bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of CTC enrichment by GPC3-IML and its genetic analysis in hepatocellular carcinoma
Authors: Yi Bin , Wu Tian , Zhu Nan , Huang Yao , Yang Xiaoyu , Yuan Lei , Wu Yingjun , Liang Xiaofei , Jiang Xiaoqing 
Published: March 2021

AbstractBackgroundThis research was to develop a special method for enriching Circulating tumor cells (CTCs) of Hepatocellular carcinoma (HCC) by Glypican-3 immunoliposomes (GPC3-IML), and to analyze the correlation between the CTCs count and tumor malignancy, as well as to investigate the mutation characteristics of CTC-derived NGS.ResultsIn this study characterization of physical parameters was performed with the preparation of GPC3-IML. CTCs in peripheral blood of HCC patients were further separated and identified. Immunofluorescence was used to identify CTCs for further counting. By this means, the correlation between CTCs count and clinicopathological features was analyzed, and the genetic mutation characteristics of NGS derived from CTCs were investigated and compared with that of tissue NGS. Results showed that compared with EpCAM and vimentin, GPC-3 had a stronger CTCs separation ability. There was a correlation between "positive" count of CTCs (≥ 5 PV-CTC per 7.5 ml blood) and BCLC stage (P = 0.055). The result of CTC-NGS was consistent with that of tissue-NGS in 60% cases, revealing thatKMT2Cwas a common highly-frequent mutated gene.ConclusionThe combination of immunomagnetic separation of CTCs and anti-tumor marker identification technology can be regarded as a new technology of CTCs detection in peripheral blood of patients with HCC.Trial registrationEHBHKY2020-k-024. Registered 17 August 2020—Retrospectively registered
Cross-cultural adaptation, validity and reliability of the Chinese Version of Miller Behavioral Style Scale
Authors: Zhuo Qiqi , Cui Changsheng , Liang Hongmin , Bai Yangjuan , Hu Qiulan , Hanum Ardani Latifah , Yang Mingfang , Wang Yanjiao , Wei Wei , Ding Lan , Ma Fang 
Published: March 2021

Abstract
Background
Health education basing on patients’ information-seeking styles can improve the effectiveness of health education and patients’ health outcomes. The Miller Behavioral Style Scale (MBSS) is widely used to identify individual’s information-seeking styles, but the Chinese version is lacking. The study aim was to translate and culturally adapt the MBSS into Chinese version and test the content validity, construct validity and internal consistency reliability of the Chinese version of MBSS (C-MBSS).

Methods
The forward-back-translation procedure was adopted in the translation of the MBSS. Content validity was assessed in a panel of experts. In a sample of 1343 individuals including patients, patients’ caregivers, university students, and medical staff, reliability and construct validity were assessed using Cronbach’s alpha coefficient and factor analysis. The measurement invariance across samples was tested using multigroup confirmatory factor analysis (MGCFA). Floor and ceiling effects were checked.

Results
The C-MBSS achieved conceptual and semantic equivalence with the original scale. The item-level content validity index (I-CVI) of each item ranged from 0.78 to 1, and the averaging scale-level content validity index (S-CVI/ Ave) was 0.95. The exploratory factor analysis resulted in 2-factor assumption for each hypothetical threat-evoking scenario. Confirmatory factor analysis demonstrated a good fit between theoretical model and data, which provided confirmatory evidence for the second-order factor structure of 2-factor solution (Monitoring and Blunting). The Cronbach's alpha coefficients for the Monitoring and Blunting sub-scales of the C-MBSS were 0.75 and 0.62 respectively. MGCFA results supported the measurement invariance for the Monitoring sub-scale of the C-MBSS across samples. No floor or ceiling effects occurred.

