bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement
Authors: Samad Navira , Nguyen Hanh H. , Hashimura Hikaru , Pasco Julie , Kotowicz Mark , Strauss Boyd J. , Ebeling Peter R. , Milat Frances , Vincent Amanda J. 
Published: May 2022

BackgroundLow bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking.ObjectiveTo assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI.MethodCross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years.ResultsWomen with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p&lt;0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p&lt;0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p&lt;0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm2 and 0.0070 (p&lt;0.05), respectively.ConclusionDeficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes.
Metabolic Stress Index Including Mitochondrial Biomarker for Noninvasive Diagnosis of Hepatic Steatosis
Authors: Chang Jae Seung , Ahn Jhii-Hyun , Kang Seong Hee , Koh Sang-Baek , Kim Jang-Young , Baik Soon Koo , Huh Ji Hye , Lee Samuel S. , Kim Moon Young , Park Kyu-Sang 
Published: May 2022

BackgroundMitochondrial dysfunction with oxidative stress contributes to nonalcoholic fatty liver disease (NAFLD) progression. We investigated the steatosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers.MethodsAltogether, 343 subjects who underwent magnetic resonance imaging-based liver examinations from a population-based general cohort, and 41 patients enrolled in a biopsy-evaluated NAFLD cohort, participated in the development and validation groups, respectively. Serologic stress biomarkers were quantitated by enzyme-linked immunosorbent assay.ResultsMultivariate regression showed that waist-to-hip ratio, fibroblast growth factor (FGF) 21, FGF19, adiponectin-to-leptin ratio, insulin, albumin, triglyceride, total-cholesterol, and alanine-aminotransferase were independent predictors of steatosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95%CI)] of the metabolic stress index for steatosis (MSI-S) was 0.886 (0.85−0.92) and 0.825 (0.69−0.96) in development and validation groups, respectively. MSI-S had higher diagnostic accuracy (78.1%−81.1%) than other steatosis indices. MSI-S notably differentiated steatosis severities, while other indices showed less discrimination.ConclusionMSI-S, as a novel non-invasive index, based on mitochondrial stress biomarker FGF21 effectively predicted steatosis. Furthermore, MSI-S may increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.
Distracted when Using Driving Automation: A Quantile Regression Analysis of Driver Glances Considering the Effects of Road Alignment and Driving Experience
Authors: He Dengbo , Kanaan Dina , Donmez Birsen 
Published: May 2022

Background: SAE Level 2 driving automation, the state-of-the-art in commercial vehicles, requires drivers to monitor the environment to resume vehicle control when automation limits are surpassed. However, this type of driving automation was found to increase distraction engagement. Although experienced drivers were shown to better regulate their visual engagement in distracting activities when driving with and without automation, the moderating effects of road demands (e.g., road alignment) have yet to be explored in detail, in particular, for driving with automation.Objective: To better understand the combined effects of road alignment, driving automation, and driving experience, we investigated the effects of these factors on driver glances to a visual-manual distraction task.Method: We present a secondary analysis, using quantile regression, of two previously reported driving simulator experiments. A total of 32 participants’ data, 16 from each experiment, were utilized. Half of these participants were novice and the other half were experienced drivers. The first experiment focused on non-automated driving, while the second focused on driving with adaptive cruise control and lane keeping assistance systems combined (i.e., SAE Level 2). The analysis reported here focuses on drivers’ visual distraction engagement in two highway drives that were identical across the two experiments.Results: With driving automation, compared to experienced driver glances, the duration of novice driver glances to the distraction task was more variable, longer, and less sensitive to variations in road alignment.Implications: These findings suggest that, with driving automation, novice drivers are more at risk of inappropriate engagement in distractions and do not adapt to road demands as well as experienced drivers, and thus should be supported accordingly.
Discovery and Validation of a Novel Metastasis-Related lncRNA Prognostic Signature for Colorectal Cancer
Authors: Tang Qiang , Hu Xin , Guo Qiong , Shi Yueyue , Liu Liming , Ying Guoguang 
Published: May 2022

