bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applied mechanical loading to mouse hindlimb acutely increases skeletal perfusion and chronically enhanced vascular porosity
Authors: Gohin Stephanie , Javaheri Behzad , Hopkinson Mark , Pitsillides Andrew Anthony , Arnett Timothy R. , Chenu Chantal 
Published: March 2020

Blood supply is essential for osteogenesis, yet its relationship to load-related increases in bone mass is poorly defined. Herein, we aim to investigate the link between load-induced osteogenesis and the blood supply (bone perfusion and vascular porosity) using an established osteogenic noninvasive model of axial loading. Accordingly, 12 N mechanical loads were applied to the right tibiae of six male C57BL6 mice at 10–12 wk of age, 3 times/wk for 2 wk. Skeletal perfusion was measured acutely (postloading) and chronically in loaded and contralateral, nonloaded hindlimbs by laser-Doppler imaging. Vascular and lacunar porosity of the cortical bone and tibia load-related changes in trabecular and cortical bone was measured by nanoCT and micro-CT, respectively. We found that the mean skeletal perfusion (loaded: nonloaded limb ratio) increased by 56% immediately following the first loading episode (vs. baseline, P < 0.01), and a similar increase was observed after all loading episodes, demonstrating that these acute responses were conserved for 2 wk of loading. Loading failed, however, to engender any significant chronic changes in mean perfusion between the beginning and the end of the experiment. In contrast, 2 wk of loading engendered an increased vascular canal number in the tibial cortical compartment (midshaft) and, as expected, also increased trabecular and cortical bone volumes and modified tibial architecture in the loaded limb. Our results indicate that each episode of loading both generates acute enhancement in skeletal blood perfusion and also stimulates chronic vascular architectural changes in the bone cortices, which coincide with load-induced increases in bone mass.NEW & NOTEWORTHY This study investigated modifications to the blood supply (bone perfusion and intracortical vascular canals) in mechanoadaptive responses in C57BL6 mice. Each episode of mechanical loading acutely increases skeletal perfusion. Two weeks of mechanical loading increased bone mass and cortical vascular canal number, while there was no chronic increase in hindlimb perfusion. Our findings suggest that the blood supply may participate in the processes that govern load-induced bone formation.
Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer
Authors: Arima Kota , Lau Mai Chan , Zhao Melissa , Haruki Koichiro , Kosumi Keisuke , Mima Kosuke , Gu Mancang , Väyrynen Juha P. , Twombly Tyler S. , Baba Yoshifumi , Fujiyoshi Kenji , Kishikawa Junko , Guo Chunguang , Baba Hideo , Richards William G. , Chan Andrew T. , Nishihara Reiko , Meyerhardt Jeffrey A. , Nowak Jonathan A. , Giannakis Marios , Fuchs Charles S. , Ogino Shuji 
Published: March 2020

Abstract

Accumulating evidence suggests that metabolic reprogramming has a critical role in carcinogenesis and tumor progression. The usefulness of formalin-fixed paraffin-embedded (FFPE) tissue material for metabolomics analysis as compared with fresh frozen tissue material remains unclear. LC/MS-MS–based metabolomics analysis was performed on 11 pairs of matched tumor and normal tissues in both FFPE and fresh frozen tissue materials from patients with colorectal carcinoma. Permutation t test was applied to identify metabolites with differential abundance between tumor and normal tissues. A total of 200 metabolites were detected in the FFPE samples and 536 in the fresh frozen samples. The preservation of metabolites in FFPE samples was diverse according to classes and chemical characteristics, ranging from 78% (energy) to 0% (peptides). Compared with the normal tissues, 34 (17%) and 174 (32%) metabolites were either accumulated or depleted in the tumor tissues derived from FFPE and fresh frozen samples, respectively. Among them, 15 metabolites were common in both FFPE and fresh frozen samples. Notably, branched chain amino acids were highly accumulated in tumor tissues. Using KEGG pathway analyses, glyoxylate and dicarboxylate metabolism, arginine and proline, glycerophospholipid, and glycine, serine, and threonine metabolism pathways distinguishing tumor from normal tissues were found in both FFPE and fresh frozen samples. This study demonstrates that informative data of metabolic profiles can be retrieved from FFPE tissue materials.

