bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Disadvantage, Healthcare Utilization, and Colorectal Cancer Screening: Leveraging Longitudinal Patient Address and Health Records Data
Authors: Hughes Amy E. , Tiro Jasmin A. , Balasubramanian Bijal A. , Skinner Celette Sugg , Pruitt Sandi L. 
Published: August 2018

AbstractBackground:Social disadvantage predicts colorectal cancer outcomes across the cancer care continuum for many populations and places. For medically underserved populations, social disadvantage is likely intersectional—affecting individuals at multiple levels and through membership in multiple disadvantaged groups. However, most measures of social disadvantage are cross-sectional and limited to race, ethnicity, and income. Linkages between electronic health records (EHR) and external datasets offer rich, multilevel measures that may be more informative.Methods:We identified urban safety-net patients eligible and due for colorectal cancer screening from the Parkland-UT Southwestern PROSPR cohort. We assessed one-time screening receipt (via colonoscopy or fecal immunochemical test) in the 18 months following cohort entry via the EHR. We linked EHR data to housing and Census data to generate measures of social disadvantage at the parcel- and block-group level. We evaluated the association of these measures with screening using multilevel logistic regression models controlling for sociodemographics, comorbidity, and healthcare utilization.Results:Among 32,965 patients, 45.1% received screening. In adjusted models, residential mobility, residence type, and neighborhood majority race were associated with colorectal cancer screening. Nearly all measures of patient-level social disadvantage and healthcare utilization were significant.Conclusions:Address-based linkage of EHRs to external datasets may have the potential to expand meaningful measurement of multilevel social disadvantage. Researchers should strive to use granular, specific data in investigations of social disadvantage.Impact:Generating multilevel measures of social disadvantage through address-based linkages efficiently uses existing EHR data for applied, population-level research.
Lack of DNA Damage Response at Low Radiation Doses in Adult Stem Cells Contributes to Organ Dysfunction
Authors: Nagle Peter W. , Hosper Nynke A. , Barazzuol Lara , Jellema Anne L. , Baanstra Mirjam , van Goethem Marc-Jan , Brandenburg Sytze , Giesen Ulrich , Langendijk Johannes A. , van Luijk Peter , Coppes Rob P. 
Published: August 2018

Abstract

Purpose:
Radiotherapy for head and neck cancer may result in serious side effects, such as hyposalivation, impairing the patient's quality of life. Modern radiotherapy techniques attempt to reduce the dose to salivary glands, which, however, results in low-dose irradiation of the tissue stem cells. Here we assess the low-dose sensitivity of tissue stem cells and the consequences for tissue function.

Experimental Design:
Postirradiation rat salivary gland secretory function was determined after pilocarpine induction. Murine and patient-derived salivary gland and thyroid gland organoids were irradiated and clonogenic survival was assessed. The DNA damage response (DDR) was analyzed in organoids and modulated using different radiation modalities, chemical inhibition, and genetic modification.

Results:
Relative low-dose irradiation to the high-density stem cell region of rat salivary gland disproportionally impaired function. Hyper-radiosensitivity at doses &lt;1 Gy, followed by relative radioresistance at doses ≥1 Gy, was observed in salivary gland and thyroid gland organoid cultures. DDR modulation resulted in diminished, or even abrogated, relative radioresistance. Furthermore, inhibition of the DDR protein ATM impaired DNA repair after 1 Gy, but not 0.25 Gy. Irradiation of patient-derived salivary gland organoid cells showed similar responses, whereas a single 1 Gy dose to salivary gland–derived stem cells resulted in greater survival than clinically relevant fractionated doses of 4 × 0.25 Gy.

Conclusions:
We show that murine and human glandular tissue stem cells exhibit a dose threshold in DDR activation, resulting in low-dose hyper-radiosensitivity, with clinical implications in radiotherapy treatment planning. Furthermore, our results from patient-derived organoids highlight the potential of organoids to study normal tissue responses to radiation.
Loss of NF2 Induces TGFβ Receptor 1–mediated Noncanonical and Oncogenic TGFβ Signaling: Implication of the Therapeutic Effect of TGFβ Receptor 1 Inhibitor on NF2 Syndrome
Authors: Cho Jung-Hyun , Oh Ah-Young , Park Soyoung , Kang So-mi , Yoon Min-Ho , Woo Tae-Gyun , Hong Shin-Deok , Hwang Jihwan , Ha Nam-Chul , Lee Ho-Young , Park Bum-Joon 
Published: August 2018

