bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and characterization of stable red, far-red (fR) and near infra-red (NIR) transfected canine prostate cancer cell lines
Authors: Liu Wen , Sender Sina , Kong Weibo , Beck Julia , Sekora Anett , Bornemann-Kolatzki Kirsten , Schuetz Ekkehart , Junghanss Christian , Brenig Bertram , Nolte Ingo , Murua Escobar Hugo 
Published: April 2020

Abstract
Background
Canine prostate cancer represents a unique model for human prostate cancer. In vitro systems offer various possibilities but Xenograft in vivo imaging allows studying complex tasks as tumor progression and drug intervention longitudinal. Herein, we established three canine prostate carcinoma cell lines stably expressing fluorescent proteins allowing deep tissue in vivo imaging.

Methods
Three canine prostate carcinoma (cPC) cell lines were stably transfected with fluorescent proteins in red, far-red and near infra-red spectrum, followed by G418 selection. Fluorescent protein expression was demonstrated by microscopy, flow cytometry and a NightOWL LB 983 in vivo imaging system. Cellular and molecular characteristics of the generated cell lines were compared to the parental cell line CT1258. Cell proliferation, metabolic activity and sphere formation capacity were analyzed. Stem cell marker expression was examined by qPCR and genomic copy number variation by genomic DNA whole genome sequencing.

Results
Three stably fluorescent protein transfected cPC cell lines were established and characterized. Compared to the parental cell line, no significant difference in cell proliferation and metabolic activity were detected. Genomic copy number variation analyses and stem cell marker gene expression revealed in general no significant changes. However, the generated cell line CT1258-mKate2C showed uniquely no distal CFA16 deletion and an elevated metabolic activity. The introduced fluorescencent proteins allowed highly sensitive detection in an in vivo imaging system starting at cell numbers of 0.156 × 106. Furthermore, we demonstrated a similar sphere formation capacity in the fluorescent cell lines. Interestingly, the clone selected CT1258-mKate2C, showed increased sphere formation ability.

Discussion
Starting from a well characterized cPC cell line three novel fluorescent cell lines were established showing high cellular and molecular similarity to the parental cell line. The introduction of the fluorescent proteins did not alter the established cell lines significantly. The red fluorescence allows deep tissue imaging, which conventional GFP labeling is not able to realize.

Conclusion
As no significant differences were detected between the established cell lines and the very well characterized parental CT1258 the new fluorescent cell lines allow deep tissue in vivo imaging for perspective in vivo evaluation of novel therapeutic regimens.
Risk and reward: extending stochastic glycaemic control intervals to reduce workload
Authors: Uyttendaele Vincent , Knopp Jennifer L. , Shaw Geoffrey M. , Desaive Thomas , Chase J. Geoffrey 
Published: April 2020

Abstract
Background
STAR is a model-based, personalised, risk-based dosing approach for glycaemic control (GC) in critically ill patients. STAR provides safe, effective control to nearly all patients, using 1–3 hourly measurement and intervention intervals. However, the average 11–12 measurements per day required can be a clinical burden in many intensive care units. This study aims to significantly reduce workload by extending STAR 1–3 hourly intervals to 1 to 4-, 5-, and 6-hourly intervals, and evaluate the impact of these longer intervals on GC safety and efficacy, using validated in silico virtual patients and trials methods. A Standard STAR approach was used which allowed more hyperglycaemia over extended intervals, and a STAR Upper Limit Controlled approach limited nutrition to mitigate hyperglycaemia over longer intervention intervals.

