bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the implementation of evidence-informed policies and practices from a policy perspective: a critical interpretive synthesis
Authors: Bullock Heather L. , Lavis John N. , Wilson Michael G. , Mulvale Gillian , Miatello Ashleigh
Published: February 2021

Background

The fields of implementation science and knowledge translation have evolved somewhat independently from the field of policy implementation research, despite calls for better integration. As a result, implementation theory and empirical work do not often reflect the implementation experience from a policy lens nor benefit from the scholarship in all three fields. This means policymakers, researchers, and practitioners may find it challenging to draw from theory that adequately reflects their implementation efforts.

Methods

We developed an integrated theoretical framework of the implementation process from a policy perspective by combining findings from these fields using the critical interpretive synthesis method. We began with the compass question: How is policy currently described in implementation theory and processes and what aspects of policy are important for implementation success? We then searched 12 databases as well as gray literature and supplemented these documents with other sources to fill conceptual gaps. Using a grounded and interpretive approach to analysis, we built the framework constructs, drawing largely from the theoretical literature and then tested and refined the framework using empirical literature.

Results

A total of 11,434 documents were retrieved and assessed for eligibility and 35 additional documents were identified through other sources. Eighty-six unique documents were ultimately included in the analysis. Our findings indicate that policy is described as (1) the context, (2) a focusing lens, (3) the innovation itself, (4) a lever of influence, (5) an enabler/facilitator or barrier, or (6) an outcome. Policy actors were also identified as important participants or leaders of implementation. Our analysis led to the development of a two-part conceptual framework, including process and determinant components.

Conclusions

This framework begins to bridge the divide between disciplines and provides a new perspective about implementation processes at the systems level. It offers researchers, policymakers, and implementers a new way of thinking about implementation that better integrates policy considerations and can be used for planning or evaluating implementation efforts.
Anterior cruciate ligament reconstruction in a rabbit model using a silk-collagen scaffold modified by hydroxyapatite at both ends: a histological and biomechanical study
Authors: Bi Fanggang , Chen Yangdi , Liu Junqi , Wang Yafei , Xu Danfeng , Tian Ke
Published: February 2021

Background

To investigate osteointegration at the graft-bone interface and the prevention of osteoarthritis after anterior cruciate ligament (ACL) reconstruction using a silk-collagen scaffold with both ends modified by hydroxyapatite (HA) in a rabbit model.

Methods

The HA/silk-collagen scaffold was fabricated using a degummed, knitted silk scaffold, collagen I matrix, and simulated body fluid (SBF). The HA/silk-collagen scaffold was rolled up to make a graft for replacing the native ACL in the experimental group (HA group), and the silk-collagen scaffold was used in the control (S group). All specimens were harvested at 16 weeks postoperatively to evaluate graft-bone healing and osteoarthritis prevention.

Results

Histological staining revealed the massive formation of more mature bone at the tendon-bone interface, and immunohistochemistry staining revealed more collagen I and osteocalcin deposition in the HA group than in the S group. Higher signals indicating more bone mineral formation were detected in the HA group than in the S group, which was consistent with the results of biomechanical testing. Better osteoarthritis prevention was also observed in the HA group, indicating a more stable knee joint in the HA group than in the S group.

Conclusion

The HA/silk-collagen scaffold promotes osteointegration at the tendon-bone interface after ACL reconstruction and has great potential for clinical applications.
Galli gigeriae endothelium corneum: its intestinal barrier protective activity in vitro and chemical composition
Authors: Li Shanshan , Zheng Meng , Zhang Zhentang , Peng Hengying , Dai Wenling , Liu Jihua
Published: February 2021

Background

Galli gigeriae endothelium corneum (GGEC) has been effectively used for centuries for the treatment of functional dyspepsia (FD) in clinical practice in Asian countries. However, its potential mechanism and chemical composition remains undertermined.

Methods

In this study, the chemical profile of GGEC ethyl acetate extract (EAE) was evaluated by HPLC-Q-TOF–MS/MS. The effects of EAE on intestinal barrier function and inflammation were investigated in IEC-6 cells and RAW264.7 cells.

