bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a Phase I study
Authors: Kawai Akira , Naka Norifumi , Shimomura Akihiko , Takahashi Shunji , Kitano Shigehisa , Imura Yoshinori , Yonemori Kan , Nakatani Fumihiko , Iwata Shintaro , Kobayashi Eisuke , Outani Hidetatsu , Tamiya Hironari , Naito Yoichi , Yamamoto Noboru , Doi Toshihiko 
Published: March 2021

Abstract
BackgroundOsteosarcoma is a rare, primary malignant bone tumour with limited available treatments for advanced or recurrent disease, resulting in a poor prognosis for patients. TAS-115 is a novel tyrosine kinase inhibitor under investigation in a Phase I study in patients with solid tumours. We report data of osteosarcoma patients in the expansion cohort of this ongoing study.Patients and methodsAn analysis of this multicentre, open-label study was performed 6 months after the final patient was enrolled, and included patients aged ≥ 15 years, with unresectable or recurrent osteosarcoma, and who had refractory to standard therapy or for whom no standard therapy was available. TAS-115 650 mg/day was orally administered in a 5 days on/2 days off schedule.ResultsA total of 20 patients with osteosarcoma were enrolled. The most common adverse drug reactions (ADRs) were neutrophil count decreased (75%), aspartate aminotransferase increased (50%), and platelet count decreased (50%); 85% of patients had grade ≥ 3 ADRs. Long-term disease control (> 1 year) with TAS-115 was achieved in three patients. The best overall response was stable disease (50%); no patient achieved a complete or partial response. Median progression-free survival was 3 months; 4-month and 12-month progression-free rates were 42% and 31%, respectively.ConclusionThe safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients.Trial registration numberJapicCTI-132333 (registered on November 8, 2013)
Factors influencing Research Engagement among Medical students in the United Kingdom (REMED-UK): protocol for a prospective, observational, national, multi-centre questionnaire - study
Authors: Osunronbi Temidayo , Adeboye William , Faluyi David , Sofela Jasmine , Sofela Agbolahan 
Published: March 2021

Abstract
Introduction: There has been a decline in the number of academic clinicians in the UK. Also, there is sex and ethnic inequalities in research opportunities amongst UK clinicians. The decision to get involved in research as a clinician is usually made as a medical student. Hence, this study aims to investigate the factors affecting UK medical students’ involvement in research, and to understand their perceptions of research, motivation for and the barriers to their engagement in research.Methods: This study is a prospective, observational, national, multi-centre study that will utilise an online questionnaire using the QualtricsTM survey tool. Medical students that are at least 18 years old and enrolled in a UK medical school in the 2020/21 academic year are eligible to partake in this study. The following data will be collected: demographic, research experience, research perception, research self-efficacy, motivation, and barriers to engaging in research. The outcome measures are: number of research projects, publications, presentations, and successful grant applications.Conclusion: This study will produce evidence-based reports that will guide UK medical schools and relevant organisations in developing resources and programmes that will increase the number of future academic clinicians and resolve inequalities in research opportunities and engagement amongst future clinicians.
Outcomes of pulpectomy in the primary dentition and age-related morphological changes in the root canal of primary molars: A retrospective study
Authors: Dou Guili , Xia Bin , Zhu Junxia , Wang Dandan , Zhao Yijiao , Sun Zhipeng , Cao Zhanqiang 
Published: March 2021

