bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Space to hide’: experiences of remote provision across child and adolescent mental health services (CAMHS)
Authors: Worsley Joanne , Hassan Shaima , Nolan Lisa , Corcoran Rhiannon 
Published: November 2022

Abstract
Background
The global COVID-19 pandemic necessitated rapid adoption of remote provision across child and adolescent mental health services (CAMHS). The study aimed to understand young people’s, parents’/carers’, and professionals’ experiences of remote provision across CAMHS in one NHS Trust in the North West of England to inform future recovery practice so that remote sessions can continue where they have been well received but re-thought or replaced where they have not.

Methods
The study sample comprised three groups: (i) young people, (ii) parents/carers, and (iii) clinical staff. Semi-structured interviews and focus groups were used to collect data. Data were analysed using thematic analysis.

Results
Three overarching themes were identified: ‘Remote therapeutic experiences’; ‘Spaces and places of therapy’; and ‘Future of CAMHS’. Although remote appointments increased flexibility within the service, the quality of the relational experience was altered, typically for the worse. Clinicians felt less able to examine vital forms of non-verbal communication, which were considered instrumental in assessing and engaging people experiencing difficulties, leaving some questioning their professionalism. Although some young people suggested that remote provision increased comfort levels, others felt their place of comfort and safety was invaded.

Conclusions
Reduced travel time for both clinicians and families may increase capacity, enabling the service to meet the increased demand if clinical effectiveness can be preserved. In considering future models of provision, assessing clinical need, patient and family preference, and access to space and hardware are all critical when deciding which modality to use for the best outcomes for each individual.
Hepatitis B virus suppresses complement C9 synthesis by limiting the availability of transcription factor USF-1 and inhibits formation of membrane attack complex: implications in disease pathogenesis
Authors: Baidya Ayana , Khatun Mousumi , Mondal Rajiv Kumar , Ghosh Suchandrima , Chakraborty Bidhan Chandra , Mallik Shreya , Ahammed S. K. Mahiuddin , Chowdhury Abhijit , Banerjee Soma , Datta Simanti 
Published: November 2022

Abstract
Background
The complement system functions primarily as a first-line host defense against invading microbes, including viruses. However, the interaction of Hepatitis B virus (HBV) with the complement-components during chronic HBV infection remains largely unknown. We investigated the mechanism by which HBV inhibits the formation of cytolytic complement membrane-attack complex (MAC) and studied its impact on MAC-mediated microbicidal activity and disease pathogenesis.

Methods
Blood/liver tissues were collected from chronically HBV-infected patients and controls. HepG2hNTCP cells were infected with HBV particles and Huh7 cells were transfected with full-length linear HBV-monomer or plasmids containing different HBV-ORFs and expression of complement components or other host genes were evaluated. Additionally, ELISA, Real-time PCR, Western blot, bioinformatics analysis, gene overexpression/knock-down, mutagenesis, chromatin immunoprecipitation, epigenetic studies, immunofluorescence, and quantification of serum HBV-DNA, bacterial-DNA and endotoxin were performed.

Results
Among the MAC components (C5b-C9), significant reduction was noted in the expression of C9, the major constituent of MAC, in HBV-infected HepG2hNTCP cells and in Huh7 cells transfected with full-length HBV as well as HBX. C9 level was also marked low in sera/liver of chronic hepatitis B (CHB) and Immune-tolerant (IT) patients than inactive carriers and healthy controls. HBX strongly repressed C9-promoter activity in Huh7 cells but CpG-island was not detected in C9-promoter. We identified USF-1 as the key transcription factor that drives C9 expression and demonstrated that HBX-induced hypermethylation of USF-1-promoter is the leading cause of USF-1 downregulation that in turn diminished C9 transcription. Reduced MAC formation and impaired lysis of HBV-transfected Huh7 and bacterial cells were observed following incubation of these cells with C9-deficient CHB sera but was reversed upon C9 supplementation. Significant inverse correlation was noted between C9 concentration and HBV-DNA, bacterial-DNA and endotoxin content in HBV-infected patients. One-year Tenofovir therapy resulted in improvement in C9 level and decline in viral/bacterial/endotoxin load in CHB patients.

Conclusion
Collectively, HBX suppressed C9 transcription by restricting the availability of USF-1 through hypermethylation of USF-1-promoter and consequently hinder the formation and lytic functions of MAC. Early therapy is needed for both CHB and IT to normalize the aberrant complement profile and contain viral and bacterial infection and limit disease progression.
The impact of sleep–wake problems on health-related quality of life among Japanese nursing college students: a cross sectional survey
Authors: Adachi Mai , Nagaura Yuki , Eto Hiromi , Kondo Hideaki , Kato Chiho 
Published: November 2022

Abstract
Aim
This study was conducted to examine the impact of sleep–wake problems on health-related quality of life of Japanese nursing college students.

Methods
This cross-sectional study was conducted in 2019 on 150 third and fourth-year nursing college students from two locations in Japan. Insomnia severity was assessed using the Insomnia Severity Index (ISI) and health-related quality of life using the SF-8 questionnaire. The total sleep time (TST) was divided into 3 groups: < 6 h, 6–7 h (reference), and ≥ 7 h. The total ISI score was divided into 2 groups: ≥ 8 points and < 8 points (reference). Logistic regression analysis was performed to evaluate sleep–wake problems related to decline in mental health.

Results
The median mental health indicated in the SF-8 questionnaire was divided into two groups, and the factors causing decline in mental health were investigated. The odds ratios (95% confidence interval) for adjusted ISI ≥ 8 and TST on weekdays < 6 h was 6.51 (2.96–14.30) and 3.38 (1.40–8.17), respectively. Mental health status was significantly lower when ISI ≥ 8 and even lower when TST < 6 h.

Conclusion
Insomnia and short sleep duration are associated with decreased mental health status in nursing college students. Many tended to lack sleep on weekdays. Sleep–wake problems identified while in university should be comprehensively dealt with.
Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism
Authors: Wang Ziran , Kong Lingjun , Luo Guoju , Zhang Han , Sun Fengchun , Liang Wenjuan , Wu Wei , Guo Zijian , Zhang Rui , Dou Yaling 
Published: November 2022

Abstract
Background
Venous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE.

Methods
A total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously.

Results
The TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group.

Conclusion
The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.
Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study
Authors: van Straalen Joeri W. , de Roock Sytze , Giancane Gabriella , Consolaro Alessandro , Rygg Marite , Nordal Ellen B. , Rubio-Pérez Nadina , Jelusic Marija , De Inocencio Jaime , Vojinovic Jelena , Wulffraat Nico M. , Bruijning-Verhagen Patricia C. J. , Ruperto Nicolino , Swart Joost F. ,   for the Paediatric Rheumatology International Trials Organisation (PRINTO), Pallotti Chiara , Scala Silvia , Angioloni Simona , Villa Luca 
Published: November 2022

Abstract
Background
Etanercept (ETN) and adalimumab (ADA) are considered equally effective biologicals in the treatment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a differential effect on patient-reported well-being in non-systemic JIA using real-world data.

Methods
Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3–12 months afterwards. Primary outcome at follow-up was the improvement in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed effects models.

Results
Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched resulting in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (interquartile range (IQR): 0.0 – 4.0) and scores were significantly better (P = 0.01) for ETN starters (median 0.0, IQR: 0.0 – 1.0) compared to ADA starters (median 1.0, IQR: 0.0 – 3.5). The estimated mean difference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 – 1.78; P = 0.06). The estimated mean difference in active joint count decrease was -0.36 (95% CI: -1.02 – 0.30; P = 0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 –1.44; P = 0.19). One uveitis event was observed in the ETN group.

Conclusions
Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger effect for ETN, but larger studies are needed to confirm this given the lack of statistical significance.
Socio-demographic factors associated with medication adherence among People Living with HIV in the Kumasi Metropolis, Ghana
Authors: Adu Collins , Mensah Kofi Akohene , Ahinkorah Bright Opoku , Osei Dorothy , Tetteh Andrews William , Seidu Abdul-Aziz 
Published: November 2022

Abstract
Background
Medication adherence is important to the survival of People Living with HIV (PLHIV) globally. Although, HIV viral load is reduced by antiretroviral therapy (ART), the number of people on ART continues to rise in Ghana. In the Kumasi Metropolis, Ghana, we looked at the socio-demographic factors associated with medication adherence among PLHIV.

Methods
A quantitative study involving 420 PLHIV who sought healthcare at the Kumasi South Regional Hospital was conducted utilizing a cross-sectional study design. We employed a structured questionnaire to collect data on medication adherence using the eight-item Morisky Medication Adherence Scale (MMAS) and socio-demographic factors that influence medication adherence. The data were analysed using Stata 14.2. Frequencies and percentages were used to present the descriptive data. The association between socio-demographic factors and medication adherence among PLHIV was investigated using both univariate and multivariate analyses.

Results
More than half (53.10%) of PLHIV adhered to ART. Place of residence was significantly established to be influencing medication adherence among PLHIV. PLHIV who were residing in urban centers (aOR = 3.61; CI = 2.24–5.82) were more likely to adhere to medication as compared to those who resided in rural areas.

Conclusion
Slightly more than half of PLHIV took their medicines as prescribed. Government and Policymakers such as the Ghana AIDS Commission, Ministry of Health, and Ghana Health Service should incorporate socio-demographic factors such as place of residence while creating and executing medication adherence initiatives to evaluate HIV management regimen for PLHIV.
Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy
Authors: Rühle Alexander , Todorovic Jovan , Spohn Simon S. K. , Gkika Eleni , Becker Christoph , Knopf Andreas , Zamboglou Constantinos , Sprave Tanja , Werner Martin , Grosu Anca-Ligia , Kayser Gian , Nicolay Nils H. 
Published: November 2022

Abstract
Background and purpose
Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population.

Material and methods
Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses.

Results
While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels.

Conclusion
LAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC.
Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial
Authors: Imbard Apolline , Toumazi Artemis , Magréault Sophie , Garcia-Segarra Nuria , Schlemmer Dimitri , Kaguelidou Florentia , Perronneau Isabelle , Haignere Jérémie , de Baulny Hélène Ogier , Kuster Alice , Feillet François , Alberti Corinne , Guilmin-Crépon Sophie , Benoist Jean-François , Schiff Manuel 
Published: November 2022

Abstract
Background
Betaine is an “alternate” methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidney. Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients.

Aims
We compared 2 betaine doses (100 mg/kg/day vs. 250 mg/kg/day) in children affected by pnrCBS or cblC deficiencies. We also measured the pharmacokinetics parameters after a single dose of betaine (100 or 250 mg/kg) in these patients.

Methods
We conducted a prospective, randomized, crossover clinical trial with blinded evaluation. The primary outcome was the equivalence of total plasma homocysteine (tHcy) concentrations upon one-month oral treatment with betaine at 100 versus 250 mg/kg/day.

Results
Eleven patients completed the study (5 pnrCBS and 6 cblC). tHcy concentrations were equivalent after a one-month treatment period for the two betaine dosages. Multivariate analysis showed a significant effect of betaine dose on methionine (Met) (p = 0.01) and S-adenosylmethionine (SAM) concentrations (p = 0.006).

Conclusions
Our analysis shows that there is no overt benefit to increasing betaine dosage higher than 100 mg/kg/day to lower tHcy concentrations in pnrCBS and cblC deficiencies. However, increasing betaine up to 250 mg/kg/d could benefit cblC patients through the increase of methionine and SAM concentrations, as low Met and SAM concentrations are involved in the pathophysiology of this disease. In contrast, in pnrCBS deficiency, betaine doses higher than 100 mg/kg/day could be harmful to these patients with pre-existing hypermethioninemia.
Trial registration: Clinical Trials, NCT02404337. Registered 23 May 2015—prospectively registered, https://clinicaltrials.gov.
Microbiome insights into pediatric familial adenomatous polyposis
Authors: Attard Thomas M. , Septer Seth , Lawson Caitlin E. , Attard Mark I. , Lee Sonny T. M. , Umar Shahid 
Published: November 2022

Abstract
Background
Individuals with familial adenomatous polyposis (FAP) harbor numerous polyps with inevitable early progression to colon cancer. Complex microbiotic-tumor microenvironment perturbations suggest a dysbiotic relationship between polyp and microbiome. In this study, we performed comprehensive analyses of stool and tissue microbiome of pediatric FAP subjects and compared with unaffected cohabiting relatives through 16S V4 region amplicon sequencing and machine learning platforms.

