bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico analysis suggests disruption of interactions between HAMP from hepatocytes and SLC40A1 from macrophages in hepatocellular carcinoma
Authors: Hu Liang , Wu Chao 
Published: May 2021

AbstractBackgroundIdentification of factors associated with proliferation in the hepatocellular carcinoma (HCC) microenvironment aids in understanding the mechanisms of disease progression and provides druggable targets. Gene expression profiles of individual cells in HCC and para-carcinoma tissues can be effectively obtained using the single-cell RNA sequencing (scRNA-Seq) technique. Here, we aimed to identify proliferative hepatocytes from HCC and para-carcinoma tissues, detect differentially expressed genes between the two types of proliferative hepatocytes, and investigate their potential roles in aberrant proliferation.ResultsTwo respective gene signatures for proliferative cells and hepatocytes were established and used to identify proliferative hepatocytes from HCC and para-carcinoma tissues based on scRNA-Seq data. Gene expression profiles between the two types of proliferative hepatocytes were compared. Overall, 40 genes were upregulated in proliferative hepatocytes from para-carcinoma tissue, whereas no upregulated genes were detected in those from HCC tissue. Twelve of the genes, includingHAMP, were specifically expressed in the liver tissue. Based on previous reports, we found thatHAMPmodulates cell proliferation through interaction with its receptorSLC40A1. Comprehensive analysis of cells in HCC and para-carcinoma tissues revealed that: (1)HAMPis specifically expressed in hepatocytes and significantly downregulated in malignant hepatocytes; (2) a subset of macrophages expressingSLC40A1and genes reacting to various infections is present in para-carcinoma but not in HCC tissue. We independently validated the findings with scRNA-Seq and large-scale tissue bulk RNA-Seq/microarray analyses.ConclusionHAMPwas significantly downregulated in malignant hepatocytes. In addition, a subset of macrophages expressingSLC40A1and genes reacting to various infections was absent in HCC tissue. These findings support the involvement ofHAMP-SLC40A1signaling in aberrant hepatocyte proliferation in the HCC microenvironment. The collective data from our in silico analysis provide novel insights into the mechanisms underlying HCC progression and require further validation with wet laboratory experiments.
Circular RNA circHECTD1 prevents Diosbulbin-B-sensitivity via miR-137/PBX3 axis in gastric cancer
Authors: Lu Yizhuo , Li Long , Li Lianghui , Wu Guoyang , Liu Guoyan 
Published: May 2021

Abstract
Backgrounds
Gastric cancer (GC) is general disease in human digestive system with malignancy. Emerging findings indicated that hsa_circ_0031452 (circHECTD1) was strictly associated with carcinogenesis. Nevertheless, the role of circHECTD1 in drug-resistance still needed to be explained.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expression profiles of circHECTD1, microRNA (miR)-137, and pre-leukemia transcription factor 3 (PBX3). The function of circHECTD1 in tumorigenesis was evaluated via xenograft tumor model. The IC50 of Diosbulbin-B (DB) was detected using Cell Counting Kit-8 (CCK8). Cell-cycle and apoptosis were reckoned by flow cytometry. Besides, western blot was administrated to reckon the levels of PBX3 and cell apoptotic indicators. Moreover, the interrelation between miR-137 and circHECTD1 or PBX3 was expounded by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull down assays.

Results
We uncovered that circHECTD1 was ectopically up-regulated in GC tissues and cells. CircHECTD1 deficiency sensitized DB-treatment in DB-evoked AGS and HGC-27 cells. In vivo assay, circHECTD1 silencing led to the tumor reduction. Also, circHECTD1 served as miR-137 sponge in a sequence-complementary manner. Furthermore, transfection of miR-137 inhibitor markedly eliminated circHECTD1 absence-mediated promotion of DB-sensitivity in GC cells. Moreover, PBX3, a target of miR-137, play a DB-resistant role in GC cells. Fascinatingly, the deletion of PBX3 reversed the impact of miR-137 repression and circHECTD1 knockdown on DB-sensitivity in vitro.

