bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary care physician volume and quality of care for older adults with dementia: a retrospective cohort study
Authors: Lane Natasha E. , Ling Vicki , Glazier Richard H. , Stukel Thérèse A. 
Published: March 2021

Abstract
Background
Some jurisdictions restrict primary care physicians’ daily patient volume to safeguard quality of care for complex patients. Our objective was to determine whether people with dementia receive lower-quality care if their primary care physician sees many patients daily.

Methods
Population-based retrospective cohort study using health administrative data from 100,256 community-living adults with dementia aged 66 years or older, and the 8,368 primary care physicians who cared for them in Ontario, Canada. Multivariable Poisson GEE regression models tested whether physicians’ daily patient volume was associated with the adjusted likelihood of people with dementia receiving vaccinations, prescriptions for cholinesterase inhibitors, benzodiazepines, and antipsychotics from their primary care physician.

Results
People with dementia whose primary care physicians saw ≥ 30 patients daily were 32% (95% CI: 23% to 41%, p < 0.0001) and 25% (95% CI: 17% to 33%, p < 0.0001) more likely to be prescribed benzodiazepines and antipsychotic medications, respectively, than patients of primary care physicians who saw < 20 patients daily. Patients were 3% (95% CI: 0.4% to 6%, p = 0.02) less likely to receive influenza vaccination and 8% (95% CI: 4% to 13%, p = 0.0001) more likely to be prescribed cholinesterase inhibitors if their primary care physician saw ≥ 30 versus < 20 patients daily.

Conclusions
People with dementia were more likely to receive both potentially harmful and potentially beneficial medications, and slightly less likely to be vaccinated by high-volume primary care physicians.
Secondary gliosarcoma: the clinicopathological features and the development of a patient-derived xenograft model of gliosarcoma
Authors: Kiang Karrie Mei-Yee , Chan Andrian A. , Leung Gilberto Ka-Kit 
Published: March 2021

Abstract
Background
Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM.

Methods
Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared.

Results
In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors.

Conclusions
Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.
Giant congenital nodular melanoma in a newborn: a case report and literature review
Authors: Zhou Jun , Lv Meng-xing , Duan Ling , Xie Yu-cheng , A Zhi-xiang , Wu Hong-fang , Gao Yan 
Published: March 2021

AbstractBackgroundMalignant melanoma (MM) arises predominantly after adolescence and is uncommon in children. Congenital MM in newborns is even rarer with a dearth of published literature; as a consequence, there is no uniform standard for the pathogenesis and treatment for neonatal malignant melanoma. Herein we report a case of giant congenital nodular MM in a newborn, including its clinical, imaging, pathological and molecular pathological features. This case is the largest giant congenital primary nodular malignant melanoma in utero in neonates currently reported in China.Case presentationA female neonatal patient was found to have a 2.97 cm× 1.82 cm×1.50 cm mass with a clear boundary at the right acromion in color Doppler ultrasound examination at 24 weeks of gestation. The mass increased to 3.0 cm×5.0 cm×9.0 cm at birth, and local ulceration was seen. MRI demonstrated that the mass was located on the right shoulder and underarm in a lobulated appearance, and surrounded the right scapula which was deformed. Clinical stage:IV(AJCC 8th Edition (2017)). α-Fetoprofein (AFP) by hematological examination: 1210ng/ml, NSE: 21.28ng/ml, LDH: 842U/L. The patient underwent surgical resection of the tumor, and was pathologically diagnosed as neonatal congenital malignant melanoma; immunohistochemistry (IHC): S-100 (+), HMB45 (+), Melan A (+), and Tyrosinase (+). Molecular pathological examination for BRAF V600E showed no mutations (Quantitative Real-time PCR, qPCR); And so were NRAS, C-kit (exons 9,11,13,14,17,18), and TERT (promoter locus, C228T and C250T) (Sanger sequencing). Non-surgical therapies were not carried out after the surgical resection of the tumor. After 6 months of follow-up, the child developed normally, and color Doppler ultrasound showed no obvious tumor growth or abnormality in the original tumor site.ConclusionsIt is extremely rare to see giant congenital primary nodular MM in utero in neonates. The pathogenesis, treatment and prognosis of congenital MM need further research. The diagnosis mainly depends on histopathology and immunohistochemistry, and it needs to be differentiated from malignant lymphoma and primitive neuroectodermal tumor. The current treatment strategy for MM relies on the surgical excision of the mass. Research directed at molecular detection for genetic mutations would contribute to targeted therapy and better prognosis.
Is the contralateral lesser trochanter a reliable reference for planning of total hip arthroplasty – a 3-dimensional analysis
Authors: Hasler Julian , Hoch Armando , Fürnstahl Philipp , Ackermann Jakob , Zingg Patrick O. , Vlachopoulos Lazaros 
Published: March 2021