Abstract
Objectives To investigate the factors influencing primary tooth survival after pulpectomy and to elucidate age-related morphological changes in the root canal of primary molars. Materials and Methods This retrospective study included 592 primary anterior teeth and 583 primary molars after pulpectomy. Survival analysis was performed to determine the predictors of pulpectomy failure. Cone-beam computed tomography (CBCT) data of the maxillary first primary teeth from 63 children aged 3–8 years were collected, and Spearman’s correlation and binary logistic regression were performed to assess age-related changes in canal morphology. Results Periapical periodontitis, Vitapex® filling, and non-general anesthesia treatment increased the failure risk of anterior primary teeth pulpectomy. Older age at treatment increased the primary molar pulpectomy failure risk. On CBCT analysis, the ratio of canal length to root length for the mesiobuccal (MB), distobuccal (DB), and palatal (P) roots negatively correlated with age (P<0.05). The ratio between the root canal wall area with inner diameter lesser than 0.15 mm and the whole root canal wall area (R.15) at plane D of the MB canals positively correlated with age (P<0.05). The number of discontinuous canals (Ndis) for the MB and DB roots increased with age and the canal area at plane D for MB and P canals negatively correlated with age (P<0.05). Conclusions Older age at treatment for primary molar pulpectomy and periapical lesions, non-general anesthesia treatment, and Vitapex® filling for anterior primary teeth pulpectomy may predict a higher failure risk. Age-related morphological changes in the primary molar root canal were evident and could be a reason for treatment failure.
High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behavior measures: Results from the DETECTCoV-19 cohort.
Authors: Lalwani Pritesh , Araujo-Castillo Roger , Ganoza Christian , Salgado Barbara , Filho Ivanildo Pereira , Silva Danielle , Morais Thiago , Jordão Maele , Ortiz Jessica , Barbosa Aguyda , Sobrinho Wlademir Salgado , Cordeiro Isabelle , Neto Júlio Souza , Assunção Enedina , Costa Cristiano da , Souza Pedro , Albuquerque Bernardino , Astofi-Filho Spartaco , Lalwani Jaila 
Published: March 2021

Abstract
We report anti-SARS-CoV-2 nucleocapsid IgG seroconversion rates from a population-based cohort in Manaus, between August and November 2020, before the COVID-19 second wave in Brazil. Among seronegative and uninfected participants, we observed an overall incidence of 13.06% (95%CI, 11.52-14.79) and 6.78% (95%CI, 5.61-8.10) for symptomatic seroconversion. Risk factors for seroconversion were: having a COVID-19 case in the household, not wearing a mask during contact, relaxation of protective measures, and non-remote work. We observed an intense infection transmission period that preceded the second wave of COVID-19 in Manaus, and identified several modifiable behaviors that increased the risk of seroconversion.
Regional trends and associated factors of childhood visual impairment: a case study in Shandong province, China
Authors: Han Lizhen , Jia Jinzhu , Wang Lu 
Published: March 2021

Abstract
Background: We analyze regional factors and spatial distribution of children's visual impairment in Shandong province, to explore the spatial changes brought by time and their influencing factors, so as to provide scientific basis for prevention of childhood visual impairment.Methods: This study covers five complete cross-sectional surveys from 2013-2017, involving about 29.24 million students. Spatial autocorrelation and hotspot analysis methods were used to analyze spatial features. The associated factors were analyzed by multinomial logistic regression.Results: The visual impairment prevalence showed a trend of decreasing first and then increasing from 2013-2017, with slight changes. In terms of regional spatial differences, Weihai and Yantai have the highest VI rates in all years, and there was a large-scale spatial aggregation phenomenon. The southern low-value clusters, however, showed a weakening year by year. Further exploration revealed that economic factors and number of full-time teachers were verified as risk factors for regional visual impairment levels.Conclusions: The slight rebound of the prevalence of visual impairment and the high rate in the eastern and northern regions of Shandong province need more attention. It is suggested that relevant departments should focus on the influence of regional economic and educational factors when formulating relevant strategies.
Insulin Increases Central Aortic Stiffness in Response To Hyperglycemia in Healthy Humans: A Randomized Four-Way Crossover Study
Authors: Horton William B , Jahn Linda A , Hartline Lee M , Aylor Kevin W , Barrett Eugene J 
Published: March 2021