Conclusions
CircHECTD1 served as an oncogene by a novel miR-137/PBX3 axis, which might supply an underlying biomarker for the diagnosis and prognosis of GC management.
The intersection of COVID-19 and cancer: signaling pathways and treatment implications
Authors: Zong Zhi , Wei Yujun , Ren Jiang , Zhang Long , Zhou Fangfang 
Published: May 2021

AbstractThe outbreak of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a serious public health concern. Patients with cancer have been disproportionately affected by this pandemic. Increasing evidence has documented that patients with malignancies are highly susceptible to severe infections and mortality from COVID-19. Recent studies have also elucidated the molecular relationship between the two diseases, which may not only help optimize cancer care during the pandemic but also expand the treatment for COVID-19. In this review, we highlight the clinical and molecular similarities between cancer and COVID-19 and summarize the four major signaling pathways at the intersection of COVID-19 and cancer, namely, cytokine, type I interferon (IFN-I), androgen receptor (AR), and immune checkpoint signaling. In addition, we discuss the advantages and disadvantages of repurposing anticancer treatment for the treatment of COVID-19.
Multifunctional nanoplatforms as cascade-responsive drug-delivery carriers for effective synergistic chemo-photodynamic cancer treatment
Authors: Li Fan , Liang Yan , Wang Miaochen , Xu Xing , Zhao Fen , Wang Xu , Sun Yong , Chen Wantao 
Published: May 2021

AbstractSynergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic chemo-photodynamic cancer treatment, was fabricated. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent was utilized for carrying the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N = CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via the cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations revealed high cancer-suppression efficacy of this ideal multifunctional nanoplatform, indicating that it could be a promising candidate for synergistic anticancer therapy.
Identification and treatment of viral hepatitis C in persons who use drugs: a prospective, multicenter outreach study in Flanders, Belgium
Authors: Busschots Dana , Kremer Cécile , Bielen Rob , Koc Özgür Muhammet , Heyens Leen , Dercon Eefje , Verrando Rita , Windelinckx Tessa , Maertens Griet , Bourgeois Stefan , Hens Niel , Matheï Catharina , Robaeys Geert 
Published: May 2021

AbstractBackgroundTargeted screening for hepatitis C viral (HCV) infection is not yet widely executed in Belgium. When performed in people who use drugs (PWUD), it is mainly focused on those receiving opiate agonist therapy (OAT). We wanted to reach out to a population of difficult to reach PWUD not on centralized OAT, using non-invasive screening as a bridge to re-integration in medical care supported by facilitated referral to a specialist.MethodsThis was a prospective, multicenter cohort study in PWUD not enrolled in a centralized OAT program in a community-based facility in Limburg or OAT program in a community-based facility in Antwerp, Belgium, from October 2018 until October 2019. Two study teams recruited participants using an outreach method at 18 different locations. Participants were tested for HCV antibodies (Ab) by finger prick, and risk factors were assessed through a face-to-face questionnaire. Univariate analyses were used to assess the association between HCV Ab and each risk factor separately. A generalized linear mixed model was used to investigate the association between the different risk factors and HCV.ResultsIn total, 425 PWUD were reached with a mean age of 41.6 ± 10.8, and 78.8% (335/425) were men. HCV Ab prevalence was 14.8% (63/425). Fifty-six (88.9%) PWUD were referred, of whom 37 (66.1%) were linked to care and tested for HCV RNA. Twenty-nine (78.4%) had a chronic HCV infection. Treatment was initiated in 17 (58.6%) patients. The adjusted odds for HCV Ab were highest in those with unstable housing 6 months before inclusion (p < .001, AOR 8.2 CI 95% 3.2–23.3) and in those who had ever shared paraphernalia for intravenous drug use (p < .001, AOR 6.2 CI 95% 2.5–16.0).ConclusionsAn important part tested positive for HCV. Treatment could be started in more than half of the chronically infected referred and tested positive for HCV-RNA. Micro-elimination is necessary to achieve the World Health Organization goals by 2030. However, it remains crucial to screen and link a broader group of PWUD to care than to focus solely on those who inject drugs.Trial registration: clinicaltrials.gov NCT04363411, Registered 27 April 2020—Retrospectively registered.https://clinicaltrials.gov/ct2/show/NCT04363411?term=NCT04363411&draw=2&rank=1
Psychometric properties of the WHOQOL-BREF(PT) in a sample of elderly citizens
Authors: Goes Margarida , Lopes Manuel , Marôco João , Oliveira Henrique , Fonseca César 
Published: May 2021

