bluuebunny/crossref_metadata_2025 huggingface dataset:
Food safety knowledge, attitudes and practices of food handlers: A cross-sectional study in school kitchens in Espírito Santo, Brazil
Authors: da Vitória Alyne Gomes , de Souza Couto Oliveira Jhenifer , de Almeida Pereira Louise Caroline , de Faria Carolina Perim , de São José Jackline Freitas Brilhante
Published: February 2021

Background

The adoption and evaluation of good practices in food handling in food service are essential to minimizing foodborne diseases. The present study aimed to evaluate food safety knowledge, attitudes, and practices of food handlers in schools in Vitória, Brazil.

Methods

A cross-sectional study was carried out in the school food services of the municipal network of Vitória-ES. The sample of food handlers was obtained by convenience and comprised food handlers involved with preparation and other kitchen-related activities. The instrument consisted of a structured questionnaire with 36 six questions that included sociodemographic characteristics, knowledge, attitudes, and practices (KAP) related to good practices and food safety. The questionnaire was answered by 172 food handlers. Pearson correlation test, T-test, Tukey’s test and multiple linear regression analysis were conducted. Data entry and analysis were done using SPSS v.20 software.

Results

Most of the participants were female (96.5%, n = 166), were 40 to 49 years old (44.8%, n = 78), attended high school (57.9%, n = 99), had up to 5 years of experience in the role (39.5%, n = 68). Some of them had participated at least 4 times in training (74.4%, n = 128) of which the most recent session had occurred within 3 months (52.0%, n = 44). The lowest score was obtained for knowledge (7.1 ± 1.22). All the models presented significant results for the F-test. This result show good model fit and results ranging from 1.5 to 2.5 on the Durbin Watson test of residual autocorrelation. The linear regression analysis allowed us to identify that the knowledge score increased with experience, but it was significant only for those who had spent up to 10 years in the role. The knowledge score was associated with experience and training time. Attitudes were significantly related to the schooling and training time. The increase in the classification of practices is shown only through a classification of attitudes.

Conclusions

Although the food handlers’ knowledge level in general was considered as sufficient, it was inferior to their scores for attitudes and practices regarding certain food safety concepts. Food safety training is ongoing in these units and covers the main aspects that favour the transformation of knowledge into appropriate attitudes and practices.
Clinical features of anti-synthetase syndrome associated interstitial lung disease: a retrospective cohort in China
Authors: Zhan Xi , Yan Wei , Wang Ying , Li Qing , Shi Xuhua , Gao Yanli , Ye Qiao
Published: February 2021

Background

Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD.

Methods

Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies.

Results

Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic’s hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05).

Conclusion

Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.
Pharmacy professionals’ views regarding the future of NHS patient medicines helpline services: a multimethod qualitative study
Authors: Williams Matt , Jordan Abbie , Scott Jenny , Jones Matthew D.
Published: February 2021

Background

Patient medicines helpline services (PMHS) have been established at some National Health Service (NHS) hospitals, to provide patients with post-discharge medicines-related support. However, findings suggest that many PMHS are provided sub-optimally due to a lack of resources. This study sought to examine pharmacy professionals’ perceptions of the future of PMHS.

Methods

Participants comprised pharmacy professionals from NHS Trusts in England that provided a PMHS. Invitations to participate in a qualitative survey and then an interview were sent to pharmacy services at all NHS Trusts that provided a PMHS. This resulted in 100 survey participants and 34 interview participants. Data were analysed using Braun and Clarke’s inductive reflexive thematic analysis.

Results

Two themes were generated:Enhancing value for service usersandImprovingefficiency.Enhancing value for service usersidentifies pharmacy professionals’ suggestions for improving the value of PMHS for service users. These include providing access methods extending beyond the telephone, and providing patients/carers with post-discharge follow-up calls from a pharmacist to offer medicines-related support.Improvingefficiencyidentifies that, in the future, and in line with NHS plans for efficiency and shared resources, PMHS may become centralised or provided by community pharmacies. Centralised services were considered to likely have more resources available to provide a patient medicines information service compared to hospital pharmacies. However, such a change was perceived to only increase efficiency if patient information can be shared between relevant healthcare settings.

