bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical records after asynchronous and synchronous e-learning courses: a multi-method randomised controlled trial on students’ performance and experience
Authors: Battista Simone , Furri Laura , de Biagi Giorgia , Depedri Lucia , Broggi Valeria , Testa Marco
Published: August 2023

Background

Clinical Record (CR) writing is a fundamental skill for healthcare professionals, but the best e-learning methods for teaching it remain unstudied. Therefore, we investigated speech therapy students’ differences in the quality production of CR at the placement and their experience after following asynchronous or synchronous e-learning courses.

Methods

A multi-method randomised controlled trial. Fifty speech therapist students were equally and randomly divided into two groups attending asynchronous or synchronous e-learning classes to learn how to write a CR. The quality of the CR was tested through an ad hoc checklist (score 0–32) and the groups’ scores were compared. The assessors and the statistician were blinded to students’ group assignment. Students’ experience was assessed through semi-structured interviews analysed with a reflexive thematic analysis.

Results

No score differences between the two groups were found (Cohen’s d = 0.1; 95% Confidence Interval [-0.6; 0.7]). Four themes were generated: (1) ‘Different Forms of Learning Interaction’, as the synchronous group reported a positive experience with being fed back immediately by the lecturer, whereas the asynchronous group reported that pushing back the question time allows for reflecting more on the learning experience; (2) ‘Different Ways to Manage the Time’, as the synchronous group had to stick to the lecturer’s schedule and the asynchronous group felt the possibility to manage its time; (3) ‘To Be or Not To Be (Present)?’ due to the different experiences of having (or not) the lecturer in front of them; (4) ‘Inspiring Relationships With The Peers’, where both groups preferred a peer-to-peer discussion instead of contacting the lecturer.

Discussion

Asynchronous and synchronous e-learning courses appeared equally effective in teaching CR writing. However, students perceive and experience these methods differently. The choice or blend of these methods should be based on students’ needs and preferences, teacher input, as well as organisational requirements rather than solely on students’ attended performance.
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

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

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

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

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

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

The 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

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

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

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

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

Breast 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.
The role of delayed aortic surgery in type A aortic dissection and mesenteric ischemia: a systematic review and meta-analysis
Authors: Eranki Aditya , Wilson-Smith Ashley R , Williams Michael L , Gupta Aashray , Flynn Campbell , Iliopoulos Jim , Manganas Con
Published: August 2023

Introduction

Approximately one third of patients with Acute Type A Aortic Dissection (ATAAD) present with pre-operative malperfusion syndromes (MPS). Of these, mesenteric malperfusion represents the greatest risk to patients with respect to increased short-term mortality. In select patients, it may be feasible to offer a staged approach by treating the mesenteric malperfusion first, optimizing the patient in the intensive care setting and then, following with a central aortic repair. The aim of this systematic review is to summarize cohort studies assessing the role of pre-operative interventions for mesenteric malperfusion.

Methods

An electronic literature search of five databases was performed to identify all relevant studies providing studies examining short-term mortality on patients who underwent either endovascular or open revascularisation of mesenteric ischemia prior to central aortic repair. The primary outcome was all-cause, short-term mortality. Secondary outcomes were comparative mortality between a delayed repair vs. aortic repair first strategy, rates of postoperative laparotomy, bowel resection, and mortality following delayed aortic repair.

Results

The search strategy identified 8 studies qualifying for inclusion, with a total of 180 patients who underwent delayed aortic surgery in the setting of mesenteric MPS. The weighted short-term mortality following a mesenteric revascularisation first, delayed aortic surgery strategy was 22.5%. This strategy was also associated with a significantly lower mortality than a central repair first strategy (OR 0.07, 95% CI 0.02–0.27), and a significantly lower rate of postoperative laparotomy/bowel resection (OR 0.05, 95% CI 0.02–0.14). If patients survive to receive central repair, the weighted short-term mortality postoperatively is low (2.1%).

