bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of cervical myelopathy and hydrocephalus in young children with achondroplasia
Authors: Shim Youngbo , Ko Jung Min , Cho Tae-Joon , Kim Seung‐Ki , Phi Ji Hoon 
Published: February 2021

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

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

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

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

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

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

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

Conclusions
FGFR1 amplification and overexpression are associated to similar adverse prognosis in hormone-positive breast cancer. Capturing all the patients with adverse prognosis-linked FGFR1 aberrations requires assessing both features. Hormonal deprivation leads to FGFR1 overexpression, and FGFR1 overexpression and/or amplification are associated with resistance to hormonal monotherapy or in combination with palbociclib. Both resistances are reverted with triple ER, CDK4/6, and FGFR1 blockade.
Neoadjuvant irradiation of retroperitoneal soft tissue sarcoma with ions (Retro-Ion): study protocol for a randomized phase II pilot trial
Authors: Seidensaal K. , Kieser M. , Hommertgen A. , Jaekel C. , Harrabi S. B. , Herfarth K. , Mechtesheimer G. , Lehner B. , Schneider M. , Nienhueser H. , Fröhling S. , Egerer G. , Debus J. , Uhl M. 
Published: February 2021

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

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

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

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

AbstractBackgroundPostprandial distress syndrome manifests as a feeling of fullness and early satiation that can significantly reduce the quality of life of the patients. In Chinese medicine (CM), the syndrome is traditionally regarded as theWei-Pisyndrome, and Banxia Xiexin decoction (BXD) has been used in the empirical treatment of the same for a long time. The current study aims to evaluate the efficacy of modified BXD in the management ofWei-Pisyndrome.Methods/designA randomized, waitlist-controlled trial will be conducted. A total of 84 patients withWei-Pisyndrome will be randomized into the BXD or waitlist control group in a ratio of 1:1. The patients in the BXD group will receive the semi-individualized BXD on the basis of the syndrome differentiation in CM, for a duration of 3 weeks and will be under follow-up for further 3 weeks after the completion of therapy. Conversely, the patients in the waitlist control group will undergo the same intervention and follow-up after a 3-week waiting period. In the current study, the primary outcome will be the variation in the scores pertaining to the global scale of the Quality of Life Questionnaire for Functional Digestive Disorders after 3 weeks. The secondary outcomes include the variations in the scores pertaining to the Hospital Anxiety and Depression Scale and the EuroQoL 5-dimension 5-level Questionnaire and the results of the liver and kidney function tests.DiscussionThis trial will assess the efficacy of modified BXD in improving the clinical symptoms and quality of life of the patients suffering fromWei-Pisyndrome.Trial registrationClinicalTrials.govNCT04398888. Registered on May 21, 2020
Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
Authors: Gobin Jonathan , Muradia Gauri , Mehic Jelica , Westwood Carole , Couvrette Lauren , Stalker Andrew , Bigelow Stewart , Luebbert Christian C. , Bissonnette Frédéric St-Denis , Johnston Michael J. W. , Sauvé Simon , Tam Roger Y. , Wang Lisheng , Rosu-Myles Michael , Lavoie Jessie R. 
Published: February 2021

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

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

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

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

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

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

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

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

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

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

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

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

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

Background Superficial parotidectomy has a potential to be performed as an outpatient procedure. The objective of the study is to evaluate the safety and selection profile of outpatient superficial parotidectomy compared to inpatient parotidectomy. Methods A retrospective review of individuals who underwent superficial parotidectomy between 2006 and 2016 at a tertiary care center was conducted. Primary outcomes included surgical complications, including transient/permanent facial nerve palsy, wound infection, hematoma, seroma, and fistula formation, as well as medical complications in the postoperative period. Secondary outcome measures included unplanned emergency room visits and readmissions within 30 days of operation due to postoperative complications. Results There were 238 patients included (124 in outpatient and 114 in inpatient group). There was no significant difference between the groups in terms of gender, co-morbidities, tumor pathology or tumor size. There was a trend towards longer distance to the hospital from home address (111 Km in inpatient vs. 27 in outpatient, mean difference 83 km [95% CI,- 1 to 162 km], p = 0.053). The overall complication rates were comparable between the groups (24.2% in outpatient group vs. 21.1% in inpatient, p = 0.56). There was no difference in the rate of return to the emergency department (3.5% vs 5.6%, p = 0.433) or readmission within 30 days (0.9% vs 0.8%, p = 0.952). Conclusion Superficial parotidectomy can be performed safely as an outpatient procedure without elevated risk of complications. Graphical Abstract
The effects of computer-based virtual learning environments on nursing students’ mathematical learning in medication processes
Authors: Zwart Diana P. , Goei Sui Lin , Noroozi Omid , Van Luit Johannes E. H. 
Published: February 2021