Abstract
Neurofibromatosis type 2 (NF2) syndrome is a very rare human genetic disease, and there has been no proper treatment for it until now. In our recent study, it has been reported that the loss of NF2 activates MAPK signaling through reduction of RKIP in a mesothelioma model. Here, we show that loss of NF2 induces reduction of the TGFβ receptor 2 (TβR2) expression, and an overwhelming expression of TGFβ receptor 1 (TβR1) is activated by physical stimuli such as pressure or heavy materials. Activated TβR1 induces the phosphorylation and degradation of RKIP. RKIP reduction consequently results in MAPK activation as well as Snail-mediated p53 suppression and occurrence of EMT in NF2-deficient cells by physical stimuli. Thus, TβR1 kinase inhibitors restore cell differentiation and induce growth suppression in NF2-deficient Schwannoma cell line and MEF. Moreover, TEW7197, a specific TβR1 kinase inhibitor, reduces tumor formation in the NF2-model mouse (Postn-Cre;NF2f/f). Gene expression profiling reveals that TEW7197 treatment induces the expression of lipid metabolism–related gene set, such as NF2-restored cells in HEI-193 (NF2-deficient Schwannoma). Our results indicate that reduction or deletion of TβR2 or NF2 induces the TβR1-mediated oncogenic pathway, and therefore inhibition of the unbalanced TGFβ signaling is a putative strategy for NF2-related cancers (NF2 syndrome and mesothelioma) and TβR2-mutated advanced cancers. Mol Cancer Ther; 17(11); 2271–84. ©2018 AACR.
Targeting MEK in a Translational Model of Histiocytic Sarcoma
Authors: Takada Marilia , Hix Jeremy M.L. , Corner Sarah , Schall Peter Z. , Kiupel Matti , Yuzbasiyan-Gurkan Vilma 
Published: August 2018

Abstract
Histiocytic sarcoma in humans is an aggressive orphan disease with a poor prognosis as treatment options are limited. Dogs are the only species that spontaneously develops histiocytic sarcoma with an appreciable frequency, and may have value as a translational model system. In the current study, high-throughput drug screening utilizing histiocytic sarcoma cells isolated from canine neoplasms identified these cells as particularly sensitive to a MEK inhibitor, trametinib. One of the canine cell lines carries a mutation in PTPN11 (E76K), and another one in KRAS (Q61H), which are associated with the activation of oncogenic MAPK signaling. Both mutations were previously reported in human histiocytic sarcoma. Trametinib inhibited sensitive cell lines by promoting cell apoptosis, indicated by a significant increase in caspase 3/7. Furthermore, in vitro findings were successfully recapitulated in an intrasplenic orthotopic xenograft mouse model, which represents a disseminated aggressive form of histiocytic sarcoma. Mice with histiocytic sarcoma xenograft neoplasms that were treated with trametinib had significantly longer survival times. Target engagement was validated as activity of ERK, downstream of MEK, was significantly downregulated in neoplasms of treated mice. Additionally, trametinib was found in plasma and neoplastic tissues within projected therapeutic levels. These findings demonstrate that in dogs, histiocytic sarcoma may be associated with a dysfunctional MAPK pathway, at least in some cases, and may be effectively targeted through MEK inhibition. Clinical trials to test safety and efficacy of trametinib in dogs with histiocytic sarcoma are warranted, and may provide valuable translational information to similar diseases in humans. Mol Cancer Ther; 17(11); 2439–50. ©2018 AACR.
Heterogeneity of Epigenetic and Epithelial Mesenchymal Transition Marks in Hepatocellular Carcinoma with Keratin 19 Proficiency
Authors: Yokomichi Naosuke , Nishida Naoshi , Umeda Yuzo , Taniguchi Fumitaka , Yasui Kazuya , Toshima Toshiaki , Mori Yoshiko , Nyuya Akihiro , Tanaka Takehiro , Yamada Takeshi , Yagi Takahito , Fujiwara Toshiyoshi , Yamaguchi Yoshiyuki , Goel Ajay , Kudo Masatoshi , Nagasaka Takeshi 
Published: August 2018

