bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bereaved parents’ perspectives on their child’s end-of-life care: connecting a self-report questionnaire and interview data from the nationwide Paediatric End-of-LIfe CAre Needs in Switzerland (PELICAN) study
Authors: Zimmermann Karin , Marfurt-Russenberger Katrin , Cignacco Eva , Bergstraesser Eva 
Published: May 2022

AbstractBackgroundPaediatric Palliative Care (PPC) focuses on ensuring the best possible quality of life for the child and his/her family by extending beyond the physical domain into psychosocial and spiritual wellbeing. A deep understanding of what is important to parents is crucial in guiding the further evaluation and improvement of PPC and end-of-life (EOL) care services. Much can be learned from specific positive and negative experiences of bereaved parents with the EOL care of their child. This report builds upon a questionnaire survey as part of the national Paediatric End-of-LIfe CAre Needs in Switzerland (PELICAN) study.MethodsOne part of the PELICAN study was set up to assess and explore the parental perspectives on their child’s EOL care. Interview data were used to explain the extremely positive and negative results of a quantitative survey in an explanatory sequential mixed-methods approach. Data integration occurred at different points: during sampling of the interview participants, when designing the interview guide and during analysis. A narrative approach was applied to combine the qualitative results reported here with the already published quantitative survey results.ResultsEighteen mothers (60%) and twelve fathers (40%) participated in 20 family interviews. All parents reported having both positive and negative experiences during their child’s illness and EOL, which was characterised by many ups and downs. The families transitioned through phases with a prospect of a cure for some children as well as setbacks and changing health status of the child which influenced prognosis, leading to the challenge of making extremely difficult decisions. Severely negative experiences still haunted and bothered the parents at the time when the interview took place.ConclusionsA deep understanding of the perspectives and needs of parents going through the devastating event of losing a child is important and a prerequisite to providing compassionate care. This complex care needs to recognise and respond to the suffering not only of the child but of the parents and the whole family. Communication and shared decision-making remain pivotal, as do still improvable elements of care that should build on trustful relationships between families and healthcare professionals.
Ursolic acid-enriched kudingcha extract enhances the antitumor activity of bacteria-mediated cancer immunotherapy
Authors: Xu Haixia , Piao Linghua , Liu Xiande , Jiang Sheng-nan 
Published: May 2022

Abstract
Background
Bacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities.

Methods
We investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.t△ppGpp in the mice colon cancer models.

Results
In the present study, KDCE combined with S.t△ppGpp BCI improved antitumor therapeutic efficacy compared to S.t△ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.t△ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK.

Conclusions
Ursolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.t△ppGpp and KDCE is a potential cancer therapeutic strategy.
Fusing pre-trained convolutional neural networks features for multi-differentiated subtypes of liver cancer on histopathological images
Authors: Dong Xiaogang , Li Min , Zhou Panyun , Deng Xin , Li Siyu , Zhao Xingyue , Wu Yi , Qin Jiwei , Guo Wenjia 
Published: May 2022