Results
Extending STAR from 1–3 hourly to 1–6 hourly provided high safety and efficacy for nearly all patients in both approaches. For STAR Standard, virtual trial results showed lower % blood glucose (BG) in the safe 4.4–8.0 mmol/L target band (from 83 to 80%) as treatment intervals increased. Longer intervals resulted in increased risks of hyper- (15% to 18% BG > 8.0 mmol/L) and hypo- (2.1% to 2.8% of patients with min. BG < 2.2 mmol/L) glycaemia. These results were achieved with slightly reduced insulin (3.2 [2.0 5.0] to 2.5 [1.5 3.0] U/h) and nutrition (100 [85 100] to 90 [75 100] % goal feed) rates, but most importantly, with significantly reduced workload (12 to 8 measurements per day). The STAR Upper Limit Controlled approach mitigated hyperglycaemia and had lower insulin and significantly lower nutrition administration rates.

Conclusions
The modest increased risk of hyper- and hypo-glycaemia, and the reduction in nutrition delivery associated with longer treatment intervals represent a significant risk and reward trade-off in GC. However, STAR still provided highly safe, effective control for nearly all patients regardless of treatment intervals and approach, showing this unique risk-based dosing approach, modulating both insulin and nutrition, to be robust in its design. Clinical pilot trials using STAR with different measurement timeframes should be undertaken to confirm these results clinically.
Magnitude and determinants of multimorbidity and health care utilization among patients attending public versus private primary care: a cross-sectional study from Odisha, India
Authors: Pati Sanghamitra , Swain Subhashisa , Knottnerus J. André , Metsemakers Job F. M. , van den Akker Marjan 
Published: April 2020

AbstractBackgroundMultimorbidity in primary care is a challenge not only for developing countries but also for low and medium income countries (LMIC). Health services in LMIC countries are being provided by both public and private health care providers. However, a critical knowledge gap exists on understanding the true extent of multimorbidity in both types of primary care settings.MethodsWe undertook a study to identify multimorbidity prevalence and healthcare utilization among both public and private primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire collecting information on 22 chronic diseases, medication use, number of hospitalization and number of outpatient visits.ResultThe overall prevalence of multimorbidity was 28.3% and nearly one third of patients of public facilities and one fourth from private facilities had multimorbidity. Leading diseases among patients visiting public facilities included acid peptic diseases, arthritis and chronic back pain. No significant difference in reporting of hypertension and diabetes across the facilities was seen. Besides age, predictors of multimorbidity among patients attending public facilities were, females [AOR: 1.6; 95% CI 1.1–1.3] and non-aboriginal groups [AOR: 1.6; 95%CI 1.1–2.3] whereas, in private females [AOR: 1.6; 95%CI 1.1–2.4], better socioeconomic conditions [AOR 1.4; 95% CI 1.0–2.1] and higher educational status [primary school completed [AOR 2.6; 95%CI 1.6–4.2] and secondary schooling and above [AOR 2.0; 95%CI 1.1–3.6] with reference to no education were seen to be the determinants of multimorbidity. Increased number of hospital visits to public facilities were higher among lower educational status patients [IRR: 1.57; 95% CI 1.13–2.18] whereas, among private patients, the mean number of hospital visits was 1.70 times more in higher educational status [IRR: 1.70; 95%CI 1.01–3.69]. The mean number of medicines taken per day was higher among patients attending private hospitals.ConclusionOur findings suggest that, multimorbidity is being more reported in public primary care facilities. The pattern and health care utilization in both types of settings are different. A comprehensive care approach must be designed for private care providers.
Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis
Authors: Vinson D. , Molet-Benhamou L. , Degboé Y. , den Broeder A. , Ibrahim F. , Pontes C. , Westhovens R. , Závada J. , Pham T. , Barnetche T. , Constantin A. , Ruyssen-Witrand A. 
Published: April 2020

Abstract
Objectives
To systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state.

Materials and methods
A meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies.

Results
Of the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (− 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups.

Conclusion
We could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.
Lemon seed allergy: a case presentation
Authors: Kayode O. Stephanie , Prado Nuevalynne , Thursfield David J. , Till Stephen J. , Siew Leonard Q. C. 
Published: April 2020

Abstract
Background
We report a case of IgE-mediated hypersensitivity to lemon seed. We demonstrate for the first time a pattern of cross-sensitisation between seeds of citrus hybrid species from similar ancestral species origins.

