bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring biological kinship in ancient datasets: comparing the response of ancient DNA-specific software packages to low coverage data
Authors: Marsh William A , Brace Selina , Barnes Ian
Published: March 2023

Background

The inference of biological relations between individuals is fundamental to understanding past human societies. Caregiving, resource sharing and sexual behaviours are often mediated by biological kinship and yet the identification and interpretation of kin relationships in prehistoric human groups is difficult. In recent years, the advent of archaeogenetic techniques have offered a fresh approach, and when combined with more traditional osteological and interpretive archaeological methods, allows for improved interpretation of the burial practices, cultural behaviours, and societal stratification in ancient societies. Although archaeogenetic techniques are developing at pace, questions remain as to their accuracy, particularly when applied to the low coverage datasets that results from the sequencing of DNA derived from highly degraded ancient material.

Results

The performance of six of the most commonly used kinship identifcation software methods was explored at a range of low and ultra low genome coverages. An asymmetrical response was observed across packages, with decreased genome coverage resulting in differences in both direction and degree of change of calculated kinship scores and thus pairwise relatedness estimates are dependant on both package used and genome coverage. Methods reliant upon genotype likelihoods methods (lcMLkin, NGSrelate and NGSremix) show a decreased level of prediction at coverage below 1x, although were consistent in the particular relationships identified at these coverages when compared to the pseudohaploid reliant methods tested (READ, the Kennett 2017 method and TKGWV2.0). The three pseudohaploid methods show predictive potential at coverages as low as 0.05x, although the accuracy of the relationships identified is questionable given the increase in the number of relationships identifIed at the low coverage (type I errors).

Conclusion

Two pseudohaploid methods (READ and Kennett 2017) show relatively consistent inference of kin relationships at low coverage (0.5x), with READ only showing a significant performance drop off at ultralow coverages (< 0.2x). More generally, our results reveal asymmetrical kinship classifications in some software packages even at high coverages, highlighting the importance of applying multiple methods to authenticate kin relationships in ancient material, along with the continuing need to develop laboratory methods that maximise data output for downstream analyses.
The transcription factor GhWRKY70 from gossypium hirsutum enhances resistance to verticillium wilt via the jasmonic acid pathway
Authors: Zhang Shuling , Dong Lijun , Zhang Xue , Fu Xiaohong , Zhao Lin , Wu Lizhu , Wang Xingfen , Liu Jianfeng
Published: March 2023

Background

The WRKY transcription factors play significant roles in plant growth, development, and defense responses. However, in cotton, the molecular mechanism of most WRKY proteins and their involvement in Verticillium wilt tolerance are not well understood.

Results

GhWRKY70 is greatly up-regulated in cotton by Verticillium dahliae. Subcellular localization suggests that GhWRKY70 is only located in the nucleus. Transcriptional activation of GhWRKY70 further demonstrates that GhWRKY70 function as a transcriptional activator. Transgenic Arabidopsis plants overexpressing GhWRKY70 exhibited better growth performance and higher lignin content, antioxidant enzyme activities and jasmonic acid (JA) levels than wild-type plants after infection with V. dahliae. In addition, the transgenic Arabidopsis resulted in an enhanced expression level of AtAOS1, a gene related to JA synthesis, further leading to a higher JA accumulation compared to the wild type. However, the disease index (DI) values of the VIGS-treated cotton plants with TRV:WRKY70 were also significantly higher than those of the VIGS-treated cotton plants with TRV:00. The chlorophyll and lignin contents of TRV:WRKY70 plants were significantly lower than those of TRV:00 plants. GhAOS1 expression and JA abundance in TRV:WRKY70 plants were decreased. The GhWRKY70 protein was confirmed to bind to the W-box element in the promoter region of GhAOS by yeast one-hybrid assay and transient expression.

