bluuebunny/crossref_metadata_2025 huggingface dataset:
A high-quality Buxus austro-yunnanensis (Buxales) genome provides new insights into karyotype evolution in early eudicots
Authors: Wang Zhenyue , Li Ying , Sun Pengchuan , Zhu Mingjia , Wang Dandan , Lu Zhiqiang , Hu Hongyin , Xu Renping , Zhang Jin , Ma Jianxiang , Liu Jianquan , Yang Yongzhi
Published: October 2022

Background

Eudicots are the most diverse group of flowering plants that compromise five well-defined lineages: core eudicots, Ranunculales, Proteales, Trochodendrales, and Buxales. However, the phylogenetic relationships between these five lineages and their chromosomal evolutions remain unclear, and a lack of high-quality genome analyses for Buxales has hindered many efforts to address this knowledge gap.

Results

Here, we present a high-quality chromosome-level genome of Buxus austro-yunnanensis (Buxales). Our phylogenomic analyses revealed that Buxales and Trochodendrales are genetically similar and classified as sisters. Additionally, both are sisters to the core eudicots, while Ranunculales was found to be the first lineage to diverge from these groups. Incomplete lineage sorting and hybridization were identified as the main contributors to phylogenetic discordance (34.33%) between the lineages. In fact, B. austro-yunnanensis underwent only one whole-genome duplication event, and collinear gene phylogeny analyses suggested that separate independent polyploidizations occurred in the five eudicot lineages. Using representative genomes from these five lineages, we reconstructed the ancestral eudicot karyotype (AEK) and generated a nearly gapless karyotype projection for each eudicot species. Within core eudicots, we recovered one common chromosome fusion event in asterids and malvids, respectively. Further, we also found that the previously reported fused AEKs in Aquilegia (Ranunculales) and Vitis (core eudicots) have different fusion positions, which indicates that these two species have different karyotype evolution histories.

Conclusions

Based on our phylogenomic and karyotype evolution analyses, we revealed the likely relationships and evolutionary histories of early eudicots. Ultimately, our study expands genomic resources for early-diverging eudicots.
An association study of IL2RA polymorphisms with cerebral palsy in a Chinese population
Authors: Qiao Yimeng , Wang Yangong , Xu Yiran , Zhang Jin , Su Yu , Cheng Ye , Bi Dan , Song Juan , Xia Lei , Li Ming , Zhang Xiaoli , Zhu Dengna , Wang Ting , Ding Jian , Wang Xiaoyang , Zhu Changlian , Xing Qinghe
Published: October 2022

Background

Cerebral palsy (CP), the most common physical disability of childhood, is a nonprogressive movement disorder syndrome. Eighty percent of cases are considered idiopathic without a clear cause. Evidence has shown that cytokine abnormalities are widely thought to contribute to CP.

Methods

An association between 6 SNPs (rs12244380, rs2025345, rs12722561, rs4749926, rs2104286 and rs706778) in IL2RA (interleukin 2 receptor subunit alpha) and CP was investigated using a case–control method based on 782 CP cases and 778 controls. The allele, genotype and haplotype frequencies of SNPs were assessed using the SHEsis program. Subgroup analyses based on complications and clinical subtypes were also conducted.

Results

Globally, no differences in genotype or allele frequencies for any SNPs remained significant after Bonferroni correction between patients and controls, except rs706778, which deviated from Hardy–Weinberg equilibrium and was excluded from further analyses. However, subgroup analysis revealed a significant association of rs2025345 with spastic tetraplegia (P genotype = 0.048 after correction) and rs12722561 with CP accompanied by global developmental delay (P allele = 0.045 after correction), even after Bonferroni correction.

