bluuebunny/crossref_metadata_2025 huggingface dataset:
TFPI2 Promotes Perivascular Migration in an Angiotropism Model of Melanoma
Authors: Mo Jing , Zhao Xiulan , Wang Wei , Zhao Nan , Dong Xueyi , Zhang Yanhui , Cheng Runfen , Sun Baocun
Published: June 2021

Purpose

Angiotropism is the process by which cancer cells attach to and migrate along blood vessels to acquire vasculature, disseminate, and metastasize. However, the molecular basis for such vessel–tumor interactions has not been fully elucidated, partly due to limited experimental models. In this study, we aimed to observe and explore the molecular mechanism underlying angiotropism in melanoma.

Methods

To monitor the interactions of human melanoma cells with the vasculature in vivo, a murine coxenograft model was employed by co-injecting highly and poorly invasive melanoma cells subcutaneously. To identify key pathways and genes involved in the angiotropic phenotype of melanoma, analysis of differentially expressed genes (DEGs) and gene set enrichment analysis (GSEA) were performed. The role of tissue factor pathway inhibitor 2 (TFPI2) in angiotropism was evaluated by immunostaining, adhesion assay, shRNA, and in vivo tumorigenicity. Angiotropism and TFPI2 expression were examined in surgical specimens of melanoma by immunohistochemical staining. Data from The Cancer Genome Atlas (TCGA) were analyzed to explore the expression and prognostic implications of TFPI2 in uveal and cutaneous melanoma.

Results

Highly invasive melanoma cells spread along the branches of intratumor blood vessels to the leading edge of invasion in the coxenograft model, resembling angiotropic migration. Mechanisms underlying angiotropism were primarily associated with molecular function regulators, regulation of cell population proliferation, developmental processes, cell differentiation, responses to cytokines and cell motility/locomotion. TFPI2 downregulation weakened the perivascular migration of highly invasive melanoma cells. High levels of TFPI2 were correlated with worse and better survival in uveal and cutaneous melanoma, respectively.

Conclusion

These results provide a straightforward in vivo model for the observation of angiotropism and suggest that TFPI2 could inhibit the angiotropic phenotype of melanoma.
Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma
Authors: Lu Lu , Liu Le-Ping , Zhao Qiang-Qiang , Gui Rong , Zhao Qin-Yu
Published: June 2021

Lung adenocarcinoma (LUAD) is a highly heterogeneous malignancy, which makes prognosis prediction of LUAD very challenging. Ferroptosis is an iron-dependent cell death mechanism that is important in the survival of tumor cells. Long non-coding RNAs (lncRNAs) are considered to be key regulators of LUAD development and are involved in ferroptosis of tumor cells, and ferroptosis-related lncRNAs have gradually emerged as new targets for LUAD treatment and prognosis. It is essential to determine the prognostic value of ferroptosis-related lncRNAs in LUAD. In this study, we obtained RNA sequencing (RNA-seq) data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and ferroptosis-related lncRNAs by co-expression analysis. The best predictors associated with LUAD prognosis, including C5orf64, LINC01800, LINC00968, LINC01352, PGM5-AS1, LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, LMO7DN, were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, and the LUAD risk prediction model was successfully constructed. Kaplan-Meier analysis, receiver operating characteristic (ROC) time curve analysis and univariate and multivariate Cox regression analysis and further demonstrated that the model has excellent robustness and predictive ability. Further, based on the risk prediction model, functional enrichment analysis revealed that 12 prognostic indicators involved a variety of cellular functions and signaling pathways, and the immune status was different in the high-risk and low-risk groups. In conclusion, a risk model of 12 ferroptosis related lncRNAs has important prognostic value for LUAD and may be ferroptosis-related therapeutic targets in the clinic.
Role of NRP1 in Bladder Cancer Pathogenesis and Progression
Authors: Dong Yang , Ma Wei-ming , Shi Zhen-duo , Zhang Zhi-guo , Zhou Jia-he , Li Yang , Zhang Shao-qi , Pang Kun , Li Bi-bo , Zhang Wen-da , Fan Tao , Zhu Guang-yuan , Xue Liang , Li Rui , Liu Ying , Hao Lin , Han Cong-hui
Published: June 2021

Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after NRP1 knockdown. After identifying differentially expressed genes (DEGs) induced by NRP1 silencing, GO/KEGG and IPA® bioinformatics analyses were performed and specific predicted pathways and targets were confirmed in vitro. Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. NRP1 knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after NRP1 silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA® pathway analysis and validated using western blot in BC cells. NRP1 knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by NRP1 knockdown may be NUPR1, and NRP1 was also the downstream target of NUPR1 and essential for regulation of FOXP3 expression to activate neovascularisation. DCBLD2 was positively regulated by NRP1, and PPAR signaling was significantly associated with low NRP1 expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of NRP1 contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers.
Abscopal Effects of Local Radiotherapy Are Dependent on Tumor Immunogenicity
Authors: Lai Jin-Zhi , Zhu Yan-Yang , Liu Ying , Zhou Lin-Lin , Hu Li , Chen Ling , Zhang Qiu-Yu
Published: June 2021

