bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR005: The dynamic tumor microenvironment: Oncostreams are self-organizing structures that modulate glioma progression and treatment
Authors: Comba Andrea , Motsch Sebastien , Dunn Patrick , Hollon Todd , Zamler Daniel , Argento Anna , Kahana Alon , Kish Phillip , Castro Maria , Lowenstein Pedro 
Published: March 2021

Abstract
Intratumoral heterogeneity is a hallmark of high grade gliomas. However, whether heterogeneity is static or dynamic remains unknown. Here we demonstrate that gliomas’ core and border regions display areas of self-organized collective motion, which we have termed oncostreams. Histologically oncostreams appear as multicellular fascicles of elongated and aligned glioma cells with mesenchymal-like morphology, and their density correlates positively with tumor malignant behavior. Using time lapse confocal imaging of organotypic brain slices of experimental glioma we discovered oncostream dynamics, namely, as two self-organizing patterns of collective motion: streams (bidirectional motion) and flocks (unidirectional motion). Oncostreams were also present in human glioblastoma multiforme, and could also be detected using objective artificial indigent approaches. They were present in 47% of TCGA-GBM grade IV tumor tissues, in 8.6 % of TCGA-LGG grade III, and were absent in TCGA-LGG grade II. Oncostreams are heterogeneous, contain GFAP+ cells, Iba1+ microglia/macrophages cells, and ACTA2+ mesenchymal cells aligned along Sox2+ tumor cells. We propose that oncostreams function as highways possibly stimulating the spread of slower-moving glioma cells and/or non-tumor cells throughout the tumor mass, reinforcing a potential role of oncostreams in determining spatial heterogeneity and remodeling of the tumor microenvironment. To analyze the molecular landscape of oncostreams we used laser capture microdissection coupled to RNA-Seq and bioinformatics analysis: we detected the existence of genetic networks specific to oncostreams. Oncostreams were aligned along highly expressed extracellular matrix proteins, among them Col1a1 was the most differentially expressed. Genetic inhibition of Col1a1 dissembled oncostreams, decreased glioma heterogeneity and improved animal survival. We propose that oncostreams dynamics will be a promising avenue to understand glioma behavior, and treat these malignant tumors.
Citation Format: Andrea Comba, Sebastien Motsch, Patrick Dunn, Todd Hollon, Daniel Zamler, Anna Argento, Alon Kahana, Phillip Kish, Maria Castro, Pedro Lowenstein. The dynamic tumor microenvironment: Oncostreams are self-organizing structures that modulate glioma progression and treatment [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PR005.
A Nonparametric Procedure to Assess the Accuracy of the Normality Assumption for Annual Rainfall Totals, Based on the Marginal Statistics of Daily Rainfall: An Application to the NOAA/NCDC Rainfall Database
Authors: Ruggiu Dario , Viola Francesco , Langousis Andreas 
Published: March 2021

AbstractWe develop a nonparametric procedure to assess the accuracy of the normality assumption for annual rainfall totals (ART), based on the marginal statistics of daily rainfall. The procedure is addressed to practitioners and hydrologists that operate in data-poor regions. To do so we use 1) goodness-of-fit metrics to conclude on the approximate convergence of the empirical distribution of annual rainfall totals to a normal shape and classify 3007 daily rainfall time series from the NOAA/NCDC Global Historical Climatology Network database, with at least 30 years of recordings, into Gaussian (G) and non-Gaussian (NG) groups; 2) logistic regression analysis to identify the statistics of daily rainfall that are most descriptive of the G/NG classification; and 3) a random-search algorithm to conclude on a set of constraints that allows classification of ART samples on the basis of the marginal statistics of daily rain rates. The analysis shows that the Anderson–Darling (AD) test statistic is the most conservative one in determining approximate Gaussianity of ART samples (followed by Cramer–Von Mises and Lilliefors’s version of Kolmogorov–Smirnov) and that daily rainfall time series with fraction of wet days fwd < 0.1 and daily skewness coefficient of positive rain rates skwd > 5.92 deviate significantly from the normal shape. In addition, we find that continental climate (type D) exhibits the highest fraction of Gaussian distributed ART samples (i.e., 74.45%; AD test at α = 5% significance level), followed by warm temperate (type C; 72.80%), equatorial (type A; 68.83%), polar (type E; 62.96%), and arid (type B; 60.29%) climates.
Removing tar and nicotine from mainstream cigarette smoke using sepiolite-modified filter tips
Authors: Sarıkaya Yüksel , Kahya Naime Didem , Pekdemir Abdullah Devrim , Önal Müşerref 
Published: March 2021