Implications:
Our findings suggest potential value of metabolic profiling using FFPE tumor tissues and may help to shape future translational studies through developing treatment strategies targeting metabolites.
Radical (and Populist) Parties in European Governments
Authors: Fagerholm Andreas 
Published: March 2020

Abstract
Existing studies on the coalitionability of radical and—oftentimes—populist (right or/and left) parties have concluded that government inclusion of these parties follows a complex and multi-causal pattern, and that the explanatory power of the conventional “size and ideology”-framework is limited. Starting from this observation, the present study sets out to further strengthen our understanding of radical government participation. First, the paper seeks to substantiate the relationships observed in a previous configurational cross-case analysis focusing on factors related to size and ideology: How is size and ideology related to radical government participation? The second aim of the paper is to further improve our understanding of why and when radical parties participate in coalition governments: If well-known factors related to electoral and parliamentary strength and ideological aptitude are—as recent cross-case evidence indicate—able to explain radical government participation only partly, which are the additional components that should be included in an enhanced explanatory framework?
Drought Monitoring in the Middle East and North Africa (MENA) Region: Participatory Engagement to Inform Early Warning Systems
Authors: Fragaszy Stephen Russell , Jedd Theresa , Wall Nicole , Knutson Cody , Fraj Makram Belhaj , Bergaoui Karim , Svoboda Mark , Hayes Michael , McDonnell Rachael 
Published: March 2020

AbstractWhen drought hits water-scarce regions, there are significant repercussions for food and water security, as well as serious issues for the stability of broader social and environmental systems. To mitigate these effects, environmental monitoring and early warning systems aimed at detecting the onset of drought conditions can facilitate timely and effective responses from government and private sector stakeholders. This study uses multistage, participatory research methods across more than 135 interviews, focus groups, and workshops to assess extant climatic, agricultural, hydrological, and drought monitoring systems; key cross-sector drought impacts; and drought monitoring needs in four countries in the Middle East and North Africa (MENA) region: Morocco, Tunisia, Lebanon, and Jordan. This extensive study of user needs for drought monitoring across the MENA region is informing and shaping the ongoing development of drought early warning systems, a composite drought indicator (CDI), and wider drought management systems in each country. Overarching themes of drought monitoring needs include technical definitions of drought for policy purposes; information-sharing regimes and data-sharing platforms; ground-truthing of remotely sensed and modeled data; improved data quality in observation networks; and two-way engagement with farmers, organizations, and end-users of drought monitoring products. This research establishes a basis for informing enhanced drought monitoring and management in the countries, and the broad stakeholder engagement can help foster the emergence of effective environmental monitoring coalitions.
Variations in Precipitating Convective Feature Populations with ITCZ Width in the Pacific Ocean
Authors: Wodzicki Kyle R. , Rapp Anita D. 
Published: March 2020

AbstractMany recent studies have aimed to better understand changes in the characteristics of the intertropical convergence zone (ITCZ), including ITCZ location, width, and precipitation intensity. However, very few studies have looked at the relationship between characteristics of convection within the ITCZ and ITCZ width. The present work uses information from an ITCZ identification database and Tropical Rainfall Measuring Mission (TRMM) precipitation feature (PF) database to quantify variations in convective characteristics across the ITCZ in the Pacific Ocean. Data are partitioned into wide and narrow ITCZ regimes to quantify differences in convection between different ITCZ regimes. Under the wide regime, convection deeper than 5 km, with areas greater than 100 km2, or stratiform rain fractions greater than 0.5 is, on average, 24%, 23%, and 12% more frequent, respectively. In the narrow regime, the signal is reversed, with average increases in the frequency of convection with heights below 5 km, areas less than 100 km2, or stratiform rain fractions less than 0.5 of 15%, 4%, and 6%, respectively. Positive and negative anomalies in columnar water vapor (CWV) and sea surface temperature (SST) across the ITCZ are observed in the wide and narrow regimes, respectively. There is also a strong positive correlation between an El Niño–Southern Oscillation (ENSO) index and ITCZ width anomalies, with wide (narrow) ITCZs occurring during warm (cold) phases of ENSO. This implies that the strengthening and weakening of the Walker circulation associated with ENSO may play a role in modulating the convective populations that contribute to the Pacific ITCZ width variations.
Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron
Authors: Ma C-L , Li L , Yang G-M , Zhang Z-B , Zhao Y-N , Zeng X-F , Zhang D-X , Yu Y , Shi Z-J , Yan Q-W , Li L-H , Hong S-J 
Published: March 2020

Objective: Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism. Methods: The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot. Results: The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity ( p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins ( p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased ( p < 0.05). Conclusion: Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF.
BESI: Behavioral and Environmental Sensing and Intervention for Dementia Caregiver Empowerment—Phases 1 and 2
Authors: Bankole Azziza , Anderson Martha S. , Homdee Nutta , Alam Ridwan , Lofton Ashley , Fyffe Nykesha , Goins Hilda , Newbold Temple , Smith-Jackson Tonya , Lach John 
Published: March 2020