Although abscopal tumor regression remains a rare phenomenon, interest in exploiting how radiation stimulates the immune system to induce systemic abscopal response is increasing. Here, we tested the hypothesis that tumor immunogenicity determined the ability of radiotherapy to induce abscopal effects. We established highly (MC-38 and E.G7-OVA) or poorly (LL/2 and B16-F10) immunogenic tumor models in this study and treated them with sham radiation, a single dose of 15 Gy, or three fractions of 5 Gy on three consecutive days. Alterations in the tumor microenvironment after radiation were examined by flow cytometry and RNA sequencing. Our results demonstrated the positive correlation between tumor immunogenicity and the abscopal effect of radiotherapy. The single dose of 15 Gy radiation was an effective regimen for inducing abscopal effects in highly immunogenic tumors. Local radiation reshaped the tumor microenvironment of irradiated and non-irradiated distant tumors by increasing CD8 T-cell infiltration and reducing suppressive immune cell accumulation. However, radiation alone was insufficient to elicit abscopal effects in poorly immunogenic tumors. No significant alterations were detected in the non-irradiated distant tumor microenvironment after radiation of poorly immunogenic tumors. In addition, tumor immunogenic subtypes were associated with the radiological response and clinical outcome of patients receiving radiotherapy. These findings indicated that tumor immunogenicity was the dominant characteristic that could predict the abscopal effect of radiotherapy. Our study provides an in-depth understanding of the immunological mechanisms involved in abscopal effects and highlights the impact of tumor heterogeneity on the therapeutic efficacy of radiotherapy and their combination with immunotherapy in clinical trials.
MDM2 Binding Protein Induces the Resistance of Hepatocellular Carcinoma Cells to Molecular Targeting Agents via Enhancing the Transcription Factor Activity of the Pregnane X Receptor
Authors: Jiang Qiyu , Ma Yan , Han Jingjing , Chu Jingdong , Ma Xuemei , Shen Lijun , Liu Bo , Li Bo-an , Hou Jun , Bi Qian
Published: June 2021

The MDM2 binding protein (MTBP) has been considered an important regulator of human malignancies. In this study, we demonstrate that the high level of MTBP’s endogenous expression is correlated with poor prognosis of advanced hepatocellular carcinoma (HCC) patients who received sorafenib. MTBP interacted with the Pregnane X receptor (PXR) and enhanced the transcription factor activity of PXR. Moreover, MTBP enhanced the accumulation of PXR in HCC cells’ nuclear and the recruitment of PXR to its downstream gene’s (cyp3a4’s) promoter region. Mechanically, the knockdown of MTBP in MHCC97-H cells with high levels of MTBP decelerated the clearance or metabolism of sorafenib in HCC cells and led to the resistance of HCC cells to sorafenib. Whereas overexpression of MTBP in in MHCC97-L cells with low levels of MTBP showed the opposite trend. By establishing the interaction between MTBP and PXR, our results indicate that MTBP could function as a co-activator of PXR and could be a promising therapeutic target to enhance the sensitivity of HCC cells to molecular targeting agents.
The Yin and the Yang of Transformative Research During the COVID-19 Pandemic—A Perspective
Authors: Sampath Venkatesh , Ramchandran Ramani
Published: June 2021

The COVID-19 pandemic has highlighted the necessity for scientists from diverse disciplines to collaboratively mitigate the singular calamity facing humanity this century. The ability of researchers to combine exponential advances in technology and scientific acumen has resulted in landmark discoveries in pediatric research and is surmounting the COVID-19 challenge. Several of these discoveries exist in a realm of research that is not classically “basic” or “clinical.” Translational research characterizes this domain partially, but does not fully capture the integrated research approaches that have spurred these discoveries. Herein, we share our perspective on the common themes underpinning the basic and clinical research. We also highlight major differences in the scope, emphasis, approach, and limitations of basic and clinical research that impede multi-disciplinary approaches that facilitate truly transformative research. These differences in research thinking and methodology are ingrained during training wherein the limitations of the chosen discipline, and strengths of alternate disciplines are not adequately explored. Insular approaches are particularly limited in impacting complex diseases pathophysiology in the era of precision medicine. We propose that integration of -omics technologies, systems biology, adaptive clinical trial designs, humanized animal models, and precision pre-clinical model systems must be incorporated into research training of future scientists. Several initiatives from the NIH and other institutions are facilitating such broad-based “research without frontiers” training that paves the way for seamless, multi-disciplinary, research. Such efforts become “transformative” when scientific challenges are tackled in partnership with a willingness to share ideas, tackle challenges, and develop tools/models from the very beginning.
Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia
Authors: Justicia-Grande Antonio José , Gómez-Ríal Jose , Rivero-Calle Irene , Pischedda Sara , Curras-Tuala María José , Gómez-Carballa Alberto , Cebey-López Miriam , Pardo-Seco Jacobo , Méndez-Gallart Roberto , Fernández-Seara María José , Salas Antonio , Martinón-Torres Federico
Published: June 2021

Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro results.
Effects of the Local Bone Renin-Angiotensin System on Titanium-Particle-Induced Periprosthetic Osteolysis
Authors: Zhao Zhiping , Wang Changyao , Xu Yingxing , Wang Xiangyu , Jia Bin , Yu Tengbo , Wang Yingzhen , Zhang Yongtao
Published: June 2021

Wear particles may induce osteoclast formation and osteoblast inhibition that lead to periprosthetic osteolysis (PPOL) and subsequent aseptic loosening, which is the primary reason for total joint arthroplasty failure. Local bone renin-angiotensin system (RAS) has been found to participate in the pathogenic process of various bone-related diseases via promoting bone resorption and inhibiting bone formation. However, it remains unclear whether and how local bone RAS participates in wear-particle-induced PPOL. In this study, we investigated the potential role of RAS in titanium (Ti) particle-induced osteolysis in vivo and osteoclast and osteoblast differentiation in vitro. We found that the expressions of AT1R, AT2R and ACE in the interface membrane from patients with PPOL and in calvarial tissues from a murine model of Ti-particle-induced osteolysis were up-regulated, but the increase of ACE in the calvarial tissues was abrogated by perindopril. Moreover, perindopril mitigated the Ti-particle-induced osteolysis in the murine model by suppressing bone resorption and increasing bone formation. We also observed in RAW264.7 macrophages that Ang II promoted but perindopril suppressed Ti-particle-induced osteoclastogenesis, osteoclast-mediated bone resorption and expression of osteoclast-related genes. Meanwhile, Ang II enhanced but perindopril repressed Ti-particle-induced suppression of osteogenic differentiation and expression of osteoblast-specific genes in mouse bone marrow mesenchymal stem cells (BMSCs). In addition, local bone RAS promoted Ti-particle-induced osteolysis by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK and Wnt/β-catenin pathways. Taken together, we suggest that inhibition of RAS may be a potential approach to the treatment of wear-particle-induced PPOL.
Reduction in Hindquarter Vascular Resistance Supports 5-HT7 Receptor Mediated Hypotension
Authors: Seitz Bridget M. , Watts Stephanie W. , Fink Gregory D.
Published: June 2021

The 5-HT7 receptor is the primary mediator of both the acute (<hours) and chronic (day-week) decreases in mean arterial pressure (MAP) during low dose 5-HT infusion in rats. Previous data show the hypotensive response during chronic 5-HT infusion is due to a decrease total peripheral resistance (TPR) and specifically splanchnic vascular resistance. We hypothesized that changes in vascular resistance in both the splanchnic and skeletal muscle vascular beds are critical to the cardiovascular effects mediated by the 5-HT7 receptor. Systemic and regional hemodynamic data were collected in conscious and anesthetized male rats using radiotelemetry, vascular catheters and transit-time flowmetry. Reversible antagonism of the 5-HT7 receptor was achieved with the selective antagonist SB269970 (33 μg/kg, iv). From the very beginning and throughout the duration (up to 5 days) of a low dose (25 μg/kg) infusion of 5-HT, TPR, and MAP were decreased while cardiac output (CO) was increased. In a separate group of rats, the contribution of the 5-HT7 receptor to the regional hemodynamic response was tested during 5-HT-induced hypertension. The decrease in MAP after 24 h of 5-HT (saline 83 ± 3 vs. 5-HT 72 ± 3 mmHg) was associated with a significant decrease in skeletal muscle vascular resistance (saline 6 ± 0.2 vs. 5-HT 4 ± 0.4 mmHg/min/mL) while splanchnic vascular resistance was similar in 5-HT and saline-treated rats. When SB269970 was administered acutely, MAP and skeletal muscle vascular resistance rapidly increased, whereas splanchnic resistance was unaffected. Our work suggests the most prominent regional hemodynamic response to 5-HT7 receptor activation paralleling the fall in MAP is a decrease in skeletal muscle vascular resistance.
Interactions of Silicon With Essential and Beneficial Elements in Plants
Authors: Pavlovic Jelena , Kostic Ljiljana , Bosnic Predrag , Kirkby Ernest A. , Nikolic Miroslav
Published: June 2021

Silicon (Si) is not classified as an essential element for plants, but numerous studies have demonstrated its beneficial effects in a variety of species and environmental conditions, including low nutrient availability. Application of Si shows the potential to increase nutrient availability in the rhizosphere and root uptake through complex mechanisms, which still remain unclear. Silicon-mediated transcriptional regulation of element transporters for both root acquisition and tissue homeostasis has recently been suggested as an important strategy, varying in detail depending on plant species and nutritional status. Here, we summarize evidence of Si-mediated acquisition, uptake and translocation of nutrients: nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), boron (B), chlorine (Cl), and nickel (Ni) under both deficiency and excess conditions. In addition, we discuss interactions of Si-with beneficial elements: aluminum (Al), sodium (Na), and selenium (Se). This review also highlights further research needed to improve understanding of Si-mediated acquisition and utilization of nutrients and vice versa nutrient status-mediated Si acquisition and transport, both processes which are of high importance for agronomic practice (e.g., reduced use of fertilizers and pesticides).
Reliability Estimation in Multidimensional Scales: Comparing the Bias of Six Estimators in Measures With a Bifactor Structure
Authors: Trizano-Hermosilla Italo , Gálvez-Nieto José L. , Alvarado Jesús M. , Saiz José L. , Salvo-Garrido Sonia
Published: June 2021