Conclusion

These results indicate that the GhWRKY70 transcription factor is a positive regulator in Verticillium wilt tolerance of cotton, and may promote the production of JA via regulation of GhAOS1 expression.
Comprehensive analysis of the biological function and immune infiltration of SLC38A2 in gastric cancer
Authors: Zhu Liang , Wang Zhengguang , Han Wenxiu , Xu Aman
Published: March 2023

Background

Solute carrier family 38 member 2 (SLC38A2) has previously been reported to participate in carcinogenesis. However, its expression and function in gastric cancer (GC) remain unclear. The present study aimed to investigate the role of SLC38A2 in GC.

Methods

The prognostic value and expression of SLC38A2 in GC was analyzed by combining bioinformatics and experimental analyses. Colony formation, Cell Counting Kit-8, wound healing, Transwell and tumor formation assays were performed to assess the biological function of SLC38A2. The cBioPortal, GeneMANIA and LinkedOmics databases were mined to determine the underlying regulatory mechanisms of SLC38A2. The role of SLC38A2 in tumor immune infiltration was explored using the TIMER database.

Results

Our results demonstrated that SLC38A2 was upregulated and was correlated with a poor prognosis in GC patients. SLC38A2 downregulation significantly inhibited the proliferation, invasion and migration of GC cells. Abnormal genetic alteration and epigenetic regulation may contribute to the upregulation of SLC38A2 expression levels in GC. The results of enrichment analysis demonstrated that SLC38A2 was associated with ‘hippo signaling’ and ‘ubiquitinyl hydrolase activity’. The results also indicated that SLC38A2 may be a key factor in GC immune infiltration and M2 macrophage polarization.

Conclusion

Overall, these data identified that SLC38A2 may serve as a potential prognostic biomarker and therapeutic target in GC.
Hospitalization costs of injury in elderly population in China: a quantile regression analysis
Authors: Ou Wenjing , Zhang Qin , He Junlin , Shao Xinye , Yang Yang , Wang Xin
Published: March 2023

Background

Trauma in the elderly is gradually growing more prevalent as the aging population increases over time. The purpose of this study is to assess hospitalization costs of the elderly trauma population and analyze the association between those costs and the features of the elderly trauma population.

Methods

In a retrospective analysis, data on trauma patients over 65 who were admitted to the hospital for the first time due to trauma between January 2017 and March 2022 was collected from a tertiary comprehensive hospital in Baotou. We calculated and analyzed the hospitalization cost components. According to various therapeutic approaches, trauma patients were divided into two subgroups: non-surgical patients (1320 cases) and surgical patients (387 cases). Quantile regression was used to evaluate the relationship between trauma patients and hospitalization costs.

Results

This study comprised 1707 trauma patients in total. Mean total hospitalization costs per patient were ¥20,741. Patients with transportation accidents incurred the highest expenditures among those with external causes of trauma, with a mean hospitalization cost of ¥24,918, followed by patients with falls at ¥19,809 on average. Hospitalization costs were dominated by medicine costs (¥7,182 per capita). According to the quantile regression results, all trauma patients' hospitalization costs were considerably increased by length of stay, surgery, the injury severity score (16–24), multimorbidity, thorax injury, and blood transfusion. For non-surgical patients, length of stay, multimorbidity, and the injury severity score (16–24) were all substantially linked to higher hospitalization costs. For surgical patients, length of stay, injury severity score (16–24), and hip and thigh injuries were significantly associated with greater hospitalization costs.

Conclusions

Using quantile regression to identify factors associated with hospitalization costs could be helpful for addressing the burden of injury in the elderly population. Policymakers may find these findings to be insightful in lowering hospitalization costs related to injury in the elderly population.
Impact of glucocorticoids on the efficacy of neoadjuvant chemoradiotherapy and survival of patients with locally advanced rectal cancer: a retrospective study
Authors: Huang Xiaoxue , Zheng Zhiyuan , Zeng Bangwei , Xiao Han , Zheng Hao , Lin Zhuangbin , Song Jianyuan , Li Anchuan , Chi Pan , Yang Yinghong , Xu Benhua , Zheng Rong
Published: March 2023

Abstracts

Background

Preclinical studies suggest that glucocorticoids (GCs) promote the proliferation and development of colorectal cancer. Because GCs are broadly prescribed for treatment-related adverse events in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT), it’s essential to assess the effect of GCs on clinical outcomes.