<b><i>Objective:</i></b> Keratin 19 (K19) expression is a potential predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). To clarify the feature of K19-proficient HCC, we traced epigenetic footprints in cultured cells and clinical materials. <b><i>Patients and Methods:</i></b> In vitro, <i>KRT19</i> promoter methylation was analyzed and 5-aza-2’-deoxycytidine with trichostatin A (TSA) treatment was performed. Among 564 surgically resected HCCs, the clinicopathological relevance of K19-proficent HCCs was performed in comparison with hepatocytic (HepPar-1 and arginase-1), epithelial-mesenchymal transition (E-cadherin and vimentin), biliary differentiation-associated (K7 and NOTCH-1) markers, and epigenetic markers (<i>KRT19</i> promoter/long interspersed nucleotide element-1 [<i>LINE-1</i>] methylation status). <b><i>Results:</i></b> <i>KRT19</i> promoter methylation was clearly associated with K19 deficiency and 5-aza-2’-deoxycytidine with TSA treatment-stimulated K19 re-expression, implicating DNA methylation as a potential epigenetic process for K19 expression. After excluding HCCs with recurrence, TNM stage as IIIB or greater, preoperative therapy, transplantation, and combined hepatocellular cholangiocarcinoma, we assessed 125 of 564 HCC cases. In this cohort, K19 expression was found in 29 HCCs (23.2%) and corresponded with poor survival following surgery (<i>p</i> = 0.025) and extrahepatic recurrence-free survival (<i>p</i> = 0.017). Compared with K19-deficient HCCs, lower <i>KRT19</i> promoter methylation level was observed in K19-proficient HCCs (<i>p</i> &#x3c; 0.0001). Conversely, HCC with genome-wide <i>LINE-1</i> hypermethylation was frequently observed in K19-proficient HCCs (<i>p</i> = 0.0079). Additionally, K19 proficiency was associated with K7 proficiency (<i>p</i> = 0.043), and reduced E-cadherin and HepPar-1 expression (<i>p</i> = 0.043 and <i>p</i> &#x3c; 0.0001, respectively). <b><i>Conclusions:</i></b> K19-proficient HCC exhibited poor prognosis owing to extrahepatic recurrence, with molecular signatures differing from those in conventional cancer stem cells, providing novel insights of the heterogeneity underlying tumor development.
Evaluation of Chitotriosidase and CC-Chemokine Ligand 18 as Biomarkers of Microglia Activation in Amyotrophic Lateral Sclerosis
Authors: Martinez-Merino Leyre , Iridoy Marina , Galbete Arkaitz , Roldán Miren , Rivero Adriana , Acha Blanca , Irún Pilar , Canosa Cecilia , Pocoví Miguel , Mendioroz Maite , Jericó Ivonne 
Published: August 2018

<b><i>Background:</i></b> The development of biomarkers for use in diagnosing, monitoring disease progression and analyzing therapeutic trials response in amyotrophic lateral sclerosis (ALS) is essential. <b><i>Objective:</i></b> The aim of this study was to identify inflammatory factors in plasma or cerebrospinal fluid (CSF) from patients with ALS with particular attention to specific markers of microglia activation as chitotriosidase (ChT) and chemokine (C-C motif) ligand 18 (CCL18) to determine its potential as ALS biomarkers. <b><i>Methods:</i></b> We studied CSF and plasma samples from 32 patients and 42 healthy controls. We assayed the ChT activity by a spectrofluorometric method and protein levels of other inflammatory ­biomarkers (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6 and CCL18) by enzyme-linked immunosorbent assay. CHIT1 gene polymorphism in exon 10 (c.1049_1072dup24) encoding inactive ChT enzyme was genotyped in all subjects. <b><i>Results:</i></b> ChT activity and TNF-alpha protein levels were significantly higher in CSF of ALS patients, but we found no correlation with the severity and progression of the disease. Nevertheless, we did not found any differences in CCL18 or IL-6 protein levels between both groups in CSF or plasma. In our sample, only 3% of subjects were homozygous carriers for the CHIT1 exon 10 duplication associated with defective enzyme. <b><i>Conclusions:</i></b> High ChT activity in CSF of patients with ALS may reflect microglia activation and could be a potential biomarker of the disease. We did not find any significant difference regarding CCL-18, another specific marker of microglia activation that is related with M2-like microglia phenotype. Deepening the understanding of the activation state of microglia (M1 and M2) may contribute to the knowledge about the specific role of neuroinflammation in ALS and future therapeutic strategies.
A simple and inexpensive method for sharpening permanent steel knives with sandpaper
Authors: Barbosa Antonio C. F. , Costa Gisele R. O. , Angyalossy Veronica , Dos Santos Tássia C. , Pace Marcelo R. 
Published: August 2018