In the context of multidimensional structures, with the presence of a common factor and multiple specific or group factors, estimates of reliability require specific estimators. The use of classical procedures such as the alpha coefficient or omega total that ignore structural complexity are not appropriate, since they can lead to strongly biased estimates. Through a simulation study, the bias of six estimators of reliability in multidimensional measures was evaluated and compared. The study is complemented by an empirical illustration that exemplifies the procedure. Results showed that the estimators with the lowest bias in the estimation of the total reliability parameter are omega total, the two versions of greatest lower bound (GLB) and the alpha coefficient, which in turn are also those that produce the highest overestimation of the reliability of the general factor. Nevertheless, the most appropriate estimators, in that they produce less biased estimates of the reliability parameter of the general factor, are omega limit and omega hierarchical.
Home Information and Communication Technology Use and Student Academic Performance: Encouraging Results for Uncertain Times
Authors: Skvarc David Robert , Talbot Matthew , Harries Travis , Wilson Christopher J. , Joshua Nicki , Byrne Linda K.
Published: June 2021

This study set out to examine the associations of certain information communication technology (ICT) factors in the home environment with academic performance. We employed existing data sets collated by Pearson Clinical Assessment in 2016 which included the WIAT-III A&NZ (Wechsler Individual Achievement Test - Australian and New Zealand Standardised, Third Edition) completed by 714 students aged between 4 and 18 years old, and the home environment questionnaire (HEQ) completed by the parents of those children. Sequential multiple regression models were used to analyze the complex interactions between home ICT factors and measures of student reading, writing, mathematical, and oral ability. The findings of this study indicate that after accounting for the known powerful predictors of household income and parental education: (a) a student’s access to an ICT rich home environment, (b) their aptitude in using home ICT, and (c) their recreational use of home ICT, are largely unrelated to academic performance. We observed some small positive correlations between academic performance and child ICT affinity, but also comparably sized negative associations with use of social media and educational TV viewing. Encouragingly, we propose that these findings suggest that increasing levels of ICT use and access in the home are unlikely to be detrimental to academic progress. These results provide important information for parents and educators given the impact of the Coronavirus global pandemic and the near world-wide adoption of ICT for home-schooling.
Explanatory Model of Perceived Stress in the General Population: A Cross-Sectional Study in Peru During the COVID-19 Context
Authors: Boluarte-Carbajal Alicia , Navarro-Flores Alba , Villarreal-Zegarra David
Published: June 2021

Background

The COVID-19 pandemic had negatively impact mental health worldwide. High prevalence of stress had been previously reported in populations during this context. Many theoretical frameworks had been proposed for explaining the stress process, we aim to proposed and explanatory model for the genesis of perceived stress in Peruvian general population.

Method

We conducted an online survey in Peruvian general population assessing sociodemographic variables and evaluating mental health conditions by using The Perceived Stress Scale (PSS-10), Positive Affect and Negative Affect Scale (PANAS), Generalized Anxiety Disorder scale (GAD-7), Patient Health Questionnaire (PHQ-9), and a numerical rating scale (NRS) for fear of COVID-19. Correlation analysis was conducted for the variables of interest. Two regression models were constructed to explore related factor to the dimensions of perceived stress. Finally, a structural regression model was performed with the independent variables.

Results

Data of 210 individuals was analyzed. Ages ranged from 15 to 74 years and 39% were women. Additionally, 65.2% of the participants had at least one mental health conditions (depression, anxiety, or stress symptoms). Perceived self-efficacy and positive affect (PA) were correlated, as perceived helplessness with anxious symptoms and negative affect (NA). Regression analysis showed that sex, anxiety symptoms, and NA explained perceived helplessness while positive and NA explained self-efficacy. The structural regression model analysis identified that fear of COVID-19 (composed of fear of infecting others and fear of contagion), predicted mental health conditions (i.e., depressive or anxiety symptoms); also, mental health conditions were predicted by PA and NA. Perceived helplessness and Perceived self-efficacy were interrelated and represented the perceived stress variable.

Conclusion

We proposed an explanatory model of perceived stress based on two correlated dimensions (self-efficacy and helplessness) in the Peruvian general population during the context of the COVID-19 pandemic, with two out of three individuals surveyed having at least one mental health condition.
Inverse Correlation Between Distress and Performance in the Medical Rescuers Against COVID-19 in Wuhan
Authors: Xie Fang , Wang Xue , Zhao Yun , Wang Shi Da , Xue Cong , Wang Xiao Tian , Chen Yu Xin , Qian Ling Jia
Published: June 2021

Background: During the COVID-19 pandemic, the Chinese government had transferred many medical rescuers to Wuhan, which provided effective support in disease control. The high-intensity working and mental stress during rescue could induce distress and negatively impact the performance of rescuer afterward.