AbstractThe objective of this work was to use air-dried sepiolite granules as an additive in cigarette filter tips to increase the removal yield of tar and nicotine from mainstream smoke. Granules with a mass of 95 mg per cigarette filter and a mean particle size (D) of 0.05–0.41 mm were used to constrain the effects of the mean particle size and mass of sepiolite in the removal process. The granules were sandwiched in common cellulose acetate filter tips. Maximum removal yields of 90% were obtained when D ≤ 0.10 mm. Filters containing granules with a mean size of 0.10 mm and mass variations from 35 to 95 mg were tested, and increasing amounts of sepiolite added led to progressively greater yields of tar and nicotine from 20% to 90%. The sepiolite granules were examined using scanning electron microscopy with energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy and X-ray diffraction techniques both before and after smoke experimentation. It is suggested that tar and nicotine were condensed both on the fibre clusters of the sepiolite granules and in the voids between them during the flow of the mainstream smoke.
Removal of cement-augmented screws in distal femoral fractures and the effect of retained screws and cement on total knee arthroplasty: a biomechanical investigation
Authors: Wähnert Dirk , Grüneweller Niklas , Gueorguiev Boyko , Vordemvenne Thomas , Gehweiler Dominic 
Published: February 2021

Abstract
Background
Given the increasing number of osteoporotic fractures of the distal femur, screw augmentation with bone cement is an option to enhance implant anchorage. However, in implant removal or revision surgeries, the cement cannot be removed from the distal femur without an extended surgical procedure. Therefore, the aims of this study were to investigate (1) whether cement augmentation has any influence on screw removal and removal torque, and (2) whether the implantation of a femoral component of a knee arthroplasty and its initial interface stability are affected by the remaining screws/cement.

Material and methods
Eight pairs of fresh-frozen human female cadaveric distal femurs (mean age, 86 years) with a simulated AO/OTA 33 A3 fracture were randomized in paired fashion to two groups and fixed with a distal femoral locking plate using cannulated perforated locking screws. Screw augmentation with bone cement was performed in one of the groups, while the other group received no screw augmentation. Following biomechanical testing until failure (results published separately), the screws were removed and the removal torque was measured. A femoral component of a knee arthroplasty was then implanted, and pull-out tests were performed after cement curing. Interference from broken screws/cement was assessed, and the maximum pull-out force was measured.

Results
The mean screw removal torque was not significantly different between the augmented (4.9 Nm, SD 0.9) and nonaugmented (4.6 Nm, SD 1.3, p = 0.65) screw groups. However, there were significantly more broken screws in in the augmented screw group (17 versus 9; p < 0.001). There was no significant difference in the pull-out force of the femoral component between the augmented (2625 N, SD 603) and nonaugmented (2653 N, SD 542, p = 0.94) screw groups.

Conclusion
The screw removal torque during implant removal surgery does not significantly differ between augmented and nonaugmented screws. In the augmented screw group, significantly more screws failed. To overcome this, the use of solid screws in holes B, C, and G can be considered. Additionally, it is possible to implant a femoral component for knee arthroplasty that retains the initial anchorage and does not suffer from interference with broken screws and/or residual cement.

Level of Evidence
5
Physical activity, resilience, emotions, moods, and weight control of older adults during the COVID-19 global crisis
Authors: Zach Sima , Zeev Aviva , Ophir Miki , Eilat-Adar Sigal 
Published: March 2021

Abstract
Background
The main purpose of the research was to examine the differences between adults in the age group 70+ and two other age groups (45–59 and 60–69), concerning their healthy and active lifestyle. The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. However, some studies of crises suggest that older adults tend to perceive events as less stressful than do younger people. Therefore, we examined healthy behavior in populations at risk according to the age cutoff-points used by the Ministry of Health at the time of vaccination, and divided the participants into three age groups (45–59, 60–69, and 70+) following health organizations’ recommendations.

Methods
Participants were 1202 people, 381 males and 821 females, aged 45–90. A survey comprised of six parts was used: Demographic background, the International Physical Activity Questionnaire–short version, Positive and Negative Affect Schedule – PANAS, the Connor and Davidson Resilience Scale, a questionnaire for measuring depressive moods, and questions regarding weight change, based on the Israeli National Health and Nutrition (MABAT) survey. Data were collected in Israel during the first complete lockdown. The questionnaire was distributed via e-mail, WhatsApp, Twitter, and Facebook using a snowball sampling method.