Results

The results showed that 33 compounds were tentatively identified, including 12 soy isoflavones, 7 bile acids for the first time in EAE. EAE significantly reinforced intestinal barrier function via increasing the tight junction protein levels of ZO-1 and Occludin, reducing the mRNA expression levels of interleukin (IL)-1β and IL-6 in tumor necrosis factor alpha (TNF-α)-challenged IEC-6 cells. The scratch wound assay showed that EAE accelerated wound healing of IEC-6 cells. EAE evidently reduced the level of NO in a dose-dependent manner with an IC50value of 18.12 μg/mL, and the mRNA expression of TNF-α, IL-1β, IL-6, iNOS and COX-2 in LPS-treated RAW264.7 cells.

Conclusion

This study revealed the intestinal barrier protective effects and chemical profile of GGEC, and the results indicated that GGEC strengthened the intestinal barrier by up-regulating protein expression of tight junctions and limiting inflammatory responses.
Dalfampridine in the treatment of multiple sclerosis: a meta-analysis of randomised controlled trials
Authors: Zhang Enyao , Tian Xin , Li Ruoming , Chen Chaoyang , Li Min , Ma Lingyun , Wei Ran , Zhou Ying , Cui Yimin
Published: February 2021

Background

Multiple sclerosis (MS) is a chronic illness involving the central nervous system (CNS) that is characterised by inflammation, demyelination, and degenerative changes. Dalfampridine is one of the available treatments for MS symptoms and comorbidities. This meta-analysis aimed to assess the safety and benefits of dalfampridine versus placebo in MS by summarising data deriving from previously published clinical randomised controlled studies (RCTs).

Results

A total of 9 RCTs were included in this meta-analysis, involving 1691 participants. There were significant differences between dalfampridine and placebo in terms of decreased 12-item Multiple Sclerosis Walking Scale score (weighted mean difference [WMD] =  − 3.68, 95% confidence interval [CI] [− 5.55, − 1.80], p = 0.0001), improved response to the timed 25-foot walk test (relative risk [RR] = 2.57, 95% CI [1.04, 6.33], p = 0.04), increased 6-min walk test (WMD = 18.40, 95% CI [1.30, 35.51], p = 0.03), increased 9-Hole Peg Test score (WMD = 1.33, 95% CI [0.60, 2.05], p = 0.0004), and increased Symbol Digit Modalities Test score (WMD = 4.47, 95% CI [3.91, 5.02], p < 0.00001). Significant differences in the incidence of side effects were also observed (RR = 1.12, 95% CI [1.04, 1.21], p = 0.002).

Conclusion

Dalfampridine exerts positive effects on walking ability, finger dexterity, and cognitive function. Treatment should be administered under the guidance of a physician or pharmacist given the higher incidence of adverse events.
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2
Authors: Tao En-Wei , Wang Hao-Lian , Cheng Wing Yin , Liu Qian-Qian , Chen Ying-Xuan , Gao Qin-Yan
Published: February 2021

Background

Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear.

Methods

Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5’tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5’tiRNA-His-GTG. The regulation of 5’tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments.

Results

Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5’tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5’tiRNA-His-GTG in CRC and found that targeting 5’tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5’tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5’tiRNA-His-GTG, which renders 5’tiRNA-His-GTG to “turn off” hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes.

Conclusions

In summary, the findings revealed a specific 5’tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians’ prescription habits
Authors: Cerimoniale Giovanni , Becherucci Paolo , Verga Maria Carmen , Di Mauro Giuseppe , Indinnimeo Luciana , Villani Alberto , Tosca Mariangela , Marseglia Gian Luigi , Duse Marzia , Biasci Paolo , Doria Mattia , Peroni Diego , Piacentini Giorgio , Di Cicco Maria , Pozzobon Gabriella , Lubrano Riccardo
Published: February 2021

Background

A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians’ ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis.

Methods

From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies.

Results

One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged.

Conclusions

Pediatricians’ ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians’ work settings and geographical distribution.
Could nutritional supplements act as therapeutic adjuvants in COVID-19?
Authors: Costagliola Giorgio , Spada Erika , Comberiati Pasquale , Peroni Diego G.
Published: February 2021

Background

The role of the immune system and inflammatory response in the pathogenesis of the severe manifestations of coronavirus disease 2019 (COVID-19) is well known. Currently, different therapies active on the immune system are used for the management of COVID-19. The involvement of the immune system also opens the opportunity for the use of nutritional supplements with antimicrobial and immunomodulatory activity.

