bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application value of Ki67 and serum CA125 in the deep myometrial invasion of endometrial adenocarcinoma
Authors: Qin Lin 
Published: March 2023

Abstract
Objective
To investigate the application value of Ki67 and serum CA125 in diagnosing the deep myometrial invasion of endometrial adenocarcinoma.

Methods
This study retrospectively analyzed 80 patients with endometrial adenocarcinoma, who underwent procedure from January 2018 to June 2021 at Senior Department of Obstetrics & Gynecology, the Seventh Medical Center of PLA General Hospital assigned to the Fourth Medical Center. The general clinical data, serum CA125 and Ki67 levels were compared between the superficial muscular infiltration group and the deep myometrial invasion group. We investigated the application value of Ki67 and serum CA125 in diagnosing the deep myometrial invasion of endometrial adenocarcinoma by the ROC curve.

Results
80 patients were retrospectively analyzed, and 53 cases were superficial muscular infiltration, 27 cases were deep myometrial invasion. There was significant difference in age, tumor diameter, lymph node metastasis, Ki67, serum CA125, p53 status, serum CA125 and Ki67 levels between the two groups (p < 0.05). As high as 35% of Ki67 was the optimal cutoff value for predicting DMI in endometrial adenocarcinoma, and the area under ROC curve was 0.691, the sensitivity and specificity of diagnosis were 88.9% and 56.6%. As high as 43.645 U/ml of serum CA125 was the optimal cutoff value for predicting DMI in endometrial adenocarcinoma, and the area under ROC curve was 0.668, the sensitivity and specificity of diagnosis were 40.7% and 92.5%. After combined detection of both, the area under ROC curve was 0.719, and its sensitivity and specificity of diagnosis were 96.3% and 43.4%.

Conclusion
Serum CA125 and Ki67 may be used to evaluate DMI in patients with endometrial adenocarcinoma, and the diagnostic value of combination is higher, which provide reference for clinical treatment.
The expression, immune infiltration, prognosis, and experimental validation of OSBPL family genes in liver cancer
Authors: Tian Kunpeng , Ying Yongling , Huang Jingjing , Wu Hao , Wei Chengyue , Li Liang , Chen Longjun , Wu Lichuan 
Published: March 2023

Abstract
Background
Liver cancer is the third most deadly malignant tumor in the world with poor prognosis and lacks early diagnostic markers. It is urgent need to explore new biomarkers and prognostic factors. The oxysterol-binding protein-like family proteins (OSBPLs) are essential mediators of lipid transportation and cholesterol balancing which has been reported to participate in cancer progression. So far, the expression, immune infiltration, and prognosis of OSBPLs have not been elucidated in liver cancer.

Methods
The differential expressions of OSBPLs between liver tumor and normal tissues were assessed by analyzing RNA-seq data from TCGA and protein data from CPTAC, respectively. Subsequently, genetic variations, potential functional enrichment analysis, and immune cell infiltration were analyzed. Further, the prognostic effects of OSBPLs were identified via constructing lasso models and performing receiver operating characteristic curve (ROC) analysis. Moreover, 10 local liver cancer specimens were involved to validate the expression of OSBPL3 via immunohistochemistry (IHC) assay. Finally, CCK-8, cell cycle, apoptosis, transwell assays, real time qPCR (RT-qPCR), and western blot assays were conducted to explore the function of OSBPL3 in liver cancer cells.

Results
The mRNA of OSBPL2, OSBPL3, and OSBPL8 were highly expressed while OSBPL6 was lowly expressed in liver cancer samples compared with normal samples. As to the protein expression, OSBPL2 and OSBPL3 were significantly elevated and OSBPL5, OSBPL6, OSBPL9, OSBPL10, OSBPL11 were downregulated in tumor samples. A positive correlation was found between copy number variations (CNV) and the expression of OSBPL2, OSBPL8, OSBPL9, OSBPL11, while DNA methylation was negatively associated with the expressions of OSBPLs. Of these, CNV amplification mainly contributed to the overexpression of OSBPL2 and DNA methylation may be responsible for the high expression of OSBPL3. Interestingly, OSBPL3, OSBPL5, SOBPL7, and OSBPL10 were significantly positively correlated with immune infiltration. Notably, OSBPL3 was identified correlated to overall survival (OS) and disease specific survival (DSS) in liver cancer. Functionally, knocking down OSBPL3 reduced liver cancer cell viability, induced a G2/M cell cycle arrest, promoted apoptosis, and restrained cell migration.

