bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying Stretch to Evoke Hyperreflexia in Spasticity Testing: Velocity vs. Acceleration
Authors: Sloot Lizeth H. , Weide Guido , van der Krogt Marjolein M. , Desloovere Kaat , Harlaar Jaap , Buizer Annemieke I. , Bar-On Lynn
Published: February 2021

In neurological diseases, muscles often become hyper-resistant to stretch due to hyperreflexia, an exaggerated stretch reflex response that is considered to primarily depend on the muscle's stretch velocity. However, there is still limited understanding of how different biomechanical triggers applied during clinical tests evoke these reflex responses. We examined the effect of imposing a rotation with increasing velocity vs. increasing acceleration on triceps surae muscle repsonse in children with spastic paresis (SP) and compared the responses to those measured in typically developing (TD) children. A motor-operated ankle manipulator was used to apply different bell-shaped movement profiles, with three levels of maximum velocity (70, 110, and 150°/s) and three levels of maximum acceleration (500, 750, and 1,000°/s2). For each profile and both groups, we evaluated the amount of evoked triceps surae muscle activation. In SP, we evaluated two additional characteristics: the intensity of the response (peak EMG burst) and the time from movement initiation to onset of the EMG burst. As expected, the amount of evoked muscle activation was larger in SP compared to TD (all muscles: p < 0.001) and only sensitive to biomechanical triggers in SP. Further investigation of the responses in SP showed that peak EMG bursts increased in profiles with higher peak velocity (lateral gastrocnemius: p = 0.04), which was emphasized by fair correlations with increased velocity at EMG burst onset (all muscles: r > 0.33–0.36, p ≤ 0.008), but showed no significant effect for acceleration. However, the EMG burst was evoked faster with higher peak acceleration (all muscles p < 0.001) whereas it was delayed in profiles with higher peak velocity (medial gastrocnemius and soleus: p < 0.006). We conclude that while exaggerated response intensity (peak EMG burst) seems linked to stretch velocity, higher accelerations seem to evoke faster responses (time to EMG burst onset) in triceps surae muscles in SP. Understanding and controlling for the distinct effects of different biological triggers, including velocity, acceleration but also length and force of the applied movement, will contribute to the development of more precise clinical measurement tools. This is especially important when aiming to understand the role of hyperreflexia during functional movements where the biomechanical inputs are multiple and changing.
Hypoxia-Induced LIN28A mRNA Promotes the Metastasis of Colon Cancer in a Protein-Coding-Independent Manner
Authors: Weng Mingjiao , Feng Yukuan , He Yan , Yang Weiwei , Li Jing , Zhu Yuanyuan , Wang Tianzhen , Wang Chuhan , Zhang Xiao , Qiao Yu , Li Qi , Zhao Lingyu , Gao Shuangshu , Zhang Lei , Wu Yiqi , Zhao Ran , Wang Guangyu , Li Zhiwei , Jin Xiaoming , Zheng Tongsen , Li Xiaobo
Published: February 2021

The hypoxic microenvironment is beneficial to the metastasis but not to the proliferation of cancer cells. However, the mechanisms regarding to hypoxia differentially regulating cancer metastasis and proliferation are largely unknown. In this study, we revealed that hypoxia induced the expression of LIN28A at mRNA level but segregated LIN28A mRNAs in the P-bodies and thus inhibits the production of LIN28A protein. This unexpected finding suggests that there may be non-coding role for LIN28A mRNA in the progression of colon cancer. We further showed that the non-coding LIN28A mRNA promotes the metastasis but not proliferation of colon cancer cells in vitro and in vivo. Mechanistically, we revealed that methionyl aminopeptidase 2 (METAP2) is one of the up-regulated metastasis regulators upon over-expression of non-coding LIN28A identified by mass spectrum, and confirmed that it is non-coding LIN28A mRNA instead of LIN28A protein promotes the expression of METAP2. Moreover, we demonstrated that knockdown of DICER abolished the promotional effects of non-coding LIN28A on the metastasis and METAP2 expression. Conclusively, we showed that hypoxia induces the production of LIN28A mRNAs but segregated them into the P-bodies together with miRNAs targeting both LIN28A and METAP2, and then promotes the metastasis by positively regulating the expression of METAP2. This study uncovered a distinctive role of hypoxia in manipulating the metastasis and proliferation by differently regulating the expression of LIN28A at mRNA and protein level.
Verbal Communication in Robotics: A Study on Salient Terms, Research Fields and Trends in the Last Decades Based on a Computational Linguistic Analysis
Authors: Marin Vargas Alessandro , Cominelli Lorenzo , Dell’Orletta Felice , Scilingo Enzo Pasquale
Published: February 2021