Case report
Described is a case of a 26-year-old female with recurrent anaphylaxis on exposure to lemon seed with sensitisation shown on prick to prick testing. Prick to prick testing was also performed to a variety of citrus fruit seeds and edible foods from additional notable families of the Sapindale order.

Conclusion
In cases of unexplained or recurrent anaphylaxis in adult patients, citrus seed allergy should be considered.
On stable entire solutions of sub-elliptic system involving advection terms with negative exponents and weights
Authors: Rahal Belgacem 
Published: April 2020

AbstractWe examine the weighted Grushin system involving advection terms given by $$ \textstyle\begin{cases} \Delta _{G} u - a \cdot \nabla _{G} u =(1+ \Vert \mathbf{z} \Vert ^{2(\alpha +1)})^{ \frac{\gamma }{2(\alpha +1)}} v^{-p} &\text{in $\mathbb {R}^{n}$}, \\ \Delta _{G} v - a \cdot \nabla _{G} v =(1+ \Vert \mathbf{z} \Vert ^{2(\alpha +1)})^{ \frac{\gamma }{2(\alpha +1)}} u^{-q} &\text{in $\mathbb {R}^{n}$}, \end{cases} $${ΔGu−a⋅∇Gu=(1+∥z∥2(α+1))γ2(α+1)v−pin Rn,ΔGv−a⋅∇Gv=(1+∥z∥2(α+1))γ2(α+1)u−qin Rn, where $\Delta _{G} u= \Delta _{x} u+ |x|^{2\alpha } \Delta _{y} u$ΔGu=Δxu+|x|2αΔyu, $\mathbf{z}=(x,y) \in \mathbb {R}^{n}:= \mathbb {R}^{n_{1}} \times \mathbb {R}^{n_{2}}$z=(x,y)∈Rn:=Rn1×Rn2 is the Grushin operator, $\alpha \geq 0$α≥0, $p \geq q >1$p≥q>1, $\|\mathbf{z}\|^{2(\alpha +1)}= |x|^{2(\alpha +1)} + |y|^{2} $∥z∥2(α+1)=|x|2(α+1)+|y|2, $\gamma \geq 0$γ≥0 and a is a smooth divergence-free vector that we will specify later. Inspired by recent progress in the study of the Lane–Emden system, we establish some Liouville-type results for bounded stable positive solutions of the system. In particular, we prove the comparison principle to establish our result. As consequences, we obtain a Liouville-type theorem for the weighted Grushin equation involving advection terms $$ \Delta _{G} u - a \cdot \nabla _{G} u =\bigl(1+ \Vert \mathbf{z} \Vert ^{2(\alpha +1)}\bigr)^{ \frac{\gamma }{2(\alpha +1)}} u^{-p} \quad \mbox{in } \mathbb {R}^{n}. $$ΔGu−a⋅∇Gu=(1+∥z∥2(α+1))γ2(α+1)u−pin Rn. The main tools in the proof of the main result are the comparison principle, nonlinear integral estimates via the stability assumption and the bootstrap argument. Our results generalize and improve the previous work in (Duong et al. in Complex Var. Elliptic Equ. 64(12):2117–2129, 2019).
Affine-periodic solutions by asymptotic and homotopy equivalence
Authors: Xing Jiamin , Yang Xue 
Published: April 2020

AbstractThis paper studies the existence of affine-periodic solutions which have the form of$x(t+T)=Qx(t)$x(t+T)=Qx(t)with some nonsingular matrixQ. Depending on the structure ofQ, they can be periodic, anti-periodic, quasi-periodic or even unbounded. Krasnosel’skii–Perov type existence theorem, asymptotic and homotopy equivalence approaches are given.
Methodological issues on “challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review”
Authors: Amir-Behghadami Mehrdad , Janati Ali , Gholizadeh Masoumeh 
Published: April 2020

