Luiz Barros , Martins Heloísa Moreira , Kobayashi Renata Katsuko Takayama , Nakazato Gerson
Published: April 2021

Biogenic silver nanoparticles (bio-AgNPs) are increasingly recognized as an antibiofilm and antivirulence strategy against P. aeruginosa, a bacterium that causes chronic infections in immunocompromised and cystic fibrosis patients. This study aimed to investigate the effects of subinhibitory concentrations of bio-AgNPs on motility and biofilm formation in P. aeruginosa. Bio-AgNPs were synthesized via reduction of ionic silver catalyzed by cell-free culture filtrate from Fusarium oxysporum. A total of 17 P. aeruginosa isolates and strains were evaluated for swarming, swimming, and twitching motility in the presence and absence (control) of bio-AgNPs, including 10 clinical isolates from patients with and without cystic fibrosis, 5 environmental isolates obtained from the public water supply system, and 2 reference strains (PAO1 and PA14). Isolates were identified by biochemical and molecular methods. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. Swarming, swimming, and twitching motility assays were performed in Petri dishes. Biofilm formation capacity was assessed quantitatively by the crystal violet method. MIC values ranged from 15.62 to 62.50 µM. The results showed that subinhibitory concentrations of bio-AgNPs (½ MIC, 7.81–31.25 µM) significantly increased (p < 0.05) swarming, swimming, and twitching motility in 40.0, 40.0, and 46.7% of isolates, respectively. Subinhibitory bio-AgNP treatment enhanced (p < 0.05) biofilm formation capacity in PA14 and a cystic fibrosis isolate (P11). It is concluded that subinhibitory concentrations of bio-AgNPs increased biofilm formation and swarming, swimming, and twitching motility in PA14 and some P. aeruginosa isolates. These virulence factors are directly involved with quorum-sensing systems. Further research should investigate the effects of AgNPs on P. aeruginosa quorum sensing to help elucidate their mechanism of action at subinhibitory concentrations.
Numerical Investigation of the Effect of Heterogeneous Pore Structures on Elastic Properties of Tight Gas Sandstones
Authors: Guo Zhiqi , Qin Xiaoying , Zhang Yiming , Niu Cong , Wang Di , Ling Yun
Published: April 2021

Strong heterogeneity of pore microstructures leads to complicated velocity-porosity relationships in tight sandstone that cannot be well explained by conventional empirical formulas. To better understand the effect of complex pore structures on elastic properties of tight gas sandstone, we compared three rock physics models. In the first model, we used a single aspect ratio value to quantify varied pore geometry in the tight sands. In the second model, complex pore space was equivalent to the combination of high-aspect-ratio round pores (stiff pores) and low-aspect-ratio compliant microcracks (soft pores). In the third multiple pore-aspect-ratio model, pore spaces are represented using a set of pores with varied values of aspect ratio following statistical normal distribution. Modeling results showed that complex velocity-porosity relationships could be interpreted by the variations in pore aspect ratio in the first model, by the fraction of soft pores in the second model, and by the mean value and variance in the third statistical model. For a given mean value in the third model, higher variance of the multiple pore-aspect-ratio indicated stronger heterogeneity of pore spaces. Further studies on rock physical inversion showed that, compared with the first single pore-aspect-ratio model, the second dual-pore model gave better prediction in shear wave velocity by regarding the soft pore fraction as a fitting parameter. This finding revealed that the dual-pore model could be a more realistic representation of tight sandstone. The third statistical model showed comparable precision in the prediction of shear wave velocity compared with the dual-pore model; however, uncertainty existed for simultaneously determining mean value and variance of pore aspect ratio. On the basis of the dual-pore model, we evaluated the elastic modulus of dry frames of the tight sandstone using logging data in a borehole. Compared with empirical formulas, such as the Krief methods, the method in this paper provided a more rigorous way to determine elastic properties of dry frames for the tight sandstone. Comparisons of rock physical modeling methods offer a better understanding of the microstructures controlling the elastic behaviors of tight gas sandstone.
High Circulating Follicle-Stimulating Hormone Level Is a Potential Risk Factor for Renal Dysfunction in Post-Menopausal Women
Authors: Li Qihang , Zheng Dongmei , Lin Haiyan , Zhong Fang , Liu Jing , Wu Yafei , Wang Zhixiang , Guan Qingbo , Zhao Meng , Gao Ling , Zhao Jiajun
Published: April 2021

Objective

Menopause contributes to renal dysfunction in women, which is generally attributed to estrogen withdrawal. In addition to decreased estrogen level, serum follicle-stimulating hormone (FSH) level increases after menopause. This study investigated the association between high circulating FSH level and renal function in post-menopausal women.

