bluuebunny/crossref_metadata_2025 huggingface dataset:
Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy
Authors: Ma Ke , Zhu Bo , Wang Zetao , Cai Peian , He Mingwei , Ye Danyan , Yan Guohua , Zheng Li , Yang Lujun , Zhao Jinmin
Published: November 2020

Background

Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported.

Results

We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy.

Conclusions

C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.
Intracholecystic papillary neoplasm arising in a patient with pancreaticobiliary maljunction: a case report
Authors: Iwasaki Toshimitsu , Otsuka Yasuhiro , Miyata Yoichi , Einama Takahiro , Tsujimoto Hironori , Ueno Hideki , Ogata Sho , Kishi Yoji
Published: November 2020

Background

Pancreaticobiliary maljunction (PBM) is a congenital abnormality in which the pancreatic and biliary ducts join anatomically outside the duodenal wall resulting in the regurgitation of pancreatic juice into the biliary tract (pancreatobiliary reflux). Persistent pancreatobiliary reflux causes injury to the epithelium of the biliary tract and promotes the risk of biliary cancer. Intracholecyctic papillary neoplasm (ICPN) has been highlighted in the context of a cholecystic counterpart of intraductal papillary mucinous neoplasm of the pancreas and the bile duct, but the tumorigenesis of ICPNs remains unclear.

Case presentation

A 52-year-old Japanese woman was referred for the assessment of dilation of the bile duct. Computed tomography which revealed an enhanced mass in the gallbladder and endoscopic retrograde cholangiopancreatography confirmed that the confluence of the main pancreatic duct and extrahepatic bile duct (EHBD) was located outside the duodenal wall. Under the diagnosis of gallbladder cancer with PBM, cholecystectomy with full thickness dissection, EHBD resection, lymph node dissection, and hepaticojejunostomy were performed. Macroscopic examination of the resected specimen showed that the cystic duct was dilated and joined into the EHBD just above its confluence with the pancreatic duct, and the inflamed change of non-tumorous mucosa of gallbladder indicating that there was considerable mucosal injury due to pancreatobiliary reflux to the gallbladder. Histopathological examination revealed that the gallbladder tumor was a gastric-type ICPN with non-invasive component. EitherKRASgene mutation or p53 protein expression that were known to be associated with the carcinogenesis of biliary cancer under the condition of pancreatobiliary reflux was not detected in the tumor cells of ICPN.

Conclusion

The present case might suggest that there was no association between PBM and ICPN. To reveal the tumorigenesis of ICPN and its attribution to pancreatobiliary reflux, however, further study is warranted.
Frequent use of emergency departments and chronic conditions in ageing societies: a retrospective analysis based in Italy
Authors: di Bella Enrico , Gandullia Luca , Leporatti Lucia , Locatelli Walter , Montefiori Marcello , Persico Luca , Zanetti Roberta
Published: November 2020

Background

Most western countries are facing relevant demographic changes, and the percentage of older people is destined to rise in the next decades. This fact is likely to affect the sustainability of healthcare systems significantly, mainly due to the connected issue of chronicity.

Methods

In this paper, using an extensive and comprehensive administrative dataset, we analyse the phenomenon of frequent use of emergency departments (ED) in the oldest region in Europe (i.e. Liguria) over 4 years (2013–2016). Two alternative approaches are used to define categories of ED users based on the intensity and frequency of accesses and splitting patients into different age groups.

Results

Results allow identifying clinical and socio-demographic risk-factors connected to different levels of ED utilisation and highlight the influential role played by chronic conditions (particularly mental disorders, respiratory diseases) and by multiple chronic conditions.

Conclusions

The study aims at representing an informative tool to support policy-makers in setting proper policies addressed, on the one side, towards the potentially preventable frequent users and, on the other, towards those accessing due to complex medical conditions. The results can help in building a warning system to help general practitioners in the identification of potential frequent users and to develop preventive policies.
Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study
Authors: Kesse-Guyot Emmanuelle , Rebouillat Pauline , Payrastre Laurence , Allès Benjamin , Fezeu Léopold K. , Druesne-Pecollo Nathalie , Srour Bernard , Bao Wei , Touvier Mathilde , Galan Pilar , Hercberg Serge , Lairon Denis , Baudry Julia
Published: November 2020

Background

Organic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors.

The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D.

Methods

A total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014–2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors).

Results

During follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43–0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95–0.99).

Conclusions

In this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations.

