bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Pharmacological Investigation into the Mechanism of Kaixinsan Powder for the Treatment of Depression
Authors: Du Li-Jing , Zhang Xin-Ning , Li Sha-Sha , Sun Yuan-Fang , Jin Hui-Zi , Yan Shikai , Han Chuan-Gang 
Published: May 2022

Abstract
Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the “herb-component-target” network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The “herb-component-target” network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, were identified in KXS, which could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).
Preparing Future Clinicians for Virtual Visiting: A Qualitative Descriptive Study
Authors: Clarke Kirsty , Borges Karen , Richardson Lauren , Taylor Jessica , Evans Robyn , Chung Bethany , Cleverdon Harriet , Xyrichis Andreas , Cook Amelia , Meyer Joel , Rose Louise , Hatab Sultan 
Published: April 2022

Abstract
BackgroundIn many UK hospitals, the COVID-19 pandemic and visiting restrictions prevented families from seeing their critically ill relatives. Consequently, strategies for virtual family communication have had a rapid and pervasive integration. Our objective was to explore the experiences of newly-graduated doctors carrying out virtual visits during the pandemic, with the view to better inform the family communications training currently provided to medical students.MethodsWe conducted a qualitative descriptive study using in-depth, semi-structured interviews and thematic analysis to explore the experiences of newly-graduated junior doctors who worked as family communication officers, facilitating virtual visiting, during the first wave of the COVID-19 pandemic (April to July 2020). Interviews lasted between 35-40 minutes, were digitally recorded and professionally transcribed. Interview transcripts were analysed thematically; NVivo software was used for data management. ResultsWe recruited 8 newly-graduated doctors; 7 female, 1 male, with ages ranging from 23-27. Three main themes were carried through the participants’ experiences. The first theme “emotional demands'', describes the participants’ emotional response to working in busy ICUs during the pandemic, where the demand for virtual visits was vast, and the participants' exposure to relatives’ grief was overwhelming. The second theme illustrates the process by which participants rapidly acquired and honed new skills to successfully deliver family communication through a virtual platform. With the third theme of “resilience,” we learn about the sources of motivation participants tapped into to sustain working in the emotionally charged role of a pandemic family communication officer.ConclusionThis qualitative study highlights the combined emotional and technical challenges experienced by non-ICU-trained junior doctors working in a family communication role using virtual technology during the COVID-19 pandemic. We recommend the incorporation of virtual communication skills training into educational practice to better prepare the next generation of doctors for a new era of virtual family communication.
Effects of the exercise-inducible myokine irisin on proliferation and malignant properties of ovarian cancer cells through the HIF-1 α signaling pathway
Authors: Zarei Marziyeh Alizadeh , Hosseini Elahe Seyed , Kashani Hamed Haddad , Ahmad Ejaz , Aslanbeigi Fatemeh , Nikzad Hossein 
Published: May 2022

Abstract
Background
Exercise has been shown to be associated with reduced risk and improving outcomes of several types of cancers. Irisin -a novel exercise-related myokine- has been proposed to exert beneficial effects in metabolic disorders including cancer. No previous studies have investigated whether irisin may regulate malignant characteristics of ovarian cancer cell lines.
Methods
In the present study, we aimed to explore the effect of irisin on viability and proliferation of ovarian cancer cells which was examined by MTT assay. Then, we evaluated migratory and invasive ability of the cells via transwell assays. Moreover, the percentage of apoptosis induction was determined by flowcytometery. Furthermore, the mRNA expression level of genes related to the aerobic respiration (HIF-1α, c-Myc, LDHA, PDK1 and VEGF) were detected by real-time PCR.
Results
Our data revealed that irisin treatment significantly attenuated the proliferation, migration and invasion of ovarian cancer cells. Besides, irisin induced apoptosis in ovarian cancer cells. We also observed that irisin regulated the expression of genes involved in aerobic respiration of ovarian cancer cells.
Conclusion
Our results indicate that irisin may play a crucial role in inhibition of cell growth and malignant characteristics of ovarian cancer. These findings may open up avenues for future studies to identify the further therapeutic use of irisin in ovarian cancer management.
Impact of COVID-19 Pandemic on Foot Care Services in Ontario, Canada
Authors: Lu Suzanne , McLaren Ann-Marie , Pinsker Ellie 
Published: April 2022

