bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic screening revealed widespread mosaicism in human early embryos
Authors: Qiao Jie , Zhai Fan , Kong Siming , Song Shi , Guo Qianying , Ding Ling , Yang Ming , Wang Jing , Zhang Jiaqi , Lian Ying , Li Rong , Zhu Xiaohui , Wang Yuqian , Wang Nan , Kuo Ying , Guan Shuo , Yuan Yifeng , Huang Jin , Yuan Peng , Yan Liying , Yan Zhiqiang 
Published: November 2022

Abstract
Pre-implantation Genetic Testing for Aneuploidy (PGT-A) is widely used in half of in vitro fertilization (IVF) cycles, leading to the unwarranted disposal of embryos with pregnancy potential. Due to the limited understanding of genetics of human embryo, current PGT-A is built on biologically uncertain assumptions and on unvalidated guidelines1. Here, we sequenced all single cells (1,072) from 20 human blastocysts and analyzed 13,897 single cells from post-implantation embryos as well as fetal organs. Unexpectedly, all blastocysts contained mitotic aneuploid cells and showed about 25% aneuploidy rate per embryo. Among the 20 blastocysts, 70% (14/20) contained chromosome ‘complementary’ cells, suggesting the possible underestimation of mosaicism in traditional PGT-A. All the post-implantation embryos and fetal organs were mosaic, and over 80% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings showed all human embryos are naturally aneuploid-mosaic and this may provide guidance to the implementation of PGT-A in clinical practice.
Androgen dihydrotestosterone promotes bladder cancer cell proliferation and invasion via EPPK1-mediated MAPK/JUP signaling
Authors: Yang Long , Huang Wen , Bai Xiaoyu , Wang Haoyu , Wang Xiaolei , Xiao Huiyuan , Li Yanlei 
Published: November 2022

Abstract
The incidence of bladder cancer (BLCA) in men is higher than that of women. Differences in androgen levels between men and women are considered the main causes of incidence rate differences. In this study, dihydrotestosterone (DHT) could significantly increase cell proliferation and invasion of BLCA cell line. In addition, BLCA formation and metastatic rates were higher in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) treated male mice than in female and castrated male mice in vivo. However, immunohistochemistry showed that androgen receptor (AR) was found low expressed in normal and BLCA cancer tissues of men and women. Here, a non-AR combination pathway of androgen that promoted BLCA development was investigated. The protein EPPK1 was bombinated with DHT determined by biotinylated DHT-binding pull-down experiments. EPPK1 was highly expressed in BLCA tissues, and EPPK1 knockdown significantly inhibited BLCA cell proliferation and invasion promoted by DHT. Moreover, JUP expression was elevated in DHT-treated high-EPPK1 expression cells, and JUP knockdown inhibited cell proliferation, and invasion. EPPK1 over-expression could increase tumor growth in nude mice and JUP expression. Furthermore, DHT increased the expression of MAPK signals p38, p-p38, and c-Jun expression, and c-Jun could combine with the JUP promoter. However, no functions in EPPK1 knockdown cells and p38 inhibitor could suppress the DHT-treated increase, indicating that p38 MAPK may be involved in the regulation of DHT-dependent EPPK1-JUP-promoting BLCA cell proliferation and invasion. The growth of bladder tumors in BBN-treated wild mice was inhibited by the addition of the hormone inhibitor Goserelin. Our findings indicated the potential oncogenic role and mechanism of DHT in BLCA pathogenesis through a non-AR pathway, which may serve as a novel therapeutic target for BLCA. Androgen inhibitors may be used as endocrine therapy for bladder cancer.
Global Research on Osteosarcoma, 1999–2019: A Bibliometric and Visual Analysis
Authors: Zhang Jixiang , Li Yongbo , Wu Han 
Published: November 2022