ABSTRACT
Good anatomical sections can only be obtained with a perfectly sharp knife. Permanent steel microtome knives are present in numerous plant anatomy labs and they yield excellent results, with the only caveat that they need to be re-sharpened after use. Automatic knife sharpeners have been especially designed for this purpose, but they require abrasives in their use, which may be expensive and hard to obtain. Here we describe and illustrate in detail an inexpensive, fast, widely accessible technique to sharpen permanent microtome knives using different sandpaper grits. Knives sharpened with this technique have already been in use for over a decade and are suitable for all types of botanical specimens both embedded and unembedded.
The Accuracy and Representativeness of the 10,000-Foot Pibal Report
Authors: Brooks Edward M. 
Published: August 2018

In the normal use of pilot-balloon reports as an aid to drawing upper-air charts, these reports are usually assumed to represent the mean air flow undisturbed by turbulence. This assumption needs to be justified if the pibals are used in the preparation of wind convergence charts.
The failure of the pibal to represent the mean undisturbed wind is due to (1) inaccuracy and (2) unrepresentativeness of the pibal observation. Most of the inaccuracy arises from incorrectly prescribed heights of the balloon based on a constant rate of ascent. In the cases studied, the average error (Table I) was 4.1° in direction and 3.3 miles/hour in speed. The unrepresentativeness due to turbulence averaged 1.3° and 2.5 miles/hour. The total inaccuracy and unrepresentativeness together averaged 5.6° and 4.1 miles/hour.
Decoding Hosing and Heating Effects on Global Temperature and Meridional Circulations in a Warming Climate
Authors: Wen Qin , Yao Jie , Döös Kristofer , Yang Haijun 
Published: August 2018

AbstractThe global temperature changes under global warming result from two effects: one is the pure radiative heating effect caused by a change in greenhouse gases, and the other is the freshwater effect related to changes in precipitation, evaporation, and sea ice. The two effects are separated in a coupled climate model through sensitivity experiments in this study. It is indicated that freshwater change has a significant cooling effect that can mitigate the global surface warming by as much as ~30%. Two significant regional cooling centers occur: one in the subpolar Atlantic and one in the Southern Ocean. The subpolar Atlantic cooling, also known as the “warming hole,” is triggered by sea ice melting and the southward cold-water advection from the Arctic Ocean, and is sustained by the weakened Atlantic meridional overturning circulation. The Southern Ocean surface cooling is triggered by sea ice melting along the Antarctic and is maintained by the enhanced northward Ekman flow. In these two regions, the effect of freshwater flux change dominates over that of radiation flux change, controlling the sea surface temperature change in the warming climate. The freshwater flux change also results in the Bjerknes compensation, with the atmosphere heat transport change compensating the ocean heat transport change by about 80% during the transient stage of global warming. In terms of global temperature and Earth’s energy balance, the freshwater change plays a stabilizing role in a warming climate.
Impacts of Assimilating Smartphone Pressure Observations on Forecast Skill during Two Case Studies in the Pacific Northwest
Authors: McNicholas Callie , Mass Clifford F. 
Published: August 2018

AbstractOver a half-billion smartphones are now capable of measuring atmospheric pressure, potentially providing a global surface observing network of unprecedented density and coverage. An earlier study by the authors described an Android app, uWx, that served as a test bed for advanced quality control and bias correction strategies. To evaluate the utility and quality of the resulting smartphone pressure observations, ensemble data assimilation experiments were performed for two case studies over the Pacific Northwest. In both case studies, smartphone pressures improved the analyses and forecasts of assimilated and nonassimilated variables. In case I, which considered the passage of a front across the region, cycled smartphone pressure assimilation consistently improved 1-h forecasts of the altimeter setting, 2-m temperature, and 2-m dewpoint. During a postfrontal period, cycled smartphone pressure assimilation improved mesoscale forecasts of hourly precipitation accumulation. In case II, which considered a major coastal windstorm, cycling experiments assimilating smartphone pressures improved 10-m wind forecasts as well as the predicted track and intensity. For both cases, free-forecast experiments initialized with smartphone data produced forecast improvements extending several hours, suggesting the utility of crowdsourced smartphone pressures for short-term numerical weather prediction.
Poverty matters: Cannabis use among people with serious mental illness: Findings from the United States survey on drug use and health, 2015
Authors: Carrà Giuseppe , Bartoli Francesco , Riboldi Ilaria , Trotta Giulia , Crocamo Cristina 
Published: August 2018