Conclusion
In aggregate, we reported a heretofore undescribed role of OSBPLs in liver cancer by analyzing multi-omics data. Importantly, we identified OSBPL3 was overexpressed in liver tumor compared with normal and its high expression was correlated with poor OS and DSS. Inhibition of OSBPL3 resulted in a pronounced decrease in cell proliferation and migration.
Development of mental health first-aid guidelines for depression: a Delphi expert consensus study in Argentina and Chile
Authors: Encina-Zúñiga Esteban , Agrest Martín , Tapia-Munoz Thamara , Vidal-Zamora Isidora , Ardila-Gómez Sara , Alvarado Rubén , Leiderman Eduardo A. , Reavley Nicola 
Published: March 2023

Abstract
Background
Depression is one of the most common mental health problems worldwide and, while prevalence rates in Latin America are relatively high, most people who meet the criteria for diagnosis do not receive treatment. Family and friends of a person with depression can play an important role in supporting a person to seek and engage with treatment. However, many people do not have the necessary skills or confidence to help. English-language mental health first aid guidelines have been developed to support people to provide such help. The aim of this study was to culturally adapt these guidelines for Chile and Argentina.

Methods
A Delphi expert consensus study was conducted with two expert panels, one of people with lived experience of depression (either their own or as a carer; n = 26) and one of health professionals (n = 29). Overall, 172 statements from the English-language guidelines were translated and compiled into a questionnaire. Participants were asked to rate statements based on how essential or important those statements were for Chile and Argentina and to suggest new statements if necessary.

Results
Data were obtained over two survey rounds. Consensus was achieved on 172 statements. A total of 137 statements were adopted from the English-language guidelines, whereas 35 new endorsed statements were generated from panel suggestions. There were similarities between the English-language guidelines and those for Chile and Argentina. The adapted guidelines did not include some of the items from the English-language guidelines related to commenting on a person’s strengths or making judgements about their character, and also incorporated new items related to the incorporation of sociocultural considerations as causes of depression and attention to inequities in mental health.

Conclusions
The significant number of new items underscores the importance of undertaking a careful process of cultural adaptation. Further research on dissemination and incorporation of the guidelines into the Mental Health First Aid training course for Chile and Argentina is still required.
Sensory evaluation of the bitterness of asenapine using D-sorbitol pretreatment: single-blind, placebo-controlled, crossover trial
Authors: Wada Shuhei , Iwamoto Kunihiro , Okumura Hiroki , Hida Hirotake , Hiraoka Shuichi , Kamei Aya , Mori Daisuke , Yamada Kiyofumi , Ozaki Norio 
Published: March 2023

Abstract
Background
Antipsychotics are essential in the acute treatment of and maintenance therapy for schizophrenia, but medication adherence and long-term treatment continuity are needed to maximize their effectiveness. Each antipsychotic has various side effects, which may affect adherence. Some patients with schizophrenia are reluctant to take asenapine because of its unique oral-related side effects, such as the bitter taste caused by sublingual administration. Our previous basic research found that D-sorbitol lowered the bitterness parameters of the taste sensors. However, whether D-sorbitol has the same effect in patients remains unclear. Therefore, using a D-sorbitol solution, we aim to evaluate changes in the bitterness of asenapine among patients with schizophrenia.

Methods
In this single-blind, placebo-controlled, crossover trial, we plan to recruit 20 adult patients with schizophrenia spectrum disorder who take sublingual asenapine tablets. The participants will be divided into two groups (n = 10 each). Each group will be given a D-sorbitol or placebo solution on the first day for rinsing before taking the sublingual asenapine tablets. After a 1-day interval, the participants will rinse their mouths again with a different liquid. Questionnaires regarding changes in taste and the willingness to continue asenapine will be conducted before the start of the study and after each rinse. The primary and secondary end points will be a taste evaluation of bitterness, and the willingness to continue asenapine, respectively. Differences in questionnaire scores between the D-sorbitol and placebo solutions will be calculated and analyzed using a McNemar test.

Discussion
This study aims to determine the efficacy of D-sorbitol in masking the bitter taste of asenapine. To our knowledge, it is the first intervention study using D-sorbitol for bitter taste of asenapine in patients with schizophrenia. Evidence of the efficacy of D-sorbitol could result in D-sorbitol pretreatment being an easy and inexpensive means of improving adherence to asenapine.

Trial registration
This study was registered in the Japan Registry of Clinical Trials jRCTs041210019, on May 14, 2021. Ethics approval was obtained from the Nagoya University Clinical Research Review Board.
Interventions addressing maternal and child health among the urban poor and homeless: an overview of systematic reviews
Authors: Nambiar Devaki , Mathew Bincy , Dubey Shubhankar , Moola Sandeep 
Published: March 2023

Abstract
Background
Inequalities in access to and utilization of maternal and child health (MCH) care are hampering progress on the path to achieving the Sustainable Development Goals. In a number of Low- and Middle-Income Countries (LMICs) population subgroups at disproportionate risk of being left behind are the urban poor. Within this neglected group is the further neglected group of the homeless. Concomitantly, a number of interventions from the antenatal period onward have been piloted, tested, and scaled in these contexts. We carried out an overview of systematic reviews (SRs) to characterize the evidence around maternal and child health interventions relevant to urban poor homeless populations in LMICs.

