bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomics‐based analysis of the mechanism by which Wang-Bi capsule alleviates joint destruction in rats with collagen‐induced arthritis
Authors: Shu Haiyang , Zhao Hanxiao , Shi Yingjie , Lu Cheng , Li Li , Zhao Ning , Lu Aiping , He Xiaojuan 
Published: April 2021

Abstract
Background
Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied with joint destruction that often leads to disability. Wang-Bi capsule (WB), a traditional Chinese medicine-based herbs formula, has exhibited inhibition effect on joint destruction of collagen-induced arthritis (CIA) animal model in our previous study. But its molecular mechanisms are still obscure.

Methods
CIA rats were treated intragastrical with WB for eight weeks, and the effect of joints protection were evaluated by hematoxylin and eosin (H&E) staining, safranin O fast green staining, tartrate-resistant acid phosphatase (TRAP) staining and micro‑CT scanning analysis. The transcriptomic of tarsal joints were used to investigate how WB alleviated joint destruction.

Results
The histological examination of ankle joints showed WB alleviated both cartilage damage and bone destruction of CIA rats. This protective effect on joints were further evidenced by micro-CT analysis. The transcriptomic analysis showed that WB prominently changed 12 KEGG signaling pathways (“calcium signaling pathway”, “cAMP signaling pathway”, “cell adhesion molecules”, “chemokine signaling pathway”, “complement and coagulation cascades”, “MAPK signaling pathway”, “NF-kappa B signaling pathway”, “osteoclast differentiation”, “PI3K-Akt signaling pathway”, “focal adhesion”, “Gap junction” and “Rap1 signaling pathway”) associated with bone or cartilage. Several genes (including Il6, Tnfsf11, Ffar2, Plg, Tnfrsf11b, Fgf4, Fpr1, Siglec1, Vegfd, Cldn1, Cxcl13, Chad, Arrb2, Fgf9, Egfr) regulating bone resorption, bone formation and cartilage development were identified by further analysis. Meanwhile, these differentially expressed genes were validated by real-time quantitative PCR.

Conclusions
Overall, the protective effect of WB treatment on joint were confirmed in CIA rats, and its basic molecular mechanisms may be associated with regulating some genes (including Il6, Tnfsf11, Ffar2 and Plg etc.) involved in bone resorption, bone formation and cartilage development.
Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors
Authors: Su Mingzhao , Liu Junhua , Yu Baocong , Zhou Kaixing , Sun Congli , Yang Mengjie , Zhao Chunjie 
Published: April 2021

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.
Comparative genomics identifies thousands of candidate structured RNAs in human microbiomes
Authors: Fremin Brayon J. , Bhatt Ami S. 
Published: April 2021

Abstract
Background
Structured RNAs play varied bioregulatory roles within microbes. To date, hundreds of candidate structured RNAs have been predicted using informatic approaches that search for motif structures in genomic sequence data. The human microbiome contains thousands of species and strains of microbes. Yet, much of the metagenomic data from the human microbiome remains unmined for structured RNA motifs primarily due to computational limitations.

Results
We sought to apply a large-scale, comparative genomics approach to these organisms to identify candidate structured RNAs. With a carefully constructed, though computationally intensive automated analysis, we identify 3161 conserved candidate structured RNAs in intergenic regions, as well as 2022 additional candidate structured RNAs that may overlap coding regions. We validate the RNA expression of 177 of these candidate structures by analyzing small fragment RNA-seq data from four human fecal samples.

Conclusions
This approach identifies a wide variety of candidate structured RNAs, including tmRNAs, antitoxins, and likely ribosome protein leaders, from a wide variety of taxa. Overall, our pipeline enables conservative predictions of thousands of novel candidate structured RNAs from human microbiomes.
The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement
Authors: Greenwood Kathryn , Webb Rebecca , Gu Jenny , Fowler David , de Visser Richard , Bremner Stephen , Abramowicz Iga , Perry Nicky , Clark Stuart , O’Donnell Anastacia , Charlton Dan , Jarvis Rebecca , Garety Philippa , Nandha Sunil , Lennox Belinda , Johns Louise , Rathod Shanaya , Phiri Peter , French Paul , Law Heather , Hodgekins Jo , Painter Michelle , Treise Cate , Plaistow James , Irwin Francis , Thompson Rose , Mackay Tanya , May Carl R. , Healey Andy , Hooper Richard , Peters Emmanuelle 
Published: April 2021

Abstract
Background
Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium–long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention.