Verbal communication is an expanding field in robotics showing a significant increase in both the industrial and research field. The application of verbal communication in robotics aims to reach a natural human-like interaction with robots. In this study, we investigated how salient terms related to verbal communication in robotics have evolved over the years, what are the topics that recur in the related literature, and what are their trends. The study is based on a computational linguistic analysis conducted on a database of 7,435 scientific publications over the last 2 decades. This comprehensive dataset was extracted from the Scopus database using specific key-words. Our results show how relevant terms of verbal communication evolved, which are the main coherent topics and how they have changed over the years. We highlighted positive and negative trends for the most coherent topics and the distribution over the years for the most significant ones. In particular, verbal communication resulted in being highly relevant for social robotics. Potentially, achieving natural verbal communication with a robot can have a great impact on the scientific, societal, and economic role of robotics in the future.
Dike Inflation Process Beneath Sakurajima Volcano, Japan, During the Earthquake Swarm of August 15, 2015
Authors: Koike Midori , Nakamichi Haruhisa
Published: February 2021

Magma intrusion usually causes seismicity and deformation in the surrounding rock and often leads to eruptions. A swarm of volcano-tectonic (VT) earthquakes associated with rapid dike intrusion in hours occurred beneath Sakurajima volcano on August 15, 2015. We determined the hypocenters and focal mechanisms of the VT earthquake swarm. The distributions of pressure (P)- and tension (T)-axes of the azimuths of the mechanisms are also obtained. The results indicate spatiotemporal changes of the distributions of the hypocenters and P- and T-axes. The hypocenters are distributed at depths of 0.3–1 km and 7:00–10:30 JST, and are located at depths of 0.3–3 km and 10:30–12:00 during which the seismic activity is the largest. At 12:00–24:00, the hypocenters are distributed in shallow and deep clusters at depths of 0.2–1 km and 1.5–3.5 km, respectively. The dike induced rapid ground deformation and is located between the shallow and deep clusters. The strike and opening directions of the dike are parallel to the NE–SW and NW–SE directions, respectively, corresponding to the regional maximum and minimum compression stress. The T-axes of the shallow cluster are distributed parallel to the opening direction of the dike. The P-axes of the deep cluster exhibit a pattern corresponding to the NE–SW direction and the T-axes are distributed in the NW–SE direction. In contrast, a 90° rotated pattern of strike-slip faulting is also observed at the deep cluster at 12:00–24:00, where the P-axes are distributed in the NW–SE direction and the T-axes are distributed in the NE–SW direction. This reflects the change in the stress field due to the dike inflation during the earthquake generation, and indicates that the alteration of stress in the vicinity of the dike due to the dike inflation and VT earthquakes are induced by the differential stress exceeding the brittle fracture strength of the rock. Future seismic and deformation observations in volcanoes will verify whether the spatiotemporal changes of the hypocenters and focal mechanism shown by this study are unique features of rapid dike intrusion.
SARS CoV-2 Spike Protein in silico Interaction With ACE2 Receptors From Wild and Domestic Species
Authors: Rendon-Marin Santiago , Martinez-Gutierrez Marlen , Whittaker Gary R. , Jaimes Javier A. , Ruiz-Saenz Julian
Published: February 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization (WHO), and since its first report, it has become a major public health concern. SARS-CoV-2 is closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been described to use angiotensin-converting enzyme 2 (ACE2) as a receptor. Natural SARS-CoV-2 infection in domestic and wildlife animals, measured by RT-qPCR, has been confirmed in different countries, especially from the Felidae family.In silicoanalysis of the interaction between the SARS-CoV-2 spike protein and the cellular receptor ACE2 in various animal species has suggested that wild felids and domestic cats could be susceptible to SARS-CoV-2 based on this interaction. Here, we performed a protein-protein molecular docking analysis of SARS-CoV-2 spike protein with the ACE2 receptor from different animals to elucidate the potential of those species as intermediate hosts or susceptible animals for SARS-CoV-2 infection. Compared to human ACE2, we found that ACE2 receptors from domestic cats and tigers could efficiently interact with RBD of SARS CoV-2 Spike protein. However, dog, ferret, and hamster ACE2 receptor interaction with SARS-CoV-2 S protein RBD was not predicted as favorable, demonstrating a potential differentiated susceptibility in the evaluated species.
Perspectives About Modulating Host Immune System in Targeting SARS-CoV-2 in India
Authors: Majumdar Sreyashi , Verma Rohit , Saha Avishek , Bhattacharyya Parthasarathi , Maji Pradipta , Surjit Milan , Kundu Manikuntala , Basu Joyoti , Saha Sudipto
Published: February 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus induced disease-2019 (COVID-19), is a type of common cold virus responsible for a global pandemic which requires immediate measures for its containment. India has the world’s largest population aged between 10 and 40 years. At the same time, India has a large number of individuals with diabetes, hypertension and kidney diseases, who are at a high risk of developing COVID-19. A vaccine against the SARS-CoV-2, may offer immediate protection from the causative agent of COVID-19, however, the protective memory may be short-lived. Even if vaccination is broadly successful in the world, India has a large and diverse population with over one-third being below the poverty line. Therefore, the success of a vaccine, even when one becomes available, is uncertain, making it necessary to focus on alternate approaches of tackling the disease. In this review, we discuss the differences in COVID-19 death/infection ratio between urban and rural India; and the probable role of the immune system, co-morbidities and associated nutritional status in dictating the death rate of COVID-19 patients in rural and urban India. Also, we focus on strategies for developing masks, vaccines, diagnostics and the role of drugs targeting host-virus protein-protein interactions in enhancing host immunity. We also discuss India’s strengths including the resources of medicinal plants, good food habits and the role of information technology in combating COVID-19. We focus on the Government of India’s measures and strategies for creating awareness in the containment of COVID-19 infection across the country.
Surface NKG2C Identifies Differentiated αβT-Cell Clones Expanded in Peripheral Blood
Authors: Kovalenko Elena I. , Zvyagin Ivan V. , Streltsova Maria A. , Mikelov Artem I. , Erokhina Sofya A. , Telford William G. , Sapozhnikov Alexander M. , Lebedev Yury B.
Published: February 2021