Conclusion

A summary of this evidence reveals a lower short-term mortality in hemodynamically stable patients with mesenteric malperfusion, along with a reduction in postoperative laparotomy/bowel resections. Of those patients who survive to receive central repair, short-term mortality remains very low in the select group of hemodynamically stable patients. Further high-quality studies with randomized or propensity matched data are required to verify these results.
LncRNA SNHG4 promotes prostate cancer cell survival and resistance to enzalutamide through a let-7a/RREB1 positive feedback loop and a ceRNA network
Authors: Dong Qingzhuo , Qiu Hui , Piao Chiyuan , Li Zhengxiu , Cui Xiaolu
Published: August 2023

Background

Prostate cancer threatens the health of men over sixty years old, and its incidence ranks first among all urinary tumors among men. Enzalutamide remains the first-line drug for castration-resistant prostate cancer, however, tumors inevitably become resistant to enzalutamide. Hence, it is of great importance to investigate the mechanisms that induce enzalutamide resistance in prostate cancer cells.

Methods

Bioinformatic analyzing approaches were used to identified the over-expressed genes in prostate cancer tumor tissues from three GEO datasets. qRT-PCR, western blotting and immunochemistry/In situ hybridization staining assays were performed to assess the expression of SNHG4, RRM2, TK1, AURKA, EZH2 and RREB1. Cell cycle was measured by flow cytometry. CCK-8, plate colony formation and EdU assays were performed to assess the cell proliferation. Senescence-associated β-Gal assay was used to detect the cell senescence level. γ-H2AX staining assay was performed to assess the DNA damages of PCa cells. Luciferase reporter assay and RNA immunoprecipitation assay were performed to verify the RNA-RNA interactions. Chromatin immunoprecipitation assay was performed to assess the bindings between protein and genomic DNA.

Results

We found that RRM2 and NUSAP1 are highly expressed in PCa tumors and significantly correlated with poor clinical outcomes in PCa patients. Bioinformatic analysis as well as experimental validation suggested that SNHG4 regulates RRM2 expression via a let-7 miRNA-mediated ceRNA network. In addition, SNHG4 or RRM2 knockdown significantly induced cell cycle arrest and cell senescence, and inhibited DNA damage repair and cell proliferation, and the effects can be partially reversed by let-7a knockdown or RRM2 reoverexpression. In vitro and in vivo experiments showed that SNHG4 overexpression markedly enhanced cell resistance to enzalutamide. RREB1 was demonstrated to transcriptionally regulate SNHG4, and RREB1 was also validated to be a target of let-7a and thereby regulated by the SNHG4/let-7a feedback loop.

Conclusion

Our study uncovered a novel molecular mechanism of lncRNA SNHG4 in driving prostate cancer progression and enzalutamide resistance, revealing the critical roles and therapeutic potential of RREB1, SNHG4, RRM2 and let-7 miRNAs in anticancer therapy.
Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis
Authors: Li Juan , Dong Xiangjun , Kong Xue , Wang Yafen , Li Yanru , Tong Yao , Zhao Wenjing , Duan Weili , Li Peilong , Wang Yanqun , Wang Chuanxin
Published: August 2023

Background

Circular RNAs (circRNAs) have been shown to play diverse biological functions in the progression of multiple diseases. However, the impacts of circRNAs on breast cancer (BC) progression remains unclear. Therefore, the objective of this paper is to investigate the role and mechanisms of a functional circRNA in BC metastasis and immune escape.

Methods

This study used a circRNA microarray and identified a novel circRNA hsa_circ_0067842. The validation and characteristics of hsa_circ_0067842 were investigated using qRT-PCR, sanger sequencing, RNase R treatment, actinomycin D treatment and fluorescence in situ hybridization (FISH). Gain- and loss-of-function assays were performed to evaluate the biological function of hsa_circ_0067842 in BC progression and immune escape. Mechanistically, the interaction between hsa_circ_0067842 and HuR was explored by RNA pull down, mass spectrometry (MS), subcellular component protein extraction and immunofluorescence (IF). The regulatory mechanisms of hsa_circ_0067842/HuR/CMTM6/PD-L1 axis were investigated by qRT-PCR, western blot, FISH, immunoprecipitation and rescue assays.

Results

The expression of hsa_circ_0067842 was upregulated in BC tissues and cells, which was found to be significantly associated with poor prognosis, regardless of other clinical covariates. Function assays showed that hsa_circ_0067842 promoted the migration and invasion capacities of BC cells. Moreover, co-culture experiment with peripheral blood mononuclear cells (PBMCs) showed that hsa_circ_0067842 played a role in the immune escape of BC cells. Mechanistically, our study showed that hsa_circ_0067842 interacted with HuR, affecting its nuclear translocation, thus enhancing the stability of CMTM6. CMTM6 not only enhances the migration and invasion ability of BC cells, but also affects the ubiquitination of PD-L1 and inhibits its degradation.