Methods

This observational cross-sectional study included 624 pre-menopausal, 121 peri-menopausal, and 2540 post-menopausal women. The levels of female sex hormones were examined by chemiluminescence and indices of renal function were measured using a clinical chemistry analyzer. The post-menopausal women were grouped into quartiles according to serum FSH levels.

Results

Renal function progressively declined from pre-menopause to peri-menopause to post-menopause, which was accompanied by increasing serum FSH level. In post-menopausal women, serum creatinine level increased with increasing FSH quartile, which was accompanied by a decrease in estimated glomerular filtration rate (eGFR) (p for trend <0.001); moreover, the prevalence of declined eGFR (<90 ml/min/1.73 m2) and chronic kidney disease (CKD; eGFR <60 ml/min/1.73 m2) increased (p for trend <0.001). Even after adjusting for confounders, the odds ratios (ORs) of declined eGFR and CKD increased with increasing FSH quartiles in post-menopausal women. The ORs of declined eGFR (OR=2.19, 95% confidence interval [CI]: 1.63–2.92) and CKD (OR=10.09, 95% CI: 2.28–44.65) in the highest FSH quartile were approximately 2- and 10-fold higher, respectively, than in the lowest FSH quartile (p<0.05). After stratifying post-menopausal women by median age (61 years), the OR for declined eGFR for each FSH quartile in the older group was higher than that for the corresponding FSH quartile in the younger group.

Conclusions

A high circulating FSH level is an independent risk factor for renal dysfunction in women after menopause. Additionally, aging may aggravate the association of high FSH levels with reduced renal function in post-menopausal women.
A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells
Authors: Otsuka Kai , Matsubara Shin , Shiraishi Akira , Takei Natsumi , Satoh Yui , Terao Miho , Takada Shuji , Kotani Tomoya , Satake Honoo , Kimura Atsushi P.
Published: April 2021

The testis expresses many long noncoding RNAs (lncRNAs), but their functions and overview of lncRNA variety are not well understood. The mouse Prss/Tessp locus contains six serine protease genes and two lncRNAs that have been suggested to play important roles in spermatogenesis. Here, we found a novel testis-specific lncRNA, Start (Steroidogenesis activating lncRNA in testis), in this locus. Start is 1822 nucleotides in length and was found to be localized mostly in the cytosol of germ cells and Leydig cells, although nuclear localization was also observed. Start-knockout (KO) mice generated by the CRISPR/Cas9 system were fertile and showed no morphological abnormality in adults. However, in adult Start-KO testes, RNA-seq and qRT-PCR analyses revealed an increase in the expression of steroidogenic genes such as Star and Hsd3b1, while ELISA analysis revealed that the testosterone levels in serum and testis were significantly low. Interestingly, at 8 days postpartum, both steroidogenic gene expression and testosterone level were decreased in Start-KO mice. Since overexpression of Start in two Leydig-derived cell lines resulted in elevation of the expression of steroidogenic genes including Star and Hsd3b1, Start is likely to be involved in their upregulation. The increase in expression of steroidogenic genes in adult Start-KO testes might be caused by a secondary effect via the androgen receptor autocrine pathway or the hypothalamus-pituitary-gonadal axis. Additionally, we observed a reduced number of Leydig cells at 8 days postpartum. Collectively, our results strongly suggest that Start is a regulator of steroidogenesis in Leydig cells. The current study provides an insight into the overall picture of the function of testis lncRNAs.
Space High-Voltage Power Module
Authors: Zhao Wenjie , Jiang Yuanyuan , Wu Jianchao , Huang Yonghui , Zhu Yan , An Junshe , Wan Cheng-an
Published: April 2021