AbstractSystematic reviews adhere to the principle that science is cumulative and attempt to identify all empirical evidence in accordance with pre-determined eligibility criteria to answer a specific research question. Therefore, in order to achieve reliable findings, these studies must use an explicit method, as they are increasingly used to guide political decision and the direction of future research. We would like to thank the authors Chhabi Lal Ranabhat et al., for the article “Challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review”. Although the authors have stated that they reported th according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, some items have not been well reported. We critically appraised it using the PRISMA guidelines. Results of the study were significantly valuable, but some important points that hamper the utility of the study need to be considered by the audors. The purpose of this letter is to improve the quality of study and present methodological issues about the search strategy, quality assessment of included studies, and data analysis and synthesis.
Methodological issues on ‘challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review’
Authors: Ranabhat Chhabi Lal , Acharya Devaraj 
Published: April 2020

AbstractChallenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review’ is a policy review paper and we published in BMC – Archives of Public Health. Policy research is the process of conducting research, analysis of, a fundamental social problem in order to provide policymakers with pragmatic, action-oriented recommendations for alleviating the problem. The objective of this paper is to illustrate some methodological issues used in that paper.
Primary breast non-Hodgkin’s lymphoma in a 14-year-old girl: a case report
Authors: Ishizuka Yumiko , Horimoto Yoshiya , Fujimura Junya , Ogata Kozue , Murakami Fumi , Onagi Hiroko , Arakawa Atsushi , Saito Mitsue 
Published: April 2020

Abstract
Background
Primary breast lymphoma is rare. Occurrence rates of malignant breast tumors in children are also quite low. We herein report a B-lymphoblastic lymphoma of the breast arisen in an adolescent girl. To the best of our knowledge, this is the youngest case with primary breast non-Hodgkin’s lymphoma.

Case presentation
A 14-year-old Japanese girl felt a lump in her right breast and came to our hospital. A circumscribed soft mass, 30 mm in diameter, was palpable. Histological examination revealed atypical lymphoid cells diffusely spreading into the breast tissue. Based on results of immunohistochemistry and flow cytometry, her disease was diagnosed as B-lymphoblastic lymphoma (stage I). She was then referred to the pediatric department and received combination chemotherapy, based on a chemotherapy regimen for children with acute lymphoblastic leukemia. Following remission induction therapy, we confirmed no FDG uptake in the right breast on PET-CT scan.

Conclusions
We have described a rare malignant lymphoma arising in the breast of an adolescent female. Histological assessment is necessary for diagnosis of breast lymphoma. However, it can be challenging with several reasons, and clinical information may contribute to the assessment. Moreover, treatments for lymphoma vary according to disease types. Thus, surgeons should collaborate closely with pathologists, pediatricians, and hematologists.
Translating pharmacogenetics from research to routine clinical practice – a survey of the IGNITE Network
Authors: Levy Kenneth D. , Wu R. Ryanne , Goto Daisuke , Ramos Michelle A. , Pratt Victoria M. , Hicks J. Kevin , Madden Ebony B. , Bell Gillian C. , Blake Kathryn V. , Cohen Michelle , Duong Benjamin Q. , Franciosi James P. , Orlando Lori A. , Sanghavi Kunal , Ginsburg Geoffrey S. 
Published: April 2020

Abstract
Background
Translating pharmacogenetic research findings that have shown clinical efficacy into sustainable, routine clinical care at the institutional level requires strong evidence of improved patient outcomes bolstered by equitable reimbursement and a sound financial analysis. Although extensive research on the clinical value of pharmacogenetics has been completed, adoption into clinical practice lags due to a lack of evidence of clinical effectiveness and limited reimbursement.

Methods
The Sustainability Working Group within the NHGRI IGNITE I Network conducted an online survey of funded and non-funded IGNITE members to determine which genes they are researching, which have been translated into clinical practice, and how tests are billed. Data from the online surveys was consolidated and analyzed with results being tabulated for key findings. Due to the limited sample size, statistical analysis was forgone and results should be considered directional in nature.