Abstract
Background
Osteosarcoma is a primary malignant bone tumor that occurs in children and adolescents. Increasing numbers of scholars have studied its development and treatment. To fully understand the current status of osteosarcoma research and global trends therein, we performed a bibliometric and visual analysis of osteosarcoma studies published between 1999 and 2019.
Methods
We searched the Web of Science database for publications on osteosarcoma. The basic characteristics of this sample of publications, such as H indices, annual outputs, languages of publication, and authors, journals, institutions, and countries of origin, were determined. Co-citation, collaboration, and keyword co-occurrence were analyzed using CiteSpace software.
Results
The sample comprised 16,934 articles. The number of publications increased annually. H indices and total numbers of citations were far higher for articles from the United States than for those from other countries. Among institutions, the largest proportion of articles originated from Shanghai Jiaotong University. R. Gorlick was the author with the highest H index and total number of citations. Oncology Letters published the largest number of articles and Cancer Research was the most frequently cited journal. The five most frequently appearing keywords were “osteosarcoma,” “cancer,” “expression,” “apoptosis,” and “metastasis.” The analysis generated 10 major clusters of keywords and 23 clusters of co-cited references.
Conclusions
The findings of this study have guiding significance for researchers seeking cooperating institutions and partners for osteosarcoma research, popular journals and important literature in the field, an understanding of the knowledge base for this research, and up-to-date identification of research hotspots and trends.
Sex modulates the human genome regulatory network during heart failure and aging.
Authors: Efimov Igor , Gams Anna , Deviatiiarov Ruslan , Kulakovskiy Ivan , Buyan Andrey , Singh Ramesh , Shah Palak , Gusev Oleg , Tatarinova Tatiana 
Published: November 2022

Abstract
Heart failure and other cardiomyopathies have distinct presentations in males versus females that are often overlooked, leading to ineffective treatment and the growing mortality from heart diseases. Understanding the sex dimorphism in the pathogenesis of heart disease can guide improved diagnostics and sex-specific therapy. Thus, we aimed to investigate the sex dimorphism of promoter and enhancer activity in the pathogenesis of heart failure and aging. We applied cap analysis of gene expression (CAGE) to characterize the sex-specific activity of transcribed regulatory elements (TRE) in 17 male and 14 female healthy and failing hearts. We show that TREs exhibit significant sex dimorphism spread throughout the entire genome in healthy and failing atria and ventricles and are related to the immune system, metabolic, cardiomyocyte function, and developmental pathways. Moreover, we found 720 genes with sex-dependent promoter switching, of which 40 switched dominant promoters. One example was CREM, a transcription factor with a short repressive dominant isoform exclusive for males. CREM is related to extensive β-adrenergic receptor stimulation that leads to heart failure, hypertrophy, and arrhythmia. Furthermore, we identified that aging in the female and male hearts is associated with metabolic and developmental pathways, respectively. We also showed sex-specific aging patterns, such as age-specific promoter usage of 1,100 genes that behaved differently depending on sex, including UCKL1 and HAND2 linked to uridine metabolism and cardiac development, respectively. In conclusion, we report evidence of significant sex dimorphism exhibited in hundreds of transcribed genome regulatory elements in health, heart failure pathogenesis, and aging.
Dissociable neural mechanisms of selective visual information processing underlie the effects of attention on visual appearance and response bias
Authors: Itthipuripat Sirawaj , Wiwatphonthana Preawpiraya , Sawetsuttipan Prapasiri , Chang Kai-Yu , Störmer Viola , Woodman Geoffrey , Serences John 
Published: November 2022

Abstract
It has been debated if attention can penetrate early perceptual representations to alter visual appearance or it simply induces response biases. Here, we tested these alternative accounts by evaluating attentional modulations of EEG responses recorded from human subjects while they compared the perceived contrasts of cued and uncued visual stimuli of varying physical contrasts. We found that attention enhanced the response gain of neural contrast response functions (CRFs) computed based on the amplitude of the P1 component, an early visually evoked potential. Quantitative models suggested that the response gain of the P1-based CRFs could account for attention-induced changes in perceived contrast. Instead, attentional cues induced changes in the baseline offset of the CRFs based on 9-12Hz alpha-band oscillations and these baseline-offset changes better accounted for cue-induced response biases. Together, these results suggest that different neural mechanisms underlie the effects of attention on perceptual experience and on response biases.
Participant characteristics and reasons for non-consent to health information linkage for research: experiences from the ATHENA COVID-19 Study.
Authors: Greaves Kim , King Amanda , Bourne Zoltan , Welsh Jennifer , Morgan Mark , Tolosa M.Ximena , Bonner Carissa , Stanton Tony , Fryer Michael , Korda Rosemary 
Published: November 2022