Methods

LARC cases treated with NCRT followed by surgery were assessed retrospectively. Evaluation of the relationship between GCs use (GCs vs. non-GCs) and neoadjuvant rectal (NAR) score (as a three-level categorical dependent variable) was performed using multivariable multinomial logistic regression (MLR). We also examined the relationship between the accumulated dose of GCs and NAR using multivariate MLR. Survival analysis of disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan–Meier method. Multivariate Cox regression was used to assess confounding factors that could influence OS and DFS.

Results

This retrospective cohort study included 790 patients with newly diagnosed non-metastatic LARC (T3-4/N + M0) who received NCRT followed by surgery between January 2012 and April 2017. The end of the follow-up period was May 11, 2022. Among the 790 patients with LARC, 342 (43.2%) received GCs treatment and 448 (56.8%) did not during the NCRT-to-surgery period. GCs medication was significantly different between mid-NAR (8–16) and low-NAR (< 8) (odds ratio [OR], 0.615; 95% CI, 0.420–0.901; P = 0.013), and the high-NAR (> 16) and low-NAR (0.563; 0.352–0.900; 0.016). Patients exposed to GCs, had a decreased 5-year OS (GCs vs. non-GCs = 80.01% (95% CI, 75.87%–84.37%) vs. 85.30% (82.06%–88.67%), P = 0.023) and poorer 5-year DFS (73.99% (69.45%–78.82%) vs. 78.7% (75.14%–82.78%), P = 0.045). The accumulated dose of GCs was an independent risk factor for OS (hazard ratio [HR], 1.007 [1.001–1.014], 0.036) and DFS (1.010 [1.004–1.017], 0.001).

Conclusions and relevance

Our study revealed that GCs were associated with reduced efficacy of NCRT and worse clinical outcomes in patients with LARC during the NCRT-to-surgery period.
Application value of Ki67 and serum CA125 in the deep myometrial invasion of endometrial adenocarcinoma
Authors: Qin Lin
Published: March 2023

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

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

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

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

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

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

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

Background

Research 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.

Methods

An 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.

Results

The 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.

Conclusion

This 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

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

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
Individual and environmental determinants associated with longer times to access pediatric rheumatology centers for patients with juvenile idiopathic arthritis, a JIR cohort study
Authors: Chausset Aurélie , Lambert Céline , Belot Alexandre , Merlin Etienne , Cannizzaro Elvira , Kone-Paut Isabelle , Ballot Claire , Devauchelle Valérie , Poignant Sylvaine , Carlomagno Raffaella , Lohse Anne , Barbier Catherine , Despert Véronique , Carbasse Aurélia , Sparsa Laetitia , Adank Eva , Vanoni Federica , Reumaux Héloise , Pillet Pascal , Kaiser Daniela , Hofer Michael , Freychet Caroline , Schott Anne-Marie
Published: March 2023

Background

Despite guidelines, poor access to appropriate care for juvenile idiopathic arthritis (JIA) patients remains a global issue. Prompt referral to a pediatric rheumatology (PR) center and effective care is known to be critical for changing the natural history of the disease and improving long-term prognosis. This project assesses socio-economic factors of delayed referral to a pediatric rheumatologist (PRst) for JIA patients in France and Switzerland within the Juvenile Inflammatory Rheumatism (JIR) Cohort.

Methods

All patients diagnosed with JIA, presenting at one center of the JIRcohort in France or Switzerland with additional data on referral pathway were included. Patient characteristics at first visit to the PR center, dates of visits to healthcare providers during referral, and parent characteristics were extracted from the JIRcohort database.

Results

Two hundred fifty children were included. The overall median time to first PR assessment was 2.4 months [1.3; 6.9] and ranged widely across the JIA subtypes, from 1.4 months [0.6; 3.8] for children with systemic juvenile idiopathic arthritis (sJIA) to 5.3 months [2.0; 19.1] for children with enthesitis-related arthritis (ERA). A diagnosis of ERA and an appointment with an orthopedist during the referral pathway were significantly associated with a longer time before the first PR visit (hazard ratio HR 0.50 [95% CI: 0.29; 0.84]) and HR 0.68 [95% CI: 0.49; 0.93], respectively) in multivariable analysis. Having a mother with a post-graduate educational attainment level was tendentially associated with a shorter time before the first PR visit, (HR 1.32 [95% CI: 0.99; 1.78]).