Conclusion

Collectively, our results demonstrated that hsa_circ_0067842 promoted BC progression through the HuR/CMTM6/PD-L1 axis, providing new insight and a potential target for BC prognosis and therapy.
Rating versus ranking in a Delphi survey: a randomized controlled trial
Authors: Del Grande Claudio , Kaczorowski Janusz
Published: August 2023

Background

The Delphi technique has steeply grown in popularity in health research as a structured approach to group communication process. Rating and ranking are two different procedures commonly used to quantify participants’ opinions in Delphi surveys. We explored the influence of using a rating or ranking approach on item prioritization (main outcome), questionnaire completion time, and evaluation of task difficulty in a Delphi survey aimed at identifying priorities for the organization of primary cardiovascular care.

Methods

A randomized controlled parallel group trial was embedded in a three-round online Delphi survey. After an “open” first round, primary care patients, trained patient partners, and primary care clinicians from seven primary care practices were allocated 1:1 to a rating or ranking assessment group for the remainder of the study by stratified permuted block randomization, with strata based on participants’ gender and status. Agreement on item prioritization between the experimental groups was measured by calculating Krippendorff’s alpha reliability coefficient on the aggregate rank order of items in each group after the final round. Self-reported ease or difficulty with the assessment task was measured with the Single Ease Question.

Results

Thirty-six panelists (13 clinic patients, 7 patient partners, 16 clinicians; 60% females) were randomized to the rating (n = 18) or ranking (n = 18) group, with 30 (83%) completing all rounds. Both groups identified the same highest priorities from a set of 41 items, but significant discrepancies were found as early as the seventh top item. There was moderately strong agreement between the priority ordering of top items common to both groups (Krippendorff’s alpha = 0.811, 95% CI = 0.669–0.920). A 9-min mean difference to complete the third-round questionnaire in favor of the rating group failed to achieve statistical significance (p = 0.053). Ranking was perceived as more difficult (p < 0.001).

Conclusions

A rating or ranking procedure led to modestly similar item prioritization in a Delphi survey, but ranking was more difficult. This study should be replicated with a larger number of participants and with variations in the ranking and rating procedures.

Trial registration

Not applicable.
Effects of 36-hour recovery on marksmanship and hormone concentrations during strenuous winter military survival training
Authors: Ojanen Tommi , Pihlainen Kai , Yli-Renko Jussi , Vaara Jani P. , Nykänen Tarja , Heikkinen Risto , Kyröläinen Heikki
Published: August 2023

Objectives

Survival training can provide a unique setting for scientific examination of human stress responses and physical performance in a realistic operational military context. The aim of the present study was to observe effects of a 36-h recovery period on serum hormone concentrations, salivary cortisol, and marksmanship during 10-day winter military survival training in north of the Arctic Circle.

Design and methods

Sixty-eight male soldiers were randomly divided into two groups; EXP (n = 26) and CON (n = 42). While CON performed the whole exercise phase in the field, EXP had 36-h recovery period between days 6 and 8. Several hormones were measured during the study to investigate recovery.

Results

Subjective physical and mental demand as well as catabolic hormone levels increased and anabolic hormones decreased in CON (p < 0.05), whereas in EXP, recovery period attenuated negative effects of survival training. Prone shooting performance decreased (87.5 ± 6.5 vs. 76.3 ± 8.8, points out of 100, p < 0.05) between days 6 and 8 in CON while EXP was able to maintain shooting performance throughout the study.

Conclusion

A short recovery during a strenuous training can prevent the degradation in psychophysiological state and shooting performance in soldiers, which can be crucial for survival in demanding operational winter environment. In the present study, 36-h rest period during the field training seems to enhance recovery but the duration of the period was inadequate for full recovery from the accumulated operative stress. In conclusion, appropriate recovery periods should be implemented in order to optimize occupational performance during high operative stress.
Blood parameters associated with residual feed intake in beef heifers
Authors: Clemmons Brooke A. , Ault-Seay Taylor B. , Henniger Madison T. , Martin M. Gabbi , Mulon Pierre-Yves , Anderson David E. , Voy Brynn H. , McLean Kyle J. , Myer Phillip R.
Published: August 2023