Main aspects

Nutritional supplements with antimicrobial and immunomodulatory activity are promising therapeutic adjuvants for the treatment of COVID-19, and also for the prevention of viral spreading. In particular, the role of vitamin D, probiotics, lactoferrin, and zinc is of significant clinical interest, although there are only a few data on their use in COVID-19 patients. Their molecular actions, together with the results of studies performed on other respiratory infections, strongly suggest their potential utility in COVID-19. This article discusses the main properties of these nutritional supplements and their potential applicability in the prevention and treatment of COVID-19.

Conclusion

The supplementation with vitamin D, probiotics, lactoferrin and zinc could have a role both in preventing SARS-CoV-2 infection and in mitigating the clinical course in infected patients, contributing in the prevention of immune-mediated organ damage.
Diaphragm echodensity in mechanically ventilated patients: a description of technique and outcomes
Authors: Coiffard Benjamin , Riegler Stephen , Sklar Michael C. , Dres Martin , Vorona Stefannie , Reid W. Darlene , Brochard Laurent J. , Ferguson Niall D. , Goligher Ewan C.
Published: February 2021

Background

Acute increases in muscle sonographic echodensity reflect muscle injury. Diaphragm echodensity has not been measured in mechanically ventilated patients. We undertook to develop a technique to characterize changes in diaphragm echodensity during mechanical ventilation and to assess whether these changes are correlated with prolonged mechanical ventilation.

Methods

Diaphragm ultrasound images were prospectively collected in mechanically ventilated patients and in 10 young healthy subjects. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes recorded included duration of ventilation and ICU complications (including reintubation, tracheostomy, prolonged ventilation, or death).

Results

Echodensity measurements were obtained serially in 34 patients comprising a total of 104 images. Baseline (admission) diaphragm ED85 was increased in mechanically ventilated patients compared to younger healthy subjects (median 56, interquartile range (IQR) 42–84, vs. 39, IQR 36–52, p = 0.04). Patients with an initial increase in median echodensity over time (≥ + 10 in ED50 from baseline) had fewer ventilator-free days to day 60 (n = 13, median 46, IQR 0–52) compared to patients without this increase (n = 21, median 53 days, IQR 49–56, unadjusted p = 0.03). Both decreases and increases in diaphragm thickness during mechanical ventilation were associated with increases in ED50 over time (adjusted p = 0.03, conditional R2 = 0.80) and the association between increase in ED50 and outcomes persisted after adjusting for changes in diaphragm thickness.

Conclusions

Many patients exhibit increased diaphragm echodensity at the outset of mechanical ventilation. Increases in diaphragm echodensity during the early course of mechanical ventilation are associated with prolonged mechanical ventilation. Both decreases and increases in diaphragm thickness during mechanical ventilation are associated with increased echodensity.
Multi-Round compared to Real-Time Delphi for consensus in core outcome set (COS) development: a randomised trial
Authors: Quirke Fiona A. , Healy Patricia , Bhraonáin Elaine Ní , Daly Mandy , Biesty Linda , Hurley Tim , Walker Karen , Meher Shireen , Haas David M. , Bloomfield Frank H. , Kirkham Jamie J. , Molloy Eleanor J. , Devane Declan
Published: February 2021

Background

The Delphi method is used in a wide variety of settings as a method of building consensus on important issues. Traditionally, the Delphi method uses multiple rounds of a survey to allow for feedback of other participants’ survey responses in between rounds. By informing participants about how others answer a question or prioritise specific topics, it allows for diverse opinions to inform the consensus process. For this reason, the Delphi method is popular as a consensus building approach in developing core outcome sets (COS), i.e. the minimum agreed set of standardised outcomes that should be measured and reported in studies on a specific health condition. In a COS setting, participants prioritise the importance of outcomes for inclusion in a COS. This usually involves participating in multiple rounds of a survey that can span several weeks or months. Challenges with participant retention have been highlighted in previous COS. We will compare a three-round with a Real-Time Delphi approach on prioritised outcomes. This trial is embedded within the COHESION study which is developing a COS for interventions treating neonatal encephalopathy.

Methods

One hundred and eighty stakeholders (parents/caregivers of infants diagnosed and treated with neonatal encephalopathy, healthcare providers and researchers) will be randomised using stratified randomisation to take part in either the Multi-Round or Real-Time Delphi. Stakeholders will rate the importance of the same set of outcomes in both arms. We will compare the prioritised outcomes at the end of both surveys as well as other parameters such as feedback, initial condition and iteration effects.