Clinical trial registry

The study was registered at ClinicalTrials.gov (NCT03335644).
Evaluation of the SureX HPV genotyping test for the detection of high-risk HPV in cervical cancer screening
Authors: Wei Baojun , Mei Ping , Huang Shengkai , Yu Xueting , Zhi Tong , Wang Guojing , Xu Xiaotian , Xiao Lin , Dong Xin , Cui Wei
Published: November 2020

Background

The SureX HPV genotyping test (SureX HPV test), which targets the human papillomavirus (HPV) E6/E7 genes was compared with the Cobas 4800 and Venus HPV tests for detecting 14 high-risk HPV (HR-HPV) types in clinical referral and follow-up patients to evaluate its value for cervical cancer screening.

Methods

Two different populations were enrolled in the study. The first population comprised 185 cases and was used for comparing the SureX HPV test (Health, China) with the Cobas 4800 test (Roche, USA). The second population comprised 290 cases and was used for comparing the SureX HPV test (Health, China) with the Venus HPV test (Zhijiang, China). Polymerase chain reaction (PCR) sequencing was performed for further confirmation of discordant results.

Results

In the first population, the overall agreement rate was 95.6% for 14 high-risk HPV types. Eight discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 75.0% between the SureX HPV test and PCR sequencing and 25.0% between the Cobas 4800 test and PCR sequencing (P < 0.01). In the second population, the overall agreement rate was 95.5%. Thirteen discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 76.9% between the SureX HPV test and PCR sequencing and 23.1% between the Venus HPV test and PCR sequencing (P < 0.01). With cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the sensitivity values of the SureX HPV test and the Venus HPV test were 93.5% and 92.0%, (P > 0.05), while the specificity values were 43.3% and 46.7%, respectively (P > 0.05).

Conclusion

The SureX HPV test had good consistency with both the Cobas 4800 and Venus HPV tests for 14 HR-HPV types. In addition, it avoided some false negatives and false positives. Therefore, the SureX HPV test can be used for cervical cancer screening.
Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model
Authors: Guha Sanjib , Fischer Sarah , Johnson Gail V. W. , Nehrke Keith
Published: November 2020

Background

A defining pathological hallmark of the progressive neurodegenerative disorder Alzheimer’s disease (AD) is the accumulation of misfolded tau with abnormal post-translational modifications (PTMs). These include phosphorylation at Threonine 231 (T231) and acetylation at Lysine 274 (K274) and at Lysine 281 (K281). Although tau is recognized to play a central role in pathogenesis of AD, the precise mechanisms by which these abnormal PTMs contribute to the neural toxicity of tau is unclear.

Methods

Human 0N4R tau (wild type) was expressed in touch receptor neurons of the genetic model organismC. elegansthrough single-copy gene insertion. Defined mutations were then introduced into the single-copy tau transgene through CRISPR-Cas9 genome editing. These mutations included T231E, to mimic phosphorylation of a commonly observed pathological epitope, and K274/281Q, to mimic disease-associated lysine acetylation – collectively referred as “PTM-mimetics” – as well as a T231A phosphoablation mutant. Stereotypical touch response assays were used to assess behavioral defects in the transgenic strains as a function of age. Genetically-encoded fluorescent biosensors were expressed in touch neurons and used to measure neuronal morphology, mitochondrial morphology, mitophagy, and macro autophagy.

Results

Unlike existing tau overexpression models,C. eleganssingle-copy expression of tau did not elicit overt pathological phenotypes at baseline. However, strains expressing disease associated PTM-mimetics (T231E and K274/281Q) exhibited reduced touch sensation and neuronal morphological abnormalities that increased with age. In addition, the PTM-mimetic mutants lacked the ability to engage neuronal mitophagy in response to mitochondrial stress.

Conclusions

Limiting the expression of tau results in a genetic model where modifications that mimic pathologic tauopathy-associated PTMs contribute to cryptic, stress-inducible phenotypes that evolve with age. These findings and their relationship to mitochondrial stress provides a new perspective into the pathogenic mechanisms underlying AD.
Pathway information extracted from 25 years of pathway figures
Authors: Hanspers Kristina , Riutta Anders , Summer-Kutmon Martina , Pico Alexander R.
Published: November 2020

Thousands of pathway diagrams are published each year as static figures inaccessible to computational queries and analyses. Using a combination of machine learning, optical character recognition, and manual curation, we identified 64,643 pathway figures published between 1995 and 2019 and extracted 1,112,551 instances of human genes, comprising 13,464 unique NCBI genes, participating in a wide variety of biological processes. This collection represents an order of magnitude more genes than found in the text of the same papers, and thousands of genes missing from other pathway databases, thus presenting new opportunities for discovery and research.
Process evaluation within pragmatic randomised controlled trials: what is it, why is it done, and can we find it?—a systematic review
Authors: French Caroline , Pinnock Hilary , Forbes Gordon , Skene Imogen , Taylor Stephanie J. C.
Published: November 2020

Background

Process evaluations are increasingly conducted within pragmatic randomised controlled trials (RCTs) of health services interventions and provide vital information to enhance understanding of RCT findings. However, issues pertaining to process evaluation in this specific context have been little discussed. We aimed to describe the frequency, characteristics, labelling, value, practical conduct issues, and accessibility of published process evaluations within pragmatic RCTs in health services research.