AbstractLiver cancer is a malignant tumor with high morbidity and mortality, which has a tremendous negative impact on human survival. However, it is a challenging task to recognize tens of thousands of histopathological images of liver cancer by naked eye, which poses numerous challenges to inexperienced clinicians. In addition, factors such as long time-consuming, tedious work and huge number of images impose a great burden on clinical diagnosis. Therefore, our study combines convolutional neural networks with histopathology images and adopts a feature fusion approach to help clinicians efficiently discriminate the differentiation types of primary hepatocellular carcinoma histopathology images, thus improving their diagnostic efficiency and relieving their work pressure. In this study, for the first time, 73 patients with different differentiation types of primary liver cancer tumors were classified. We performed an adequate classification evaluation of liver cancer differentiation types using four pre-trained deep convolutional neural networks and nine different machine learning (ML) classifiers on a dataset of liver cancer histopathology images with multiple differentiation types. And the test set accuracy, validation set accuracy, running time with different strategies, precision, recall and F1 value were used for adequate comparative evaluation. Proved by experimental results, fusion networks (FuNet) structure is a good choice, which covers both channel attention and spatial attention, and suppresses channel interference with less information. Meanwhile, it can clarify the importance of each spatial location by learning the weights of different locations in space, then apply it to the study of classification of multi-differentiated types of liver cancer. In addition, in most cases, the Stacking-based integrated learning classifier outperforms other ML classifiers in the classification task of multi-differentiation types of liver cancer with the FuNet fusion strategy after dimensionality reduction of the fused features by principle component analysis (PCA) features, and a satisfactory result of 72.46% is achieved in the test set, which has certain practicality.
The role of retinoid-related orphan receptor-α in cigarette smoke-induced autophagic response
Authors: Kim Hak-Su , An Chang Hyeok , Teller Danielle , Moon Su-Jin , Hwang Gi Won , Song Jin Woo 
Published: May 2022

Abstract
Background
Retinoid-related orphan receptor-α (RORα) and autophagy dysregulation are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD), but little is known regarding their association. We investigated the role of RORα in COPD-related autophagy.

Methods
The lung tissues and cells from a mouse model were analyzed for autophagy markers by using western blot analysis and transmission electron microscopy.

Results
Cigarette smoke increased the LC3-II level and decreased the p62 level in whole lung homogenates of a chronic cigarette smoking mouse model. Although cigarette smoke did not affect the levels of p62 in Staggerer mutant mice (RORαsg/sg), the baseline expression levels of p62 were significantly higher than those in wild type (WT) mice. Autophagy was induced by cigarette smoke extract (CSE) in Beas-2B cells and in primary fibroblasts from WT mice. In contrast, fibroblasts from RORαsg/sg mice failed to show CSE-induced autophagy and exhibited fewer autophagosomes, lower LC3-II levels, and higher p62 levels than fibroblasts from WT mice. Damage-regulated autophagy modulator (DRAM), a p53-induced modulator of autophagy, was expressed at significantly lower levels in the fibroblasts from RORαsg/sg mice than in those from WT mice. DRAM knockdown using siRNA in Beas-2B cells inhibited CSE-induced autophagy and cell death. Furthermore, RORα co-immunoprecipitated with p53 and the interaction increased p53 reporter gene activity.

Conclusions
Our findings suggest that RORα promotes autophagy and contributes to COPD pathogenesis via regulation of the RORα-p53-DRAM pathway.
Harm reduction calls to action from young people who use drugs on the streets of Vancouver and Lisbon
Authors: Canêdo Joana , Sedgemore Kali-olt , Ebbert Kelly , Anderson Haleigh , Dykeman Rainbow , Kincaid Katey , Dias Claudia , Silva Diana ,   Youth Health Advisory Council, Charlesworth Reith , Knight Rod , Fast Danya 
Published: May 2022

AbstractVancouver, Canada, and Lisbon, Portugal, are both celebrated for their world-leading harm reduction policies and programs and regarded as models for other cities contending with the effects of increasing levels of drug use in the context of growing urban poverty. However, we challenge the notion that internationally celebrated places like Lisbon and Vancouver are meeting the harm reduction needs of young people who use drugs (YPWUD; referring here to individuals between the ages of 14 and 29). In particular, the needs of YPWUD in the context of unstable housing, homelessness, and ongoing poverty—a context which we summarize here as “street involvement”—are not being adequately met. We are a group of community and academic researchers and activists working in Vancouver, Lisbon, and Pittsburgh. Most of us identify as YPWUD and have lived and living experience with the issues described in this comment. We make several calls to action to support the harm reduction needs of YPWUD in the context of street involvement in and beyond our settings.
Surgical resection for esophageal adenosquamous carcinoma: an analysis of 56 cases
Authors: Chen Shao-bin , Liu Di-tian , Chen Yu-ping 
Published: May 2022

Abstract
Background
Esophageal adenosquamous carcinoma (EASC) is a rare disease. The biological behavior and treatment of this malignancy are not well studied.

