bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEVO: an ontology to assist with dermoscopic feature standardization
Authors: Zhang Xinyuan , Lin Rebecca Z. , Amith Muhammad “Tuan” , Wang Cynthia , Light Jeremy , Strickley John , Tao Cui 
Published: August 2023

Abstract
Background
The utilization of dermoscopic analysis is becoming increasingly critical for diagnosing skin diseases by physicians and even artificial intelligence. With the expansion of dermoscopy, its vocabulary has proliferated, but the rapid evolution of the vocabulary of dermoscopy without standardized control is counterproductive. We aimed to develop a domain-specific ontology to formally represent knowledge for certain dermoscopic features.

Methods
The first phase involved creating a fundamental-level ontology that covers the fundamental aspects and elements in describing visualizations, such as shapes and colors. The second phase involved creating a domain ontology that harnesses the fundamental-level ontology to formalize the definitions of dermoscopic metaphorical terms.

Results
The Dermoscopy Elements of Visuals Ontology (DEVO) contains 1047 classes, 47 object properties, and 16 data properties. It has a better semiotic score compared to similar ontologies of the same domain. Three human annotators also examined the consistency, complexity, and future application of the ontology.

Conclusions
The proposed ontology was able to harness the definitions of metaphoric terms by decomposing them into their visual elements. Future applications include providing education for trainees and diagnostic support for dermatologists, with the goal of generating responses to queries about dermoscopic features and integrating these features to diagnose skin diseases.
The quality of German - language patient decision aids for oncological patients on the internet
Authors: Möller Julia , Josfeld Lena , Keinki Christian , Zieglowski Nathalie , Büntzel Jens , Hübner Jutta 
Published: August 2023

Abstract
Background
Previous studies have already shown that decision aids are a suitable tool for patient decision-making. The aim of this work is to conduct an online search for freely available, German-language patient decision aids (PDAs) for cancer patients, followed by an assessment of their quality. For this purpose, a rating tool that is as manageable as possible was developed on the basis of already existing quality criteria.

Methods
A simulated patient online search was conducted via the four most frequently used search engines in Germany. A quality assessment tool was created utilizing international and national guidelines, with a focus on practicality and manageability. Subsequently, the identified PDAs were rated by 4 raters based on the rating tool.

Results
The number of German-language oncology PDAs is low (n = 22 of 200 URLs) with limited variability regarding rare cancers. Most originate from non-profit organizations. The overall quality is low, as indicated by an average of 57.52% of the maximum evaluation points of the developed quality assessment tool. Reference values used to assess quality were related to e.g. support/effectiveness, adaptation, layout, etc. No qualitative differences were found regarding different publishers. Quality differed between PDAs of different length, with longer PDAs achieving better results.

Conclusion
Overall, the supply and quality of German-language PDAs is not satisfactory. The assessment tool created in this study provides a solid, but more manageable basis, for developing and identifying high-quality PDAs.

Practice implications
PDAs should be increasingly used by physicians in practice. For this, a quick qualitative assessment of PDAs in everyday life must be possible. Future research has to investigate especially the aspect of the length of a PDA in more detail.
Attenuation of pathogenesis of Eimeria stiedae sporulated oocysts using Egyptian alginate propolis nanoparticles
Authors: Hegazi Ahmed G. , Shanawany Eman E. El , El-Houssiny Asmaa S. , Hassan Soad E. , Desouky Hassan M. , El-Metenawy T. M. , Abdel-Rahman Eman H. 
Published: August 2023

Abstract
Background
Coccidiosis is a costly and widespread infectious disease that affects mammals and causes huge losses for the global rabbit meat industry. This study evaluated the potency of Egyptian alginate propolis nanoparticles (NPs) in attenuating the infectivity of Eimeria stiedae sporulated oocysts. The gelification method was used to prepare alginate propolis NPs, which were then characterized using a transmission electron microscope and zeta potential analysis.