Conclusions
This study indicates that the C-MBSS has good content and construct validity. The Monitoring sub-scale of the C-MBSS had acceptable internal consistency reliability while the Blunting sub-scale had unsatisfactory one, which suggest that the Monitoring sub-scale of the C-MBSS can be used to identify individuals’ information-seeking styles in Chinese contexts across different populations.
Identification of the Urogenital Distress Inventory-6 and the Incontinence Impact Questionnaire-7 cutoff scores in urinary incontinent women
Authors: Skorupska Katarzyna , Grzybowska Magdalena Emilia , Kubik-Komar Agnieszka , Rechberger Tomasz , Miotla Pawel 
Published: March 2021

Abstract
Purpose
Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire-7 (IIQ-7) and The International Consultation on Incontinence (ICIQ-SF) Short Form are used to diagnose individuals with urinary incontinence (UI) and to assess the impact of the dysfunction on patient quality of life. While ICIQ-SF has fixed cutoff values—UDI-6 and IIQ-7 do not. We aimed to find the cutoff scores for UDI-6 and IIQ-7 in women with UI.

Methods
The study involved 205 women aged between 31 and 83 years—155 with, and 50 without UI symptoms. All participants completed all three questionnaires: ICIQ-SF, UDI-6 and IIQ-7. Patients were categorized according to their ICIQ-SF scores, as symptomatic ICIQ-SF ≥ 6 (n = 134) and asymptomatic ICIQ < 6 (n = 60). The Receiver Operating Characteristics (ROC) curve was used to test how well UDI-6 allowed a discrimination between patients suffering from UI and those who do not. Area under Curve (AUC) statistic was calculated to measure the UDI-6 and IIQ-7 Total Score efficiency.

Results
The cutoff values were selected. On the basis of the ROC curve analysis, the UDI-6 Total Score of 33.33 and IIQ-7 Total Score of 9.52 were determined to be the optimal cutoff for distinguishing between symptomatic and asymptomatic women (AUC = 0.94-UDI-6 and 0.91-IIQ-7).

Conclusions
For UDI-6 scores more than 33.33 indicate higher distress caused by UI symptoms. Moreover, the higher impact of UI on health- related quality of life is seen in women who scored 9 or more in the IIQ-7 questionnaire, and such women felt impaired quality of life.
Trial registration number NCT04433715, 11.06.2020 “retrospectively registered”.
Impacts of Cyclosporin A on clinical pregnancy outcomes of patients with a history of unexplained transfer failure: a retrospective cohort study
Authors: Qu Danni , Tian Xiangming , Ding Ling , Li Yuan , Zhou Wenhui 
Published: March 2021

AbstractBackgroundA rapid development in assisted reproductive technology (ART) has led to a surge in its popularity among target couples. However, elucidation on the molecular mechanism and effective solutions for a common problem posed by ART, namely transfer failure, is still lacking. The new therapeutic potential of cyclosporin A (CsA), a typical immunosuppressant widely used in the treatment of rejection after organ transplantation, in recurrent pregnancy loss (RPL) patients may inspire some novel transfer failure therapies in the future. To further explore the clinical effects of CsA, this study investigated whether its application can improve clinical pregnancy outcomes in patients with a history of unexplained transfer failure in frozen-thawed embryo transfer (FET) cycles.MethodsData from a retrospective cohort investigation (178 frozen-thawed embryo transfer cycles in 178 patients) were analysed using binary logistic regression to explore the relationship between CsA treatment and clinical pregnancy outcomes; the odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated as a measure of relevancy. Implantation rate was the main outcome measure.ResultsThere was no difference in the fine adjusted OR (95 % CI) of the implantation rate [1.251 (0.739–2.120)], clinical pregnancy rate [1.634 (0.772–3.458)], chemical pregnancy rate [1.402 (0.285–6.909)], take-home baby rate [0.872 (0.423–1.798)], multiple births rate [0.840 (0.197–3.590)], preterm birth [1.668 (0.377–7.373)], abnormal birth weight [1.834 (0.533–6.307)] or sex ratio [0.956 (0.339–2.698)] between the CsA-treated group and control group. No birth defects were observed in the present study.ConclusionsAlthough CsA does not affect infant characteristics, it has no beneficial effects on the clinical pregnancy outcomes in patients with a history of unexplained transfer failure in FET cycles.
A versatile web app for identifying the drivers of COVID-19 epidemics
Authors: Getz Wayne M. , Salter Richard , Luisa Vissat Ludovica , Horvitz Nir 
Published: March 2021