Abstract
Background
The goal of this article was to research the psychometric properties of the WHOQOL-BREF(PT) instrument in a sample of elderly citizens residing in a rural area in their own homes or at family members’ or friends’ homes and to compare the results: (i) to those reported by the team of Portuguese researchers that undertaken the instrument's translation/validation to the Portuguese language and (ii) to those reported internationally by the World Health Organization Quality of Life group. An overall quality of life scoring (QOL24—all facets) is also proposed in this article as novelty. The correlation level between QOL24 and the instrument’s general facet was also investigated.

Methods
This was a cross-sectional study with a sample of 351 elderly citizens (46.4% males and 53.6% females) randomly selected from the official dataset of the Local Health Unit of Baixo Alentejo. All the data were collected by health professionals at the participants’ homes following the structured interview methodology and using the WHOQOL-BREF(PT) instrument. Three different structural equation models were developed: (i) a first-order confirmatory factor analysis, to assess the instrument’s psychometric properties; (ii) a hierarchical second-order confirmatory factor analysis model, to allow determining the QOL24 scoring; and (iii) a more generic structural equation model, to investigate the correlation level between QOL24 and the instrument’s general facet.

Results
The WHOQOL-BREF(PT) showed an “almost very good” goodness of fit (comparative fit index of 0.949 and Tucker-Lewis index of 0.943), an adequate internal consistency (Cronbach’s alpha: from 0.64 to 0.90; composite reliability: from 0.59 to 0.88) and tolerable convergent validity (average variance extracted: from 0.374 to 0.614). However, discriminant validity was not reached because strong correlations between the first-order factors (four QOL domains) were obtained, together with low values of the average variance extracted. The scoring of QOL domains and QOL24, determined as weighted averages (proposed in this article as novelty) were significantly different than those determined as unweighted averages. The standardized correlation coefficient between QOL24 and the instrument’s general facet was of 0.89 (statistically highly significant).

Conclusions
The WHOQOL-BREF(PT) is a psychometrically sound instrument to assess the QOL of the considered population sample. However, the QOL domains were found strongly intertwined. More studies are necessary to validate the weighted average scoring strategy of QOL domains and QOL24. Concurrent validity between QOL24 and the instrument’s general facet was considered as “strong”.
Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome
Authors: Yu Li , Liu Miao , Wang Zhenxin , Liu Te , Liu Suying , Wang Beili , Pan Baishen , Dong Xi , Guo Wei 
Published: May 2021

AbstractBackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear.MethodsTwenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR.ResultsThe estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels ofCYP11A, CYP19AandHSD17B2of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels ofCYP11AandHSD17B2were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst.ConclusionOur results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related toHSD17B1,CYP19A1andCYP11A1expression change in FF exosomes.
Setting the global research agenda for community-based HIV service delivery through the faith sector
Authors: Ndlovu-Teijema Martha T. , Kok Maarten O. , van Elsland Sabine L. , Smeets Hilleen , Barstow David , van Rooyen Lyn , van Furth A. M. 
Published: May 2021

Abstract
Background
While leading AIDS organizations expect faith and health collaborations to play a crucial role in organizing and scaling up community-based HIV services, it is unclear how this can be realized. Little primary research has been conducted into which strategies for collaboration and service provision are most effective, efficient, scalable and sustainable. Seeking to align research with urgent needs, enhance coordination and increase the likelihood that results are used, this study aimed to set an inclusive global research agenda that reflects priority research questions from key stakeholders at the intersection of HIV healthcare and faith.

Methods
In order to develop this global research agenda, we drew from document analyses, focus group discussions, interviews with purposively selected key informants from all continents (policy-makers, healthcare providers, faith leaders, academics and HIV activists), an online questionnaire, and expert meetings at several global conferences. We carried out focus group discussions and interviews with faith leaders in South Africa. Other stakeholder focus groups and interviews were carried out online or in person in France, Switzerland, the Netherlands and South Africa, and virtual questionnaires were distributed to stakeholders worldwide. Respondents were purposively sampled.