Methods

We used a 2-phase systematic search process to (1) identify an index sample of journal articles reporting primary outcome results of pragmatic RCTs published in 2015 and then (2) identify all associated publications. We used an operational definition of process evaluation based on the Medical Research Council’s process evaluation framework to identify both process evaluations reported separately and process data reported in the trial results papers. We extracted and analysed quantitative and qualitative data to answer review objectives.

Results

From an index sample of 31 pragmatic RCTs, we identified 17 separate process evaluation studies. These had varied characteristics and only three were labelled ‘process evaluation’. Each of the 31 trial results papers also reported process data, with a median of five different process evaluation components per trial. Reported barriers and facilitators related to real-world collection of process data, recruitment of participants to process evaluations, and health services research regulations. We synthesised a wide range of reported benefits of process evaluations to interventions, trials, and wider knowledge. Visibility was often poor, with 13/17 process evaluations not mentioned in the trial results paper and 12/16 process evaluation journal articles not appearing in the trial registry.

Conclusions

In our sample of reviewed pragmatic RCTs, the meaning of the label ‘process evaluation’ appears uncertain, and the scope and significance of the term warrant further research and clarification. Although there were many ways in which the process evaluations added value, they often had poor visibility. Our findings suggest approaches that could enhance the planning and utility of process evaluations in the context of pragmatic RCTs.

Trial registration

Not applicable for PROSPERO registration
Genomics in the era of COVID-19: ethical implications for clinical practice and public health
Authors: Geller Gail , Duggal Priya , Thio Chloe L. , Mathews Debra , Kahn Jeffrey P. , Maragakis Lisa L. , Garibaldi Brian T.
Published: November 2020

Genomic studies of patients with COVID-19, or exposed to it, are underway to delineate host factors associated with variability in susceptibility, infectivity, and disease severity. Here, we highlight the ethical implications—both potential benefits and harms—of genomics for clinical practice and public health in the era of COVID-19.
Single-cell transcriptome conservation in a comparative analysis of fresh and cryopreserved human skin tissue: pilot in localized scleroderma
Authors: Mirizio Emily , Tabib Tracy , Wang Xinjun , Chen Wei , Liu Christopher , Lafyatis Robert , Jacobe Heidi , Torok Kathryn S.
Published: November 2020

Background

The purpose of this study was to assess variability in cell composition and cell-specific gene expression in the skin of patients with localized scleroderma (LS) utilizing CryoStor® CS10 in comparison to RPMI to produce adequate preservation of tissue samples and cell types of interest for use in large-scale multi-institutional collaborations studying localized scleroderma and other skin disorders.

Methods

We performed single-cell RNA sequencing on paired skin biopsy specimens from 3 patients with LS. Each patient with one sample cryopreserved in CryoStor® CS10 and one fresh in RPMI media using 10× Genomics sequencing.

Results

Levels of cell viability and yield were comparable between CryoStor® CS10 (frozen) and RPMI (fresh) preserved cells. Furthermore, gene expression between preservation methods was collectively significantly correlated and conserved across all 18 identified cell cluster populations.

Conclusion

Comparable cell population and transcript expression yields between CryoStor® CS10 and RPMI preserved cells support the utilization of cryopreserved skin tissue in single-cell analysis. This suggests that employing standardized cryopreservation protocols for the skin tissue will help facilitate multi-site collaborations looking to identify mechanisms of disease in disorders characterized by cutaneous pathology.
Mycophenolic acid, the active form of mycophenolate mofetil, interferes with IRF7 nuclear translocation and type I IFN production by plasmacytoid dendritic cells
Authors: Shigesaka Minoru , Ito Tomoki , Inaba Muneo , Imai Kai , Yamanaka Hideki , Azuma Yoshiko , Tanaka Akihiro , Amuro Hideki , Nishizawa Tohru , Son Yonsu , Satake Atsushi , Ozaki Yoshio , Nomura Shosaku
Published: November 2020

Background

Both humoral and cellular immune mechanisms are involved in the onset and progression of autoimmune responses in systemic lupus erythematosus (SLE). Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of SLE via the dysregulation of type I interferon (IFN) production; these cells act together with activated myeloid DCs (mDCs) to amplify the vicious pathogenic spiral of autoimmune disorders. Therefore, control of aberrant DC activation in SLE may provide an alternative treatment strategy against this disease. Mycophenolate mofetil (MMF), which has been used to treat lupus nephritis, specifically blocks the proliferation of B and T lymphocytes via inhibition of inosine-5-monophosphate dehydrogenase. Here, we focus on the effects of MMF in targeting DC functions, especially the IFN response of pDCs.