Discussion

This trial will provide evidence to inform decisions on the use of Multi-Round compared to Real-Time Delphi survey methods.

Trial registration

NCT04471103. Registered on 14 July 2020.
Ethical care requires pragmatic care research to guide medical practice under uncertainty
Authors: Darsaut Tim E. , Raymond Jean
Published: February 2021

Background

The current research-care separation was introduced to protect patients from explanatory studies designed to gain knowledge for future patients. Care trials are all-inclusive pragmatic trials integrated into medical practice, with no extra tests, risks, or cost, and have been designed to guide practice under uncertainty in the best medical interest of the patient.

Proposed revision

Patients need a distinction between validated care, previously verified to provide better outcomes, and promising but unvalidated care, which may include unnecessary or even harmful interventions. While validated care can be practiced normally, unvalidated care should only be offered within declared pragmatic care research, designed to protect patients from harm. The validated/unvalidated care distinction is normative, necessary to the ethics of medical practice. Care trials, which mark the distinction and allow the tentative use of promising interventions necessarily involve patients, and thus the design and conduct of pragmatic care research must respect the overarching rule of care ethics “to always act in the best medical interest of the patient.” Yet, unvalidated interventions offered in contexts of medical uncertainty cannot be prescribed or practiced as if they were validated care. The medical interests of current patients are best protected when unvalidated practices are restricted to a care trial protocol, with 1:1 random allocation (or “hemi-prescription”) versus previously validated care, to optimize potential benefits and minimize risks for each patient.

Conclusion

Pragmatic trials can regulate medical practice by providing (i) a transparent demarcation between unvalidated and validated care; (ii) norms of medical conduct when using tests and interventions of yet unknown benefits in practice; and eventually (iii) a verdict regarding optimal care.
How effective are three methods of teaching oral hygiene for adolescents undergoing orthodontic treatment? The MAHO protocol: an RCT comparing visual, auditory and kinesthetic methods
Authors: Le Fouler Alisée , Jeanne Sylvie , Sorel Olivier , Brézulier Damien
Published: February 2021

Background

Fixed orthodontic appliances hamper oral hygiene procedures. The consequences are gingivitis and white spot lesions. Fifty to 70% of patients treated with braces encounter these problems. Their care in the USA represents an annual cost of five hundred million dollars. Initial education and motivation for oral hygiene depend on two categories of factors: firstly, practical prophylactic measures (instruments and medication, professional care) and secondly, the educational component: choice of communication technique, frequency, and nature of hygiene instructions. This trial aims to study this last component. Its main objective is to compare three methods’ effectiveness of oral hygiene education in adolescent patients treated with braces in terms of biofilm (plaque) control. The secondary objectives are the evaluation of these methods’ effectiveness regarding gingival inflammation and the maintenance of hygiene during the first 6 months of treatment.

Methods

This study is a prospective randomized controlled trial of superiority. It evaluates the effectiveness of three hygiene education techniques. A total of 90 patients from the University Hospital Center of Rennes will be randomized into 3 parallel groups with a 1:1:1 ratio. Each will benefit from a different educational method: oral and/or practical. The main outcome will be the average plaque index for each group after 6 months of treatment. Additional outcomes will be the average gingival index for each group and the plaque and gingival indices over 6 months.

Discussion

The effectiveness of preventive procedures for optimizing oral hygiene during orthodontics is based on ambiguous literature. As a result, it is difficult to draw conclusions and to translate them into everyday practice. Sixty-eight percent of the orthodontists support the development of guidelines for education. The aim of this study is to standardize methods of oral hygiene education during orthodontic fixed treatment. The purpose of this study would be to provide practitioners with a concrete education program through guidelines dedicated to the method having the best results.

Trial registration

ClinicalTrials.gov NCT04444154. Registered on 22 June 2020. SI CNRIPH ID 8011N° 20.04.27.58337. Registered on 29 July 2020
Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model
Authors: Gao Hai-Jun , Sun Xu-Dong , Luo Yan-Ping , Pang Hua-Sheng , Ma Xing-Ming , Zhang Ting , Jing Tao , Hu Wei , Shen Yu-Juan , Cao Jian-Ping
Published: February 2021

Background

Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice.

Methods

The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction.

Results

In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 μg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm.

Conclusions

Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.