Conclusions

PMHS are perceived by pharmacy professionals as likely to become centralised in the future (i.e., provided regionally/nationally). However, such change is dependent upon the sharing of patients’ information between hospitals and the centralised hub/s or pharmacies. To enhance the value of PMHS for service users, providers should consider establishing other methods of access, such as email and video consultation. Considering the uncertainty around the future of PMHS, research should establish the best way to support all patients and carers regarding medicines following hospital discharge.
Characteristics and mortality rates among patients requiring intermediate care: a national cohort study using linked databases
Authors:   on behalf of SPACE, Evans Catherine J. , Potts Laura , Dalrymple Ursula , Pring Andrew , Verne Julia , Higginson Irene J. , Gao Wei
Published: February 2021

Background

Adults increasingly live and die with chronic progressive conditions into advanced age. Many live with multimorbidity and an uncertain illness trajectory with points of marked decline, loss of function and increased risk of end of life. Intermediate care units support mainly older adults in transition between hospital and home to regain function and anticipate and plan for end of life. This study examined the patient characteristics and the factors associated with mortality over 1 year post-admission to an intermediate care unit to inform priorities for care.

Methods

A national cohort study of adults admitted to intermediate care units in England using linked individual-level Hospital Episode Statistics and death registration data. The main outcome was mortality within 1 year from admission. The cohort was examined as two groups with significant differences in mortality between main diagnosis of a non-cancer condition and cancer. Data analysis used Kaplan-Meier curves to explore mortality differences between the groups and a time-dependant Cox proportional hazards model to determine mortality risk factors.

Results

The cohort comprised 76,704 adults with median age 81 years (IQR 70–88) admitted to 220 intermediate care units over 1 year in 2016. Overall, 28.0% died within 1 year post-admission. Mortality varied by the main diagnosis of cancer (total n = 3680, 70.8% died) and non-cancer condition (total n = 73,024, 25.8% died). Illness-related factors had the highest adjusted hazard ratios [aHRs]. At 0–28 days post-admission, risks were highest for non-cancer respiratory conditions (pneumonia (aHR 6.17 [95%CI 4.90–7.76]), chronic obstructive pulmonary disease (aHR 5.01 [95% CI 3.78–6.62]), dementia (aHR 5.07 [95% CI 3.80–6.77]) and liver disease (aHR 9.75 [95% CI 6.50–14.6]) compared with musculoskeletal disorders. In cancer, lung cancer showed largest risk (aHR 1.20 [95%CI 1.04–1.39]) compared with cancer ‘other’. Risks increased with high multimorbidity for non-cancer (aHR 2.57 [95% CI 2.36–2.79]) and cancer (aHR 2.59 [95% CI 2.13–3.15]) (reference: lowest).

Conclusions

One in four patients died within 1 year. Indicators for palliative care assessment are respiratory conditions, dementia, liver disease, cancer and rising multimorbidity. The traditional emphasis on rehabilitation and recovery in intermediate care units has changed with an ageing population and the need for greater integration of palliative care.
The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis
Authors: Mostafaei Shayan , Sayad Babak , Azar Maryam Ebadi Fard , Doroudian Mohammad , Hadifar Shima , Behrouzi Ava , Riahi Parisa , Hussen Bashdar Mahmud , Bayat Bahareh , Nahand Javid Sadri , Moghoofei Mohsen
Published: February 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Several risk factors such as smoking, air pollution, inhaled toxins, high body mass index and infectious agents are involved in the pathogenesis of IPF. In the present study, this meta-analysis study investigates the prevalence of viral and bacterial infections in the IPF patients and any possible association between these infections with pathogenesis of IPF.

Methods

The authors carried out this systematic literature review from different reliable databases such as PubMed, ISI Web of Science, Scopus and Google Scholar to December 2020.Keywords used were the following “Idiopathic pulmonary fibrosis”, “Infection”, “Bacterial Infection” and “Viral Infection”, alone or combined together with the Boolean operators "OR”, “AND” and “NOT” in the Title/Abstract/Keywords field. Pooled proportion and its 95% CI were used to assess the prevalence of viral and bacterial infections in the IPF patients.

Results

In this systematic review and meta-analyses, 32 studies were selected based on the exclusion/inclusion criteria. Geographical distribution of included studies was: eight studies in American people, 8; in European people, 15 in Asians, and one in Africans. The pooled prevalence for viral and bacterial infections w ere 53.72% (95% CI 38.1–69.1%) and 31.21% (95% CI 19.9–43.7%), respectively. The highest and lowest prevalence of viral infections was HSV (77.7% 95% CI 38.48–99.32%), EBV (72.02%, 95% CI 44.65–90.79%) and Influenza A (7.3%, 95% CI 2.66–42.45%), respectively. Whereas the highest and lowest prevalence in bacterial infections were related to Streptococcus sp. (99.49%, 95% CI 96.44–99.9%) and Raoultella (1.2%, 95% CI 0.2–3.08%), respectively.