Methods
Data from 56 patients with EASC who underwent esophagectomy were retrospectively analyzed and compared with 5028 patients with esophageal squamous cell carcinoma (ESCC). The impact of clinicopathological factors on the survival of patients with EASC was analyzed. The survival differences between patients with EASC and ESCC were also compared.

Results
There were 43 males and 13 females with a mean age of 59.7 ± 1.3 years (range, 39–79 years). Only 1 of the 43 patients who received preoperative esophagoscopic biopsy was diagnosed with EASC. The median survival time for patients with EASC was 32.0 months, and the 1-, 3-, and 5-year overall survival rates were 78.3%, 46.1%, and 29.6%, respectively. Resection margin, pN category, and adjuvant chemotherapy were found to be independent predictors. After 1:1 propensity score matching, the 5-year overall survival rate of 29.6% for patients with EASC was similar to that of 42.5% for patients with ESCC (P = 0.179).

Conclusions
EASC is a rare disease and is easily misdiagnosed by esophagoscopic biopsy. The prognosis of EASC was similar to that of ESCC. Postoperative adjuvant chemotherapy may improve the survival of patients with EASC after esophagectomy.
Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis
Authors: Wang Jiaqian , Xue Yuan , Zhou Liang 
Published: May 2022

Abstract
Background
Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are chronic autoimmune diseases, but they are usually difficult to distinguish in the early stage of the diseases. The purpose of this study is to explore the differences of immune mechanism and diagnostic markers through bioinformatics analysis.

Methods
First, microarray datasets from patients with SpA, RA and normal controls were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between groups were identified in R software. Functional and pathway enrichment of DEGs were analyzed by David database. Then, we screened the hub genes using Cytoscape plugin, and constructed the protein–protein interaction (PPI) network and heatmap of hub genes. After that, CIBERSORT was used to evaluate the differences and connections of immune cells in SpA and RA, and screened out diagnostic markers. Correlation analysis was used to analyze the relationship between immune cells and diagnostic markers. Finally, quantitative real-time polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of immunodiagnostic markers.

Results
We obtained three datasets, from which we can see that the functional enrichment of DEGs is mainly in cell chemotaxis, lymphocyte activation, primary immunodeficiency and other immune responses. The difference of immune cells between SpA, RA and normal control was concentrated in B, T lymphocytes cells, macrophages and dendritic cells. C19orf12 + S1PR3 is most associated with these immune cells and S1PR3 can be used as a diagnostic marker of this kind of immune diseases. In addition, MZB1 + XIST is closely related to T cells, NK cells and dendritic cells, and is expected to be used as a marker to distinguish the two diseases.

Conclusion
Although the clinical manifestations of SpA and RA are similar, the pathogenesis is different. The screening of immune cells and diagnostic markers provides a more accurate target for the treatment of this kind of diseases.
Single-cell N6-methyladenosine regulator patterns guide intercellular communication of tumor microenvironment that contribute to colorectal cancer progression and immunotherapy
Authors: Gao Yuzhen , Wang Hao , Chen Shipeng , An Rui , Chu Yadong , Li Guoli , Wang Yanzhong , Xie Xinyou , Zhang Jun 
Published: May 2022

Abstract
Background
N6-methyladenosine (m6A) RNA methylation plays a critical role in key genetic events for various cancers; yet, how m6A functions within the tumor microenvironment (TME) remains to be elucidated.

Methods
A total of 65,362 single cells from single-cell RNA-seq data derived from 33 CRC tumor samples were analyzed by nonnegative matrix factorization (NMF) for 23 m6A RNA methylation regulators. CRC and Immunotherapy cohorts from public repository were used to determine the prognosis and immune response of TME clusters.