Methods

We isolated human blood pDCs and mDCs by flow cytometry and examined the effect of mycophenolic acid (MPA), which is a metabolic product of MMF, on the toll-like receptor (TLR) ligand response of DC subsets. Additionally, we cultured pDCs with serum from SLE patients in the presence or absence of MPA and then examined the inhibitory function of MPA on SLE serum-induced IFN-α production.

Results

We found that treatment with 1−10 μM of MPA (covering the clinical trough plasma concentration range) dose-dependently downregulated the expression of CD80 and CD86 on mDCs (but not pDCs) without inducing apoptosis, in response to R848 or CpG-ODN, respectively. Notably, in pDCs, MPA significantly suppressed IFN-α production with IRF7 nuclear translocation and repressed the AKT activity. In addition, MPA inhibited IL-12 production with STAT4 expression in mDCs. We further identified that MPA had an inhibitory effect on SLE serum-induced IFN-α production by pDCs.

Conclusions

Our data suggest that MPA can interrupt the vicious pathogenic spiral of autoimmune disorders by regulating the function of DC subsets. This work unveiled a novel mechanism for the therapeutic ability of MMF against SLE.
Autism-linked mutations of CTTNBP2 reduce social interaction and impair dendritic spine formation via diverse mechanisms
Authors: Shih Pu-Yun , Hsieh Bing-Yuan , Tsai Ching-Yen , Lo Chiu-An , Chen Brian E. , Hsueh Yi-Ping
Published: November 2020

Abnormal synaptic formation and signaling is one of the key molecular features of autism spectrum disorders (ASD). Cortactin binding protein 2 (CTTNBP2), an ASD-linked gene, is known to regulate the subcellular distribution of synaptic proteins, such as cortactin, thereby controlling dendritic spine formation and maintenance. However, it remains unclear how ASD-linked mutations of CTTNBP2 influence its function. Here, using cultured hippocampal neurons and knockin mouse models, we screen seven ASD-linked mutations in the short form of the Cttnbp2 gene and identify that M120I, R533* and D570Y mutations impair CTTNBP2 protein–protein interactions via divergent mechanisms to reduce dendritic spine density in neurons. R533* mutation impairs CTTNBP2 interaction with cortactin due to lack of the C-terminal proline-rich domain. Through an N–C terminal interaction, M120I mutation at the N-terminal region of CTTNBP2 also negatively influences cortactin interaction. D570Y mutation increases the association of CTTNBP2 with microtubule, resulting in a dendritic localization of CTTNBP2, consequently reducing the distribution of CTTNBP2 in dendritic spines and impairing the synaptic function of CTTNBP2. Finally, we generated heterozygous M120I knockin mice to mimic the genetic variation of patients and found they exhibit reduced social interaction. Our study elucidates that different ASD-linked mutations of CTTNBP2 result in diverse molecular deficits, but all have the similar consequence of synaptic impairment.
Spinal muscular atrophy type III complicated by spinal superficial siderosis: a case report with molecular and neuropathological findings
Authors: Pringle Catherine Elizabeth , Nelson Robert , Miller Willie , Kothary Rashmi , Michaud Jean
Published: November 2020

Spinal muscular atrophy (SMA) is largely linked to deletion or mutation of the Survival motor neuron 1 (SMN1) gene located on chromosome 5q13. Type III (Kugelberg–Welander disease) is the mildest childhood form and patients may become ambulatory and have a normal life expectancy. We report the clinical history and morphological findings of a 55-year-old woman who began to experience motor problems at the age of two. She was never fully ambulatory, and her severe scoliosis required the insertion of surgical rod at age 19. Unexpectedly, around 35 years of age, she began to experience sensory symptoms best characterized as a myelo-radiculo-neuropathy with pain as the dominant symptom. Investigations never clarified the etiology of these symptoms. Molecular confirmation of SMA type III was done post-mortem. Neuropathological examination showed classic changes of lower motor neuron neurodegeneration, in line with those reported in the single molecularly confirmed case published so far, and with findings in rare cases reported prior to the discovery of the gene defect. A key autopsy finding was the presence of a severe superficial siderosis of the lower half of the spinal cord. In recent years, the concept of duropathy was put forward, associating superficial siderosis of the spinal cord with various spinal abnormalities, some of which were present in our patient.
The presence of significant hemosiderin deposits in the spinal cord and sensory nerve roots with associated tissue and axonal damage provide a plausible explanation for the unexpected sensory symptomatology in this mild lower motor neurodegeneration.
Planar free-standing metal layer fabrication: implementing sub-structures in micromirror arrays for light steering applications
Authors: Worapattrakul Natalie , Tatzel Andreas , Viereck Volker , Hillmer Hartmut
Published: November 2020