T cells that express CD56 in peripheral blood of healthy humans represent a heterogeneous and poorly studied subset. In this work, we analyzed this subset for NKG2C expression. In both CD56+ and CD56− subsets most of the NKG2C+ T cells had a phenotype of highly differentiated CD8+ TEMRA cells. The CD56+NKG2C+ T cells also expressed a number of NK cell receptors, such as NKG2D, CD16, KIR2DL2/DL3, and maturation marker CD57 more often than the CD56−NKG2C+CD3+ cells. TCR β-chain repertoire of the CD3+CD56+NKG2C+ cell fraction was limited by the prevalence of one or several clonotypes which can be found within the most abundant clonotypes in total or CD8+ T cell fraction TCRβ repertoire. Thus, NKG2C expression in highly differentiated CD56+ T cells was associated with the most expanded αβ T cell clones. NKG2C+ T cells produced almost no IFN-γ in response to stimulation with HCMV pp65-derived peptides. This may be partially due to the high content of CD45RA+CD57+ cells in the fraction. CD3+NKG2C+ cells showed signs of activation, and the frequency of this T-cell subset in HCMV-positive individuals was positively correlated with the frequency of NKG2C+ NK cells that may imply a coordinated in a certain extent development of the NKG2C+ T and NK cell subsets under HCMV infection.
The Role of BMI and Blood Pressure in the Relationship Between Total Cholesterol and Disability in Chinese Centenarians: A Cross-Sectional Study
Authors: Wang Shengshu , Jia Wangping , Yang Shanshan , Han Ke , Cao Wenzhe , Ren Xueling , Li Jing , Tai Penggang , Kou Fuyin , Liu Miao , He Yao
Published: February 2021

Background: Lower serum lipid metabolism might be associated with the decline of activity of daily living in the extreme longevity group. However, studies on models and possible paths of this correlation between total cholesterol (TC) and disability in centenarians are scarce. The aim of this study was to verify this correlation and explore the mediating effect of BMI and blood pressure on this relationship in Hainan centenarians.

Methods: We conducted a cross-sectional analysis of 1002 centenarians from the China Hainan Centenarians Cohort Study (CHCCS). Data on demographics, anthropometry data, lifestyle, and TC levels were collected through interviews, physical examinations, and laboratory tests. The Barthel index and Lawton index, measuring the disability status, were used to estimate the activity of daily living (ADL) and instrumental activity of daily living (IADL). A multivariable logistic regression model was used to explore the correlation between disability and TC levels. Mediation analyses were used to explore the both direct and indirect effects of TC level on disability.

Results: After adjusting for covariates, with 1 mmol/L increment in TC, the adjusted odds ratios (ORs) of ADL severe disability and ADL moderate & severe disability were 0.789(95%CI: 0.650–0.959) and 0.822(95%CI: 0. 0.699–0.966), respectively. There was a significant declining trend in the prevalence of different types of disability with increment in TC. The correlation was more pronounced among Hainan female centenarians. In the analysis of mediating effect among the female population, BMI significantly mediated the effect of TC levels on different types of disability. BMI and SBP, as chain mediators, multiply and chain mediated the effect of TC levels on IADL.

