bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-fibrotic potential of erythropoietin signaling on bone marrow derived fibrotic cell
Authors: Iwata Yasunori , Sakai Norihiko , Nakajima Yuki , Oshima Megumi , Nakagawa-Yoneda Shiori , Ogura Hisayuki , Sato Koichi , Minami Taichiro , Kitajima Shinji , Toyama Tadashi , Yamamura Yuta , Miyagawa Taro , Hara Akinori , Shimizu Miho , Furuichi Kengo , Wada Takashi 
Published: May 2021

Abstract
Introduction
The number of patients with end stage kidney disease (ESKD) are increasing world-side. While interstitial fibrosis (IF) is a common step for the progression to ESKD, therapeutic options for IF is still limited in clinical settings. We have reported that bone marrow-derived fibrotic cell, fibrocyte, is involved in the pathogenesis of kidney fibrosis. Also recent studies revealed that erythropoietin has protective effect on kidney diseases. However, it is unknown whether erythropoietin (EPO) inhibits fibrosis in progressive kidney injury. Therefore, we explored the impacts of EPO on kidney fibrosis with focusing on fibrocyte.

Method
Fibrocyte was differentiated from peripheral mononuclear cells of healthy donor. Fibrocyte was stimulated with transforming growth factor beta (TGF)-β with/without EPO treatment. Moreover, the therapeutic effect of EPO was evaluated in murine unilateral ureteral obstruction (UUO) model.

Result
TGF-β stimulation increased the expression of COL1 mRNA in fibrocyte. EPO signal reduced the expression of COL1 mRNA in dose dependent manner. EPO reduced mitochondrial oxidative stress and ameliorated mitochondrial membrane depolarization induced by TGF-β stimulation. Moreover, EPO reduced the mRNA expression of mitochondria related molecules, TRAF6, in fibrocyte. In addition, the count of CD45+/αSMA + double-positive fibrocyte was decreased in the EPO-administered UUO kidneys.

Conclusion
EPO signals function to prevent kidney fibrosis, particularly in fibrocyte. Regulating the renal accumulation of fibrocyte is a part of the anti-fibrotic functions of EPO.
Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients
Authors: Wang Ding , Wei Guodong , Ma Ju , Cheng Shuai , Jia Longyuan , Song Xinyue , Zhang Ming , Ju Mingyi , Wang Lin , Zhao Lin , Xin Shijie 
Published: May 2021

Abstract
Background
Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which is a threat to women’s health worldwide. Ferroptosis is closely related to the occurrence and development of breast cancer. Here, we aimed to establish a ferroptosis-related prognostic gene signature for predicting patients’ survival.

Methods
Gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis model was utilized to construct a multigene signature. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and single-sample gene set enrichment analysis (ssGSEA) were performed for patients between the high-risk and low-risk groups divided by the median value of risk score.

Results
We constructed a prognostic signature consisted of nine ferroptosis-related genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD and ACSF2). The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the ROC curves manifested that the ferroptosis-related signature had moderate predictive power. GO and KEGG functional analysis revealed that immune-related responses were largely enriched, and immune cells, including activated dendritic cells (aDCs), dendritic cells (DCs), T-helper 1 (Th1), were higher in high-risk groups (p < 0.001). Oppositely, type I IFN response and type II IFN response were lower in high-risk groups (p < 0.001).

Conclusion
Our study indicated that the ferroptosis-related prognostic signature gene could serve as a novel biomarker for predicting breast cancer patients’ prognosis. Furthermore, we found that immunotherapy might play a vital role in therapeutic schedule based on the level and difference of immune-related cells and pathways in different risk groups for breast cancer patients.
Genomic stratification based on microenvironment immune types and PD-L1 for tailoring therapeutic strategies in bladder cancer
Authors: Lyu Xintong , Wang Ping , Qiao Qiao , Jiang Yuanjun 
Published: May 2021

Abstract
Background
The tumour microenvironment (TME) not only plays a role during tumour progression and metastasis but also profoundly influences treatment efficacy. Environment-mediated drug resistance is a result of crosstalk between tumour cells and stroma. The presence of a “stromal exhaustion” response is suggested by the T cell exhaustion signature and PD-L1 expression. The prognostic role of PD-L1 in bladder cancer has been investigated in previous studies, but the results remain inconclusive. For a more comprehensive study, we discuss potential strategies to improve effectiveness in patients with various TME statuses and PD-L1 expression levels.

Methods
We estimated the prognostic role of PD-L1 using immunohistochemistry and identified four immune subtypes according to the type of stromal immune modulation and PD-L1 expression status.