Results
Resilience and negative feelings and depression symptoms were higher in age group 45–59 compared to 70+ year-old participants, and the depression symptoms score was also higher among participants aged 45–59 compared to ages 60–69. Physical activity was associated with higher resilience, fewer depression symptoms, and fewer negative emotions. Regarding gender and psychological variables, no differences were found. During the time of lockdown, weight change was not prevalent and sleeping hours increased.

Conclusion
In adults at 70+, the physical activity level, physical activity before and during the lockdown, emotions, sleeping hours, and weight change were similar to the other adult groups that were examined (45–59 and 60–69). However, in the older adults groups (70+ and 60–69), resilience and depression symptoms were lower than in the youngest age group.
A data visualisation method for assessing exposure misclassification in case-crossover studies: the example of tricyclic antidepressants and the risk of hip fracture in older people
Authors: Leach Michael J. , Roughead Elizabeth E. , Pratt Nicole L. 
Published: February 2021

Abstract
Background
The case-crossover design is suited to medication safety studies but is vulnerable to exposure misclassification. Using the example of tricyclic antidepressants and the risk of hip fracture, we present a data visualisation tool for observing exposure misclassification in case-crossover studies.

Methods
A case-crossover study was conducted using Australian Government Department of Veterans’ Affairs claims data. Beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012 were included. The case window was defined as 1–50 days pre fracture. Control window one and control window two were defined as 101–150 and 151–200 days pre fracture, respectively. Patients were stratified by whether exposure status changed when control window two was specified instead of control window one. To visualise potential misclassification, each subject’s tricyclic antidepressant dispensings were plotted over the 200 days pre fracture.

Results
The study population comprised 8828 patients with a median age of 88 years. Of these subjects, 348 contributed data to the analyses with either control window. The data visualisation suggested that 14% of subjects were potentially misclassified with control window one while 45% were misclassified with control window two. The odds ratio for the association between tricyclic antidepressants and hip fracture was 1.18 (95% confidence interval = 0.91–1.52) using control window one, whereas risk was significantly increased (odds ratio = 1.43, 95% confidence interval = 1.11–1.83) using control window two.

Conclusions
Exposure misclassification was less likely to be present with control window one than with an earlier control window, control window two. When specifying different control windows in a case-crossover study, data visualisation can help to assess the extent to which exposure misclassification may contribute to variable results.
Automated segmentation of the individual branches of the carotid arteries in contrast-enhanced MR angiography using DeepMedic
Authors: Ziegler Magnus , Alfraeus Jesper , Bustamante Mariana , Good Elin , Engvall Jan , de Muinck Ebo , Dyverfeldt Petter 
Published: February 2021

Abstract
Background
Non-invasive imaging is of interest for tracking the progression of atherosclerosis in the carotid bifurcation, and segmenting this region into its constituent branch arteries is necessary for analyses. The purpose of this study was to validate and demonstrate a method for segmenting the carotid bifurcation into the common, internal, and external carotid arteries (CCA, ICA, ECA) in contrast-enhanced MR angiography (CE-MRA) data.

Methods
A segmentation pipeline utilizing a convolutional neural network (DeepMedic) was tailored and trained for multi-class segmentation of the carotid arteries in CE-MRA data from the Swedish CardioPulmonsary bioImage Study (SCAPIS). Segmentation quality was quantitatively assessed using the Dice similarity coefficient (DSC), Matthews Correlation Coefficient (MCC), F2, F0.5, and True Positive Ratio (TPR). Segmentations were also assessed qualitatively, by three observers using visual inspection. Finally, geometric descriptions of the carotid bifurcations were generated for each subject to demonstrate the utility of the proposed segmentation method.

Results
Branch-level segmentations scored DSC = 0.80 ± 0.13, MCC = 0.80 ± 0.12, F2 = 0.82 ± 0.14, F0.5 = 0.78 ± 0.13, and TPR = 0.84 ± 0.16, on average in a testing cohort of 46 carotid bifurcations. Qualitatively, 61% of segmentations were judged to be usable for analyses without adjustments in a cohort of 336 carotid bifurcations without ground-truth. Carotid artery geometry showed wide variation within the whole cohort, with CCA diameter 8.6 ± 1.1 mm, ICA 7.5 ± 1.4 mm, ECA 5.7 ± 1.0 mm and bifurcation angle 41 ± 21°.