Conclusion: Low TC levels might be correlated with a higher frequency of disability in female centenarians, and this correlation might be mediated by BMI and blood pressure.
Novel Asaia bogorensis Signal Sequences for Plasmodium Inhibition in Anopheles stephensi
Authors: Grogan Christina , Bennett Marissa , Moore Shannon , Lampe David
Published: February 2021

Mosquitoes vector many pathogens that cause human disease, such as malaria that is caused by parasites in the genusPlasmodium. Current strategies to control vector-transmitted diseases are hindered by mosquito and pathogen resistance, so research has turned to altering the microbiota of the vectors. In this strategy, calledparatransgenesis, symbiotic bacteria are genetically modified to affect the mosquito’s phenotype by engineering them to deliver antiplasmodial effector molecules into the midgut to kill parasites. One paratransgenesis candidate isAsaia bogorensis, a Gram-negative, rod-shaped bacterium colonizing the midgut, ovaries, and salivary glands ofAnophelessp. mosquitoes. However, common secretion signals fromE. coliand closely related species do not function inAsaia. Here, we report evaluation of 20 nativeAsaiaN-terminal signal sequences predicted from bioinformatics for their ability to mediate increased levels of antiplasmodial effector molecules directed to the periplasm and ultimately outside the cell. We tested the hypothesis that by increasing the amount of antiplasmodials released from the cell we would also increase parasite killing power. We scanned theAsaia bogorensisSF2.1 genome to identify signal sequences from extra-cytoplasmic proteins and fused these to the reporter protein alkaline phosphatase. Six signals resulted in significant levels of protein released from theAsaiabacterium. Three signals were successfully used to drive the release of the antimicrobial peptide, scorpine. Further testing in mosquitoes demonstrated that these threeAsaiastrains were able to suppress the number of oocysts formed after a blood meal containingP. bergheito a significantly greater degree than wild-typeAsaia, although prevalence was not decreased beyond levels obtained with a previously isolated siderophore receptor signal sequence. We interpret these results to indicate that there is a maximum level of suppression that can be achieved when the effectors are constitutively driven due to stress on the symbionts. This suggests that simply increasing the amount of antiplasmodial effector molecules in the midgut is insufficient to create superior paratransgenic bacterial strains and that symbiont fitness must be considered as well.
EEGs Vary Less Between Lab and Home Locations Than They Do Between People
Authors: Mikkelsen Kaare B. , Tabar Yousef R. , Christensen Christian B. , Kidmose Preben
Published: February 2021

Given the rapid development of light weight EEG devices which we have witnessed the past decade, it is reasonable to ask to which extent neuroscience could now be taken outside the lab. In this study, we have designed an EEG paradigm well suited for deployment “in the wild.” The paradigm is tested in repeated recordings on 20 subjects, on eight different occasions (4 in the laboratory, 4 in the subject's own home). By calculating the inter subject, intra subject and inter location variance, we find that the inter location variation for this paradigm is considerably less than the inter subject variation. We believe the paradigm is representative of a large group of other relevant paradigms. This means that given the positive results in this study, we find that if a research paradigm would benefit from being performed in less controlled environments, we expect limited problems in doing so.
Association Between Ultrasound Parameters and History of Ischemic or Hemorrhagic Stroke in Patients With Moyamoya Disease
Authors: Zheng Shuai , Ge Peicong , Li Yi , Wang Jingzhe , Shi Zhiyong , Zhang Jinghan , He Lei , Cheng Linggang , Zhang Dong , He Wen
Published: February 2021

Objective: To explore the association between ultrasound parameters and previous ischemic or hemorrhagic stroke in patients with moyamoya disease (MMD), and develop an ultrasound-based nomogram to identify stroke in patients with MMD.

Methods: We prospectively enrolled 52 consecutive patients (92 hemispheres) with MMD at the Beijing Tiantan Hospital. Thirty-six patients (65 hemispheres) were assigned to the training dataset from September 2019 to February 2020, and 16 patients (27 hemispheres) were assigned to the validation dataset from March 2020 to July 2020. Multivariate logistic regression analysis was applied to identify ultrasound parameters associated with previous history of ipsilateral stroke in patients with MMD, and a nomogram was subsequently constructed to identify stroke in patients with MMD. The performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness.

Results: Multivariate analysis indicated that the flow volume (FV) of the extracranial internal carotid artery (EICA) and the peak systolic velocity (PSV) of the posterior cerebral artery (PCA) were independently associated with ipsilateral stroke in patients with MMD, a nomogram incorporating these two parameters was constructed to identify stroke patients. The area under the receiver operating characteristic (AUROC) curves was 0.776 (95% CI, 0.656–0.870) in the training dataset and 0.753 (95% CI, 0.550–0.897) in the validation dataset suggested that the model had good discrimination ability. The calibration plot showed good agreement in both the two datasets. The decision curve analysis (DCA) revealed that the nomogram was clinically useful.

Conclusions: Ultrasound parameters of EICA and PCA are independently associated with history of previous ipsilateral ischemic or hemorrhagic stroke in patients with MMD. The present ultrasound-based nomogram might provide information to identify MMD patients with high risk of stroke. Future long-term follow-up studies are needed to prove the predictive value in other independent cohorts.

