bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystatin C-derived estimated glomerular filtration rate in children with sickle cell anaemia
Authors: Babatunde Hakeem Edun , Bello Afeez Oyesola , Adeboye Muhammed A. Nurudeen , Folayan Olumuyiwa Shola , Ojewole Olugoke Ezekiel , Abubakar Usman
Published: November 2023

Background

Sickle cell disease is the most common inherited blood disorder in humans and constitutes a major public health burden. It is a multisystemic condition with long-term renal complications. Early detection of sickle cell nephropathy and initiation of appropriate interventions are associated with improved survival and quality of life. This study aimed to compare the cystatin C-derived estimated glomerular filtration rate (GFR) of the study groups and also, to correlate the clinical features of chronic kidney disease (CKD) with decreased GFR in children with sickle cell anaemia (SCA).

Methods

This hospital-based cross-sectional analytic study recruited 86 SCA subjects in steady-state and 86 age and sex-matched healthy HbAA controls aged 1–14 years who attended the Paediatric Haematology and Outpatient clinics of Federal Medical Centre Bida over six months. Data were collected using a semi-structured questionnaire, and participants’ length/height, weight, and blood pressure were measured using standard procedures. Blood samples were drawn for serum cystatin C assay via the sandwich enzyme-linked immunosorbent assay (ELISA) technique. Filler’s equation was used to calculate the glomerular filtration rate.

Results

There was a significant difference in the mean cystatin C-derived GFR between the two groups, i.e. 116 ± 30mL/min/1.73m2 vs. 106 ± 24mL/min/1.73m2 for the SCA and control groups, respectively (p = 0.017). The prevalence of supernormal GFR (i.e. GFR > 140mL/min/1.73m2) and decreased GFR (i.e. GFR < 90mL/min/1.73m2) was 19.8% and 22.1%, respectively, in children with SCA. There was no significant association between the age at diagnosis of SCA, blood transfusions, blood pressure, packed cell volume and presence of peripheral oedema with decreased GFR in the study subjects.

Conclusions

Supernormal GFR is common in children with SCA and there is no significant association between clinical features of CKD with decreased GFR. Regular evaluation of renal function is, however, recommended in children with SCA for early detection and treatment of renal complications in order to halt the progression to end-stage kidney disease (ESKD).
Development and validation of a prognostic nomogram model incorporating routine laboratory biomarkers for preoperative patients with endometrial cancer
Authors: Cong Rong , Li Mingyang , Xu Wan , Ma Xiaoxin , Wang Shuhe
Published: November 2023

Background

Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application.

Methods

A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker’s prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves.

Results

Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810–0.960) and 0.850 (95% CI, 0.761–0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866–0.940) and 0.825 (95% CI, 0.711–0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks.

Conclusions

Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.
A qualitative study exploring the perceptions of children, parents and school staff towards the development and implementation of school lunch provision within primary schools in the Netherlands
Authors: Rongen Frédérique C. , Coosje Dijkstra S. , Hupkens Tobie H. , Vingerhoeds Monique H. , Seidell Jacob C. , van Kleef Ellen
Published: November 2023

Background

There is no tradition of serving school lunches in primary schools in the Netherlands. Most children tend to bring their own packed lunch, however these are often nutritionally suboptimal. While school lunch provision can aid healthy eating behavior amongst children, its introduction would constitute a profound change for children, parents and school staff. Therefore, this qualitative study aims to explore children’s, parents and school staffs’ perceptions of both the current lunch situation and the implementation of school lunch provision within primary schools in the Netherlands.

Methods

In this qualitative study we conducted nine interviews with school principals, 98 interviews with children, and held six focus groups with teachers and six with parents at primary schools in two Dutch cities. The data was analysed via iterative coding.

Results

The results showed that most children and parents are satisfied with the current lunch situation, although existing school food policies are not always put in place. Most teachers felt that children had insufficient time to consume their lunch in the current situation. The children were generally positive about the idea of a school lunch, and stressed that it was important to have the ability to choose. While both parents and school staff saw school lunch provision as an opportunity to educate families about healthy food options, they also expressed concern about who would be responsible, as well as the financial and organizational implications of its introduction.

Conclusions

Perceptions of children, parents and school staff about a school provided lunch are mixed. A complex intervention such as a new school lunch program is difficult to envisage for all parties involved and more research is needed regarding the effects, organization, logistics and the costs of school lunch provision in the Netherlands.
The transcriptional factor Clr-5 is involved in cellulose degradation through regulation of amino acid metabolism in Neurospora crassa
Authors: Xue Fanglei , Zhao Zhen , Gu Shuying , Chen Meixin , Xu Jing , Luo Xuegang , Li Jingen , Tian Chaoguang
Published: November 2023

Background

Filamentous fungi are efficient degraders of plant biomass and the primary producers of commercial cellulolytic enzymes. While the transcriptional regulation mechanisms of cellulases have been continuously explored in lignocellulolytic fungi, the induction of cellulase production remains a complex multifactorial system, with several aspects still largely elusive.