Method
The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts.
The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14–35 years) with first episode psychosis, and EIP staff.
The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians.
The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months.
A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective.

Discussion
The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation.

Trial registration
ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.
Yoga for older adults with multimorbidity (the Gentle Years Yoga Trial): study protocol for a randomised controlled trial
Authors: Tew Garry A. , Bissell Laura , Corbacho Belen , Fairhurst Caroline , Howsam Jenny , Hugill-Jones Jess , Maturana Camila , Paul Shirley-Anne S. , Rapley Tim , Roche Jenny , Rose Fi , Torgerson David J. , Ward Lesley , Wiley Laura , Yates David , Hewitt Catherine 
Published: April 2021

Abstract
Background
Multimorbidity is common in older adults and associated with high levels of illness burden and healthcare expenditure. The evidence base for how to manage older adults with multimorbidity is weak. Yoga might be a useful intervention because it has the potential to improve health-related quality of life, physical functioning, and several medical conditions. The British Wheel of Yoga’s Gentle Years Yoga© (GYY) programme was developed specifically for older adults, including those with chronic medical conditions. Data from a pilot trial suggested feasibility of using GYY in this population, but its effectiveness and cost-effectiveness remain uncertain.

Methods
This is a multi-site, individually randomised, superiority trial with an embedded process evaluation and an economic analysis of cost-effectiveness. The trial will compare an experimental strategy of offering a 12-week GYY programme against a control strategy of no offer in community-dwelling adults aged 65 or over who have multimorbidity, defined as having two or more chronic conditions from a predefined list. The primary outcome is health-related quality of life measured using the EQ-5D-5L, the primary endpoint being the overall difference over 12 months. Both groups will continue to be able to access their usual care from primary, secondary, community, and social services. Participants, care providers, and yoga teachers will not be blinded to the allocated intervention. Outcome measures are primarily self-reported. The analysis will follow intention-to-treat principles.

Discussion
This pragmatic randomised controlled trial will demonstrate if the GYY programme is an effective, cost-effective, and viable addition to the management of older adults with multimorbidity.

Trial registration
ISRCTN ISRCTN13567538. Registered on 18 March 2019
In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers
Authors: Chen Menglong , Shi Hui , Gou Shixue , Wang Xiaomin , Li Lei , Jin Qin , Wu Han , Zhang Huili , Li Yaqin , Wang Liang , Li Huan , Lin Jinfu , Guo Wenjing , Jiang Zhiwu , Yang Xiaoyu , Xu Anding , Zhu Yuling , Zhang Cheng , Lai Liangxue , Li Xiaoping 
Published: April 2021

Abstract
Background
Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD.

Methods
In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors.

Results
Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan.

Conclusions
We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.
DNA methylation in cord blood in association with prenatal depressive symptoms
Authors: Kallak Theodora Kunovac , Bränn Emma , Fransson Emma , Johansson Åsa , Lager Susanne , Comasco Erika , Lyle Robert , Skalkidou Alkistis 
Published: April 2021

AbstractBackgroundPrenatal symptoms of depression (PND) and anxiety affect up to every third pregnancy. Children of mothers with mental health problems are at higher risk of developmental problems, possibly through epigenetic mechanisms together with other factors such as genetic and environmental. We investigated DNA methylation in cord blood in relation to PND, taking into consideration a history of depression, co-morbidity with anxiety and selective serotonin reuptake inhibitors (SSRI) use, and stratified by sex of the child. Mothers (N = 373) prospectively filled out web-based questionnaires regarding mood symptoms and SSRI use throughout pregnancy. Cord blood was collected at birth and DNA methylation was measured using Illumina MethylationEPIC array at 850 000 CpG sites throughout the genome. Differentially methylated regions were identified using Kruskal–Wallis test, and Benjamini-Hochberg adjustedp-values < 0.05 were considered significant.ResultsNo differential DNA methylation was associated with PND alone; however, differential DNA methylation was observed in children exposed to comorbid PND with anxiety symptoms compared with healthy controls inABCF1(log twofold change − 0.2), but not after stratification by sex of the child. DNA methylation in children exposed to PND without SSRI treatment and healthy controls both differed in comparison with SSRI exposed children at several sites and regions, among which hypomethylation was observed in CpGs in the promoter region ofCRBN (log2 fold change − 0.57), involved in brain development, and hypermethylation inMDFIC(log2 fold change 0.45), associated with the glucocorticoid stress response.ConclusionAlthough it is not possible to assess if these methylation differences are due to SSRI treatment itself or to more severe depression, our findings add on to existing knowledge that there might be different biological consequences for the child depending on whether maternal PND was treated with SSRIs or not.
Shorter anogenital distance is observed in patients with testicular microlithiasis using magnetic resonance imaging
Authors: Pedersen Malene Roland Vils , Osther Palle Jørn , Rafaelsen Søren Rafael 
Published: April 2021

