bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical care requires pragmatic care research to guide medical practice under uncertainty
Authors: Darsaut Tim E. , Raymond Jean 
Published: February 2021

Abstract
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

Abstract
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

Abstract
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
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

Abstract
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

Abstract
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

Abstract
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.
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

AbstractCOVID-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

AbstractClustering, 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

AbstractIn 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

Abstract
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

AbstractBackgroundThe 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.MethodsA 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.ResultsNinety-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.ConclusionsThe 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.