Conclusions

The results of this review were confirmed that the presence of viral and bacterial infections are the risk factors in the pathogenesis of IPF. In further analyses, which have never been shown in the previous studies, we revealed the geographic variations in the association strengths and emphasized other methodological parameters (e.g., detection method). Also, our study supports the hypothesis that respiratory infection could play a key role in the pathogenesis of IP.
Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma
Authors: Yu Kai , Yang Huan , Lv Qiao-li , Wang Li-chong , Tan Zi-long , Zhang Zhe , Ji Yu-long , Lin Qian-xia , Chen Jun-jun , He Wei , Chen Zhen , Shen Xiao-li
Published: February 2021

Background

Glioblastoma is the most common primary malignant brain tumor. Because of the limited understanding of its pathogenesis, the prognosis of glioblastoma remains poor. This study was conducted to explore potential competing endogenous RNA (ceRNA) network chains and biomarkers in glioblastoma by performing integrated bioinformatics analysis.

Methods

Transcriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma and normal tissues. Biological pathways potentially associated with the differentially expressed genes were explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan–Meier curve method. A ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by quantitative reverse-transcription polymerase chain reaction analysis and by determining the Pearson correlation coefficient. Additionally, an MTS assay and the wound-healing and transwell assays were performed to evaluate the effects of complement C1s (C1S) on the viability and migration and invasion abilities of glioblastoma cells, respectively.

Results

We detected 2842 differentially expressed (DE) mRNAs, 2577 DE long non-coding RNAs (lncRNAs), and 309 DE microRNAs (miRNAs) that were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DE mRNAs and one DE lncRNA were correlated with overall survival (p < 0.05). C1S was significantly correlated with overall survival (p= 0.015). In functional assays, knockdown of C1S inhibited the proliferation and invasion of glioblastoma cell lines.

Conclusions

We established four ceRNA networks that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis is a potential marker and therapeutic target for glioblastoma. Knockdown of C1S inhibited the proliferation, migration, and invasion of glioblastoma cells. These findings clarify the role of the ceRNA regulatory network in glioblastoma and provide a foundation for further research.
Down‐regulation of the Sp1 transcription factor by an increase of microRNA-4497 in human placenta is associated with early recurrent miscarriage
Authors: Tang Huaiyun , Pan Linqing , Xiong Yun , Wang Leilei , Cui Yugui , Liu Jiayin , Tang Lisha
Published: February 2021

Background

The pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts.

Methods

Bioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3’-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497.

Results

Bioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3’-untranslated region (3’-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497.

Conclusions

An increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage.
Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation
Authors: Sonawane Shweta Kishor , Uversky Vladimir N. , Chinnathambi Subashchandrabose
Published: February 2021

Background

Amyloid aggregate deposition is the key feature of Alzheimer’s disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (Aβ) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Prion diseases.

Methods

We analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques.

Results

The potency of Baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against in vitro Tau aggregation and PHF dissolution has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD.

Conclusion

In conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.
The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia
Authors: Han Caixia , He Shujiao , Wang Ruiqi , Gao Xuefeng , Wang Hong , Qiao Jingqiao , Meng Xiangyu , Li Yonghui , Yu Li
Published: February 2021

Background

Rho GTPase activating protein 9 (ARHGAP9) is expressed in various types of cancers and can inactivate Rho GTPases that mainly regulate cytoskeletal dynamics. However, the exact role of ARHGAP9 in acute myeloid leukemia (AML) has yet to be clarified.

Methods

We compared the transcriptional expression, prognosis, differentially expressed genes, functional enrichment, and hub genes in AML patients on the basis of the data published in the following databases: UALCAN, GEPIA, Gene Expression Omnibus, the Human Protein Atlas, Cancer Cell Line Encyclopedia, LinkedOmics, Metascape, and String. Data from the Cancer Genome Atlas database was used to evaluate the correlations between ARHGAP9 expression and various clinicopathological parameters, as well as the significantly different genes associated with ARHGAP9 expression.

Results

We found that ARHGAP9 expression was higher in the tissues and cell lines extracted from patients with AML than corresponding control tissues and other cancer types. ARHGAP9 overexpression was associated with decreased overall survival (OS) in AML. Compared with the ARHGAP9lowgroup, the ARHGAP9highgroup, which received only chemotherapy, showed significantly worse OS and event-free survival (EFS); however, no significant difference was observed after treatment with autologous or allogeneic hematopoietic stem cell transplantation (auto/allo-HSCT). The ARHGAP9highpatients undergoing auto/allo-HSCT also had a significantly better prognosis with respect to OS and EFS than those receiving only chemotherapy. Most overlapping genes of the significantly different genes and co-expression genes exhibited enriched immune functions, suggesting the immune regulation potential of ARHGAP9 in AML. A total of 32 hub genes were identified from the differentially expressed genes, within which the KIF20A had a significant prognostic value for AML.