Abstract
Background
The linkage of primary care, hospital and other health registry data is a global goal, and a consent-based approach is often used. Understanding the attitudes of why participants take part is important, yet little is known about reasons for non-participation. The ATHENA COVID-19 feasibility study investigated: 1) health outcomes of people diagnosed with COVID-19 in Queensland, Australia through primary care health data linkage using consent, and 2) created a cohort of patients willing to be re-contacted in future to participate in clinical trials. This report describes the characteristics of participants declining to participate and reasons for non-consent.
Methods
Patients diagnosed with COVID-19 from January 1st, 2020, to December 31st, 2020, were invited to consent to having their primary healthcare data extracted from their GP into a Queensland Health database and linked to other data sets for ethically approved research. Patients were also asked to consent to future recontact for participation in clinical trials. Outcome measures were proportions of patients consenting to data extraction, permission to recontact, and reason for consent decline.
Results
996 participants were approached and 853(86%) reached a consent decision. 581(69%), 623(73%) and 567(67%) consented to data extraction, recontact, or both, respectively. Mean (range) age of consenters and non-consenters were 50.6(range) and 46.1(range) years, respectively. Adjusting for age, gender and remoteness, older participants were more likely to consent than younger (aOR 1.02, 95%CI 1.01 to 1.03). The least socio-economically disadvantaged were more likely to consent than the most disadvantaged (aOR 2.20, 95% 1.33 to 3.64). There was no difference in consent proportions regarding gender or living in more remote regions. The main reasons for non-consent were ‘not interested in research’ (37%), ‘concerns about privacy’ (15%), ‘not registered with a GP’ (8%) and ‘too busy/no time’ (7%). ‘No reason’ was given in 20%.
Conclusion
Younger participants and the more socio-economically deprived are more likely to non-consent to primary care data linkage. Lack of patient interest in research, time required to participate and privacy concerns, were the most common reasons cited for non-consent. Future health care data linkage studies addressing these issues may prove helpful.
Trial registration details:
not applicable
Comparison of QuickNAT and FSL-FIRST for segmentation of subcortical structures in patients with epilepsy
Authors: Joković Zorica , Pejović Aleksa , Jerković Vera Miler , Sokić Dragoslav , Vojvodić Nikola , Mijaljević Marija , Ristić Aleksandar 
Published: November 2022

Abstract
Epilepsy is a neurological disorder that causes seizures and involves widespread structural alteration. Magnetic resonance (MR) is the preferred imaging tool for investigating patients with epilepsy and is also used for segmentation. We used to compare QuickNAT and FSL-FIRST software for the segmentation of subcortical structures in patients with temporal lobe epilepsy (TLE-R and TLE-L) and healthy control. We found that there were statistically significant differences among the automated methods in all groups (TLE-R, TLE-L, and control; mean ± SD) at the left pallidum (16.397 ± 9.326; 18.333 ± 11.062;39.322 ± 23.711) left putamen (29.561 ± 13.642;27.713 ± 13.696;22.499 ± 7.994), right amygdala (26.173 ± 19.743;22.822 ± 12.787;19.429 ± 11.617), right pallidum (24.205 ± 11.674;24.706 ± 10.647;38.976 ± 20.405), and right putamen (37.223 ± 19.498;31.143 ± 18.714;20.914 ± 9.885). We found the superiority of FSL-FIRST software over QuickNAT in calculating both volumes (raw and normalized) of subcortical structures.
The Genome Stability-Related lncRNA ZFPM2-AS1 Promotes Tumor Progression via miR-3065-5p/XRCC4 in Hepatocellular Carcinoma
Authors: Liu Jie , Zhang Hao , Xia Peng , Zhu Yimin , Xu Kequan , Liu Zhisu , Yuan Yufeng 
Published: November 2022

