bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic implication of heterogeneity and trajectory progression induced by enzalutamide in prostate cancer
Authors: Feng Yuanfa , Deng Yulin , Tang Zhenfeng , Cai Shanghua , Li Jinchuang , Liu Ren , Wan Jiaming , He Huichan , Zeng Guohua , Ye Jianheng , Han Zhaodong , Zhong Weide 
Published: March 2023

BackgroundEnzalutamide, as a second-generation endocrine therapy drug for prostate cancer (PCa), is prominent representative among the synthetic androgen receptor antagonists. Currently, there is lack of enzalutamide-induced signature (ENZ-sig) for predicting progression and relapse-free survival (RFS) in PCa.MethodsEnzalutamide-induced candidate markers were derived from single-cell RNA sequencing analysis integrating three enzalutamide-stimulated models (0-, 48-, and 168-h enzalutamide stimulation). ENZ-sig was constructed on the basis of candidate genes that were associated with RFS in The Cancer Genome Atlas leveraging least absolute shrinkage and selection operator method. The ENZ-sig was further validated in GSE70768, GSE94767, E-MTAB-6128, DFKZ, GSE21034, and GSE70769 datasets. Biological enrichment analysis was used to discover the underlying mechanism between high ENZ-sig and low ENZ-sig in single-cell RNA sequencing and bulk RNA sequencing.ResultsWe identified a heterogenous subgroup that induced by enzalutamide stimulation and found 53 enzalutamide-induced candidate markers that are related to trajectory progression and enzalutamide-stimulated. The candidate genes were further narrowed down into 10 genes that are related to RFS in PCa. A 10-gene prognostic model (ENZ-sig)—IFRD1, COL5A2, TUBA1A, CFAP69, TMEM388, ACPP, MANEA, FOSB, SH3BGRL, and ST7—was constructed for the prediction of RFS in PCa. The effective and robust predictability of ENZ-sig was verified in six independent datasets. Biological enrichment analysis revealed that differentially expressed genes in high ENZ-sig were more activated in cell cycle–related pathway. High–ENZ-sig patients were more sensitive to cell cycle–targeted drugs (MK-1775, AZD7762, and MK-8776) than low–ENZ-sig patients in PCa.ConclusionsOur results provided evidence and insight on the potential utility of ENZ-sig in PCa prognosis and combination therapy strategy of enzalutamide and cell cycle–targeted compounds in treating PCa.
The effect of systemic iron status on osteoarthritis: A mendelian randomization study
Authors: Ruan Guangfeng , Ying Yi , Lu Shilong , Zhu Zhaohua , Chen Shibo , Zeng Muhui , Lu Ming , Xue Song , Zhu Jianwei , Cao Peihua , Chen Tianyu , Wang Xiaoshuai , Li Shengfa , Li Jia , Liu Yu , Liu Yanqi , Zhang Yan , Ding Changhai 
Published: March 2023

Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design.Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches.Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80).Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.
Case report and discussion: Pre-implantation genetic diagnosis with surrogacy in vascular Ehlers–Danlos syndrome
Authors: Angwin Chloe , Ghali Neeti , Stephanie van Dijk Fleur 
Published: March 2023

Introduction: Vascular Ehlers–Danlos syndrome (vEDS) is an autosomal dominant inherited connective tissue condition, characterized by generalized tissue fragility with an increased risk of arterial dissection and hollow organ rupture. In women with vEDS, pregnancy and childbirth carry significant risks of both morbidity and mortality. The Human Fertilisation and Embryology Authority has approved vEDS for pre-implantation genetic diagnosis (PGD), given the potential for life-limiting complications. PGD avoids implantation of embryos that are affected by specific disorders by carrying out genetic testing (either for a familial variant or whole gene) and selecting unaffected embryos prior to implantation.Case: We present an essential clinical update to the only published clinical case of a woman with vEDS undergoing PGD with surrogacy, initially through stimulated in vitro fertilization (IVF) and in vitro maturation (IVM) and subsequently through natural IVF.Discussion: In our experience, a subset of women with vEDS do wish to have biological, unaffected children through PGD despite being aware of the risks of pregnancy and delivery. Given the clinical heterogeneity in vEDS, these women could be considered on a case-by-case basis for PGD. Controlled studies with comprehensive patient monitoring evaluating the safety of PGD are essential to equitable healthcare provision.
Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
Authors: Lunardelli Victória Alves Santos , Almeida Bianca da Silva , Apostolico Juliana de Souza , Rezende Thais , Yamamoto Marcio Massao , Pereira Samuel Santos , Bueno Maria Fernanda Campagnari , Pereira Lennon Ramos , Carvalho Karina Inacio , Slhessarenko Renata Dezengrini , de Souza Ferreira Luis Carlos , Boscardin Silvia Beatriz , Rosa Daniela Santoro 
Published: March 2023