Results

In this study, we identified a Zn2Cys6 transcription factor, designated as Clr-5, which regulates the expression of cellulase genes by influencing amino acid metabolism in Neurospora crassa during growth on cellulose. The deletion of clr-5 caused a significant decrease in secreted protein and cellulolytic enzyme activity of N. crassa, which was partially alleviated by supplementing with yeast extract. Transcriptomic profiling revealed downregulation of not only the genes encoding main cellulases but also those related to nitrogen metabolism after disruption of Clr-5 under Avicel condition. Clr-5 played a crucial role in the utilization of multiple amino acids, especially leucine and histidine. When using leucine or histidine as the sole nitrogen source, the Δclr-5 mutant showed significant growth defects on both glucose and Avicel media. Comparative transcriptomic analysis revealed that the transcript levels of most genes encoding carbohydrate-active enzymes and those involved in the catabolism and uptake of histidine, branched-chain amino acids, and aromatic amino acids, were remarkably reduced in strain Δclr-5, compared with the wild-type N. crassa when grown in Avicel medium with leucine or histidine as the sole nitrogen source. These findings underscore the important role of amino acid metabolism in the regulation of cellulase production in N. crassa. Furthermore, the function of Clr-5 in regulating cellulose degradation is conserved among ascomycete fungi.

Conclusions

These findings regarding the novel transcription factor Clr-5 enhance our comprehension of the regulatory connections between amino acid metabolism and cellulase production, offering fresh prospects for the development of fungal cell factories dedicated to cellulolytic enzyme production in bio-refineries.
Clinical application of a digital semi-rigid bridge space maintainer fabricated from polyetheretherketone for premature loss of primary molars
Authors: Wang Qi , Zhang Zhenzhen , Zhong Sheng , Liu Jiajia , Hu Ying , Zhou Ziling , Zhang Caidi , Bai Shizhu , Wu Li’an
Published: November 2023

Background

Premature loss of primary molars can be treated with a band loop space maintainer (SM). However, fabricating a conventional band loop SM requires multiple clinical and laboratory procedures, which can potentially affect the accuracy of the SM. Moreover, the conventional SM is unable to fully restore masticatory function and maintain the vertical dimension of the edentulous space. In this current study, a fully digital workflow to fabricate a semi-rigid bridge SM made from polyetheretherketone (PEEK) has been described and evaluated for its clinical effectiveness.

Methods

A total of 15 children (eight males and seven females) between the ages of 4–8 years, who experienced the premature loss of a single primary molar, were included in this study. Digital impressions were taken using the CEREC CAD/CAM chair system and imported into CAD software to design the semi-rigid bridge SM, which was fabricated using PEEK block as the maintainer material. The digital SM was tried-in and bonded to the abutment with resin cement. The edentulous space was measured immediately after bonding (T0) and 1 month (T1), 3 months (T2), and 6 months (T3) after treatment. The periodontal condition and mobility of the SM and abutment were also examined.

Results

The use of digital impressions resulted in a decreased occurrence of the pharyngeal reflex. The digital semi-rigid bridge SM, fabricated with PEEK, was both convenient and aesthetically pleasing, and successfully restored the anatomy and masticatory function of the missing primary molar. None of the 15 semi-rigid bridge SMs or abutments became loose or fell off during the study, and only one child presented with gingivitis. Furthermore, the difference in the edentulous space at T0, T1, T2, and T3 was not statistically significant (all P > 0.05).

Conclusions

The digital semi-rigid bridge SM fabricated with PEEK was clinically effective in maintaining the missing space and had advantages over the traditional band/crown loop SM.
Prevention of STAT3-related pathway in SK-N-SH cells by natural product astaxanthin
Authors: Sun Shao-Qian , Du Feng-Xiang , Zhang Li-Hua , Hao-Shi  , Gu Fu-Ying , Deng Yu-Lin , Ji Yi-Zhi
Published: November 2023

Purpose

Neuroblastoma (NB) is the most common solid malignancy in children. Despite current intensive treatment, the long-term event-free survival rate is less than 50% in these patients. Thus, patients with NB urgently need more valid treatment strategies. Previous research has shown that STAT3 may be an effective target in high-risk NB patients. However, there are no effective inhibitors in clinical evaluation with low toxicity and few side effects. Astaxanthin is a safe and natural anticancer product. In this study, we investigated whether astaxanthin could exert antitumor effects in the SK-N-SH neuroblastoma cancer cell line.

Method

MTT and colony formation assays were used to determine the effect of astaxanthin on the proliferation and colony formation of SK-N-SH cells. Flow cytometry assays were used to detect the apoptosis of SK-N-SH cells. The migration and invasion ability of SK-N-SH cells were detected by migration and invasion assays. Western blot and RT-PCR were used to detect the protein and mRNA levels. Animal experiments were carried out and cell apoptosis in tissues were assessed using a TUNEL assay.