AbstractBackgroundPreoperative templating in total hip arthroplasty (THA) is mandatory to achieve appropriate offset and leg length equality. However, templating methods using the contralateral hip might be susceptible to errors resulting from side-differences in the femoral morphology. The distance of the lesser trochanter to the femoral head center (LTFHD) is a frequently used reference parameter for preoperative planning and intraoperative validation during THA. However, currently no three-dimensional (3D) analysis of side differences of the LTFHD exists.MethodsUsing Computer tomography (CT)-based surface models from 100 paired femora (50 cadavers), side-to-side asymmetry of the LTFHD, femoral length, femoral head diameter (FHD) and femoral antetorsion were analyzed. Univariate linear regression models were established to evaluate potential associations between sides regarding LTFHD and FHD as well as a correlation of these parameters with each other.ResultsStatistically significant side-differences were found for the LTFHD (p = 0.02) and FHD (p = 0.03) with a mean absolute side-difference of 1.6 ± 1.4mm (range 0.1–5.5mm) and 0.4mm ± 0.6mm (range 0–3mm), respectively. The ratio between the LTFHD and FHD was consistent with an average value of 1.16 ± 0.08 and reliable between sides with a correlation coefficient (r) of 0.72 (p < 0.01).ConclusionsThe LTFHD is a reliable reference parameter for preoperative templating and intraoperative validation during THA with a high correlation between sides (r = 0.93,p < 0.01). However, 8 % of the investigated specimens revealed a LTFHD of more than 4mm, which should be anticipated during THA to avoid unsatisfiable results.
A method for interoperable knowledge-based data quality assessment
Authors: Tute Erik , Scheffner Irina , Marschollek Michael 
Published: March 2021

AbstractBackgroundAssessing the quality of healthcare data is a complex task including the selection of suitable measurement methods (MM) and adequately assessing their results.ObjectivesTo present an interoperable data quality (DQ) assessment method that formalizes MMs based on standardized data definitions and intends to support collaborative governance of DQ-assessment knowledge, e.g. which MMs to apply and how to assess their results in different situations.MethodsWe describe and explain central concepts of our method using the example of its first real world application in a study on predictive biomarkers for rejection and other injuries of kidney transplants. We applied our open source tool—openCQA—that implements our method utilizing the openEHR specifications. Means to support collaborative governance of DQ-assessment knowledge are the version-control system git and openEHR clinical information models.ResultsApplying the method on the study’s dataset showed satisfactory practicability of the described concepts and produced useful results for DQ-assessment.ConclusionsThe main contribution of our work is to provide applicable concepts and a tested exemplary open source implementation for interoperable and knowledge-based DQ-assessment in healthcare that considers the need for flexible task and domain specific requirements.
Divergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold
Authors: Hervás Rubén , del Carmen Fernández-Ramírez María , Galera-Prat Albert , Suzuki Mari , Nagai Yoshitaka , Bruix Marta , Menéndez Margarita , Laurents Douglas V. , Carrión-Vázquez Mariano 
Published: March 2021

AbstractBackgroundAmyloids are ordered, insoluble protein aggregates, characterized by a cross-β sheet quaternary structure in which molecules in a β-strand conformation are stacked along the filament axis via intermolecular interactions. While amyloids are typically associated with pathological conditions, functional amyloids have also been identified and are present in a wide variety of organisms ranging from bacteria to humans. The cytoplasmic polyadenylation element-binding (CPEB) prion-like protein is an mRNA-binding translation regulator, whose neuronal isoforms undergo activity-dependent aggregation, a process that has emerged as a plausible biochemical substrate for memory maintenance. CPEB aggregation is driven by prion-like domains (PLD) that are divergent in sequence across species, and it remains unknown whether such divergent PLDs follow a similar aggregating assembly pathway. Here, we describe the amyloid-like features of the neuronalAplysiaCPEB (ApCPEB) PLD and compare them to those of theDrosophilaortholog, Orb2 PLD.ResultsUsing in vitro single-molecule and bulk biophysical methods, we find transient oligomers and mature amyloid-like filaments that suggest similarities in the late stages of the assembly pathway for both ApCPEB and Orb2 PLDs. However, while prior to aggregation the Orb2 PLD monomer remains mainly as a random coil in solution, ApCPEB PLD adopts a diversity of conformations comprising α-helical structures that evolve to coiled-coil species, indicating structural differences at the beginning of their amyloid assembly pathways.ConclusionOur results indicate that divergent PLDs of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms.
BG-flow, a new flow cytometry tool for G-quadruplex quantification in fixed cells
Authors: De Magis Alessio , Kastl Melanie , Brossart Peter , Heine Annkristin , Paeschke Katrin 
Published: March 2021