Graphical Abstract
Correction to: The influence of different sources of blood meals on the physiology of Aedes aegypti harboring Wolbachia wMel: mouse blood as an alternative for mosquito rearing
Authors: Farnesi Luana Cristina , Carvalho Fabiano Duarte , Lacerda Anna Paula Canuto , Moreira Luciano Andrade , Bruno Rafaela Vieira
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Increase of aerobic glycolysis mediated by activated T helper cells drives synovial fibroblasts towards an inflammatory phenotype: new targets for therapy?
Authors: Kvacskay Peter , Yao Nina , Schnotz Jürgen-Heinz , Scarpone Roberta , Carvalho Rui de Albuquerque , Klika Karel D. , Merkt Wolfgang , Tretter Theresa , Lorenz Hanns-Martin , Tykocinski Lars-Oliver
Published: February 2021

Background

A dysregulated glucose metabolism in synovial fibroblasts (SF) has been associated with their aggressive phenotype in rheumatoid arthritis (RA). Even though T helper (Th) cells are key effector cells in the propagation and exacerbation of synovitis in RA, little is known about their influence on the metabolism of SF. Thus, this study investigates the effect of Th cells on the glucose metabolism and phenotype of SF and how this is influenced by the blockade of cytokines, janus kinases (JAKs) and glycolysis.

Methods

SF from patients with RA or osteoarthritis (OA) were cultured in the presence of a stable glucose isotopomer ([U-13C]-glucose) and stimulated with the conditioned media of activated Th cells (ThCM). Glucose consumption and lactate production were measured by proton nuclear magnetic resonance (1H NMR) spectroscopy. Cytokine secretion was quantified by ELISA. The expression of glycolytic enzymes was analysed by PCR, western blot and immunofluorescence. JAKs were blocked using either baricitinib or tofacitinib and glycolysis by using either 3-bromopyruvate or FX11.

Results

Quiescent RASF produced significantly higher levels of lactate, interleukin (IL)-6 and matrix metalloproteinase (MMP) 3 than OASF. Stimulation by ThCM clearly changed the metabolic profile of both RASF and OASF by inducing a shift towards aerobic glycolysis with strongly increased lactate production together with a rise in IL-6 and MMP3 secretion. Interestingly, chronic stimulation of OASF by ThCM triggered an inflammatory phenotype with significantly increased glycolytic activity compared to unstimulated, singly stimulated or re-stimulated OASF. Finally, in contrast to cytokine-neutralizing biologics, inhibition of JAKs or glycolytic enzymes both significantly reduced lactate production and cytokine secretion by Th cell-stimulated SF.

Conclusions

Soluble mediators released by Th cells drive SF towards a glycolytic and pro-inflammatory phenotype. Targeting of JAKs or glycolytic enzymes both potently modulate SF’s glucose metabolism and decrease the release of IL-6 and MMP3. Thus, manipulation of glycolytic pathways could represent a new therapeutic strategy to decrease the pro-inflammatory phenotype of SF.
The effectiveness of preoperative assessment using a patient-specific three-dimensional pseudoarticulation model for minimally invasive posterior resection in a patient with Bertolotti’s syndrome: a case report
Authors: Shinonara Kensuke , Kaneko Michiya , Ugawa Ryo , Arataki Shinya , Takeuchi Kazuhiro
Published: February 2021

Background

Bertolotti’s syndrome is widely known to cause low back pain in young patients and must be considered as a differential diagnosis. Its treatment such as conservative therapy or surgery remains controversial. Surgical procedure is recommended for intractable low back pain. The three-dimensional (3D) lumbosacral transitional vertebrae anatomy should be completely understood for a successful surgery. Using an intraoperative 3D navigation and preoperative preliminary surgical planning with a patient-specific 3D plaster model contribute for safe surgery and good outcome.

Case presentation

A case of a 22-year-old Japanese male patient with intractable left low back pain due to lumbosacral transitional vertebrae with Bertolotti’s syndrome. The symptom resisted the conservative treatment, and anesthetic injection at pseudoarticulation only provided a short-term pain relief. Posterior resection using intraoperative three-dimensional (3D) navigation has been performed through microendoscopic view. Pseudoarticulation was totally and successfully resected in a safe manner.

Conclusions

Preoperative surgical planning and rehearsal using a patient-specific 3D plaster model was greatly useful and effective for surgeons in performing accurate and safe pseudoarticulation resection.
Tophaceous gout of the atlantoaxial joint: a case report
Authors: Romero Andrew Benjamin , Johnson Evan Paul , Kirkpatrick John S.
Published: February 2021

Background

To report the occurrence of tophaceous gout in the cervical spine and to review the literature on spinal gout.