We present a method to fabricate planar metal layers to be used as micromachined mirrors. Released mirrors of pure metal involve severe stress and reveal specific challenges to obtain planar mirror structures. Introducing sub-structures generating corrugated patterns, the metal mirror layers can be mechanically stabilized and undesired mirror bending can be reduced. For our investigations we used different arrangements of line structures on our metal mirrors, such as a group of straight or curved lines oriented differently. Comparing all the implemented different designs, planar micromirrors were achieved via sub-structures with a combination of straight lines arranged orthogonally to a single line. These planar micromirrors allow steering of the incident light by reflection and adjustment of the window transmittance. The presented low-cost method is suitable for large area fabrication of micromirror arrays, but also can be customized for other applications, where planar free-standing metal layers are required.
Sclerotherapy and prolotherapy for chronic patellar tendinopathies - a promising therapy with limited available evidence, a systematic review
Authors: Morath Oliver , Beck Manuel , Taeymans Jan , Hirschmüller Anja
Published: November 2020

Chronic Patellar tendinopathy (CPT) is a frequent overuse disorder in athletes and active people. Sclerotherapy (ST) and prolotherapy (PT) are, among a wide range of conservative treatment options, two promising therapies and have shown positive results in other tendinopathies. Since the treatments’ efficacy and safety are still not defined, this review sought to answer questions on recommendations for use in clinical utility, safety, and how to perform the injection in the most effective way. An electronic database search was conducted following the PRISMA guidelines. Inclusion criteria were set up according to the PICOS-scheme. Included were athletes and non-athletes of all ages with diagnosed painful CPT. Studies including patients suffering from patellar tendinopathy which can be originated to any systemic condition affecting the musculoskeletal system (e.g. disorders associated with rheumatism) and animal studies were excluded. Methodological quality (modified Coleman Methodology Score) and risk of bias (Cochrane Risk of Bias Assessment Tool 2.0) were assessed by two independent reviewers, with disagreements resolved with a third reviewer. The search yielded a total of 416 entries. After screening titles, abstracts, and full texts, ten articles were found for qualitative analysis. The mean Coleman Score was 64.57. Three randomized-controlled trials showed positive results with an increase in VISA-P score or a decrease in VAS or NPPS, respectively. The non-randomized studies confirmed the positive results as well. Among all ten studies no serious adverse events were reported. Based on this limited set of studies, there seems to be some evidence that ST and PT may be effective treatment options to treat pain and to improve function in patients with CPT. To strengthen this recommendation, more research is needed with larger volume studies and randomized controlled studies with long term follow up.

Level of evidence

IV
Optimising recruitment to the HAND-1 RCT feasibility study: integration of the QuinteT Recruitment Intervention (QRI)
Authors: Husbands Samantha , Elliott Daisy , Davis Tim R. C. , Blazeby Jane M. , Harrison Eleanor F. , Montgomery Alan A. , Sprange Kirsty , Duley Lelia , Karantana Alexia , Hollingworth William , Mills Nicola
Published: November 2020

Background

Recruitment to randomised controlled trials (RCTs) can be challenging, with most trials not reaching recruitment targets. Randomised feasibility studies can be set up prior to a main trial to identify and overcome recruitment obstacles. This paper reports on an intervention—the QuinteT Recruitment Intervention (QRI)—to optimise recruitment within a randomised feasibility study of surgical treatments for patients with Dupuytren’s contracture (the HAND-1 study).

Methods

The QRI was introduced in 2-phases: phase 1 sought to understand the recruitment challenges by interviewing trial staff, scrutinising screening logs and analysing audio-recorded patient consultations; in phase 2 a tailored plan of action consisting of recruiter feedback and training was delivered to address the identified challenges.

Results

Two key recruitment obstacles emerged: (1) issues with the recruitment pathway, in particular methods to identify potentially eligible patients and (2) equipoise of recruiters and patients. These were addressed by liaising with centres to share good practice and refine their pathway and by providing bespoke feedback and training on consent discussions to individual recruiters and centres whilst recruitment was ongoing. The HAND-1 study subsequently achieved its recruitment target.