Blood chemistry may provide indicators to greater feed efficient cattle. As a side objective to previous research, 17 Angus heifers approximately two years old underwent a feed efficiency trial to determine residual feed intake (RFI) and identify variation in blood chemistry in beef cattle divergent in feed efficiency. Heifers were categorized as high- or low-RFI based ± 0.25 standard deviations around mean RFI. Blood samples were analyzed using an i-STAT handheld blood analyzer to measure sodium, potassium, glucose, blood urea nitrogen (BUN), creatinine, hematocrit, and hemoglobin. BUN was greater in high-RFI heifers (µ = 8.7 mg/dL) contrasted to low-RFI heifers (µ = 6.5 mg/dL; P = 0.01), whereas glucose was greater in low-RFI heifers (µ = 78.1 mg/dL) contrasted to high-RFI heifers (µ = 82.0 mg/dL; P = 0.05). No other blood chemistry parameters differed by RFI. The greater abundance of BUN in high-RFI heifers may indicate inefficient utilization of protein or mobilization of tissue protein for non-protein use. Greater blood glucose concentrations in low-RFI heifers may indicate greater utilization of energy precursors, such as volatile fatty acids, or metabolites. These data suggest there are readily measurable indicators of physiological variation in nutrient utilization; however, this warrants additional studies to explore.
Hereditary breast and ovarian cancer triggered by occult fallopian tube cancer: a case report
Authors: Murakami Hikaru , Fujiwara Satoe , Nishie Ruri , Ueda Shoko , Terada Shinichi , Yamada Takashi , Ohmichi Masahide
Published: August 2023

Background

At the time of benign gynecological surgery, a prophylactic salpingo-oophorectomy or salpingectomy is increasingly being performed concurrently to reduce the risk of future ovarian and fallopian tube cancer. We herein describe a case of hereditary breast and ovarian cancer syndrome in which a hysterectomy and bilateral adnexectomy were performed with a preoperative diagnosis of benign tumor. A detailed pathological examination revealed occult fallopian tube cancer, and additional staging surgery provided an accurate pathology diagnosis.

Case presentation

A 72-year-old Japanese woman with a past history of breast cancer underwent a hysterectomy and bilateral oophoro-salpingectomy for the preoperative diagnosis of uterine myoma and a right para-ovarian cyst. In the detailed pathological examination, high-grade serous carcinoma of the right fallopian tube was detected incidentally, and a subsequent staging laparotomy confirmed single para-aortic lymph node metastasis. Furthermore, a mutation in germline BRCA2 was detected postoperatively, and the patient was finally diagnosed with hereditary breast and ovarian cancer syndrome. She was diagnosed with fallopian tube cancer International Federation of Gynecology and Obstetrics Stage IIIA1(i) and started on adjuvant therapy (six courses of paclitaxel and carboplatin followed by maintenance therapy with olaparib), and 18 months after surgery, she was free of disease.

Conclusion

This is a case of fallopian tube cancer that was diagnosed incidentally and then accurately staged with additional advanced staging surgery. Even in the absence of grossly malignant findings, a detailed pathological search of the fallopian tubes and accurate staging surgery are important to make the necessary treatment decisions for the patient.
Multi-attention-based approach for deepfake face and expression swap detection and localization
Authors: Waseem Saima , Abu-Bakar Syed Abdul Rahman Syed , Omar Zaid , Ahmed Bilal Ashfaq , Baloch Saba , Hafeezallah Adel
Published: August 2023

Advancements in facial manipulation technology have resulted in highly realistic and indistinguishable face and expression swap videos. However, this has also raised concerns regarding the security risks associated with deepfakes. In the field of multimedia forensics, the detection and precise localization of image forgery has become essential tasks. Current deepfake detectors perform well with high-quality faces within specific datasets, but often struggle to maintain their performance when evaluated across different datasets. To this end, we propose an attention-based multi-task approach to improve feature maps for classification and localization tasks. The encoder and the attention-based decoder of our network generate localized maps that highlight regions with information about the type of manipulation. These localized features are shared with the classification network, improving its performance. Instead of using encoded spatial features, attention-based localized features from the decoder’s first layer are combined with frequency domain features to create a discriminative representation for deepfake detection. Through extensive experiments on face and expression swap datasets, we demonstrate that our method achieves competitive performance in comparison to state-of-the-art deepfake detection approaches in both in-dataset and cross-dataset scenarios. Code is available athttps://github.com/saimawaseem/Multi-Attention-Based-Approach-for-Deepfake-Face-and-Expression-Swap-Detection-and-Localization.
New fixed point theorems via measure of noncompactness and its application on fractional integral equation involving an operator with iterative relations
Authors: Deb Sudip , Jafari Hossein , Das Anupam , Parvaneh Vahid
Published: August 2023