AbstractComputer-based virtual learning environments (CBVLEs) are potentially useful teaching tools for training nursing students in professional duties such as the mathematical tasks associated with medication processes. In this study, a CBVLE was designed with well-structured instructional activities such as interleaved practice and feedback. Mathematical medication scenarios and basic arithmetic exercises were integrated into the CBVLE. Four training conditions were used in the CBVLE to facilitate extra support for mathematical medication learning: (1) learning without worked examples, (2) learning with worked examples involving domain-specific knowledge, (3) learning with worked examples involving regular thinking strategies, and (4) learning with combined worked examples. This study was conducted with 118 nursing students enrolled in post-secondary nursing education and Bachelor’s nursing programmes. Students were pre-tested and post-tested on their mathematical medication learning. Training in the CBVLE improved mathematical medication learning for all students from pre-test to the post-test stages, but no differences were found among the four different conditions. Nursing students’ prior knowledge, non-verbal intelligence, and number of correct tasks predicted mathematical medication learning outcomes. When controlling for non-verbal intelligence, students in the condition 1 benefited more than students in condition 3 in terms of their mathematical medication learning outcomes. The same accounted for the support of the low-achieving students in the CBVLE. The support conditions for the high-achieving group appeared to be unimportant for mathematical medication learning. It seems that technology is taken over some of the capacity of working memory, which accounts for the benefits to the low-achieving learners.
Trampolines injuries are bouncing back
Authors: Ibrahim Yahya , Huq Sumon , Shanmuganathan Kanatheepan , Gille Helen , Buddhdev Pranai 
Published: February 2021

Aims This observational study examines the effect of the COVID-19 pandemic upon the paediatric trauma burden of a district general hospital. We aim to compare the nature and volume of the paediatric trauma during the first 2020 UK lockdown period with the same period in 2019. Methods Prospective data was collected from 23 March 2020 to 14 June 2020 and compared with retrospective data collected from 23 March 2019 to 14 June 2019. Patient demographics, mechanism of injury, nature of the injury, and details of any surgery were tabulated and statistically analyzed using the independent-samples t-test for normally distributed data and the Mann-Whitney-U test for non-parametric data. Additionally, patients were contacted by telephone to further explore the mechanism of injury where required, to gain some qualitative insight into the risk factors for injury. Results The 2020 lockdown resulted in 30% fewer paediatric trauma presentations (441 vs 306), but no significant change in the number of patients requiring surgery (47 vs 51; p = 0.686). Trampolining injuries increased in absolute numbers by 168% (p < 0.001), almost four times more common when considered as percentage of all injuries observed in 2020 vs 2019. There was a decrease in high energy trauma from road traffic accidents and falls from height (21.5% decrease, p < 0.001). Despite a shift towards more conservative treatment options, trampolining injuries continued to require surgery in similar proportions (19.4 vs 20%; p = 0.708). Qualitative investigation revealed that the most common risk factor for trampolining injury was concurrent usage, especially with an older child. Conclusion COVID-19 lockdown has resulted in a decrease in paediatric orthopaedic presentations and high energy trauma. However, due to a marked increase in home trampolining injuries, and their unchanged requirement for surgery, there has been no change in the requirement for surgery during the lockdown period. As home exercise becomes more prevalent, a duty of public health falls upon clinicians to advise parents against trampoline usage. Cite this article: Bone Jt Open 2021;2(2):86–92.