With the rapid development of the world’s aerospace technologies, a high-power and high-reliability space high-voltage power supply is significantly required by new generation of applications, including high-power electric propulsion, space welding, deep space exploration, and space solar power stations. However, it is quite difficult for space power supplies to directly achieve high-voltage output from the bus, because of the harshness of the space environment and the performance limitations of existing aerospace-grade electronic components. This paper proposes a high-voltage power supply module design for space welding applications, which outputs 1 kV and 200 W when the input is 100 V. This paper also improves the efficiency of the high-voltage converter with a phase-shifted full-bridge series resonant circuit, then simulates the optimized power module and the electric field distribution of the high-voltage circuit board.
Prediction of Overall Survival Rate in Patients With Hepatocellular Carcinoma Using an Integrated Model Based on Autophagy Gene Marker
Authors: Wang Shuaiqun , Yang Dalu , Kong Wei
Published: April 2021

The autophagy cell, which can inhibit the formation of tumor in the early stage and can promote the development of tumor in the late stage, plays an important role in the development of tumor. Therefore, it has potential significance to explore the influence of autophagy-related genes (AAGs) on the prognosis of hepatocellular carcinoma (HCC). The differentially expressed AAGs are selected from HCC gene expression profile data and clinical data downloaded from the TCGA database, and human autophagy database (HADB). The role of AAGs in HCC is elucidated by GO functional annotation and KEGG pathway enrichment analysis. Combining with clinical data, we selected age, gender, grade, stage, T state, M state, and N state as Cox model indexes to construct the multivariate Cox model and survival curve of Kaplan Meier (KM) was drawn to estimate patients’ survival between high- and low-risk groups. Through an ROC curve drawn by univariate and multivariate Cox regression analysis, we found that seven genes with high expression levels, including HSP90AB1, SQSTM1, RHEB, HDAC1, ATIC, HSPB8, and BIRC5 were associated with poor prognosis of HCC patients. Then the ICGC database is used to verify the reliability and robustness of the model. Therefore, the prognosis model of HCC constructed by autophagy genes might effectively predict the overall survival rate and help to find the best personalized targeted therapy of patients with HCC, which can provide better prognosis for patients.
Genetic Complexity of Sinoatrial Node Dysfunction
Authors: Wallace Michael J. , El Refaey Mona , Mesirca Pietro , Hund Thomas J. , Mangoni Matteo E. , Mohler Peter J.
Published: April 2021

The pacemaker cells of the cardiac sinoatrial node (SAN) are essential for normal cardiac automaticity. Dysfunction in cardiac pacemaking results in human sinoatrial node dysfunction (SND). SND more generally occurs in the elderly population and is associated with impaired pacemaker function causing abnormal heart rhythm. Individuals with SND have a variety of symptoms including sinus bradycardia, sinus arrest, SAN block, bradycardia/tachycardia syndrome, and syncope. Importantly, individuals with SND report chronotropic incompetence in response to stress and/or exercise. SND may be genetic or secondary to systemic or cardiovascular conditions. Current management of patients with SND is limited to the relief of arrhythmia symptoms and pacemaker implantation if indicated. Lack of effective therapeutic measures that target the underlying causes of SND renders management of these patients challenging due to its progressive nature and has highlighted a critical need to improve our understanding of its underlying mechanistic basis of SND. This review focuses on current information on the genetics underlying SND, followed by future implications of this knowledge in the management of individuals with SND.
Camptothecin Regulates Microglia Polarization and Exerts Neuroprotective Effects via Activating AKT/Nrf2/HO-1 and Inhibiting NF-κB Pathways In Vivo and In Vitro
Authors: He Dewei , Fu Shoupeng , Zhou Ang , Su Yingchun , Gao Xiyu , Zhang Yufei , Huang Bingxu , Du Jian , Liu Dianfeng
Published: April 2021