Abstract
BACKGROUND: The COVID-19 pandemic has directly affected the delivery of health care services in Canada, including foot care. The goal of this descriptive study was to understand the impact of the early COVID-19 pandemic (March 2020 to April 2021) on chiropodists’ and podiatrists’ clinical practices and foot care service delivery in Ontario, Canada. METHODS: A web-survey was completed by participating chiropodists and podiatrists registered with the College of Chiropodists of Ontario. The survey consisted of 31 multiple choice and open-ended items on clinical practice characteristics, foot care service delivery changes, perceived barriers during the pandemic, and its impact on clinicians. Descriptive statistics were used to characterize the sample and examine clinicians’ responses, and qualitative content analysis was used to explore opened-ended items.RESULTS: Of the 773 eligible clinicians, 279 participated for a response rate of 36.1%. Most respondents reported a decline in patient volume, an increase in urgent foot health problems, a financial impact on their clinical practices, an emotional impact, and substantial changes to how they provided foot care services. Factors that impact clinicians’ perception of future pandemic preparedness are identified.CONCLUSION: This study describes foot care service delivery in Ontario, Canada during the COVID-19 pandemic. The COVID-19 pandemic saw an increase in urgent foot health problems, decline in patient volume, and impacted clinicians’ mental health and emotional well-being. Future studies should examine patients’ experiences of foot care service delivery and maintaining their foot health during the pandemic, and further examination of factors that impact clinicians' perception of pandemic preparedness.
Risk Factors of Poor Fitting for a New Orthokeratology Lens: a case control study
Authors: Liu LF , Wang G , XH Lu , Luo L , QM Wang , JC Lin , MZ Zhang 
Published: May 2022

Abstract
Background: The purpose of this study is to compare differences between the good and poor fitting group in Orthokeratology patients and look for risk factors of poor fitting.Methods: A total of 382 eyes (216 patients) were retrospectively analyzed. Eyes being enrolled were 41 (24 patients) and 36 (22 patients) in the good fitting and poor fitting group. Re-fitting time, reason, lens parameters before and after re-fitting were assessed in the poor fitting group. Patients information, refractive outcomes, topography and lens parameters were compared between the two groups. Risk factors and diagnostic value of each risk factor were discovered for poor fitting. Results: (1) There were no significant differences in age (p=0.209), sex (p=0.376) and eye (p=0.649) between the two groups; (2) The median re-fitting time was 6.5 weeks (range: 2-28 weeks). Main reasons for re-fitting were lens binding and unsatisfactory uncorrected visual acuity; (3) After re-fitting, lens type (p=0.415), toric value (p=0.747), and alignment curve (AC) (p=0.050) remained unchanged, but lens diameter decreased (10.64±0.20mm vs 10.53±0.24mm, p=0.002), the proportion of lens with a diameter less than 10.6mm increased (p=0.020); (4) Spherical refraction (p=0.004), refractive astigmatism (p<0.001), flat k (p<0.001), steep k (p<0.001), corneal astigmatism (p=0.048), and AC (p<0.001) differed significantly between the two groups; (5) Steep K (B=-0.960, p=0.001), refractive astigmatism (B=1.646, p=0.015) and lens diameter (B=-3.744, p=0.040) were independent risk factors for poor fitting. Steep k has the most valuable diagnostic value, with a cut off value of 44.69 (sensitivity 0.69, specificity 0.85). Conclusions: The main reasons for re-fitting were lens binding and unsatisfactory uncorrected visual acuity. Steep K, refractive astigmatism and lens diameter were independent risk factors of poor fitting. The strongest diagnostic value was steep K. Patients with a steep k<44.69 are good candidate for lens fitting . When fitting this brand of Ortho-k lens, the lens diameter should not be too large.
METTL3 promotes esophageal squamous cell carcinoma progression through the GLUT4-mTORC1 axis
Authors: Zhou Xi , Zhong Xiaowu , Gao Chuanli , Chen Xin , Zou Jiang , Li Qingrong , Cheng Jibing , Yuan Zichun , Wang Qing , Yang Miyuan , Xu Lei , Ma Qiang , Guo Xiaolan 
Published: April 2022

Abstract
Background: Methyltransferase-like 3 (METTL3) is an essential methyltransferase for N6-methyladenosine (m6A) modification that participates in the pathogenesis of various malignancies including esophageal cancer. Yet, its mechanism of action is still not very clear. In this study, we hypothesized that METTL3 might control the progression of esophageal squamous cell carcinoma (ESCC) by regulating its glycolysis metabolism.Methods: The expression and role of METTL3 in ESCC were elucidated based on the TCGA database. METTL3 expression in ESCC tissues was validated by immunohistochemical assay (IHC). The Cell Counting Kit-8 (CCK8), colony formation assay, wound healing, and cell migration assays were used to analyze the efﬁcacy of targeting METTL3 on ESCC proliferation and migration in ESCC cell overexpressing METTL3 or with METTL3 knockdown. The biological mechanisms of METTL3 in glycolysis metabolism of ESCC were evaluated using western blot and quantitative real-time PCR (qRT-PCR).Results: METTL3 was signiﬁcantly upregulated in ESCC both in the TCGA database and our cohort. Functionally, knockdown of METTL3 repressed ESCC cell proliferation and migration in vitro, while these phenomena were reversed after METTL3 was overexpressed in ESCC cells. In addition, METTL3 interacted with and mediated the glucose uptake and lactate production of ESCC cells. Intriguingly, METTL3 epigenetically regulated GLUT4 expression and lactate production, thereby activating the mTORC1 signaling pathway. Moreover, in METTL3-depleted ESCC cells, inhibiting mTORC1 had a significant anticancer effect.Conclusion: METTL3 is an oncogenic gene that can promote ESCC tumorigenesis via the GLUT4-mTORC1 axis, thus representing a promising therapeutic target for ESCC.
A Risk Model Based on Tumor Microenvironment to Predict Survival and Immunotherapy Efficacy for Ovarian Cancer
Authors: Song Junwei , Wang Yaru , Wu Wenlong , Li Wan , Liu Zengyou 
Published: May 2022