IntroductionIn the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes.MethodsIn this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV.ResultsTesting of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses.ConclusionIn conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.
Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation
Authors: Pérez-Diego Mario , Angelina Alba , Martín-Cruz Leticia , de la Rocha-Muñoz Andrés , Maldonado Angel , Sevilla-Ortega Carmen , Palomares Oscar 
Published: March 2023

IntroductionChronic or uncontrolled activation of myeloid cells including monocytes, macrophages and dendritic cells (DCs) is a hallmark of immune-mediated inflammatory disorders. There is an urgent need for the development of novel drugs with the capacity to impair innate immune cell overactivation under inflammatory conditions. Compelling evidence pointed out cannabinoids as potential therapeutic tools with anti-inflammatory and immunomodulatory capacity. WIN55,212-2, a non-selective synthetic cannabinoid agonist, displays protective effects in several inflammatory conditions by mechanisms partially depending on the generation of tolerogenic DCs able to induce functional regulatory T cells (Tregs). However, its immunomodulatory capacity on other myeloid cells such as monocytes and macrophages remains incompletely understood.MethodsHuman monocyte-derived DCs (hmoDCs) were differentiated in the absence (conventional hmoDCs) or presence of WIN55,212-2 (WIN-hmoDCs). Cells were stimulated with LPS, cocultured with naive T lymphocytes and their cytokine production and ability to induce T cell responses were analysed by ELISA or flow cytometry. To evaluate the effect of WIN55,212-2 in macrophage polarization, human and murine macrophages were activated with LPS or LPS/IFNγ, in the presence or absence of the cannabinoid. Cytokine, costimulatory molecules and inflammasome markers were assayed. Metabolic and chromatin immunoprecipitation assays were also performed. Finally, the protective capacity of WIN55,212-2 was studied in vivo in BALB/c mice after intraperitoneal injection with LPS.ResultsWe show for the first time that the differentiation of hmoDCs in the presence of WIN55,212-2 generates tolerogenic WIN-hmoDCs that are less responsive to LPS stimulation and able to prime Tregs. WIN55,212-2 also impairs the pro-inflammatory polarization of human macrophages by inhibiting cytokine production, inflammasome activation and rescuing macrophages from pyroptotic cell death. Mechanistically, WIN55,212-2 induced a metabolic and epigenetic shift in macrophages by decreasing LPS-induced mTORC1 signaling, commitment to glycolysis and active histone marks in pro-inflammatory cytokine promoters. We confirmed these data in ex vivo LPS-stimulated peritoneal macrophages (PMΦs), which were also supported by the in vivo anti-inflammatory capacity of WIN55,212-2 in a LPS-induced sepsis mouse model.ConclusionOverall, we shed light into the molecular mechanisms by which cannabinoids exert anti-inflammatory properties in myeloid cells, which might well contribute to the future rational design of novel therapeutic strategies for inflammatory disorders.
TR score: A noninvasive model to predict histological stages in patients with primary biliary cholangitis
Authors: Tu Zhixin , Wang Yao , Wang Yan , Huang Jianjie , Han Yujin , Ji Qijia , Cao Xiaoxuan , Wen Xiaoyu , Wang Yang , Jin Qinglong 
Published: March 2023