Methods
We searched Medline, Cochrane Library, Health Systems Evidence and EBSCOhost databases for SRs published between January 2009 and 2020 (with an updated search through November 2021). Our population of interest was women or children from urban poor settings in LMICs; interventions and outcomes corresponded with the World Health Organization’s (WHO) guidance document. Each SR was assessed by two reviewers using established standard critical appraisal checklists. The overview was registered in PROSPERO (ID: CRD42021229107).

Results
In a sample of 33 high quality SRs, we found no direct relevant evidence for pregnant and lactating homeless women (and children) in the reviewed literature. There was a lack of emphasis on evidence related to family planning, safe abortion care, and postpartum care of mothers. There was mixed quality evidence that the range of nutritional interventions had little, unclear or no effect on several child mortality and development outcomes. Interventions related to water, sanitation, and hygiene, ensuring acceptability of community health services and health promotion type programs could be regarded as beneficial, although location seemed to matter. Importantly, the risk of bias reporting in different reviews did not match, suggesting that greater attention to rigour in their conduct is needed.

Conclusion
The generalizability of existing systematic reviews to our population of interest was poor. There is a clear need for rigorous primary research on MCH interventions among urban poor, and particularly homeless populations in LMICs, as it is as yet unclear whether the same, augmented, or altogether different interventions would be required.
Development of a brief menstrual quality of life measure for women with heavy menstrual bleeding
Authors: Lancastle Deborah , Kopp Kallner Helena , Hale Gabrielle , Wood Bethan , Ashcroft Lauren , Driscoll Holly 
Published: March 2023

Abstract
Background
The National Institute for Health and Care Excellence advises that considerations around quality of life should be made when assessing and treating heavy menstrual bleeding. A quick and reliable method for women to assess the impact of HMB on their quality of life might encourage help-seeking. This research aimed to develop a new 10-item measure of menstrual quality of life (the PERIOD-QOL).

Methods
Three pilot studies describe PERIOD-QOL development and a cross-sectional survey (N = 376) assessed PERIOD-QOL scores in women who reported HMB and those who did not. A population sample of women (mean age 30.29, SD = 9.06) completed the PERIOD-QOL and rated their menstrual bleeding as heavy/very heavy/extremely heavy (HMB group) or very light/light/moderate bleeding (LMMB) group. Data were analysed using independent samples Analysis of Variance and independent samples t-tests.

Results
Cronbach’s Alpha for the PERIOD-QOL = .88. A significant reduction in PERIOD-QOL scores was found across the 6 levels of bleeding from very light to extremely heavy, and significantly lower PERIOD-QOL scores were reported in the HMB than the LMMB group.

Conclusion
The results suggest that the PERIOD-QOL is a reliable measure and that women experiencing HMB reported significantly lower menstrual quality of life than those who did not. Further validation of the PERIOD-QOL is required to determine its relationships with existing measures of menstrual quality of life and to establish whether PERIOD-QOL scores are associated with decisions to seek help from health professionals and with verified diagnoses of conditions that cause HMB.
Digital feedback during clinical education in the emergency medical services: a qualitative study
Authors: Nilsson Tomas , Masiello I. , Broberger E. , Lindström V. 
Published: March 2023

Abstract
Background
Clinical education is essential for students’ progress towards becoming registered nurses (RN) in Sweden. Assessment of caring skills in the Emergency Medical Services (EMS) is complex due to the ever-changing scenarios and the fact that multiple supervisors are involved in the student’s education. Currently, assessments of student’s skills are summative and occur twice during the six weeks of clinical education. A digitalized assessment tool (DAT) with an adaptation for formative assessment is a new approach to assessment of nursing skills in the EMS. Since new technologies and changes in procedures are likely to affect both students and supervisors, our aim in this study is to describe students’ and clinical supervisors’ experience of formative assessments using DAT in the EMS.

Method
This study is qualitative, using semi-structured group interviews (N = 2) with students and semi-structured individual telephone interviews (N = 13) with supervisors. The data was analysed according to Graneheim and Landman’s method for content analysis. This analysis generated 221 codes organized into 10 categories within which three themes were identified. The students in this study were nursing students in their last semester and all supervisors were experienced RNs.

