bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response
Authors: Liu Long , Huang Yanping , Fu Yanan , Rao Jingjing , Zeng Feng , Ji Manshan , Xu Xiang , Zhu Jianyong , Du Weixing , Liu Zhixin 
Published: October 2022

Abstract
Background
Hepatitis B virus (HBV) causes acute and chronic infection in the clinic. Hepatocellular carcinoma (HCC) is closely linked to HBV infection. Serum Golgi protein 73 (GP73) increases during HBV infection. However, the role of GP73 during HBV infection and the occurrence of HBV-related HCC is still poorly understood.

Methods
The underlying role of HBV-induced GP73 in regulating HCC development was investigated in this study. GP73 expression in HBV-related clinical HCC tissues and in HBV-infected hepatoma cells and primary human hepatocytes was evaluated by immunohistochemistry, ELISAs, Western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tumorigenicity of GP73 overexpressed cells was detected by flow cytometry, qRT-PCR, xenograft nude mouse analyses and sphere formation assays. The effects of GP73 and HBV infection on host innate immune responses in hepatocytes were further investigated by Western blotting and qRT-PCR analysis.

Results
Initially, we confirmed that HBV-positive HCC tissues had significantly higher expression of GP73. Ectopic expression of the HBV gene could induce GP73 expression in primary human hepatocytes and hepatoma cells in vitro. In addition, we discovered that GP73 promotes HCC in both normal liver cells and hepatoma cells. We also found that ectopic expression of HBV genes increases GP73 expression, suppressing the host's innate immune responses in hepatocytes.

Conclusions
Our results demonstrate that HBV facilitates HCC development by activating GP73 to repress the host's innate immune response. This study adds to our understanding of the pathogenesis of HBV infection-induced HCC. The findings also provide preclinical support for GP73 as a potential HCC prevention or treatment target.
KAGE: fast alignment-free graph-based genotyping of SNPs and short indels
Authors: Grytten Ivar , Dagestad Rand Knut , Sandve Geir Kjetil 
Published: October 2022

AbstractGenotyping is a core application of high-throughput sequencing. We present KAGE, a genotyper for SNPs and short indels that is inspired by recent developments within graph-based genome representations and alignment-free methods. KAGE uses a pan-genome representation of the population to efficiently and accurately predict genotypes. Two novel ideas improve both the speed and accuracy: a Bayesian model incorporates genotypes from thousands of individuals to improve prediction accuracy, and a computationally efficient method leverages correlation between variants. We show that the accuracy of KAGE is at par with the best existing alignment-free genotypers, while being an order of magnitude faster.
Psychosocial stress induction in vivo vs. in virtuo and the influence of a health app on the acute stress reaction in youths: a study protocol for a randomized controlled trial
Authors: Schleicher Daniel , Ecker Angelika , Kocur Martin , Jarvers Irina , Nash Colin , Götz Leonie , Otto Alexandra H. , Kandsperger Stephanie , Brunner Romuald 
Published: October 2022

AbstractBackgroundAcute and everyday stress is substantial for the development of mental and physical diseases, therefore it is crucial to get a better understanding of its pathogenesis. Different methods (e.g., Ambulatory Assessment) and stress reactivity paradigms (e.g., Trier Social Stress Test / TSST) in laboratory settings are often used to investigate basic mechanisms of this process. Due to the technological progress of the last years and especially due to children and adolescents growing up with it, the application of these developments in clinical research is reasonable. The aim of this project is to successfully transfer the TSST for children and adolescents into the virtual world, which will be compared to a real TSST situation. Physiological and psychological stress reactions will be analyzed in order to assess similarities and differences. Moreover, it will be investigated whether a Heart Coherence Exercise (HCE) has a stronger influence on coping with acute stress compared to Natural Relaxation (NR).MethodsThis single-center experimental study will examine acute and everyday stress and coping processes in eighty-four healthy children and adolescents between the ages of 11 and 17. For everyday stress, different parameters (e.g., hormonal profiles and mood ratings) as well as a history of stressful life events and utilized coping methods will be recorded and a relaxation exercise will be practiced on a smartphone over 2 days. Regarding the acute stress reaction, the participants will be confronted either with the virtual or the real version of the TSST, followed by the trained relaxation exercise (HCE vs. NR). Physiological (e.g., cortisol and heart rate) and psychological stress markers (e.g., mood and gaze behavior) will be recorded continuously.DiscussionStudies are sparse using a virtual version of the TSST in children and adolescents. A successful virtual TSST would constitute an economical variant, which would also make it easier to administer it in clinical or population-based samples. Effective ambulatory relaxation exercises would be a useful addition to clinical treatment approaches.Trial registrationThe study is registered in the German Clinical Trials Register since 10 August 2020 (DRKS00022063).
Development of a measure to assess the quality of proxy decisions about research participation on behalf of adults lacking capacity to consent: the Combined Scale for Proxy Informed Consent Decisions (CONCORD scale)
Authors: Shepherd Victoria , Hood Kerenza , Gillies Katie , Wood Fiona 
Published: October 2022

Abstract
Background
Recruitment of adults lacking the capacity to consent to trials requires the involvement of an alternative ‘proxy’ decision-maker, usually a family member. This can be challenging for family members, with some experiencing emotional and decisional burdens. Interventions to support proxy consent decisions in non-emergency settings are being developed. However, the ability to evaluate interventions is limited due to a lack of measures that capture outcomes of known importance, as identified through a core outcome set (COS).