Abstract
Long noncoding RNAs (lncRNAs) have a certain link to genomic stability (GS). However, the regulatory relationship of lncRNAs and GS has not been thoroughly investigated in hepatocellular carcinoma (HCC). We retrieved the TCGA samples that had somatic mutations and lncRNA expression data. The RNA levels were determined by quantitative polymerase chain reaction (qPCR) and protein levels were detected by Western blotting (WB). Cell counting kit 8 (CCK8) and colony formation assays were used to assess cell viability. Cell apoptosis and cell cycle progression were measured by flow cytometry. GS was detected by alkaline comet and chromosomal aberration assays. The xenograft model and lung metastasis model were used to assess the role of ZFPM2-AS1 in tumor growth in vivo. The molecular mechanism underlying the biological functions of ZFPM2-AS1 was investigated through bioinformatic prediction, RNA pull down and luciferase reporter assays. We identified 85 genomic instability-related lncRNAs and developed a prognostic model. The prognostic model showed good predictive power (area under the curve [AUC] = 0.797). ZFPM2-AS1 was significantly highly expressed in tumor tissues (P < 0.001), and it promoted DNA damage repair (P = 0.004) and tumor progression in vitro and in vivo. Luciferase reporter assays demonstrated that miR-3065-5p could bind directly with ZFPM2-AS1 and X-ray repair cross complementing 4 (XRCC4). ZFPM2-AS1 upregulated XRCC4 expression by acting as a sponge (P < 0.001). We developed and validated a prognostic model for HCC and experimentally investigated one lncRNA of its components. ZFPM2-AS1 in the model regulates XRCC4 by sponging miR-3065-5p to promote GS and HCC progression.
Quality of life and anxiety in an underdeveloped city in IRAN during the COVID-19 pandemic: a cross-sectional study
Authors: Abdi Mohammadamin , Dahouei Arefeh Arabpour , Araghi Navid Mirzakhani 
Published: November 2022

Abstract
Introduction: Previous Studies have widely explored the Quality of life in wealthy communities during the COVID-19 pandemic; the present study selected the earthquake-prone and underdeveloped city of Zarand (Iran) and aimed to evaluate the Quality of life and anxiety.
Methods: 291 patients infected with COVID-19 in the last 14 days were included in the study. They were selected using systematic non-random sampling. The participants' Quality of life and anxiety were evaluated using the online WHO-Quality of Life-BREF and Beck Anxiety Inventory (BAI). The analysis was not limited to the significance and included the effect size. Data were analyzed by SPSS software version 26 using Spearman's correlation, T-test, and Kruskal-Wallis.
Results: On average, the Quality of life scores were less than 50 out of 100. 58% of patients reported moderate to severe anxiety, and there was a negative correlation between all of the four physical (P-value<0.001), psychological(P-value<0.001), social(P-value<0.007), and environmental(P-value<0.001) domains of Quality of life and anxiety, respectively. Education and Quality of life were positively correlated in all domains except for the environmental part. Participants' Age ranged from 18 to 58, and the correlation between Age and the physical and psychological domain was significant. No significant correlation was found between the Quality of life, sex, and marital status.
Conclusions: The current study provides evidence of low Quality of life and high anxiety levels in patients who experienced COVID-19. This consequence implicates immediate considerations to be considered by policymakers and officials.
Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy
Authors: Spiliopoulou Pavlina , Rensburg Helena Janse van , Avery Lisa , Kulasingam Vathany  , Razak Albiruni , Bedard Philippe , Hansen Aaron , Chruscinski Andrzej , Wang Ben , Kulikova Maria , Chen Rachel , Speers Vanessa , Nguyen Alisa , Lee Jasmine , Coburn Bryan , Spreafico Anna , Siu Lillian 
Published: November 2022

Abstract
Background
Despite more than 2 years having elapsed since the onset of SARS-CoV-2 pandemic, a level of hesitation around increased SARS-CoV-2 vaccine toxicity in cancer patients receiving immunotherapy (IO) remains. Here, we explore serological responses to SARS-CoV-2 vaccination in patients treated with IO and we describe blood cytokines, autoantibody levels and immune-related adverse events (irAEs) post vaccination.
Methods
Serum anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibodies, surrogate viral neutralization test (sVNT), Th1/Th2 cytokines and antibodies against self-antigens were quantified at baseline, between 1st and 2nd vaccine doses, at 1 week (1W), 1 month (1M), 4–6 months and 10–12 months after the 2nd dose. Grade 2 or higher (≥ gr2+) irAEs were captured prospectively.
Results
Fifty-one evaluable patients were enrolled in this longitudinal study, 35 on immunotherapy (IO) and 16 on non-immunotherapy (non-IO) treatment. Absolute levels and neutralization potential of anti-SARS-CoV-2 antibodies were not significantly different in the IO group compared to non-IO. Chemotherapy adversely affects seroconversion when compared to IO and/or targeted treatment with antibody levels of 67.6 U/mL vs 1441 U/mL (p = 0.006) and sVNT of 70.9% vs 94.5% (p = 0.009), at 1M after 2nd vaccine dose. Following vaccination, the prevalence of grade ≥ 2 irAEs in patients treated with IO was not higher than the usual reported IO toxicity. We report, for the first time, that post-vaccination, IgM autoantibodies against beta 2 glycoprotein (p = 0.02), myeloperoxidase (p = 0.03), nucleosome (p = 0.041), SPLUNC2 (p < 0.001) and IgG autoantibody against Myosin Heavy Chain 6 (MYH6) (p < 0.001), were significantly elevated and this increase was unrelated to the type of treatment.
Discussion
Comprehensive analysis of a small cohort showed that co-administration of SARS-CoV-2 vaccine and IO is not associated with increased irAEs. The detection of autoantibodies post anti-SARS-CoV-2 vaccination warrants further investigation. (NCT03702309)
Ultrasonography characteristics of cystic components in primary salivary gland tumors
Authors: Ding AngAng , Lv Huan , Cao Jinye , Wang Xin , Xiong Ping 
Published: November 2022