Microglia, the main immune cells in the brain, participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidence suggests that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson’s disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However, the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. In our study we found that CPT improved motor performance of mice and reduced the loss of neurons in the substantia nigra (SN) of the midbrain in LPS-injected mice. In the mechanism study, we found that CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1 and NF-κB signals. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from damage mediated by microglia activation. In conclusion, our results demonstrate that CPT regulates the microglia polarization phenotype via activating AKT/Nrf2/HO-1 and inhibiting NF-κB pathways, inhibits neuro-inflammatory responses, and exerts neuroprotective effects in vivo and in vitro.
RNA-Seq Identifies Marked Th17 Cell Activation and Altered CFTR Expression in Different Atopic Dermatitis Subtypes in Chinese Han Populations
Authors: Tian Xin , Liu Baoyi , Chen Lijie , Xie Yongyi , Liang Jingyao , Yang Yan , Shao Lei , Zhang Jing , Wang Jianqin , Zhang Xibao , Wu Zhouwei , Liu Yumei
Published: April 2021

Background

Patients with atopic dermatitis (AD) exhibit phenotypic variability in ethnicity and IgE status. In addition, some patients develop other allergic conditions, such as allergic rhinitis (AR), in subsequent life. Understanding the heterogeneity of AD would be beneficial to phenotype-specific therapies.

Methods

Twenty-eight Chinese AD patients and 8 healthy volunteers were enrolled in the study. High-throughput transcriptome sequencing was conducted on lesional and nonlesional skin samples from 10 AD patients and matched normal skin samples from 5 healthy volunteers. Identification of differentially expressed genes (DEGs), KEGG pathway analyses, and sample cluster analyses were conducted in the R software environment using the DEseq2, ClusterProfiler, and pheatmap R packages, respectively. qRT-PCR, Western blotting, and ELISA were used to detect gene expression levels among subtypes. Correlation analysis was performed to further investigate their correlation with disease severity.

Results

A total of 25,798 genes were detected per sample. Subgroup differential expression analysis and functional enrichment analysis revealed significant changes in the IL17 signaling pathway in Chinese EAD patients but not in IAD patients. DEGs enriched in cytokine-cytokine receptor interactions and gland secretion were considered to be associated with atopic march. Further investigations confirmed a marked IL17A upregulation in Chinese EAD with a positive relationship with total IgE level and AD severity. In addition, increased IL17A in AD patients with AR demonstrated a closer association with AR severity than IL4R. Moreover, AQP5 and CFTR were decreased in the lesions of AD patients with AR. The CFTR mRNA expression level was negatively associated with the skin IL17A level and AR severity.

Conclusion

Our research characterized marked Th17 activation in Chinese EAD patients, and altered expression of IL17A, IL4R, AQP5, and CFTR in AD patients with AR was associated with AR severity. It partially explained the phenotypic differences of AD subtypes and provided potential references for endotype-targeted therapy.
Using Deep Learning in a Monocentric Study to Characterize Maternal Immune Environment for Predicting Pregnancy Outcomes in the Recurrent Reproductive Failure Patients
Authors: Huang Chunyu , Xiang Zheng , Zhang Yongnu , Tan Dao Shen , Yip Chun Kit , Liu Zhiqiang , Li Yuye , Yu Shuyi , Diao Lianghui , Wong Lap Yan , Ling Wai Lim , Zeng Yong , Tu Wenwei
Published: April 2021