Abstract
Background:Ovarian cancer(OC) is the most lethal carcinoma among all gynecological malignancies.Based on the continued understanding of interaction relationships between immune components in tumor microenvironment (TME) and OC cells,immunotherapies have demonstrated to be dramatically effective in increasing survival rates.This research aims to construct a risk model and identify landmark genes which are of vital importance to improve the prognosis of OC. Methods:The gene expression data of 379 OC patients were extracted from The Cancer Genome Atlas(TCGA) database,and immune and stromal related genes were analyzed by difference analysis and weighted correlation network analysis (WGCNA).Subsequently,univariate and multivariate Cox regression analyses were used to build an risk model for OC.Kaplan-Meier survival curves were then taken to depict survival difference between high- and low-risk subgroups.Meanwhile,receiver operating characteristic (ROC) curves and the nomograms were applied to assess the accuracy and validity of the model.Finally,differentiation of immune cells,immune checkpoint molecules,and biological functions between high- and low-risk categories were identified to predict immunotherapy efficacy for OC.Results:GIMAP7,HTRA4,CCL5,ICOS,CD40LG,CD3G,VSIG4,CD2,ANKRD22 were obtained to construct the prognosis risk model;high risk score was an prognosis factor of poor survival rate of OC patients.Further ROC curve and nomogram analyses showed that this model exhibited excellent performance in predicting the 1-,3-,and 5-year survival rate.We obtained 17 functional immune cells,17 immune checkpoint molecules,several immune-related reactions,and GO items which might change the prognosis of OC patients.Conclusions:The 9-genes prognostic model may play critical roles as potential prognostic markers and offer personalized immunotherapy protocols for OC and may provide a theoretical foundation for new immunotherapy combinations.
The Dynamic Intermediate Convective Toroidal Trigger and the Solar Magnetic Field Flip Problem
Authors: Ziegler Martin 
Published: April 2022

Abstract
The sun flips its magnetic field intermittently roughly every 11 years because of a triggering dynamic intermediate axis formed by the outer convective zone. Following the wedge sunspot model, it can heuristically be shown that the emergence of sun spots changes the mass distribution of the equator region relative to the polar region. Considering Poinsot's theorem, this results in a flipping motion of the semisolid convective zone and its magnetic field near surface, temporarily enhancing toroidal fields underneath. Due to an elevated steady energy state, the magnetic field in the inner convective zone sequentially flips as well. Elaborate calculations based on accepted mass density estimations illustrate the triggering flip. Furthermore, two perpendicular dynamic smallest axes can occur which might explain the Dalton-Minimum. Consequently, a self-regulating solar energy feedback mechanism is conjectured.
Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism
Authors: Kiamanesh Omid , Prosperi-Porta Graeme , Harper Lea , Solverson Kevin , Boiteau Paul , Helmersen Doug , Ferland André , Fine Nowell , Weatherald Jason 
Published: April 2022

Abstract
Purpose
During acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE.
Methods
We assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and right ventricular fractional area change (FAC)/PASP as well as stroke volume index (SVI)/PASP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis.
Results
In 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1mm/mmHg decrease in TAPSE/PASP the odds of an adverse event increased by 2.5-fold (adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46–4.24, p = 0.001), for every 0.1%/mmHg decrease in FAC/PASP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09–1.86, p = 0.010), and for every 0.1mL/mmHg•m2 decrease in SVI/PASP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72–4.50, p < 0.001). In multivariate analysis, TAPSE/PASP and SVI/PASP were independent of other risk stratification methods including computed tomography-derived RVD, the Bova score, and subjective assessment of TTE-derived RVD.
Conclusion
In patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are strongly associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD.
Lightweight Human Pose Estimation Algorithm Based on Polarized Self-Attention
Authors: Shengjie Liu , Ning He , Cheng Wang , Haigang Yu , Wenjing Han 
Published: April 2022