Conclusions

ARHGAP9 overexpression was associated with poor OS in AML patients and can be used as a prognostic biomarker. AML patients with ARHGAP9 overexpression can benefit from auto/allo-HSCT rather than chemotherapy.
Changes in cannabis use, exposure, and health perceptions following legalization of adult recreational cannabis use in California: a prospective observational study
Authors: Gali Kathleen , Winter Sandra J. , Ahuja Naina J. , Frank Erica , Prochaska Judith J.
Published: February 2021

Background

Most U.S. states have legalized cannabis for medical and/or recreational use. In a 6-month prospective observational study, we examined changes in adult cannabis use patterns and health perceptions following broadened legalization of cannabis use from medical to recreational purposes in California.

Methods

Respondents were part of Stanford University’s WELL for Life registry, an online adult cohort concentrated in Northern California. Surveys were administered online in the 10 days prior to state legalization of recreational use (1/1/18) and 1-month (2/1/18–2/15/18) and 6-months (7/1/2018–7/15/18) following the change in state policy. Online surveys assessed self-reported past 30-day cannabis use, exposure to others’ cannabis use, and health perceptions of cannabis use. Logistic regression models and generalized estimating equations (GEE) examined associations between participant characteristics and cannabis use pre- to 1-month and 6-months post-legalization.

Results

The sample (N = 429, 51% female, 55% non-Hispanic White, age mean = 56 ± 14.6) voted 58% in favor of state legalization of recreational cannabis use, with 26% opposed, and 16% abstained. Cannabis use in the past 30-days significantly increased from pre-legalization (17%) to 1-month post-legalization (21%; odds ratio (OR) = 1.28, p-value (p) = .01) and stayed elevated over pre-legalization levels at 6-months post-legalization (20%; OR = 1.28, p = .01). Exposure to others’ cannabis use in the past 30 days did not change significantly over time: 41% pre-legalization, 44% 1-month post-legalization (OR = 1.18, p = .11), and 42% 6-months post-legalization (OR = 1.08, p = .61). Perceptions of health benefits of cannabis use increased from pre-legalization to 6-months post-legalization (OR = 1.19, p = .02). Younger adults, those with fewer years of education, and those reporting histories of depression were more likely to report recent cannabis use pre- and post-legalization. Other mental illness was associated with cannabis use at post-legalization only. In a multivariate GEE adjusted for sociodemographic characteristics and diagnoses, favoring legalization and the interaction of time and positive health perceptions were associated with a greater likelihood of using cannabis.

Conclusions

Legalized recreational cannabis use was associated with greater self-reported past 30-day use post-legalization, and with more-positive health perceptions of cannabis use. Future research is needed to examine longer-term perceptions and behavioral patterns following legalization of recreational cannabis use, especially among those with mental illness.
Validation of the 5-domain Niemann-Pick type C Clinical Severity Scale
Authors: Patterson Marc C. , Lloyd-Price Lucy , Guldberg Christina , Doll Helen , Burbridge Claire , Chladek Michael , íDali Christine , Mengel Eugen , Symonds Tara
Published: February 2021

Background

Niemann-Pick disease type C (NPC) is an ultra-rare, progressive, genetic disease leading to impaired lysosomal function and neurodegeneration causing serious morbidity and shortened life expectancy.

The Niemann-Pick type C Clinical Severity Scale (NPCCSS) is a 17 domain, disease-specific, clinician-reported outcome measure of disease severity and progression. An abbreviated 5-domain NPCCSS scale has been developed (measuring Ambulation, Swallow, Cognition, Speech, and Fine Motor Skills) and the scale reliability has been established. Additional psychometric properties and meaningful change of the scale need, however, to be assessed.

Methods

Mixed method studies were conducted to ascertain which NPCCSS domains were most important, as well as to explore meaningful change: 1) surveys in caregivers/patients (n = 49) and 2) interviews with clinicians (n = 5) as well as caregivers/patients (n = 28). Clinical trial data (n = 43) assessed construct validity and meaningful change through an anchor-based approach.

Results

Domains identified as most important by clinicians, caregivers, and patients (independent of current age, age of onset, and disease severity) were Ambulation, Swallow, Cognition, Speech, and Fine Motor Skills, indicating content validity of the 5-domain NPCCSS.