Result

We confirmed that astaxanthin repressed proliferation, clone formation ability, migration and invasion and induced apoptosis in SK-N-SH cells through the STAT3 pathway. Furthermore, the highest inhibitory effect was observed when astaxanthin was combined with si-STAT3. The reason for this may be that the combination of astaxanthin and si-STAT3 can lower STAT3 expression further than astaxanthin or si-STAT3 alone.

Conclusion

Astaxanthin can exert anti-tumor effect on SK-N-SH cells. The inhibitory effect was the higher when astaxanthin was combined with si-STAT3.
Maternal satisfaction on quality of childhood vaccination services and its associated factors at public health centers in Addis Ababa, Ethiopia
Authors: Tesfaye Eyasu , Debie Ayal , Sisay Fasil , Tafere Tesfahun Zemene
Published: November 2023

Background

Vaccination is one of the most important public health interventions to reduce child mortality and morbidity. In Ethiopia, about 472,000 children die each year by vaccine-preventable diseases. A satisfied mother is assumed to use the services and complies with the service provider for better health care outcomes. However, there was no adequate evidence regarding maternal satisfaction with quality of childhood vaccination services. This study aimed to assess maternal satisfaction on quality of childhood vaccination services and its associated factors at public health centers in Addis Ababa, Ethiopia.

Methods

A facility-based cross-sectional study was conducted from 12 July to 12 August 2021 at public health centers in Addis Ababa, Ethiopia. A total of 366 mothers (caretakers) of under one-year-old children participated in the study. A systematic sampling technique with an interviewer-administered questionnaire and inventory checklist were used to collect the data. A binary logistic regression model was fitted. Adjusted Odds Ratio (AOR) with 95% confidence interval (CI) and p-value < 0.05 were used to identify the factors associated with the outcome.

Results

Nearly two-thirds (61.2%) of mothers (caretakers) were satisfied with the quality of childhood vaccination services. Service providers’ greeting [AOR = 1.60; 95%CI: 1.37–1.99] and information about the types of vaccines [AOR = 1.54; 95%CI: 1.32–1.89] were positively associated with maternal satisfaction. On the contrary, long waiting time of mothers (caretakers) to receive services [AOR = 0.29; 95%CI: 0.14–0.62] was negatively associated with services.

Conclusion

The overall maternal satisfaction towards the quality of childhood vaccination services in this study was found to be low. Minimizing waiting time at the health facility, enhancing greetings and providing adequate information regarding childhood vaccination for mothers (caretakers) improved their satisfaction with the services.
Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1
Authors: Birgersson Madeleine , Indukuri Rajitha , Lindquist Linnéa , Stepanauskaite Lina , Luo Qing , Deng Qiaolin , Archer Amena , Williams Cecilia
Published: November 2023

Background

Estrogen receptor beta (ERβ, Esr2) plays a pivotal role in folliculogenesis and ovulation, yet its exact mechanism of action is mainly uncharacterized.

Results

We here performed ERβ ChIP-sequencing of mouse ovaries followed by complementary RNA-sequencing of wild-type and ERβ knockout ovaries. By integrating the ERβ cistrome and transcriptome, we identified its direct target genes and enriched biological functions in the ovary. This demonstrated its strong impact on genes regulating organism development, cell migration, lipid metabolism, response to hypoxia, and response to estrogen. Cell-type deconvolution analysis of the bulk RNA-seq data revealed a decrease in luteal cells and an increased proportion of theca cells and a specific type of cumulus cells upon ERβ loss. Moreover, we identified a significant overlap with the gene regulatory network of liver receptor homolog 1 (LRH-1, Nr5a2) and showed that ERβ and LRH-1 extensively bound to the same chromatin locations in granulosa cells. Using ChIP-reChIP, we corroborated simultaneous ERβ and LRH-1 co-binding at the ERβ-repressed gene Greb1 but not at the ERβ-upregulated genes Cyp11a1 and Fkbp5. Transactivation assay experimentation further showed that ERβ and LRH-1 can inhibit their respective transcriptional activity at classical response elements.

Conclusions

By characterizing the genome-wide endogenous ERβ chromatin binding, gene regulations, and extensive crosstalk between ERβ and LRH-1, along with experimental corroborations, our data offer genome-wide mechanistic underpinnings of ovarian physiology and fertility.
Epidemiology and Genomic characteristics of arenavirus in rodents from the southeast coast of P.R. China
Authors: Xie Qinghua , Zhu Changqiang , Ai Lele , Nie Danyue , Wu Yifan , Wang Chongcai , He Ji , Tan Weilong , Zhang Lingling
Published: November 2023

Background

Wenzhou virus (WENV), a member of the Mammarenavirus genus in the Arenaviridae family, has been detected in wild rodents from eight provinces in China, including Zhejiang, Shandong, Hainan, Xinjiang, Hunan, Guangdong, Yunnan, and Jiangxi provinces, and some countries from Southeast Asia. The IgG-antibodies of WENV have been detected in both healthy populations and patients with unknown fever and respiratory symptoms. However, the potential harmfulness of WENV to humans has been underestimated due to mild symptoms after infection, similar to respiratory diseases. Thus, it is imperative to enhance the surveillance of WENV in wild rodents, particularly Rattus norvegicus, and continuously monitor its prevalence.

