bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reprogramming anchorage dependency by adherent-to-suspension transition promotes metastatic dissemination
Authors: Huh Hyunbin D. , Sub Yujin , Oh Jongwook , Kim Ye Eun , Lee Ju Young , Kim Hwa-Ryeon , Lee Soyeon , Lee Hannah , Pak Sehyung , Amos Sebastian E. , Vahala Danielle , Park Jae Hyung , Shin Ji Eun , Park So Yeon , Kim Han Sang , Roh Young Hoon , Lee Han-Woong , Guan Kun-Liang , Choi Yu Suk , Jeong Joon , Choi Junjeong , Roe Jae-Seok , Gee Heon Yung , Park Hyun Woo 
Published: March 2023

Abstract
Background
Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge.

Methods
We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival.

Results
We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell–matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth.

Conclusion
We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.
Seminoma arising in splenogonadal fusion: a case report and literature review
Authors: Shen Donglai , Li Yuzhu , Zhang Yu , Chang Xiao , Zhao Xupeng , Li Jiabin , Zhang Xu , Guo Gang 
Published: March 2023

Abstract
Background
Splenogonadal fusion (SGF) is a rare congenital malformation in which the spleen is abnormally connected to the gonads or to the mesonephric derivatives. There is no obvious causality between SGF and testicular neoplasm. However, cryptorchidism, which is a well-known risk factor of testicular germ cell tumors, are the most frequent malformations associated with SGF. To our knowledge, there are only four reported cases of SGF associated with testicular neoplasm so far. Herein, we reported a patient of this condition, and briefly reviewed the related literature.

Case presentation
A 48-year-old man was diagnosed with bilateral cryptorchidism 30 years prior, and only underwent a right orchiopexy for the left testicle could not be explored during the operation. At that time, doctors failed to realize the possibility of SGF due to the lack of sufficient knowledge of this condition. This time, the patient was treated for a left abdomen mass that was diagnosed as stage III metastatic seminoma. Then, a right orchiectomy, robot-assisted laparoscopic left retroperitoneal tumor resection, and left retroperitoneal lymph node dissection was performed after four cycles of BEP (bleomycin + etoposide + cisplatin) systemic chemotherapy in our center. The final diagnosis of SGF was made by postoperative pathology. The patient was re-examined in our center at 3 months and 6 months after the operation, and no obvious abnormalities were found.

Conclusions
Surgeons should always bear in mind the possibility of association between bilateral cryptorchidism and splenogonadal fusion to avoid malignant transformation caused by delayed treatment.
Protective effects of Qing-Re-Huo-Xue formula on bleomycin-induced pulmonary fibrosis through the p53/IGFBP3 pathway
Authors: Yang Fangyong , Du Wenjing , Tang Zhao , Wei Ying , Dong Jingcheng 
Published: March 2023

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with high mortality. Inflammation and epithelial mesenchymal transformation (EMT) may play an important role in the occurrence and development of IPF. Qing-Re-Huo-Xue formula (QRHXF) has been used clinically by our team for half a century and has obvious therapeutic effects on lung disease. Nevertheless, the role and mechanism of QRHXF in the treatment of IPF have never been studied.

Methods
A mouse pulmonary fibrosis model was established by intratracheal injection of BLM. The effects of QRHXF on the treatment of pulmonary fibrosis were studied by pulmonary function testing, imaging examination, pathological staining, transmission electron microscopy (TEM) observation and mRNA expression. Tandem mass tag (TMT)-based quantitative proteomics was carried out to analyse the lung protein expression profiles between the control (CTL), bleomycin (BLM) and QRHXF (BLM + QRHXF) groups. Immunohistochemistry and qRT-PCR were used to verify the possible existence of drug target proteins and signalling pathways.