Abstract
Introduction: Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear.Materials and Methods: We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults.Results: Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.36 m/s; p=0.032), while other markers of arterial stiffness did not change (all p>0.05). Heart rate (+3.62 bpm; p=0.009), mean arterial pressure (+4.14 mmHg; p=0.033), central diastolic blood pressure (+4.16 mmHg; p=0.038), and peripheral diastolic blood pressure (+4.09 mmHg; p=0.044) also significantly increased during hyperglycemic-hyperinsulinemia.Conclusions: We conclude that the acute combination of moderate hyperglycemia and hyperinsulinemia preferentially stiffens central elastic arteries. This effect may be due to increased sympathetic activity. (ClinicalTrials.gov number NCT03520569; registered 9 May 2018).
Ahmed valve implantation results in children with uveitic glaucoma
Authors: Katargina L. A. , Denisova E. V. , Bahaaeddin I. N. A. , Khrabrova M. A. 
Published: March 2021

The purposeis to evaluate the effectiveness and safety of Ahmed valve implantation in children with refractory postuveitic glaucoma (PUG).Material and methods. Ahmed valve was implanted to 10 children aged 7 to 17 years (10 eyes) with open-angle or mixed PUG uncompensated even by a maximum antihypertensive mode. Previously, all patients had undergone an average of 2.1 ± 0.9 surgeries aimed at normalizing the intraocular pressure (IOP) (predominantly, sinus trabeculectomy). 6 eyes were pseudophakic, 2 phakic, 2 aphakic. Ahmed valves were implanted according to the generally accepted technique. At the time of surgery IOP was 30.50 ± 4.35 mm Hg on average. The follow-up postsurgical period ranged from 3.9 to 23.6 months (averagely, 14.1 ± 6.5).Results.A stable hypotensive effect of the intervention was achieved in 90 % of cases, of which 3 patients had no hypotensives while 6 patients received hypotensive drugs even though their quantity was significantly smaller than before surgery (1.7 ± 1.49, p=0.028). At the end of the follow-up the average IOP was 18.1 ± 5.34 mm Hg, (significantly lower than before surgery, p = 0.008). During surgery, 1 patient experienced bleeding from the vessels of the anterior chamber angle after paracentesis, which was stopped by tamponade with sterile air. In other cases, the surgery as well as the immediate and distant postoperative period showed no complications.Conclusion.Ahmed valve implantation is an effective and safe method of the surgical treatment of refractory PUG in children and can be recommended in cases when previous antiglaucomatous operations proved ineffective, including patients with pseudophakia and aphakia.
Explantation of domestic models of posterior chamber phakic intraocular lenses in the development of subcapsular cataract in higly myopic patients: clinical features
Authors: Sorokoletov G. V. , Tumanyan E. R. , Bessarabov A. N. , Soboleva M. A. 
Published: March 2021

To date, the operation of choice in young patients with high myopia, is the implantation of posterior chamber phakic intraocular lenses (PIOL), provided that there are contraindications to keratorefractive interventions, However, in the late postoperative period, cataracts may occur, which requires the development of surgical tactics for lens explantation with simultaneous phacoemulsification of cataract (FEC) implementation.The purpose is to develop and analyze a method for removing a PIOL through a 2 mm corneal incision in subcapsular cataract cases.Material and methods. Posterior chamber domestic models of PIOL type RSK-1(3) and RSK-3 in 22 patients (37 eyes), implanted in the S.N. FEDOROV “EYE MICROSURGERY” clinic in 1994 – 2001 had to be removed due to the development of secondary cataracts. PIOL stayed in the eye 2 to 26 years (averagely 14.30 ± 1.30 yrs). In all cases, the P IOL was removed followed by FEC with implantation of a posterior chamber IOL. The optical power of the IOL was calculated mainly in such a way that the residual myopic refraction was 2.0–3.0 D.Results. The intraoperative condition of the anterior chamber was stable, the volume of irrigation fluid consumed was within 90–120 ml. No complications were detected in the early and late postoperative periods. The results of dynamic ophthalmological follow up of patients showed that visual acuity without correction and with correction after surgery averaged 0.2 ± 0.1 and 0.60 ± 0.15, respectively.Conclusion. The proposed method of explantation of domestic lenses of S.N. FEDOROV NMRC MNTK “EYE MICROSURGERY” shows that it enables a safe, simple removal of PIOL in the event of secondary subcapsular cataract, which allows achieving high clinical and functional results without overspending the irrigation solution.
Research of effects of plant preparation with integrated action in cough therapy in school children
Authors: Rashitova Elina L. , Zakirova Alfiia M. , Moroz Tatyana B. , Shayapova Dilyara T. S , Kadriev Albert G. , Kadriev Amir G. 
Published: March 2021

Introduction. Cough accompanies an acute infectious process in the respiratory tract. The article focuses on the symptomatic treatment of cough using a modern herbal preparation with complex action and standard therapy.Goal. To study the effects of a herbal preparation with complex action in the treatment of cough in children.Materials and methods. The study included 72 patients of both sexes (mean age 14.6 ± 2.3 years) with a symptom of unproductive/unproductive cough, against the background of acute bronchitis or community-acquired pneumonia.Results and discussion. When using a herbal preparation with complex action was used in ¾ of the children, cough decreased by the 3rd day and in most patients it stopped by the 10 th day. The severity of daytime and nighttime coughs decreased by 3.0–3.5 points, the number of seizures decreased to 2–4 per day, the duration of seizures also decreased significantly, the median of this indicator in the main group reached 0 points. In both groups, the proportion of patients with seizure frequency of no more than 4 per day increased. While taking a herbal preparation, a more pronounced decrease in all indicators of cough by 3.5 times was noted throughout the treatment, and the corresponding effects developed 3 days ahead of time against the background of a full course of therapy. The average value of the efficacy and safety assessment given by the medical researchers to the action of the herbal preparation with complex action was 3.6 points. Analysis of objective and subjective data based on the results of evaluating case histories and individually developed questionnaires for patients on drug tolerance showed equivalence in terms of excellent and good results. Against the background of the full course of treatment with the herbal preparation, a 1.8 times more pronounced decrease in the characteristics of the cough syndrome was noted.Conclusion. The drug has shown high efficacy and safety, which makes it possible to recommend it as a symptomatic therapy for cough in school-age children as part of a combination or monotherapy.
Management of functional gastrointestinal disorders in children. Focus on restoring intestinal microenvironment and motility
Authors: Ipatov Andrey A. , Ipatova Maria G. 
Published: March 2021

Functional gastrointestinal disorders in children are one of the most common reasons why parents visit a pediatrician. Functional gastrointestinal disorders include various persistent combinations of chronic or recurrent gastrointestinal symptoms in the absence of any organic pathology in the gastrointestinal tract (structural abnormalities, inflammatory changes, infections, or tumours) and metabolic disturbances. The article presents details on the mechanisms of development, clinical manifestations, diagnostic criteria and approaches to the treatment of functional gastrointestinal disorders. Clinical manifestations of functional gastrointestinal disorders vary depending on age and characteristics of physical and intellectual development. In more than half of children, they are observed in various combinations, less often as one isolated symptom. The drug therapy should consider the main components of pathogenesis and facilitate the solution of the following issues: improvement of digestion; restoration of intestinal microenvironment and motility; reduction of visceral hypersensitivity. Special attention is paid to the management of motor disorders and restoration of intestinal microenvironment using symbiotics. When choosing a supplement, it is advisable to focus on the composition of probiotic strains, which should comply with the WGO global guidelines (Bifidobacterium bifidum, Lactobacillus acidophilus, etc.).Prescription of peripheral δ-, μ- и κ-receptor agonists – trimebutine and pre- and probiotics combinations to children with functional gastrointestinal disorders results in decreased signs of functional disorders of the digestive tract. By acting on the enkephalinergic system, trimebutine regulates the bowel activity, improves motility, and reduces visceral hypersensitivity. Trimebutine is included in the Russian guidelines for the diagnosis and treatment of functional disorders of the digestive tract in children, as well as in the clinical guidelines for the treatment of irritable bowel syndrome, functional dyspepsia, and functional abdominal pain.
Modern approaches to the prevention and rehydration therapy of antibiotic-associated diarrhea affected by ARI in children
Authors: Kanner Ekaterina V. , Gorelov Aleksandr V. , Maksimov Maksim L. , Kanner Ilya D. , Lapkin Nikita M. 
Published: March 2021