Results

From 2017 to 2021, a total of 390 wild rodents were collected from six provinces in the eastern and southern coastal areas, containing nine species of rats. Samples of each tissue were collected, and PCR amplified for identification. Four R. norvegicus samples were detected to be WENV-positive. No genomic sequence of WENV was detected in Rattus flavipectus, Rattus losea, Suncus murinus, Apodemus agrarius, Mus musculus, Microtus fortis, Micromys minutus, and Niviventer niviventer from Jiangsu, Zhejiang, Fujian, Hainan, Guangdong and Guangxi provinces. Three genomic sequences were identified to be WENV by phylogenetic analysis. The full-length sequences of HAIKOU-40 were amplified in R. norvegicus from Hainan, which showed a close relationship to Wufeng/ WFS, sharing 84.5–89.4% homology at the nucleotide level and 91.6–98.9% homology at the amino acid level. Phylogenetic analysis revealed that HAIKOU-40 formed an Asia-specific cluster with all WENVs and Loie River mammarenavirus (LORV), provisionally named Asian ancestry. This cluster has diverged earlier from the remaining mammarenavirus. The sequences obtained in Xiamen, Fujian province showed more than 90% nucleotide identities with WENV, which may be a strain of WENV. Additionally, the sequence of Wuxi-87 which was a positive sequence detected in Wuxi, Jiangsu province exhibited 83% nucleotide identity with Lassa virus (LASV). Further efforts will be made to isolate and identify this virus strain, verify the relationship between Wuxi-87 and LASV, and confirm whether R. norvegicus is a new host of LASV.

Conclusions

In this study, we conducted a systematic examination of the prevalence of WENV among rodents on the southeast coast of China. Additionally, we characterized the genome of a newly discovered WENV strain, that confirmed the role of R. norvegicus in the transmission of WENV. This highlights the importance of investigating the prevalence of WENV in both wild rodents and humans.
Distribution of water turnover by sex and age as estimated by prediction equation in Japanese adolescents and adults: the 2016 National Health and Nutrition Survey, Japan
Authors: Watanabe Daiki , Inoue Yumiko , Miyachi Motohiko
Published: November 2023

Background

Although water is essential to the maintenance of health and life, standard values for human water requirements are yet to be determined. This study aimed to evaluate the distribution of water turnover (WT) according to sex and age, estimated using a prediction equation, in Japanese adolescents and adults.

Methods

This cross-sectional study used data from the 2016 National Health and Nutrition Survey, Japan. Data were obtained from electronically available aggregated reports in the survey’s official website. Participants aged between 15 and 80 years (10,546 men, 12,355 women) were selected using stratified random sampling. WT was calculated considering lifestyle and environmental factors, and using an equation (coefficient of determination = 0.471) previously developed by the international doubly labelled water (DLW) database group. As data on physical activity levels (PAL) were not collected in the survey, we used two evaluation methods: (1) energy intake assessed by dietary records and (2) total energy expenditure measured by the DLW method reported in previous Japanese studies, divided by basal metabolic rate predicted using the equation. We evaluated the relationship between WT and age using a restricted cubic spline model.

Results

The average WT for the 15–19, 20–29, 30–39, 40–49, 50–59, 60–69, and ≥ 70 years was 3291, 3151, 3213, 3243, 3205, 3104, and 2790 ml/day, respectively in men, and 2641, 2594, 2741, 2739, 2753, 2707, and 2482 ml/day, respectively in women. In the spline model, WT showed an inverse association with age in men older than 50 years, whereas women showed a reverse U-shaped relationship between WT and age (p for non-linearity < 0.001), although results differed with body weight adjustment. Similar results were found for both PAL evaluation methods, and the range of WT per body weight was 45–56 ml/day for both sexes.

Conclusions

We determined the standard values of WT in Japanese population using a prediction equation and national large-scale survey data. These findings may be useful for setting water requirements for dietary guidelines in future.
Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study
Authors: Guo Junchen , Liu XiaoXuan , Wang Zeng , Lu Rongzhe , Liu Yige , Zhang Yiying , Tian Wei , Fang Shaohong , Wang Shanjie , Yu Bo
Published: November 2023

Background

The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD.

Methods

The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk.

Results

Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31–2.20) for all-cause mortality, and 2.00 (1.39–2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001).