Materials and Methods: To identify the characteristics of stress load and its possible effects on performance, the study surveyed 90 medical rescuers in Wuhan using a mobile phone–based self-rated questionnaire.

Results: The results showed an existence of universal but mostly mild distress in rescuers. About 95.6% of the participants reported that they had at least one symptom of distress, whereas, the median scores were <30 (100 as max). Compared with civilian rescuers, a higher proportion of working with immediate virus contact was found in military medical rescuers (P = 0.008); however, no statistical differences of stress load were found between civilians and militaries. The rescuers with positive cognition or good psychological preparation were found having lower stress loads than other rescuers. An inverse correlation between the stress load and performance (R = −0.24, P = 0.023) and a positive correlation between social support and working performance (R = 0.349, P = 0.001) were found in our survey, suggesting the possible negative effects of stress and the beneficial effects of social support on performance.

Conclusion: Our study indicated that more attention should be paid to the distress of medical rescuers against COVID-19. Positive cognitions, good psychological preparations, and sufficient social support would be necessary to reduce the distress and improve the performance in COVID-19 rescue.
The Psychological Effect of Forming WeChat Groups Between Medical Staff and Patients With COVID-19
Authors: Yuan Li-Ping , Yu Zheng-Hao , Zhang Xian-Cui , Zhang Wei , Jin Ling-Li , Wang Zhen , Yang Jin-Sun , Huang Hou-Bao , Zhang Qu , Tao Xiu-Bin
Published: June 2021

Background: This study was conducted in order to explore the effect of psychological intervention based on the use of WeChat with coronavirus disease 2019 (COVID-19) patients.

Methods: A total of 65 patients with COVID-19, from two wards, were divided into an experimental group and a control group with the ward as the basic unit. Communication concerning routine treatment and nursing was established between the medical staff and patients in the experimental group via WeChat groups. Within 48 h of admission, at 7 days, and on discharge, all 65 patients completed two self-evaluation questionnaires: the Positive and Negative Affect Schedule (PANAS) and the Hospital Anxiety and Depression Scale (HADS). Hospital stay statistics and a satisfaction survey on discharge were also collated for both groups of patients.

Results: The PANAS scores of the experimental group were 26.61 ± 7.99 points on admission, 20.81 ± 5.48 points at 7 days, and 19.58 ± 6.61 points on discharge (P < 0.05). The scores of HADS in the experimental group were 27.74 ± 9.35 points on admission, 12.19 ± 1.92 points at 7 days, and 11.71 ± 3.64 points on discharge (P < 0.05). The differences in the PANS and HADS scores between the experimental and control groups at 7 days and on discharge were statistically significant. The discharge satisfaction ratings of the two groups of patients were 99.87 ± 0.34 and 98.68 ± 1.09 points, the difference being statistically significant (t = 5.827, P < 0.05).

Conclusion: Establishing WeChat groups between medical staff and patients with COVID-19 and building a bridge for better communication improved patients' positive mentality and their compliance with doctors, shortened their hospital stay, and promoted their recovery.
Rapid Point-Of-Care Serology and Clinical History Assessment Increase Protection Provided by RT-PCR Screening: A Pilot Study Involving Three Nursing Homes in Brescia, a Hotspot of Lombardy
Authors: Savio Antonella , Calza Stefano , Guerrini Gianbattista , Romano Valentina , Marchina Eleonora
Published: June 2021

Background: COVID-19 outbursts have been registered worldwide within care homes with asymptomatic transmission combined with shortage/inaccuracy of diagnostic tests undermining the efforts at containment of the disease. Nursing facilities in Lombardy (Italy) were left with no, or limited, access to testing for 8 weeks after the outbreak of COVID-19.

Methods: This study includes 246 residents and 286 workers of three different nursing homes in Brescia-Lombardy. Clinical questionnaires and rapid serology tests were devised to integrate the data of the first available RT-PCR screening. Follow-up serology after 60-days was performed on 67 of 86 workers with positive serology or clinically suspicious.

Findings: Thirty-seven residents and 18 workers had previous positive RT-PCR. Thorough screening disclosed two additional RT-PCR-positive workers. Serology screening revealed antibodies in 59 residents and 48 workers, including 32/37 residents and all workers previously positive at RT-PCR. Follow up serology disclosed antibodies in two additional workers with recent symptoms at the time of screening. The professionals in close contact with residents had more infections (47/226–20.79% vs. 1/60–1.66%; p = 0.00013 Fisher exact-test). A suspicious clinical score was present in 44/64 residents and in 41/50 workers who tested positive with either method with totally asymptomatic disease more frequent among residents 28.1 vs. 10.0% (p = 0.019 Fisher exact-test).