Results
The results revealed that the zeta potential of the prepared alginate propolis NPs increased from − 60.60 ± 9.10 mV to –72.26 ± 6.04 mV. The sporulated oocysts were treated with 50 mg/mL of the alginate propolis NPs. Thereafter, the treated oocysts were tested for their ability to infect rabbits. The rabbits were divided into three groups: the healthy control (G1) group, the infected control (G2) group, and the treated oocyst-infected (G3) group. The rabbits were sacrificed 43 days post-infection (dpi). The infectivity of the oocysts was assessed. The treated oocyst-infected rabbits exhibited slight abdominal distension and dullness symptoms. The G3 group had no oocyst output, with a 100% reduction from 41 dpi until the end of the experiment. Immunologically, the IgG level of the G2 group gradually increased (p ≤ 0.05) much more than that of the G3 group. The IL-12 level in the G3 group significantly increased from 16 dpi until the end of the experiment, nearly reaching the level in healthy animals. Decreased CD4+ and CD8+ immunolabelling was observed in the liver sections of the group infected with the alginate propolis NP-treated oocysts, and there was a remarkable improvement in the histopathological parameters.

Conclusions
These data indicate that Alg propolis NPs are sufficient to reduce the infectivity of E. stiedae oocysts.
m6A genotypes and prognostic signature for assessing the prognosis of patients with acute myeloid leukemia
Authors: Fu Caizhu , Kou Ruirui , Meng Jie , Jiang Duanfeng , Zhong Ruilan , Dong Min 
Published: August 2023

Abstract
Background
N6-methyladenosine (m6A) has been confirmed to function critically in acute myeloid leukemia (AML) progression. Hitherto, the subtyping and prognostic predictive significance of m6A-correlated genes in AML is unclear.

Method
From The Cancer Genome Atlas (TCGA-LAML), Therapeutically Applicable Research to Generate Effective Treatments (TARGET-AML) and Gene Expression Omnibus (GEO, GSE71014) databases, we collected the sequencing data of AML patients. The batch effect was removed via limma package for TCGA-LAML and TARGET-AML, and the aggregated samples were AML cohorts. Samples in the AML cohort identified m6A models in AML by consensus clustering based on 23-m6A-related modulators. M6A-related differentially expressed genes (m6ARDEGs) influencing the overall survival (OS) of AML were determined by performing differential expression analysis and univariate COX analysis, and consensus-based clustering was utilized to access AML molecular subtypes. LASSO and multivariate COX analyses were performed to obtain the optimized m6ARDEGs to construct the m6A Prognostic Risk Score (m6APR_Score). Whether the model was robust was evaluated according to Kaplan–Meier (K-M) and receiver operator characteristic (ROC) curves. Further, the abundance of immune cell infiltration was explored in different m6A modification patterns and molecular subtypes and m6APR_Score groupings. Finally, nomogram was constructed to predict OS in AML. Quantitative real-time polymerase chain reaction (RT-qPCR) and cell counting kit-8 (CCK-8) assay were used to validate the genes in m6APR_Score in AML cells.

Results
The m6A models (m6AM1, m6AM2, m6AM3) and molecular subtypes (C1, C2, C3) were identified in the AML cohort, exhibiting different prognosis and immunoreactivity. We recognized novel prognostic biomarkers of AML such as CD83, NRIP1, ACSL1, METTL7B, OGT, and C4orf48. AML patients were grouped into high-m6APR_Score and low-m6APR_Score groups, with the later group showing a better prognosis than former one. Both the AML cohort and the validation cohort GSE71014 demonstrated excellent prediction. Finally, the nomogram accurately predicted the survival of patients suffering from AML. Further, the decision curves showed that both nomogram and m6APR_Score showed excellent prediction. It was confirmed in vitro experiments that mRNA expressions of NRIP1, ACSL1, METTL7B and OGT were elevated, while CD83 and C4orf48 mRNA expressions downregulated in AML cells. A significant increase in the viability of U937 and THP-1 cell lines after inhibition of CD83, while siMETTL7B had contrast results.