Conclusion

MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.
Natural killer cells in the central nervous system
Authors: Ning Zhiyuan , Liu Ying , Guo Daji , Lin Wei-Jye , Tang Yamei
Published: November 2023

Natural killer (NK) cells are essential components of the innate lymphoid cell family that work as both cytotoxic effectors and immune regulators. Accumulating evidence points to interactions between NK cells and the central nervous system (CNS). Here, we review the basic knowledge of NK cell biology and recent advances in their roles in the healthy CNS and pathological conditions, with a focus on normal aging, CNS autoimmune diseases, neurodegenerative diseases, cerebrovascular diseases, and CNS infections. We highlight the crosstalk between NK cells and diverse cell types in the CNS and the potential value of NK cells as novel therapeutic targets for CNS diseases.
HIV viral suppression at different thresholds and duration of treatment in the dolutegravir treatment era in Sierra Leone: a nationwide survey
Authors: Song Jin-Wen , Yang Guang , Kamara Matilda N. , Sun Wei , Guan Qun , Barrie Umu , Jiba Darlinda F. , Jalloh Abdulai Tejan , Liu Ming , Tamba Francis K. , Yendewa George A. , Wang Ligui , Zhao Rongtao , Lakoh Sulaiman
Published: November 2023

Introduction

Viral load assessment for people living with HIV is key for monitoring treatment and achieving the 95-95-95. In this study, we aimed to assess the degree of viral suppression at different thresholds and treatment duration after the introduction of dolutegravir-based therapy in ten public hospitals in Sierra Leone.

Methods

We used a cross-sectional study design to recruits patients aged 18 years or older between August 2022 and January 2023. Statistical analyses were performed using R-software. Logistic regression was used to assess factors independently associated with viral suppression. The level of significance was set at P < 0.05.

Results

Of the 2,253 patients recruited, 1,720 (76%) were women and 1,705 (76%) were receiving a fixed dose combination of tenofovir, lamivudine and dolutegravir. The median age and duration of anti-retroviral therapy (ART) was 36.0 (IQR, 28.0–45.0) years and 40.9 (IQR, 14.4–79.6) months, respectively. Using a threshold of HIV RNA < 1000 copies/mL, 1,715 (88.4%) patients on ART for more than 6 months were virally suppressed. Viral suppression rates were higher with dolutegravir-based (1,277, 89.5%) than efavirenz-based (418, 86.2%) ART. HIV RNA was < 200 copies/mL in 1,643 (84.6%) patients or < 50 copies/mL in 1,487 (76.6%) patients or between 50 and 999 copies/mL in 228 (11.7%) patients. Viral suppression rates at different ART durations (months) were as follows: 84.2% (≤ 3), 88.8% (4–6), 90.9% (6–12), and 88.1% (> 12). Viral suppression rates were higher for patients aged 40 or older (40–50 years: aOR 2.05, 95%CI 1.41–3.04, P < 0.01; 50–60 years: aOR 2.51, 95%CI 1.53–4.35, P < 0.01; >60 years: aOR 2.69, 95%CI 1.28–6.63, P = 0.02). Men had 49% lower odds of viral suppression than women (aOR 0.50, 95% CI 0.38–0.67, P < 0.01).

Conclusion

We report a viral suppression rate of 88.4% among patients on treatment for at least 6 months, with higher rate of suppression with dolutegravir than efavirenz. Factors associated with virological suppression were age and gender, emphasizing the need for innovative differentiated ART delivery models to optimize viral suppression and achieve the 95% target.
Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data
Authors: Chen Chen , Zheng Linli , Zeng Gang , Chen Yanbo , Liu Wenzhou , Song Weidong
Published: November 2023

Purpose

Tenosynovial giant cell tumour (TGCT) is a benign hyperplastic and inflammatory disease of the joint synovium or tendon sheaths, which may be misdiagnosed due to its atypical symptoms and imaging features. We aimed to identify biomarkers with high sensitivity and specificity to aid in diagnosing TGCT.

Methods

Two scRNA-seq datasets (GSE210750 and GSE152805) and two microarray datasets (GSE3698 and GSE175626) were downloaded from the Gene Expression Omnibus (GEO) database. By integrating the scRNA-seq datasets, we discovered that the osteoclasts are abundant in TGCT in contrast to the control. The single-sample gene set enrichment analysis (ssGSEA) further validated this discovery. Differentially expressed genes (DEGs) of the GSE3698 dataset were screened and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Osteoclast-specific up-regulated genes (OCSURGs) were identified by intersecting the osteoclast marker genes in the scRNA-seq and the up-regulated DEGs in the microarray and by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The expression levels of OCSURGs were validated by an external dataset GSE175626. Then, single gene GSEA, protein–protein interaction (PPI) network, and gene-drug network of OCSURGs were performed.

Result

22 seurat clusters were acquired and annotated into 10 cell types based on the scRNA-seq data. TGCT had a larger population of osteoclasts compared to the control. A total of 159 osteoclast marker genes and 104 DEGs (including 61 up-regulated genes and 43 down-regulated genes) were screened from the scRNA-seq analysis and the microarray analysis. Three OCSURGs (MMP9, SPP1, and TYROBP) were finally identified. The AUC of the ROC curve in the training and testing datasets suggested a favourable diagnostic capability. The PPI network results illustrated the protein–protein interaction of each OCSURG. Drugs that potentially target the OCSURGs were predicted by the DGIdb database.

