bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of attitudes, awareness, and perceptions regarding oral healthcare between dental and nursing students before and after oral healthcare education
Authors: Haresaku Satoru , Umezaki Yojiro , Egashira Rui , Naito Toru , Kubota Keiko , Iino Hidechika , Aoki Hisae , Nakashima Fuyuko
Published: April 2021

Background

Oral healthcare education for health professional students is important to promote collaborative oral healthcare practice among health professionals. The purpose of this follow-up, cross-sectional study was to investigate attitudes, awareness, and perceptions regarding oral healthcare among dental and nursing students and to compare them both between baseline and the completion of the education programme and between dental and nursing students to identify problems with oral healthcare programmes in dental education.

Method

The subjects included 88 dental and 119 nursing students. The dental students participated in geriatric and preventive dentistry courses for oral healthcare education. The nursing students participated in independent oral healthcare courses comprising 45 h of training with case-based learning and were taught and instructed by multiple health professionals, including dentists. Questionnaires were distributed to the participants to compare attitudes, awareness, and perceptions regarding oral healthcare between baseline and the completion of the education programme and between dental and nursing students. A chi-square test, Wilcoxon signed-rank test, and Mann–Whitney U test were used to compare the data.

Result and Conclusion

The data of 48 (28 male and 20 female) dental students and 103 (9 male and 94 female) nursing students who completed the questionnaires both at baseline and after the education programme were used for the comparisons. After the education programme, more than 90% of the students were interested in oral healthcare practice; hoped to practise oral healthcare post-qualification; and perceived oral healthcare to be effective for preventing dental caries, periodontal diseases, and aspiration pneumonia. These attitudes and perceptions were statistically significantly improved after the education. However, the level of awareness of oral healthcare and the level of perception of the importance of collaboration with healthcare workers in oral healthcare practice after education were lower in the dental students than in the nursing students. Multi-professional oral healthcare education with case-based learning has the potential to improve awareness of oral healthcare and perceptions of the importance of collaborative oral healthcare practice.
Pediatric dental treatments with pharmacological and non-pharmacological interventions: a cross‐sectional study
Authors: Baakdah Rania A. , Turkistani Jihan M. , Al-Qarni Amjad M. , Al-Abdali Asuf N. , Alharbi Heba A. , Bafaqih Joud A. , Alshehri Zaina S.
Published: April 2021

Objectives

Behaviour management strategies involving pharmacological or non-pharmacological interventions during dental procedures should be considered to attain safe and successful treatment outcomes. This study compared the frequencies of use and the completeness of treatment with these interventions.

Methods

A total of 1725 dental records of patients up to 18 years old, who were treated in the King Abdulaziz Medical City in Jeddah City from October 2018 to June 2019, were used in this retrospective, cross-sectional study. Inferential analysis, Chi-square test, Kruskal–Wallis test, and regression model were used in the data analysis.

Results

About two-thirds of the patients were treated with attendant non-pharmacological interventions, while one-third, with pharmacological interventions. The application of General Anesthesia (GA) was the most frequently used intervention. Restorative procedures and extractions were done in higher frequencies with pharmacological interventions. Treatments with space maintainers and orthodontic appliances were carried out in higher frequencies with non-pharmacological strategies. The choice of intervention was significantly influenced by the systemic conditions of the patients. Patients treated with non-pharmacological intervention comprised the dominant type of patients, because they required treatments with less pain. Those treated with GA needed restorative treatments and extractions, or treatments that involve pain, but these treatments had higher frequencies of being completed.

Conclusions

The treatments with pharmacological intervention through GA have higher frequencies of being completed, compared to those with non-pharmacological interventions. Factors, such as age, potential to complete the treatment, and the type of dental treatment applied, influence the choice of treatment intervention.
Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS
Authors: Lin Yan , Xiao Rong , Xia Bo-hou , Zhang Zhi-min , Li Chun , Wu Ping , Liao Duan-fang , Lin Li-mei
Published: April 2021

Background

The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.

Methods

Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites.

Results

The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism.

Conclusions

These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.
Nurses’ perception of patient safety culture and its relationship with adverse events: a national questionnaire survey in Iran
Authors: Kakemam Edris , Gharaee Hojatolah , Rajabi Mohamad Reza , Nadernejad Milad , Khakdel Zahra , Raeissi Pouran , Kalhor Rohollah
Published: April 2021

Background

Patient safety culture is an important factor in determining hospitals’ ability to address and reduce the occurrence of adverse events (AEs). However, few studies have reported on the impact of nurses’ perceptions of patient safety culture on the occurrence of AEs. Our study aimed to assess the association between nurses’ perception of patient safety culture and their perceived proportion of adverse events.