Recurrent reproductive failure (RRF), such as recurrent pregnancy loss and repeated implantation failure, is characterized by complex etiologies and particularly associated with diverse maternal factors. It is currently believed that RRF is closely associated with the maternal environment, which is, in turn, affected by complex immune factors. Without the use of automated tools, it is often difficult to assess the interaction and synergistic effects of the various immune factors on the pregnancy outcome. As a result, the application of Artificial Intelligence (A.I.) has been explored in the field of assisted reproductive technology (ART). In this study, we reviewed studies on the use of A.I. to develop prediction models for pregnancy outcomes of patients who underwent ART treatment. A limited amount of models based on genetic markers or common indices have been established for prediction of pregnancy outcome of patients with RRF. In this study, we applied A.I. to analyze the medical information of patients with RRF, including immune indicators. The entire clinical samples set (561 samples) was divided into two sets: 90% of the set was used for training and 10% for testing. Different data panels were established to predict pregnancy outcomes at four different gestational nodes, including biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth, respectively. The prediction models of pregnancy outcomes were established using sparse coding, based on six data panels: basic patient characteristics, hormone levels, autoantibodies, peripheral immunology, endometrial immunology, and embryo parameters. The six data panels covered 64 variables. In terms of biochemical pregnancy prediction, the area under curve (AUC) using the endometrial immunology panel was the largest (AUC = 0.766, accuracy: 73.0%). The AUC using the autoantibodies panel was the largest in predicting clinical pregnancy (AUC = 0.688, accuracy: 78.4%), ongoing pregnancy (AUC = 0.802, accuracy: 75.0%), and live birth (AUC = 0.909, accuracy: 89.7%). Combining the data panels did not significantly enhance the effect on prediction of all the four pregnancy outcomes. These results give us a new insight on reproductive immunology and establish the basis for assisting clinicians to plan more precise and personalized diagnosis and treatment for patients with RRF.
VectorMOD: Method for Bottom-Up Proteomic Characterization of rAAV Capsid Post-Translational Modifications and Vector Impurities
Authors: Rumachik Neil G. , Malaker Stacy A. , Paulk Nicole K.
Published: April 2021

Progress in recombinant AAV gene therapy product and process development has advanced our understanding of the basic biology of this critical delivery vector. The discovery of rAAV capsid post-translational modifications (PTMs) has spurred interest in the field for detailed rAAV-specific methods for vector lot characterization by mass spectrometry given the unique challenges presented by this viral macromolecular complex. Recent concerns regarding immunogenic responses to systemically administered rAAV at high doses has highlighted the need for investigators to catalog and track potentially immunogenic vector lot components including capsid PTMs and PTMs on host cell protein impurities. Here we present a simple step-by-step guide for academic rAAV laboratories and Chemistry, Manufacturing and Control (CMC) groups in industry to perform an in-house or outsourced bottom-up mass spectrometry workflow to characterize capsid PTMs and process impurities.
TREX1 as a Novel Immunotherapeutic Target
Authors: Hemphill Wayne O. , Simpson Sean R. , Liu Mingyong , Salsbury Freddie R. , Hollis Thomas , Grayson Jason M. , Perrino Fred W.
Published: April 2021

Mutations in the TREX1 3’ → 5’ exonuclease are associated with a spectrum of autoimmune disease phenotypes in humans and mice. Failure to degrade DNA activates the cGAS-STING DNA-sensing pathway signaling a type-I interferon (IFN) response that ultimately drives immune system activation. TREX1 and the cGAS-STING DNA-sensing pathway have also been implicated in the tumor microenvironment, where TREX1 is proposed to degrade tumor-derived DNA that would otherwise activate cGAS-STING. If tumor-derived DNA were not degraded, the cGAS-STING pathway would be activated to promote IFN-dependent antitumor immunity. Thus, we hypothesize TREX1 exonuclease inhibition as a novel immunotherapeutic strategy. We present data demonstrating antitumor immunity in the TREX1 D18N mouse model and discuss theory surrounding the best strategy for TREX1 inhibition. Potential complications of TREX1 inhibition as a therapeutic strategy are also discussed.
Perspectives on the Use of Coral Reef Restoration as a Strategy to Support and Improve Reef Ecosystem Services
Authors: Hein Margaux Y. , Vardi Tali , Shaver Elizabeth C. , Pioch Sylvain , Boström-Einarsson Lisa , Ahmed Mohamed , Grimsditch Gabriel , McLeod Ian M.
Published: April 2021