Interpretation: Based on the available RT-PCR ± results at the time of symptoms/contacts, our integrated clinical and serological screening demonstrated sensitivity 89% and specificity 87%. This multimodal assessment proved extremely useful in understanding the viral spread in nursing homes, in defining its stage and in implementing protective measures. Rapid serology tests demonstrated efficient and particularly suited for older people less able to move/cooperate.
“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”
Authors: Swain Susan L. , Kugler-Umana Olivia , Tonkonogy Susan L.
Published: June 2021

As mice age their adaptive immune system changes dramatically, leading to weakened responses to newly encountered antigens and poor efficacy of vaccines. A shared pattern emerges in the aged, with both CD4 T and B cell responses requiring higher levels of pathogen recognition. Moreover, in aged germ-free mice we find accumulation of the same novel age-associated T and B cell subsets that we and others have previously identified using mice maintained in normal laboratory animal housing conditions, suggesting that their development follows an intrinsic program.
Symptom Prediction and Mortality Risk Calculation for COVID-19 Using Machine Learning
Authors: Jamshidi Elham , Asgary Amirhossein , Tavakoli Nader , Zali Alireza , Dastan Farzaneh , Daaee Amir , Badakhshan Mohammadtaghi , Esmaily Hadi , Jamaldini Seyed Hamid , Safari Saeid , Bastanhagh Ehsan , Maher Ali , Babajani Amirhesam , Mehrazi Maryam , Sendani Kashi Mohammad Ali , Jamshidi Masoud , Sendani Mohammad Hassan , Rahi Sahand Jamal , Mansouri Nahal
Published: June 2021

Background: Early prediction of symptoms and mortality risks for COVID-19 patients would improve healthcare outcomes, allow for the appropriate distribution of healthcare resources, reduce healthcare costs, aid in vaccine prioritization and self-isolation strategies, and thus reduce the prevalence of the disease. Such publicly accessible prediction models are lacking, however.

Methods: Based on a comprehensive evaluation of existing machine learning (ML) methods, we created two models based solely on the age, gender, and medical histories of 23,749 hospital-confirmed COVID-19 patients from February to September 2020: a symptom prediction model (SPM) and a mortality prediction model (MPM). The SPM predicts 12 symptom groups for each patient: respiratory distress, consciousness disorders, chest pain, paresis or paralysis, cough, fever or chill, gastrointestinal symptoms, sore throat, headache, vertigo, loss of smell or taste, and muscular pain or fatigue. The MPM predicts the death of COVID-19-positive individuals.

Results: The SPM yielded ROC-AUCs of 0.53–0.78 for symptoms. The most accurate prediction was for consciousness disorders at a sensitivity of 74% and a specificity of 70%. 2,440 deaths were observed in the study population. MPM had a ROC-AUC of 0.79 and could predict mortality with a sensitivity of 75% and a specificity of 70%. About 90% of deaths occurred in the top 21 percentile of risk groups. To allow patients and clinicians to use these models easily, we created a freely accessible online interface at www.aicovid.net.

Conclusion: The ML models predict COVID-19-related symptoms and mortality using information that is readily available to patients as well as clinicians. Thus, both can rapidly estimate the severity of the disease, allowing shared and better healthcare decisions with regard to hospitalization, self-isolation strategy, and COVID-19 vaccine prioritization in the coming months.
The Promise of the Dual Prevention Pill: A Framework for Development and Introduction
Authors: Friedland Barbara A. , Mathur Sanyukta , Haddad Lisa B.
Published: June 2021

Women of reproductive age need multipurpose prevention technology (MPT) products to address two overlapping health risks: unintended pregnancy and HIV. Currently, condoms are the only available MPT, however male condoms are not within the control of a woman, and the use of female condoms has been limited by low acceptability and cost. Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, yet uptake and adherence among women have been low to date. Women globally need more options for HIV and pregnancy prevention. Several MPTs for simultaneous HIV and pregnancy prevention are in various stages of development and clinical testing, although most are many years away from market launch. A dual prevention pill (DPP), a daily oral pill combining oral contraceptives and PrEP, both of which are licensed, approved products in many low- and middle-income countries (LMIC), is likely to be the fastest route to getting an MPT product into the hands of women. The DPP is one option that could enhance method choice, particularly for women who are already using oral contraceptives. By leveraging the oral contraceptive market and reaching women currently using condoms or with an unmet need for contraception, the DPP has the potential to increase the uptake of PrEP. The successful rollout of the DPP will require careful consideration of user-, provider-, and product-centered factors during product development and introduction. Early attention to these interrelated factors can help ensure that the DPP has the ideal characteristics for maximum product acceptability, that effective and quality services are designed and implemented, and that users can make informed choices, demand the product, and use it effectively. The proposed framework outlines key considerations for the effective development and introduction of the DPP, which could also facilitate integration models for future MPTs.
Acceleration of Charged Particles in Astrophysical Plasmas
Authors: Liu Siming , Jokipii J. Randy
Published: June 2021

