bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer‐Associated Fibroblast‐Mediated Cellular Crosstalk Supports Hepatocellular Carcinoma Progression
Authors: Song Mengjia , He Junyi , Pan Qiu‐Zhong , Yang Jieying , Zhao Jingjing , Zhang Yao‐Jun , Huang Yue , Tang Yan , Wang Qijing , He Jia , Gu Jiamei , Li Yongqiang , Chen Shiping , Zeng Jianxiong , Zhou Zi‐Qi , Yang Chaopin , Han Yulong , Chen Hao , Xiang Tong , Weng De‐Sheng , Xia Jian‐Chuan 
Published: March 2021

Background and Aims
Cancer‐associated fibroblasts (CAFs) are key players in multicellular, stromal‐dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor‐associated neutrophils (TANs) during different stages of HCC pathogenesis.

Approach and Results
In the HCC‐TME, CAF‐derived cardiotrophin‐like cytokine factor 1 (CLCF1) increased chemokine (C‐X‐C motif) ligand 6 (CXCL6) and TGF‐β secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGF‐β secreted by HCC cells activated extracellular signal‐regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1‐mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up‐regulation of the CLCF1−CXCL6/TGF‐β axis exhibited a marked correlation with increased cancer stem cells, “N2”‐polarized TANs, tumor stage, and poor prognosis.

Conclusions
This study reveals a cytokine‐mediated cellular crosstalk and clinical network involving the CLCF1−CXCL6/TGF‐β axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.
Epoxyazadiradione induced apoptosis/anoikis in triple‐negative breast cancer cells, MDA‐MB‐231, by modulating diverse cellular effects
Authors: Lakshmi Sreerenjini , Renjitha Jalaja , B. Sasidhar Somappa , Priya Sulochana 
Published: March 2021

AbstractTriple‐negative breast cancer (TNBC) is one of the most aggressive forms of its kind, which accounts for 15–20% of all breast cancers. As this cancer form lacks hormone receptors, targeted chemotherapy remains the best treatment option. Apoptosis and anoikis (detachment‐induced cell death) induction by small molecules can prevent TNBC metastasis to a greater extent. Epoxyazadiradione (EAD) is a limonoid from the neem plant with an anticancer property. Here, we demonstrate that EAD induced mitochondria‐mediated apoptosis and anoikis in TNBC cells (MDA‐MB‐231). Apart from this, it promotes antimigration, inhibition of colony formation, downregulation of MMP‐9 and fibronectin, induction of G2/M phase arrest with downregulation of cyclin A2/cdk2, interference in cellular metabolism, and inhibition of nuclear factor kappa‐B (NF‐kB) nuclear translocation. Moreover, a significant reduction is observed in the expression of EGFR on the plasma membrane and nucleus upon treatment with EAD. Among the diverse cellular effects, anoikis induction, metabolic interference, and downregulation of membrane/nuclear EGFR expression by EAD are reported here for the first time. To summarize, EAD targets multiple cellular events to induce growth arrest in TNBC, and hence can be developed into the best antineoplastic agent in the future.
RETRACTED: Long non‐coding RNA KCNQ1OT1 promotes the progression of gastric cancer via the miR‐145‐5p/ARF6 axis
Authors: Zhong Xiongdong , Wen Xiaoyan , Chen Lei , Gu Ni , Yu Xianchang , Sui Kang 
Published: March 2021