Results
The results of pulmonary function, lung pathology and imaging examinations showed that QRHXF could significantly alleviate BLM-induced pulmonary fibrosis in vivo. Additionally, inflammatory cell infiltration and EMT were markedly reduced in BLM-induced PF mice administered QRHXF. Proteomics detected a total of 35 proteins, of which 17 were upregulated and 18 were downregulated. A total of 19 differentially expressed proteins (DEPs) overlapped between the BLM versus CTL groups and the BLM + QRHXF versus BLM groups. The expression of p53 and IGFBP3 was reversed in the QRHXF intervention group, which was verified by immunohistochemistry and qRT-PCR.

Conclusions
QRHXF attenuated BLM-induced pulmonary fibrosis, and regulation of the p53/IGFBP3 pathway might be associated with its efficacy, which holds promise as a novel treatment strategy for pulmonary fibrosis patients.

Graphical Abstract
Thinning effects on stand growth, carbon stocks, and soil properties in Brutia pine plantations
Authors: Erkan Neşat , Güner Şükrü Teoman , Aydın Ali Cem 
Published: March 2023

AbstractBackgroundThe purpose of this study was to investigate the effects of thinning on stand growth, carbon (C) sequestration, and soil properties in Brutia pine (Pinus brutiaTen.) plantations. The study was conducted at two experimental sites -the Antalya-Kaş and Isparta-Eğirdir plantation areas- in Turkey between 1985 and 2015. Different thinning intensities -unthinned (control), moderate, and heavy- were replicated in four blocks. We determined the C in the living biomass, litter, soil, and some soil features for each experimental parcel.ResultsWe found no statistically significant difference in total stand volume between thinning-intensity treatments 30 years after thinning. This may be due to more light availability and less competition between trees and faster tree-diameter growth rate after thinning, thus explaining the volume in the treated parcels compared to the control over time. The C stocks in the biomass, litter, and soil were not significantly influenced by the thinning intensity. The nutrients in the litter and soil, and other soil properties, were not significantly different among thinning parcels. This implies that the C and other nutrients in the litter and soil are related to the stand volume and biomass, which were not changed by thinning in time.ConclusionThis finding is important in terms of showing that there was no change in total stand volume by thinning, which has been debated in the literature. This information is useful for forest managers when determining thinning strategy.
circACTR2 attenuates gemcitabine chemoresiatance in pancreatic cancer through PTEN mediated PI3K/AKT signaling pathway
Authors: Xu Chao , Ye Qinwen , Ye Chao , Liu Shaojun 
Published: March 2023

Abstract
Background
Recently, accumulating studies have unveiled that circRNAs exert critical function in a variety of tumor biological processes including chemoresistance. Our previous study has found circACTR2 is significantly down-regulated in acquired gemcitabine (GEM)- resistant pancreatic cancer (PC) cells, which has not been well-explored. Our study aimed to research the function and molecular mechanism of circACTR2 in PC chemoresistance.

Methods
qRT-PCR and western blot analysis was performed to detect gene expression. The effect of circACTR2 on PC GEM resistance were examined by CCK-8 and flow cytometry assays. Whether circACTR2 could sponge miR-221-3p and regulate PTEN expression were determined by bioinformatics analysis, RNA pull-down, and Dual-luciferase reporter assay.

Results
circACTR2 was notably down-regulated in a panel of GEM-resistant PC cells lines, and negatively associated with aggressive phenotype and poor prognosis of PC. circACTR2 downregulation contributed to GEM chemoresistance of PC cells with decreased S phase ratio of cell cycle and cell apoptosis, as confirmed by gain- and loss-of-function assays in vitro. In addition, circACTR2 overexpression retarded GEM resistance in vivo. Further, circACTR2 acted as a ceRNA against miR-221-3p, which directly targeted PTEN. The mechanistic studies revealed that loss of circACTR2 promoted GEM resistance in PC through activating the PI3K/AKT signaling pathway by downregulating PTEN expression in a miR-221-3p dependent manner.

