bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function and autophagy of monocyte-derived dendritic cells is affected by hepatitis B virus infection
Authors: Xu Hua , Kang Juan , Zhong Shan , Chen Min , Hu Peng , Ren Hong , Zhou Zhi , Lei Yu 
Published: September 2023

Abstract
Background
The role of dendritic cells and the autophagy state of dendritic cells in the immune response of hepatitis B virus (HBV) infection was still controversial. In this study, we carefully examined the phenotype, function and autophagy pathway of dendritic cells in HBV infection.

Methods
Monocyte-derived dendritic cells from healthy blood donors and patients with chronic HBV infection were stimulated by lipopolysaccharide, supernatant of HepG2.2.15 cells or supernatant of HepG2 cells respectively. Phenotype of dendritic cells was examined by flow cytometry and cytokines secretion was detected by enzyme-linked immunosorbent assay. Autophagy related proteins were detected by western blot and immunofluorescence analysis.

Results
Our results showed that the expression of both major histocompatibility complex II molecules and co-stimulated molecules including cluster of differentiation antigen 80, cluster of differentiation antigen 86 in the monocyte-derived dendritic cells from patients with chronic HBV infection was significantly higher than that from healthy donors when cultured with supernatant of HepG2.2.15 cells. The amount of cytokines, including tumour necrosis factor-α, interleukin-10 and interleukin-12, secreted by monocyte-derived dendritic cells from patients with chronic HBV infection was also significantly higher than that from healthy donors when stimulate by HBV. Interestingly, the expression level of autophagy-related proteins including autophagy-related protein5 and associated protein 1 light chain in dendritic cells from patients with chronic HBV infection was significantly increased when compared with that from healthy donors when re-exposed to HBV.

Conclusions
Our results indicated that dendritic cells from patients with chronic HBV infection could intensively present antigen and express co-stimulatory molecules. The increased activation of dendritic cells might be related to the enhanced autophagy of dendritic cells in HBV infection.
Genealogical tracing of Olea europaea species and pedigree relationships of var. europaea using chloroplast and nuclear markers
Authors: Mariotti Roberto , Belaj Angjelina , de la Rosa Raúl , Muleo Rosario , Cirilli Marco , Forgione Ivano , Valeri Maria Cristina , Mousavi Soraya 
Published: September 2023

Abstract
Background
Olive is one of the most cultivated species in the Mediterranean Basin and beyond. Despite being extensively studied for its commercial relevance, the origin of cultivated olive and the history of its domestication remain open questions. Here, we present a genealogical and kinship relationships analysis by mean of chloroplast and nuclear markers of different genera, subgenus, species, subspecies, ecotypes, cultivated, ancient and wild types, which constitutes one of the most inclusive research to date on the diversity within Olea europaea species. A complete survey of the variability across the nuclear and plastid genomes of different genotypes was studied through single nucleotide polymorphisms, indels (insertions and deletions), and length variation.

Results
Fifty-six different chlorotypes were identified among the Oleaceae family including Olea europaea, other species and genera. The chloroplast genome evolution, within Olea europaea subspecies, probably started from subsp. cuspidata, which likely represents the ancestor of all the other subspecies and therefore of wild types and cultivars. Our study allows us to hypothesize that, inside the subspecies europaea containing cultivars and the wild types, the ancestral selection from var. sylvestris occurred both in the eastern side of the Mediterranean and in the central-western part of Basin. Moreover, it was elucidated the origin of several cultivars, which depends on the introduction of eastern cultivars, belonging to the lineage E1, followed by crossing and replacement of the autochthonous olive germplasm of central-western Mediterranean Basin. In fact, our study highlighted that two main ‘founders’ gave the origin to more than 60% of analyzed olive cultivars. Other secondary founders, which strongly contributed to give origin to the actual olive cultivar diversity, were already detected.

Conclusions
The application of comparative genomics not only paves the way for a better understanding of the phylogenetic relationships within the Olea europaea species but also provides original insights into other elusive evolutionary processes, such as chloroplast inheritance and parentage inside olive cultivars, opening new scenarios for further research such as the association studies and breeding programs.
Pseudoaneurysm of the mitral-aortic intervalvular fibrosa: a rare case after percutaneous transluminal coronary angioplasty
Authors: Xie Debo , Jiang Lulu , Zhang Jun , Li Xin , Guo Yanli 
Published: September 2023

Abstract
Background
Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is an uncommon but potentially life-threatening condition. The most common pathogenic factors of P-MAIVF are infective endocarditis and surgical valve operation. Here, we report a rare case of P-MAIVF which occurred one year after percutaneous transluminal coronary angioplasty (PTCA).

