bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrous cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours
Authors: Bernhardt Sarah M , Dasari Pallave , Glynn Danielle J , Woolford Lucy , Moldenhauer Lachlan M , Walsh David , Townsend Amanda R , Price Timothy J , Ingman Wendy V 
Published: July 2020

Abstract
Background: The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods: ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results: Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p≤0.05) and a significant increase in 21-gene recurrence score (21.8±2.4; mean±SEM) compared to tumours dissected at estrus (15.5±1.9; p=0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p<0.001) and invasion-group (p=0.01) genes, and increased 21-gene recurrence score (p=0.01). These tumours also exhibited higher expression of estrogen-group genes (p=0.005) suggesting increased sensitivity to hormonal fluctuations during the ovarian cycle. Conclusions: Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature and recurrence scores in Mmtv-Pymt murine mammary tumours. Whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage is not yet known. To address this question and ensure young breast cancer patients receive optimal treatment advice, future prospective studies using breast cancer samples from premenopausal women with known cycle stage are required.
Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 axis
Authors: Zhou Qi , Li Yuan , Chen Lujun , Zheng Xiao , Jiang Tianwei , Liu Juan , Fu Yuanyuan , Guan Liping , Ju Jingfang , Wu Changping 
Published: July 2020

Abstract
Backgroud Long non-coding RNAs (lncRNAs) played important roles in various biological processes and human diseases, including cancer. Methods In this study, RNAi technology, RNA-FISH, RNA-pull down assay and cellular function studies were used to demonstrate a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Results Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target gene of miR-375, and established the important role of GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Conclusions Our results revealed a novel mechanism of GRIK1-AS1 as sponge to miR-375that impact gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, open a new strategy to future GRIK1-AS1 based therapeutic development.
Clinical diagnosis of patients subjected to surgical lung biopsy with a probable usual interstitial pneumonia pattern on high-resolution computed tomography
Authors: Tibana Regina , Soares Maria Raquel , Storrer Karin Mueller , Meirelles Gustavo de Souza Portes , Nishiyama Katia , Missrie Israel , Coletta Ester Nei Aparecida Martins , Ferreira Rimarcs Gomes , Pereira Carlos Alberto de Castro 
Published: July 2020

Abstract
Background: Usual interstitial pneumonia (UIP) can present with a probable pattern on high-resolution computed tomography (HRCT), but the probability of UIP by surgical lung biopsy in such cases remains controversial. We aimed to determine the final clinical diagnosis in patients with a probable UIP pattern on HRCT subjected to surgical lung biopsy.Methods: HRCT images were assessed and categorized by three radiologists, and tissue slides were evaluated by two pathologists, all of whom were blinded to the clinical findings. The final clinical diagnosis was accomplished via a multidisciplinary discussion. Patients with a single layer of honeycombing located outside of the lower lobes on HRCT were not excluded.Results: A total of 50 patients were evaluated. The most common final clinical diagnosis was fibrotic hypersensitivity pneumonitis (38.0%; 95% CI: 24.7% to 52.8%), followed by idiopathic pulmonary fibrosis (24.0%; 95% CI: 13.1% to 38.2%) and interstitial lung disease ascribed to gastroesophageal reflux disease (12.0%; 95% CI: 4.5% to 24.3%) and familial interstitial lung disease (10.0%; 95% CI: 3.3% to 21.8%). In the group without environmental exposure (n = 22), 10 patients had a final clinical diagnosis of idiopathic pulmonary fibrosis (45.5%; 95% CI: 24.4% to 67.8%). Irrespective of the final clinical diagnosis, by multivariate Cox analysis, patients with honeycombing, dyspnoea and the presence of fibroblastic foci on surgical lung biopsy had a high risk of death.Conclusions: The most common disease associated with a probable UIP pattern on HRCT is fibrotic hypersensitivity pneumonitis, followed by idiopathic pulmonary fibrosis and interstitial lung disease ascribed to gastroesophageal reflux disease. In patients without environmental exposure, the frequency of UIP and a final clinical diagnosis of idiopathic pulmonary fibrosis are not sufficiently high to obviate the indication for surgical lung biopsy.
Long-Term Survival With Sebelipase Alfa Enzyme Replacement Therapy in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency Final Results From 2 Open-Label Studies
Authors: Vijay Suresh , Brassier Anais , Ghosh Arunabha , Fecarotta Simona , Abel Florian , Marulkar Sachin , Jones Simon A. 
Published: July 2020