Methods
Using established measure development principles, a four-stage process was used to develop and refine items for a new measure of proxy decision quality: (1) findings from a recent scoping review and consensus study were reviewed to identify items for inclusion in the scale and any existing outcome measures, (2) assessment of content coverage by existing measures and identification of insufficiency, (3) construction of a novel scale, and (4) cognitive testing to explore comprehension of the scale and test its content adequacy through interviews with family members of people with impaired capacity.

Results
A range of outcome measures associated with healthcare decision-making and informed consent decisions, such as the Decisional Conflict Scale, were identified in the scoping review. These measures were mapped against the key constructs identified in the COS to assess content coverage. Insufficient coverage of areas such as proxy-specific satisfaction and knowledge sufficiency by existing instruments indicated that a novel measure was needed. An initial version of a combined measure (the CONCORD scale) was drafted and tested during cognitive interviews with eleven family members. The interviews established comprehension, acceptability, feasibility, and content adequacy of the scale. Participants suggested re-phrasing and re-ordering some questions, leading to the creation of a revised version.

Conclusions
The CONCORD scale provides a brief measure to evaluate the quality of decisions made on behalf of an adult who lacks the capacity to consent in non-emergency settings, enabling the evaluation of interventions to improve proxy decision quality. Initial evaluation indicates it has content adequacy and is feasible to use. Further statistical validation work is being undertaken.
Digital fetal scalp stimulation (dFSS) versus fetal blood sampling (FBS) to assess fetal wellbeing in labour—a multi-centre randomised controlled trial: Fetal Intrapartum Randomised Scalp Stimulation Trial (FIRSST NCT05306756)
Authors: Murphy D. J. , Shahabuddin Y. , Yambasu S. , O’Donoghue K. , Devane D. , Cotter A. , Gaffney G. , Burke L. A. , Molloy E. J. , Boland F. 
Published: October 2022

Abstract
Background
Cardiotocography (CTG) is a screening test used to detect fetal hypoxia in labour. It has a high false positive rate resulting in many potentially unnecessary caesarean sections. Fetal blood sampling (FBS) is a second-line test of the acid-base status of the fetus. It is used to provide either reassurance that it is safe for labour to continue or objective evidence of compromise so that delivery can be expedited. Digital fetal scalp stimulation (dFSS) to elicit a fetal heart rate acceleration is an alternative less invasive second-line test of fetal wellbeing. This study aims to provide robust evidence on the role of these two second-line tests in assessing fetal wellbeing and potentially preventing operative delivery.

Methods
A multi-centre parallel group randomised controlled trial (RCT) is planned in four maternity centres in Ireland. The study aims to recruit 2500 nulliparous women with a term (≥37+0 weeks) singleton pregnancy who require a second-line test of fetal wellbeing in labour due to an abnormal CTG. Women will be allocated randomly to dFSS or FBS on a 1:1 ratio. The primary outcome is caesarean section. With 1250 women in each arm, the study will have 90% power to detect a difference of 5–6%, at a two-sided alpha significance level of 5%, assuming a caesarean section rate of at least 20% in the dFSS group.

Discussion
If the proposed study shows evidence that dFSS is a safe, reliable and effective alternative to FBS, this would have ground-breaking implications for labour management worldwide. It could potentially lead to a reduction in invasive procedures and emergency caesarean sections.

Trial registration
ClinicalTrials.gov NCT05306756. Registered on 31 March 2022. The trial commenced enrolment on 10 May 2022. Ethical committee approval has been granted by the Research Ethics Committee (REC) of each hospital: Dublin/CWIUH REC: 12.06.2019; Cork/UCC REC: 29.11.2019; Galway/NUIG REC: 06.09.2019; Limerick/UL REC: 30.09.2019.
Development and evaluation of couple-based coping strategies with infertility: a protocol for a mixed-methods study
Authors: Reisi Marzie , Kazemi Ashraf , Abedi Mohammad Reza 
Published: October 2022

Abstract
Background
Different coping strategies have been associated with various effects on infertile couples’ mental health. Considering the close interaction between couples, the present study aims to develop coping strategies for infertile couples using a couple-based approach.