Results
The results showed that students and supervisors had mainly positive views of the DAT and the formative assessment stating that the information they provided while using the DAT offered opportunities for reflection. The DAT supported the students’ learning by visualizing strengths and areas of improvement, as well as displaying progress using a Likert scale. The application improved communication, but additional features linking the assessment tool with the university were requested. The application contributed to transparency in the assessments and was seen as preferable to the traditional ‘pen and paper’ method.

Conclusion
A digital system was described in a positive manner, and the assessment using the DAT facilitated reflection and formative assessment. The use of a Likert scale was considered positive in order to demonstrate progression which with advantage could be demonstrated visually.
Ethical concerns when recruiting children with cancer for research: Swedish healthcare professionals’ perceptions and experiences
Authors: Norbäck Kajsa , Höglund Anna T. , Godskesen Tove , Frygner-Holm Sara 
Published: March 2023

AbstractBackgroundResearch is crucial to improve treatment, survival and quality of life for children with cancer. However, recruitment of children for research raises ethical challenges. The aim of this study was to explore and describe ethical values and challenges related to the recruitment of children with cancer for research, from the perspectives and experiences of healthcare professionals in the Swedish context. Another aim was to explore their perceptions of research ethics competence in recruiting children for research.MethodsAn explorative qualitative study using semi-structured interviews with key informants. Seven physicians and ten nurses were interviewed. Interviews were analysed using inductive qualitative content analysis.ResultsThe respondents’ ethical challenges and values in recruitment mainly concerned establishing relationships and trust, meeting informational needs, acknowledging vulnerability, and balancing roles and interests. Ensuring ethical competence was raised as important, and interpersonal and communicative skills were highlighted.ConclusionThis study provides empirical insight into recruitment of children with cancer, from the perspectives of healthcare professionals. It also contributes to the understanding of recruitment as a relational process, where aspects of vulnerability, trust and relationship building are important, alongside meeting informational needs. The results provide knowledge on the complexities raised by paediatric research and underpin the importance of building research ethics competence to ensure that the rights and interests of children with cancer are protected in research.
Short-chain fatty acids as a link between diet and cardiometabolic risk: a narrative review
Authors: Birkeland Eline , Gharagozlian Sedegheh , Valeur Jørgen , Aas Anne-Marie 
Published: March 2023

Abstract
Aim
Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk.

Findings
Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration.

Conclusion
This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant–based foods and discouraging the intake of animal foods rich in saturated fatty acids.
Mechanical force induces macrophage-derived exosomal UCHL3 promoting bone marrow mesenchymal stem cell osteogenesis by targeting SMAD1
Authors: Pu Panjun , Wu Shengnan , Zhang Kejia , Xu Hao , Guan Jiani , Jin Zhichun , Sun Wen , Zhang Hanwen , Yan Bin 
Published: March 2023

Abstract
Background
Orthodontic tooth movement (OTM), a process of alveolar bone remodelling, is induced by mechanical force and regulated by local inflammation. Bone marrow-derived mesenchymal stem cells (BMSCs) play a fundamental role in osteogenesis during OTM. Macrophages are mechanosensitive cells that can regulate local inflammatory microenvironment and promote BMSCs osteogenesis by secreting diverse mediators. However, whether and how mechanical force regulates osteogenesis during OTM via macrophage-derived exosomes remains elusive.

Results
Mechanical stimulation (MS) promoted bone marrow-derived macrophage (BMDM)-mediated BMSCs osteogenesis. Importantly, when exosomes from mechanically stimulated BMDMs (MS-BMDM-EXOs) were blocked, the pro-osteogenic effect was suppressed. Additionally, compared with exosomes derived from BMDMs (BMDM-EXOs), MS-BMDM-EXOs exhibited a stronger ability to enhance BMSCs osteogenesis. At in vivo, mechanical force-induced alveolar bone formation was impaired during OTM when exosomes were blocked, and MS-BMDM-EXOs were more effective in promoting alveolar bone formation than BMDM-EXOs. Further proteomic analysis revealed that ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3) was enriched in MS-BMDM-EXOs compared with BMDM-EXOs. We went on to show that BMSCs osteogenesis and mechanical force-induced bone formation were impaired when UCHL3 was inhibited. Furthermore, mothers against decapentaplegic homologue 1 (SMAD1) was identified as the target protein of UCHL3. At the mechanistic level, we showed that SMAD1 interacted with UCHL3 in BMSCs and was downregulated when UCHL3 was suppressed. Consistently, overexpression of SMAD1 rescued the adverse effect of inhibiting UCHL3 on BMSCs osteogenesis.

Conclusions
This study suggests that mechanical force-induced macrophage-derived exosomal UCHL3 promotes BMSCs osteogenesis by targeting SMAD1, thereby promoting alveolar bone formation during OTM.

Graphical Abstract