Background and Objectives: Caregiver burden associated with dementia-related agitation is one of the commonest reasons a community-dwelling person with dementia (PWD) transitions to a care facility. Behavioral and Environmental Sensing and Intervention for Dementia Caregiver Empowerment (BESI) is a system of body-worn and in-home sensors developed to provide continuous, noninvasive agitation assessment and environmental context monitoring to detect early signs of agitation and its environmental triggers. Research Design and Methods: This mixed methods, remote ethnographic study is explored in a 3-phase, multiyear plan. In Phase 1, we developed and refined the BESI system and completed usability studies. Validation of the system and the development of dyad-specific models of the relationship between agitation and the environment occurred in Phase 2. Results: Phases 1 and 2 results facilitated targeted changes in BESI, thus improving its overall usability for the final phase of the study, when real-time notifications and interventions will be implemented. Conclusion: Our results show a valid relationship between the presence of dementia related agitation and environmental factors and that persons with dementia and their caregivers prefer a home-based monitoring system like BESI.
Cytomegalovirus Retinitis in a Patient Taking Tocilizumab: A Case Report
Authors: Ong Erin S. , Thompson John T. 
Published: March 2020

Purpose: This report discusses a case of cytomegalovirus (CMV) retinitis in a patient taking tocilizumab for maintenance and remission of giant cell arteritis (GCA). Methods: A case report is presented. Results: A 78-year-old African American woman with no significant past medical history and an ocular history of primary open-angle glaucoma presented to the retina clinic with vitritis in the right eye. Four months earlier, she had been diagnosed with biopsy-proven GCA and prescribed 30 mg of prednisone daily and 162 mg tocilizumab subcutaneously weekly. Diagnostic vitrectomy with polymerase chain reaction of the vitreous was positive for CMV. Her retinitis gradually resolved after 3 months of treatment with valganciclovir, with no recurrence 4 months after discontinuing the valganciclovir. Conclusions: Physicians should be aware of the potential to develop CMV retinitis in the setting of tocilizumab use for GCA treatment.
Reliability and reproducibility of the new AO/OTA 2018 classification system for proximal humeral fractures: a comparison of three different classification systems
Authors: Marongiu Giuseppe , Leinardi Lorenzo , Congia Stefano , Frigau Luca , Mola Francesco , Capone Antonio 
Published: March 2020

Abstract
Background
The classification systems for proximal humeral fractures routinely used in clinical practice include the Neer and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) 2007 systems. Currently used systems have low inter- and intraobserver reliability. In 2018, AO/OTA introduced a new classification system with the aim of simplifying the coding process, in which the Neer four-part classification was integrated into the fracture description. The aim of the present work is to assess the inter- and intraobserver agreement of the new AO/OTA 2018 compared with the Neer and AO/OTA 2007 classifications.

Materials and methods
A total of 116 radiographs of consecutive patients with proximal humeral fracture were selected and classified by three observers with different levels of experience. All three observers independently reviewed and classified the images according to the Neer, AO/OTA 2007, and new AO/OTA 2018 systems. To determine the intraobserver agreement, the observers reviewed the same set of radiographs after an interval of 8 weeks. The inter- and intraobserver agreement were determined through Cohen’s kappa coefficient analysis.

Results
The new AO/OTA 2018 classification showed substantial mean inter- (k = 0.67) and intraobserver (k = 0.75) agreement. These results are similar to the reliability observed for the Neer classification (interobserver, k = 0.67; intraobserver, k = 0.85) but better than those found for the AO/OTA 2007 system, which showed only moderate inter- (k = 0.57) and intraobserver (k = 0.58) agreement. The two more experienced observers showed better overall agreement, but no statistically significant difference was found. No differences were found between surgical experience and agreement regarding specific fracture types or groups.

Conclusions
The results showed that the Neer system still represents the more reliable and reproducible classification. However, the new AO/OTA 2018 classification improved the agreement among observers compared with the AO/OTA 2007 system, while still maintaining substantial descriptive power and simplifying the coding process. The universal modifiers and qualifications, despite their possible complexity, allowed a more comprehensive fracture definition without negatively affecting the reliability or reproducibility of the classification system.
Level of evidence: Level III, diagnostic studies
PD-L1 monoclonal antibody-decorated nanoliposomes loaded with Paclitaxel and P-gp transport inhibitor for the synergistic chemotherapy against multidrug resistant gastric cancers
Authors: Yu Jinling , Hu Fengli , Zhu Qiankun , Li Xiaodong , Ren Haiyang , Fan Shengjie , Qian Bo , Zhai Bo , Yang Dongdong 
Published: March 2020