Conclusion

MMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.
Performance of DNA methylation analysis in the detection of high-grade cervical intraepithelial neoplasia or worse (CIN3+): a cross-sectional study
Authors: Liu Yuxiang , Chen Yan , Xiong Jing , Zhu Peng , An Yuhang , Li Shu , Chen Puxiang , Li Qing
Published: November 2023

It is commonly accepted that host genes show high methylation in cervical intraepithelial neoplasia 3 (CIN3) or worse (CIN3+). However, study quality varies, as does the clinical performance of markers in different populations. We aimed to validate candidate gene DNA methylation with standardized testing methods in the same batch of samples. We first compared the performance of 16 DNA methylation markers for detecting CIN3+ in the 82-sample training set, including 24 subjects with ≤ CIN1, 10 subjects with CIN2, 23 subjects with CIN3, and 25 subjects with cervical cancer (CC). Then five methylation markers were selected and subsequently validated among an independent set of 74 subjects, including 47 subjects with ≤ CIN1, 13 subjects with CIN2, 6 subjects with CIN3, and 8 subjects with CC. The results in the validation set revealed that methylation analysis of the SOX1 (SOX1m) showed a superior level of clinical performance (AUC = 0.879; sensitivity = 85.7%; specificity = 90.0%). SOX1m had better accuracy than cytology, with a reduced referral rate (23.0% vs. 31.4%) and a lower number of overtreatment (5 vs. 13) cases among high-risk human papillomavirus (hrHPV)-positive women. Importantly, among hrHPV-positive and SOX1m-negative women, only 1 CIN3 patient was at risk for follow-up after 1 year, whereas 1 CIN3 patient and 1 CC patient were at risk among hrHPV-positive and cytology-negative women. In this investigation, we screened 16 reported methylation markers to provide a basis for future studies related to potential precancerous lesion/cancer methylation markers in the Chinese population. The study also revealed that SOX1m has optimal CIN3+ detection performance, suggesting that it may be a promising biomarker for detecting CIN3+ in the Chinese population.
Comparison of diagnostic methods for assessment of Ostertagia ostertagi exposure in Norwegian dairy herds
Authors: Opsal Tonje , Toftaker Ingrid , Robertson Lucy , Woolsey Ian , Hektoen Lisbeth
Published: November 2023

Background

The gastrointestinal nematode (GIN) Ostertagia ostertagi can cause severe disease in first season grazers (FSG) and impaired performance due to subclinical infections in adult cows. Diagnostic methods to assess exposure include faecal egg count and detection of specific antibodies using antibody-ELISAs resulting in an optical density ratio (ODR). Using the ELISA test on bulk tank milk (BTM) allows for a herd level diagnosis. Appropriate use of diagnostic methods for evaluation of O. ostertagi exposure is required to optimize herd parasite surveillance and aid in a sustainable control regime. The aim of this study was to describe the relationship between different diagnostic tests used to assess GIN exposure in Norwegian production systems. A cross-sectional field study was carried out in twenty herds in Norway in the fall of 2020. Serum and faecal samples were taken from 380 individuals, of which 181 were FSG and 199 were cows. In addition, milk was collected from every cow and one BTM sample was taken from each herd. Faecal egg counts were performed. The distribution of ODR values in individual samples within and between herds and the associations between BTM ODR and individual ODR values were described. The data were analysed using visual assessment of scatter plots, Pearson correlation coefficients and linear regression.

Results

A high variability of the within-herd individual ODR values in serum and milk in every herd was detected. The ODR in BTM explained a low degree of the variation in the individual serum and milk samples. When plotting the ODR results in milk or serum according to four BTM categories, the distribution of ODR values were notably different in the highest and lowest BTM categories. The correlation between individual milk and serum samples was moderate (r = 0.68), while the highest correlation (r = 0.81) was between the BTM ODR and the group average individual milk samples.

Conclusions

A poor predictive ability for BTM ODR to assess individual ODR values in both FSG and cows was demonstrated. However, the study indicates that the evaluation by ELISA test on BTM to assess exposure to GIN could be useful in herds with a very high or low BTM ODR.
A peer-volunteer led active ageing programme to prevent decline in physical function in older people at risk of mobility disability (Active, Connected, Engaged [ACE]): study protocol for a randomised controlled trial
Authors: Stathi Afroditi , Withall Janet , Crone Diane , Hawley-Hague Helen , Playle Rebecca , Frew Emma , Fenton Sally , Hillsdon Melvyn , Pugh Christopher , Todd Chris , Jolly Kate , Cavill Nick , Western Max , Roche Sarah , Kirby Nigel , Boulton Elisabeth , Thompson Janice , Chatwin Katie , Davies Amy , Szekeres Zsofia , Greaves Colin
Published: November 2023

Background

The Active Connected Engaged [ACE] study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial [RCT] with an internal pilot phase. The ACE study incorporates a multi-level mixed methods process evaluation including a systems mapping approach and an economic evaluation. ACE aims to test the effectiveness and cost-effectiveness of a peer-volunteer led active ageing intervention designed to support older adults at risk of mobility disability to become more physically and socially active within their communities and to reduce or reverse, the progression of functional limitations associated with ageing.