Results
Patients in the PD-L1-low-exhausted group had the worst prognosis and showed the worst antigen-presenting cell (APC) immunosuppression status. The PD-L1-low-exhausted group showed the highest amount of infiltration by macrophage M2 cells, naïve B cells and resting mast cells. The TMB and the effectiveness of anti-PD-1 treatment were significantly increased in the PD-L1-high expression groups compared with the PD-L1-low expression groups. In the PD-L1-high groups, patients who underwent chemotherapy exhibited better overall survival rates than patients who did not undergo chemotherapy, whereas there was no significant difference in the PD-L1-low groups. We performed gene set enrichment analysis (GSEA) to explore the critical pathways that were active in the PD-L1-low-exhausted group, including the myogenesis, epithelial-mesenchymal transition and adipogenesis pathways. Copy number variations (CNVs) were related to the expression levels of differentially expressed genes upregulated in the PD-L1-low-exhausted group, including LCNL1, FBP1 and RASL11B. In addition, RASL11B played a role in predicting overall survival according to The Cancer Genome Atlas data, and this finding was validated in the PD-L1-low-exhausted group in the Gene Expression Omnibus database (GEO).

Conclusion
The immune environment of tumours plays an important role in the therapeutic response rate, and defining the immune groups plays a critical role in predicting disease outcome and strategy effectiveness.
Predicting breast cancer drug response using a multiple-layer cell line drug response network model
Authors: Huang Shujun , Hu Pingzhao , Lakowski Ted M. 
Published: May 2021

Abstract
Background
Predicting patient drug response based on a patient’s molecular profile is one of the key goals of precision medicine in breast cancer (BC). Multiple drug response prediction models have been developed to address this problem. However, most of them were developed to make sensitivity predictions for multiple single drugs within cell lines from various cancer types instead of a single cancer type, do not take into account drug properties, and have not been validated in cancer patient-derived data. Among the multi-omics data, gene expression profiles have been shown to be the most informative data for drug response prediction. However, these models were often developed with individual genes. Therefore, this study aimed to develop a drug response prediction model for BC using multiple data types from both cell lines and drugs.

Methods
We first collected the baseline gene expression profiles of 49 BC cell lines along with IC50 values for 220 drugs tested in these cell lines from Genomics of Drug Sensitivity in Cancer (GDSC). Using these data, we developed a multiple-layer cell line-drug response network (ML-CDN2) by integrating a one-layer cell line similarity network based on the pathway activity profiles and a three-layer drug similarity network based on the drug structures, targets, and pan-cancer IC50 profiles. We further used ML-CDN2 to predict the drug response for new BC cell lines or patient-derived samples.

Results
ML-CDN2 demonstrated a good predictive performance, with the Pearson correlation coefficient between the observed and predicted IC50 values for all GDSC cell line-drug pairs of 0.873. Also, ML-CDN2 showed a good performance when used to predict drug response in new BC cell lines from the Cancer Cell Line Encyclopedia (CCLE), with a Pearson correlation coefficient of 0.718. Moreover, we found that the cell line-derived ML-CDN2 model could be applied to predict drug response in the BC patient-derived samples from The Cancer Genome Atlas (TCGA).

Conclusions
The ML-CDN2 model was built to predict BC drug response using comprehensive information from both cell lines and drugs. Compared with existing methods, it has the potential to predict the drug response for BC patient-derived samples.
Secondary choroidal neovascularization due to choroidal osteoma after 9 years follow-up
Authors: Zhang Yun , Fang Jia , Zhao Shixin , She Xiangjun , Wang Jun , Shen Lijun 
Published: May 2021

Abstract
Background
Choroidal osteoma is a benign intraocular tumor that can increase risk of developing choroidal neovascularization. The visual prognosis is influenced by the tumor location, decalcification status, overlying RPE atrophy, presence of choroidal neovascularization, persistence of subretinal fluid and occurrence of subretinal hemorrhages.

Case presentation
The authors present a 40-year-old woman diagnosed with choroidal osteoma of the right eye. Her best corrected visual acuity was 12/20 but decreased to 5/20 due to secondary choroidal neovascularization after 8 years follow up. Fundus examination revealed an enlarged choroidal osteoma in most margins at posterior pole with schistose hemorrhage beside macula. Optical coherence tomography angiography revealed unique features in the vascular changes of choroidal neovascularization in choroidal osteoma in the outer retinal layer and choroid capillary layers, and subretinal neovascularization. Indocyanine green fluorescence angiography showed there was hypo-fluorescence at the peripapillary with faint hyper-fluorescence at the macular, corresponding to the location on the fundus photograph. The patient received 3 injections of intravitreal ranibizumab. After 1 year follow up, her visual acuity of the right eye was 18/20 and the CNV had regressed.