AbstractMultidrug resistance (MDR) based on ATP-dependent efflux transporters (p-glycoprotein (p-gp)) remains a major obstacle in successful chemotherapy treatment. Herein, we have investigated the potential of PD-L1 mAb-conjugated nanoliposome to serve as a targeted delivery platform for the co-delivery of paclitaxel (PTX) and p-gp specific transport inhibitor (TQD, tariquidar) in drug-resistant gastric cancers. Two drugs, PTX and TQD, were co-loaded in a single vehicle in a precise ratio to enhance the prospect of combination chemotherapeutic effect. Cellular uptake study indicated that PD-PTLP had higher internalization efficiency in PD-L1 receptor overexpressing SGC7901/ADR cells than non-targeted PTLP. Highest synergy was observed at a weight fraction of 1/0.5 (PTX/TQD) and the combination of PTX and TQD resulted in obvious synergistic effect compared to that of individual drugs alone. Our in vitro results showed that TQD was effective in reversing the multidrug resistance in SGC7901/ADR cells. The IC50 value of PD-PTLP was 0.76 μg/ml compared to 6.58 μg/ml and 7.64 μg/ml for PTX and TQD, respectively. PD-TPLP triggered significantly higher levels of reactive oxygen species (ROS) and cell apoptosis compared to that of free PTX or TQD. Furthermore, the in vivo antitumor study showed that the combination chemotherapy of PD-PTLP displayed a significant inhibition of tumor burden of drug-resistant xenograft tumors with significantly higher terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Furthermore, free PTX resulted in significant increase in the levels of AST and ALT while PD-PTLP insignificantly different compared to that of control indicating the safety index. Overall, we believe that combination of anticancer drug with a p-gp inhibitor could provide a potential direction toward the treatment of drug-resistant gastric tumors.
A machine learning approach on multiscale texture analysis for breast microcalcification diagnosis
Authors: Fanizzi Annarita , Basile Teresa M. A. , Losurdo Liliana , Bellotti Roberto , Bottigli Ubaldo , Dentamaro Rosalba , Didonna Vittorio , Fausto Alfonso , Massafra Raffaella , Moschetta Marco , Popescu Ondina , Tamborra Pasquale , Tangaro Sabina , La Forgia Daniele 
Published: March 2020

Abstract
Background
Screening programs use mammography as primary diagnostic tool for detecting breast cancer at an early stage. The diagnosis of some lesions, such as microcalcifications, is still difficult today for radiologists. In this paper, we proposed an automatic binary model for discriminating tissue in digital mammograms, as support tool for the radiologists. In particular, we compared the contribution of different methods on the feature selection process in terms of the learning performances and selected features.

Results
For each ROI, we extracted textural features on Haar wavelet decompositions and also interest points and corners detected by using Speeded Up Robust Feature (SURF) and Minimum Eigenvalue Algorithm (MinEigenAlg). Then a Random Forest binary classifier is trained on a subset of a sub-set features selected by two different kinds of feature selection techniques, such as filter and embedded methods. We tested the proposed model on 260 ROIs extracted from digital mammograms of the BCDR public database. The best prediction performance for the normal/abnormal and benign/malignant problems reaches a median AUC value of 98.16% and 92.08%, and an accuracy of 97.31% and 88.46%, respectively. The experimental result was comparable with related work performance.

Conclusions
The best performing result obtained with embedded method is more parsimonious than the filter one. The SURF and MinEigen algorithms provide a strong informative content useful for the characterization of microcalcification clusters.
Network hub-node prioritization of gene regulation with intra-network association
Authors: Chang Hung-Ching , Chu Chiao-Pei , Lin Shu-Ju , Hsiao Chuhsing Kate 
Published: March 2020

Abstract
Background
To identify and prioritize the influential hub genes in a gene-set or biological pathway, most analyses rely on calculation of marginal effects or tests of statistical significance. These procedures may be inappropriate since hub nodes are common connection points and therefore may interact with other nodes more often than non-hub nodes do. Such dependence among gene nodes can be conjectured based on the topology of the pathway network or the correlation between them.

Results
Here we develop a pathway activity score incorporating the marginal (local) effects of gene nodes as well as intra-network affinity measures. This score summarizes the expression levels in a gene-set/pathway for each sample, with weights on local and network information, respectively. The score is next used to examine the impact of each node through a leave-one-out evaluation. To illustrate the procedure, two cancer studies, one involving RNA-Seq from breast cancer patients with high-grade ductal carcinoma in situ and one microarray expression data from ovarian cancer patients, are used to assess the performance of the procedure, and to compare with existing methods, both ones that do and do not take into consideration correlation and network information. The hub nodes identified by the proposed procedure in the two cancer studies are known influential genes; some have been included in standard treatments and some are currently considered in clinical trials for target therapy. The results from simulation studies show that when marginal effects are mild or weak, the proposed procedure can still identify causal nodes, whereas methods relying only on marginal effect size cannot.

Conclusions
The NetworkHub procedure proposed in this research can effectively utilize the network information in combination with local effects derived from marker values, and provide a useful and complementary list of recommendations for prioritizing causal hubs.