Abstract
Objective
To investigate the anogenital distance in patients with and without testicular microlithiasis (TML).

Methods
A total of 101 patients underwent a conventional standard clinical B-mode scrotal ultrasonography and scrotal MRI. The patients were divided into two groups: patients with TML and non-TML. The latter served as control group. The anogenital distance was measured by a straight line from center of the anus to the posterior base of scrotum using MRI.

Results
In the TML group, mean AGD was 5.4 (± 1.07) cm (range 29–79 mm), and in non-TML 5.9 (± 1.03) cm (range 35–85 mm) (p = 0.04).

Conclusion
MRI is a useful tool to measure the AGD. It is easy to perform without any discomfort to patients. We found AGD to be lower in patients with TML.
Sacral chordoma with incidental rectal adenocarcinoma: a case report
Authors: Alshahri Jaffar , Alshehri Mohammed , Alnafesa Aminah , Widinly Mohammed , Alzaid Tariq , Alsulaimani Saleh , Abduljabbar Alaa 
Published: April 2021

Abstract
Background
We report a unique case of synchronous sacrococcygeal chordoma in association with rectal invasive adenocarcinoma. Retrorectal tumors are a rare disease caused by a variety of pathologies. To our knowledge, no prior cases of such a coincidental finding of both cancers have been reported in the literature.

Case presentation
This is the case of a 74-year-old white middle eastern man, with known hypertension under treatment, who presented with complaints of progressive lower back pain associated with urinary incontinence over the past 12 months. Magnetic resonance imaging (MRI) of the pelvis showed a large midline, well-defined, oval-shaped lesion replacing the sacrococcygeal portion of the spine, with extension to the presacral region. Computed tomography (CT)-guided Tru-Cut biopsy revealed features suggestive of chordoma. At surgery, we performed excision of the entire mass en bloc, sacrectomy with rectus abdominis myocutaneous flap reconstruction and end sigmoid colostomy. Surgical histopathology proved it to be sacral dedifferentiated chordoma and rectal invasive adenocarcinoma. Overall, the patient recovered well postoperatively, was discharged home with functional stoma and on permanent Foley catheter use.

Conclusion
To the best of our knowledge, this is the only reported case of such a presentation, and sheds light on the approach and management. We hope that reporting such a case will add value to the medical literature.
Improved characterisation of clinical text through ontology-based vocabulary expansion
Authors: Slater Luke T. , Bradlow William , Ball Simon , Hoehndorf Robert , Gkoutos Georgios V 
Published: April 2021

AbstractBackgroundBiomedical ontologies contain a wealth of metadata that constitutes a fundamental infrastructural resource for text mining. For several reasons, redundancies exist in the ontology ecosystem, which lead to the same entities being described by several concepts in the same or similar contexts across several ontologies. While these concepts describe the same entities, they contain different sets of complementary metadata. Linking these definitions to make use of their combined metadata could lead to improved performance in ontology-based information retrieval, extraction, and analysis tasks.ResultsWe develop and present an algorithm that expands the set of labels associated with an ontology class using a combination of strict lexical matching and cross-ontology reasoner-enabled equivalency queries. Across all disease terms in the Disease Ontology, the approach found51,362additional labels, more than tripling the number defined by the ontology itself. Manual validation by a clinical expert on a random sampling of expanded synonyms over the Human Phenotype Ontology yielded a precision of0.912. Furthermore, we found that annotating patient visits in MIMIC-III with an extended set of Disease Ontology labels led to semantic similarity score derived from those labels being a significantly better predictor of matching first diagnosis, with a mean average precision of0.88for the unexpanded set of annotations, and0.913for the expanded set.ConclusionsInter-ontology synonym expansion can lead to a vast increase in the scale of vocabulary available for text mining applications. While the accuracy of the extended vocabulary is not perfect, it nevertheless led to a significantly improved ontology-based characterisation of patients from text in one setting. Furthermore, where run-on error is not acceptable, the technique can be used to provide candidate synonyms which can be checked by a domain expert.
Low-complexity artificial noise suppression methods for deep learning-based speech enhancement algorithms
Authors: Ke Yuxuan , Li Andong , Zheng Chengshi , Peng Renhua , Li Xiaodong 
Published: April 2021