Conclusions

These findings indicated that genetic variations in IL2RA are significantly associated with CP susceptibility in the Chinese Han population, suggesting that IL2RA is likely involved in the pathogenesis of CP. Further investigation with a larger sample size in a multiethnic population is needed to confirm the association.
Identification of a HOXD13 variant in a Mongolian family with incomplete penetrance syndactyly by exon sequencing
Authors: Husile Husile , Wu Zhifeng , Yang Liqing , Cao Yaning , Wu Qizhu
Published: October 2022

Background

Syndactyly (SD) refers to a deformity caused by the fusion and limb differentiation disorder of soft tissues and/or skeletons to varying extents between adjacent fingers (toes). The main features of this disease are phenotypic heterogeneity and genetic heterogeneity. In this study, we examined four generations of a Chinese Mongolian with different phenotypes of syndactylia and analysed and identified the pathogenic genetic variants of SD by exon sequencing.

Methods

The clinical phenotypes of patients were analysed, and the hands and feet were examined by X-ray. The pedigree was drawn, and the family data were analysed. Peripheral blood was collected from the family members, and genomic DNA was extracted. The candidate genes of SD were identified by exon sequencing, and the mutation sites of the captured candidate genes were amplified by PCR and verified by Sanger sequencing.

Results

The family has congenital syndactyly, which is an autosomal dominant disease. At present, this condition has been passed down for 4 generations and was identified in 9 patients, including 4 males and 5 females. Five patients, I2, II4, III5, III,7and III10, had unilateral syndactyly, and four patients, III16, IV3, IV6and IV7, had bilateral finger syndactyly. All of their toes were unaffected. The proband and the other patients in this family had a c.917G > A (p.R306Q) mutation, which is located at position 917 of the second exon of theHOXD13gene. This mutation results in a change in the amino acid at position 306, in which arginine is changed to glutamine. This mutation cosegregates in unaffected individuals and affected patients in this family. Moreover, 201 Mongolian genome databases and a thousand human genome databases were referenced to further confirm that the pathogenic genetic variant that causes syndactyly in this family is found inHOXD13.

Conclusion

This study found that the mutation site of the pathogenic gene in this family wasHOXD13, c.917G > A (p.R306Q). The phenotype of the family member III12was normal, but this member was also a carrier of the pathogenic genetic variant. This indicates that the disease of this family has incomplete penetrance characteristics. Our results further enrich the expression profile of theHOXD13gene.
Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy
Authors: Mao Liang , Li Yun-Da , Chen Ruo-Lan , Li Gang , Zhou Xiao-Xia , Song Fei , Wu Chan , Hu Yu , Hong Yi-Xiang , Dang Xitong , Li Gui-Rong , Wang Yan
Published: October 2022

Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of β-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.
Platelet membrane-camouflaged nanoparticles carry microRNA inhibitor against myocardial ischaemia‒reperfusion injury
Authors: Wang Tianyi , Zhou Tingting , Xu Mingming , Wang Shuo , Wu Anqi , Zhang Mingyang , Zhou You Lang , Shi Jiahai
Published: October 2022

The incidence of myocardial ischaemia‒reperfusion injury (MIRI) is increasing every year, and there is an urgent need to develop new therapeutic approaches. Nrf2 is thought to play a protective role during MIRI and it is regulated by microRNAs (miRNAs). This study focused on PLGA nanoparticles camouflaged by platelet membrane vesicles (PMVs) (i.e., PMVs@PLGA complexes) carrying microRNA inhibitors, which regulate Nrf2 and can play a therapeutic role in the MIRI process. In vitro and in vivo characterization showed that PMVs@PLGA has excellent transfection efficiency, low toxicity and good targeting. MicroRNAs that effectively regulate Nrf2 were identified, and then PMVs@PLGA-miRNA complexes were prepared and used for in vitro and in vivo treatment. PMVs@PLGA-miRNA complexes can effectively target the delivery of inhibitors to cardiomyocytes. Our results suggest that PMVs@PLGA complexes are a novel delivery system and a novel biological approach to the treatment of MIRI.
Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection
Authors: Yang Rui , Zhang Yunshan , Liang Xiaoyan , Song Xueru , Wei Zhaolian , Liu Jianqiao , Yang Yezhou , Tan Jichun , Zhang Qingxue , Sun Yingpu , Wang Wei , Qian Weiping , Jin Lei , Wang Shuyu , Xu Yang , Yang Jing , Goethberg Marie , Mannaerts Bernadette , Wu Wen , Zheng Zugeng , Qiao Jie
Published: October 2022

Background

To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. 