The origin of high-energy particles in the Universe is one of the key issues of high-energy solar physics, space science, astrophysics, and particle astrophysics. Charged particles in astrophysical plasmas can be accelerated to very high energies by electric fields. Based on the characteristics of interactions between charged particles and electric fields carried by the background plasma, the mechanisms of charged particle acceleration can be divided into several groups: resonant interactions between plasma waves and particles, acceleration by electric fields parallel to magnetic fields, and acceleration caused by drift of the guiding center of particle gyro-motion around magnetic fields in magnetic field in-homogeneity-related curvature and gradient, etc. According to macroscopic energy conversion mechanisms leading to acceleration of particles, several theories of particle acceleration have been developed: stochastic particle acceleration by turbulent electromagnetic fields, diffusive shock acceleration of particles, and particle acceleration during magnetic re-connections. These theories have their own assumptions and characteristics and find applications in different astrophysical contexts. With advances in high-energy astrophysical observations and in combination with analyses of characteristics of high-energy particle acceleration and radiation, we can better understand the underlying physical processes in dramatically evolving astrophysical environments.
Whole Genome or Single Genes? A Phylodynamic and Bibliometric Analysis of PRRSV
Authors: Frias-De-Diego Alba , Jara Manuel , Pecoraro Brittany M. , Crisci Elisa
Published: June 2021

Diversity, ecology, and evolution of viruses are commonly determined through phylogenetics, an accurate tool for the identification and study of lineages with different pathological characteristics within the same species. In the case of PRRSV, evolutionary research has divided into two main branches based on the use of a specific gene (i.e., ORF5) or whole genome sequences as the input used to produce the phylogeny. In this study, we performed a review on PRRSV phylogenetic literature and characterized the spatiotemporal trends in research of single gene vs. whole genome evolutionary approaches. Finally, using publicly available data, we produced a Bayesian phylodynamic analysis following each research branch and compared the results to determine the pros and cons of each particular approach. This study provides an exploration of the two main phylogenetic research lines applied for PRRSV evolution, as well as an example of the differences found when both methods are applied to the same database. We expect that our results will serve as a guidance for future PRRSV phylogenetic research.
Ornithodoros puertoricensis (Ixodida: Argasidae) Associated With Domestic Fowl in Rural Dwellings From Córdoba Department, Caribbean Colombia
Authors: López Yesica , Robayo-Sánchez Laura Natalia , Muñoz-Leal Sebastián , Aleman Ader , Arroyave Esteban , Ramírez-Hernández Alejandro , Cortés-Vecino Jesús Alfredo , Mattar Salim , Faccini-Martínez Álvaro A.
Published: June 2021

Ticks of genus Ornithodoros are nidicolous parasites associated with a wide array of vertebrates. In humans, their bites cause hypersensitivity reactions and are capable to transmit pathogens of health concern. In the department of Córdoba, Caribbean region of Colombia, the first report of an Ornithodoros soft tick was made in 1980 by Betancourt, who described the collection of Ornithodoros talaje in human dwellings. Nevertheless, current the records of O. talaje made in South America have been questioned and likely correspond to misidentifications with morphologically similar species. Between October and December of 2020, we visited rural areas of four localities from three municipalities within the department of Córdoba: Cuero Curtido and Severá (municipality of Cereté), El Espanto (municipality of Planeta Rica), and Arroyo Negro (municipality of San Carlos). Search for soft ticks was performed in 46 human domiciles and peridomiciliary areas. We searched in areas frequented by domestic animals, inspecting cracks in the walls and fowl nests. Infestation by soft ticks was found in 13% (6/46) of visited houses. Overall, 215 ticks were collected (26 larvae, 144 nymphs and 45 adults) from nests of domestic birds or in the adjacent walls. Larvae, nymphs and adults were morphologically identified as Ornithodoros puertoricensis. Molecular identification of ticks was confirmed by sequencing the tick mitochondrial 16S gene of adults, pools of nymphs and larvae. Pairwise comparisons showed a 99% of identity with O. puertoricensis from Panama. This study reports for the first time O. puertoricensis associated with domestic fowl in rural dwellings in Colombia, and expands the geographical distribution of this tick species toward the Córdoba department. Importantly, local people described exposure to tick bites while sleeping in infested houses; therefore, the transmission of soft tick-borne pathogens is now of concern in the region.
Use the Force: Review of High-Rate Actuation of Shape Memory Alloys
Authors: Dana Asaf , Vollach Shahaf , Shilo Doron
Published: June 2021