Abstract
Background
If symptomatic in infants, the autosomal recessive disease lysosomal acid lipase deficiency (LAL-D; sometimes called Wolman disease or LAL-D/Wolman phenotype) is characterized by complete loss of LAL enzyme activity. This very rare, rapidly progressive form of LAL-D results in severe manifestations leading to failure to thrive and death, usually by 6 months of age. We report results from 2 open-label studies of enzyme replacement therapy with sebelipase alfa, a recombinant human LAL, in infants with LAL-D: the phase 2/3 Survival of LAL-D Infants Treated With Sebelipase Alfa (VITAL) study (NCT01371825) and a phase 2 dose-escalation study (LAL-CL08 [CL08]; NCT02193867). In both, infants received once-weekly intravenous infusions of sebelipase alfa.
Results
The analysis population contained 19 patients (9 in VITAL; 10 in CL08). Kaplan-Meier estimates of survival to 12 months and 5 years of age were 79% and 68%, respectively, in the combined population, and the median age of surviving patients was 5.2 years in VITAL and 3.2 years in CL08. In both studies, median weight-for-age, length-for-age, and mid-upper arm circumference-for-age z scores increased from baseline to end of study. Decreases in median liver and spleen volume over time were noted in both studies. Short-term transfusion-free hemoglobin normalization was achieved by 100% of patients eligible for assessment in VITAL, in an estimated median (95% confidence interval [CI]) time of 4.6 (0.3–16.6) months. In CL08, short-term transfusion-free hemoglobin normalization was achieved by 70% of patients eligible for assessment, in an estimated median (95% CI) time of 5.5 (3.7–19.6) months. No patient discontinued treatment because of treatment-emergent adverse events. Most infusion-associated reactions (94% in VITAL and 88% in CL08) were mild or moderate in severity.
Conclusions
The findings of these 2 studies of infants with rapidly progressive LAL-D demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival with normal psychomotor development, improved growth, hematologic, and liver parameters, and was generally well tolerated, with an acceptable safety profile.
A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases
Authors: de Gruijter Nina M , Naja Meena , Peckham Hannah , Radziszewska Anna , Kinsella Matthew , Glenister James , Rosser Elizabeth , Butler Gary E , Jury Elizabeth C , Ciurtin Coziana 
Published: July 2020

Abstract
Background: Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARDs related outcomes.Methods: Studies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS).Results: 14 non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 6), or both (n = 1) have been identified. The impact of puberty on ARD outcomes have been investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4–9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment.Conclusion: A bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.
Diagnostic capability of different morphological parameters for primary open-angle glaucoma in the Chinese population.
Authors: Li Ruoshi , Wang Xia , Wei Yahui , Fang Yuan , Tian Tian , Kang Lei , Li Mei , Cai Yu , Pan Yingzi 
Published: July 2020

Abstract
Background
To assess the diagnostic capability of novel Bruch’s membrane opening (BMO)-based disc parameters, the BMO-minimum rim width (BMO-MRW) and the BMO-minimum rim area (BMO-MRA) in the Chinese population and compare them to the retinal nerve fiber layer (RNFL) from optical coherence tomography (OCT) and the rim area (RA) from the Heidelberg retinal tomograph-III (HRT-III).
Methods
In total, 200 eyes of 77 healthy and 123 primary open-angle glaucoma (POAG) subjects were included in this cross-sectional study. All participants underwent the visual field test and structural measurements by OCT and HRT-III. The areas under the receiver operating characteristic curves (AUCs) of different structural parameters were calculated to assess their diagnostic power and compared using the DeLong test.
Results
In populations with different characteristics, the BMO-MRW and BMO-MRA had better diagnostic power than the RA. In discriminating between all POAG subjects and healthy controls and between early-stage patients and controls, the global BMO-MRW had comparable AUCs with the RNFL, but the BMO-MRA had lower AUCs than the RNFL. In healthy subjects with macrodiscs, both the global and sectoral BMO-MRW were thinner than those in healthy subjects with normal disc size. The AUCs of BMO-MRA, BMO-MRW and RNFL in subjects with macrodiscs were comparable. Additionally, in the myopic population, the BMO-MRA and BMO-MRW had comparable AUCs with the RNFL.
Conclusions
The BMO-MRW had comparable diagnostic power with the RNFL, and compared with BMO-MRW, the BMO-MRA might have advantages in certain populations, such as macrodiscs. All OCT-derived parameters exceeded the RA in diagnostic capability.
Post-transplant monitoring of lymphocyte counts predict the occurrence of CMV infection in early phase of kidney transplantation
Authors: Feng Sujuan , Yang Jing , Zhang Xiaodong 
Published: July 2020