Methods

This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20–40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10–11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%).

Results

378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3—11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa.

Conclusion

Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.

Clinical trial registration number

NCT03296527.
Sociodemographic differences in 24-hour time-use behaviours in New Zealand children
Authors: Hedayatrad Leila , Stewart Tom , Paine Sarah-Jane , Marks Emma , Walker Caroline , Duncan Scott
Published: October 2022

Background

The time that children spend in physical activity, sedentary behaviour, and sleep each day (i.e., 24-h time-use behaviours), is related to physical and mental health outcomes. Currently, there is no comprehensive evidence on New Zealand school-aged children’s 24-h time-use behaviours, adherence to the New Zealand 24-h Movement Guidelines, and how these vary among different sociodemographic groups.

Methods

This study utilises data from the 8-year wave of the Growing Up in New Zealand longitudinal study. Using two Axivity AX3 accelerometers, children’s 24-h time-use behaviours were described from two perspectives: activity intensity and activity type. Compositional data analysis techniques were used to explore the differences in 24-h time-use compositions across various sociodemographic groups.

Results

Children spent on average, 31.1%, 22.3%, 6.8%, and 39.8% of their time in sedentary, light physical activity, moderate-to-vigorous physical activity, and sleep, respectively. However, the daily distribution of time in different activity types was 33.2% sitting, 10.8% standing, 7.3% walking, 0.4% running, and 48.2% lying. Both the activity intensity and activity type compositions varied across groups of child ethnicity, gender, and household income or deprivation.

The proportion of children meeting each of the guidelines was 90% for physical activity, 62.5% for sleep, 16% for screen time, and 10.6% for the combined guidelines. Both gender and residence location (i.e., urban vs. rural) were associated with meeting the physical activity guideline, whereas child ethnicity, mother’s education and residence location were associated with meeting the screen time guideline. Child ethnicity and mother’s education were also significantly associated with the adherence to the combined 24-h Movement Guidelines.

Conclusions

This study provided comprehensive evidence on how New Zealand children engage in 24-h time-use behaviours, adherence to the New Zealand 24-h Movement Guidelines, and how these behaviours differ across key sociodemographic groups. These findings should be considered in designing future interventions for promoting healthy time-use patterns in New Zealand children.
Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis
Authors: Hu Xinli , Zhang Haojie , Zhang Qianxin , Yao Xue , Ni Wenfei , Zhou Kailiang
Published: October 2022

Stimulator of interferons genes (STING), which is crucial for the secretion of type I interferons and proinflammatory cytokines in response to cytosolic nucleic acids, plays a key role in the innate immune system. Studies have revealed the participation of the STING pathway in unregulated inflammatory processes, traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid haemorrhage (SAH) and hypoxic–ischaemic encephalopathy (HIE). STING signalling is markedly increased in CNS injury, and STING agonists might facilitate the pathogenesis of CNS injury. However, the effects of STING-regulated signalling activation in CNS injury are not well understood. Aberrant activation of STING increases inflammatory events, type I interferon responses, and cell death. cGAS is the primary pathway that induces STING activation. Herein, we provide a comprehensive review of the latest findings related to STING signalling and the cGAS–STING pathway and highlight the control mechanisms and their functions in CNS injury. Furthermore, we summarize and explore the most recent advances toward obtaining an understanding of the involvement of STING signalling in programmed cell death (autophagy, necroptosis, ferroptosis and pyroptosis) during CNS injury. We also review potential therapeutic agents that are capable of regulating the cGAS–STING signalling pathway, which facilitates our understanding of cGAS–STING signalling functions in CNS injury and the potential value of this signalling pathway as a treatment target.
Accuracy and comparison of sensor-based gait speed estimations under standardized and daily life conditions in children undergoing rehabilitation
Authors: Rast Fabian Marcel , Aschwanden Seraina , Werner Charlotte , Demkó László , Labruyère Rob
Published: October 2022