Abstract
Objectives The present study aimed to characterize the ultrasonography (US) features of cystic components in salivary gland tumors (SGTs).
Material and methods A total of 207 patients (218 lesions) with pathologically confirmed primary SGTs were analyzed. Preoperative US revealed the presence of cystic components in lesions. Lesion size, shape, margin, and US findings of the cystic components, including number, distribution, margin, occupying rate, and internal characteristics, were evaluated.
Results Similarities were observed between the US performance of benign SGTs (B-SGTs) and malignant SGTs (M-SGTs) with cystic components. Differences in sex and age of patients, number, distribution, and internal characteristics of cystic components were statistically significant. For SGTs with cystic components, the proportions of M-SGTs to ill-defined margins (P = 0.002), eccentric distribution (P = 0.019), and none of the internal characteristics (P = 0.019) were significantly higher than those of B-SGTs. For every one-year increase in age, the presence of B-SGTs increased by 4.9%
(95% confidence interval for the odds ratio, 1.020-1.078). The risk of ill-defined margins for the presence of M-SGTs was 10.030 times higher than that for well-defined margins (95% confidence interval for odds ratio, 3.377-29.787). Cystic component features needed to be combined with lesion indicators (border and shape) to improve diagnostic sensitivity.
Conclusions US features of the B-SGTs and M-SGTs were significantly different. Cystic component is of interest in the US-related differential diagnosis of B-SGT and M-SGT.
Clinical Relevance Cystic components are potentially valuable in the differential diagnosis of B-SGTs and M-SGTs on US.
Who Provides Anesthesia Services in Canada?
A Methodology to Identify the Physician Anesthesia Workforce Using Health Administrative Data
Authors: Simkin Sarah , Orser Beverley A. , Wilson C. Ruth , Bourgeault Ivy Lynn 
Published: November 2022

Abstract
Background
Safe and timely anesthesia services are an integral component of modern health care systems. There are, however, increasing concerns about the availability of anesthesia services in Canada. Thus, a comprehensive approach to assess the capacity of the anesthesia workforce to provide service is of critical need. Data regarding the anesthesia services provided by specialists and family physicians are available through the Canadian Institute for Health Information (CIHI) but collating these across delivery jurisdictions has proven challenging. As a result, critical information related to physician anesthesia providers is routinely excluded from annual physician workforce reports. Our goal was to develop a novel approach to identifying and characterizing the anesthesia workforce on a pan-Canadian scale.
Methods
The study was approved by the University of Ottawa Office of Research Ethics and Integrity. We developed a methodology to identify physicians who provided anesthesia services in Canada between 1996 and 2018 using data elements from the CIHI National Physician Database. We iteratively consulted with expert advisors and compared the results with Scott’s Medical Database, the Canadian Medical Association Masterfile, and the College of Family Physicians of Canada membership database.
Results
The methodology identified providers of anesthesia services using data elements from the CIHI National Physician Database, including categories of the National Grouping System, specialty designations, activity levels and participation thresholds. Physicians who provided anesthesia services only sporadically and medical residents-in-training were excluded. This methodology produced estimates of anesthesia providers that aligned with other sources. The process we followed was sequential, transparent, and intuitive, and was strengthened by collaboration and iterative consultation with experts and stakeholders.
Conclusions
Using physician activity patterns, this novel methodology allows stakeholders to identify which physician provide anesthesia services in Canada. It is an essential step in developing a pan-Canadian anesthesia workforce strategy which will examine patterns and trends related to the workforce and support evidence-informed workforce decision-making. It also establishes a foundation for assessing the effectiveness of policy interventions aimed at optimizing physician anesthesia services in Canada.