Conclusion
Our study demonstrated that m6APR_Score and CD83, NRIP1, ACSL1, METTL7B, OGT, and C4orf48 potentially provided novel and promising prognostic support for AML patients.
Development of an individual index of social vulnerability that predicts negative healthcare events: a proposed tool to address healthcare equity in primary care research and practice
Authors: Haggerty Jeannie , Minotti Simona C. , Bouharaoui Fatima 
Published: August 2023

Abstract
Purpose
Socially disadvantaged patients may lack self-efficacy to navigate a complex health system making them vulnerable to healthcare inequity. We aimed to develop an Index of social vulnerability that predicts increased risk of negative healthcare events (e.g. emergency hospitalization), independent of chronic disease burden. The analysis illustrates the conceptual and practical steps leading to the development of a pragmatic Index of social vulnerability to limited healthcare self-efficacy.

Methods
Using data from a 3-year cohort of 2507 adult primary care patients in Québec (Canada), we applied two complementary structural equation modelling approaches—Partial Least Squares Path Modelling (PLS-PM) and Multiple indicators and Multiple Causes (MIMIC) modelling—to identify a minimal set of social characteristics that could be summed into an Index related to limited healthcare self-efficacy. We then used logistic regression to determine if the Index predicted: hospital emergency department use; hospital admissions; unmet need for care, and others. We privileged parsimony over explanatory capacity in our analytic decisions to make the Index pragmatic for epidemiologic and clinical use.

Results
The Individual Social Vulnerability Index is the weighted sum of five indicators: two indicators of social support; educational achievement; financial status; limited language proficiency. The Index predicts increased likelihood of all negative healthcare outcomes except unmet need, with a clear threshold at Index ≥ 2. The effect is independent of chronic disease burden.

Conclusion
When social deficits outweigh social assets by two or more (Index ≥ 2), there is an increased risk of negative healthcare events beyond the risk attributable to poor health. The Index is a pragmatic tool to identify a minority of patients who will require additional support to receive equitable healthcare.
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
Authors: Glaviano Antonino , Foo Aaron S. C. , Lam Hiu Y. , Yap Kenneth C. H. , Jacot William , Jones Robert H. , Eng Huiyan , Nair Madhumathy G. , Makvandi Pooyan , Geoerger Birgit , Kulke Matthew H. , Baird Richard D. , Prabhu Jyothi S. , Carbone Daniela , Pecoraro Camilla , Teh Daniel B. L. , Sethi Gautam , Cavalieri Vincenzo , Lin Kevin H. , Javidi-Sharifi Nathalie R. , Toska Eneda , Davids Matthew S. , Brown Jennifer R. , Diana Patrizia , Stebbing Justin , Fruman David A. , Kumar Alan P. 
Published: August 2023

AbstractThe PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.
Expanding Community Health Worker decision space: learning from a Participatory Action Research training intervention in a rural South African district
Authors: D’Ambruoso Lucia , Abruquah Nana Akua , Mabetha Denny , van der Merwe Maria , Goosen Gerhard , Sigudla Jerry , Witter Sophie ,   the Verbal Autopsy with Participatory Action Research (VAPAR)/Wits/Mpumalanga Department of Health Learning Platform
Published: August 2023

Abstract
Background
While integral to decentralising health reforms, Community Health Workers (CHWs) in South Africa experience many challenges. During COVID-19, CHW roles changed rapidly, shifting from communities to clinics. In the contexts of new roles and re-engineered primary healthcare (PHC), the objectives were to: (a) implement a training intervention to support local decision-making capability of CHWs; and (b) assess learning and impacts from the perspectives of CHWs.

Methods
CHWs from three rural villages (n = 9) were trained in rapid Participatory Action Research (PAR) with peers and community stakeholders (n = 33). Training equipped CHWs with tools and techniques to convene community groups, raise and/or respond to local health concerns, understand concerns from different perspectives, and facilitate action in communities and public services. CHWs’ perspectives before and after the intervention were gained through semi-structured interviews. Data were collected and analysed using the decision space framework to understand local actors’ power to affect devolved decision-making.