Conclusions
circACTR2 reversed the chemoresistance of PC cells to GEM through inhibiting PI3K/AKT signaling pathway by sponging miR-221-3p and upregulating PTEN expression.
Development of models to predict 10-30-year cardiovascular disease risk using the Da Qing IGT and diabetes study
Authors: Chen Fei , Wang Jinping , Chen Xiaoping , Yu Liping , An Yali , Gong Qiuhong , Chen Bo , Xie Shuo , Zhang Lihong , Shuai Ying , Zhao Fang , Chen Yanyan , Li Guangwei , Zhang Bo 
Published: March 2023

Abstract
Background
This study aimed to develop cardiovascular disease (CVD) risk equations for Chinese patients with newly diagnosed type 2 diabetes (T2D) to predict 10-, 20-, and 30-year of risk.

Methods
Risk equations for forecasting the occurrence of CVD were developed using data from 601 patients with newly diagnosed T2D from the Da Qing IGT and Diabetes Study with a 30-year follow-up. The data were randomly assigned to a training and test data set. In the training data set, Cox proportional hazard regression was used to develop risk equations to predict CVD. Calibration was assessed by the slope and intercept of the line between predicted and observed probabilities of outcomes by quintile of risk, and discrimination was examined using Harrell’s C statistic in the test data set. Using the Sankey flow diagram to describe the change of CVD risk over time.

Results
Over the 30-year follow-up, corresponding to a 10,395 person-year follow-up time, 355 of 601 (59%) patients developed incident CVD; the incidence of CVD in the participants was 34.2 per 1,000 person-years. Age, sex, smoking status, 2-h plasma glucose level of oral glucose tolerance test, and systolic blood pressure were independent predictors. The C statistics of discrimination for the risk equations were 0.748 (95%CI, 0.710–0.782), 0.696 (95%CI, 0.655–0.704), and 0.687 (95%CI, 0.651–0.694) for 10-, 20-, and 30- year CVDs, respectively. The calibration statistics for the CVD risk equations of slope were 0.88 (P = 0.002), 0.89 (P = 0.027), and 0.94 (P = 0.039) for 10-, 20-, and 30-year CVDs, respectively.

Conclusions
The risk equations forecast the long-term risk of CVD in patients with newly diagnosed T2D using variables readily available in routine clinical practice. By identifying patients at high risk for long-term CVD, clinicians were able to take the required primary prevention measures.
Ethnicity and survival after a dementia diagnosis: a retrospective cohort study using electronic health record data
Authors: Co Melissa , Mueller Christoph , Mayston Rosie , Das-Munshi Jayati , Prina Matthew 
Published: March 2023

AbstractBackgroundIndividuals from minority ethnic groups in the UK are thought to be at higher risk of developing dementia while facing additional barriers to receiving timely care. However, few studies in the UK have examined if there are ethnic disparities in survival once individuals receive a dementia diagnosis.MethodsWe conducted a retrospective cohort study using electronic health record data of individuals diagnosed with dementia from a large secondary mental healthcare provider in London. Patients from Black African, Black Caribbean, South Asian, White British, and White Irish ethnic backgrounds were followed up for a 10-year period between 01 January 2008 and 31 December 2017. Data were linked to death certificate data from the Office of National Statistics to determine survival from dementia diagnosis. Standardised mortality ratios were calculated to estimate excess deaths in each ethnicity group as compared to the gender- and age-standardised population of England and Wales. We used Cox regression models to compare survival after dementia diagnosis across each ethnicity group.ResultsMortality was elevated at least twofold across all ethnicity groups with dementia compared to the general population in England and Wales. Risk of death was lower in Black Caribbean, Black African, White Irish, and South Asian groups as compared to the White British population, even after adjusting for age, gender, neighbourhood-level deprivation, indicators of mental and physical comorbidities. Risk of death remained lower after additionally accounting for those who emigrated out of the cohort.ConclusionsWhile mortality in dementia is elevated across all ethnic groups as compared to the general population, reasons for longer survival in minority ethnic groups in the UK as compared to the White British group are unclear and merit further exploration. Implications of longer survival, including carer burden and costs, should be considered in policy and planning to ensure adequate support for families and carers of individuals with dementia.
Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting
Authors: Burrows Alyssa G. , Linton Sophia , Thiele Jenny , Sheth Prameet M. , Evans Gerald A. , Archer Stephen , Doliszny Katharine M. , Finlayson Marcia , Flynn Leslie , Huang Yun , Kasmani Azim , Hugh Guan T. , Maier Allison , Hansen-Taugher Adrienne , Moore Kieran , Sanfilippo Anthony , Snelgrove-Clarke Erna , Tripp Dean A. , Walker David M. C. , Vanner Stephen , Ellis Anne K. 
Published: March 2023