Background: Little is known about the influence of contextual characteristics on comorbid substance use and serious mental illness (SMI). Aims: To explore the role of poverty on comorbid SMI and cannabis use. Methods: We used data from the 2015 National Survey on Drug Use and Health, considering those in poverty, with income under 100% of the US poverty threshold. Results: People in poverty were more likely to suffer from concurrent SMI and cannabis use (3.07%, 95% confidence interval (CI):1.84%; 5.07%), even controlling for gender, age, tobacco and alcohol use (odds ratio (OR) = 2.77, 95% CI: 1.27; 6.03, p = .010). Conclusion: The magnitude of the association between SMI and cannabis use is influenced by poverty status. More research on potential mediators like income inequality and impoverished social capital is needed.
Virtual design of knitted compression garments based on bodyscanning technology and the three-dimensional-to-two-dimensional approach
Authors: Kuzmichev Victor E , Tislenko Ilya V , Adolphe Dominique C 
Published: August 2018

The interdisciplinary approach for the design of compression garments was developed by means of establishing new databases about the elongation of knitted materials, the morphology of female bodies, and the relations between both with the pressure under the garment. We used KES-FB1 and a cylinder made of cosmetology silicone to investigate the relationship between the knitted material strain and the pressure produced. To find the factors that are responsible for comfort perception of compression garments, a sensory analysis with female participants was used to establish the pressure range that is permissible for the human body and the effect of its reshaping. The experimental data obtained was used for validating the theoretical approaches about, firstly, the transformation of a solid polygonal avatar of the scanned body to the soft one, secondly, the virtual three-dimensional (3D) creation of a compression garment in a “relaxed non-elongation state” and, thirdly, obtaining virtual two-dimensional (2D) pattern blocks. Science explorations dedicated to 3D-to-2D flattening of pattern blocks of the avatar surface and to the creation of tight-fitted garments were considered as the background of our research. Several compression garments for females with different morphological features, which were designing by means of a new 3D-to-2D method for flattening of pattern blocks and the traditional 2D “Müller and Sohn” manual, were obtained. The mean value of absolute difference between the predicted and measured pressure was improved from 33% to 14%. Thus, the developed approach based on contemporary virtual reality collection of input data allows one to predict the pressure of compression garments with higher accuracy.
Maximum lesions area and orthogonal values accessed from DWI images would be alternative imaging markers for predicting the outcome of acute ischemia in the middle cerebral artery territory
Authors: Yuan Tao , Ren Guoli , Quan Guanmin , Liu Yawu 
Published: August 2018

Background Evaluating the acute ischemic volume on diffusion-weighted imaging (DWI) in the middle cerebral artery (MCA) territory would predict outcome. Purpose To investigate the correlations between maximum area with restricted diffusion (MaxA), the orthogonal diameters (OD) as well as lesion volume on DWI, and to explore the role of MaxA and OD on predicting unfavorable outcome after an acute MCA ischemic stroke. Material and Methods Sixty consecutive adult patients, including modified Rankin Scale score (mRS) ≤2 (n = 31) and mRS > 2 (n = 29) groups, were retrospectively enrolled. The MaxA and OD of lesions were assessed at the slice containing the largest infarction size on DWI images. We compared the prediction efficiencies of these methods on unfavorable outcomes. Results The correlation coefficients between the MaxA and infarction volume and OD and infarction volume were 0.982 ( P < 0.001) and 0.952 ( P < 0.001), respectively. The times required for measuring MaxA (150 s [130–160]) and OD (30 s [20–60]) were much shorter than that for infarction volume measurement (1240 s [180–1480]) ( P = 0.001, P = 0.004). With thresholds of ≥57.3 mL for infarction volume, ≥15.2 cm2 for MaxA, and ≥38.1 for the arithmetic product of OD, the AUCs of infarction volume, MaxA, and OD for predicting an unfavorable outcome were 0.818, 0.821, and 0.820, respectively. Conclusion Since they correlated well with the infarction volume, MaxA and OD assessed on DWI were time-saving and achieved comparable diagnostic efficiencies; thus, they may represent alternative imaging markers for predicting unfavorable outcomes of acute ischemic stroke in MCA territory.