bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress
Authors: Panelli Danielle M. , Leonard Stephanie A. , Wong Ronald J. , Becker Martin , Mayo Jonathan A. , Wu Erica , Girsen Anna I. , Gotlib Ian H. , Aghaeepour Nima , Druzin Maurice L. , Shaw Gary M. , Stevenson David K. , Bianco Katherine 
Published: May 2022

Abstract
Background
Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.

Methods
In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.

Results
A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change − 0.03 ± 0.26, p = 0.39); 2 and 3 (− 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (− 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).

Conclusions
In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.
Evaluating the predictive value of fetal Doppler indices and neonatal outcome in late-onset preeclampsia with severe features: a cross-sectional study in a resource-limited setting
Authors: Moawad Eman Mohamed Ibraheim , Tammam Amr Samir Fouad , Mosaad Maha Mohamed , Sayed Hadeer Mashaal El , Atef Adel 
Published: May 2022

Abstract
Background
Preeclampsia constitutes a major health problem with substantial maternal and perinatal morbidity and mortality. The aim of this study was to detect the diagnostic efficacy of fetal Doppler in predicting adverse outcomes in severe late onset preeclampsia (LOP).

Methods
A prospective study was conducted among childbearing women who presented with severe LOP and matched controls. Umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) and cerebroplacental ratio (CPR) were measured.

Results
All UA indices were significantly higher in the case group compared to the controls (p < 0.001). UA PI and RI were significantly correlated with all neonatal adverse outcomes except cord pH status (p < 0.05). Abnormal CPR was the most sensitive index that positively correlated with intrauterine growth retardation (IUGR), low 5- minute Apgar score and neonatal intensive care unit admission (79, 72.8 and 73.3%, respectively). In the same context, Abnormal UA PI and RI represented the most specific tool for predicting IUGR, low 1- and 5- minutes Apgar score with positive predictive values were 52, 87 and 57%, respectively.

Conclusion
In severe LOP, UA Doppler remains the preferential indicator for adverse birth outcomes with CPR is the best index that could be solely used for predicting such outcome.
Preterm delivery rate in China: a systematic review and meta-analysis
Authors: Song Qinfeng , Chen Junxi , Zhou Yubo , Li Zhiwen , Li Hongtian , Liu Jianmeng 
Published: May 2022

Abstract
Background
Preterm delivery rate is a crucial public health indicator, yet reliable statistic is currently not available in China. In this systematic review and meta-analysis, we aimed to review studies on preterm delivery rate in China, explore sources of heterogeneity, and estimate the preterm delivery rate in China.

Methods
Published studies on preterm delivery rate in China since 2010 were electronically searched from PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database, and complemented by manual search. Study selection, data extraction, and quality and bias assessment (using the Joanna Briggs Institute Critical Appraisal Checklist) were conducted by two reviewers independently. Random-effects meta-analysis was performed to estimate the pooled preterm delivery rate, and prespecified stratified analysis was conducted to explore sources of heterogeneity.

Results
The database search returned 4494 articles and manual search identified 10 additional studies. In total, 162 studies were eligible, of which 124 were hospital-based and 38 population-based. The pooled preterm delivery rate of hospital-based studies (7.2%; 95% CI: 6.9% to 7.6%) was significantly higher than that of population-based studies (4.9%; 95% CI: 4.5% to 5.4%) (P for subgroup difference < 0.001). Among population-based studies, the rate tended to differ by geography (P for subgroup difference = 0.07): 5.3% for Eastern, 4.6% for Central, and 3.8% for Western.

Conclusions
According to population-based studies, the preterm delivery rate in China is around 5%. This rate is substantially lower than estimates from hospital-based studies or estimates from a combination of both hospital-based and population-based studies as having been done in previous studies.
A protocol to clinically evaluate liquid biopsies as a tool to speed up diagnosis of children and young adults with aggressive infection-related lymphoma in East Africa “(AI-REAL)”
Authors: Legason Ismail D. , Ogwang Martin D. , Chamba Clara , Mkwizu Elifuraha , El Mouden Claire , Mwinula Hadija , Chirande Lulu , Schuh Anna , Chiwanga Faraja 
Published: May 2022

Abstract
Background
The capacity for invasive tissue biopsies followed by histopathology diagnosis in sub-Saharan Africa is severely limited. Consequently, many cancer patients are diagnosed late and outcomes are poor. Here, we propose to evaluate circulating tumour (ct) DNA analysis (“liquid biopsy”), a less invasive and faster approach to diagnose endemic EBV-driven lymphomas (EBVL) in East Africa.