Case presentation
A 31-year-old man developed a P-MAIVF one year after PTCA. Transthoracic echocardiography (TTE) revealed a pseudoaneurysm between the aortic root and the left atrium. Three-dimensional transesophageal echocardiography (3D-TEE) clearly demonstrated the orifice of the pseudoaneurysm. This case was initially diagnosed by ultrasound, and the prognosis was good after surgical repair.

Conclusions
We report a rare case of P-MAIVF that occurred one year after PTCA.
Echocardiography-based machine learning algorithm for distinguishing ischemic cardiomyopathy from dilated cardiomyopathy
Authors: Zhou Mei , Deng Yongjian , Liu Yi , Su Xiaolin , Zeng Xiaocong 
Published: September 2023

Abstract
Background
Machine learning (ML) can identify and integrate connections among data and has the potential to predict events. Heart failure is primarily caused by cardiomyopathy, and different etiologies require different treatments. The present study examined the diagnostic value of a ML algorithm that combines echocardiographic data to automatically differentiate ischemic cardiomyopathy (ICM) from dilated cardiomyopathy (DCM).

Methods
We retrospectively collected the echocardiographic data of 200 DCM patients and 199 ICM patients treated in the First Affiliated Hospital of Guangxi Medical University between July 2016 and March 2022. All patients underwent invasive coronary angiography for diagnosis of ICM or DCM. The data were randomly divided into a training set and a test set via 10-fold cross-validation. Four ML algorithms (random forest, logistic regression, neural network, and XGBoost [ML algorithm under gradient boosting framework]) were used to generate a training model for the optimal subset, and the parameters were optimized. Finally, model performance was independently evaluated on the test set, and external validation was performed on 79 patients from another center.

Results
Compared with the logistic regression model (area under the curve [AUC] = 0.925), neural network model (AUC = 0.893), and random forest model (AUC = 0.900), the XGBoost model had the best identification rate, with an average sensitivity of 72% and average specificity of 78%. The average accuracy was 75%, and the AUC of the optimal subset was 0.934. External validation produced an AUC of 0.804, accuracy of 78%, sensitivity of 64% and specificity of 93%.

Conclusions
We demonstrate that utilizing advanced ML algorithms can help to differentiate ICM from DCM and provide appreciable precision for etiological diagnosis and individualized treatment of heart failure patients.
Public transit stop density is associated with walking for exercise among a national sample of older adults
Authors: Twardzik Erica , Falvey Jason R. , Clarke Philippa J. , Freedman Vicki A. , Schrack Jennifer A. 
Published: September 2023

Abstract
Background
Walking is the primary and preferred mode of exercise for older adults. Walking to and from public transit stops may support older adults in achieving exercise goals. This study examined whether density of neighborhood public transit stops was associated with walking for exercise among older adults.

Methods
2018 National Health and Aging Trends Study (NHATS) data were linked with the 2018 National Neighborhood Data Archive, which reported density of public transit stops (stops/mile2) within participants’ neighborhood, defined using census tract boundaries. Walking for exercise in the last month was self-reported. The extent to which self-reported public transit use mediated the relationship between density of neighborhood public transit stops and walking for exercise was examined. Covariates included sociodemographic characteristics, economic status, disability status, and neighborhood attributes. National estimates were calculated using NHATS analytic survey weights.

Results
Among 4,836 respondents with complete data, 39.7% lived in a census tract with at least one neighborhood public transit stop and 8.5% were public transit users. The odds of walking for exercise were 32% higher (OR = 1.32; 95% confidence interval: 1.08, 1.61) among respondents living in a neighborhood with > 10 transit stops per mile compared to living in a neighborhood without any public transit stops documented. Self-reported public transit use mediated 24% of the association between density of neighborhood public transit stops and walking for exercise.

Conclusions
Density of neighborhood public transit stops was associated with walking for exercise, with a substantial portion of the association mediated by self-reported public transit use. Increasing public transit stop availability within neighborhoods may contribute to active aging among older adults.
Validation of sTREM-1 and IL-6 based algorithms for outcome prediction of COVID-19
Authors: Van Singer Mathias , Brahier Thomas , Koch Jana , Hugli Pr. Olivier , Weckman Andrea M. , Zhong Kathleen , Kain Taylor J. , Leligdowicz Aleksandra , Bernasconi Enos , Ceschi Alessandro , Parolari Sara , Vuichard-Gysin Danielle , Kain Kevin C. , Albrich Werner C. , Boillat-Blanco Noémie 
Published: September 2023

Abstract
Background
A prospective observational cohort study of COVID-19 patients in a single Emergency Department (ED) showed that sTREM-1- and IL-6-based algorithms were highly predictive of adverse outcome (Van Singer et al. J Allergy Clin Immunol 2021). We aim to validate the performance of these algorithms at ED presentation.