Conclusions
We present the findings and treatment of a case of choroidal osteoma with secondary choroidal neovascularization. Optical coherence tomography angiography combined with FFA and ICGA is used to analysis the characteristics of secondary choroidal neovascularization. Optical coherence tomography angiography can reveal some unique characteristics in the vascular changes compared to fundus fluorescein angiography.
A de novo 10q11.23q22.1 deletion detected by whole genome mate-pair sequencing: a case report
Authors: Fu Dalin , Lin Weisheng , Lu Fen , Du Senjie , Zhu Min , Zhao Xiaoke , Tang Jian , Chen Chuan , Chui Xiaoli , Tang Shanmei , Wang Kai , Yang Chuanchun , Han Bei 
Published: May 2021

Abstract
Background
Interstitial deletions of chromosome band 10q11-q22 was a genomic disorder distinguished by developmental delay, congenital cleft palate and muscular hypotonia. The phenotypes involved were heterogeneous, hinge on the variable breakpoints and size.

Case presentation
Here, we presented a patient with soft palate cleft, growth and development delay. The patient was a 2 years and 5 months girl who was not able to walk unless using a children’s crutches to support herself. Whole-exome sequencing (WES) and whole-genome mate-pair sequencing (WGMS) were both performed by next generation sequencing (NGS). A 20.76 Mb deletion at 10q11.23q22.1 (seq[GRCh37/hg19]del(10)(50,319,387-71,083,899) × 1) was revealed by the WGMS, which was verified as de novo by quantitative polymerase chain reaction (QPCR).

Conclusion
Children with 10q11-q22 deletions greater than 20 MB have never been reported before, and we are the first to report and provide a detailed clinical phenotype, which brings further knowledge of 10q11-q22 deletions.
Discrepancy between experience and importance of recovery components in the symptomatic and recovery perceptions of people with severe mental disorders
Authors: Penas Patricia , Uriarte Jose-Juan , Gorbeña Susana , Slade Mike , Moreno-Calvete María-Concepción , Iraurgi Ioseba 
Published: May 2021

AbstractBackgroundPersonal recovery has become an increasingly important approach in the care of people with severe mental disorders and consequently in the orientation of mental health services. The objective of this study was to assess the personal recovery process in people using mental health services, and to clarify the role of variables such as symptomatology, self-stigma, sociodemographic and treatment.MethodsStandardised measures of personal recovery process, clinical recovery, and internalized stigma were completed by a sample of 312 participants in a Severe Mental Disorder program.ResultsUsers valued most the recovery elements of: improving general health and wellness; having professionals who care; hope; and sense of meaning in life. Significant discrepancies between perceived experience and relative importance assigned to each of the components of the REE were observed. Regression modeling (χ2 = 6.72,p = .394; GFI = .99, SRMR = .03) identified how positive discrepancies were associated with a higher presence of recovery markers (β = .12,p = .05), which in turn were negatively related to the derived symptomatology index (β = −.33,p < .001). Furthermore, the relationship between clinical and personal recovery was mediated by internalized stigma.ConclusionsAn improvement in psychiatric services should be focused on recovery aspects that have the greatest discrepancy between importance and experience, in particular social roles, basic needs and hope. Personal and clinical recovery are correlated, but the relationship between them is mediated by internalized stigma, indicating the need for clinical interventions to target self-stigma.
Patterns and predictors of sick leave after Covid-19 and long Covid in a national Swedish cohort
Authors: Westerlind Emma , Palstam Annie , Sunnerhagen Katharina S. , Persson Hanna C. 
Published: May 2021

Abstract
Background
The impact of Covid-19 and its long-term consequences is not yet fully understood. Sick leave can be seen as an indicator of health in a working age population, and the present study aimed to investigate sick-leave patterns after Covid-19, and potential factors predicting longer sick leave in hospitalised and non-hospitalised people with Covid-19.

Methods
The present study is a comprehensive national registry-based study in Sweden with a 4-month follow-up. All people who started to receive sickness benefits for Covid-19 during March 1 to August 31, 2020, were included. Predictors of sick leave ≥1 month and long Covid (≥12 weeks) were analysed with logistic regression in the total population and in separate models depending on inpatient care due to Covid-19.

Results
A total of 11,955 people started sick leave for Covid-19 within the inclusion period. The median sick leave was 35 days, 13.3% were on sick leave for long Covid, and 9.0% remained on sick leave for the whole follow-up period. There were 2960 people who received inpatient care due to Covid-19, which was the strongest predictor of longer sick leave. Sick leave the year prior to Covid-19 and older age also predicted longer sick leave. No clear pattern of socioeconomic factors was noted.