Results
Fifteen out of twenty (75%) online survey responses were received and analyzed from IGNITE member sites delivering clinical care. Forty different genes were identified as being used for either research or clinical care. Thirty-two different genes were reported as being used clinically, an average of 6.9 genes were reported per site. Twenty-two and twenty-one genes were reported as being billed to third party payers or patients respectively. Although the survey did not ask whether sites submitting for reimbursement received payment, Medicare and Medicaid only reimburse for 6 of the 40 (15%) genes being tested. Of the 40 genes, 18 are rated by CPIC as having A/B level of evidence with the remainder being rated as C/D or having no rating. Approximately 32% more A/B rated genes were being reported clinically than non-A/B.

Conclusion
Adoption of pharmacogenetic testing continues to lag even at sites where leading experts conduct research and have the capability to report tests clinically. Clinical research that supports CPIC A level of evidence is important for provider and payer support. Adoption of pharmacogentic testing must also be justified financially, reimbursement is one key factor, and more health economic studies are needed in order to capture the value created by preventing drug-gene adverse events, emergency room visits, and hospitalizations.
Machine learning applications for electroencephalograph signals in epilepsy: a quick review
Authors: Si Yang 
Published: April 2020

AbstractMachine learning (ML) is a fundamental concept in the field of state-of-the-art artificial intelligence (AI). Over the past two decades, it has evolved rapidly and been employed wildly in many fields. In medicine the widespread usage of ML has been observed in recent years. The present review examines various ML approaches for electroencephalograph (EEG) signal procession in epilepsy research, highlighting applications in the aspect of automated seizure detection, prediction and orientation. The present review also presents advantage, challenge and future direction of ML techniques in the analysis of EEG signals in epilepsy.
A CRISPR/Cas9 genome editing pipeline in the EndoC-βH1 cell line to study genes implicated in beta cell function
Authors: Grotz Antje K. , Abaitua Fernando , Navarro-Guerrero Elena , Hastoy Benoit , Ebner Daniel , Gloyn Anna L. 
Published: April 2020

Type 2 diabetes (T2D) is a global pandemic with a strong genetic component, but most causal genes influencing the disease risk remain unknown. It is clear, however, that the pancreatic beta cell is central to T2D pathogenesis. In vitro gene-knockout (KO) models to study T2D risk genes have so far focused on rodent beta cells. However, there are important structural and functional differences between rodent and human beta cell lines. With that in mind, we have developed a robust pipeline to create a stable CRISPR/Cas9 KO in an authentic human beta cell line (EndoC-βH1). The KO pipeline consists of a dual lentiviral sgRNA strategy and we targeted three genes (INS, IDE, PAM) as a proof of concept. We achieved a significant reduction in mRNA levels and complete protein depletion of all target genes. Using this dual sgRNA strategy, up to 94 kb DNA were cut out of the target genes and the editing efficiency of each sgRNA exceeded >87.5%. Sequencing of off-targets showed no unspecific editing. Most importantly, the pipeline did not affect the glucose-responsive insulin secretion of the cells. Interestingly, comparison of KO cell lines for NEUROD1 and SLC30A8 with siRNA-mediated knockdown (KD) approaches demonstrate phenotypic differences. NEUROD1-KO cells were not viable and displayed elevated markers for ER stress and apoptosis. NEUROD1-KD, however, only had a modest elevation, by 34%, in the pro-apoptotic transcription factor CHOP and a gene expression profile indicative of chronic ER stress without evidence of elevated cell death. On the other hand, SLC30A8-KO cells demonstrated no reduction in KATP channel gene expression in contrast to siRNA silencing. Overall, this strategy to efficiently create stable KO in the human beta cell line EndoC-βH1 will allow for a better understanding of genes involved in beta cell dysfunction, their underlying functional mechanisms and T2D pathogenesis.