Results
CHWs demonstrated significant resilience and commitment in the face of COVID-19. They experienced multiple, intersecting challenges including: limited financial, logistical and health systems support, poor role clarity, precarious employment, low and no pay, unstable organisational capacity, fragile accountability mechanisms and belittling treatment in clinics. Together, these restricted decision space and were seen to reflect a low valuing of the cadre in the system. CHWs saw the training as a welcome opportunity to assert themselves as a recognised cadre. Regular, spaces for dialogue and mutual learning supported CHWs to gain tools and skills to rework their agency in more empowered ways. The training improved management capacity, capabilities for dialogue, which expanded role clarity, and strengthened community mobilisation, facilitation and analysis skills. Development of public speaking skills was especially valued. CHWs reported an overall ‘tripe-benefit’ from the training: community-acceptance; peer support; and dialogue with and recognition by the system. The training intervention was recommended for scale-up by the health authority as an implementation support strategy for PHC.

Conclusions
Lack of recognition of CHWs is coupled with limited opportunities for communication and trust-building. The training supported CHWs to find and amplify their voices in strategic partnerships, and helped build functionality for local decision-making.
Embryonic signals mediate extracellular vesicle biogenesis and trafficking at the embryo–maternal interface
Authors: Guzewska Maria M. , Myszczynski Kamil , Heifetz Yael , Kaczmarek Monika M. 
Published: August 2023

Abstract
Background
Extracellular vesicles (EVs) are membrane-coated nanoparticles secreted by almost all cell types in living organisms. EVs, as paracrine mediators, are involved in intercellular communication, immune response, and several reproductive events, including the maintenance of pregnancy. Using a domestic animal model (Sus scrofa) with an epitheliochorial, superficial type of placentation, we focused on EV biogenesis pathway at the embryo–maternal interface, when the embryonic signaling occurs for maternal recognition and the maintenance of pregnancy.

Results
Transmission electron microscopy was used during early pregnancy to visualize EVs and apocrine and/or merocrine pathways of secretion. Immunofluorescent staining localized proteins responsible for EV biogenesis and cell polarization at the embryo–maternal interface. The expression profiles of genes involved in biogenesis and the secretion of EVs pointed to the possible modulation of endometrial expression by embryonic signals. Further in vitro studies showed that factors of embryonic origin can regulate the expression of the ESCRT-II complex and EV trafficking within endometrial luminal epithelial cells. Moreover, miRNA-mediated rapid negative regulation of gene expression was abolished by delivered embryonic signals.

Conclusions
Our findings demonstrated that embryonic signals are potent modulators of ESCRT-dependent EV-mediated secretory activity of the endometrium during the critical stages of early pregnancy.
TLR7 activation by miR-21 promotes renal fibrosis by activating the pro-inflammatory signaling pathway in tubule epithelial cells
Authors: Kim Jeongwon , Ha Sugyeong , Son Minjung , Kim Doyeon , Kim Mi-Jeong , Kim Bumseok , Kim Donghwan , Chung Hae Young , Chung Ki Wung 
Published: August 2023

Abstract
Background
Toll-like receptor 7 (TLR7) is an endosomal TLR activated by single-stranded RNA, including endogenous microRNAs. Although TLR7 is known to promote inflammatory responses in pathophysiological conditions, its role in renal fibrosis has not been investigated. Here, we aim to investigate the inflammatory roles of TLR7 in kidney inflammation and fibrosis.

Methods
TLR7 knockout mice (Tlr7 −/−) subjected to AD-induced kidney injury were utilized to examine the role of TLR7 in kidney fibrosis. To elucidate the role of TLR7 in renal epithelial cells, NRK52E rat renal tubule epithelial cells were employed.