Results
We interviewed 53 participants, and 110 stakeholders responded to the online questionnaire. The participants worked in 54 countries, with the majority having research experience (84%), experience with policy processes (73%) and/or experience as a healthcare provider (60%) and identifying as religious (79%). From interviews (N = 53) and questionnaires (N = 110), we identified 10 research themes: addressing sexuality, stigma, supporting specific populations, counselling and disclosure, agenda-setting, mobilizing and organizing funding, evaluating faith-health collaborations, advantage of faith initiatives, gender roles, and education. Respondents emphasized the need for more primary research and prioritized two themes: improving the engagement of faith communities in addressing sexuality and tackling stigma.

Conclusions
A wide range of respondents participated in developing the research agenda. To align research to the prioritized themes and ensure that results are used, it is essential to further engage key users, funders, researchers and other stakeholders, strengthen the capacity for locally embedded research and research uptake and contextualize priorities to diverse religious traditions, key populations and local circumstances.
Equity-specific effects of interventions to promote physical activity among middle-aged and older adults: results from applying a novel equity-specific re-analysis strategy
Authors: Czwikla Gesa , Boen Filip , Cook Derek G. , de Jong Johan , Harris Tess , Hilz Lisa K. , Iliffe Steve , Lechner Lilian , Morris Richard W. , Muellmann Saskia , Peels Denise A. , Pischke Claudia R. , Schüz Benjamin , Stevens Martin , Telkmann Klaus , van Lenthe Frank J. , Vanderlinden Julie , Bolte Gabriele 
Published: May 2021

Abstract
Background
Reducing inequalities in physical activity (PA) and PA-associated health outcomes is a priority for public health. Interventions to promote PA may reduce inequalities, but may also unintentionally increase them. Thus, there is a need to analyze equity-specific intervention effects. However, the potential for analyzing equity-specific effects of PA interventions has not yet been sufficiently exploited. The aim of this study was to set out a novel equity-specific re-analysis strategy tried out in an international interdisciplinary collaboration.

Methods
The re-analysis strategy comprised harmonizing choice and definition of outcomes, exposures, socio-demographic indicators, and statistical analysis strategies across studies, as well as synthesizing results. It was applied in a collaboration of a convenience sample of eight European PA intervention studies in adults aged ≥45 years. Weekly minutes of moderate-to-vigorous PA was harmonized as outcome. Any versus no intervention was harmonized as exposure. Gender, education, income, area deprivation, and marital status were harmonized as socio-demographic indicators. Interactions between the intervention and socio-demographic indicators on moderate-to-vigorous PA were analyzed using multivariable linear regression and random-effects meta-analysis.

Results
The collaborative experience shows that the novel re-analysis strategy can be applied to investigate equity-specific effects of existing PA interventions. Across our convenience sample of studies, no consistent pattern of equity-specific intervention effects was found. Pooled estimates suggested that intervention effects did not differ by gender, education, income, area deprivation, and marital status.

Conclusions
To exploit the potential for equity-specific effect analysis, we encourage future studies to apply the strategy to representative samples of existing study data. Ensuring sufficient representation of ‘hard to reach’ groups such as the most disadvantaged in study samples is of particular importance. This will help to extend the limited evidence required for the design and prioritization of future interventions that are most likely to reduce health inequalities.
CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma
Authors: Fu Qianmei , Tan Xiaohong , Tang Huaming , Liu Jijiang 
Published: May 2021

Abstract
Background
As a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Despite the limitations of effective therapy, immunotherapy has emerged as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C–C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis.

Methods
Bioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down and RNA binding protein immunoprecipitation experiments were performed to determine the MALAT1-microRNA-202-3p (miR-203-3p) interaction and miR-202-3p-SRSF1 interaction followed by the analysis of their effect on the mTOR pathway.

Results
CCL21 was identified as a key GC immune gene. Overexpressed CCL21, MALAT1, and SRSF1 along with poorly expressed miR-202-3p were identified in the GC cells. CCL21 induced the MALAT1 expression in a time- and dose-dependent manner. Functionally, MALAT1 targeted miR-202-3p but upregulated SRSF1 and activated mTOR. Crucially, evidence was obtained indicating that CCL21 promoted both the malignant phenotypes and EMT of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo by increasing the MALAT1-induced upregulation of SRSF1.

Conclusions
Taken together, the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC.