bluuebunny/crossref_metadata_2025_split huggingface dataset:
Training and expertise in undertaking assisted vaginal delivery (AVD): a mixed methods systematic review of practitioners views and experiences
Authors: Feeley Claire , Crossland Nicola , Betran Ana Pila , Weeks Andrew , Downe Soo , Kingdon Carol 
Published: May 2021

Abstract
Background
During childbirth, complications may arise which necessitate an expedited delivery of the fetus. One option is instrumental assistance (forceps or a vacuum-cup), which, if used with skill and sensitivity, can improve maternal/neonatal outcomes. This review aimed to understand the core competencies and expertise required for skilled use in AVD in conjunction with reviewing potential barriers and facilitators to gaining competency and expertise, from the point of view of maternity care practitioners, funders and policy makers.

Methods
A mixed methods systematic review was undertaken in five databases. Inclusion criteria were primary studies reporting views, opinions, perspectives and experiences of the target group in relation to the expertise, training, behaviours and competencies required for optimal AVD, barriers and facilitators to achieving practitioner competencies, and to the implementation of appropriate training. Quality appraisal was carried out on included studies. A mixed-methods convergent synthesis was carried out, and the findings were subjected to GRADE-CERQual assessment of confidence.

Results
31 papers, reporting on 27 studies and published 1985–2020 were included. Studies included qualitative designs (3), mixed methods (3), and quantitative surveys (21). The majority (23) were from high-income countries, two from upper-middle income countries, one from a lower-income country: one survey included 111 low-middle countries. Confidence in the 10 statements of findings was mostly low, with one exception (moderate confidence). The review found that AVD competency comprises of inter-related skill sets including non-technical skills (e.g. behaviours), general clinical skills; and specific technical skills associated with particular instrument use. We found that practitioners needed and welcomed additional specific training, where a combination of teaching methods were used, to gain skills and confidence in this field. Clinical mentorship, and observing others confidently using the full range of instruments, was also required, and valued, to develop competency and expertise in AVD. However, concerns regarding poor outcomes and litigation were also raised.

Conclusion
Access to specific AVD training, using a combination of teaching methods, complements, but does not replace, close clinical mentorship from experts who are positive about AVD, and opportunities to practice emerging AVD skills with supportive supervision. Further research is required to ascertain effective modalities for wider training, education, and supportive supervision for optimal AVD use.
Predictors of mortality rate among adult HIV-positive patients on antiretroviral therapy in Metema Hospital, Northwest Ethiopia: a retrospective follow-up study
Authors: Workie Kefale Lejadiss , Birhan Tilahun Yemanu , Angaw Dessie Abebaw 
Published: May 2021

Abstract
Background
Globally Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is an ongoing public health issue associated with high morbidity and mortality. Efforts have been made to reduce HIV/AIDS-related morbidity and mortality by delivering antiretroviral therapy. However, the incidence and predictors of mortality in border areas like Metema were not investigated. This study aimed to assess predictors of mortality rate among adult HIV-positive patients on antiretroviral therapy at Metema Hospital.

Methods
Retrospective follow-up study was employed among ART patients from January 1, 2013, to December 30, 2018. Data were entered in Epi-data 3.1 and exported to STATA 14 for analysis. Kaplan–Meier and Log-Rank test was used to compare survival differences among categories of different variables. In bi-variable analysis p-values < 0.20 were entered into a multivariable analysis. Multivariate Weibull model was used to measure the risk of death and identify the significant predictors of death. Variables that were statistically significant at p-value < 0.05 were concluded as predictors of mortality.

Result
A total of 542 study participants were included. The overall incidence rate was 6.7 (95% CI: 5.4–8.4) deaths per 100 person-years of observation. Being male (HR = 2.4; 95% CI: 1.24–4.62), STAGE IV (HR = 5.64; 95% CI: 2.53–12.56), stage III (HR = 3.31; 95% CI: 1.35–8.10), TB-coinfection (HR = 3.71; 95% CI: 1.59–8.64), low hemoglobin (HR = 4.14; 95% CI: 2.18–7.86), BMI ≤ 15.4 kg/m2 (HR = 2.45; 95% CI: 1.17–5.10) and viral load > 1000 copy/ml (HR = 6.70; 95% CI: 3.4–13.22) were found to be a significant predictor for mortality among HIV patients on ART treatment.

Conclusion
The incidence of death was high. Being male, viral load, those with advanced STAGE (III & IV), TB co-infected, low BMI, and low hemoglobin were at a higher risk of mortality. Special attention should be given to male patients and high public interventions needed among HIV patients on ART to reduce the mortality rate.
Development of an indirect ELISA to specifically detect antibodies against African swine fever virus: bioinformatics approaches
Authors: Gao Zhan , Shao Jun-Jun , Zhang Guang-Lei , Ge Su-Dan , Chang Yan-Yan , Xiao Lei , Chang Hui-Yun 
Published: May 2021

Abstract
Background
African swine fever (ASF), characterized by acute, severe, and fast-spreading, is a highly lethal swine infectious disease caused by the African swine fever virus (ASFV), which has caused substantial economic losses to the pig industry worldwide in the past 100 years.

Methods
This study started with bioinformatics methods and verified the epitope fusion protein method's reliability that does not rely on traditional epitope identification. Meanwhile, it will also express and purify the constructed genes through prokaryotic expression and establish antibody detection methods.

Results
The results indicated that the protein had good reactivity and did not cross-react with other swine diseases. The receiver-operating characteristic analysis was performed to verify the determination. The area under the receiver-operating characteristic curve was 0.9991 (95% confidence interval 0.9973 to 1.001).

Conclusions
It was proved that the recombinant protein is feasible as a diagnostic antigen to distinguish ASFV and provides a new idea for ASFV antibody detection.
Anterior hybrid construction of multilevel cervical disc disease and spondylotic spinal stenosis: surgical results and factors affecting adjacent segment problems
Authors: Yilmaz Murat , Yucesoy Kemal , Erbayraktar Resat S. , Altinag Rıfat S. 
Published: May 2021

Abstract
Objective
We aimed to evaluate reliability, radiological outcomes, and the impacts of anterior cervical hybrid construction on the adjacent segments for the multilevel cervical degenerative disc disease (mCDDD) and spondylotic spinal stenosis (SSS).

Methods
A retrospective analysis was performed using data extracted from the medical files of 195 patients (105 males, 90 females; mean age: 47.7 years). From 2008 to 2018, these patients underwent anterior cervical hybrid construction for symptomatic contiguous at least 2-level cervical degenerative disc diseases and cervical spondylosis. Clinical and radiological data including Neck Disability Index (NDI), visual analogue scale (VAS), local cervical degenerative disk disease in adjacent segments on magnetic resonance imaging (MRI) views, and complications were reviewed.

Results
The mean clinical and radiological follow-up was 45.2 months (range 24 to 102). Radiculopathy and/or myelopathy were the main clinical problems in all patients. The mean VAS scores of HC for arm pain were 7.4 ± 0.8 preoperatively; 2.8 ± 0.6, 1 month after surgery; 2.3 ± 0.6, 6 months after surgery; 1.8 ± 0.6, 12 month after surgery; and 1.6 ± 0.6, 24 months after surgery. The mean NDI scores (mean ± SD) of HC significantly improved after surgery (on admission, 57.2 ± 5.5%; 1 month after surgery, 27.35 ± 5.3%; 6 month after surgery, 21.43 ± 2.8%; 12 months after surgery, 21.9 ± 2.3%; 24 months after surgery, 20.6 ± 2.6%, p = 0.006). Hoarseness and dysphagia were the most common complications and osteophyte formation was the most frequent radiographic change.