AbstractBackgroundLong non‐coding RNA KCNQ1 opposite strand/antisense transcript one gene (KCNQ1OT1) has been reported to be involved in the progression of many types of human cancer, whereas its role in gastric cancer (GC) remains unknown. The present study aimed to investigate the role of KCNQ1OT1 in GC.MethodsIn total, 25 GC tissues and adjacent normal tissues were collected. The expression of KCNQ1OT1, miR‐145‐5p and ARF6 in GC tissues and cell lines was detected by quantitative reverse transcriptase‐polymerase chain reaction or western blotting. Bioinformatics analysis and a dual luciferase reporter assay were performed to determine the relationship between KCNQ1OT1 and miR‐145‐5p or miR‐145‐5p and ARF6. Gain‐ and loss‐of function of KCNQ1OT1 and miR‐145‐5p were achieved to confirm their roles in GC cells. Cell counting kit‐8, colony formation and flow cytometry assays were used to evaluate cell viability, proliferation and apoptosis. A xenograft tumor model was established with BGC803 tumor cells transfected with sh‐KCNQ1OT1 or empty vector to determine the role of LINC01089 in vivo.ResultsThe expression levels of KCNQ1OT1 were markedly elevated in GC tissues and cells. Knockdown of KCNQ1OT1 inhibited GC tumor growth, reduced GC cell viability and colony formation, and induced GC cell apoptosis. The expression levels of miR‐145‐5p were significantly decreased in GC cells and correlated with the expression of KCNQ1OT1 in GC tumors. Moreover, KCNQ1OT1 directly binds with miR‐145‐5p, which is targeting ARF6. Knockdown of KCNQ1OT1 increased the expression levels of miR‐145‐5p. Inhibition of miR‐145‐5p increased the expression levels of KCNQ1OT1 and also attenuated the effects of knockdown of KCNQ1OT1 on the viability, proliferation and apoptosis of GC cells. In addition, overexpression of miR‐145‐5p reduced GC cell viability and colony formation and induced GC cell apoptosis, whereas overexpression of ARF6 attenuated the effects of overexpression of miR‐145‐5p on GC cell viability, colony formation and apoptosis.ConclusionsKCNQ1OT1 can promote GC progression through the miR‐145‐5p/ARF6 axis. KCNQ1OT1 may serve as a therapeutic target and a diagnostic biomarker of GC.
Sodium houttuyfonate attenuates dextran sulfate sodium associated colitis precolonized withCandida albicansthrough inducing β-glucan exposure
Authors: Ma Kelong , Chen Mengli , Liu Juanjuan , Ge Yuzhu , Wang Tianming , Wu Daqiang , Yan Guiming , Wang Changzhong , Shao Jing 
Published: March 2021

AbstractInflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis is a chronic intestinal disease most likely associated with gut dysbiosis. Candida related mycobiota has been demonstrated to play a role in IBD progression. Traditional Chinese herbal medicines (TCHMs) with antifungal activity have a potential in prevention and treatment of fungi-related IBD. Sodium houttuyfonate (SH) is a promising anti-Candida TCHMs. In this study, a dextran sulfate sodium induced colitis model with Candida albicans precolonization is established. SH gavage can significantly decrease the fungal burdens in feces and colon tissues, reduce disease activity index score, elongate colon length, and attenuate colonic damages. Moreover, SH markedly inhibits the levels of anti-Saccharomyces cerevisiae antibodies, β-glucan, and proinflammatory cytokine (IL-1β, IL-6, IL-8, TNF-α), and increases anti-inflammatory factor IL-10 level in serum and colon tissue. Further experiments demonstrate that SH could induce β-glucan exposure, priming intestinal macrophages to get rid of colonized C. albicans through the collaboration of Dectin-1 and TLR2/4. With the decreased fungal burden, the protein levels of Dectin-1, TLR2, TLR4, and NF-κBp65 are fallen back, indicating the primed macrophages calm down and the colitis is alleviated. Collectively, these results manifest that SH can attenuate C. albicans associated colitis via β-glucan exposure, deepening our understanding of TCHMs in the prevention and treatment of fungi associated IBD.
Immunotherapeutic effect of adenovirus encoding antimicrobial peptides in experimental pulmonary tuberculosis
Authors: Ramos-Espinosa Octavio , Mata-Espinosa Dulce , Francisco-Cruz Alejandro , López-Torres Manuel Othoniel , Hernández-Bazán Sujhey , Barrios-Payán Jorge , Marquina-Castillo Brenda , Carretero Marta , del Río Marcela , Hernández-Pando Rogelio 
Published: March 2021