Conclusions

Time to first PRst visit was most often short compared to other studies and close to the British recommendations. However, this time remained too long for many patients. We observed no social inequities in access to a PRst, but we show the need to improve effective pathway and access to a PR center for JIA patients.
Illicit drug use in university students in the UK and Ireland: a PRISMA-guided scoping review
Authors: Boden Maeve , Day Ed
Published: March 2023

Background

Interest in the health and well-being of university students has increased in the UK and Ireland in the past two decades as their numbers have grown. Recent high-profile deaths of students after using illicit drugs have highlighted the importance of the topic for policy makers. This scoping review maps the state of the existing literature evaluating use of illicit drugs in university students in the UK and Ireland. It aims to highlight research gaps and inform policy.

Method

We conducted a systematic search of papers related to psychoactive drug use in university students in the UK and Ireland published before August 2021. The 18 extracted study characteristics included author(s); year of publication; journal; location of data collection; study design; delivery method (e.g., online survey, in-person, postal survey); number of participants; response rate; participant course of study, year of study, degree level (i.e., undergraduate, postgraduate), gender and age; time-period assessed (e.g., lifetime, current use, past 12 months); primary aim; primary outcome; ethical approval; and funding source.

Results

The PRISMA-guided search strategy identified 1583 papers for abstract review; of 110 papers retained for full-text review, 54 studies met criteria for inclusion for this paper. Primary outcomes were coded into five groups: prevalence and patterns of drug use; factors associated with drug use; attitudes and knowledge about, and motivation for, drug use; supply of drugs; consequences of drug use. The results show that there is no coherent body of research in this area. The prevalence of reported drug use has crept up and the range of substances reported has broadened over time, and attitudes to drugs on average have normalised. However, there are significant methodological limitations that limit the utility of these findings. There was little evidence of published work on prevention of, or intervention to reduce, drug-related harms.

Conclusion

The domains identified offer a framework for university administrators, researchers and policy makers to understand the potential response to drug use in university students in the UK and Ireland. Recommendations are made to fill the gaps in the research evidence base.
Cell-specific clock-controlled gene expression program regulates rhythmic fiber cell growth in cotton
Authors: Wang Dehe , Hu Xiao , Ye Hanzhe , Wang Yue , Yang Qian , Liang Xiaodong , Wang Zilin , Zhou Yifan , Wen Miaomiao , Yuan Xueyan , Zheng Xiaomin , Ye Wen , Guo Boyu , Yusuyin Mayila , Russinova Eugenia , Zhou Yu , Wang Kun
Published: March 2023

Background

The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood.

Results

Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless (fl) cotton (Gossypiumhirsutum). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by thetrans factors GhTCP14sto modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells.

Conclusions

We uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.
Clearance of bacteria from lymph nodes in sheep immunized with Brucella suis S2 vaccine is associated with M1 macrophage activation
Authors: Chen Si , Chen Yuanyuan , Jiao Zizhuo , Wang Chengqiang , Zhao Dantong , Liu Yongbin , Zhang Wenguang , Zhao Shihua , Yang Bin , Zhao Qinan , Fu Shaoyin , He Xiaolong , Chen Qiaoling , Man Churiga , Liu Guoying , Wei Xuefeng , Du Li , Wang Fengyang
Published: March 2023