Conclusion
Anterior cervical hybrid construction appears to be an acceptable option in the management of multilevel cervical degenerative disc diseases and spondylotic spinal stenosis.
Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value
Authors: Liu Hua , Qin Guangzhen , Ji Yanan , Wang Xiaojian , Bao Hailin , Guan Xiaojun , Wei Aichun , Cai Zhigang 
Published: May 2021

Abstract
Background
Osteosarcoma is a disease with high mortality in children and adolescents, and metastasis is one of the important clinical features of osteosarcoma. N6-Methyladenosine (m6A) is the most abundant methylation modification in mRNA, which is regulated by m6A regulators. It is reported that it is related to the occurrence and development of tumors. However, the mechanism of its action in osteosarcoma is rarely known. The purpose of this study was to identify the potential role of m6A regulatory factor in osteosarcoma and its clinical prognostic value.

Methods
Here, we used The Cancer Genome Atlas (TCGA) to comprehensively analyze the relationship between m6A regulatory factors and osteosarcoma (metastasis group and non-metastasis group). We analyzed their survival relationship and analyzed all the m6A regulatory factors in TCGA tumor data set by using the univariate Cox proportional hazard regression model. Finally, we selected two survival-related methylation regulators (FTO and IGF2BP2) as risk gene signature.

Results
According to the median risk, patients were divided into low-risk group and high-risk group. Multivariate Cox regression analysis showed that these two risk genes were considered to be the key factors independently predicting the prognosis of patients with osteosarcoma. In addition, we verified their characteristics with gene expression omnibus (GEO) DataSets and confirmed that they are related to tumor and immune-related signaling pathways through gene set enrichment analysis (GESA) and immune infiltration analysis.

Conclusions
In conclusion, m6A regulators might play an important role in the metastasis of osteosarcoma and have potential important value for the prognosis and treatment strategy of osteosarcoma patients.
Dynamic exacerbation in inflammation and oxidative stress during the formation of peritendinous adhesion resulted from acute tendon injury
Authors: Li Pengfei , Zhou Haiying , Tu Tian , Lu Hui 
Published: May 2021

AbstractBackgroundPeritendinous adhesion is among the common complications after tendon injury. Numerous studies have been carried out to prevent its formation, including modifications of surgical procedures, postoperative cares, application of medicines, etc. This study dynamically monitored fluctuations of inflammation, state of oxidative stress, and histopathologic changes around injured tendon to provide theoretical basis for further exploration in mechanisms of peritendinous adhesion formation.MethodsEighteen mature Sprague-Dawley male rats were randomly allocated into 6 equal groups. Compared with control and sham group, every rat’s right hind Achilles tendon in experimental groups was cut and repaired by the modified Kessler technique. Besides control and sham group, samples of tendon margin and serum were collected at different time points after the surgery. Content of TNF-α, IL-1β, and TGF-β were assayed in harvested serum. Reactive oxygen species (ROS) were detected, expression levels of related genes (IL-1β, IL-6, SOD1, SOD2, COL1, HIF1A) were quantified by qPCR, and various histopathological evaluations were performed.ResultsIndicators (TNF-α, IL-1β, TGF-β1, ROS) were noticed to have a similar trend of significant rising 24 h after the surgery except TGF-β which was rising 72 h later. So were the expression trends of IL-1β, IL-6, SOD1, SOD2, and COL1. HIF1A, inversely correlated with SOD2, showed the progressive relief of regional tissue hypoxia. Histological evaluation showed the same tendency that fibrosis and inflammation were getting serious 48 h later after the surgery.ConclusionsInflammation, oxidative stress in injured tendon resulted from acute trauma, would be getting intense in 24 h. Peritendinous adhesion emerges and aggravates after 48 h. Thus, prompt efficient measures are advised to be taken after the injury as soon as possible.
Initial forest age distribution may generate computational sinks or sources of carbon: A generic approach to test assumptions underlying the EU LULUCF forest reference levels
Authors: Vauhkonen Jari , Mutanen Antti , Packalen Tuula , Asikainen Antti 
Published: May 2021

Abstract
Background
The current EU LULUCF regulation calls for member state-specific Forest Reference Levels (FRLs) for benchmark in the accounting of greenhouse gas emissions and removals of managed forest land during the compliance period (2021–2030). According to the technical guidance on developing and reporting the FRLs, it could be actualized by projecting a ratio of harvested to total available biomass. We tested how the initial age distribution may affect the aforementioned ratio by simulating the continuation of forest management based on several descriptive shapes of forest age class distribution.