AbstractAs components of the innate immune response, antimicrobial peptides (AMPs) efficiently contribute to infection control and maintenance of a latent state in pulmonary tuberculosis (TB). As a therapeutic strategy, the administration of recombinant AMPs could be limited by enzymatic degradation and high production costs. Likewise, strategies based on the induction of AMPs have generated controversial results. In this study, 2 recombinant type-5 adenoviruses (Ad) expressing the human β-defensin 3 (HβD3) or cathelicidin (LL37) were assessed in a murine pulmonary TB model. Mice infected with either a high dose of a drug-sensitive (H37Rv) or a multidrug-resistant (MDR) strain of Mycobacterium tuberculosis (Mtb) were treated with a single administration of AdHβD3, AdLL37, AdGFP (control vector expressing a green fluorescent protein), or saline solution (SS). Lungs were obtained to determine the bacterial burden, histologic damage, and cytokine expression at different time points. Mice treated with AdHβD3 or AdLL37 showed significantly lower bacterial load and pneumonia, and higher proinflammatory cytokine expression than the control groups AdGFP and SS. A synergistic therapeutic effect could be observed when first- or second-line antibiotics (ABs) were administered with adenoviral therapy in animals infected with H37Rv or MDR strains, respectively. Adenovirus-delivered AMP's administration constitutes a promising adjuvant therapy for current anti-TB drugs by enhancing a protective immune response and potentially reducing current AB regimes' duration.
Evaluation of Carotid Artery Elasticity in Early Stage of Kawasaki Disease by Two‐Dimensional Speckle Tracking Imaging
Authors: Yang Guiming , Xu Qiuqin , Hou Cui , Wang Hui , Ding Yueyue , Gu Peipei , Chen Long , Tang Yunjia , Chen Ye , Sun Ling , Lv Haitao 
Published: March 2021

ObjectivesChildren with Kawasaki disease (KD) often develop impaired arterial function. The aim of the study was to assess the feasibility and efficacy of two‐dimensional speckle tracking technique (2DSTI) for the evaluation of carotid artery elasticity in children with early‐stage KD.MethodsChildren with KD (n = 97), age and sex‐matched children with fever (n = 18), and healthy controls (n = 24) were included. Children with KD were subsequently divided into a coronary artery lesion group (CAL group, 27 cases) and a noncoronary artery lesion group (nCAL group, 70 cases) based on the results of echocardiography. The carotid circumferential peak strain (CCS) and carotid intima‐media thickness (CIMT) for the children in each group were measured, and the laboratory indicators for each group were collected.ResultsThe CCS of children with KD was lower than that of children with fever and healthy controls (P = .001 and .008), whereas CIMT was not significantly different among the groups. Moreover, the CCS of children in the CAL group was lower than that of children in the nCAL group and healthy controls (P = .001 and .000, respectively), whereas the CIMT of children in the CAL group was higher than that of children in the nCAL group (P = .014). In children with KD, CCS was negatively correlated with C‐reactive protein (CRP) and alanine aminotransferase (ALT) (r = −.419, P = .001; and r = −.305, P = .003). However, CCS was negatively correlated with CRP (r = −.508, P = .007) but not ALT (r = −.176, P = .379) in children in the CAL group.ConclusionCCS determined based on 2DSTI can reflect changes in the carotid artery elasticity function in the early stage of KD.
Type 2 Diabetes as a Determinant of Parkinson's Disease Risk and Progression
Authors: Chohan Harneek , Senkevich Konstantin , Patel Radhika K. , Bestwick Jonathan P. , Jacobs Benjamin M. , Bandres Ciga Sara , Gan‐Or Ziv , Noyce Alastair J. 
Published: March 2021

AbstractBackgroundType 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta‐analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting.ObjectiveThe objective was to investigate T2DM as a determinant of PD through a meta‐analysis of observational and genetic summary data.MethodsA systematic review and meta‐analysis of observational studies was undertaken by searching 6 databases. We selected the highest‐quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome‐wide association studies.ResultsIn the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07–1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39–0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 to −0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse‐variance weighted method [IVW] OR 1.08, 95% CI 1.02–1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01–1.20; P = 0.032) but not on cognitive progression.ConclusionsUsing meta‐analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Novel SLC12A2-ROS1 Fusion in Non-Small Cell Lung Cancer with a Significant Response to Crizotinib: The Importance of Choosing the Appropriate Next-Generation Sequencing Assay
Authors: Rodríguez-Antolín Carlos , Rosas-Alonso Rocío , Cruz Patricia , Higuera Oliver , Sánchez-Cabrero Darío , Esteban-Rodríguez Isabel , Peláez-García Alberto , Fernández Montaño Victoria Eugenia , Rodríguez-Jiménez Carmen , Ibáñez de Cáceres Inmaculada , Castro Javier 
Published: March 2021