Clinical Trial Registration:http://www.chictr.org.cn/index.aspx. Unique Identifier: ChiCTR1900026075.
Knowledge Representation for Multi-Scale Physiology Route Modeling
Authors: Kokash Natallia , de Bono Bernard
Published: February 2021

We present a framework for the topological and semantic assembly of multiscale physiology route maps. The framework, called ApiNATOMY, consists of a knowledge representation (KR) model and a set of knowledge management (KM) tools. Using examples of ApiNATOMY route maps, we present a KR format that is suitable for the analysis and visualization by KM tools. The conceptual KR model provides a simple method for physiology experts to capture process interactions among anatomical entities. In this paper, we outline the KR model, modeling format, and the KM procedures to translate concise abstraction-based specifications into fully instantiated models of physiology processes.
Immune Infiltration Landscape in Clear Cell Renal Cell Carcinoma Implications
Authors: Wang Yongfeng , Yin Ci , Geng Lele , Cai Weiyang
Published: February 2021

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment.
An Approach Based on Mammographic Imaging and Radiomics for Distinguishing Male Benign and Malignant Lesions: A Preliminary Study
Authors: Huang Yan , Xiao Qin , Sun Yiqun , Wang Zhe , Li Qin , Wang He , Gu Yajia
Published: February 2021

Purpose

To develop and validate an imaging-radiomics model for the diagnosis of male benign and malignant breast lesions.

Methods

Ninety male patients who underwent preoperative mammography from January 2011 to December 2018 were enrolled in this study (63 in the training cohort and 27 in the validation cohort). The region of interest was segmented into a mediolateral oblique view, and 104 radiomics features were extracted. The minimum redundancy and maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) methods were used to exclude radiomics features to establish the radiomics score (rad-score). Mammographic features were evaluated by two radiologists. Univariate logistic regression was used to select for imaging features, and multivariate logistic regression was used to construct an imaging model. An imaging-radiomics model was eventually established, and a nomogram was developed based on the imaging-radiomics model. Area under the curve (AUC) and decision curve analysis (DCA) were applied to assess the clinical value.

Results

The AUC based on the imaging model in the validation cohort was 0.760, the sensitivity was 0.750, and the specificity was 0.727. The AUC, sensitivity and specificity based on the radiomics in the validation cohort were 0.820, 0.750, and 0.867, respectively. The imaging-radiomics model was better than the imaging and radiomics models; the AUC, sensitivity, and specificity of the imaging-radiomics model in the validation cohort were 0.870, 0.824, and 0.900, respectively.

Conclusion

The imaging-radiomics model created by the imaging characteristics and radiomics features exhibited a favorable discriminatory ability for male breast cancer.
Immunosuppression in Gliomas via PD-1/PD-L1 Axis and Adenosine Pathway
Authors: Scheffel Thamiris Becker , Grave Nathália , Vargas Pedro , Diz Fernando Mendonça , Rockenbach Liliana , Morrone Fernanda Bueno
Published: February 2021

Glioblastoma is the most malignant and lethal subtype of glioma. Despite progress in therapeutic approaches, issues with the tumor immune landscape persist. Multiple immunosuppression pathways coexist in the tumor microenvironment, which can determine tumor progression and therapy outcomes. Research in immune checkpoints, such as the PD-1/PD-L1 axis, has renewed the interest in immune-based cancer therapies due to their ability to prevent immunosuppression against tumors. However, PD-1/PD-L1 blockage is not completely effective, as some patients remain unresponsive to such treatment. The production of adenosine is a major obstacle for the efficacy of immune therapies and is a key source of innate or adaptive resistance. In general, adenosine promotes the pro-tumor immune response, dictates the profile of suppressive immune cells, modulates the release of anti-inflammatory cytokines, and induces the expression of alternative immune checkpoint molecules, such as PD-1, thus maintaining a loop of immunosuppression. In this context, this review aims to depict the complexity of the immunosuppression in glioma microenvironment. We primarily consider the PD-1/PD-L1 axis and adenosine pathway, which may be critical points of resistance and potential targets for tumor treatment strategies.
Zinc Finger Protein CTCF Regulates Extracellular Matrix (ECM)-Related Gene Expression Associated With the Wnt Signaling Pathway in Gastric Cancer
Authors: Liu Chenbin , Deng Linyi , Lin Jinrong , Zhang Jianjun , Huang Shu , Zhao Jinglin , Jin Peipei , Xu Peiqing , Ni Peihua , Xu Dakang , Ying Le , Hu Yiqun
Published: February 2021

Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients. Interestingly, putative CCCTC-binding factor (CTCF) regulatory elements were identified within the promoters of these ECM-related genes and were confirmed by chromatin immunoprecipitation sequencing (ChIP-Seq). CTCF binding sites also overlapped with histone activation markers, indicating direct regulation. In addition, CTCF was also correlated with the Wnt signaling pathway. A comparison of human GC cell lines with high or low expression of ECM-related genes revealed different levels of tumor aggressiveness, suggesting the cancer development-promoting functions of ECM-related genes. Furthermore, CTCF regulated COL1A1 and COLA31 expression in vitro. Silencing CTCF or COL1A1/COL1A3 markedly inhibited cell growth and migration in the metastatic GC cell line BGC823. Collectively, this ECM-related 7-gene signature provides a novel insight for survival prediction among GC patients. The zinc finger protein CTCF regulates ECM-related genes, thereby promoting GC cell growth and migration.
A 7 Tesla Amygdalar-Hippocampal Shape Analysis of Lithium Response in Bipolar Disorder
Authors: Athey Thomas L. , Ceritoglu Can , Tward Daniel J. , Kutten Kwame S. , DePaulo J. Raymond , Glazer Kara , Goes Fernando S. , Kelsoe John R. , Mondimore Francis , Nievergelt Caroline M. , Rootes-Murdy Kelly , Zandi Peter P. , Ratnanather J. Tilak , Mahon Pamela B.
Published: February 2021

Research to discover clinically useful predictors of lithium response in patients with bipolar disorder has largely found them to be elusive. We demonstrate here that detailed neuroimaging may have the potential to fill this important gap in mood disorder therapeutics. Lithium treatment and bipolar disorder have both been shown to affect anatomy of the hippocampi and amygdalae but there is no consensus on the nature of their effects. We aimed to investigate structural surface anatomy changes in amygdala and hippocampus correlated with treatment response in bipolar disorder. Patients with bipolar disorder (N = 14) underwent lithium treatment, were classified by response status at acute and long-term time points, and scanned with 7 Tesla structural MRI. Large Deformation Diffeomorphic Metric Mapping was applied to detect local differences in hippocampal and amygdalar anatomy between lithium responders and non-responders. Anatomy was also compared to 21 healthy comparison participants. A patch of the ventral surface of the left hippocampus was found to be significantly atrophied in non-responders as compared to responders at the acute time point and was associated at a trend-level with long-term response status. We did not detect an association between response status and surface anatomy of the right hippocampus or amygdala. To the best of our knowledge, this is the first shape analysis of hippocampus and amygdala in bipolar disorder using 7 Tesla MRI. These results can inform future work investigating possible neuroimaging predictors of lithium response in bipolar disorder.
Correlation Between Screen Time and Autistic Symptoms as Well as Development Quotients in Children With Autism Spectrum Disorder
Authors: Dong Han-Yu , Wang Bing , Li Hong-Hua , Yue Xiao-Jing , Jia Fei-Yong
Published: February 2021

Background: Electronic screen media play an increasingly vital role in children's entertainment; however, excessive screen time may negatively influence child development. The purpose of this study was to investigate the relationship between the screen time of children with autism spectrum disorder (ASD) and their autistic symptoms and development quotients (DQs).

Methods: We compared the screen time of 101 children with ASD and 57 typically developing (TD) children. Then, we performed a correlation analysis to determine the correlations between the screen time and the ASD-related scale scores and developmental quotients of the Gesell Developmental Schedules (GDS) of ASD children. We further divided the ASD group into subgroups according to the screen time and age and then separately conducted the above correlation analyses by subgroup.

Result: The results showed that the screen time of the children with ASD was longer than that of the TD children (3.34 ± 2.64 h vs. 0.91 ± 0.93 h). The screen time of the children with ASD was positively correlated with the Childhood Autism Rating Scale (CARS) score (r = 0.242, P = 0.021) and “taste, smell and touch” item of CARS(r = 0.304, P = 0.005), and negatively correlated with the language DQ of the GDS (r = −0.236, P = 0.047). The subgroup analysis showed that in the longer screen time subgroup of ASD children, the screen time was positively correlated with the CARS score (r = 0.355, P = 0.026) and negatively correlated with the DQs of all domains of the GDS (P < 0.05). In addition, in the younger age group of ASD children, the screen time was positively correlated with the CARS score (r = 0.314, P = 0.021) and negatively correlated with the DQs of all domains of the GDS, except for the personal-social behavior domain (P < 0.05).

Conclusion: Compared with TD children, children with ASD have a longer screen time. The screen time is related to autism-like symptoms and the DQs of children with ASD. The longer the screen time, the more severe the symptoms of ASD (especially sensory symptoms), and the more obvious the developmental delay, especially in ASD children with a longer screen time and younger age, particularly in the language domain.
Perceived Thermal Response of Stone Quarry Workers in Hot Environment
Authors: Dutta Priya , Chorsiya Varsha , Nag Pranab Kumar
Published: February 2021

Introduction: Impact of heat on health of workers goes unrecognized by the virtue of the indispensable fact that every individual has varied perception and tolerance capacity. The present study determine the physiological signs with perceived subjective responses under the thermal stress.

Materials and Methods: The study was spread on open field stone quarry workers (N = 934) during the summer (May to June), post monsoon (September to October), and winter (December to January).