Methods
We will evaluate the clinical utility of an already validated ctDNA test prospectively in a head-to-head comparison against histopathology. The primary endpoint is the time from presentation to the specialist centre to a final diagnosis of EBV- Lymphoma. Secondary endpoints include the sensitivity and specificity of liquid biopsy and health economic benefits over histopathology. One hundred forty-six patients will be recruited over 18 months. Patients will be eligible if they are 3–30 years of age and have provided written consent or assent as per IRB guidelines. Tissue and venous blood samples will be processed as per established protocols. Clinical data will be captured securely and in real-time into a REDCap database. The time from presentation to diagnosis will be documented. The sensitivity and specificity of the methods can be estimated within 5% error margin with 95% confidence level using 73 cases and 73 controls. Health-economic assessment will include micro-costing of ctDNA test and histopathology. All results will be reviewed in a multidisciplinary tumour board.

Discussion
The study evaluates the clinical utility of ctDNA in improving the speed of diagnostic pathways for EBVL in sub-Saharan Africa. Our results would provide proof-of-principle that ctDNA can be used as a diagnostic tool in areas without access to regular pathology, that transfer of the tool is feasible, and that it leads to an earlier and faster diagnosis. The potential clinical and economic impact of this proposal is thus significant. If successful, this study will provide appropriate, and cost-effective diagnostic tools that will promote earlier diagnosis of EBVL and potentially other cancers in countries with restricted healthcare resources.

Trial registration
Pan African Clinical Trials Registry: PACTR202204822312651, registered on 14th-April-2022.
High MICAL-L2 expression and its role in the prognosis of colon adenocarcinoma
Authors: Yang Yixing , Ye Fengwen , Xia Tianxiang , Wang Qianwen , Zhang Yujie , Du Jun 
Published: May 2022

Abstract
Background
MICAL-like protein 2 (MICAL-L2), a member of the molecules interacting with CasL (MICAL) family of proteins, is strongly associated with the malignancy of multiple types of cancer. However, the role of MICAL-L2 in colon adenocarcinoma (COAD) has not been well characterized.

Methods
In this study, we analyzed the role of MICAL-L2 in COAD using datasets available from public databases. The mRNA and protein expression of MICAL-L2 was investigated using TCGA, UALCAN, and independent immunohistochemical assays. Overall survival (OS) and disease-specific survival (DSS) of COAD patients were assessed based on the MICAL-L2 expression level using the Kaplan–Meier method. Univariate and multivariate analysis was employed to determine whether MICAL-L2 could serve as an independent prognostic indicator of OS. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were further utilized to explore the possible cellular mechanism underlying the role of MICAL-L2 in COAD. In addition, the correlation between MICAL-L2 expression and immune cell infiltration levels was investigated via single-sample gene set enrichment analysis (ssGSEA).

Results
Data from TCGA, HPA, and UALCAN datasets indicated that MICAL-L2 expression was significantly higher in COAD tissue than in adjacent normal tissues, and this was confirmed by immunohistochemical assays. Kaplan–Meier survival analysis revealed that patients with MICAL-L2 had shorter OS and DSS. Furthermore, multivariate Cox analysis indicated that MICAL-L2 was an independent risk factor for OS in COAD patients. ROC analysis confirmed the diagnostic value of MICAL-L2, and a prognostic nomogram involving age, M stage, and MICAL-L2 expression was constructed for OS. Functional enrichment analyses revealed that transport-related activity was closely associated with the role of MICAL-L2 in COAD. Regarding immune infiltration levels, MICAL-L2 was found to be positively associated with CD56bright NK cells.

Conclusions
Our results suggested that MICAL-L2 is a promising biomarker for determining prognosis and correlated with immune infiltration levels in COAD.
Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
Authors: Wang Guiran , Yan Guiling , Sang Kanru , Yang Huijie , Sun Ni , Bai Yuanyuan , Xu Feng , Zheng Xiaoqun , Chen Zhanguo 
Published: May 2022

Abstract
Background
Acute promyelocytic leukaemia (APL) is a unique subtype of acute myeloid leukaemia (AML) characterized by haematopoietic failure caused by the accumulation of abnormal promyelocytic cells in bone marrow (BM). However, indispensable BM biopsy frequently afflicts patients in leukaemia surveillance, which increases the burden on patients and reduces compliance. This study aimed to explore whether the novel circulating long noncoding RNA LOC100506453 (lnc-LOC) could be a target in diagnosis, assess the treatment response and supervise the minimal residual disease (MRD) of APL, thereby blazing a trail in noninvasive lncRNA biomarkers of APL.