Abstract

Identifying the druggable target is crucial for patients with nonsquamous advanced non-small cell lung cancer (NSCLC). This article adds to the spectrum of ROS1 fusion cases described in NSCLC. We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers: a fusion that has clinical and radiological sensitivity to crizotinib. Fluorescence in situ hybridization detected the SLC12A2-ROS1 fusion and it was confirmed through hybrid capture-based next-generation sequencing (NGS); however, the fusion could not be detected by amplicon-based assay. The success of implementing NGS into routine clinical practice depends on the accuracy of testing. The test's methodological features should then be considered because they significantly affect the results. Given this patient's response to crizotinib, identifying patients with undescribed ROS1 fusions has important therapeutic implications.

Key Points
This is the first known description of an SLC12A2-ROS1 fusion. Considering the patient's clinical features and tumor response observed after crizotinib therapy, the authors confirm that this new rearrangement has relevant clinical impact for patients with non-small cell lung cancer. The success of implementing next-generation sequencing (NGS) into routine clinical practice depends on the accuracy of the testing. Different assays and NGS platforms can achieve differing results. Each assay's limitations need to be considered to ensure the quality of precision medicine in clinical practice.
Optimal one‐ and two‐sided adaptive EWMA scheme for monitoring Poisson count data
Authors: Tang Anan , Castagliola Philippe , Hu Xuelong , Zhou Xiaojian 
Published: March 2021

AbstractThe Poisson distribution assumption often arises in several industrial applications for modeling defects or nonconformities. In this work, we investigate the one‐ and two‐sided performance of a new adaptive EWMA (exponentially weighted moving average)‐type chart for monitoring Poisson count data. An appropriate discrete‐state Markov chain technique is provided to compute the exact ARL (average run length) properties. Moreover, comparative studies are conducted to demonstrate the higher sensitivity of the proposed chart in the detection of shifts with various magnitudes. Advices on how to select the appropriate chart parameters are provided and an illustrative numerical example is proposed.
Multimodality treatment in immunocompromised patients with severe COVID‐19: the role of IL‐6 inhibitor, intravenous immunoglobulin, and haemoperfusion
Authors: Leelayuwatanakul Nophol , Kongpolprom Napplika , Sriprasart Thitiwat , Phoophiboon Vorakamol , Thanthitaweewat Vorawut , Thawanaphong Sarita , Sirichana Worawan , Chirakalwasan Naricha , Kawkitinarong Kamon , Sittipunt Chanchai , Putcharoen Opass , Paitoonpong Leilani , Suwanpimolkul Gompol , Jantarabenjakul Watsamon , Srisawat Nattachai , Pachinburavan Monvasi 
Published: March 2021

AbstractCytokine release syndrome (CRS) is known to be associated with severe coronavirus disease 2019 (COVID‐19). Multiple anti‐inflammatory therapies such as tocilizumab, corticosteroids, intravenous immunoglobulin (IVIG), and haemoadsorption or haemoperfusion have been used to combat this life‐threatening condition. However, immunocompromised hosts are often omitted from research studies, and knowledge on the clinical efficacy of these therapies in immunocompromised patients is therefore limited. We report two cases of immunocompromised patients with severe COVID‐19‐related CRS requiring mechanical ventilation who were treated with multimodality treatment consisting of tocilizumab, IVIG, and haemoperfusion. Within 48 h, both patients showed clinical improvement with PaO2:FiO2 ratio and haemodynamic stability. Both survived to discharge. There were no adverse events following these therapies. In conclusion, combined therapeutic modalities, possibly tailored to individual inflammatory profiles, are promising treatment for severe COVID‐19 infection in the immunocompromised host. Timely administration of adjunctive therapies that alleviate overwhelming inflammation may provide the best outcome.
Minimally invasive treatment of an intramural monolateral ectopic urether in a French bulldog with 78, XX (SRY‐negative) ovotesticular disorder of sexual development
Authors: Ferriani Riccardo , Moyano Hugo Rubens , Verde Davide , Bottero Enrico 
Published: March 2021