Abstract
Objectives The aim of this study was to assess whether monitoring of the number of lymphocytes in peripheral blood was helpful for evaluating the risk of cytomegalovirus (CMV) infection after kidney transplantation. Methods The total numbers of lymphocyte in peripheral blood were measured at baseline and posttransplant months 1, 3 and 6. Risk factors for DNAemia in KTRs were analyzed using univariate logistic regression analyses. Areas under receiver operating characteristic (ROC) curves were applied to assess the accuracy of lymphocyte counts for predicting CMV DNAemia. Results After follow-up 6 months, CMV replication was detected in 12 (31.6%) kidney transplant recipients (KTRs). The total lymphocyte counts were significantly decreased in KTRs with CMV DNAemia in 1, 3 and 6 months. There was a negative correlation between CMV copies and the lymphocyte counts in 1, 3 and 6 months post-transplantation, and the decrease of lymphocyte counts in the 6 months post-transplantation was the risk factor of CMV DNAemia in the KTR. Patients with lymphocyte counts 1.085×109 cells/L had higher cumulative incidence of CMV infection.Conclusions The lymphocyte counts post kidney transplantation may be used as a simple and effective indicator for monitoring the CMV infection status in KTR and for predicting the risk of CMV DNAemia.
Preserving Professional Identities, Behaviors, and Values in Digital Professionalism: A Scoping Review
Authors: Guraya Shaista Salman , Guraya Salman Yousuf , Yusoff Muhammad Saiful Bahri 
Published: July 2020

Abstract
Background Despite a rapid rise of use of social media in medical disciplines, uncertainty prevails among healthcare professionals for providing medical content on social media. There are also growing concerns about unprofessional behaviors and blurring of professional identities that are undermining digital professionalism. This review tapped the literature to determine the impact of social media on medical professionalism and how can professional identities and values be maintained in digital era. Methods We searched the databases of PubMed, ProQuest, ScienceDirect, Web of Science, and EBSCO host using (professionalism AND (professionalism OR (professional identity) OR (professional behaviors) OR (professional values) OR (professional ethics))) AND ((social media) AND ((social media) OR (social networking sites) OR Twitter OR facebook)) AND (health professionals). The research questions were based on participants (health professionals), concept (professionalism), and context (social media, digital world). We screened initial yield of titles using pre-determined inclusion and exclusion criteria and selected a group of articles for qualitative analysis. We used the Biblioshiny® software package for generation of popular concepts as clustered keywords. Results Our search yielded 44 articles with four leading themes; marked rise in use of social media by healthcare professionals and students, negative impact of social media on digital professionalism, blurring of medical professional values, behaviors, and identity in digital era, limited evidence for teaching and assessing digital professionalism. A high occurrence of violation of patient privacy and professional integrity and cyberbullying is reported. There are no existing guidelines and policies for digital professionalism that can safeguard healthcare professionals, students and patients. Conclusion Our scoping review reports a rapid rise of unprofessional behaviors on social media among healthcare professionals. The boundaries between personal and professional practices are mystified in digital professionalism. These findings call for potential educational ramifications to resurrect professional virtues, behaviors and identities of healthcare professionals and students.
Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles
Authors: Mehrnia Somayeh Sadat , Hashemi Bijan , Mowla Seyed Javad , Nikkhah Maryam , Arbabi Azim 
Published: July 2020

Abstract
Background: Gold nanoparticles (GNPs) have used to sensitize cancer cells and enhance the absorbed dose delivered to such cells. Active targeting can provide specific effect and higher uptake of the GNPs in the tumor cells, while having small effect on healthy cells. The aim of this study was to assess possible radiosensitiazation effect of conjugation of the GNPs with AS1411 aptamer (AS1411/GNPs) on cancer cells treated with 4 MeV electron beams.Materials and Methods: Cytotoxicity studies of the GNPs and AS1411/GNPs were carried out with MTT and MTS assay in different cancer cell lines of MCF-7, MDA-MB-231 and mammosphere of MCF-7 cells. Atomic absorption spectroscopy (AAS) confirmed the cellular uptake of the gold particles. Radiosensitizing effect of the GNPs and AS1411/GNPs on the cancer cells was assessed by clonogenic assay.Result: AS1411 aptamer increased the Au uptake in MCF-7 and MDA-MB-231 cells. Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L could result in radiosensitization of the breast cancer cells and lead to a sensitizer enhancement ratio (SER) of 1.35 and 1.66 and 1.91 for MCf-7, MDA-MB-231 and mammosphere cells.Conclusion: Gold nanoparticles delivery to the cancer cells was enhanced by AS1411 aptamer and led to enhanced radiation induced cancer cells death. The combination of our clonogenic assay and Au cell uptake results suggested that AS1411 aptamer has enhanced the radiation-induced cell death by increasing Au uptake. This enhanced sensitization contributed to cancer stem cell-like cells to 4 MeV electron beams. This is particularly important for future preclinical testing to open a new insight for the treatment of cancers.
A Malignant Lymphoma Growing Inside a Cardiac Mixoma: A Case Report
Authors: Pirola Sergio , Mastroiacovo Giorgio , Fiori Stefano , Maffini Fausto , Mostardini Giulia , Polvani Gianluca 
Published: July 2020