Ovine brucellosis is a global zoonotic disease of sheep caused by Brucella melitensis, which inflicts a significant burden on human and animal health. Brucella suis strain S2 (B. suis S2) is a smooth live attenuated vaccine for the prevention of ovine brucellosis in China. However, no previous studies have assessed the immunogenicity of B. suis S2 vaccine after oral immunization in sheep. Here, we attempted to evaluate the ovine immune response over the course of B. suis S2 immunization and to identify in vivo predictors for vaccine development. Body temperature, serum Brucella antibodies, serum cytokines (IL-12p70 and interferon [IFN]-γ), and bacterial load in the mandibular lymph nodes (LN), superficial cervical LN, superficial inguinal LN, and spleen were investigated to determine the safety and efficacy of the vaccine. The abnormal body temperature of sheep occurred within 8 days post-infection (dpi). Brucella suis S2 persisted for a short time (< 21 dpi) in the mandibular LN. The highest level of IL-12p70 was observed at 9 dpi, whereas serum IFN-γ levels peaked at 12 dpi. Transcriptome analysis and quantitative reverse transcription PCR were performed to determine gene expression profiles in the mandibular LN of sheep. Antigen processing and presentation pathway was the dominant pathway related to the dataset. Our studies suggest that the immune response in ovine LN resembled type 1 immunity with the secretion of IL-12p70 and IFN-γ after B.suis S2 immunization and the vaccine may eliminate Brucella via stimulation of M1 macrophages through the course of Th cells.
Contraceptive dynamics among women with disabilities in low- and middle-income countries: a scoping review protocol
Authors: Beyene Getalem Aychew , Abebe Solomon Mekonnen , Fekadu Gedefaw Abeje , Muche Achenef Asmamaw , Geremew Bisrat Misganaw
Published: March 2023

Introduction

Contraceptive dynamics is the use of contraception, unmet need, discontinuation, and/or switching of contraception. Women with disabilities (WWDs) in low- and middle-income countries (LMICs) face a common problem: a low prevalence of contraceptive usage and a high unmet need. Even though certain studies have been conducted in high-income countries, research is scarce on the degree of contraceptive method mix, unmet needs, contraception discontinuation, and switching among WWDs in LMICs. As a result, the scoping review’s goal is to investigate, map available evidence, and identify knowledge gaps on contraceptive dynamics within LMICs WWDs.

Methods

The scoping review is guided by the six-stage Arksey and O’Malley methodology framework. Published articles will be retrieved from databases such as PubMed (MEDLINE), the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Global Health. Grey literature databases will be searched using electronic search engines such as Google Scholar, Google, OpenGrey, and Worldcat. In addition, a manual search of reference lists from recognized studies will be conducted, as well as a hand search of the literature. Any type of study design (e.g., randomized controlled trials, quasi-experimental studies, prospective and retrospective cohort studies, case-control or nested case-control studies, qualitative, cross-sectional studies) will be included in this scoping review. There will be no restrictions on publication year. Two independent reviewers will screen relevant publications, and data will be charted accordingly. The Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist and reporting guidelines will be used to report all parts of the protocol and scoping review.

Discussion

When compared to non-disabled women, WWDs had a lower prevalence of contraceptive usage and a higher unmet need in LMICs. Despite these facts, they are the most marginalized people on the planet. This is, therefore, critical to map available evidence and identify knowledge gaps on contraceptive dynamics. As a result, the findings of this scoping review will be significant in terms of the contraceptive dynamic among WWDs in LMICs.

Systematic review registration

Open Science Framework (OSF), with registration number; DOI/10.17605/OSF.IO/XCKPT.
Facial nerve in skullbase tumors: imaging and clinical relevance
Authors: Yao Longping , Wang Baoyan , Lu Fengfei , He Xiaozheng , Lu Guohui , Zhang Shizhong
Published: March 2023

Facial nerve, the 7th cranial nerve, is a mixed nerve composed of sensory and motor fibers, and its main branch is situated in the cerebellopontine angle. Facial nerve dysfunction is a debilitating phenomenon that can occur in skullbase tumors and Bell’s pals. Recovery of the facial nerve dysfunction after surgery for skullbase tumors can be disappointing, but is usually favorable in Bell’s palsy. Advances in magnetic resonance imaging (MRI) allow to visualize the facial nerve and its course in the cerebellopontine angle, also when a large tumor is present and compresses the nerve. Here, we describe the anatomical, neurochemical and clinical aspects of the facial nerve and highlight the recent progress in visualizing the facial nerve with MRI.