Criterion validity was shown with the 5-domain NPCCSS being highly correlated with the 17-item NPCCSS total score (excluding hearing domains), r2 = 0.97. Convergent validity was demonstrated against the 9 Hole Peg Test, r2 = 0.65 (n = 31 patients), and the Scale for Assessment and Rating of Ataxia (SARA), r2 = 0.86 (n = 49 patients). Any change was seen as meaningful by patients/caregivers across domains. Meaningful change using trial data and interviews with NPC experts (n = 5) and patients/caregivers (n = 28) suggested that a 1-category change on a domain is equivalent to 1-point change or greater in the 5-domain NPCCSS total score.

Conclusions

Qualitative and quantitative data support content and construct validity of the 5-domain NPCCSS score as a valid endpoint in NPC trials. A 1-category change on any domain is equivalent to 1-point change or greater in the 5 domain NPCCSS total score, representing a clinically meaningful transition and reflecting loss of complex function and increased disability.

Trial registrationNCT02612129. Registered 23 November 2015,https://clinicaltrials.gov/ct2/show/NCT02612129
Predictors of cervical myelopathy and hydrocephalus in young children with achondroplasia
Authors: Shim Youngbo , Ko Jung Min , Cho Tae-Joon , Kim Seung‐Ki , Phi Ji Hoon
Published: February 2021

Background

Cervical myelopathy and hydrocephalus occasionally occur in young children with achondroplasia. However, these conditions are not evaluated in a timely manner in many cases. The current study presents significant predictors for cervical myelopathy and hydrocephalus in young children with achondroplasia.

Methods

A retrospective analysis of 65 patients with achondroplasia who visited Seoul National University Children’s Hospital since 2012 was performed. The patients were divided into groups according to the presence of cervical myelopathy and hydrocephalus, and differences in foramen magnum parameters and ventricular parameters by magnetic resonance imaging between groups were analyzed. Predictors for cervical myelopathy and hydrocephalus were analyzed, and the cut-off points for significant ones were calculated.

Results

The group with cervical myelopathy showed foramen magnum parameters that indicated significantly lower cord thickness than in the group without cervical myelopathy, and the group with hydrocephalus showed significantly higher ventricular parameters and ‘Posterior indentation’ grade than the group without hydrocephalus. ‘Cord constriction ratio’ (OR 5199.90, p = 0.001) for cervical myelopathy and ‘Frontal horn width’ (OR 1.14, p = 0.001) and ‘Posterior indentation’ grade (grade 1: OR 9.25, p = 0.06; grade 2: OR 18.50, p = 0.01) for hydrocephalus were significant predictors. The cut-off points for cervical myelopathy were ‘Cord constriction ratio’ of 0.25 and ‘FM AP’ of 8 mm (AUC 0.821 and 0.862, respectively) and ‘Frontal horn width’ of 50 mm and ‘Posterior indentation’ grade of 0 (AUC 0.788 and 0.758, respectively) for hydrocephalus.

Conclusion

‘Cord constriction ratio’ for cervical myelopathy and ‘Frontal horn width’ and ‘Posterior indentation’ grade for hydrocephalus were significant predictors and may be used as useful parameters for management. ‘Posterior indentation’ grade may also be used to determine the treatment method for hydrocephalus.
FGFR1 amplification or overexpression and hormonal resistance in luminal breast cancer: rationale for a triple blockade of ER, CDK4/6, and FGFR1
Authors: Mouron Silvana , Manso Luis , Caleiras Eduardo , Rodriguez-Peralto Jose L. , Rueda Oscar M. , Caldas Carlos , Colomer Ramon , Quintela-Fandino Miguel , Bueno Maria J.
Published: February 2021

Background

FGFR1 amplification, but not overexpression, has been related to adverse prognosis in hormone-positive breast cancer (HRPBC). Whether FGFR1 overexpression and amplification are correlated, what is their distribution among luminal A or B HRPBC, and if there is a potential different prognostic role for amplification and overexpression are currently unknown features. The role of FGFR1 inhibitors in HRPBC is also unclear.

Methods

FGFR1 amplification (FISH) and overexpression (RNAscope) were investigated in a N = 251 HRPBC patients cohort and the METABRIC cohort; effects on survival and FISH-RNAscope concordance were determined. We generated hormonal deprivation resistant (LTED-R) and FGFR1-overexpressing cell line variants of the ER+ MCF7 and T47-D and the ER+, FGFR1-amplified HCC1428 cell lines. The role of ER, CDK4/6, and/or FGFR1 blockade alone or in combinations in Rb phosphorylation, cell cycle, and survival were studied.