In 2019, the United Nations Environment Assembly requested that the United Nations Environment Programme (UNEP) and the International Coral Reef Initiative (ICRI) define best practices for coral restoration. Guidelines led by the UNEP were prepared by a team of 20 experts in coral reef management, science, and policy to catalog the best-available knowledge in the field and provide realistic recommendations for the use of restoration as a reef management strategy. Here, we provide a synthesis of these guidelines. Specifically, we present (1) a case for the value of coral reef restoration in the face of increasing frequency and intensity of disturbances associated with climate change, (2) a set of recommendations for improving the use of coral reef restoration as a reef management strategy, tailored to goals and current methods. Coral reef restoration can be a useful tool to support resilience, especially at local scales where coral recruitment is limited, and disturbances can be mitigated. While there is limited evidence of long-term, ecologically relevant success of coral reef restoration efforts, ongoing investments in research and development are likely to improve the scale, and cost-efficiency of current methods. We conclude that coral reef restoration should not be seen as a “silver bullet” to address ecological decline and should be applied appropriately, with due diligence, and in concert with other broad reef resilience management strategies.
Patterns of Macrofaunal Biodiversity Across the Clarion-Clipperton Zone: An Area Targeted for Seabed Mining
Authors: Washburn Travis W. , Menot Lenaick , Bonifácio Paulo , Pape Ellen , Błażewicz Magdalena , Bribiesca-Contreras Guadalupe , Dahlgren Thomas G. , Fukushima Tomohiko , Glover Adrian G. , Ju Se Jong , Kaiser Stefanie , Yu Ok Hwan , Smith Craig R.
Published: April 2021

Macrofauna are an abundant and diverse component of abyssal benthic communities and are likely to be heavily impacted by polymetallic nodule mining in the Clarion-Clipperton Zone (CCZ). In 2012, the International Seabed Authority (ISA) used available benthic biodiversity data and environmental proxies to establish nine no-mining areas, called Areas of Particular Environmental Interest (APEIs) in the CCZ. The APEIs were intended as a representative system of protected areas to safeguard biodiversity and ecosystem function across the region from mining impacts. Since 2012, a number of research programs have collected additional ecological baseline data from the CCZ. We assemble and analyze macrofaunal biodiversity data sets from eight studies, focusing on three dominant taxa (Polychaeta, Tanaidacea, and Isopoda), and encompassing 477 box-core samples to address the following questions: (1) How do macrofaunal abundance, biodiversity, and community structure vary across the CCZ, and what are the potential ecological drivers? (2) How representative are APEIs of the nearest contractor areas? (3) How broadly do macrofaunal species range across the CCZ region? and (4) What scientific gaps hinder our understanding of macrofaunal biodiversity and biogeography in the CCZ? Our analyses led us to hypothesize that sampling efficiencies vary across macrofaunal data sets from the CCZ, making quantitative comparisons between studies challenging. Nonetheless, we found that macrofaunal abundance and diversity varied substantially across the CCZ, likely due in part to variations in particulate organic carbon (POC) flux and nodule abundance. Most macrofaunal species were collected only as singletons or doubletons, with additional species still accumulating rapidly at all sites, and with most collected species appearing to be new to science. Thus, macrofaunal diversity remains poorly sampled and described across the CCZ, especially within APEIs, where a total of nine box cores have been taken across three APEIs. Some common macrofaunal species ranged over 600–3000 km, while other locally abundant species were collected across ≤ 200 km. The vast majority of macrofaunal species are rare, have been collected only at single sites, and may have restricted ranges. Major impediments to understanding baseline conditions of macrofaunal biodiversity across the CCZ include: (1) limited taxonomic description and/or barcoding of the diverse macrofauna, (2) inadequate sampling in most of the CCZ, especially within APEIs, and (3) lack of consistent sampling protocols and efficiencies.
Excess Li2O Additives to Promote Grain Boundary Growth and Improve Ionic Conductivity of LiTa2PO8 Solid Electrolytes
Authors: Zhang Qian , Meng Fuhai , Liao Ruixiong , Chen Long , Xu Mengqian , Zhong Shengwen , Chen Jun , Lu Anxian
Published: April 2021