Results: In the summer months, dry bulb temperature range from 36.1 to 43.2°C and the distribution of Wet Bulb Globe temperature (WBGT) outdoor values were outlier-prone than normal distribution indicated heat vulnerability. The environmental effect on weighted average skin temperature (Tsk) local segmental Tsk and deep body temperature (Tcr) were greater than the effects that might be attributed to work severity. The tolerance time level in summer months (65 ± 13 min at WBGT 35 ± 2.3°C) was less than in other two season. About 85% of workers in summer, 68% in post monsoon and 79% in winter recorded working heart rate greater than 90 beats/min. Physiological and subjective responses to heat stress indicated that during summer month the workers complained of excessive sweating (93.5%), feeling of thirst/dry mouth (88.7%), elevated Core temperature (Tcr) (58.7%) and decreased working capacity (75.6%). The observation found that around 14% workers were vulnerable to heat stress and the workers had no knowledge to mitigate the heat related illnesses.

Discussion and Conclusions: The stone quarry work as compared to other outdoor workers have environmental adversaries which becomes confounding variables in the study of such occupations. There was significant difference (p < 0.001) as far as the physiological and thermoregulatory responses were concerned in three different months of investigation.
Emergent Change in a Mexican Midwifery Center Organization Amidst the COVID-19 Crisis
Authors: Alonso Cristina , Storey Akane Sugimoto , Fajardo Ilse , Borboleta Hannah S.
Published: February 2021

Luna Maya is a Mexican NGO that operates two full-scope midwifery centers in Mexico City and Chiapas, Mexico, providing woman-centered, culturally appropriate midwifery model maternity care on a sliding cost scale. The COVID-19 health crisis has made it necessary for Luna Maya to quickly incorporate safety protocols for out-of-hospital maternity care. Yet many of the emerging guidelines on maternity care have focused on high-income and hospital settings; there are no specific guidelines for such care in out-of-hospital settings in low- and middle-income countries. Thus we have had to create our own, based on best available and emerging evidence. In this article, we describe the guidelines and protocols we have created in response to COVID-19, the international evidence and recommendations on which we base them, and precisely how we carry them out in practice. We also present and analyze the results of qualitative interviews we conducted for this article with eight of our midwives and eight of our midwifery clients. These interviews reveal the tremendous stresses both midwives and pregnant and birthing women are experiencing as a result of the pandemic, their creative adaptations, and the structural flaws, deficiencies, and inequities of the Mexican healthcare system. The article also addresses Luna Maya’s ongoing challenges in continuing to provide care completely outside of governmental support and in difficult economic times, and demonstrates the extreme need for improvements in the Mexican system of maternity care and for full integration of community-based midwives and out-of-hospital birth.
The local face of NGOs in Poland
Authors: Murawska Daria
Published: February 2021

The recognition of NGOs is increasing every year, but they are still identified with large, usually nationwide entities, and it is local NGOs that are closest to the community and know its needs. In the 2015 survey, as many as 40% of respondents had no association with a non-governmental organization. From this perspective, an interesting issue is the analysis of the local face of non-governmental organizations and the specificity of their activities in the local dimension and for the benefit of local communities.
Kantian Ethics and the Animal Turn. On the Contemporary Defence of Kant’s Indirect Duty View
Authors: Camenzind Samuel
Published: February 2021

Criticism of Kant’s position on our moral relationship with animals dates back to the work of Arthur Schopenhauer and Leonard Nelson, but historically Kantian scholars have shown limited interest in the human-animal relationship as such. This situation changed in the mid-1990s with the arrival of several publications arguing for the direct moral considerability of animals within the Kantian ethical framework. Against this, another contemporary Kantian approach has continued to defend Kant’s indirect duty view. In this approach it is argued, first, that it is impossible to establish direct duties to animals, and second, that this is also unnecessary because the Kantian notion that we have indirect duties to animals has far-reaching practical consequences and is to that extent adequate. This paper explores the argument of the far-reaching duties regarding animals in Kant’s ethics and seeks to show that Kantians underestimate essential differences between Kant and his rivals today (i.e., proponents of animal rights and utilitarians) on a practical and fundamental level. It also argues that Kant’s indirect duty view has not been defended convincingly: the defence tends to neglect theory-immanent problems in Kant’s ethics connected with unfounded value assumptions and unconvincing arguments for the denial of animals’ moral status. However, it is suggested that although the human-animal relationship was not a central concern of Kant’s, examination of the animal question within the framework of Kant’s ethics helps us to develop conceptual clarity about his duty concept and the limitations of the reciprocity argument.
The Association of an SNP in the EXOC4 Gene and Reproductive Traits Suggests Its Use as a Breeding Marker in Pigs
Authors: He Yingting , Zhou Xiaofeng , Zheng Rongrong , Jiang Yao , Yao Zhixiang , Wang Xilong , Zhang Zhe , Zhang Hao , Li Jiaqi , Yuan Xiaolong
Published: February 2021