Results

FGFR1 overexpression and amplification was non-concordant in > 20% of the patients, but both were associated to a similar relapse risk (~ 2.5-fold; P < 0.05). FGFR1 amplification or overexpression occurred regardless of the luminal subtype, but the incidence was higher in luminal B (16.3%) than A (6.6%) tumors; P < 0.05. The Kappa index for overexpression and amplification was 0.69 (P < 0.001). Twenty-four per cent of the patients showed either amplification and/or overexpression of FGFR1, what was associated to a hazard ratio for relapse of 2.6 (95% CI 1.44–4.62, P < 0.001). In vitro, hormonal deprivation led to FGFR1 overexpression. Primary FGFR1 amplification, engineered mRNA overexpression, or LTED-R-acquired FGFR1 overexpression led to resistance against hormonotherapy alone or in combination with the CDK4/6 inhibitor palbociclib. Blocking FGFR1 with the kinase-inhibitor rogaratinib led to suppression of Rb phosphorylation, abrogation of the cell cycle, and resistance-reversion in all FGFR1 models.

Conclusions

FGFR1 amplification and overexpression are associated to similar adverse prognosis in hormone-positive breast cancer. Capturing all the patients with adverse prognosis-linked FGFR1 aberrations requires assessing both features. Hormonal deprivation leads to FGFR1 overexpression, and FGFR1 overexpression and/or amplification are associated with resistance to hormonal monotherapy or in combination with palbociclib. Both resistances are reverted with triple ER, CDK4/6, and FGFR1 blockade.
Author Correction: Assembly of hundreds of novel bacterial genomes from the chicken caecum
Authors: Glendinning Laura , Stewart Robert D. , Pallen Mark J. , Watson Kellie A. , Watson Mick
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Neoadjuvant irradiation of retroperitoneal soft tissue sarcoma with ions (Retro-Ion): study protocol for a randomized phase II pilot trial
Authors: Seidensaal K. , Kieser M. , Hommertgen A. , Jaekel C. , Harrabi S. B. , Herfarth K. , Mechtesheimer G. , Lehner B. , Schneider M. , Nienhueser H. , Fröhling S. , Egerer G. , Debus J. , Uhl M.
Published: February 2021

Background

Following surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Radiotherapy is utilized to reduce recurrence rates but the efficacy of this strategy has not been definitely established. As treatment tolerability is more favorable with preoperative radiotherapy, normofractionated neoadjuvant treatment is the current approach. The final results of the prospective, randomized STRASS (EORTC 62092) trial, which compared the efficacy of this combined treatment to that of surgery alone, are still awaited; preliminary results presented at the 2019 ASCO Annual Meeting indicated that combined treatment is associated with better local control in patients with liposarcoma (74.5% of the cohort, 11% benefit in abdominal progression free survival after 3 years, p = 0.049). Particles allow better sparing of surrounding tissues at risk, e.g., bowel epithelium, and carbon ions additionally offer biologic advantages and are preferred in slow growing tumors. Furthermore, hypofractionation allows for a significantly shorter treatment interval with a lower risk of progression during radiotherapy.

Methods and design

We present a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the retroperitoneum will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5–6 fractions per week] in each arm). The primary objective is the safety and feasibility based on the proportion of grade 3–5 toxicity (CTCAE, version 5.0) in the first 12 months after surgery or discontinuation of treatment for any reason related to the treatment. Local control, local progression-free survival, disease-free survival, overall survival, and quality of life are the secondary endpoints of the study.

Discussion

The aim of this study is to confirm that hypofractionated, accelerated preoperative radiotherapy is safe and feasible. The rationale for the use of particle therapy is the potential for reduced toxicity. The data will lay the groundwork for a randomized phase III trial comparing hypofractionated proton and carbon ion irradiation with regard to local control.

Trial registration

ClinicalTrials.gov NCT04219202. Retrospectively registered on January 6, 2020
Efficacy of modified Banxia Xiexin decoction in the management of Wei-Pi syndrome (postprandial distress syndrome): study protocol for a randomized, waitlist-controlled trial
Authors: Sin Sai Ho , Wu Jing , Kang Yuchen , Yip Kar Hung Kevin , Kong Ngo Suet , Wan Hei , Ng Bacon Fung Leung , Chen Haiyong
Published: February 2021

Background

Postprandial distress syndrome manifests as a feeling of fullness and early satiation that can significantly reduce the quality of life of the patients. In Chinese medicine (CM), the syndrome is traditionally regarded as theWei-Pisyndrome, and Banxia Xiexin decoction (BXD) has been used in the empirical treatment of the same for a long time. The current study aims to evaluate the efficacy of modified BXD in the management ofWei-Pisyndrome.