Results
Our simulations suggest that when the FRLs are prepared by employing the harvest ratio and forest management is assumed strictly age dynamics driven, the shape of the initial forest age class distribution gives rise to computational sinks or sources of carbon in managed forest land. Harvests projected according to the ratio corresponded those resulting from the age dynamics only in the case of uniform age distribution.

Conclusions
The result calls for a better consideration of variation in initial states between countries when determining the future LULUCF regulation. Our exercise demonstrates how generic simulations in a standardized modeling framework could help in ex-ante impact assessment of proposed changes to the LULUCF regulation.
Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations
Authors: Stephenson Kirk A. J. , Zhu Julia , Wynne Niamh , Dockery Adrian , Cairns Rebecca M. , Duignan Emma , Whelan Laura , Malone Conor P. , Dempsey Hilary , Collins Karen , Routledge Shana , Pandey Rajiv , Crossan Elaine , Turner Jacqueline , O’Byrne James J. , Brady Laura , Silvestri Giuliana , Kenna Paul F. , Farrar G. Jane , Keegan David J. 
Published: May 2021

Abstract
Introduction
Inherited retinal degenerations (IRD) are rare genetic disorders with > 300 known genetic loci, manifesting variably progressive visual dysfunction. IRDs were historically underserved due to lack of effective interventions. Many novel therapies will require accurate diagnosis (phenotype and genotype), thus an efficient and effective pathway for assessment and management is required.

Methods
Using surveys of existing practice patterns and advice from international experts, an all-Ireland IRD service (Target 5000) was designed. Detailed phenotyping was followed by next generation genetic sequencing in both a research and accredited laboratory. Unresolved pedigrees underwent further studies (whole gene/whole exome/whole genome sequencing). Novel variants were interrogated for pathogenicity (cascade screening, in silico analysis, functional studies). A multidisciplinary team (MDT; ophthalmologists, physicians, geneticists, genetic counsellors) reconciled phenotype with genotype. A bespoke care plan was created for each patient comprising supports, existing interventions, and novel therapies/clinical trials.

Results and discussion
Prior to Target 5000, a significant cohort of patients were not engaged with healthcare/support services due to lack of effective interventions. Pathogenic or likely pathogenic variants in IRD-associated genes were detected in 62.3%, with 11.6% having variants of unknown significance. The genotyping arm of Target 5000 allowed a 42.73% cost saving over independent testing, plus the value of MDT expertise/processing. Partial funding has transferred from charitable sources to government resources.

Conclusion
Target 5000 demonstrates efficacious and efficient clinical/genetic diagnosis, while discovering novel IRD-implicated genes/variants and investigating mechanisms of disease and avenues of intervention. This model could be used to develop similar IRD programmes in small/medium-sized nations.
Genome-wide histone acetylation analysis reveals altered transcriptional regulation in the Parkinson’s disease brain
Authors: Toker Lilah , Tran Gia T. , Sundaresan Janani , Tysnes Ole-Bjørn , Alves Guido , Haugarvoll Kristoffer , Nido Gonzalo S. , Dölle Christian , Tzoulis Charalampos 
Published: May 2021

Abstract
Background
Parkinson’s disease (PD) is a complex, age-related neurodegenerative disorder of largely unknown etiology. PD is strongly associated with mitochondrial respiratory dysfunction, which can lead to epigenetic dysregulation and specifically altered histone acetylation. Nevertheless, and despite the emerging role of epigenetics in age-related brain disorders, the question of whether aberrant histone acetylation is involved in PD remains unresolved.

Methods
We studied fresh-frozen brain tissue from two independent cohorts of individuals with idiopathic PD (n = 28) and neurologically healthy controls (n = 21). We performed comprehensive immunoblotting to identify histone sites with altered acetylation levels in PD, followed by chromatin immunoprecipitation sequencing (ChIP-seq). RNA sequencing data from the same individuals was used to assess the impact of altered histone acetylation on gene expression.