Results
Within our FAP and control patient population, Firmicutes and Bacteroidetes were the predominant phyla in the tissue and stool samples, while Proteobacteria dominated the polyp/non-polyp mucosa. A decline in Faecalibacterium in polyps contrasted with a decline in Bacteroides in the FAP stool. The alpha- and beta-diversity indices differed significantly within the polyp/non-polyp groups, with a concurrent shift towards lower diversity in polyps. In a limited 3-year longitudinal study, the relative abundance of Proteobacteria and Fusobacteria was higher in polyps compared to non-polyp and stool specimens over time. Through machine learning, we discovered that Archaeon_enrichment_culture_clone_A13, Micrococcus_luteus, and Eubacterium_hallii in stool and PL-11B10, S1-80, and Blastocatellaceae in tissues were significantly different between patients with and without polyps.

Conclusions
Detection of certain bacterial concentrations within stool or biopsied polyps could serve as adjuncts to current screening modalities to help identify higher-risk patients.
metaMIC: reference-free misassembly identification and correction of de novo metagenomic assemblies
Authors: Lai Senying , Pan Shaojun , Sun Chuqing , Coelho Luis Pedro , Chen Wei-Hua , Zhao Xing-Ming 
Published: November 2022

AbstractEvaluating the quality of metagenomic assemblies is important for constructing reliable metagenome-assembled genomes and downstream analyses. Here, we present metaMIC (https://github.com/ZhaoXM-Lab/metaMIC), a machine learning-based tool for identifying and correcting misassemblies in metagenomic assemblies. Benchmarking results on both simulated and real datasets demonstrate that metaMIC outperforms existing tools when identifying misassembled contigs. Furthermore, metaMIC is able to localize the misassembly breakpoints, and the correction of misassemblies by splitting at misassembly breakpoints can improve downstream scaffolding and binning results.
Bioactive isopimarane and 3,4-seco isopimarane diterpenoids from Isodon amethystoides
Authors: Zhao Chenliang , Zhou Lang , Xie Wenjian , Zhao Lihan , Zhang Chiyuan , He Kang , Ye Jianghai , Zhang Jingjie , Pan Lutai , Zou Juan , Zhang Hongjie 
Published: November 2022

AbstractIsodon amethystoides (Lamiaceae) is a popular plant in folk medicine in the southern provinces of China. Our phytochemical investigation of the twigs and leaves of this plant led to the discovery of five new diterpenoids with isopimarane and 3,4-seco isopimarane scaffolds [isoamethinols A–E (1–5)], along with the known compound 3,4-seco isopimara-4(18),7,15-triene-3-oic acid methylester (6). The chemical structures of these compounds, including the absolute configurations of the new diterpenoids, were determined by comprehensive spectroscopic analyses and single crystal X-ray diffraction measurements. These compounds were evaluated for their biological activities against a panel of human cancer cell lines, gram-positive bacterial strains and HIV. Notably, the 3,4-seco-isopimarane isoamethinol D (4) showed toxicity to the cervical Hela cancer (Hela) cells with an IC50 value of 27.21 μM and the lung (A549) cancer cells with an IC50 value of 21.47 μM. Compound 4 also exhibited mild antimicrobial activity against the oral bacterial strain Streptococcus mutans. These findings suggested that the diterpenoids with a 3,4-seco-isopimarane diterpenoids isolated from I. amethystoides could provide a novel structure scaffold for the discovery of anticancer and antimicrobial compounds.
Graphical Abstract