Conclusions

Transferable lessons learnt from the QRI in the feasibility study will be implemented in the definitive RCT, enabling a “head start” in the tackling of wider issues around screening methods and consent discussions in the set up/early recruitment study phases, with ongoing QRI addressing specific issues with new centres and recruiters. Findings from this study are likely to be relevant to other surgical and similar trials that are anticipated to encounter issues around patient and recruiter equipoise of treatments and variation in recruitment pathways across centres. The study also highlights the value of feasibility studies in fine-tuning design and conduct issues for definitive RCTs. Embedding a QRI in an RCT, at feasibility or main stage, offers an opportunity for a detailed and nuanced understanding of key recruitment challenges and the chance to address them in “real-time” as recruitment proceeds.
Phytochemical and pharmacological activities of methanol extract of Artemisia vulgaris L. leaves
Authors: Thangjam Nurpen Meitei , Taijong Jasmina , Kumar Awadhesh
Published: November 2020

Background

Artemisia vulgaris commonly known as “mugwort” is a very important medicinal plant which is used widely for the treatment of various ailments traditionally. The present studies aimed to conduct preliminary phytochemical screening and evaluate antioxidants and analgesic activities of leaves extract.

Results

Phytochemical screening showed the presence of saponins, glycosides, flavanoids, protein, triterpenoids in leaves extract. In DPPH, percentage inhibition of the scavenging activity (68.06%) by the extract in comparison with ascorbic acid (93.53%) at 60 μg/ml while in reducing power assay, the result shown the reducing power increases with the increase of concentration as (0.13 ± 0.02), (0.27 ± 0.03), (0.42 ± 0.03), (0.62 ± 0.05), (0.79 ± 0.02), (0.95 ± 0.05) at concentration of 5, 10, 15, 30, 60 and 100 μg/ml respectively. The evaluation of analgesic activities revealed that at the dose of 200 and 400 mg/kg of the extract showed significantly inhibited the writhing response induced by acetic acid by 8.60% and 32.03% comparatively with indomethacin at a dose of 10 mg/kg b. wt. exhibited 56.87% inhibition. Whereas, in the tail immersion methods, at the dose of 400 mg/kg b. wt. was showed higher deflexion value as 3.40 ± 0.300, while 200 mg/kg b. wt. was resulted at 2.90 ± 0.200 value in dose dependent manner at the maximum time of the studies (60 min). Comparatively, the reference drug indomethacin at dose 10 mg/kg b. wt. has shown the highest deflexion value (5.134 ± 0.351).

Conclusion

This finding concludes that the methanolic leaves extract has a potent antioxidants and analgesic activities and it could be attributed to the presence of flavonoids, triterpenoids, saponin, glycosides and proteins. A further study is required to find out the novel bioactive compound of Artemisia vulgaris L. which can lead more effective in various biological activities.
Can chest CT improve sensitivity of COVID-19 diagnosis in comparison to PCR? A meta-analysis study
Authors: Mahmoud Heba , Taha Mohamed Shehata , Askoura Anas , Aleem Mohammed , Omran Azza , Aboelela Soha
Published: November 2020

Background

In December 2019, SARS-CoV-2 was identified as the causative agent of pneumonia cases in China. This virus is spread by coughing or sneezing and can infect other persons by on contacting mucous membranes. SARS-Cov-2 most frequent serious manifestation is pneumonia. Chest computed tomography in COVID-19 patients usually shows ground-glass opacities that may be accompanied by consolidation lesions. Early diagnosis of the disease and rapid isolation of the patient is of great importance. So far, confirmation of COVID-19 infection is made by RT-PCR of nasopharyngeal or respiratory specimens. Recent research reported that the sensitivity of computed tomography in diagnosing COVID-19 is 98% while RT-PCR sensitivity is 71%. Herein, we compare the sensitivity of both chest CT and RT-PCR in diagnosing COVID-19 at initial patient presentation through a meta-analysis study.

Main body

Using MEDLINE database a systematic literature search was conducted to identify relevant published studies within from November 2019 to April 2020. Only articles with full text were examined to determine eligibility and extract data by two reviewers. It was decided to include studies mentioning sensitivity of chest CT scan and sensitivity of RT-PCR and both done at the same time.

Results

Potentially relevant 15,300 studies were identified in our search in MEDLINE whose titles were quickly reviewed. Potentially eligible studies missing any of the forementioned inclusion criteria were excluded. This process left 7 eligible articles that fulfilled the inclusion criteria and were thus included in the meta-analysis and used for further analyses.

Conclusion

The meta-analysis study showed that chest CT may be beneficial in early detection of cases of COVID-19. Imaging, in adjunct to clinical and laboratory findings, should be used for monitoring of disease course, until further evidence is available.
Diabetes, Brain Infarcts, Cognition, and Small Vessels in the Canadian Alliance for Healthy Hearts and Minds Study
Authors: Gerstein Hertzel C , Smith Eric E , Ramasundarahettige Chinthanie , Desai Dipika , Awadalla Philip , Broet Philippe , Black Sandra , Dummer Trevor J B , Hicks Jason , Moody Alan , Tardif Jean-Claude , Teo Koon K , Vena Jennifer , Yusuf Salim , Lee Douglas S , Friedrich Matthias G , Anand Sonia S
Published: November 2020

Background

Diabetes is a risk factor for cerebrovascular disease and cognitive impairment. The anatomical basis for this is uncertain.