Abstract
In recent years, human pose estimation has been widely used in human-computer interaction, augmented reality, video surveillance, and many other fields, but the task of pose estimation still faces many challenges. To address the large number of parameters and complicated calculation in the current mainstream human pose estimation network, this paper proposes a lightweight pose estimation network (Lightweight Polarized Network, referred to as LPNet) based on a polarized self-attention mechanism. First, ghost convolution is used to reduce the number of parameters of the feature extraction network; second, by introducing the polarized self-attention module, the pixel-level regression task can be better solved, the lack of extracted features due to the decrease in the number of parameters can be reduced, and the accuracy of the regression of human keypoints can be improved; finally, a new coordinate decoding method is designed to reduce the error in the heatmap decoding process and improve the accuracy of keypoint regression. The method proposed in this paper was evaluated on the human keypoint detection datasets COCO and MPII, and compared with the current mainstream methods. The experimental results show that the proposed method greatly reduces the number of parameters of the model while ensuring a small loss in accuracy.
Identification of a novel necroptosis-related lncRNA-based prognostic model and immunological characteristics of Lung Adenocarcinoma
Authors: Xia Peng , Wang Degui , Shen Rong , Guo Zhao , Ouyang Siwei , Yang Xuguang , Liu Xiangwen , Xie Kun 
Published: April 2022

Abstract
Lung adenocarcinoma (LUAD) is one of the most common pathological types of lung malignant tumor with high morbidity and mortality. LncRNAs are gradually recognized to play crucial roles in tumor occurrence and development. Necroptosis is a newly established way for cell programmed death, undertaking essential roles in anti-tumor. Therefore, identifying necroptosis-related lncRNAs and based on them to evaluate the signatures of LUAD is essential for patients’ survival prediction and therapy. This study identified 41 lncRNAs related to LUAD patients’ prognosis and necroptosis from The Cancer Genome Atlas (TCGA). Particularly, a 13-lncRNAs (LINC02693, FGD5-AS1, TMPO-AS1, LINC01116, LINC02802, RHOQ-AS1, LINC02273, LINC01800, LINC00996, CADM3-AS1, SFTA3, CRNDE, PARP11-AS1) prognostic model was constructed via LASSO regression based on these 41 lncRNAs. The model’s prediction accuracy was evaluated by receiver operating characteristic (ROC) and independent-prognosis analysis; besides, a Gene Expression Omnibus (GEO) dataset was applied for external validation. In addition, we also implemented a consensus clustering analysis based on the 41 genes to separate LUAD patients into two subgroups. We compared the features of subgroups in multiple dimensions, including survival, immune microenvironment, immune cells infiltration, and gene co-expression network analysis. Based on this study, we established a prognosis necroptosis-related risk model to predict LUAD patients’ prognosis and systematically understood the correlation between immune and necroptosis. This study can applicate in clinical to predict the prognosis of LUAD patients and provide new insight into LUAD immune therapy.
Calcineurin signaling promotes Takotsubo cardiomyopathy
Authors: Bruns Bastian , Antoniou Marilena , Baier Irena , Sevinchan Meryem , Moog Marie-Christine , Joos Maximilian , Dieterich Christoph , Khan Hilal , Wilson Heather , Dawson Dana , Frey Norbert , Schultz Jobst-Hendrik , Backs Johannes 
Published: May 2022

Abstract
Aims: Takotsubo cardiomyopathy (TTC) presents an acute heart failure (AHF) syndrome that mimics the symptoms of acute myocardial infarction and is often preceded by an episode of emotional and/or physical stress. There is no specific treatment available, and evidence is based mostly on retrospective data. Here, we show that a high-dose of epinephrine (EPI) recapitulates numerous features of human TTC in mice, enabling genetic KO studies. By gene set enrichment network analysis and studies involving myocardial KO of the endogenous calcineurin inhibitor calcium-calmodulin-dependent kinase II (CaMKII), we identify cyclosporine A (CSA) as a novel potential therapy for TTC.Methods and results: high-dose EPI caused reversible AHF with significant ST-segment changes and high-sensitive Troponin T (hs-TnT) elevation. Male mice displayed markedly elevated hs-TnT and mortality when compared to females, mimicking the clinical syndrome. Left ventricular (LV) catecholamines revealed a distinct pattern of blunted norepinephrine as opposed to elevated EPI in male vs. female mice. Gene set enrichment analysis of LV RNA-sequencing after EPI revealed calcineurin-dependent pro-inflammatory gene networks to be significantly enriched, particularly in male hearts. Cardiac-specific deletion of CaMKII caused exacerbated AHF and myocardial damage, that was attenuated by CSA. In human peripheral blood mononuclear cells from TTC patients, expression of the calcineurin reporter regulator of calcineurin 1 isoform 4 (rcan1-4) was significantly increased compared to age- and gender matched controls, indicating human relevance of this pathway.Conclusion: Combining TTC disease modeling and mouse genetics identified calcineurin inhibition as a novel specific therapeutic concept to treat human TTC.