LiTa2PO8 (LTPO) is a new solid-state lithium ion electrolyte material reported in the latest research, which has high bulk ionic conductivity and low grain boundary ion conductivity. However, it is difficult to density with conventional sintering methods. Herein, in this work, the solid-phase synthesis method was used to prepared the LTPO solid-state electrolyte, and the influence of the amount of lithium on the structure and performance of LTPO electrolyte material was investigated. The results show that the excess Li2O does not increase other impurities and does not change the structure of the material, but the liquid phase produced by the excess Li2O can promote the elimination of interfacial pores, accelerate the direct bonding of grains and improve the ionic conductivity of grain boundary, thus improving the overall ionic conductivity of the material. Considering the volatilization of lithium and the impact of liquid phase sintering at high temperatures and the content restructuring, after adding 20 wt% excess formulation of Li2O, the resultant of LTPO density is 5.0 g/cm3, the density reaches 85.58%. As a result, the total ionic conductivity of the electrolyte is 3.28 × 10–4 S/cm at 25°C, and the Li-ion diffusion activation energy is 0.27 eV. In addition, after loading this electrolyte into a Li–Li symmetric battery, it is proved that the electrolyte has lithium ion transport performance and can be used in all-solid-state batteries. However, it is also found from cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) analysis that the interface between LTPO material and Li is unstable, and Ta5+ ions are reduced, which will be another key issue to be addressed in the future.
Disruption of Cigarette Smoking Addiction After Dorsal Striatum Damage
Authors: Jing Chuya , Jing Changxin , Zheng Liangcheng , Hong Ganji , Zheng Jingjing , Yu Lu , Song Ningning , Zhang Tengkun , Ma Qilin , Fang Jie
Published: April 2021

Studies have shown that addictive behavior is associated with many brain regions, such as the insula, globus pallidus, amygdala, nucleus accumbens, and midbrain dopamine system, but only a few studies have explored the role of the dorsal striatum in addictive behavior. In June 2020, we started contacting 608 patients who were hospitalized between January 2017 and December 2019, and we recruited 11 smoking addicts with dorsal striatum damage and 20 controls with brain damage that did not involve the dorsal striatum (the damaged areas included the frontal lobe, temporal lobe, parietal lobe, brain stem, thalamus, internal capsule, and so on). All study participants had brain damage due to acute cerebral infarction. Disruption of smoking addiction was found to be significantly associated with the dorsal striatum (Phi = 0.794770, P = 0.000015). Our findings suggested that patients in the dorsal striatum group were more likely to discontinue smoking than those in the non-dorsal striatum group. The characteristics of this interruption is that smoking can be quit more easily and quickly without recurrence and that the impulse to smoke is reduced. These results suggest that the dorsal striatum is a key area for addiction to smoking.
SeBioGraph: Semi-supervised Deep Learning for the Graph via Sustainable Knowledge Transfer
Authors: Ma Yugang , Li Qing , Hu Nan , Li Lili
Published: April 2021

Semi-supervised deep learning for the biomedical graph and advanced manufacturing graph is rapidly becoming an important topic in both academia and industry. Many existing types of research focus on semi-supervised link prediction and node classification, as well as the application of these methods in sustainable development and advanced manufacturing. To date, most manufacturing graph neural networks are mainly evaluated on social and information networks, which improve the quality of network representation y integrating neighbor node descriptions. However, previous methods have not yet been comprehensively studied on biomedical networks. Traditional techniques fail to achieve satisfying results, especially when labeled nodes are deficient in number. In this paper, a new semi-supervised deep learning method for the biomedical graph via sustainable knowledge transfer called SeBioGraph is proposed. In SeBioGraph, both node embedding and graph-specific prototype embedding are utilized as transferable metric space characterized. By incorporating prior knowledge learned from auxiliary graphs, SeBioGraph further promotes the performance of the target graph. Experimental results on the two-class node classification tasks and three-class link prediction tasks demonstrate that the SeBioGraph realizes state-of-the-art results. Finally, the method is thoroughly evaluated.
Deep Brain Stimulation for Parkinson’s Disease During the COVID-19 Pandemic: Patient Perspective
Authors: Zhang Chencheng , Zhang Jing , Qiu Xian , Zhang Yingying , Lin Zhengyu , Huang Peng , Pan Yixin , Storch Eric A. , Sun Bomin , Li Dianyou
Published: April 2021

Background

Public health guidelines have recommended that elective medical procedures, including deep brain stimulation (DBS) surgery for Parkinson’s disease (PD), should not be scheduled during the coronavirus (COVID-19) pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.