Methods

The Canadian Alliance for Healthy Hearts and Minds collected brain and carotid magnetic resonance imaging (MRI) and 2 cognitive tests (the Digit Symbol Substitution Test and the Montreal Cognitive Assessment test) in a cross-sectional sample of men and women. Brain MRIs identified brain infarcts (BI), lacunar BI, high white matter hyperintensity (WMH), vascular brain injury (VBI; BI or high WMH), and small vessel VBI (lacunar BI or high WMH). Carotid MRIs estimated carotid wall volume, a measure of subclinical atherosclerosis. Cognitive scores were standardized to each site’s mean score, and cognitive impairment was identified by 1 or both test scores ≤1 standard deviation below the site’s mean score on that test.

Results

The 7733 participants included 495 participants (6.4%) with diabetes, of whom 388 were taking diabetes drugs. After age and sex adjustment, diabetes was independently associated with BI (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.05, 2.24), VBI (OR 1.64, 95% CI 1.26, 2.13), small vessel VBI (OR 1.67, 95% CI 1.28, 2.19), and cognitive impairment (OR 1.47, 95% CI 1.20, 1.80). The association between diabetes and small vessel VBI persisted after adjustment for cerebrovascular disease risk factors and nonlacunar infarcts (OR 1.52, 95% CI 1.15, 2.01), and the association with cognitive impairment persisted after adjustment for small vessel VBI (OR 1.27, 95% CI 1.03, 1.56).

Conclusion

Small vessel disease characterizes much of the relationship between diabetes and VBI. However, additional factors are required to disentangle the relationship between diabetes and cognitive impairment.
Unfavorable Triglyceride-rich Particle Profile in Subclinical Thyroid Disease: A Cross-sectional Analysis of ELSA-Brasil
Authors: Janovsky Carolina Castro Porto Silva , Bittencourt Marcio Sommer , Goulart Alessandra C , Santos Raul D , Blaha Michael J , Jones Steven , Toth Peter P , Lotufo Paulo A , Benseñor Isabela M
Published: November 2020

Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. As triglyceride-rich lipoprotein particles (TRLPs) have recently emerged as a casual factor for atherogenesis, the aim of this study was to evaluate the relationship between subclinical hypo- and hyperthyroidism and TRLP subfractions.

We selected 5066 participants from the ELSA-Brasil cohort with available data of thyroid function and lipid profile measured by nuclear magnetic resonance (NMR) spectroscopy. Individuals were divided into 3 groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). Triglyceride-rich lipoprotein particle subfractions were analyzed through NMR spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted univariate and multivariate linear regression models adjusted for demographic characteristics, body mass index, diabetes, smoking status, and alcohol use.

Of 3304 individuals, 54% were women, with a mean age of 50.6 ± 8.7 years, 51% white, and 53% with at least a college education. Of these individuals, 92% were euthyroid, whereas 6.8% had subclinical hypothyroidism and 1.2% had subclinical hyperthyroidism. The univariate linear regression showed that very small TRLPs (P = 0.026) and very large TRLPs (P = 0.008) were statistically increased in subclinical hypothyroidism when compared with euthyroidism. In subclinical hyperthyroidism, there was a reduction in total TRLPs (P = 0.003), seemingly driven by reduced very small TRLPs (P = 0.067).

The findings were confirmed when adjusted for demographic characteristics, as well as comorbidities. This study suggests that subclinical hypothyroidism is associated with very small and very large TRLPs, which are related to an unfavorable atherogenic profile. Subclinical hyperthyroidism is associated to lower very small TRLPs.
Neuronal circuits and the magnetic sense: central questions
Authors: Malkemper E. Pascal , Nimpf Simon , Nordmann Gregory C. , Keays David A.
Published: November 2020

Magnetoreception is the ability to sense the Earth's magnetic field, which is used for orientation and navigation. Behavioural experiments have shown that it is employed by many species across all vertebrate classes; however, our understanding of how magnetic information is processed and integrated within the central nervous system is limited. In this Commentary, we review the progress in birds and rodents, highlighting the role of the vestibular and trigeminal systems as well as that of the hippocampus. We reflect on the strengths and weaknesses of the methodologies currently at our disposal, the utility of emerging technologies and identify questions that we feel are critical for the advancement of the field. We expect that magnetic circuits are likely to share anatomical motifs with other senses, which culminates in the formation of spatial maps in telencephalic areas of the brain. Specifically, we predict the existence of spatial cells that encode defined components of the Earth's magnetic field.
Minimally Invasive Approaches in Locally Advanced Cervical Cancer Patients Undergoing Radical Surgery After Chemoradiotherapy: A Propensity Score Analysis
Authors: Ferrandina G. , Gallotta V. , Federico A. , Fanfani F. , Ercoli A. , Chiantera V. , Cosentino F. , Turco L. C. , Legge F. , Anchora L. Pedone , Bizzarri N. , Moroni R. , Macchia G. , Valentini V. , Scambia G.
Published: November 2020

Purpose

Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role in locally advanced cervical cancer (LACC) patients with suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Our aim is to evaluate oncological and surgical outcomes of minimally invasive radical surgery (MI-RS) compared with open radical surgery (O-RS).