AbstractDeep learning-based speech enhancement algorithms have shown their powerful ability in removing both stationary and non-stationary noise components from noisy speech observations. But they often introduce artificial residual noise, especially when the training target does not contain the phase information, e.g., ideal ratio mask, or the clean speech magnitude and its variations. It is well-known that once the power of the residual noise components exceeds the noise masking threshold of the human auditory system, the perceptual speech quality may degrade. One intuitive way is to further suppress the residual noise components by a postprocessing scheme. However, the highly non-stationary nature of this kind of residual noise makes the noise power spectral density (PSD) estimation a challenging problem. To solve this problem, the paper proposes three strategies to estimate the noise PSD frame by frame, and then the residual noise can be removed effectively by applying a gain function based on thedecision-directedapproach. The objective measurement results show that the proposed postfiltering strategies outperform the conventional postfilter in terms of segmental signal-to-noise ratio (SNR) as well as speech quality improvement. Moreover, the AB subjective listening test shows that the preference percentages of the proposed strategies are over 60%.
Microbial community characterization of shrimp survivors to AHPND challenge test treated with an effective shrimp probiotic (Vibrio diabolicus)
Authors: Restrepo Leda , Domínguez-Borbor Cristóbal , Bajaña Leandro , Betancourt Irma , Rodríguez Jenny , Bayot Bonny , Reyes Alejandro 
Published: April 2021

Abstract
Background
Acute hepatopancreatic necrosis disease (AHPND) is an important shrimp bacterial disease caused by some Vibrio species. The severity of the impact of this disease on aquaculture worldwide has made it necessary to develop alternatives to prophylactic antibiotics use, such as the application of probiotics. To assess the potential to use probiotics in order to limit the detrimental effects of AHNPD, we evaluated the effect of the ILI strain, a Vibrio sp. bacterium and efficient shrimp probiotic, using metabarcoding (16S rRNA gene) on the gastrointestinal microbiota of shrimp after being challenged with AHPND-causing V. parahaemolyticus.

Results
We showed how the gastrointestinal microbiome of shrimp varied between healthy and infected organisms. Nevertheless, a challenge of working with AHPND-causing Vibrio pathogens and Vibrio-related bacteria as probiotics is the potential risk of the probiotic strain becoming pathogenic. Consequently, we evaluated whether ILI strain can acquire the plasmid pV-AHPND via horizontal transfer and further cause the disease in shrimp. Conjugation assays were performed resulting in a high frequency (70%) of colonies harboring the pv-AHPND. However, no shrimp mortality was observed when transconjugant colonies of the ILI strain were used in a challenge test using healthy shrimp. We sequenced the genome of the ILI strain and performed comparative genomics analyses using AHPND and non-AHPND Vibrio isolates. Using available phylogenetic and phylogenomics analyses, we reclassified the ILI strain as Vibrio diabolicus. In summary, this work represents an effort to study the role that probiotics play in the normal gastrointestinal shrimp microbiome and in AHPND-infected shrimp, showing that the ILI probiotic was able to control pathogenic bacterial populations in the host's gastrointestinal tract and stimulate the shrimp’s survival. The identification of probiotic bacterial species that are effective in the host’s colonization is important to promote animal health and prevent disease.

Conclusions
This study describes probiotic bacteria capable of controlling pathogenic populations of bacteria in the shrimp gastrointestinal tract. Our work provides new insights into the complex dynamics between shrimp and the changes in the microbiota. It also addresses the practical application of probiotics to solve problems with pathogens that cause high mortality-rate in shrimp farming around the world.