Methods
The present mixed-methods study will be conducted in three phases. In order to develop coping strategies, a qualitative study will be conducted in the first phase, during which semi-structured interviews will be implemented with infertile couples in order to collect data related to their lived experiences in using coping strategies. These data will be inductively analyzed using qualitative content analysis and interpretative phenomenological analysis. In the second phase, using the Delphi method, an initial draft of coping strategies will be designed using a couple-based approach based on the data obtained from the qualitative study and the related literature review. In the third phase, the designed couple-based strategies will be provided to two groups of infertile couples as a randomized field superiority trial study. The couples’ levels of stress, anxiety, depression, and adjustment will be evaluated using validated questionnaires before and 3 months after the intervention.

Discussion
Couple-based coping strategies encourage couples to become aware of each other’s feelings while interacting and choose a strategy based on such feelings.

Trial registration
Iranian Registry of Clinical Trials IRCT20191014045102N1. Registered on 19 October 2021. Protocol version: Current protocol: version 1 (22 May 2022)
Aseptic meningitis in multisystem inflammatory syndrome in children associated with coronavirus disease 2019: a case report
Authors: Keka-Sylaj Alije , Ramosaj Atifete , Baloku Arbana , Beqiraj Qëndresa , Gjaka Petrit 
Published: October 2022

Abstract
Background
As the coronavirus disease 2019 infections are still ongoing, there is an increasing number of case reports and case series with various manifestations of life-threatening multisystem inflammatory syndrome in children . Our case aims to remind all providers to scrutinize for clinical manifestations, including neurological symptoms, which may mimic aseptic meningitis.

Case presentation
A 5-year-old Albanian male child with obesity was admitted to the pediatric intensive care unit due to persistent fever, headache, vomiting, abdominal pain, mucocutaneous manifestations, and fatigue. Initial laboratory results revealed high level of inflammatory markers, including C-reactive protein of 156.8 mg/l, erythrocyte sedimentation rate of 100 mm/hour, procalcitonin of 13.84, leukocytosis with neutrophilia, and lymphopenia. Liver and renal functions, and capillary blood electrolytes (Na, K, Ca), were also altered. Cerebrospinal fluid was slightly turbid, with a white blood cell count of 128/mm3 (80% mononuclear cells and 20% polymorphonuclear), consistent with aseptic meningitis. The clinical presentation with prolonged fever, multiorgan dysfunction, and elevated inflammatory markers, with no plausible alternative diagnosis, matches the case definition of multisystem inflammatory syndrome in children. Combining corticosteroid methylprednisolone with intravenous immunoglobulin was effective.

Conclusions
Apart from the most common presentation of multisystem organ dysfunction, neurological manifestations of multisystem inflammatory syndrome in children such as aseptic meningitis, may be present as an immune response post-viral to coronavirus disease 2019. Given the rapid deterioration of children with multisystem inflammatory syndrome, early treatment with immunoglobulins and corticosteroids should be considered.
Combining Weibull distribution and k-nearest neighbor imputation method to predict wall-to-wall tree lists for the entire forest region of Northeast China
Authors: Fu Yuanyuan , He Hong S. , Wang Shaoqiang , Wang Lunche 
Published: October 2022

Abstract
Key message
We propose a coupled framework to combine the strengths of the Weibull function in modeling diameter distributions and the ability of the k-nearest neighbor (kNN) method to impute spatially continuous forest stand attributes for the prediction of wall-to-wall tree lists (lists of stems per hectare by species and diameter at breast height (DBH)) at regional scales. The tree lists of entire Northeast China’s forests predicted by the above framework reasonably reflect the species-specific tree density and diameter distributions.

Context
Detailed tree lists provide information about forest stocks disaggregated by species and size classes, which are crucial for forest managers to accurately characterize the current forest stand state to formulate targeted forest management strategies. However, regional tree list information is still lacking due to limited forest inventory.

Aims
We aimed to develop a coupled framework to enable the prediction of wall-to-wall tree lists for the entire forest region of Northeast China, then analyze the species-specific diameter distributions and reveal the spatial patterns of tree density by species.

Methods
A two-parameter Weibull function was used to model the species-specific diameter distributions in the sample plots, and a maximum likelihood estimation (MLE) was used to predict the parameters of the Weibull distributions. The goodness-of-fit of the predicted species-specific Weibull diameter distributions in each plot was evaluated by Kolmogorov-Smirnov (KS) test and an error index. The kNN model was used to impute the pixel-level stand mean DBH.

Results
Weibull distribution accurately described the species-specific diameter distributions. The imputed stand mean DBH from the kNN model showed comparable accuracy with earlier studies. No difference was detected between predicted and observed tree lists, with a small error index (0.24–0.58) of diameter distributions by species. The fitted species-specific diameter distributions generally showed a right-skewed unimodal or reverse J-shaped pattern.