IntroductionThe aim of this study was to develop a noninvasive prediction model for histological stages in PBC that is simple, easy to implement, and highly accurate.MethodsA total of 114 patients with PBC were included in this study. Demographic, laboratory data and histological assessments were collected. The independent predictors of histological stages were selected to establish a noninvasive serological model. The scores of 22 noninvasive models were calculated and compared with the established model.ResultsThis study included 99 females (86.8%) and 15 males (13.2%). The number of patients in Scheuer’s stage 1, 2, 3 and 4 was 33 (29.0%), 34 (29.8%), 16 (14.0%), and 31 (27.2%), respectively. TBA and RDW are independent predictors of PBC histological stages. The above indexes were used to establish a noninvasive model-TR score. When predicting early histological change (S1) or liver fibrosis and cirrhosis (S3-S4), the AUROC of TR score were 0.887 (95% CI, 0.809-0.965) and 0.893 (95% CI, 0.816-0.969), higher than all of the other 22 models included in this study. When predicting cirrhosis (S4), its AUROC is still as high as 0.921 (95% CI, 0.837-1.000).ConclusionTR score is an easy, cheap and stable noninvasive model, without complex calculation formulas and tools, and shows good accuracy in diagnosing the histological stages of PBC.
Integrative analysis revealed that distinct cuprotosis patterns reshaped tumor microenvironment and responses to immunotherapy of colorectal cancer
Authors: Xu Ximo , Ding Chengsheng , Zhong Hao , Qin Wei , Shu Duohuo , Yu Mengqin , Abuduaini Naijipu , Zhang Sen , Yang Xiao , Feng Bo 
Published: March 2023

BackgroundCuprotosis is a novel form of programmed cell death that involves direct targeting of key enzymes in the tricarboxylic acid (TCA) cycle by excess copper and may result in mitochondrial metabolic dysfunction. However, whether cuprotosis may mediate the tumor microenvironment (TME) and immune regulation in colorectal cancer (CRC) remains unclear.MethodsTen cuprotosis-related genes were selected and unsupervised consensus clustering was performed to identify the cuprotosis patterns and the correlated TME characteristics. Using principal component analysis, a COPsig score was established to quantify cuprotosis patterns in individual patients. The top 9 most important cuprotosis signature genes were analyzed using single-cell transcriptome data.ResultsThree distinct cuprotosis patterns were identified. The TME cell infiltration characteristics of three patterns were associated with immune-excluded, immune-desert, and immune-inflamed phenotype, respectively. Based on individual cuprotosis patterns, patients were assigned into high and low COPsig score groups. Patients with a higher COPsig score were characterized by longer overall survival time, lower immune cell as well as stromal infiltration, and greater tumor mutational burden. Moreover, further analysis demonstrated that CRC patients with a higher COPsig score were more likely to respond to immune checkpoint inhibitors and 5-fluorouracil chemotherapy. Single-cell transcriptome analysis indicated that cuprotosis signature genes recruited tumor-associated macrophages to TME through the regulation of TCA and the metabolism of glutamine and fatty acid, thus influencing the prognosis of CRC patients.ConclusionThis study indicated that distinct cuprotosis patterns laid a solid foundation to the explanation of heterogeneity and complexity of individual TME, thus guiding more effective immunotherapy as well as adjuvant chemotherapy strategies.
Sequelae and mortality in patients with HIV/AIDS and Progressive Multifocal Leukoencephalopathy: Systematic review and case series in the Brazilian Amazon
Authors: Valente Jefferson , Del-Tejo Paola López , Cubas-Vega Nadia Carolina , Rodrigues Maria Gabriela de Almeida , de Barros Francisco Railson Bispo , Alexandre Márcia Araújo , Arêas Guilherme Peixoto Tinoco , Bastos Michele , Pinto Sérgio Damasceno , Barros Camila Miriam S. S. , Marinho Eveny Perlize , Mello Sabrina , Ferreira Ewerton , Aprigio Valderjane , Monte Rossiclea Lins , Sampaio Vanderson , Lacerda Marcus , Baia-da-Silva Djane Clarys , Val Fernando 
Published: March 2023