The use of antibiotic drugs (ABDs) has significantly reduced the number of severe bacterial infectious diseases and mortality in children, especially in infants. But the widespread and unnecessary use of ABDs, including reserve antibiotics (the use of carbapenems increased by 45%, polymyxins – by 13%), to treat uncomplicated acute respiratory infections is open to many hazards, such as increased antibiotic resistance of pathogens. Antibiotic-associated diarrhea is one of the common complications of antibiotic therapy. According to various authors, the incidence of antibiotic-associated diarrhea is 6–80% among patients treated with antibiotics, on average 35% of patients (approximately every third patient) receiving antibiotics report symptoms of antibiotic-associated diarrhea. Disruptive changes in the qualitative and quantitative composition of the intestinal microbiota are accompanied by a decrease in the protective functions of the intestinal mucosa and contribute to the growth of pathogenic and opportunistic microorganisms (Clostridium spp., Candida spp., Salmonella spp., Staphyloccus aureus). The findings of most studies obtained on a large sample of paediatric population, as well as the clinical guidelines of the World Association of Gastroenterologists recommend the use of L. rhamnosus GGprobiotic strain (level of evidence 1) to prevent antibiotic-associated diarrhea in children. L. rhamnosus GGpresents chromosomal resistance to a range of antibiotics, which varies with species and strain. They do not contain plasmid DNA, which is dangerous for the spread of antibiotic resistance among other bacteria, which enables their wide therapeutic and prophylactic use. Clinical case studies of the course of antibiotic-associated diarrhea in children are presented to demonstrate the variability of clinical symptoms. Fever in children with ARI, particularly in tender-age infants, requires special attention from parents and doctors, as its main risk lies with a dehydration due to significant water loss during breathing, and especially increased sweating (including sweating induced by antipyretics). Therefore, oral rehydration therapy is an important method for treating infectious diseases in children. Complications that develop in patients, especially in children, after administration of antibiotics, diseases that can lead to water and electrolyte imbalance are life-threatening conditions that require immediate medical attention. Correction of water and electrolyte balance, timely restoration of intestinal microflora improve prognosis in such patients and promote faster recovery.
Is it always easy for children with mild asthma?
Authors: Glushkova Evgeniya F. , Surovenko Tatiana N. 
Published: March 2021

Bronchial asthma is the most common chronic disease of children, the worst way is their quality of life. Compliance in the treatment of children is very important, since the actual effect of a drug is determined by both the effective drugs and patient adherence and correct use. A relevant test is the use of mild asthma, which is able to control bronchial hyperreactivity associated with exercise, cold air, and other nonspecific irritants (smoke, odors, etc.). Planning of baseline therapy for children with mild asthma aged 5 years old and younger is particularly problematic for paediatricians due to high incidences of acute respiratory viral diseases and viral-induced exacerbations of bronchial asthma among them. In these children, allergen-specific immunotherapy, long-acting B-agonists, the use of many metered-dose inhaled glucocorticosteroids. are not recommended.Montelukast, an oral antileukotriene drug, has advantages in the treatment of children with mild asthma with virus-induced exacerbations, with asthma of physical exertion and severe bronchial hyperreactivity, especially when combined with allergic rhinitis, as well as in special clinical cases, when parents refuse to use ICS for treatment children with mild asthma or inability to use them for some reason. The use of montelukast for mild asthma in children in the current context of the COVID-19 pandemic also has advantages that pediatricians can use when observing these children in the pediatric area, taking into account contraindications.