Background

Gait speed is a widely used outcome measure to assess the walking abilities of children undergoing rehabilitation. It is routinely determined during a walking test under standardized conditions, but it remains unclear whether these outcomes reflect the children's performance in daily life. An ankle-worn inertial sensor provides a usable opportunity to measure gait speed in the children's habitual environment. However, sensor-based gait speed estimations need to be accurate to allow for comparison of the children's gait speed between a test situation and daily life. Hence, the first aim of this study was to determine the measurement error of a novel algorithm that estimates gait speed based on data of a single ankle-worn inertial sensor in children undergoing rehabilitation. The second aim of this study was to compare the children’s gait speed between standardized and daily life conditions.

Methods

Twenty-four children with walking impairments completed four walking tests at different speeds (standardized condition) and were monitored for one hour during leisure or school time (daily life condition). We determined accuracy by comparing sensor-based gait speed estimations with a reference method in both conditions. Eventually, we compared individual gait speeds between the two conditions.

Results

The measurement error was 0.01 ± 0.07 m/s under the standardized and 0.04 ± 0.06 m/s under the daily life condition. Besides, the majority of children did not use the same speed during the test situation as in daily life.

Conclusion

This study demonstrates an accurate method to measure children's gait speed during standardized walking tests and in the children's habitual environment after rehabilitation. It only requires a single ankle sensor, which potentially increases wearing time and data quality of measurements in daily life. We recommend placing the sensor on the less affected side, unless the child wears one orthosis. In this latter case, the sensor should be placed on the side with the orthosis. Moreover, this study showed that most children did not use the same speed in the two conditions, which encourages the use of wearable inertial sensors to assess the children's walking performance in their habitual environment following rehabilitation.
One-stop computerized virtual planning system for the surgical management of posterior wall acetabular fractures
Authors: Chen Jianan , Zheng Yifan , Fang Zhixun , Zhou Wei , Xu Dan , Wang Guodong , Cai Xianhua , Liu Ximing
Published: October 2022

Background

Posterior wall acetabular fractures remain one of the most difficult fracture injuries to treat. Accurate assessment of fracture characteristics and appropriate preoperative surgical strategies are essential for excellent reduction. This paper evaluates the feasibility and effectiveness of a one-stop computerized virtual planning system for the surgical management of posterior wall acetabular fractures.

Methods

52 cases of posterior wall acetabular fractures treated surgically were selected in our department between January 2015 and December 2020 for retrospective analysis. 52 cases were classified into group A (25 patients) and group B (27 patients) according to whether computerized virtual planning procedures were performed preoperatively. In group A, virtual surgical simulation was conducted using a one-stop computerized planning system preoperatively. In group B, traditional surgery was employed. Reduction quality, surgical time, blood loss, hip function, complications, and instrumentation time were compared between the two groups.

Results

The actual surgery for all patients in group A was essentially the same as the virtual surgery before the operation. Compared to group B, patients in group A had markedly shorter surgical time (−43 min), shorter instrumentation time (−20 min), and less intraoperative blood loss (−130 ml). However, no significant statistical difference was observed in reduction quality and hip function. The complication rate was slightly lower in group A (4/25) than in group B (7/27), without a significant difference.

Conclusion

The one-stop computerized virtual planning system is a highly effective, user-friendly and educational tool for allowing the cost-efficient surgical simulation of posterior wall acetabular fractures and providing a more individualized therapeutic schedule. The one-stop computerized planning system is feasible to treat posterior wall acetabular fractures, which is an effective method than the conventional treatment of posterior wall acetabular fractures.