Background: Cancer metastasis-related chemoresistance and tumour progression are the leading causes of death among CRC patients. Therefore, it is urgent to identify reliable novel biomarkers for predicting the metastasis of CRC.Methods: The gene expression and corresponding clinical data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate and multivariate analyses were performed to identify prognostic metastasis-related lncRNAs. Nomograms were constructed, and the predictive accuracy of the nomogram model was assessed by ROC curve analysis. Then, the R package “pRRophetic” was used to predict chemotherapeutic response in CRC patients. In addition, the CIBERSORT database was introduced to evaluate tumour infiltrating immune cells between the high—and low-risk groups. The potential roles of SNHG7 and ZEB1-AS1 in CRC cell lines were further confirmed by in vitro experiments.Results: An 8-lncRNA (LINC00261, RP1-170O19.17, CAPN10-AS1, SNHG7, ZEB1-AS1, U47924.27, NIFK-AS1, and LINC00925) signature was constructed for CRC prognosis prediction, which stratified patients into two risk groups. Kaplan-Meier analysis revealed that patients in the higher-risk group had a lower survival probability than those in the lower-risk group [p &lt; 0.001 (TCGA); P = 0.044 (GSE39582); and P = 0.0078 (GSE29621)] The AUCs of 1-, 3-, and 5-year survival were 0.678, 0.669, and 0.72 in TCGA; 0.58, 0.55, and 0.56 in GSE39582; and 0.75, 0.54, and 0.56 in GSE29621, respectively. In addition, the risk score was an independent risk factor for CRC patients. Nomograms were constructed, and the predictive accuracy was assessed by ROC curve analysis. This signature could effectively predict the immune status and chemotherapy response in CRC patients. Moreover, SNHG7 and ZEB1-AS1 depletion significantly suppressed the colony formation, migration, and invasion of CRC cells in vitro.Conclusion: We constructed a signature that could predict the metastasis of CRC and provide certain theoretical guidance for novel therapeutic approaches for CRC.
Benchmarking Low-Frequency Variant Calling With Long-Read Data on Mitochondrial DNA
Authors: Lüth Theresa , Schaake Susen , Grünewald Anne , May Patrick , Trinh Joanne , Weissensteiner Hansi 
Published: May 2022

Background: Sequencing quality has improved over the last decade for long-reads, allowing for more accurate detection of somatic low-frequency variants. In this study, we used mixtures of mitochondrial samples with different haplogroups (i.e., a specific set of mitochondrial variants) to investigate the applicability of nanopore sequencing for low-frequency single nucleotide variant detection.Methods: We investigated the impact of base-calling, alignment/mapping, quality control steps, and variant calling by comparing the results to a previously derived short-read gold standard generated on the Illumina NextSeq. For nanopore sequencing, six mixtures of four different haplotypes were prepared, allowing us to reliably check for expected variants at the predefined 5%, 2%, and 1% mixture levels. We used two different versions of Guppy for base-calling, two aligners (i.e., Minimap2 and Ngmlr), and three variant callers (i.e., Mutserve2, Freebayes, and Nanopanel2) to compare low-frequency variants. We used F1 score measurements to assess the performance of variant calling.Results: We observed a mean read length of 11 kb and a mean overall read quality of 15. Ngmlr showed not only higher F1 scores but also higher allele frequencies (AF) of false-positive calls across the mixtures (mean F1 score = 0.83; false-positive allele frequencies &lt; 0.17) compared to Minimap2 (mean F1 score = 0.82; false-positive AF &lt; 0.06). Mutserve2 had the highest F1 scores (5% level: F1 score &gt;0.99, 2% level: F1 score &gt;0.54, and 1% level: F1 score &gt;0.70) across all callers and mixture levels.Conclusion: We here present the benchmarking for low-frequency variant calling with nanopore sequencing by identifying current limitations.
Family Planning Experiences and Needs of Young Women Living With and Without HIV Accessing an Integrated HIV and SRH Intervention in Zimbabwe-An Exploratory Qualitative Study
Authors: Mavodza Constancia V. , Busza Joanna , Mackworth-Young Constance R. S. , Nyamwanza Rangarirai , Nzombe Portia , Dauya Ethel , Dziva Chikwari Chido , Tembo Mandikudza , Simms Victoria , Mugurungi Owen , Apollo Tsitsi , Madzima Bernard , Ferrand Rashida A. , Bernays Sarah 
Published: May 2022