Methods/design

Community-dwelling, older adults aged 65 years and older (n = 515), at risk of mobility disability due to reduced lower limb physical functioning (Short Physical Performance Battery (SPPB) score of 4–9 inclusive) will be recruited. Participants will be randomised to receive either a minimal control intervention or ACE, a 6-month programme underpinned by behaviour change theory, whereby peer volunteers are paired with participants and offer them individually tailored support to engage them in local physical and social activities to improve lower limb mobility and increase their physical activity. Outcome data will be collected at baseline, 6, 12 and 18 months. The primary outcome analysis (difference in SPPB score at 18 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals.

Discussion

ACE is the largest, pragmatic, community-based randomised controlled trial in the UK to target this high-risk segment of the older population by mobilising community resources (peer volunteers). A programme that can successfully engage this population in sufficient activity to improve strength, coordination, balance and social connections would have a major impact on sustaining health and independence.

ACE is also the first study of its kind to conduct a full economic and comprehensive process evaluation of this type of community-based intervention. If effective and cost-effective, the ACE intervention has strong potential to be implemented widely in the UK and elsewhere.

Trial registration

ISRCTN, ISRCTN17660493. Registered on 30 September 2021.

Trial Sponsor: University of Birmingham, Contact: Dr Birgit Whitman, Head of Research Governance and Integrity; Email: researchgovernance@contacts.bham.ac.uk.

Protocol Version 5 22/07/22.
Tolerance of engineered Rhodosporidium toruloides to sorghum hydrolysates during batch and fed-batch lipid production
Authors: Woodruff William , Deshavath Narendra Naik , Susanto Vionna , Rao Christopher V. , Singh Vijay
Published: November 2023

Background

Oleaginous yeasts are a promising candidate for the sustainable conversion of lignocellulosic feedstocks into fuels and chemicals, but their growth on these substrates can be inhibited as a result of upstream pretreatment and enzymatic hydrolysis conditions. Previous studies indicate a high citrate buffer concentration during hydrolysis inhibits downstream cell growth and ethanol fermentation in Saccharomyces cerevisiae. In this study, an engineered Rhodosporidium toruloides strain with enhanced lipid accumulation was grown on sorghum hydrolysate with high and low citrate buffer concentrations.

Results

Both hydrolysis conditions resulted in similar sugar recovery rates and concentrations. No significant differences in cell growth, sugar utilization rates, or lipid production rates were observed between the two citrate buffer conditions during batch fermentation of R. toruloides. Under fed-batch growth on low-citrate hydrolysate a lipid titer of 16.7 g/L was obtained.

Conclusions

Citrate buffer was not found to inhibit growth or lipid production in this engineered R. toruloides strain, nor did reducing the citrate buffer concentration negatively affect sugar yields in the hydrolysate. As this process is scaled-up, $131 per ton of hydrothermally pretreated biomass can be saved by use of the lower citrate buffer concentration during enzymatic hydrolysis.

Graphical Abstract
Differential associations of horizontally and vertically transmitted symbionts on Ixodes ricinus behaviour and physiology
Authors: Bakker Julian W. , Begemann Hannah L. M. , Fonville Manoj , Esser Helen J. , de Boer Willem F. , Sprong Hein , Koenraadt Constantianus J. M.
Published: November 2023

Background

Ixodes ricinus ticks are infected with a large diversity of vertically and horizontally transmitted symbionts. While horizontally transmitted symbionts rely on a vertebrate host for their transmission, vertically transmitted symbionts rely more on the survival of their invertebrate host for transmission. We therefore hypothesized horizontally transmitted symbionts to be associated with increased tick activity to increase host contact rate and vertically transmitted symbionts to be associated with higher tick weight and lipid fraction to promote tick survival.

Methods

We used a behavioural assay to record the questing activity of I. ricinus ticks. In addition, we measured weight and lipid fraction and determined the presence of ten symbiont species in these ticks using qPCR, of which six were vertically transmitted and four horizontally transmitted.

Results

Vertically transmitted symbionts (e.g. Midichloria mitochondrii) were associated with an increase in tick weight, whereas horizontally transmitted symbionts (e.g. Borrelia burgdorferi sensu lato) were often associated with lower weight and lipid fraction of ticks. Moreover, horizontally transmitted symbionts (e.g. B. burgdorferi s.l.) were associated with increased tick activity, which may benefit pathogen transmission and increases tick-borne disease hazard.

Conclusions

Our study shows that horizontally and vertically transmitted symbionts differentially influence the behaviour and physiology of I. ricinus and warrants future research to study the underlying mechanisms and effects on transmission dynamics of tick-borne pathogens.