AbstractThe novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27th, 2020, to June 23rd 2021; at a time when B.1.1.7 (alpha) and B.1.617.2 (delta) were the dominant circulating variants, PCR testing was conducted on 1,237 nasopharyngeal swabs collected from 454 asymptomatic health care professional students as they returned to their studies from across Canada to Kingston, ON, a low prevalence area during that period for COVID-19. Despite 46.7% of COVID-19 infections occurring in the 18–29 age group in Kingston, severe-acute-respiratory coronavirus-2 was not detected in any of the samples suggesting that negligible asymptomatic infection occurred in this group and that PCR testing in this setting may not be warranted as a screening tool.
Integrative diagnostics: the time is now—a report from the International Society for Strategic Studies in Radiology
Authors: Beauchamp Norman J. , Bryan R. Nick , Bui Marilyn M. , Krestin Gabriel P. , McGinty Geraldine B. , Meltzer Carolyn C. , Neumaier Michael 
Published: March 2023

Abstract
Enormous recent progress in diagnostic testing can enable more accurate diagnosis and improved clinical outcomes. Yet these tests are increasingly challenging and frustrating; the volume and diversity of results may overwhelm the diagnostic acumen of even the most dedicated and experienced clinician. Because they are gathered and processed within the “silo” of each diagnostic discipline, diagnostic data are fragmented, and the electronic health record does little to synthesize new and existing data into usable information. Therefore, despite great promise, diagnoses may still be incorrect, delayed, or never made. Integrative diagnostics represents a vision for the future, wherein diagnostic data, together with clinical data from the electronic health record, are aggregated and contextualized by informatics tools to direct clinical action. Integrative diagnostics has the potential to identify correct therapies more quickly, modify treatment when appropriate, and terminate treatment when not effective, ultimately decreasing morbidity, improving outcomes, and avoiding unnecessary costs. Radiology, laboratory medicine, and pathology already play major roles in medical diagnostics. Our specialties can increase the value of our examinations by taking a holistic approach to their selection, interpretation, and application to the patient’s care pathway. We have the means and rationale to incorporate integrative diagnostics into our specialties and guide its implementation in clinical practice.

Graphic abstract
Dual-energy CT quantification of extracellular liver volume predicts short-term disease progression in patients with hepatitis B liver cirrhosis-acute decompensation
Authors: Xu Yuan , Li Yufeng , Li Shenglin , Xue Shouxiao , Liu Jianli 
Published: March 2023

Abstract
Background
Liver cirrhosis-acute decompensation (LC-AD) has rapid short-term disease progression and difficult early risk stratification. The purpose is to develop and validate a model based on dual-energy CT quantification of extracellular liver volume (ECVIC-liver) for predicting the occurrence of acute-on-chronic liver failure (ACLF) within 90 days in patients with hepatitis B (HBV) LC-AD.

Methods
The retrospective study included patients with HBV LC-AD who underwent dual-energy CT scans of the liver from January 2018 to March 2022 and were randomized to training group (215 patients) and validation group (92 patients). The primary outcome was the need for readmission within 90 days due to ACLF. Based on the training group data, independent risk factors for disease progression in clinical and dual-energy CT parameters were identified and modeled by logistic regression analysis. Based on the training and validation groups data, receiver operating characteristic (ROC) curves, calibration curves, and decision analysis curves (DCA) were used to verify the discrimination, calibration, and clinical validity of the nomogram.