BackgroundPeople living with HIV have higher unmet family planning needs compared to those without HIV. This is heightened for young people. However, the provision of family planning for young people within HIV programmes is uncommon. We investigated family planning uptake, acceptability of, and engagement with a service offering integrated HIV and sexual and reproductive health services for youth in a community-based setting in Zimbabwe.MethodsCHIEDZA, a community-based intervention offering integrated HIV and sexual and reproductive health services to young people aged 16–24 years, is being trialed in Zimbabwe. This exploratory qualitative study was nested within an ongoing study process evaluation. Data was collected between March-May 2021 with two sets of interviews conducted: I) twelve semi-structured interviews with young women living with HIV aged 17–25 years and II) fifteen interviews conducted with young women without HIV aged between 20 and 25 years who used a contraceptive method. A thematic analysis approach was used.ResultsBefore engaging with CHIEDZA, young women had experienced judgmental providers, on account of their age, and received misinformation about contraceptive use and inadequate information about ART-contraceptive interactions. These presented as barriers to uptake and engagement. Upon attending CHIEDZA, all the young women reported receiving non-judgmental care. For those living with HIV, they were able to access integrated HIV and family planning services that supported them having broader sexual and reproductive needs beyond their HIV diagnosis. The family planning preference of young women living with HIV included medium to long-acting contraceptives to minimize adherence challenges, and desired partner involvement in dual protection to prevent HIV transmission. CHIEDZA's ability to meet these preferences shaped uptake, acceptability, and engagement with integrated HIV and family services.ConclusionsRecommendations for an HIV and family planning integrated service for young people living with HIV include: offering a range of services (including method-mix contraceptives) to choose from; supporting their agency to engage with the services which are most acceptable to them; and providing trained, supportive, knowledgeable, and non-judgmental health providers who can provide accurate information and counsel. We recommend youth-friendly, differentiated, person-centered care that recognize the multiple and intersecting needs of young people living with HIV.
Platelet-to-Albumin Ratio: A Novel IgA Nephropathy Prognosis Predictor
Authors: Tan Jiaxing , Song Guojiao , Wang Siqing , Dong Lingqiu , Liu Xiang , Jiang Zheng , Qin Aiya , Tang Yi , Qin Wei 
Published: May 2022

BackgroundChronic inflammation is related to the development of IgA nephropathy (IgAN). Emerging studies have reported that platelet-related parameters including platelet (PLT), platelet-to-albumin ratio (PAR), and platelet-to-lymphocyte ratio (PLR) are proved to be novel prognostic indicators for several inflammatory diseases. Whether platelet-related parameters could serve as predictors for IgAN remains unknown.MethodsA total of 966 IgAN patients were enrolled in this retrospective study and were divided into several groups based on the optimal cut-off value of the platelet-related parameters. End-stage renal disease was used as the renal endpoint. A 1:2 propensity score (PS) match was then carried out to eliminate significant differences at baseline. The area under the receiver operating characteristic curve (AUROC), Kaplan–Meier (K-M) curve, and Cox proportional hazards analyses were performed to evaluate their predictive effect.ResultsWithout considering the effect of covariates, the K-M curve showed that PLT, PLR, and PAR were strongly correlated with the renal outcomes of IgAN. However, the AUROC revealed that the PAR and PLR had better predictive power than the PLT. Multivariate Cox regression adjusting for demographic data, pathological findings, treatment, and laboratory results indicated that compared with PLR, albumin and PLT, PAR seemed to be a better marker of adverse renal outcome, implying that PAR was the only platelet-related parameter that could be used as an independent risk factor. Notably, high PAR patients seemed to have more severe clinical manifestations and pathological lesions. However, after eliminating the influence of different baselines on outcome variables, the PAR could still predict the poor prognosis of IgAN. To more accurately evaluate the predictive power of the PAR, we analyzed the predictive effect of the PAR on patients with different clinicopathological characteristics through subgroup analysis. It was indicated that the PAR might better predict the prognosis and outcome of patients whose disease was already very severe.ConclusionPAR might be used as an independent risk factor for IgAN progression.
Structural and Temporal Dynamics of Mesenchymal Stem Cells in Liver Diseases From 2001 to 2021: A Bibliometric Analysis
Authors: Shao Bo , Qin Ya-fei , Ren Shao-hua , Peng Qiu-feng , Qin Hong , Wang Zhao-bo , Wang Hong-da , Li Guang-ming , Zhu Yang-lin , Sun Cheng-lu , Zhang Jing-yi , Li Xiang , Wang Hao 
Published: May 2022

BackgroundMesenchymal stem cells (MSCs) have important research value and broad application prospects in liver diseases. This study aims to comprehensively review the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in liver diseases from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and discover hot trends and emerging topics.MethodsThe articles and reviews related to MSCs in liver diseases were retrieved from the Web of Science Core Collection using Topic Search. A bibliometric study was performed using CiteSpace and VOSviewer.ResultsA total of 3404 articles and reviews were included over the period 2001-2021. The number of articles regarding MSCs in liver diseases showed an increasing trend. These publications mainly come from 3251 institutions in 113 countries led by China and the USA. Li L published the most papers among the publications, while Pittenger MF had the most co-citations. Analysis of the most productive journals shows that most are specialized in medical research, experimental medicine and cell biology, and cell &amp; tissue engineering. The macroscopical sketch and micro-representation of the whole knowledge field are realized through co-citation analysis. Liver scaffold, MSC therapy, extracellular vesicle, and others are current and developing areas of the study. The keywords “machine perfusion”, “liver transplantation”, and “microRNAs” also may be the focus of new trends and future research.ConclusionsIn this study, bibliometrics and visual methods were used to review the research of MSCs in liver diseases comprehensively. This paper will help scholars better understand the dynamic evolution of the application of MSCs in liver diseases and point out the direction for future research.
The Presence of Tertiary Lymphoid Structures Provides New Insight Into the Clinicopathological Features and Prognosis of Patients With Breast Cancer
Authors: Wang Bin , Liu Jie , Han Yin , Deng Yaotiao , Li Jinze , Jiang Yu 
Published: May 2022