Case presentation

This report details the occurrence of a large and clinically significant finding of tophaceous gout in the atlantoaxial joint of the cervical spine in an 82-year-old Caucasian man with a 40-year history of crystal-proven gout and a 3-month history of new-onset progressive myelopathy. The patient's American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria score was 15.0.

Conclusion

Spinal gout is more common than previously thought, and it should be considered in patients who present with symptoms of myelopathy. Diagnosis can be made without a tissue sample of the affected joint(s) with tools like the ACR/EULAR criteria and the use of the “diagnostic clinical rule” for determining the likelihood of gout. Early conservative management with neck immobilization and medical management can avoid the need for surgical intervention.
Retraction Note: microRNA-140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5
Authors: Yu Lihui , Lu Ying , Han Xiaocui , Zhao Wenyue , Li Jiazhi , Mao Jun , Wang Bo , Shen Jie , Fan Shujun , Wang Lu , Wang Mei , Li Lianhong , Tang Jianwu , Song Bo
Published: February 2021

This arcticle has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13287-016-0438-5.
Humoral responses to SARS-CoV-2 by healthy and sick dogs during the COVID-19 pandemic in Spain
Authors: Perisé-Barrios Ana Judith , Tomeo-Martín Beatriz Davinia , Gómez-Ochoa Pablo , Delgado-Bonet Pablo , Plaza Pedro , Palau-Concejo Paula , González Jorge , Ortiz-Díez Gustavo , Meléndez-Lazo Antonio , Gentil Michaela , García-Castro Javier , Barbero-Fernández Alicia
Published: February 2021

COVID-19 is a zoonotic disease caused by SARS-CoV-2. Infections of animals with SARS-CoV-2 have recently been reported, and an increase of severe lung pathologies in domestic dogs has also been detected by veterinarians in Spain. Therefore, further descriptions of the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19 would be highly valuable. The potential for companion animals to contribute to the continued transmission and community spread of this known human-to-human disease is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound analysis, and computed tomography. Nasopharyngeal and rectal swabs were analyzed to detect canine pathogens, including SARS-CoV-2. An additional twenty healthy dogs living in SARS-CoV-2-positive households were included. Immunoglobulin detection by several immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. The forty sick dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with α-SARS-CoV-2 IgG, we never obtained a positive RT-qPCR for SARS-SoV-2, not even in dogs with severe pulmonary disease; suggesting that even in the case of canine infection, transmission would be unlikely. Moreover, dogs living in COVID-19-positive households could have been more highly exposed to infection with SARS-CoV-2.
A quantitative discriminant method of elbow point for the optimal number of clusters in clustering algorithm
Authors: Shi Congming , Wei Bingtao , Wei Shoulin , Wang Wen , Liu Hai , Liu Jialei
Published: February 2021

Clustering, a traditional machine learning method, plays a significant role in data analysis. Most clustering algorithms depend on a predetermined exact number of clusters, whereas, in practice, clusters are usually unpredictable. Although the Elbow method is one of the most commonly used methods to discriminate the optimal cluster number, the discriminant of the number of clusters depends on the manual identification of the elbow points on the visualization curve. Thus, experienced analysts cannot clearly identify the elbow point from the plotted curve when the plotted curve is fairly smooth. To solve this problem, a new elbow point discriminant method is proposed to yield a statistical metric that estimates an optimal cluster number when clustering on a dataset. First, the average degree of distortion obtained by the Elbow method is normalized to the range of 0 to 10. Second, the normalized results are used to calculate the cosine of intersection angles between elbow points. Third, this calculated cosine of intersection angles and the arccosine theorem are used to compute the intersection angles between elbow points. Finally, the index of the above-computed minimal intersection angles between elbow points is used as the estimated potential optimal cluster number. The experimental results based on simulated datasets and a well-known public dataset (Iris Dataset) demonstrated that the estimated optimal cluster number obtained by our newly proposed method is better than the widely used Silhouette method.
An algorithm for approximating a common solution of some nonlinear problems in Banach spaces with an application
Authors: Bello Abdulmalik U. , Nnakwe Monday O.
Published: February 2021