Trial registration: retrospective registration.
Metabolic profiling and pharmacokinetic studies of Baihu-Guizhi decoction in rats by UFLC-Q-TOF–MS/MS and UHPLC-Q-TRAP-MS/MS
Authors: He Yan , Zhou Zhenkun , Li Weijie , Zhang Yanqiong , Shi Ruoyao , Li Tao , Jin Linlin , Yao Hongliang , Lin Na , Wu Hao
Published: October 2022

Background

Baihu-Guizhi decoction (BHGZD) is a well-documented traditional Chinese Medicine (TCM) prescription that has been extensively applied to treating rheumatoid arthritis. Despite of its beneficial outcomes, the chemical constituents of BHGZD have not been fully portrayed and the in vivo absorption, distribution, metabolism, and excretion (ADME) patterns of absorbed components have never been described.

Methods

Characterization of absorbed components and in vivo biotransformation profiling of these feature compounds were based on the ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Furthermore, the ultra-high-performance liquid chromatography tandem ion trap quadrupole mass spectrometry (UHPLC-Q-TRAP-MS/MS) system were performed to investigate the pharmacokinetics of active ingredients from BHGZD.

Results

In this study, we have identified and tentatively characterized 18 feature absorbed prototype and 15 metabolites of BHGZD in rat serum and the in vivo transformation pathways of these absorbed constituents were proposed. Besides, we have established novel quantitative methodology of five crucial components of BHGZD and have monitored the pharmacokinetic behaviors of these constituents spontaneously in rat serum after BHGZD gavage. After rats received two ways of BHGZD gavage, the pharmacokinetic behaviors of each compound exhibited relatively similar behaviors, as evidenced by similar curve track as well as relatively close time to reach maximum concentration (Tmax) and half washout time (T1/2). Whereas the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) values of five analytes with multiple dosage were a bit higher than single dosage.

Conclusion

This study added knowledge into the material basis and bio-transformation patterns of BHGZD in vivo, which would be of great value for exploring pharmacological effects and mechanism of BHGZD.
Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy
Authors: Eichler F. , Sevin Caroline , Barth M. , Pang F. , Howie K. , Walz M. , Wilds A. , Calcagni C. , Chanson C. , Campbell L.
Published: October 2022

Background

Metachromatic leukodystrophy (MLD), a relentlessly progressive and ultimately fatal condition, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA). Historically management has been palliative or supportive care. Hematopoietic stem cell transplantation is poorly effective in early-onset MLD and benefit in late-onset MLD remains controversial. Hematopoietic stem cell gene therapy, Libmeldy (atidarsagene autotemcel), was recently approved by the European Medicines Agency for early-onset MLD. Treatment benefit is mainly observed at an early disease stage, indicating the need for early diagnosis and intervention. This study contributes insights into the caregiver language used to describe initial MLD symptomatology, and thereby aims to improve communication between clinicians and families impacted by this condition and promote a faster path to diagnosis.

Results

Data was collected through a moderator-assisted online 60-min survey and 30-min semi-structured follow-up telephone interview with 31 MLD caregivers in the United States (n = 10), France (n = 10), the United Kingdom (n = 5), and Germany (n = 6). All respondents were primary caregivers of a person with late infantile (n = 20), juvenile (n = 11) or borderline late infantile/juvenile (n = 1) MLD (one caregiver reported for 2 children leading to a sample of 32 individuals with MLD). Caregivers were asked questions related to their child’s initial signs and symptoms, time to diagnosis and interactions with healthcare providers. These results highlight the caregiver language used to describe the most common initial symptoms of MLD and provide added context to help elevate the index of suspicion of disease. Distinctions between caregiver descriptions of late infantile and juvenile MLD in symptom onset and disease course were also identified.

Conclusions

This study captures the caregiver description of the physical, behavioral, and cognitive signs of MLD prior to diagnosis. The understanding of the caregiver language at symptom onset sheds light on a critical window of often missed opportunity for earlier diagnosis and therapeutic intervention in MLD.
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

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

Genotyping 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

Background

Acute 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).

Methods

This 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.

Discussion

Studies 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 registration

The 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

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

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

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

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

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

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

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.