Conclusion
Overall, the coupled framework developed in this study was well-suited for predicting the tree lists of large forested areas. Our results evidenced the spatial patterns and abundance of tree species in Northeast China and captured the forest regions affected by disturbances such as fire.
Effect of bioactive glass paste on efficacy and post-operative sensitivity associated with at-home bleaching using 20% carbamide peroxide: a randomized controlled clinical trial
Authors: Bizreh Yazan , Milly Hussam 
Published: October 2022

Abstract
Background
The aim of this study was to evaluate the effect of bioactive glass (BAG) 45S5 paste on colour change and tooth sensitivity (TS) when used in combination with 20% carbamide peroxide (CP) during at-home vital tooth bleaching.

Methods
Twenty-four patients were selected and assigned into two experimental groups (n = 12) in a double-blind study design. Each patient received 20% CP followed by the application of either BAG paste or non-active placebo paste. The shade evaluation was performed using a digital spectrophotometer based on the CIE L*a*b* colour space system at different time points and the overall colour changes ΔE were calculated. TS was evaluated using visual analogue scale (VAS). The values of ΔE and TS were statistically analysed using paired t-test. The level of statistical significance was established at p = 0.05.

Results
The overall colour changes (ΔE) between baseline and each time point showed no significant differences between BAG and placebo groups (p > 0.05). The use of BAG paste significantly decreased TS reported by the participants.

Conclusions
The association of BAG paste with at-home bleaching treatment presents a promising method as it decreased TS and did not deteriorate bleaching efficacy.
Trial registration This study was approved and registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) under Registration number: ACTRN12621001334897.
A framework proposal for resilience assessment in traditional commercial centres: case of the historical bazaar of bursa as a resilient world heritage site
Authors: Tlemsani Bozdağ Havva , Benabbou Rachida , Vural Arslan Tulin 
Published: October 2022

Abstract
Throughout history, the different cycles of change that traditional commercial centres (bazaars) have undergone in different Islamic cities call attention to the hidden abilities insuring their resilience until today. To understand the way in which these bazaar areas absorb and adapt to change, this paper investigates the resilience awareness of a specific case study ‘the bazaar of Bursa’, by dealing with key morphological, behavioural and institutional aspects. Several resilience assessment frameworks have been developed, including cultural, economic, and spatial proxies. However, most of them have focused on physical structures while assessing resilience concretely. This study represents a first step towards a Framework Proposal for resilience assessment in traditional commercial centres (bazaars) combining together tangible and intangible features specific to the historical bazaar of Bursa as a case study using a quantitative approach in a form of a survey. The findings showed a clear overlap between the tradesmen’s perception of factors affecting resilience in the bazaar of Bursa and those proposed by authors. This research may help decision-makers gain a better understanding of the key hidden factors promoting resilience in such historical urban fabrics and guide them in making adequate planning decisions in the future.
Blood flow restriction added to usual care exercise in patients with early weight bearing restrictions after cartilage or meniscus repair in the knee joint: a feasibility study
Authors: Jakobsen Thomas Linding , Thorborg Kristian , Fisker Jakob , Kallemose Thomas , Bandholm Thomas 
Published: October 2022

AbstractPurposeBlood flow restriction – low load strength training (BFR-LLST) is theoretically superior to traditional heavy strength training when rehabilitating patients who cannot heavily load tissues following surgery. The main purpose of this study was to examine the feasibility of BFR-LLST added to usual care exercise early after cartilage or meniscus repair in the knee joint.MethodsWe included 42 patients with cartilage (n = 21) or meniscus repair (n = 21) of the knee joint. They attended 9 weeks of BFR-LLST added to a usual care exercise program at an outpatient rehabilitation center. Outcome measures were assessed at different time points from four (baseline) to 26 weeks postoperatively and included adherence, harms, knee joint and thigh pain, perceived exertion, thigh circumference (muscle size proxy), isometric knee-extension strength, self-reported disability and quality of life.ResultsOn average, patients with cartilage or meniscus repair completed > 84% of the total BFR-LLST supervised sessions. Thirty-eight patients reported 146 adverse events of which none were considered serious. No decrease in thigh circumference or exacerbation of knee joint or quadriceps muscle pain of the operated leg was found in either group during the intervention period.ConclusionsBFR-LLST added to usual care exercise initiated early after cartilage or meniscus repair seems feasible and may prevent disuse thigh muscle atrophy during a period of weight bearing restrictions. Harms were reported, but no serious adverse events were found. Our findings are promising but need replication using a RCT-design.Trial registrationNCT03371901, preprint (open access): https://www.medrxiv.org/content/10.1101/2022.03.31.22272398v1