In this paper, we construct a new Halpern-type subgradient extragradient iterative algorithm. The sequence generated by this algorithm converges strongly to a common solution of a variational inequality, an equilibrium problem, and aJ-fixed point of a continuousJ-pseudo-contractive map in a uniformly smooth and two-uniformly convex real Banach space. Also, the theorem is applied to approximate a common solution of a variational inequality, an equilibrium problem, and a convex minimization problem. Moreover, a numerical example is given to illustrate the implementability of our algorithm. Finally, the theorem proved complements, improves, and unifies some related recent results in the literature.
A smartphone application to objectively monitor music listening habits in adolescents
Authors: Paping Danique E. , Vroegop Jantien L. , Koenraads Simone P. C. , le Clercq Carlijn M.P. , Goedegebure André , Baatenburg de Jong Robert J. , van der Schroeff Marc P.
Published: February 2021

Background

Listening to music through personal listening devices (PLDs) has become more prevalent during last decades. The aim of this study was to evaluate music listening habits through PLDs in adolescents with a smartphone application, and to assess the accuracy of self-reported listening habits.

Methods

This study was embedded in the Generation R Study, a population-based prospective birth cohort in Rotterdam, the Netherlands. A smartphone application for Android operating systems was developed to objectively monitor music listening habits for a period of 35 days. A postal questionnaire was used to subjectively assess listening habits. The level of agreement between the objectively measured and self-reported listening habits were evaluated using weighted kappa coefficients. Data were collected from May 2017 to March 2019.

Results

A total of 311 adolescents aged 12 to 15 years were included, of whom 237 (76.2%) completed the postal questionnaire. The results of the smartphone application showed that the median listening frequency was 2.1 days a week (IQR 1.0–3.4), the median listening time 21.1 min a day (IQR 9.1–53.7), and the mean listening level 54.5% (SD 18.1%). There was a slight to fair agreement between the objectively measured, and self-reported listening habits according to the weighted kappa coefficients (k = 0.179 to 0.364).

Conclusions

The results of the current study suggest that self-reported measures of listening habits are not always accurate. We consider a smartphone application to monitor listening habits of added value in future research investigating the possible damaging effects of PLDs on hearing acuity.

Graphical Abstract
Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development
Authors: Altaf Reem , Nadeem Humaira , Babar Mustafeez Mujtaba , Ilyas Umair , Muhammad Syed Aun
Published: February 2021

Background

Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers.

Methods

Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified.

Results

From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these genes in breast cancer and their interaction with other signaling pathways involved in the progression of disease metastasis. The miRNA targets identified through miRDB predictor provided potential miRNA targets for these genes that can be involved in breast cancer progression. Several FDA approved drug targets were identified for the signature genes easing the therapeutic options for breast cancer treatment.

Conclusion

The study provides a more clarified role of signature genes, their interaction with other genes as well as signaling pathways. The miRNA prediction and the potential drugs identified will aid in assessing the role of these targets in breast cancer.
Diagnostic Utility of New SCAT5 Neurological Screen Sub-tests
Authors: Fuller Gordon Ward , Miles John , Tucker Ross , Douglas Marc , Raftery Martin , Falvey Eanna , Mathema Prabhat
Published: February 2021

Background

The Sports Concussion Assessment Tool (SCAT) is recommended to screen for concussion following head impact events in elite sport. The most recent 5th edition (SCAT5) included a ‘rapid neurological screen’ which introduced new subtests examining comprehension, passive neck movement, and diplopia. This study evaluated the additional diagnostic value of these new subtests.

Methods

A prospective cohort study was performed in the Pro14 elite Rugby Union competition between September 2018 and January 2020. The SCAT5 was administered by the team doctor to players undergoing off-field screening for concussion during a medical room assessment. Sensitivity, specificity, false negatives, and positives were examined for SCAT5 comprehension, passive neck movement, and diplopia subtests. The reference standard was a final diagnosis of concussion, established by serial standardised clinical assessments over 48 h.

Results

Ninety-three players undergoing off-field screening for concussion were included. Sensitivity and specificity of the comprehension, passive neck movement, and diplopia subtests were 0, 8, 5% and 0, 91, 97%, respectively (concussion prevalence 63%). No players had any abnormality in comprehension. No players had abnormal passive neck movement or diplopia in the absence of abnormalities in other SCAT5 sub-components.