Results
The fibroblasts, macrophages, T and B cells were respectively grouped into 4 to 5 subclusters and then classified according to various biological processes and different marker genes. Furthermore, it revealed that the m6A RNA methylation regulators might be significantly related to the clinical and biological features of CRC, as well as the pseudotime trajectories of main TME cell types. Bulk-seq analysis suggested that these m6A-mediated TME cell subclusters had significant prognostic value for CRC patients and distinguished immune response for patients who underwent ICB therapy, especially for the CAFs and macrophages. Notably, CellChat analysis revealed that RNA m6A methylation-associated cell subtypes of TME cells manifested diverse and extensive interaction with tumor epithelial cells. Further analysis showed that ligand-receptor pairs, including MIF −  (CD74 + CXCR4), MIF −  (CD74 + CD44), MDK–NCL and LGALS9 − CD45, etc. mediated the communication between m6A associated subtypes of TME cells and tumor epithelial cells.

Conclusions
Taken together, our study firstly revealed the m6A methylation mediated intercellular communication of the tumor microenvironment in the regulation of tumor growth and antitumor immunomodulatory processes.
CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling
Authors: Zhu Lili , Yang Xiaobei , Feng Jingyu , Mao Jian , Zhang Qidong , He Mengru , Mi Yang , Mei Yingwu , Jin Ge , Zhang Haifeng 
Published: May 2022

AbstractObjectiveKnowledge of the role of CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus on the role of CYP2E1 in metabolic activation of procarcinogens. Few studies have directly assessed the effects of CYP2E1 on HCC malignant phenotypes.MethodsThe expression of CYP2E1 in HCC tissues was determined by qRT-PCR, western blotting and immunohistochemistry. Overexpression of CYP2E1 in HCC cell was achieved by lentivirus transfection. The function of CYP2E1 were detected by CCK-8, wound healing, transwell assays, xenograft models and pulmonary metastasis model. TOP/FOPFlash reporter assay, western blotting, functional rescue experiments, Co-immunoprecipitation and reactive oxygen species detection were conducted to reveal the underlying mechanism of the tumor suppressive role of CYP2E1.ResultsCYP2E1 expression is down-regulated in HCC tissues, and this downregulation was associated with large tumor diameter, vascular invasion, poor differentiation, and shortened patient survival time. Ectopic expression of CYP2E1 inhibits the proliferation, invasion and migration and epithelial-to-mesenchymal transition of HCC cells in vitro, and inhibits tumor formation and lung metastasis in nude mice. Mechanistic investigations show that CYP2E1 overexpression significantly inhibited Wnt/β-catenin signaling activity and decreased Dvl2 expression in HCC cells. An increase in Dvl2 expression restored the malignant phenotype of HCC cells. Notably, CYP2E1 promoted the ubiquitin-mediated degradation of Dvl2 by strengthening the interaction between Dvl2 and the E3 ubiquitin ligase KLHL12 in CYP2E1-stable HCC cells. CYP2E1-induced ROS accumulation was a critical upstream event in the Wnt/β-Catenin pathway in CYP2E1-overexpressing HCC cells.ConclusionsThese results provide novel insight into the role of CYP2E1 in HCC and the tumor suppressor role of CYP2E1 can be attributed to its ability to manipulate Wnt/Dvl2/β-catenin pathway via inducing ROS accumulation, which provides a potential target for the prevention and treatment of HCC.Graphical Abstract
Enhanced DNA and RNA pathogen detection via metagenomic sequencing in patients with pneumonia
Authors: He Yukun , Fang Kechi , Shi Xing , Yang Donghong , Zhao Lili , Yu Wenyi , Zheng Yali , Xu Yu , Ma Xinqian , Chen Li , Xie Yu , Yu Yan , Wang Jing , Gao Zhancheng 
Published: May 2022

Abstract
Background
Metagenomic next-generation sequencing (mNGS) is an important supplement to conventional tests for pathogen detections of pneumonia. However, mNGS pipelines were limited by irregularities, high proportion of host nucleic acids, and lack of RNA virus detection. Thus, a regulated pipeline based on mNGS for DNA and RNA pathogen detection of pneumonia is essential.