BackgroundProgressive Multifocal Leukoencephalopathy (PML) is an opportunistic neurological disease that mainly affects individuals with HIV/AIDS and has high morbidity and mortality, due to its demyelinating characteristic. This co-infection has been reported since the begging of HIV/Aids epidemic with increasing unfavorable outcomes, however, factors associated to sequelae and death are greatly unknown. In this study we aimed to understand factors associated with the main outcomes of individuals diagnosed with PML and HIV/AIDS, in addition to reporting the characteristics of patients presenting to a referral center in infectious diseases in the Brazilian Amazon.MethodsA systematic review was performed until July 2022, following the PRISMA guidelines, at Medline/Pubmed, Web of Science, Lilacs and Scielo databases using combinations of HIV, Aids, JC Virus and Progressive Multifocal Leukoencephalopathy, with no restriction to publication date. Additional cases, meeting the eligibility criteria, were added from our hospital database, which consisted of patients presenting PML/HIV between 2010 and 2022. A meta-analysis aiming to explore factors associated to sequelae and death was performed. Baseline characteristics were described using mean and standard deviation, or median and interquartile range when appropriate; multivariate analysis was performed to study factors associated to death and sequelae outcomes.ResultsEighteen patients were diagnosed between 2010 and 2022, of these, 10 had positive PCR for JC virus. In the Systematic Review, 216 studies yielded 235 confirmed cases of co-infection. A total of 245 were included for analysis. The rates of death and sequelae were, respectively, 47.1% (114/242) and 41.2% (54/131). The use of antiretroviral therapy was more associated with a lower chance of death (OR 0.30, 95% CI: 0.11-0.83), while muscle weakness (OR 4.82, 95% CI: 2.07-11.21) and muscle spasms (OR 6.12, 95% CI: 1.05-35.76) were associated with greater chances of sequelae.ConclusionThose on antiretroviral therapy appear to be less likely to die, and among those who survive, those who have muscle weakness as a symptom on admission are more likely to develop sequelae. Adherence to ART, as well as a comprehensive clinical evaluation and follow-up may help to improve clinical outcomes and awareness of morbidities.
Soil organic carbon storage in Liaohe River Estuary Wetlands under restoration and multiple management strategies, based on landscape patterns
Authors: Wang Guanxun , Pan Jingyu , Yu Jing , Yan Wenwen , Gu Dongqi , Du Jun 
Published: March 2023

IntroductionManagement of coastal wetlands has resulted in extensive conservation of this natural resource; however, changes in carbon storage function are not yet known. There is a direct link between landscape and soil carbon storage. Predicting future changes in the landscape and carbon storage in coastal wetlands is important for developing wetland management policies.MethodHere, remote sensing and physical methods were used to measure and calculate the landscape and surface soil carbon stocks of the Liaohe River Estuary Wetland (LREW). The changes in the landscape and soil carbon stocks under three scenarios: natural development, strict protection, and culture pond transfer, were then predicted using the PLUS model.ResultThe results indicate that the surface soil organic carbon storage was 2107.97×103 t, while soil organic carbon density decreased from land to sea. Anthropogenic activity was found to be the main driver of the current landscape evolution. However, the impact of sea level rise is increasing. By 2030, considerably more storage will be gained under the culture pond transfer scenario than at present.DiscussionOur results reveal that some of the methods of ecological restoration may diminish the carbon storage capacity of coastal wetlands. Making full use of areas with high carbon storage potential may be an effective wetland carbon sink management strategy. Governments should consider more comprehensively for a better carbon pool when developing restoration strategies.
Characteristics and patients’ portrayals of Norwegian social media memes. A mixed methods analysis
Authors: Jarmund Anders Hagen , Tollefsen Sofie Eline , Ryssdal Mariell , Jensen Audun Bakke , Sakshaug Baard Cristoffer , Unneland Eirik , Solberg Berge , Mjølstad Bente Prytz 
Published: March 2023

BackgroundDespite reports on troublesome contents created and shared online by healthcare professionals, a systematic inquiry of this potential problem has been missing. Our objective was to characterize the content of healthcare-associated social media memes in terms of common themes and how patients were portrayed.Materials and methodsThis study applied a mixed methods approach to characterize the contents of Instagram memes from popular medicine- or nursing-associated accounts in Norway. In total, 2,269 posts from 18 Instagram accounts were included and coded for thematic contents. In addition, we conducted a comprehensive thematic analysis of 30 selected posts directly related to patients.ResultsA fifth of all posts (21%) were related to patients, including 139 posts (6%) related to vulnerable patients. Work was, however, the most common theme overall (59%). Nursing-associated accounts posted more patient-related contents than medicine-associated accounts (p &lt; 0.01), but the difference may be partly explained by the former focusing on work life rather than student life. Patient-related posts often thematized (1) trust and breach of trust, (2) difficulties and discomfort at work, and (3) comical aspects of everyday life as a healthcare professional.DiscussionWe found that a considerable number of Instagram posts from healthcare-associated accounts included patients and that these posts were diverse in terms of contents and offensiveness. Awareness that professional values also apply online is important for both healthcare students and healthcare providers. Social media memes can act as an educational resource to facilitate discussions about (e-)professionalism, the challenges and coping of everyday life, and ethical conflicts arising in healthcare settings.