Abstract
Background
Nucleic acids can fold into non-canonical secondary structures named G-quadruplexes (G4s), which consist of guanine-rich sequences stacked into guanine tetrads stabilized by Hoogsteen hydrogen bonding, π-π interactions, and monovalent cations. G4 structure formation and properties are well established in vitro, but potential in vivo functions remain controversial. G4s are evolutionarily enriched at distinct, functional genomic loci, and both genetic and molecular findings indicate that G4s are involved in multiple aspects of cellular homeostasis. In order to gain a deeper understanding of the function of G4 structures and the trigger signals for their formation, robust biochemical methods are needed to detect and quantify G4 structures in living cells. Currently available methods mostly rely on fluorescence microscopy or deep sequencing of immunoprecipitated DNA or RNA using G4-specific antibodies. These methods provide a clear picture of the cellular or genomic localization of G4 structures but are very time-consuming. Here, we assembled a novel protocol that uses the G4-specific antibody BG4 to quantify G4 structures by flow cytometry (BG-flow).

Results
We describe and validate a flow cytometry-based protocol for quantifying G4 levels by using the G4-specific antibody BG4 to label standard cultured cells (Hela and THP-1) as well as primary cells obtained from human blood (peripheral blood mononuclear cells (PBMCs)). We additionally determined changes in G4 levels during the cell cycle in immortalized MCF-7 cells, and validated changes previously observed in G4 levels by treating mouse macrophages with the G4-stabilizing agent pyridostatin (PDS).

Conclusion
We provide mechanistic proof that BG-flow is working in different kinds of cells ranging from mouse to humans. We propose that BG-flow can be combined with additional antibodies for cell surface markers to determine G4 structures in subpopulations of cells, which will be beneficial to address the relevance and consequences of G4 structures in mixed cell populations. This will support ongoing research that discusses G4 structures as a novel diagnostic tool.
Association of NAT2 genetic polymorphism with the efficacy of Neurotropin® for the enhancement of aggrecan gene expression in nucleus pulposus cells: a pilot study
Authors: Nakai Tomoko , Sakai Daisuke , Nakamura Yoshihiko , Horikita Natsumi , Matsushita Erika , Naiki Mitsuru , Watanabe Masahiko 
Published: March 2021

Abstract
Background
Intervertebral disc degeneration, one of the major causes of low-back pain, results from altered biosynthesis/turnover of extracellular matrix in the disc. Previously, we reported that the analgesic drug Neurotropin® (NTP) had an anabolic effect on glycosaminoglycan synthesis in cultured nucleus pulposus (NP) cells via the stimulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1. However, its effect on the aggrecan core protein was not significantly detected, because of the data variance. A microarray analysis suggested that the effect of NTP on aggrecan was correlated with N-acetyltransferase 2 (NAT2), a drug-metabolizing enzyme. Specific NAT2 alleles are known to correlate with rapid, intermediate, and slow acetylation activities and side effects of various drugs. We investigated the association between the efficacy of NTP on aggrecan expression and the NAT2 genotype in cell donors.

Methods
NP cells were isolated from intervertebral disc tissues donated by 31 Japanese patients (28–68 years) who underwent discectomy. NTP was added to the primary cell cultures and its effect on the aggrecan mRNA was analyzed using real-time quantitative PCR. To assess acetylator status, genotyping was performed based on the inferred NAT2 haplotypes of five common single-nucleotide polymorphisms using allele-specific PCR.

Results
The phenotype frequencies of NAT2 in the patients were 0%, 42.0%, and 58.0% for slow, intermediate, and rapid acetylators, respectively. The proportions of responders to NTP treatment (aggrecan upregulation, ≥ 1.1-fold) in the intermediate and rapid acetylators were 76.9% and 38.9%, respectively. The odds ratio of the comparison of the intermediate acetylator status between responders and nonresponders was 5.2 (95% CI 1.06–26.0, P = 0.036), and regarding the 19 male patients, this was 14.0 (95% CI 1.54–127.2, P = 0.012). In the 12 females, the effect was not correlated with NAT2 phenotype but seemed to become weaker along with aging.

Conclusions
An intermediate acetylator status significantly favored the efficacy of NTP treatment to enhance aggrecan production in NP cells. In males, this tendency was detected with higher significance. This study provides suggestive data of the association between NAT2 variants and the efficacy of NTP treatment. Given the small sample size, results should be further confirmed.
A pan-cancer study of selenoprotein genes as promising targets for cancer therapy
Authors: Wu Wentao , Li Daning , Feng Xiaojie , Zhao Fanfan , Li Chengzhuo , Zheng Shuai , Lyu Jun 
Published: March 2021

Abstract
Background
The most important health benefit of selenium (Se) is in the prevention and control of cancer. Glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs) are selenoenzymes that are thought to play a role in oxidative stress. The differential expression of genes of the TXNRD and GPX families is closely related to carcinogenesis and the occurrence of cancer. This study comprehensively analyzed the expression profiles of seven genes in the TXNRD and GPX families, in terms of their correlations with patient survival and immune-cell subtypes, tumor microenvironment, and drug sensitivity.