Methods/design

A randomized, waitlist-controlled trial will be conducted. A total of 84 patients withWei-Pisyndrome will be randomized into the BXD or waitlist control group in a ratio of 1:1. The patients in the BXD group will receive the semi-individualized BXD on the basis of the syndrome differentiation in CM, for a duration of 3 weeks and will be under follow-up for further 3 weeks after the completion of therapy. Conversely, the patients in the waitlist control group will undergo the same intervention and follow-up after a 3-week waiting period. In the current study, the primary outcome will be the variation in the scores pertaining to the global scale of the Quality of Life Questionnaire for Functional Digestive Disorders after 3 weeks. The secondary outcomes include the variations in the scores pertaining to the Hospital Anxiety and Depression Scale and the EuroQoL 5-dimension 5-level Questionnaire and the results of the liver and kidney function tests.

Discussion

This trial will assess the efficacy of modified BXD in improving the clinical symptoms and quality of life of the patients suffering fromWei-Pisyndrome.

Trial registration

ClinicalTrials.govNCT04398888. Registered on May 21, 2020
Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
Authors: Gobin Jonathan , Muradia Gauri , Mehic Jelica , Westwood Carole , Couvrette Lauren , Stalker Andrew , Bigelow Stewart , Luebbert Christian C. , Bissonnette Frédéric St-Denis , Johnston Michael J. W. , Sauvé Simon , Tam Roger Y. , Wang Lisheng , Rosu-Myles Michael , Lavoie Jessie R.
Published: February 2021

Background

Extracellular vesicles (EVs) produced by human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are currently investigated for their clinical effectiveness towards immune-mediated diseases. The large amounts of stem cell-derived EVs required for clinical testing suggest that bioreactor production systems may be a more amenable alternative than conventional EV production methods for manufacturing products for therapeutic use in humans.

Methods

To characterize the potential utility of these systems, EVs from four hBM-MSC donors were produced independently using a hollow-fiber bioreactor system under a cGMP-compliant procedure. EVs were harvested and characterized for size, concentration, immunophenotype, and glycan profile at three separate intervals throughout a 25-day period.

Results

Bioreactor-inoculated hBM-MSCs maintained high viability and retained their trilineage mesoderm differentiation capability while still expressing MSC-associated markers upon retrieval. EVs collected from the four hBM-MSC donors showed consistency in size and concentration in addition to presenting a consistent surface glycan profile. EV surface immunophenotypic analyses revealed a consistent low immunogenicity profile in addition to the presence of immuno-regulatory CD40 antigen. EV cargo analysis for biomarkers of immune regulation showed a high abundance of immuno-regulatory and angiogenic factors VEGF-A and IL-8.

Conclusions

Significantly, EVs from hBM-MSCs with immuno-regulatory constituents were generated in a large-scale system over a long production period and could be frequently harvested with the same quality and quantity, which will circumvent the challenge for clinical application.
Co-culture of ASCs/EPCs and dermal extracellular matrix hydrogel enhances the repair of full-thickness skin wound by promoting angiogenesis
Authors: Lin Shuang , He Xiaoning , He Yuanjia
Published: February 2021

Background

The repair of large-scale full-thickness skin defects represents a challenging obstacle in skin tissue engineering. To address the most important problem in skin defect repair, namely insufficient blood supply, this study aimed to find a method that could promote the formation of vascularized skin tissue.

Method

The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of dermal and angiogenic genes. Furthermore, the co-culture system combined with dermal extracellular matrix hydrogel was used to repair the full-scale skin defects in rats.

Result

The co-culture of ASCs/EPCs could increase skin- and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could significantly accelerate the repair of skin defects by promoting the regeneration of vascularized skin.