Typical shape memory alloy actuators provide a unique combination of large stresses and strains that result in work-per-volume larger by more than two orders of magnitude than all other actuation methods that are based on active materials. High-rate actuation of shape memory alloys can provide improved energy efficiency, and shorter response and total actuation times, along with large travel-per-wire-length, with respect to slow-rate SMA applications. In this article, we review the different aspects of high-rate actuation of shape memory alloy wires in the high-driving-force regime. We briefly survey previous experimental results about the kinetics and thermodynamics of the phase transformation in view of its practical implications. New experimental results, regarding energy efficiency, total actuation time, repeatability, and fatigue, are presented and discussed. The paper provides general design guidelines for obtaining high actuator performance, as well as guidelines for selecting the source of the electric pulse and its parameters. Finally, we construct and solve detailed simulations of actuator response that can serve as accurate design tools.
Freshwater Cladophora glomerata Biomass as Promising Protein and Other Essential Nutrients Source for High Quality and More Sustainable Feed Production
Authors: Nutautaitė Monika , Vilienė Vilma , Racevičiūtė-Stupelienė Asta , Bliznikas Saulius , Karosienė Jūratė , Koreivienė Judita
Published: June 2021

A scientific justification, focused on the development of the sustainability of feed ingredients and farm animals’ ecosystems, is required. Thus, it is crucial to search for alternative feed materials from natural sources for potential applications. The aim of this study was to evaluate the prospective utilization of freshwater Cladophora glomerata (C. glomerata) as an alternative source of protein and other essential nutrients in animals’ feed. For this purpose, chemical analysis was performed on collected biomass samples from the Lithuanian rivers, Dubysa (B1), Šventoji (B2), Nevėžis (B3), and Jūra (B4). Microelements (Ca > K > N > P > Mg), trace elements (Zn > Cu), and heavy metals (Cr > Ni > Pb > Cd) have not exceeded permissible levels. The crude protein content of C. glomerata biomass ranged from 16% to 21.5% DM. The essential amino acid profile excelled, with the highest total amino acid amount of 140.99 g/kg in B4. The highest total presence of polyunsaturated fatty acids (11.71%) as well as the ratio of polyunsaturated to saturated fatty acids (0.22) was observed in B1. The lowest ratio of omega-6/omega-3 was in B1 (1.30). As a result of bioaccumulation, C. glomerata could serve as a source of proteins, as well as amino and fatty acids, implying that biomass could be an alternative and a beneficial component of animal feed.
Soil Health Evaluation of Farmland Based on Functional Soil Management—A Case Study of Yixing City, Jiangsu Province, China
Authors: Zhao Rui , Wu Kening
Published: June 2021

Given that farmland serves as a strategic resource to ensure national food security, blind emphasis on the improvement of food production capacity can lead to soil overutilization and impair other soil functions. Hence, the evaluation of soil health (SH) should comprehensively take soil productivity and ecological environmental effects into account. In this study, five functions from the perspective of functional soil management were summarized, including primary productivity, provision and cycling of nutrients, the provision of functional and intrinsic biodiversity, water purification and regulation, and carbon sequestration and regulation. For each soil function, in view of the natural and ameliorable conditions affecting SH, basic indicators were selected from the two aspects of inherent and dynamic properties, and restrictive indicators were chosen considering the external properties or environmental elements, with the minimum limiting factor method coupled with weighted linear model. The new evaluation system was tested and verified in Yixing City, China. The healthy and optimally functional soils were concentrated in the northeast and mid-west of Yixing City, whereas unhealthy soils were predominant in the south and around Taihu Lake. The main limitations to SH improvement included cation exchange capacity, nutrient elements, and soluble carbon. The SH evaluation method was verified using the crop performance validation method, and a positive correlation was noted between food production stability index and soil health index, indicating that the evaluation system is reasonable.
Critical Time for Weed Removal in Corn as Influenced by Planting Pattern and PRE Herbicides
Authors: Nedeljković Dejan , Knežević Stevan , Božić Dragana , Vrbničanin Sava
Published: June 2021

Determining the critical time for weed removal (CTWR) is essential for the development of an integrated weed management plan. Therefore, field experiments were conducted to evaluate the effects of two planting patterns (standard and twin-row) with and without PRE-applied herbicides on CTWR in corn. Experiments were laid out in a split-plot arrangement with two main plots: (i) standard row planting (SRP) that is 70 cm wide, and (ii) twin-row planting (TRP) with 50 cm distance between each set of double rows. Each main plot was divided into two sub-plots (with and without PRE herbicides). The sub-sub-plots consisted of seven weed removal timings for PRE herbicides, and tank mixes were utilized (S-metolachlor (1.44 kg a.i. ha−1) + terbutylazine (0.75 kg a.i. ha−1)). The CTWR without PRE herbicides was similar in both the SRP and TRP systems, where it was around the V1 to V2 (16 to 19 d after emergence (DAE)) growth stages. The use of PRE-applied herbicides delayed CTWR in SRP to the V4 to V10 (25 to 58 DAE) stages and up to the V11 (60 DAE) stage in TRP. These results clearly indicate that PRE herbicides are important for protecting corn yields regardless of the planting pattern. In more meteorologically favorable seasons (sufficient heat and precipitation) in both sowing systems, corn plants produce their biological maximum with the fact that over the number of plants per unit area (SRP = 80,000 plants ha−1, TRP = 93,900 plants ha−1) provide higher yields in variants with PRE herbicides, and thus the advantage of the TRP system can be justified.