Results
Under fibrotic conditions induced by an adenine diet (AD), TLR7 was significantly increased in damaged tubule epithelial cells, where macrophages were highly infiltrated. TLR7 deficiency protected against AD-induced tubular damage, inflammation, and renal fibrosis. Under in vitro conditions, TLR7 activation increased NF-κB activity and induced chemokine expression, whereas TLR7 inhibition effectively blocked NF-κB activation. Furthermore, among the known TLR7 endogenous ligands, miR-21 was significantly upregulated in the tubular epithelial regions. In NRK52E cells, miR-21 treatment induced pro-inflammatory responses, which could be blocked by a TLR7 inhibitor. When the TLR7 inhibitor, M5049, was administered to the AD-induced renal fibrosis model, TLR7 inhibition significantly attenuated AD-induced renal inflammation and fibrosis.

Conclusions
Overall, activation of TLR7 by endogenous miR-21 in renal epithelial cells contributes to inflammatory responses in a renal fibrosis model, suggesting a possible therapeutic target for the treatment of renal fibrosis.
Dynamic alterations in metabolomics and transcriptomics associated with intestinal fibrosis in a 2,4,6-trinitrobenzene sulfonic acid-induced murine model
Authors: Wu Jinzhen , Tian Zhenyi , Zhuang Xiaoduan , Chen Yiru , Fan Tingting , Li Jiayun , Wang Xinying 
Published: August 2023

Abstract
Background & aims
Intestinal fibrosis is a common and severe complication of inflammatory bowel disease without clear pathogenesis. Abnormal expression of host genes and metabolic perturbations might associate with the onset of intestinal fibrosis. In this study, we aimed to investigate the relationship between the development of intestinal fibrosis and the dynamic alterations in both fecal metabolites and host gene expression.

Methods
We induced intestinal fibrosis in a murine model using 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS-treated or control mice were sacrificed after 4 and 6 weeks of intervention; alterations in colonic genes and fecal metabolites were determined by transcriptomics and metabolomics, respectively. Differential, tendency, enrichment, and correlation analyses were performed to assess the relationship between host genes and fecal metabolites.

Results
RNA-sequencing analysis revealed that 679 differential genes with enduring changes were mainly enriched in immune response-related signaling pathways and metabolism-related biological processes. Among them, 15 lipid metabolism-related genes were closely related to the development of intestinal fibrosis. Moreover, the fecal metabolic profile was significantly altered during intestinal fibrosis development, especially the lipid metabolites. Particularly, dynamic perturbations in lipids were strongly associated with alterations in lipid metabolism-related genes expression. Additionally, six dynamically altered metabolites might serve as biomarkers to identify colitis-related intestinal fibrosis in the murine model.

Conclusions
Intestinal fibrosis in colitis mice might be related to dynamic changes in gene expression and metabolites. These findings could provide new insights into the pathogenesis of intestinal fibrosis.
Long non-coding RNAs as the critical regulators of PI3K/AKT, TGF-β, and MAPK signaling pathways during breast tumor progression
Authors: Maharati Amirhosein , Moghbeli Meysam 
Published: August 2023

AbstractBreast cancer (BC) as one of the most common causes of human deaths among women, is always considered one of the global health challenges. Despite various advances in diagnostic and therapeutic methods, a significant percentage of BC patients have a poor prognosis due to the lack of therapeutic response. Therefore, investigating the molecular mechanisms involved in BC progression can improve the therapeutic and diagnostic strategies in these patients. Cytokine and growth factor-dependent signaling pathways play a key role during BC progression. In addition to cytokines and growth factors, long non-coding RNAs (lncRNAs) have also important roles in regulation of such signaling pathways. Therefore, in the present review we discussed the role of lncRNAs in regulation of PI3K/AKT, MAPK, and TGF-β signaling pathways in breast tumor cells. It has been shown that lncRNAs mainly have an oncogenic role through the promotion of these signaling pathways in BC. This review can be an effective step in introducing the lncRNAs inhibition as a probable therapeutic strategy to reduce tumor growth by suppression of PI3K/AKT, MAPK, and TGF-β signaling pathways in BC patients. In addition, considering the oncogenic role and increased levels of lncRNAs expressions in majority of the breast tumors, lncRNAs can be also considered as the reliable diagnostic markers in BC patients.