Methods
This multicentric prospective observational study of PCR-confirmed COVID-19 adult patients was conducted in the ED of three Swiss hospitals. Data of the three centers were retrospectively completed and merged. We determined the predictive accuracy of the sTREM-1-based algorithm for 30-day intubation/mortality. We also determined the performance of the IL-6-based algorithm using data from one center for 30-day oxygen requirement.

Results
373 patients were included in the validation cohort, 139 (37%) in Lausanne, 93 (25%) in St.Gallen and 141 (38%) in EOC. Overall, 18% (93/373) patients died or were intubated by day 30. In Lausanne, 66% (92/139) patients required oxygen by day 30. The predictive accuracy of sTREM-1 and IL-6 were similar compared to the derivation cohort. The sTREM-1-based algorithm confirmed excellent sensitivity (90% versus 100% in the derivation cohort) and negative predictive value (94% versus 100%) for 30-day intubation/mortality. The IL-6-based algorithm performance was acceptable with a sensitivity of 85% versus 98% in the derivation cohort and a negative predictive value of 60% versus 92%.

Conclusion
The sTREM-1 algorithm demonstrated good reproducibility. A prospective randomized controlled trial, comparing outcomes with and without the algorithm, is necessary to assess its safety and impact on hospital and ICU admission rates. The IL-6 algorithm showed acceptable validity in a single center and need additional validation before widespread implementation.
Effect of virtual reality combined with repetitive transcranial magnetic stimulation on musculoskeletal pain and motor development in children with spastic cerebral palsy: a protocol for a randomized controlled clinical trial
Authors: Li Xin , Huang Zefan , Lu Tijiang , Liang Juping , Guo Haibin , Wang Lixia , Chen Zhengquan , Zhou Xuan , Du Qing 
Published: September 2023

Abstract
Purpose
This trial aims to investigate the efficacy and safety of virtual reality (VR) combined with repetitive transcranial magnetic stimulation (rTMS) for improving musculoskeletal pain and motor development in children with unilateral spastic cerebral palsy (CP).

Methods
This study protocol is for a randomized controlled trial consisting of 2 treatment sessions (3 days/week for 4 weeks in each session, with a 1-week interval between sessions). We will recruit children aged 3–10 years with unilateral spastic CP (Gross Motor Function Classification System level I or II). Participants will be randomly divided into 3 groups: the VR + rTMS group (immersive VR intervention, rTMS and routine rehabilitation therapy), rTMS group (rTMS and routine rehabilitation therapy), and control group (sham rTMS and routine rehabilitation therapy). VR therapy will involve a daily 40-minute movement training session in a fully immersive environment. rTMS will be applied at 1 Hz over the primary motor cortex for 20 min on the contralateral side. The stimulation intensity will be set at 90% of the resting motor threshold, with 1200 pulses applied. A daily 60-minute routine rehabilitation therapy session including motor training and training in activities of daily living will be administered to all participants. The primary outcome will be pain intensity, assessed by the Revised Face, Legs, Activity, Cry, and Consolability Scale (R-FLACC). The secondary outcomes will include motor development, evaluated by the 66-item version of the Gross Motor Function Measure (GMFM-66) and Fine Motor Function Measure (FMFM); balance capacity, measured by the interactive balance system; activities of daily living; and quality of life, measured by the Barthel index and the Chinese version of the Cerebral Palsy Quality of Life scale for Children (C-CP QOL-Child). Safety will be monitored, and adverse events will be recorded during and after treatment.

Discussion
Combined application of VR therapy and rTMS may reveal additive effects on pain management and motor development in children with spastic CP, but further high-quality research is needed. The results of this trial may indicate whether VR therapy combined with rTMS achieves a better analgesic effect and improves the motor development of children with spastic CP.

Trial registration
Registration number: ChiCTR230069853. Trial registration date: 28 March 2023. Prospectively registered.
Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial
Authors: Corti Francesca , Brizzi Maria Pia , Amoroso Vito , Giuffrida Dario , Panzuto Francesco , Campana Davide , Prinzi Natalie , Milione Massimo , Cascella Tommaso , Spreafico Carlo , Randon Giovanni , Oldani Simone , Leporati Rita , Scotto Giulia , Pulice Iolanda , Stocchetti Benedetta Lombardi , Porcu Luca , Coppa Jorgelina , Di Bartolomeo Maria , de Braud Filippo , Pusceddu Sara 
Published: September 2023

Abstract
Background
Well-differentiated (WD) neuroendocrine tumors (NETs) are a group of rare neoplasms with limited therapeutic options. Cabozantinib is an inhibitor of multiple tyrosine kinases with a pivotal role in NET pathogenesis, including c-MET and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). LOLA is the first prospective phase II trial aiming to assess the safety and activity of cabozantinib combined with lanreotide in WD NETs of gastroenteropancreatic (GEP), thoracic and of unknown origin.