Methods
We performed a retrospective study of 151 patients with pneumonia. Three conventional tests, culture, loop-mediated isothermal amplification (LAMP) and viral quantitative real-time polymerase chain reaction (qPCR) were conducted according to clinical needs, and all samples were detected using our optimized pipeline based on the mNGS (DNA and RNA) method. The performances of mNGS and three other tests were compared. Human DNA depletion was achieved respectively by MolYsis kit and pre-treatment using saponin and Turbo DNase. Three RNA library preparation methods were used to compare the detection performance of RNA viruses.

Results
An optimized mNGS workflow was built, which had only 1-working-day turnaround time. The proportion of host DNA in the pre-treated samples decreased from 99 to 90% and microbiome reads achieved an approximately 20-fold enrichment compared with those without host removal. Meanwhile, saponin and Turbo DNase pre-treatment exhibited an advantage for DNA virus detection compared with MolYsis. Besides, our in-house RNA library preparation procedure showed a more robust RNA virus detection ability. Combining three conventional methods, 76 (76/151, 50.3%) cases had no clear causative pathogen, but 24 probable pathogens were successfully detected in 31 (31/76 = 40.8%) unclear cases using mNGS. The agreement of the mNGS with the culture, LAMP, and viral qPCR was 60%, 82%, and 80%, respectively. Compared with all conventional tests, mNGS had a sensitivity of 70.4%, a specificity of 72.7%, and an overall agreement of 71.5%.

Conclusions
A complete and effective mNGS workflow was built to provide timely DNA and RNA pathogen detection for pneumonia, which could effectively remove the host sequence, had a higher microbial detection rate and a broader spectrum of pathogens (especially for viruses and some pathogens that are difficult to culture). Despite the advantages, there are many challenges in the clinical application of mNGS, and the mNGS report should be interpreted with caution.
Entropy as the main justification for research in medical ethics
Authors: Zarzavadjian Le Bian Alban , Pantel Louis , Tresallet Christophe , Mamzer Marie-France 
Published: May 2022

AbstractEthics is an unconventional field of research for a surgeon, as ethics in surgery owns several specificities and surgery is considered an aggressive specialty. Therefore, the interest of research in medical ethics is sometimes unclear.In this short essay, we discussed the interest of research in medical ethics using a comparison to thermodynamics and mainly, entropy. During the transformation of a figure from one state to another, some energy is released or absorbed; yet, a part of this energy is wasted because of “unordered” (and unsuccessful) reactions: it is Entropy.This “wasted energy” exists in Medical practice and justifies research in Medical ethics.
3D chromatin architecture and transcription regulation in cancer
Authors: Deng Siwei , Feng Yuliang , Pauklin Siim 
Published: May 2022

AbstractChromatin has distinct three-dimensional (3D) architectures important in key biological processes, such as cell cycle, replication, differentiation, and transcription regulation. In turn, aberrant 3D structures play a vital role in developing abnormalities and diseases such as cancer. This review discusses key 3D chromatin structures (topologically associating domain, lamina-associated domain, and enhancer–promoter interactions) and corresponding structural protein elements mediating 3D chromatin interactions [CCCTC-binding factor, polycomb group protein, cohesin, and Brother of the Regulator of Imprinted Sites (BORIS) protein] with a highlight of their associations with cancer. We also summarise the recent development of technologies and bioinformatics approaches to study the 3D chromatin interactions in gene expression regulation, including crosslinking and proximity ligation methods in the bulk cell population (ChIA-PET and HiChIP) or single-molecule resolution (ChIA-drop), and methods other than proximity ligation, such as GAM, SPRITE, and super-resolution microscopy techniques.