Graphical abstract
Impact of thermodynamical rotational flow of cerebrospinal fluid in the presence of elasticity
Authors: Balasundaram Hemalatha
Published: November 2023

Objective

To explore the experimental justification of cerebrospinal fluid (CSF) amplitude and elastic fluctuations of ventricles, we extend our previous computational study to models with rotational flow and suitable boundary conditions. In the present study, we include an elastic effect due to the interaction with the thermal solutal model which accounts for CSF motion which flows rotationally due to hydrocephalus flows within the spinal canal.

Methods

Using an analytical pertubation method, we have attempted a new model to justify CSF flow movement using the influences of wall temperature difference.

Results

This paper presents results from a computational study of the biomechanics of hydrocephalus, with special emphasis on a reassessment of the parenchymal elastic module. CSF amplitude in hydrocephalus patients is 2.7 times greater than that of normal subjects.

Conclusions

This finding suggests a non-linear mechanical system to present the hydrocephalic condition using a numerical model. The results can be useful to relieve the complexities in the mechanism of hydrocephalus and can shed light to support clinically for a convincing simulation.
Determinants of adoption of female headed household in microfinance program: a case study on Oromia Credit and Saving Share Company (OCSSCO) in Guto Gida district, Ethiopia
Authors: Hinkosa Bonsa
Published: November 2023

Since its introduction in the 1970, the word microfinance is being used very often in the development vocabulary today. It is taken as a strategy to overcome the constraints of conventional bank in reaching the poor and seen as one of the most efficient instruments for livelihood improvement. However, empirically the effectiveness of these programs on the livelihood of household is still inconclusive and debatable. Additionally, the relationships between socio-economic, demographic factors and participation in microfinance program are not seen in the study area and this motivated the researcher to undertake the study. The objectives of this study were identifying the factors that affect female headed household participation in microfinance program. Multi-stage sampling technique was used to draw representative sample and used cross-sectional survey. Cross-sectional survey data were collected from randomly selected 169 female headed household using interview/survey schedules. Descriptive and econometric methods were used to analyze the data. The results of descriptive statistics indicate that the majority of client household use microcredit to purchase agricultural input. Logit results indicate that program participation was significantly affected by seven explanatory variables. Among the variable’s family size of the household, livestock ownership and land size affected household participation in the program positively, whereas age of household head, distance of household home from microfinance office, wealth status of the household and household perception of risk have negative effect. Finally, the study recommends that microfinance institutions should broaden their outreach and expand its access in to large.
Development of an amperometric sensor for epinephrine determination using an Azure A/silver nanocluster modified electrode
Authors: Priya C. , Anuja S. , Babu R. Suresh , Narayanan S. Sriman
Published: November 2023

A novel electrochemical sensor was developed for the detection of Epinephrine (EP) utilizing Azure A (AzA), a phenothiazine dye, and citrate-capped silver nanoparticles. The interaction between Azure A and silver nanoparticles facilitated the formation of AzA/silver nanoclusters through a self-assembled approach. The morphological analysis of AzA/silver nanoclusters was conducted using field-emission scanning electron microscopy (FESEM). The nanoclusters were then immobilized on a graphite electrode via a simple drop-casting method, resulting in a modified electrode. The electrochemical properties of the modified electrode were investigated using cyclic voltammetry and linear sweep voltammetry techniques. The modified electrode exhibited enhanced electrocatalytic oxidation of EP at a lower oxidation potential of 0.27 V. The electrochemical analysis demonstrated that the modified electrode functioned as an amperometric sensor, enabling the detection of EP within a concentration range of 4.6 × 10–7 to 3.6 × 10–3 M, with a correlation coefficient of 0.9950 and a detection limit of 2.2 × 10–7 M (S/N = 3). The modified electrode exhibited excellent selectivity, sensitivity, and a remarkably low detection limit, making it highly suitable for EP determination. Its ease of preparation further adds to the practicality and potential applications of this electrode.
Child maltreatment among victims of violent death: an analysis of national violent death reporting system data, 2014–2018
Authors: Barrett Nicole M. , Michaels Nichole L. , Kistamgari Sandhya , Smith Gary A. , Brink Farah W.
Published: November 2023

Background

Limited information is known about the impact of childhood maltreatment on lifetime risk of violent death. This study aimed to compare manner of death, demographics, age at time of death, and the presence of a mental health or substance use disorder among decedents of violent deaths with a history of child maltreatment to those without.

Methods

This cross-sectional study compared characteristics of pediatric and adult violent deaths with and without a history of child maltreatment that were captured in the National Violent Death Reporting System from 2014 through 2018.

Results

Decedents who were male, multiracial, and had adulthood substance or mental health disorders were more likely to have a history of maltreatment. All-age decedents with a history of maltreatment were more likely to die by homicide. Adult decedents with a history of maltreatment were more likely to die by suicide. Maltreated decedents died significantly younger than non-maltreated decedents.

Conclusions

Among victims of violent deaths, an identified history of child maltreatment was associated with increased risk of homicide across the lifespan, adult suicide, and earlier death. A history of child maltreatment was also associated with mental health and substance use disorders, which may reflect one of the pathways through which the child maltreatment-to-death association functions.