Conclusion

It is feasible to replace traditional single-seed cells with the ASC/EPC co-culture system for vascularized skin regeneration. This system could ultimately enable clinicians to better repair the full-thickness skin defects and avoid donor site morbidity.
Comparative genomics of Flavobacterium columnare unveils novel insights in virulence and antimicrobial resistance mechanisms
Authors: Declercq Annelies Maria , Tilleman Laurentijn , Gansemans Yannick , De Witte Chloë , Haesebrouck Freddy , Van Nieuwerburgh Filip , Smet Annemieke , Decostere Annemie
Published: February 2021

This study reports the comparative analyses of four Flavobacterium columnare isolates that have different virulence and antimicrobial resistance patterns. The main research goal was to reveal new insights into possible virulence genes by comparing the genomes of bacterial isolates that could induce tissue damage and mortality versus the genome of a non-virulent isolate. The results indicated that only the genomes of the virulent isolates possessed unique genes encoding amongst others a methyl-accepting chemotaxis protein possibly involved in the initial colonization of tissue, and several VgrG proteins engaged in interbacterial competition. Furthermore, comparisons of genes unique for the genomes of the highly virulent (HV) carp and trout isolates versus the, respectively, low and non-virulent carp and trout isolates were performed. An important part of the identified unique virulence genes of the HV-trout isolate was located in one particular gene region identified as a genomic island. This region contained araC and nodT genes, both linked to pathogenic and multidrug-resistance, and a luxR-gene, functional in bacterial cell-to-cell communication. Furthermore, the genome of the HV-trout isolate possessed unique sugar-transferases possibly important in bacterial adhesion. The second research goal was to obtain insights into the genetic basis of acquired antimicrobial resistance. Several point-mutations were discovered in gyrase-genes of an isolate showing phenotypic resistance towards first and second-generation quinolones, which were absent in isolates susceptible to quinolones. Tetracycline-resistance gene tetA was found in an isolate displaying acquired phenotypic resistance towards oxytetracycline. Although not localized on a prophage, several flanking genes were indicative of the gene’s mobile character.
Considerations when offering mental health first aid to a person with an intellectual disability: a Delphi study
Authors: Bond Kathy S. , Cottrill Fairlie A. , Kelly Louise , Broughan Joan , Davies Kimberley , Ross Anna M. , Kelly Claire M.
Published: February 2021

Background

People with an intellectual disability experience higher rates of mental health problems, but experience significant barriers to receiving professional help. Increasing the knowledge and skills of those who support them can help to reduce some of these barriers. This study aimed to develop guidelines for offering mental health first aid to a person with an intellectual disability.

Methods

Using the Delphi research method, a systematic search of websites, books and journal articles was conducted to develop a survey containing items about the knowledge, skills and actions needed for assisting a person with an intellectual disability who is experiencing mental health problems. These items were rated over three survey rounds by an expert panel according to whether they should be included in the guidelines.

Results

Fifty-three experts completed all three survey rounds (67% retention rate). A total of 202 items were rated over the three rounds to yield 170 endorsed items that were incorporated into the guidelines. The developed guidelines emphasise the need to recognise the unique signs of mental health problems in people with an intellectual disability, and provide appropriate support, communication and respect for people with an intellectual disability. The guidelines will also build the capacity of carers to address behaviours of concern, socially limiting behaviours or seeking professional help when the need arises. The guidelines will be used to develop a mental health first aid course.

Conclusion

The guidelines and the resultant mental health first aid course will be a helpful resource with the potential to address some of the barriers to mental health help-seeking that people with an intellectual disability experience.
Outpatient versus inpatient superficial parotidectomy: Clinical and pathological characteristics
Authors: Lee Daniel J. , Forner David , End Christopher , Yao Christopher M. K. L. , Samargandy Shireen , Monteiro Eric , Witterick Ian J. , Freeman Jeremy L.
Published: February 2021

Background

Superficial parotidectomy has a potential to be performed as an outpatient procedure. The objective of the study is to evaluate the safety and selection profile of outpatient superficial parotidectomy compared to inpatient parotidectomy.

Methods

A retrospective review of individuals who underwent superficial parotidectomy between 2006 and 2016 at a tertiary care center was conducted. Primary outcomes included surgical complications, including transient/permanent facial nerve palsy, wound infection, hematoma, seroma, and fistula formation, as well as medical complications in the postoperative period. Secondary outcome measures included unplanned emergency room visits and readmissions within 30 days of operation due to postoperative complications.

Results

There were 238 patients included (124 in outpatient and 114 in inpatient group). There was no significant difference between the groups in terms of gender, co-morbidities, tumor pathology or tumor size. There was a trend towards longer distance to the hospital from home address (111 Km in inpatient vs. 27 in outpatient, mean difference 83 km [95% CI,- 1 to 162 km], p = 0.053). The overall complication rates were comparable between the groups (24.2% in outpatient group vs. 21.1% in inpatient, p = 0.56). There was no difference in the rate of return to the emergency department (3.5% vs 5.6%, p = 0.433) or readmission within 30 days (0.9% vs 0.8%, p = 0.952).

Conclusion

Superficial parotidectomy can be performed safely as an outpatient procedure without elevated risk of complications.

Graphical Abstract