Results
The expression profiles of genes in the TXNRD and GPX families differ between different types of cancer, and also between and within individual cancer cases. The expression levels of the seven analyzed genes are related to the overall survival of patients. The TXNRD1 and TXNRD3 genes are mainly related to poor prognoses, while other genes are related to good or poor prognoses depending on the type of cancer. All of the genes were found to be correlated to varying degrees with immune-cell subtypes, level of mechanistic cell infiltration, and tumor cell stemness. The TXNRD1, GPX1, and GPX2 genes may exert dual effects in tumor mutagenesis and development, while the TXNRD1, GPX1, GPX2, and GPX3 genes were found to be related to drug sensitivity or the formation of drug resistance.

Conclusions
The results will greatly help in identifying the association between genes and tumorigenesis, especially in the immune response, tumor microenvironment, and drug resistance, and very important when attempting to identify new therapeutic targets.
“A piece of paper is not the same as having someone to talk to”: accessing post-diagnostic dementia care before and since COVID-19 and associated inequalities
Authors: Giebel Clarissa , Hanna Kerry , Tetlow Hilary , Ward Kym , Shenton Justine , Cannon Jacqueline , Butchard Sarah , Komuravelli Aravind , Gaughan Anna , Eley Ruth , Rogers Carol , Rajagopal Manoj , Limbert Stan , Callaghan Steve , Whittington Rosie , Shaw Lisa , Gabbay Mark 
Published: March 2021

Abstract
Background
Social support services such as day care centres are important in post-diagnostic dementia care to enable people living with dementia stay at home for longer. Little research has addressed potential inequalities in access, with no research on variations before and since COVID-19. The aim of this study was to explore inequalities in social support service usage before and since the pandemic.

Methods
Unpaid carers and people living with dementia were interviewed over the phone about their experiences of accessing social support services before and since the COVID-19 pandemic. Transcripts were analysed for key themes using inductive and deductive thematic analysis.

Results
Fifty participants (42 unpaid carers; eight people living with dementia) were interviewed, and five themes identified: (1) Service issues; (2) Access issues; (3) Relying on own initiative; (4) New inequalities due to COVID-19; and (5) Missing out on the benefits of support services. Participants reported transport, finances, and location as factors reducing their ability to access support service pre-COVID, with inequalities remaining and at times exacerbated since. Carers and people living with dementia also reported struggling with accessing basic necessities during COVID, including food and medicines.

Conclusions
Considering the benefits of accessing support services, resourced procedures and facilities are needed to maintain access to support services with more accessible remote support provision, enabling people from all backgrounds to access the care they need.
Evaluating cancer research impact: lessons and examples from existing reviews on approaches to research impact assessment
Authors: Hanna Catherine R. , Boyd Kathleen A. , Jones Robert J. 
Published: March 2021

Abstract
Background
Performing cancer research relies on substantial financial investment, and contributions in time and effort from patients. It is therefore important that this research has real life impacts which are properly evaluated. The optimal approach to cancer research impact evaluation is not clear. The aim of this study was to undertake a systematic review of review articles that describe approaches to impact assessment, and to identify examples of cancer research impact evaluation within these reviews.

Methods
In total, 11 publication databases and the grey literature were searched to identify review articles addressing the topic of approaches to research impact assessment. Information was extracted on methods for data collection and analysis, impact categories and frameworks used for the purposes of evaluation. Empirical examples of impact assessments of cancer research were identified from these literature reviews. Approaches used in these examples were appraised, with a reflection on which methods would be suited to cancer research impact evaluation going forward.

Results
In total, 40 literature reviews were identified. Important methods to collect and analyse data for impact assessments were surveys, interviews and documentary analysis. Key categories of impact spanning the reviews were summarised, and a list of frameworks commonly used for impact assessment was generated. The Payback Framework was most often described. Fourteen examples of impact evaluation for cancer research were identified. They ranged from those assessing the impact of a national, charity-funded portfolio of cancer research to the clinical practice impact of a single trial. A set of recommendations for approaching cancer research impact assessment was generated.

Conclusions
Impact evaluation can demonstrate if and why conducting cancer research is worthwhile. Using a mixed methods, multi-category assessment organised within a framework, will provide a robust evaluation, but the ability to perform this type of assessment may be constrained by time and resources. Whichever approach is used, easily measured, but inappropriate metrics should be avoided. Going forward, dissemination of the results of cancer research impact assessments will allow the cancer research community to learn how to conduct these evaluations.