AbstractBackgroundNo versatile web app exists that allows epidemiologists and managers around the world to comprehensively analyze the impacts of COVID-19 mitigation. Thehttp://covid-webapp.numerusinc.com/web app presented here fills this gap.MethodsOur web app uses a model that explicitly identifies susceptible, contact, latent, asymptomatic, symptomatic and recovered classes of individuals, and a parallel set of response classes, subject to lower pathogen-contact rates. The user inputs a CSV file of incidence and, if of interest, mortality rate data. A default set of parameters is available that can be overwritten through input or online entry, and a user-selected subset of these can be fitted to the model using maximum-likelihood estimation (MLE). Model fitting and forecasting intervals are specifiable and changes to parameters allow counterfactual and forecasting scenarios. Confidence or credible intervals can be generated using stochastic simulations, based on MLE values, or on an inputted CSV file containing Markov chain Monte Carlo (MCMC) estimates of one or more parameters.ResultsWe illustrate the use of our web app in extracting social distancing, social relaxation, surveillance or virulence switching functions (i.e., time varying drivers) from the incidence and mortality rates of COVID-19 epidemics in Israel, South Africa, and England. The Israeli outbreak exhibits four distinct phases: initial outbreak, social distancing, social relaxation, and a second wave mitigation phase. An MCMC projection of this latter phase suggests the Israeli epidemic will continue to produce into late November an average of around 1500 new case per day, unless the population practices social-relaxation measures at least 5-fold below the level in August, which itself is 4-fold below the level at the start of July. Our analysis of the relatively late South African outbreak that became the world’s fifth largest COVID-19 epidemic in July revealed that the decline through late July and early August was characterised by a social distancing driver operating at more than twice the per-capita applicable-disease-class (pc-adc) rate of the social relaxation driver. Our analysis of the relatively early English outbreak, identified a more than 2-fold improvement in surveillance over the course of the epidemic. It also identified a pc-adc social distancing rate in early August that, though nearly four times the pc-adc social relaxation rate, appeared to barely contain a second wave that would break out if social distancing was further relaxed.ConclusionOur web app provides policy makers and health officers who have no epidemiological modelling or computer coding expertise with an invaluable tool for assessing the impacts of different outbreak mitigation policies and measures. This includes an ability to generate an epidemic-suppression or curve-flattening index that measures the intensity with which behavioural responses suppress or flatten the epidemic curve in the region under consideration.
Creating a measure to operationalize engaged well-being at work
Authors: Bosle Catherin , Fischer Joachim E. , Herr Raphael M. 
Published: March 2021

Abstract
Background
Mental well-being and work engagement are both desirable, positive states of mind that help employees to better function in the workplace. While occupational researchers have argued in favor of considering both states concurrently, it is less clear how this might be translated to provide an instrument characterizing the workforce accordingly. The present study describes empirical efforts to operationalize a construct called engaged well-being.

Methods
We used employee-level data (n = 13,538) from three waves of the German linked personnel panel (LPP; 2012–2017). Exploratory factor analysis and a combination of hierarchical and non-hierarchical cluster analyses linked with within-sum-of-squares statistics were used to identify distinct profiles describing mental well-being and work engagement concurrently. These profiles were then used as the basis to identify cut-offs to create replicable categories of engaged well-being. Using the longitudinal data from a subgroup providing data across more than one wave, we observed whether the newly constructed indicator changed over time.