Conclusions

The new SCAT5 neurological screen subtests are normal in the majority of players undergoing off-field concussion screening and appear to lack diagnostic utility over and above other SCAT5 subtests.
Migraine prevalence, clinical characteristics, and health care-seeking practice in a sample of medical students in Egypt
Authors: Oraby Mohammed I. , Soliman Rasha H. , Mahmoud Mustafa A. , Elfar Eman , Abd ElMonem Noha A.
Published: February 2021

Introduction

Migraine is a common disabling primary headache disorder with significant personal and socio-economic impacts. Medical students usually have multiple triggers for migraine, particularly stress and irregular sleep.

Objective

To assess the prevalence, characteristics, and degree of disability of migraine in a sample of Egyptian medical students and to study their health care-seeking practice when having migraine

Patients and methods

A descriptive cross-sectional, questionnaire-based study included 631 undergraduate medical students enrolled in the Faculty of Medicine. Participants’ sociodemographic data, migraine prevalence, characteristic, migraine disability, and health care-seeking practice were evaluated. By using the MIDAS test in the questionnaire, we assessed the impact of migraine headache on the daily activities of the students. The severity of headache was assessed using the visual analog scale (VAS) scores.

Results

Prevalence of migraine in medical students was found to be 17.9% causing moderate disability. Migraine was significantly more prevalent and caused more disability among female students compared to males (p value 0.001 and 0.001). Only 35.4% of the migraineurs had already seen doctors for their migraine, and self-prescription of medications for migraine was practiced by 58.4%. Statistically significant positive correlation was found between migraine frequency, migraine severity, and low academic performance (p value 0.001 and 0.003 respectively).

Conclusion

Migraine is highly prevalent among medical students with predominant female prevalence and has a negative impact on their academic performance and other activities.
Development and validation of a simple and rapid ICP-OES method for quantification of elemental impurities in voriconazole drug substance
Authors: Merusomayajula Kishore V. , Tirukkovalluri Siva Rao , Kommula Rama Srinivas , Chakkirala Sathyendranath Venkata , Vundavilli Jagadeesh Kumar , Kottapalli Pavan Kumar S. R.
Published: February 2021

Background

The aim of the present study was to develop and validate an inductively coupled plasma optical emission spectroscopic (ICP–OES) method for quantification of elemental impurities, i.e., Lead, Palladium, and Zinc, in voriconazole drug substance, and this method was employed for the regular sample analysis of Lead, Palladium, and Zinc in voriconazole drug substance for pharmaceutical use. The method has been validated using RF power of 1150 W, auxiliary gas of 0.5 L/min, and nebulizer flow of 0.4 L/min and plasma view at axial mode for Lead and Palladium and radial mode for Zinc. The wavelength was monitored for Lead, Palladium, and Zinc at 220.3 nm, 340.4 nm, and 213.8 nm respectively.

Results

The method is selective and is capable of detecting desired elemental impurities with regulatory acceptance limits in the presence of other elements. The validation experiments involve the demonstration of system suitability, specificity, LOD and LOQ, linearity, precision, and accuracy experiments. The linearity results obtained ˃ 0.9990 for all three impurities.

Conclusion

The proposed method is simple, sensitive quality control tool for the simultaneous quantitative determination of Lead, Palladium, and Zinc at low levels in voriconazole drug substance.

Graphical abstract
Increased Mortality Risk in Patients With Primary and Secondary Adrenal Insufficiency
Authors: Ngaosuwan Kanchana , Johnston Desmond G , Godsland Ian F , Cox Jeremy , Majeed Azeem , Quint Jennifer K , Oliver Nick , Robinson Stephen
Published: February 2021

Context

Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations.

Objective

To compare mortality risk and causes of death in adrenal insufficiency with an individually matched reference population.

Methods

A retrospective cohort study was done using a UK general practitioner database (CPRD). A total of 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) were compared with 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcomes were all-cause and cause-specific mortality, and hospital admission from adrenal crisis.

Results

With follow-up of 40 799 and 406 899 person-years for patients and controls respectively, the hazard ratio (HR [95% CI]) for all-cause mortality was 1.68 [1.58-1.77]. HRs were greater in primary (1.83 [1.66-2.02]) than in secondary (1.52 [1.40-1.64]) disease; primary versus secondary disease (1.16 [1.03-1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15-7.46]). Adrenal crisis contributed to 10% of all deaths. In the first 2 years following diagnosis, the patients’ mortality rate and hospitalization from adrenal crisis were higher than in later years.

Conclusion

Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.