Methods
This is a multicenter, open-label, double-cohort, non comparative, non-randomized, three-stage phase II trial. Eligible patients have to meet the following inclusion criteria: diagnosis of advanced or metastatic, progressive, non-functioning WD thoracic NETs, GEP-NETs or NETs of unknown origin with Ki67 ≥ 10%; positive 68 Ga-PET uptake or somatostatin receptor 2 immunohistochemical (IHC) stain; maximum 1 prior systemic regimen for metastatic disease. Two cohorts will be considered: pNETs and carcinoids (typical or atypical lung and thymus NETs, gastro-intestinal NETs or NETs of unknown origin). In stage I, the primary objective is to find the optimal dose of cabozantinib in combination with lanreotide and to evaluate the safety of the combination (percentage of patients experiencing grade 3–5 toxicities according to NCI-CTCAE version 5.0). Starting dose of cabozantinib is 60 mg/day continuously, plus lanreotide 120 mg every 28 days. In stage II and III, co-primary endpoints are safety and overall response rate (ORR) according to RECIST version 1.1. The uninteresting antitumor activity is fixed in ORR ≤ 5%. Secondary endpoints are progression-free survival and overall survival. Exploratory objectives include the assessment of c-MET, AXL and VEGFR2 IHC expression, to identify predictive or prognostic tissue biomarkers. Enrolment started in July 2020, with an expected trial duration of 42 months comprehensive of accrual, treatment and follow-up. Considering a drop-out rate of 5%, the maximum number of enrolled patients will be 69.

Discussion
Supported by a solid rationale, the trial has the potential to generate milestone data about the synergistic effects of cabozantinib plus lanreotide in a group of NET patients with relatively aggressive disease and limited therapeutic options.

Trial registration
LOLA is registered at ClinicalTrials.gov (NCT04427787) and EudraCT (2019–004506-10).
Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2
Authors: Xu Yahong , Zhu Yongjie , Wu Zhenru , Li Shengfu , Shao Mingyang , Tao Qing , Xu Qing , Chen Yuwei , Shu Yuke , Chen Menglin , Zhou Yongjie , Shi Yujun 
Published: September 2023

Abstract
Background
Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages.

Methods
Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6−/−) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells.

Results
We observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC.

Conclusion
In summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.
Effectiveness of wheelchair skills training for improving manual wheelchair mobility in children and adolescents: protocol for a multicenter randomized waitlist-controlled trial
Authors: Best K. L. , Rushton P. W. , Sheriko J. , Arbour-Nicitopoulos K. P. , Dib T. , Kirby R. L. , Lamontagne M. E. , Moore S. A. , Ouellet B. , Routhier F. 
Published: September 2023

Abstract
Background
Self-directed mobility during childhood can influence development, social participation, and independent living later in life. For children who experience challenges with walking, manual wheelchairs (MWCs) provide a means for self-directed mobility. An effective MWC skills training program exists for adults, but controlled trials have not yet been documented in children and adolescents. This paper outlines the protocol for a multi-centre randomized wait-list controlled trial. The primary objective is to test the hypothesis that children and adolescents who receive MWC skills training will have higher MWC skills capacity compared to children and adolescents in the control group who receive usual care. The secondary objectives are to explore the influence of MWC skills training in children and adolescents (MWC use self-efficacy and satisfaction with participation in meaningful activities), and parents (perceived MWC skills); and to measure retention three months later.

Methods
A multi-centre, parallel-group, single-blind randomized wait-list controlled trial will be conducted. A sample of 60 children and adolescents who use MWCs will be recruited in rehabilitation centres, specialized schools, and the communities of three Canadian cities. Participants will be randomized (1:1) to the experimental (Wheelchair Skills Training Program [WSTP]) or wait-list control group (usual care). Performance-based and self-report measures will be completed at baseline (T1), three months (post-intervention, T2), and three months post-intervention (T3). The primary outcome will be MWC skills capacity post-intervention. Secondary outcomes will be MWC use self-efficacy and satisfaction with participation of the child/adolescent, and parent-perceived MWC skills. The WSTP will consist of 12 sessions, 45–60 min each, delivered 1–2 times per week by trained personnel with health professions education. Training will be customized according to the child’s baseline skills and participation goals that require the use of the MWC. The wait-list control group will receive usual care for 3 months and then receive the WSTP after completing T2 evaluations. Data will be analysed using ANCOVA (controlling for baseline scores).

Discussion
MWC skills training may be one way to improve self-directed mobility and related outcomes for children and adolescents. The results of this multi-centre randomized wait-list controlled trial will allow for the effectiveness of the intervention to be evaluated in a variety of clinical contexts and geographical regions.

Trial registration
ClinicalTrials.gov: NCT05564247, Version October 3, 2022.