In mammals, the exocyst complex component 4 (EXOC4) gene has often been reported to be involved in vesicle transport. The SNP rs81471943 (C/T) is located in the intron of porcine EXOC4, while six quantitative trait loci (QTL) within 5–10 Mb around EXOC4 are associated with ovary weight, teat number, total offspring born alive, and corpus luteum number. However, the molecular mechanisms between EXOC4 and the reproductive performance of pigs remains to be elucidated. In this study, rs81471943 was genotyped from a total of 994 Duroc sows, and the genotype and allele frequency of SNP rs81471943 (C/T) were statistically analyzed. Then, the associations between SNP rs81471943 and four reproductive traits, including number of piglets born alive (NBA), litter weight at birth (LWB), number of piglets weaned (NW), and litter weight at weaning (LWW), were determined. Sanger sequencing and PCR restriction fragment length polymorphism (PCR-RFLP) were utilized to identify the rs81471943 genotype. We found that the genotype frequency of CC was significantly higher than that of CT and TT, and CC was the most frequent genotype for NBA, LWB, NW, and LWW. Moreover, 5′-deletion and luciferase assays identified a positive transcription regulatory element in the EXOC4 promoter. After exploring the EXOC4 promoter, SNP −1781G/A linked with SNP rs81471943 (C/T) were identified by analysis of the transcription activity of the haplotypes, and SNP −1781 G/A may influence the potential binding of P53, E26 transformation specific sequence -like 1 transcription factor (ELK1), and myeloid zinc finger 1 (MZF1). These findings provide useful information for identifying a molecular marker of EXOC4-assisted selection in pig breeding.
Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis
Authors: Tanaka Urara , Kajioka Shunichi , Finoti Livia S. , Palioto Daniela B. , Kinane Denis F. , Benakanakere Manjunatha R.
Published: February 2021

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.
Platelet-Derived Growth Factor Stimulated Migration of Bone Marrow Mesenchymal Stem Cells into an Injectable Gelatin-Hydroxyphenyl Propionic Acid Matrix
Authors: Niu Wanting , Lim Teck Chuan , Alshihri Abdulmonem , Rajappa Ravikumar , Wang Lishan , Kurisawa Motoichi , Spector Myron
Published: February 2021

Bone marrow mesenchymal stem cells (bMSCs) are responsible in the repair of injured tissue through differentiation into multiple cell types and secretion of paracrine factors, and thus have a broad application profile in tissue engineering/regenerative medicine, especially for the musculoskeletal system. The lesion due to injury or disease may be a closed irregular-shaped cavity deep within tissue necessitating an injectable biomaterial permissive of host (endogenous) cell migration, proliferation and differentiation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) is a natural biopolymer hydrogel which is covalently cross-linked by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) in situ and can be delivered to the lesion by needle injection. Growth factors and cytokines can be directly incorporated into the gel or into nano- and micro-particles, which can be employed for sustained release of biomolecules while maintaining their bioactivity. In this study, we selected polyelectrolyte complex nanoparticles (PCNs) prepared with dextran sulfate and chitosan as the carrier for platelet-derived growth factor (PDGF)-BB and stromal cell-derived factor (SDF)-1α, which have been tested effectively in recruiting stem cells. Our in vitro results showed a high degree of viability of bMSCs through the process of Gtn-HPA covalent cross-linking gelation. The Gtn-HPA matrix was highly permissive of bMSC migration, proliferation, and differentiation. PDGF-BB (20 ng/mL) directly incorporated into the gel and, alternatively, released from PCNs stimulated bMSC migration and proliferation. There were only small differences in the results for the direct incorporation of PDGF into the gel compared with its release from PCNs, and for increased doses of the growth factor (200 ng/mL and 2 µg/mL). In contrast, SDF-1α elicited an increase in migration and proliferation only when released from PCNs; its effect on migration was notably less than PDGF-BB. The in vitro results demonstrate that PDGF-BB substantially increases migration of bMSCs into Gtn-HPA and their proliferation in the gel, and that these benefits can be derived from incorporation of a relatively low dose of the growth factor directly into the gel. These findings commend the use of Gtn-HPA/PDGF-BB as an injectable therapeutic agent to treat defects in musculoskeletal tissues.
Parkinson’s Disease in Romania: A Scoping Review Protocol
Authors: Rosca Elena Cecilia , Tudor Raluca , Cornea Amalia , Simu Mihaela
Published: February 2021

Parkinson’s disease (PD) is a significant cause of disability, with a fast-growing prevalence. This review will summarize the epidemiological and clinical data in Romania and the interventions and diagnostic approaches used in this Eastern European country. This scoping review will primarily follow the recommendations on the scoping review methodology made by the Joanna Briggs Institute. In order to answer our research questions, we will search four databases using appropriate search terms. We will use pre-defined inclusion criteria and the data of eligible studies will be extracted in a standardized form. Results will be reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The proposed scoping review will map the evidence on PD in Romania through a literature review, focusing on epidemiology, clinical characteristics, interventions, and diagnosis, contributing to PD research advancement. We will provide information for policy-makers, public health specialists, and clinicians.