Methods
Our study comprised 100 patients (40 with APL and 60 with non-APL AML) and 60 healthy donors. BM and peripheral blood (PB) sample collection was accomplished from APL patients at diagnosis and postinduction. Quantitative real-time PCR (qRT–PCR) was conducted to evaluate lnc-LOC expression. A receiver operating characteristic (ROC) analysis was implemented to analyse the value of lnc-LOC in the diagnosis of APL and treatment monitoring. For statistical analysis, the Mann–Whitney U test, a t test, and Spearman’s rank correlation test were utilized.

Results
Our results showed that BM lnc-LOC expression was significantly different between APL and healthy donors and non-APL AML. lnc-LOC was drastically downregulated in APL patients’ BM after undergoing induction therapy. Lnc-LOC was upregulated in APL cell lines and downregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation, preliminarily verifying that lnc-LOC has the potential to be considered a treatment monitoring biomarker. PB lnc-LOC was positively correlated with BM lnc-LOC in APL patients, non-APL AML patients and healthy donors and decreased sharply after complete remission (CR). However, upregulated lnc-LOC was manifested in relapsed-refractory patients. A positive correlation was revealed between PB lnc-LOC and PML-RARα transcript levels in BM samples. Furthermore, we observed a positive correlation between PB lnc-LOC and BM lnc-LOC expression in APL patients, suggesting that lnc-LOC can be utilized as a noninvasive biomarker for MRD surveillance.

Conclusions
Our study demonstrated that PB lnc-LOC might serve as a novel noninvasive biomarker in the treatment surveillance of APL, and it innovated the investigation and application of newly found lncRNAs in APL noninvasive biomarkers used in diagnosis and detection.
The clinical features and estimated incidence of MIS-C in Cape Town, South Africa
Authors: Butters Claire , Abraham Deepthi Raju , Stander Raphaella , Facey-Thomas Heidi , Abrahams Debbie , Faleye Ayodele , Allie Nazneen , Soni Khushbu , Rabie Helena , Scott Christiaan , Zühlke Liesl , Webb Kate 
Published: May 2022

Abstract
Background
Multisystem inflammatory syndrome is a severe manifestation of SARS-CoV-2 in children. The incidence of MIS-C after infection is poorly understood. There are very few cohorts describing MIS-C in Africa despite MIS-C being more common in Black children worldwide.

Methods
A cohort of children with MIS-C and healthy children was recruited from May 2020 until May 2021 from the two main paediatric hospitals in Cape Town, South Africa. Clinical and demographic data were collected, and serum was tested for SARS-CoV-2 antibodies. The incidence of MIS-C was calculated using an estimation of population exposure from seroprevalence in the healthy group. Summary data, non-parametric comparisons and logistic regression analyses were performed.

Results
Sixty eight children with MIS-C were recruited with a median age of 7 years (3.6, 9.9). Ninety seven healthy children were recruited with a 30% seroprevalence. The estimated incidence of MIS-C was 22/100 000 exposures in the city in this time. Black children were over-represented in the MIS-C group (62% vs 37%, p = 0.002). The most common clinical features in MIS-C were fever (100%), tachycardia (98.5%), rash (85.3%), conjunctivitis (77.9%), abdominal pain (60.3%) and hypotension (60.3%). The median haemoglobin, sodium, neutrophil count, white cell count, CRP, ferritin, cardiac (pro-BNP, trop-T) and coagulation markers (D-dimer and fibrinogen) were markedly deranged in MIS-C. Cardiac, pulmonary, central nervous and renal organ systems were involved in 71%, 29.4%, 27.9% and 27.9% respectively. Ninety four percent received intravenous immune globulin, 64.7% received methylprednisolone and 61.7% received both. Forty percent required ICU admission, 38.2% required inotropic support, 38.2% required oxygen therapy, 11.8% required invasive ventilation and 6% required peritoneal dialysis. Older age was an independent predictor for the requirement for ionotropic support (OR = 1.523, CI 1.074, 2.16, p = 0.018). The median hospital stay duration was 7 days with no deaths.