Methods

We administered a newly developed phone questionnaire to 20 consecutive patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic. The questionnaire was designed to gather the patients’ experiences and perceptions on the impact of COVID-19 on their everyday activities and access to medical care.

Results

Most of the patients felt confident about the preventive measures taken by the government and hospitals, and they have changed their daily living activities accordingly. Moreover, a large majority of patients felt confident obtaining access to regular and COVID-19-related health care services if needed. Routine clinical referral, sense of security in the hospital during the outbreak, and poor control of PD symptoms were the three main reasons given by patients for seeking DBS surgery during the COVID-19 pandemic.

Conclusion

The COVID-19 pandemic has considerably impacted medical care and patients’ lives but elective procedures, such as DBS surgery for PD, do not need to be rescheduled when the health care system is not overloaded and adequate public health regulations are in place.
Work-Related Mental Health Issues in Graduate Student Population
Authors: Gallea José Ignacio , Medrano Leonardo Adrián , Morera Luis Pedro
Published: April 2021

The scientific and educational community is becoming increasingly aware of the impact of current academic working conditions on graduate students’ mental health and how this is affecting scientific progress and ultimately society as a whole. Our study aimed to shed light on the work-related mental health issues affecting graduate students, providing a comprehensive research work including psychological and biological assessment. Our findings showed that a sizeable number of graduate student present anxiety, depression, or high burnout and that the time spent in academia plays an important role. The graduate student population displayed a specific work-related mental health issues profile with an altered hypothalamic–pituitary–adrenal (HPA) axis and low levels of work engagement. Finally, graduate students were equally stressed, with less work engagement, and more anxious and depressed than general workers.
Similar EEG Activity Patterns During Experimentally-Induced Auditory Illusions and Veridical Perceptions
Authors: Faramarzi Maryam , Kasten Florian H. , Altaş Gamze , Aleman André , Ćurčić-Blake Branislava , Herrmann Christoph S.
Published: April 2021

Hallucinations and illusions are two instances of perceptual experiences illustrating how perception might diverge from external sensory stimulations and be generated or altered based on internal brain states. The occurrence of these phenomena is not constrained to patient populations. Similar experiences can be elicited in healthy subjects by means of suitable experimental procedures. Studying the neural mechanisms underlying these experiences not only has the potential to expand our understanding of the brain’s perceptual machinery but also of how it might get impaired. In the current study, we employed an auditory signal detection task to induce auditory illusions by presenting speech snippets at near detection threshold intensity embedded in noise. We investigated the neural correlates of auditory false perceptions by examining the EEG activity preceding the responses in speech absent (false alarm, FA) trials and comparing them to speech present (hit) trials. The results of the comparison of event-related potentials (ERPs) in the activation period vs. baseline revealed the presence of an early negativity (EN) and a late positivity (LP) similar in both hits and FAs, which were absent in misses, correct rejections (CR) and control button presses (BPs). We postulate that the EN and the LP might represent the auditory awareness negativity (AAN) and centro-parietal positivity (CPP) or P300, respectively. The event-related spectral perturbations (ERSPs) exhibited a common power enhancement in low frequencies (<4 Hz) in hits and FAs. The low-frequency power enhancement has been frequently shown to be accompanied with P300 as well as separately being a marker of perceptual awareness, referred to as slow cortical potentials (SCP). Furthermore, the comparison of hits vs. FAs showed a significantly higher LP amplitude and low frequency power in hits compared to FAs. Generally, the observed patterns in the present results resembled some of the major neural correlates associated with perceptual awareness in previous studies. Our findings provide evidence that the neural correlates associated with conscious perception, can be elicited in similar ways in both presence and absence of externally presented sensory stimuli. The present findings did not reveal any pre-stimulus alpha and beta modulations distinguishing conscious vs. unconscious perceptions.