Conclusions
A substantial number of people are on sick leave due to Covid-19. Sick leave may be protracted, and sick leave for long Covid is quite common. The severity of Covid-19 (needing inpatient care), prior sick leave, and age all seem to predict the likelihood of longer sick leave. However, no socioeconomic factor could clearly predict longer sick leave, indicating the complexity of this condition. The group needing long sick leave after Covid-19 seems to be heterogeneous, indicating a knowledge gap.
Understanding mobile application development and implementation for monitoring Posyandu data in Indonesia: a 3-year hybrid action study to build “a bridge” from the community to the national scale
Authors: Rinawan Fedri Ruluwedrata , Susanti Ari Indra , Amelia Indah , Ardisasmita Mulya Nurmansyah , Widarti  , Dewi Rima Kusumah , Ferdian Dani , Purnama Wanda Gusdya , Purbasari Ayi 
Published: May 2021

Abstract
Background
Limited information is available on how mobile health (mHealth) application (app) technology on mother and child health (MCH) is developed. This research aimed (a) to explore the process of developing mobile apps for MCH community-based services in the Indonesian setting of Pos Pelayanan Terpadu (Posyandu/Integrated Health Service Post), (b) to determine the feasibility of using the app by community health workers (CHWs), and (c) to evaluate the scalability of the mobile app at the national level in Indonesia.

Methods
A hybrid method was used to synergistically combine the action research principles and mixed methods comprising qualitative and quantitative methods. This study was conducted in the Pasawahan District, Purwakarta, Indonesia, from 2017 to 2019. Content analysis, coding, and categorizing were performed using NVivo 12 Pro for transcribed data. The Wilcoxon test (2018 and 2019) was conducted using STATA 15 Special Edition.

Results
(1) The use of a CHW notebook for data entry into the Posyandu Information System book delayed the data reporting process, resulting in the need to develop a mobile app. (2) There were significant differences in CHWs’ knowledge (p = 0.000) and skills (p = 0.0097) on training (2018) and Posyandu phases (2019). (3) A total of 964 Posyandu have been registered in the Posyandu mobile app from almost all provinces in Indonesia.

Conclusions
The three-year hybrid approach includes the crucial phases that are necessary to develop a mobile app that is more user-friendly and can act as a substitute for CHWs’ book. Hence, its implementation is promising for use at the national level.
Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study
Authors: Ruan Sheng-Yuan , Huang Chun-Ta , Chien Ying-Chun , Huang Chun-Kai , Chien Jung-Yien , Kuo Lu-Cheng , Kuo Ping-Hung , Ku Shih-Chi , Wu Huey-Dong 
Published: May 2021

Abstract
Background
Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.

Methods
In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal–Wallis rank tests and Chi-squared tests were used to compare between-etiology differences.

Results
From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.

Conclusion
This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.
Design and evaluation of a learning assignment in the undergraduate medical curricula on the four dimensions of care: a mixed method study
Authors: Pieters Jolien , Verstegen Daniëlle M. L. , Dolmans Diana H. J. M. , Warmenhoven Franca C. , van den Beuken - van Everdingen Marieke H. J. 
Published: May 2021

Abstract
Background
Chronic and palliative care are rapidly gaining importance within the physician’s range of duties. In this context, it is important to address the four dimensions of care: physical, psychological, social, and spiritual. Medical students, however, feel inadequately equipped to discuss these dimensions with the patient. To bridge this gap, a new assignment was developed and implemented, in which students talked to a chronic or palliative patient about the four dimensions of care during an internship. This study, reports the evaluation of this assignment by students and teachers using a design-based approach.

Methods
Mixed methods were used, including a) student questionnaires, b) student focus groups, c) teacher interviews, and d) student’s written reflections. Two researchers performed analyses of the qualitative data from the focus groups, interviews, and written reflections using qualitative research software (ALTLAS.TI). Descriptive statistics were computed for the quantitative data using SPSS 21.0.

Results
Students and teachers valued talking to an actual patient about the four dimensions of care. Reading and providing peer feedback on each other’s reports was considered valuable, especially when it came to the diversity of illnesses, the way that patients cope and communication techniques. The students considered reflection useful, especially in the group and provided it was not too frequent. All the dimensions were addressed in the interviews, however the spiritual dimension was found to be the most difficult to discuss. The analysis of the written reflections revealed an overlap between the social and spiritual dimensions. Students pay a lot of attention to the relationship between the illness and the patient’s daily life, but the reflections do often not show insight in the potential relationship between the four dimensions and decisions in patient care.

Conclusions
During internships, medical students can practice talking about four dimensions of care with a chronically ill or palliative patient. Due to the format, it can be implemented across existing internships with relatively little extra time and effort. Reflection, peer feedback, and group discussion under the guidance of a teacher are important additions.