Results
The exploratory factor analysis suggested that both states were two distinct factors. Cluster analysis linked with within-sum-of-squares statistics suggested a four-cluster solution: engaged well-being (46.9%), disengaged well-being (27.5%), engaged strain (8.8%), and disengaged strain (16.8%). One cut-off for each state was identified to replicate the cluster solution. Across observation periods, we could observe changes in engaged well-being.

Conclusions
Our measure of engaged well-being can be used to simultaneously characterize a workforce’s mental well-being and work engagement. Changes in this measure over time suggest its potential utility in organizational interventions. Future studies are needed to further explore both the antecedents, correlates, and potential effects of engaged well-being.
The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex
Authors: Wang Xin , Jiang Wei , Luo Shuo , Yang Xiaoyu , Wang Changnan , Wang Bingying , Dang Yongjun , Shen Yin , Ma Dengke K. 
Published: March 2021

AbstractTMEM132Dis a human gene identified with multiple risk alleles for panic disorders, anxiety and major depressive disorders. Defining a conserved family of transmembrane proteins, TMEM132D and its homologs are still of unknown molecular functions. By generating loss-of-function mutants of the soleTMEM132ortholog inC. elegans, we identify abnormal morphologic phenotypes in the dopaminergic PDE neurons. Using a yeast two-hybrid screen, we find that NAP1 directly interacts with the cytoplasmic domain of human TMEM132D, and mutations inC. elegans tmem-132that disrupt interaction with NAP1 cause similar morphologic defects in the PDE neurons. NAP1 is a component of the WAVE regulatory complex (WRC) that controls F-actin cytoskeletal dynamics. Decreasing activity of WRC rescues the PDE defects intmem-132mutants, whereas gain-of-function ofTMEM132Din mammalian cells inhibits WRC, leading to decreased abundance of select WRC components, impaired actin nucleation and cell motility. We propose that metazoan TMEM132 family proteins play evolutionarily conserved roles in regulating NAP1 protein homologs to restrict inappropriate WRC activity, cytoskeletal and morphologic changes in the cell.
Long non‐coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer
Authors: Hu Chuan-yi , Chen Juan , Qin Xin-hua , You Pan , Ma Jie , Zhang Jing , Zhang He , Xu Ji-dong 
Published: March 2021

AbstractBackgroundBone metastasis is the leading cause of mortality and reduced quality of life in patients with metastatic prostate cancer (PCa). Long non-coding RNA activated by DNA damage (NORAD) has been observed to have an abnormal expression in various cancers. This article aimed to explore the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of PCa.MethodsNORAD expression in clinical PCa tissues and cell lines was detected with the application of qRT-PCR. Cancer cells were then transfected with plasmids expressing NORAD, after which Transwell assay and CCK-8 assay were carried out to detect proliferation, migration, and bone metastasis of PCa. NORAD downstream target molecules were screened through bioinformatics analysis, followed by further verification using dual luciferase assay. Extracellular vesicles (EVs) were labeled with PKH67 and interacted with bone marrow stromal cells. The gain- and loss-function method was applied to determine the internalization and secretion of PCa cells-derived EVs under the intervention of downstream target molecules or NORAD.ResultsPCa tissues and cell lines were observed to have a high expression of NORAD, particularly in tissues with bone metastasis. NORAD knockdown resulted in reduced secretion and internalization of EVs, and suppressed proliferation, migration, and bone metastasis of PCa cells. It was indicated that NORAD interacted with miR-541-3p, leading to the upregulation of PKM2. Forced expression of PKM2 promoted the transfer of PKH67-labeled EVs to bone marrow stromal cells.ConclusionsNORAD might serve as a ceRNA of miR-541-3p to promote PKM2 expression, thereby enhancing the development of bone metastasis in PCa by promoting internalization and transfer of EVs of cancer cells, providing an insight into a novel treatment for the disorder.
YAP promotes autophagy and progression of gliomas via upregulating HMGB1
Authors: Zhao Min , Zhang Yu , Jiang Yang , Wang Kai , Wang Xiang , Zhou Ding , Wang Yan , Yu Rutong , Zhou Xiuping 
Published: March 2021

Abstract
Background
Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this study is to delve out the role and mechanism of yes-associated protein (YAP) in GBM autophagy and progression.