Methods

A cross-sectional survey was carried out among 2295 nurses employed in thirty-two teaching hospitals in Iran. Nurses completed the Persian version of the hospital survey of patients’ safety culture between October 2018 and September 2019.

Results

Positive Response Rates of overall patient safety culture was 34.1% and dimensions of patient safety culture varied from 20.9 to 43.8%. Also, nurses estimated that the occurrence of six adverse events varied from 51.2–63.0% in the past year. The higher nurses’ perceptions of “Staffing”, “Hospital handoffs and transitions”, “Frequency of event reporting”, “Non-punitive response to error”, “Supervisor expectation and actions promoting safety”, “Communication openness”, “Organizational learning continuous improvement”, “Teamwork within units”, and “Hospital management support patient safety” were significantly related to lower the perceived occurrence at least two out of six AEs (OR = 0.69 to 1.46).

Conclusions

Our findings demonstrated that nurses’ perception regarding patient safety culture was low and the perceived occurrence of adverse events was high. The research has also shown that the higher level of nurses’ perception of patient safety culture was associated with lowered occurrence of AEs. Hence, managers could provide prerequisites to improve patient safety culture and reduce adverse events through different strategies, such as encouraging adverse events’ reporting and holding training courses for nurses. However, further research is needed to assess how interventions addressing patient safety culture might reduce the occurrence of adverse events.
A cell-to-patient machine learning transfer approach uncovers novel basal-like breast cancer prognostic markers amongst alternative splice variants
Authors: Villemin Jean-Philippe , Lorenzi Claudio , Cabrillac Marie-Sarah , Oldfield Andrew , Ritchie William , Luco Reini F.
Published: April 2021

Background

Breast cancer is amongst the 10 first causes of death in women worldwide. Around 20% of patients are misdiagnosed leading to early metastasis, resistance to treatment and relapse. Many clinical and gene expression profiles have been successfully used to classify breast tumours into 5 major types with different prognosis and sensitivity to specific treatments. Unfortunately, these profiles have failed to subclassify breast tumours into more subtypes to improve diagnostics and survival rate. Alternative splicing is emerging as a new source of highly specific biomarkers to classify tumours in different grades. Taking advantage of extensive public transcriptomics datasets in breast cancer cell lines (CCLE) and breast cancer tumours (TCGA), we have addressed the capacity of alternative splice variants to subclassify highly aggressive breast cancers.

Results

Transcriptomics analysis of alternative splicing events between luminal, basal A and basal B breast cancer cell lines identified a unique splicing signature for a subtype of tumours, the basal B, whose classification is not in use in the clinic yet. Basal B cell lines, in contrast with luminal and basal A, are highly metastatic and express epithelial-to-mesenchymal (EMT) markers, which are hallmarks of cell invasion and resistance to drugs. By developing a semi-supervised machine learning approach, we transferred the molecular knowledge gained from these cell lines into patients to subclassify basal-like triple negative tumours into basal A- and basal B-like categories. Changes in splicing of 25 alternative exons, intimately related to EMT and cell invasion such as ENAH, CD44 and CTNND1, were sufficient to identify the basal-like patients with the worst prognosis. Moreover, patients expressing this basal B-specific splicing signature also expressed newly identified biomarkers of metastasis-initiating cells, like CD36, supporting a more invasive phenotype for this basal B-like breast cancer subtype.

Conclusions

Using a novel machine learning approach, we have identified an EMT-related splicing signature capable of subclassifying the most aggressive type of breast cancer, which are basal-like triple negative tumours. This proof-of-concept demonstrates that the biological knowledge acquired from cell lines can be transferred to patients data for further clinical investigation. More studies, particularly in 3D culture and organoids, will increase the accuracy of this transfer of knowledge, which will open new perspectives into the development of novel therapeutic strategies and the further identification of specific biomarkers for drug resistance and cancer relapse.
Overexpressing PTTG family genes predict poor prognosis in kidney renal clear cell carcinoma
Authors: Gui Yonghui , Liu Xueni , Wang Chao , Yang Peng
Published: April 2021

Background

Pituitary tumor transforming genes (PTTG1, PTTG2, and PTTG3P) play key roles in the pathogenesis and development of human cancers. The studies show that overexpression of the PTTG genes is associated with tumor progression and migration. However, the function of the PTTG genes in the prognostic value of kidney renal clear cell carcinoma is rarely known by people.