Patients and Methods

Data for stage IB2–IVA cervical cancer patients managed by CT/RT and RS were retrospectively analyzed.

Results

Beginning with 686 patients, propensity score matching resulted in 462 cases (231 per group), balanced for FIGO stage, lymph node status, histotype, tumor grade, and clinical response to CT/RT. The 5-year disease-free survival (DFS) was 73.7% in the O-RS patients and 73.0% in the MI-RS patients (HR 1.034, 95% CI 0.708–1.512, p = 0.861). The 5-year locoregional recurrence rate was 12.5% (O-RS) versus 15.2% (MI-RS) (HR 1.174, 95% CI 0.656–2.104, p = 0.588). The 5-year disease-specific survival (DSS) was 80.4% in O-RS patients and 85.3% in the MI-RS group (HR 0.731, 95% CI 0.438–1.220, p = 0.228). Estimated blood loss was lower in the MI-RS group (p < 0.001), as was length of hospital stay (p < 0.001). Early postoperative complications occurred in 77 patients (33.3%) in the O-RS group versus 88 patients (38.1%) in the MI-RS group (p = 0.331). Fifty-six (24.2%) patients experienced late postoperative complications in the O-RS group, versus 61 patients (26.4%) in the MI-RS group (p = 0.668).

Conclusion

MI-RS and O-RS are associated with similar rates of recurrence and death in LACC patients managed by surgery after CT/RT. No difference in early or late complications was reported.
The Future of European Values
Authors: Grayling AC
Published: November 2020

The EU’s values of transnational peace, cooperation, secularism, rationality,
and protection of civil liberties and human rights are amongst the most valuable
legacies of the Enlightenment. The European project has weathered several crises
in the first third of the 21st century, including a change of political direction in the
United Kingdom. Brexit is viewed as a consequence of the UK’s flawed electoral
system, exposed as susceptible to hijacking by militant and disruptive minorities.
The future of European values must be protected from politically unreliable
systems such as the UK’s FPTP.
La COVID-19 y sus efectos en la asimetría de las relaciones UE-China: ¿hacia un nuevo paradigma económico?
Authors: García-Weil Augusto
Published: November 2020

La COVID-19 es una pandemia devastadora. El vehículo para su propagación
ha sido la misma red de transportes necesaria para la globalización. El objeto de
este trabajo es determinar hasta qué punto la presente situación puede provocar
una alteración de las cadenas logísticas de valor entre China y la UE, que a su
vez implique un aumento de las asimetrías entre ambas partes. Analizaremos si
triunfará el offshoring, el reshoring o el nearshoring. Para ello, realizaremos
un análisis de ambos actores internacionales y de sus respectivas reacciones a
la pandemia, tanto desde el punto de vista idiosincrático, como económico y
administrativo.
Predicting Labor Market Competition: Leveraging Interfirm Network and Employee Skills
Authors: Liu Yuanyang , Pant Gautam , Sheng Olivia R. L.
Published: November 2020

Human capital is a key component of the knowledge economy. Firms compete not only for consumers in the product market but also for human capital in the labor market. In this study, we perform an interfirm labor market competitor analysis using the online profiles of more than 89,000 employees and their career histories that span more than 3,000 public firms. Using these profiles, we characterize firms through the granular skill distribution of their employees. Also, using employee migrations across firms, we derive and analyze a human capital flow (HCF) network. Such information allows us to measure the interfirm human capital overlap in terms of similarity in their employees’ skills and HCF network structure. We show that our proposed human capital overlap metrics have superior predictive power over conventional firm-level measures in predicting future labor market competitors. We further demonstrate how our proposed metrics and the prediction framework can be incorporated into a comprehensive two-dimensional competitor analysis that includes both product and labor overlap between firms. By evaluating interfirm relationships in the product and labor markets simultaneously, this two-dimensional competitor analysis framework can help managers make strategic decisions beyond human resources, such as product development and customer relationship management.
Child public health part 4: paramedics at the forefront of child protection
Authors: Robinson Simon
Published: November 2020

Paramedics are ideally placed in communities to facilitate screening and promote healthy behaviour in children, as well as identify those who may at risk of abuse or neglect. This last instalment of this four-part series on child public health explores the position of paramedics in the larger picture of child protection.