BackgroundTertiary lymphoid structures (TLSs) have been proven to be predictive biomarkers of favorable clinical outcomes and response to immunotherapies in several solid malignancies. Nevertheless, the effect of TLSs in patients with breast cancer (BC) remains controversial. The objective of the current study is to investigate the clinicopathological and prognostic significance of TLSs in BC. Given the unique difficulties for detecting and quantifying TLSs, a TLS-associated gene signature based on The Cancer Genome Atlas (TCGA) BC cohort was used to validate and supplement our results.MethodsElectronic platforms (PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and Wanfang) were searched systematically to identify relevant studies as of January 11, 2022. We calculated combined odds ratios (ORs) with 95% confidence intervals (CIs) to determine the relationship between clinicopathological parameters and TLSs. The pooled hazard ratios (HRs) and 95% CIs were also calculated to evaluate the prognostic significance of TLSs. The TLS signature based on the TCGA BC cohort was applied to validate and supplement our results.ResultsFifteen studies with 3,898 patients were eligible for enrollment in our study. The combined analysis indicated that the presence of TLSs was related to improved disease-free survival (DFS) (HR = 0.61, 95% CI: 0.41–0.90, p &lt; 0.05) and overall survival (OS) (HR = 1.66, 95% CI: 1.26–2.20, p &lt; 0.001). Additionally, the presence of TLSs was positively correlated with early tumor TNM stage and high tumor-infiltrating lymphocytes. TLS presence was positively related to human epidermal growth factor receptor 2 (HER-2) and Ki-67 but inversely correlated with the status of estrogen and progesterone receptor. Simultaneously, our study found that tumor immune microenvironment was more favorable in the high-TLS signature group than in the low-TLS signature group. Consistently, BC patients in the high-TLS signature group exhibited better survival outcomes compared to those in the low-TLS signature group, suggesting that TLSs might be favorable prognostic biomarkers.ConclusionsTLS presence provides new insight into the clinicopathological features and prognosis of patients with BC, whereas the factors discussed limited the evidence quality of this study. We look forward to consistent methods to define and characterize TLSs, and more high-quality prospective clinical trials designed to validate the value of TLSs alone or in combination with other markers.
Predicting Pathological Complete Response in Neoadjuvant Dual Blockade With Trastuzumab and Pertuzumab in HER2 Gene Amplified Breast Cancer
Authors: Xiao Yi , Ding Jiahan , Ma Dachang , Chen Sheng , Li Xun , Yu Keda 
Published: May 2022

BackgroundDual-targeted therapy is the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and effective biomarkers to predict the response to neoadjuvant trastuzumab and pertuzumab treatment need further investigation. Here, we developed a predictive model to evaluate the dual-targeted neoadjuvant treatment efficacy in HER2 gene-amplified breast cancer.MethodThis retrospective study included 159 HER2-amplified patients with locally advanced breast cancer who received neoadjuvant trastuzumab, pertuzumab, and chemotherapy. The correlation between clinicopathological factors and pathological complete response (pCR, in the breast and axilla) was evaluated. Patients were randomly assigned into the training set (n=110) and the testing set (n=49). We used an independent cohort (n=65) for external validation. We constructed our predictive nomogram model with the results of risk variables associated with pCR identified in the multivariate logistic analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, decision curve analysis, and calibration curves were employed to assess the nomogram’s performance.ResultsWe revealed that the HER2/CEP17 ratio (p=0.001), CD8 levels (p=0.005), and histological grade (p=0.007) were independent indicators for pCR in dual-targeted neoadjuvant treatment after multivariate adjustment. The combined prediction efficacy of the three indicators was significantly higher than that of each single indicator alone. The AUCs were 0.819, 0.773, and 0.744 in the training, testing, and external validation sets, respectively.ConclusionsThe HER2/CEP17 ratio, CD8 levels, and histological grade were significantly correlated with pCR in dual-targeted neoadjuvant treatment. The combined model using these three markers provided a better predictive value for pCR than the HER2/CEP17 ratio, CD8 levels, and the histological grade alone, which showed that an immunological effect partially mediates the predictive impact of neoadjuvant treatment.