In this paper, Darbo’s fixed point theorem is generalized and it is applied to find the existence of solution of a fractional integral equation involving an operator with iterative relations in a Banach space. Moreover, an example is provided to illustrate the results.
PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer
Authors: Liu Jiahao , Liu Baiying , Li Yanan , Mi Ze , Tan Hongpei , Rong Pengfei
Published: August 2023

Background

Liver cancer is a prevalent and deadly form of cancer with high incidence and mortality rates. The PCMT1 protein has been linked to cell anti-apoptosis and tumor metastasis, but its significance in liver hepatocellular carcinoma (LIHC) remains largely unexplored.

Methods

We conducted a pan-cancer analysis to examine the expression differences of PCMT1. Kaplan–Meier curves were employed to assess the prognostic impact of PCMT1 on LIHC patients, and we investigated the association between PCMT1 and clinical features, which we validated using a GEO therapeutic dataset. Gene enrichment analysis helped identify signaling pathways associated with PCMT1 expression. Moreover, we evaluated the relationship between PCMT1 and immune cell infiltration, as well as the differences in gene mutations between high-expression and low-expression groups. In vitro and in vivo experiments were performed to assess the effect of PCMT1 on tumor cell lines and mouse tumor models, and potential pathways were explored through gene sequencing.

Result

PCMT1 is highly expressed in most tumors and exhibits a significant association with prognosis in LIHC patients. Pathway enrichment analysis revealed that PCMT1 is involved in cell cycle regulation, immunity, and other processes. Further immune analysis demonstrated that high expression of PCMT1 could reduce tumor-killing immune cell infiltration. In vitro experiments indicated that PCMT1 knockdown could inhibit cancer cell proliferation and migration while promoting apoptosis. In vivo experiments showed that PCMT1 knockdown significantly reduced tumor growth rate, enhanced CD8+T cell infiltration, and increased caspase-3 expression in the tumor area. Gene sequencing suggested that PCMT1 may function through the PI3K–AKT pathway.

Conclusion

Our findings suggest that PCMT1 acts as a promoter of liver cancer progression and may serve as a novel prognostic indicator and therapeutic target for patients with LIHC.
A predictive model for the risk of sepsis within 30 days of admission in patients with traumatic brain injury in the intensive care unit: a retrospective analysis based on MIMIC-IV database
Authors: Hu Fangqi , Zhu Jiaqiu , Zhang Sheng , Wang Cheng , Zhang Liangjia , Zhou Hui , Shi Hui
Published: August 2023

Purpose

Traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) are at a high risk of infection and sepsis. However, there are few studies on predicting secondary sepsis in TBI patients in the ICU. This study aimed to build a prediction model for the risk of secondary sepsis in TBI patients in the ICU, and provide effective information for clinical diagnosis and treatment.

Methods

Using the MIMIC IV database version 2.0 (Medical Information Mart for Intensive Care IV), we searched data on TBI patients admitted to ICU and considered them as a study cohort. The extracted data included patient demographic information, laboratory indicators, complications, and other clinical data. The study cohort was divided into a training cohort and a validation cohort. In the training cohort, variables were screened by LASSO (Least absolute shrinkage and selection operator) regression and stepwise Logistic regression to assess the predictive ability of each feature on the incidence of patients. The screened variables were included in the final Logistic regression model. Finally, the decision curve, calibration curve, and receiver operating character (ROC) were used to test the performance of the model.

Results

Finally, a total of 1167 patients were included in the study, and these patients were randomly divided into the training (N = 817) and validation (N = 350) cohorts at a ratio of 7:3. In the training cohort, seven features were identified as key predictors of secondary sepsis in TBI patients in the ICU, including acute kidney injury (AKI), anemia, invasive ventilation, GCS (Glasgow Coma Scale) score, lactic acid, and blood calcium level, which were included in the final model. The areas under the ROC curve in the training cohort and the validation cohort were 0.756 and 0.711, respectively. The calibration curve and ROC curve show that the model has favorable predictive accuracy, while the decision curve shows that the model has favorable clinical benefits with good and robust predictive efficiency.

Conclusion

We have developed a nomogram model for predicting secondary sepsis in TBI patients admitted to the ICU, which can provide useful predictive information for clinical decision-making.