Methods
The level of autophagy or autophagy flux were assessed by using western blotting, GFP-LC3 puncta (Live) imaging, transmission electron microscopy and GFP-RFP-LC3 assay. The GBM progression was detected by using CCK8, EdU, nude mouse xenograft and Ki67 staining. Isobaric tags for relative and absolute quantification (iTraq) quantitative proteomics was used to find out the mediator of YAP in autophagy. Expression levels of YAP and HMGB1 in tissue samples from GBM patients were examined by Western blotting, tissue microarray and immunohistochemistry.

Results
YAP over-expression enhanced glioma cell autophagy under basal and induced conditions. In addition, blocking autophagy by chloroquine abolished the promoting effect of YAP on glioma growth. Mechanistically, YAP over-expression promoted the transcription and translocation of high mobility group box 1(HMGB1), a well-known regulator of autophagy, from nucleus to cytoplasm. Down-regulation of HMGB1 abolished the promoting effect of YAP on autophagy and glioma growth. Furthermore, the expression of YAP and HMGB1 were positively associated with each other and suggested poor prognosis for clinical GBM.

Conclusion
YAP promoted glioma progression by enhancing HMGB1-mediated autophagy, indicating that YAP-HMGB1 axis was a feasible therapeutic target for GBM. Our study revealed a clinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression.
Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression
Authors: Gao Pan , Lyu Qing , Ghanam Amr R. , Lazzarotto Cicera R. , Newby Gregory A. , Zhang Wei , Choi Mihyun , Slivano Orazio J. , Holden Kevin , Walker John A. , Kadina Anastasia P. , Munroe Rob J. , Abratte Christian M. , Schimenti John C. , Liu David R. , Tsai Shengdar Q. , Long Xiaochun , Miano Joseph M. 
Published: March 2021

Abstract
Background
Most single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Here, a comparative analysis of CRISPR-mediated homology-directed repair (HDR) versus the recently reported prime editing 2 (PE2) system was carried out in mice over a TFBS called a CArG box in the Tspan2 promoter.

Results
Quantitative RT-PCR showed loss of Tspan2 mRNA in aorta and bladder, but not heart or brain, of mice homozygous for an HDR-mediated three base pair substitution in the Tspan2 CArG box. Using the same protospacer, mice homozygous for a PE2-mediated single-base substitution in the Tspan2 CArG box displayed similar cell-specific loss of Tspan2 mRNA; expression of an overlapping long noncoding RNA was also nearly abolished in aorta and bladder. Immuno-RNA fluorescence in situ hybridization validated loss of Tspan2 in vascular smooth muscle cells of HDR and PE2 CArG box mutant mice. Targeted sequencing demonstrated variable frequencies of on-target editing in all PE2 and HDR founders. However, whereas no on-target indels were detected in any of the PE2 founders, all HDR founders showed varying levels of on-target indels. Off-target analysis by targeted sequencing revealed mutations in many HDR founders, but none in PE2 founders.

Conclusions
PE2 directs high-fidelity editing of a single base in a TFBS leading to cell-specific loss in expression of an mRNA/long noncoding RNA gene pair. The PE2 platform expands the genome editing toolbox for modeling and correcting relevant noncoding SNVs in the mouse.
Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma
Authors: Yu Jie , Chai Peiwei , Xie Minyue , Ge Shengfang , Ruan Jing , Fan Xianqun , Jia Renbing 
Published: March 2021

Abstract
Background
Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear.

Results
Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.

Conclusion
We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.