Conclusion
The proposed segmentation method automatically generates branch-level segmentations of the carotid arteries that are suitable for use in further analyses and help enable large-cohort investigations.
Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia
Authors: Lan Yang , Liu Fang , Chang Lixian , Liu Lipeng , Zhang Yingchi , Yi Meihui , Cai Yuli , Feng Jing , Han Zhibo , Han Zhongchao , Zhu Xiaofan 
Published: February 2021

Abstract
Background
Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA).

Methods
We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone.

Results
Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153).

Conclusions
Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).
Levothyroxine and the risk of adverse pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis
Authors: Bein Magnus , Yu Oriana Hoi Yun , Grandi Sonia Marzia , Frati Francesca Y. E. , Kandil Ihab , Filion Kristian B. 
Published: February 2021

AbstractBackgroundLevothyroxine replacement therapy may decrease the risk of adverse pregnancy outcomes among women with subclinical hypothyroidism (SCH). The aim of this study is to conduct a systematic review and meta-analysis to examine the risk of adverse pregnancy, perinatal, and early childhood outcomes among women with SCH treated with levothyroxine.MethodsA systematic literature search was conducted using Ovid-Medline, Ovid-EMBASE, Pubmed (non-Medline), Ebsco-CINAHL Plus with full text and Cochrane Library databases. Randomized controlled studies (RCTs) and observational studies examining the association between treatment of SCH during pregnancy and our outcomes of interest were included. Studies that compared levothyroxine treatment versus no treatment were eligible for inclusion. Data from included studies were extracted and quality assessment was performed by two independent reviewers.ResultsSeven RCTs and six observational studies met our inclusion criteria. A total of 7342 individuals were included in these studies. RCTs demonstrated several sources of bias, with lack of blinding of the participants or research personnel; only one study was fully blinded. In the observational studies, there was moderate to serious risk of bias due to lack of adjustment for certain confounding variables, participant selection, and selective reporting of results. Pooled analyses showed decreased risk of pregnancy loss (RR: 0.79; 95% CI: 0.67 to 0.93) and neonatal death (RR: 0.35; 95% CI: 0.17 to 0.72) associated with levothyroxine treatment during pregnancy among women with SCH. There were no associations between levothyroxine treatment and outcomes during labour and delivery, or cognitive status in children at 3 or 5 years of age.ConclusionTreatment of SCH with levothyroxine during pregnancy is associated with decreased risks of pregnancy loss and neonatal death. Given the paucity of available data and heterogeneity of included studies, additional studies are needed to address the benefits of levothyroxine use among pregnant women with SCH.
Access to after-hours primary care: a key determinant of children’s medical home status
Authors: Han Bing , Chen Peggy Guey-Chi , Yu Hao 
Published: February 2021

AbstractBackgroundThe medical home (MH) model has been promoted by both the federal and state governments in the United States in recent years. To ascertain American children’s MH status, many studies have relied on a large set of survey items, posing a considerable burden on their parents. We aimed to identify individual survey items or domains that best predict MH status for children and use them to develop brief markers of MH status. We also examined whether the identified items differed by status of special health care needs and by racial/ethnic group.MethodUsing the 9-year data from Medical Expenditure Panel Survey, we examined associations between children’s MH status and individual survey items or domains. We randomly split the data into two halves with the first half (training sample,n = 8611) used to identify promising items, and the second half (validation sample,n = 8779) used to calculate all statistical measures. After discovering significant predictors of children’s MH status, we incorporated them into several brief markers of MH status. We also conducted stratified analyses by status of special health care needs and by racial/ethnic group.ResultsLess than half (48.7%) of the 8779 study children had a MH. The accessibility domain has stronger association with children’s MH status (specificity = 0.84, sensitivity = 1, Kappa = 0.83) than other domains. The top two items with the strongest association with MH status asked about after-hours primary care access, including doctors’ office hours at night or on the weekend and children’s difficulty accessing care after hours. Both belong to the accessibility domain and are one of several reliable markers for children’s MH status. While each of the two items did not differ significantly by status of special health care needs, there were considerable disparities across racial/ethnic groups with Latino children lagging behind other children.ConclusionAccessibility, especially the ability to access health care after regular office hours, appears to be the major predictor of having a MH among children. The ongoing efforts to promote the MH model need to target improving accessibility of health care after regular hours for children overall and especially for Latino children.