Abstract
BackgroundLymphomas arising in cardiac myxomas represent a particularly rare pathology, with only few cases reported in the literature.Case presentation:We report a completely exeresis of malignant lymphoma arising in a cardiac myxoma in a 44 years-old female patient. The myxoma presented like a floating mass within the left atrium with a maximum diameter of 3.5 cm. The clinical post-operative period was uneventful and the patient was dismissed on sixth post-operative day.ConclusionsThis case reinforces the concept of a radical exeresis of cardiac neoplasms.
Utility of silhouette showcards to assess adiposity in three countries across the epidemiological transition
Authors: Reese Tyler , Bovet Pascal , Choo-Kang Candice , Bedu-Addo Kweku , Forrester Terrence , Gilbert Jack , Goedecke Julia , Lambert Estelle , Layden Brian , Micklesfield Lisa , Plange-Rhule Jacob , Rae Dale , Viswanathan Bharathi , Luke Amy , Dugas Lara 
Published: July 2020

Abstract
Background: The Pulvers’ silhouette showcards provide a non-invasive, easy-to-use, and possibly cross-culturally acceptable way of assessing an individual’s perception of their body size. This study examined, in three different populations: 1) the relationship between silhouettes and body mass index (BMI), 2) the predictive performance of silhouettes to predict dichotomous adiposity categories, and 3) whether silhouette ranking performed similarly in predicting BMI, waist circumference (WC), and waist-to-height ratio (WHR). Methods: This study included 751 participants of African-origin from the United States of America (USA), the Republic of Seychelles, and Ghana, from the ongoing cohort Modeling the Epidemiological Transition Study. We assessed the mean BMI for each silhouette rank by country and sex and performed a least-squares linear regression for the silhouette’s performance by country and sex. The performance of the silhouettes to predict overweight and obesity (BMI ≥ 25 kg/m2), and obesity alone (BMI ≥ 30 kg/m2) was examined through a receiver operator curve (ROC) analysis with corresponding sensitivities and specificities. Finally, a ROC analysis area under the curve (AUC) was also performed for the detection of elevated waist circumference (men ≥ 94 cm; women ≥ 80 cm) and waist-to-height ratio (> 0.5) by country and sex.Results: Mean measured BMI (kg/m2) in men/women differed largely across countries: 28.9/35.8 in the USA, 28.3/30.5 in Seychelles, and 23.9/28.5 in Ghana. The slope of the relation between silhouette ranking and BMI (i.e., linear regression coefficient and 95% confidence intervals) was similar between sexes of the same country but differed between countries: 3.65 [95% CI: 3.34-3.97 BMI units/silhouette unit] in the USA, 3.23 [2.93-3.74] in Seychelles, and 1.99 [1.72-2.26] in Ghana. Different silhouette cut-offs predicted dichotomous adiposity categories differently in the three countries. For example, a silhouette ≥ 5 had sensitivity/specificity of 77.3%/90.6% to predict BMI ≥ 25 kg/m2 in the USA, but 77.8%/85.9% in Seychelles and 84.9%/71.4% in Ghana. Finally, silhouettes predicted BMI, WC, and WHR similarly, within each country and sex, based on Spearman correlations coefficients (continuous scale) and c-statistic (dichotomous classification).Conclusion: Our data suggest that Pulvers’ silhouette showcards can be a useful tool to objectively predict different adiposity measures in different populations when direct measurement cannot be performed. However, population-specific differences in the slopes of the associations, which possibly partly reflect differences in perceptions of one’s body size according to country adiposity prevalence, stress the need to calibrate silhouette showcards when using them as a survey tool.