AbstractA one‐year‐old phenotypically female French Bulldog was referred for urinary incontinence. Physical examination disclosed the presence of hypertrophic clitoris. Computer tomography highlighted the presence of a left intramural ectopic ureter, in presence of a fully constituted female reproductive tract. Retrograde cystoscopy confirmed the presence of the ectopic ureter that was treated with cystoscopic‐guided laser ablation although incontinence persisted. Ovariohysterectomy and clitoridectomy were performed and histopathology of gonads was consistent with ovotestis. The subject's karyotype was defined as XX SRY‐negative and the case was diagnosed with a 78 XX (SRY‐negative) disorder of sexual development. A treatment with phenylpropanolamine led to the resolution of the incontinence. The association of such disorder with ectopic ureter and urinary incontinence has never been reported in dogs. Our findings suggest that the displacement of the ureter might be related to an incorrect secretion of sexual hormones in fetal life due to the presence of ovotestis.
A Rasch model analysis of two interpretations of ‘not relevant’ responses on the Dermatology Life Quality Index (DLQI)
Authors: Rencz Fanni , Mitev Ariel Z. , Szabó Ákos , Beretzky Zsuzsanna , Poór Adrienn K. , Holló Péter , Wikonkál Norbert , Sárdy Miklós , Kárpáti Sarolta , Szegedi Andrea , Remenyik Éva , Brodszky Valentin 
Published: March 2021

Abstract
Purpose
Eight of the ten items of the Dermatology Life Quality Index (DLQI) have a ‘not relevant’ response (NRR) option. There are two possible ways to interpret NRRs: they may be considered ‘not at all’ or missing responses. We aim to compare the measurement performance of the DLQI in psoriasis patients when NRRs are scored as ‘0’ (hereafter zero-scoring) and ‘missing’ (hereafter missing-scoring) using Rasch model analysis.

Methods
Data of 425 patients with psoriasis from two earlier cross-sectional surveys were re-analysed. All patients completed the paper-based Hungarian version of the DLQI. A partial credit model was applied. The following model assumptions and measurement properties were tested: dimensionality, item fit, person reliability, order of response options and differential item functioning (DIF).

Results
Principal component analysis of the residuals of the Rasch model confirmed the unidimensional structure of the DLQI. Person separation reliability indices were similar with zero-scoring (0.910) and missing-scoring (0.914) NRRs. With zero-scoring, items 6 (sport), 7 (working/studying) and 9 (sexual difficulties) suffered from item misfit and item-level disordering. With missing-scoring, no misfit was observed and only item 7 was illogically ordered. Six and three items showed DIF for gender and age, respectively, that were reduced to four and three by missing-scoring.

Conclusions
Missing-scoring NRRs resulted in an improved measurement performance of the scale. DLQI scores of patients with at least one vs. no NRRs cannot be directly compared. Our findings provide further empirical support to the DLQI-R scoring modification that treats NRRs as missing and replaces them with the average score of the relevant items.
An Identity Process Theory Account of the Impact of Boarding School on Sense of Self and Mental Health: an Interpretative Phenomenological Analysis
Authors: Simpson Frances , Haughton Melanie , Van Gordon William 
Published: March 2021

AbstractBoarding schools exist to provide education for children, but this involves the child leaving the family home and residing in an educational institution. Identity Process Theory suggests that such a change in circumstances can threaten the child’s identity, which triggers coping strategies and impacts on the individual’s self-concept during both childhood and adulthood. This study undertook an Interpretative Phenomenological Analysis of semi-structured interviews conducted with five adults who boarded as children. The focus was on exploring participants’ beliefs in terms of how the boarding experience affected their sense of self. Emerging themes relate to the (i) coping strategies used by participants during childhood, such as amnesia, compartmentalising, compliance and acceptance, and (ii) long-term effects of boarding on identity, self-concept and intimate relationships. Findings also highlight the interplay of factors such as privilege and social class, which were reported as motives for participants’ parents choosing boarding for their children. The study raises important questions about the long-term health impacts of sending children away to board.