Results
Chronic liver failure consortium-acute decompensation score (CLIF-C ADs) (p = 0.008) and ECVIC-liver (p < 0.001) were independent risk factors for ACLF within 90 days. The AUC of the model combined ECVIC-liver and CLIF-C ADs were 0.893 and 0.838 in the training and validation groups, respectively. The calibration curves show good agreement between predicted and actual risks. The DCA indicates that the model has good clinical application.

Conclusion
The model combined ECVIC-liver and CLIF-C ADs can early predict the occurrence of ACLF within 90 days in HBV LC-AD patients.
Stem cell sources and characterization in the development of cell-based products for treating retinal disease: An NEI Town Hall report
Authors: Fortress Ashley M. , Miyagishima Kiyoharu J. , Reed Amberlynn A. , Temple Sally , Clegg Dennis O. , Tucker Budd A. , Blenkinsop Timothy A. , Harb George , Greenwell Thomas N. , Ludwig Tenneille E. , Bharti Kapil 
Published: March 2023

AbstractNational Eye Institute recently issued a new Strategic Plan outlining priority research areas for the next 5 years. Starting cell source for deriving stem cell lines is as an area with gaps and opportunities for making progress in regenerative medicine, a key area of emphasis within the NEI Strategic Plan. There is a critical need to understand how starting cell source affects the cell therapy product and what specific manufacturing capabilities and quality control standards are required for autologous vs allogeneic stem cell sources. With the goal of addressing some of these questions, in discussion with the community-at-large, NEI hosted a Town Hall at the Association for Research in Vision and Ophthalmology annual meeting in May 2022. This session leveraged recent clinical advances in autologous and allogeneic RPE replacement strategies to develop guidance for upcoming cell therapies for photoreceptors, retinal ganglion cells, and other ocular cell types. Our focus on stem cell-based therapies for RPE underscores the relatively advanced stage of RPE cell therapies to patients with several ongoing clinical trials. Thus, this workshop encouraged lessons learned from the RPE field to help accelerate progress in developing stem cell-based therapies in other ocular tissues. This report provides a synthesis of the key points discussed at the Town Hall and highlights needs and opportunities in ocular regenerative medicine.
H3K27me3-H3K4me1 transition at bivalent promoters instructs lineage specification in development
Authors: Yu Yue , Li Xinjie , Jiao Rui , Lu Yang , Jiang Xuan , Li Xin 
Published: March 2023

Abstract
Background
Bivalent genes, of which promoters are marked by both H3K4me3 (trimethylation of histone H3 on lysine 4) and H3K27me3 (trimethylation of histone H3 on lysine 27), play critical roles in development and tumorigenesis. Monomethylation on lysine 4 of histone H3 (H3K4me1) is commonly associated with enhancers, but H3K4me1 is also present at promoter regions as an active bimodal or a repressed unimodal pattern. Whether the co-occurrence of H3K4me1 and bivalent marks at promoters plays regulatory role in development is largely unknown.

Results
We report that in the process of lineage differentiation, bivalent promoters undergo H3K27me3-H3K4me1 transition, the loss of H3K27me3 accompanies by bimodal pattern loss or unimodal pattern enrichment of H3K4me1. More importantly, this transition regulates tissue-specific gene expression to orchestrate the development. Furthermore, knockout of Eed (Embryonic Ectoderm Development) or Suz12 (Suppressor of Zeste 12) in mESCs (mouse embryonic stem cells), the core components of Polycomb repressive complex 2 (PRC2) which catalyzes H3K27 trimethylation, generates an artificial H3K27me3-H3K4me1 transition at partial bivalent promoters, which leads to up-regulation of meso-endoderm related genes and down-regulation of ectoderm related genes, thus could explain the observed neural ectoderm differentiation failure upon retinoic acid (RA) induction. Finally, we find that lysine-specific demethylase 1 (LSD1) interacts with PRC2 and contributes to the H3K27me3-H3K4me1 transition in mESCs.

Conclusions
These findings suggest that H3K27me3-H3K4me1 transition plays a key role in lineage differentiation by regulating the expression of tissue specific genes, and H3K4me1 pattern in bivalent promoters could be modulated by LSD1 via interacting with PRC2.