Methods

The expression of PTTG family genes was analyzed by the ONCOMINE, Human Protein Atlas, GEPIA2, and UALCAN database. The relationship between PTTG family genes expression level and clinical indicators including prognostic data in kidney renal clear cell carcinoma was analyzed by GEPIA2, TCGA portal, and UALCAN. cBioPortal database was used to analyze the genetic mutations of differentially expressed PTTG family members. Similar genes of the PTTG family (90 in total) obtained from GEPIA2 and Metascape were used for GO enrichment to explore the interaction among similar genes. The online tools of Metascape and STRING were used for functional and pathway enrichment analysis.

Results

PTTG1, 2, and 3P mRNA and protein expression upregulated in kidney renal clear cell carcinoma kidney renal clear cell carcinoma patients compared with normal tissues. And higher expression level of PTTG family genes was associated with shorter overall survival (OS) and disease-free survival (DFS). Furthermore, overexpression of the PTTG family genes had been found correlated with individual cancer stages and pathological tumor grades. In addition, 18% of mutations in the PTTG family genes were associated with short-term survival in kidney renal clear cell carcinoma patients.

Conclusions

A single PTTG gene or PTTG family genes as a whole may be a potential prognostic biomarker for kidney renal clear cell carcinoma.
Survival analysis of extramammary Paget’s disease (EMPD) in a tertiary hospital in Taiwan
Authors: Chang Yu-Wei , Ma Hsu , Liao Wen-Chieh
Published: April 2021

Background

This study aimed to investigate the survival analysis of extramammary Paget’s disease (EMPD) in a Taiwanese population and to provide data for comparison with other studies in various locations and racial populations.

Methods

We retrospectively analyzed the medical records of 63 patients with EMPD who were surgically treated from 2002 to 2019 at a single institution. The primary endpoint was the 5-year overall survival rate of EMPD, and the secondary endpoint was recurrence-free 5-year survival. Independent variables included patients’ demographic data, concurrent malignancy (i.e., non-EMPD-related cancers), tumor size, distant metastasis, and surgery and/or radiation.

Results

Of all the 63 patients, 8 cases were excluded. A total of 43 patients (78.18%) were male, and 12 were female, with a mean age of 72.67 years (range 44–89 years). The most common affected anatomic site was the penoscrotal region (22 patients, 40.00%), followed by the perianal and perineal regions (17 patients, 30.91%). Among the 55 patients, 41 patients (74.55%) were diagnosed with at least one underlying disease, whereas the most common underlying disease was cardiovascular disease (30 patients, 54.55%). The overall survival rate was 80.00% at 36 months and 65.45% at the end of follow-up. EMPD with deep dermal invasion was a significant poor prognostic factor of overall survival in cause-specific hazard model (sub-hazard ratio (HR) 5.167, p = 0.0015, 95% confidence interval (CI) 1.876–14.230). Patients with regional metastasis or distant metastasis had poorer prognosis of 5-year survival (sub-HR 4.513, p = 0.0028, CI 1.683–12.103). The limitations of this study include its retrospective nature and sample size.

Conclusions

In our series, EMPD with metastasis and deep dermal invasion was the significant harmful factors in both overall 5-year survival and 5-year recurrence-free survival. The surgical excision is not associated with a low risk of local recurrence or overall survival, and long-term follow-up is still needed.
Investigating the nature and quality of locally commissioned evaluations of the NHS Vanguard programme: an evidence synthesis
Authors: Wilson Paul , Billings Jenny , MacInnes Julie , Mikelyte Rasa , Welch Elizabeth , Checkland Kath
Published: April 2021

Background

With innovation in service delivery increasingly viewed as crucial to the long-term sustainability of health systems, NHS England launched an ambitious new model of care (Vanguard) programme in 2015. Supported by a £350 million transformation fund, 50 Vanguard sites were to act as pilots for innovation in service delivery, to move quickly to change the way that services were delivered, breaking down barriers between sectors and improving the coordination and delivery of care.

Methods

As part of a national evaluation of the Vanguard programme, we conducted an evidence synthesis to assess the nature and quality of locally commissioned evaluations. With access to a secure, online hub used by the Vanguard and other integrated care initiatives, two researchers retrieved any documents from a locally commissioned evaluation for inclusion. All identified documents were downloaded and logged, and details of the evaluators, questions, methodological approaches and limitations in design and/or reporting were extracted. As included evaluations varied in nature and type, a narrative synthesis was undertaken.

Results

We identified a total of 115 separate reports relating to the locally commissioned evaluations. Five prominent issues relating to evaluation conduct were identified across included reports: use of logic models, number and type of evaluation questions posed, data sharing and information governance, methodological challenges and evaluation reporting in general. A combination of resource, data and time constraints means that evaluations often attempted to but did not fully address the wide range of questions posed by individual Vanguards.