Conclusion
The lack of reports from Southern Africa does not reflect a lack of cases of MIS-C. MIS-C poses a significant burden to children in the region as long as the pandemic continues. MIS-C disproportionately affects black children. The clinical manifestations and outcomes of MIS-C in this region highlight the need for improved surveillance, reporting and data to inform diagnosis and treatment.
Explaining the effect on food selection of altering availability: two experimental studies on the role of relative preferences
Authors: Pechey Rachel , Hollands Gareth J. , Marteau Theresa M. 
Published: May 2022

Abstract
Background
Increasing the availability of healthier or plant-based foods increases their selection. The current studies aimed to examine the extent to which relative preferences account for food selections following availability interventions. In particular, (a) whether increasing the availability of lower-energy options increases the likelihood that individuals’ highest-ranked option is lower-energy, and (b) the extent to which selections reflect individuals’ highest-ranked option from the available range.

Methods
UK adults (Study 1: n = 1976; Study 2: n = 1078) took part in within-subjects online studies. In both studies, the order of preference between food options was established by participants choosing the option that they would prefer “to eat right now” from every possible pairing within a pool of eight options. Then, participants were shown either predominantly higher-energy options (three higher- and one lower-energy) or predominantly lower-energy options (vice versa), presented in a random order.

Results
When predominantly lower-energy options were presented, the odds of the highest-ranked option being a lower-energy option increased ten-fold (Study 1: odds ratio: 10.1; 95%CI: 8.9,11.4; Study 2: odds ratio: 10.4; 95%CI: 7.4,14.7), compared to when predominantly higher-energy options were available. In both studies, around 90% of selections reflected the highest-ranked option in the range offered in the studied availability conditions (range 88–92%).

Conclusions
These studies suggest that increased availability of lower-energy options increases the likelihood of an individual’s highest-ranked option being lower-energy, and that the highest-ranked option has the greatest likelihood of selection. As such, preferences may be a key contributor to the effects of altering availability on food selections.

Trial registration
ISRCTN (http://www.isrctn.com/ISRCTN27598623; 3/12/19 [Study 1]; http://www.isrctn.com/ISRCTN61010183; 20/4/20 [Study 2]).
Integrated analysis of mRNA and long noncoding RNA profiles in peripheral blood mononuclear cells of patients with bronchial asthma
Authors: Cui Han , Duan Ruirui , Niu Hongtao , Yu Tao , Huang Ke , Chen Chen , Hao Ke , Yang Ting , Wang Chen 
Published: May 2022

Abstract
Background
Bronchial asthma is a heterogeneous disease with distinct disease phenotypes and underlying pathophysiological mechanisms. Long non-coding RNAs (lncRNAs) are involved in numerous functionally different biological and physiological processes. The aim of this study was to identify differentially expressed lncRNAs and mRNAs in patients with asthma and further explore the functions and interactions between lncRNAs and mRNAs.

Methods
Ten patients with asthma and 9 healthy controls were enrolled in this study. RNA was isolated from peripheral blood mononuclear cells. We performed microarray analysis to evaluate lncRNA and mRNA expression. The functions of the differentially expressed mRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. A global signal transduction network was constructed to identify the core mRNAs. An lncRNA–mRNA network was constructed. Five mRNAs showing the greatest differences in expression levels or high degrees in the gene–gene functional interaction network, with their correlated lncRNAs, were validated by real-time quantitative polymerase chain reaction.

Results
We identified 2229 differentially expressed mRNAs and 1397 lncRNAs between the asthma and control groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified many pathways associated with inflammation and cell survival. The gene–gene functional interaction network suggested that some core mRNAs are involved in the pathogenesis of bronchial asthma. The lncRNA–mRNA co-expression network revealed correlated lncRNAs. CXCL8, FOXO3, JUN, PIK3CA, and G0S2 and their related lncRNAs NONHSAT115963, AC019050.1, MTCYBP3, KB-67B5.12, and HNRNPA1P12 were identified according to their differential expression levels and high degrees in the gene–gene network.

Conclusions
We identified the core mRNAs and their related lncRNAs and predicted the biological processes and signaling pathways involved in asthma.