Results
Immunoblotting analyses revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. ChIP-seq analysis further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data from the same individuals revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Strikingly, this decoupling was most pronounced among nuclear-encoded mitochondrial genes, corroborating the notion that impaired crosstalk between the nucleus and mitochondria is involved in the pathogenesis of PD. Our findings independently replicated in the two cohorts.

Conclusions
Our findings strongly suggest that aberrant histone acetylation and altered transcriptional regulation are involved in the pathophysiology of PD. We demonstrate that PD-associated genes are particularly prone to epigenetic dysregulation and identify novel epigenetic signatures associated with the disease.
“We do not know how to screen and provide treatment”: a qualitative study of barriers and enablers of implementing perinatal depression health services in Ethiopia
Authors: Dadi Abel Fekadu , Miller Emma R. , Azale Telake , Mwanri Lillian 
Published: May 2021

Abstract
Background
Qualitative studies evaluating maternal mental health services are lacking in Ethiopia, and the available evidence targets severe mental illnesses in the general population. We conducted a qualitative study to explore barriers to, enablers of, or opportunities for perinatal depression health services implementations in Ethiopia.

Methods
We conducted a total of 13 face to face interviews with mental and maternal health service administrators from different levels of the Ethiopian healthcare system. We interviewed in Amharic (a local language), transcribed and translated into English, and imported into NVivo. We analysed the translated interviews inductively using thematic framework analysis.

Results
The study identified: (i) health administrators’ low literacy about perinatal depression as individual level barriers; (ii) community low awareness, health-seeking behaviours and cultural norms about perinatal depression as socio-cultural level barriers; (iii) lack of government capacity, readiness, and priority of screening and managing perinatal depression as organisational level barriers; and (iv) lack of mental health policy, strategies, and healthcare systems as structural level barriers of perinatal mental health implementation in Ethiopia. The introduction of the new Mental Health Gap Action Programme (mhGap), health professionals’ commitment, and simplicity of screening programs were identified enablers of, or opportunities for, perinatal mental health service implementation.

Conclusions
This qualitative inquiry identified important barriers and potential opportunities that could be used to address perinatal depression in Ethiopia. Building the capacity of policy makers and planners, strengthening the mental healthcare system and governance should be a priority issue for an effective integration of maternal mental health care with the routine maternal health services in Ethiopia.
When a maternal heterozygous mutation of the CYP24A1 gene leads to infantile hypercalcemia through a maternal uniparental disomy of chromosome 20
Authors: Hureaux Marguerite , Chantot-Bastaraud Sandra , Cassinari Kévin , Martinez Casado Edouard , Cuny Ariane , Frébourg Thierry , Vargas-Poussou Rosa , Bréhin Anne-Claire 
Published: May 2021

Abstract
Background
Infantile hypercalcemia is an autosomal recessive disorder caused either by mutations in the CYP24A1 gene (20q13.2) or in the SLC34A1 gene (5q35.3). This disease is characterized by hypercalcemia, hypercalciuria and nephrocalcinosis in paediatric patients.
Maternal uniparental disomy of chromosome 20 [UPD(20)mat], resulting in aberrant expression of imprinted transcripts at the GNAS locus, is a poorly characterized condition. UPD(20)mat patients manifest a phenotype similar to that of Silver-Russell syndrome and small for gestational age-short stature.

Case presentation
We report here the genetic and clinical characterization of a male child with a phenotype of infantile hypercalcemia, postnatal growth retardation, and minor dysmorphic features. Genetic analysis using a next generation sequencing panel revealed a homozygous pathogenic variant of CYP24A1. The absence of the variant in the father led to microsatellite segregation analysis, suggestive of UPD. SNP-array revealed a large terminal copy neutral loss of heterozygosity leading to CYP24A1 homozygosity. SNP-array data of parent–child trio confirmed a UPD(20)mat responsible for both infantile hypercalcemia and Silver-Russell syndrome-like traits.

Conclusion
This is the first report of uniparental disomy of chromosome 20 revealed by infantile hypercalcemia related to CYP24A1 biallelic homozygous variants, underlying the importance of controlling allelic segregation in cases of homozygosity.