Conclusions

Significant investment was made in independent local evaluations of the Vanguard programme by NHS England. This synthesis represents the only comprehensive attempt to capture methodological learning and may serve as a key resource for researchers and policy-makers seeking to understand investigating large-scale system change, both within the NHS and internationally.

PROSPERO (Registration number: CRD42017069282).
Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-, 12-, and 20-month old mice
Authors: Ma Lina , Tao Xinxin , He Xiaoyan , Wang Peng , Ma Long , Shi Bin , Yao Xinsheng
Published: April 2021

The number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mice central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5’D insertion, and 5’D trimming with age. The BCR H-CDR3 repertoire diversity of mice bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.
A stepped wedge cluster randomized control trial to evaluate the implementation and effectiveness of optimized initiatives in improving quality of care for ST segment elevation myocardial infarction in response to the COVID-19 outbreak
Authors: Zhou Shuduo , Dong Xuejie , Liu Fangjing , Zhang Yan , Yue Dahai , Zhou Qiang , Jin Yinzi , Zheng Zhi-Jie
Published: April 2021

Background

The National Chest Pain Center Accreditation Program (CHANGE) is the first hospital-based, multifaceted, nationwide quality improvement (QI) initiative, to monitor and improve the quality of the ST segment elevation myocardial infarction (STEMI) care in China. The QI initiatives, as implementation strategies, include a bundle of evidence-based interventions adapted for implementation in China. During the pandemic of coronavirus disease 2019 (COVID-19), fear of infection with severe acute respiratory syndrome coronavirus 2, national lockdowns, and altered health care priorities have highlighted the program’s importance in improving STEMI care quality. This study aims to minimize the adverse impact of the COVID-19 pandemic on the quality of STEMI care, by developing interventions that optimize the QI initiatives, implementing and evaluating the optimized QI initiatives, and developing scale-up activities of the optimized QI initiatives in response to COVID-19 and other public health emergencies.

Methods

A stepped wedge cluster randomized control trial will be conducted in three selected cities of China: Wuhan, Suzhou, and Shenzhen. Two districts have been randomly selected in each city, yielding a total of 24 registered hospitals. This study will conduct a rollout in these hospitals every 3 months. The 24 hospitals will be randomly assigned to four clusters, and each cluster will commence the intervention (optimized QI initiatives) at one of the four steps. We will conduct hospital-based assessments, questionnaire surveys among health care providers, community-based household surveys, and key informant interviews during the trial. All outcome measures will be organized using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, including implementation outcomes, service outcomes (e.g., treatment time), and patient outcomes (e.g., in-hospital mortality and 1-year complication). The Consolidated Framework for Implementation Research framework will be used to identify factors that influence implementation of the optimized QI interventions.

Discussion

The study findings could be translated into a systematic solution to implementing QI initiatives in response to COVID-19 and future potential major public health emergencies. Such actionable knowledge is critical for implementors of scale-up activities in low- and middle-income settings.

Trial registration

ChiCTR 2100043319. Registered on 10 February 2021
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

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.
Correction to: Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study
Authors: Marino Federica Zito , Sabetta Rosalaura , Pagliuca Francesca , Brunelli Matteo , Aquino Gabriella , Perdonà Sisto , Botti Gerardo , Facchini Gaetano , Fiorentino Francesco , Di Lauro Giovanni , De Sio Marco , De Vita Ferdinando , Toni Giorgio , Reis Rodolfo Borges Dos , Neder Luciano , Franco Renato
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
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

The 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.
Correction to: ACTN1 supports tumor growth by inhibiting Hippo signaling in hepatocellular carcinoma
Authors: Chen Qian , Zhou Xiao-Wei , Zhang Ai-Jun , He Kang
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Comparative genomics identifies thousands of candidate structured RNAs in human microbiomes
Authors: Fremin Brayon J. , Bhatt Ami S.
Published: April 2021

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

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

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

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

Background

Prenatal 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.

Results

No 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.

Conclusion

Although 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

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

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

Background

Biomedical 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.

Results

We 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.

Conclusions

Inter-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

Deep 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%.
∗-fuzzy measure model for COVID-19 disease
Authors: Ghaffari Abbas , Saadati Reza
Published: April 2021

We introduce a mathematical model, namely, ∗-fuzzy measure model for COVID-19 disease and consider some properties of ∗-fuzzy measure such as Lebesque–Radon–Nikodym theorem.
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

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.