bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling
Authors: Nakai Sho , Tamiya Hironari , Imura Yoshinori , Nakai Takaaki , Yasuda Naohiro , Wakamatsu Toru , Tanaka Takaaki , Outani Hidetatsu , Takenaka Satoshi , Hamada Kenichiro , Myoui Akira , Araki Nobuhito , Ueda Takafumi , Yoshikawa Hideki , Naka Norifumi 
Published: December 2019

AbstractClear cell sarcoma (CCS) is a rare but chemotherapy-resistant and often fatal high-grade soft-tissue sarcoma (STS) characterized by melanocytic differentiation under control of microphthalmia-associated transcription factor (MITF). Eribulin mesilate (eribulin) is a mechanistically unique microtubule inhibitor commonly used for STS treatment, particularly liposarcoma and leiomyosarcoma. In this study, we examined the antitumor efficacy of eribulin on four human CCS cell lines and two mouse xenograft models. Eribulin inhibited CCS cell proliferation by inducing cell-cycle arrest and apoptosis, shrunk CCS xenograft tumors, and increased tumor vessel density. Eribulin induced MITF protein upregulation and stimulated tumor cell melanocytic differentiation through ERK1/2 inactivation (a MITF negative regulator) in vitro and in vivo. Moreover, tumor reoxygenation, probably caused by eribulin-induced vascular remodeling, attenuated cell growth and inhibited ERK1/2 activity, thereby upregulating MITF expression and promoting melanocytic differentiation. Finally, downregulation of MITF protein levels modestly debilitated the antiproliferative effect of eribulin on CCS cells. Taken together, eribulin suppresses CCS through inhibition of cell proliferation and promotion of tumor differentiation by acting both directly on tumor cells and indirectly through tumor reoxygenation.
Breast Cancer Characteristics and Survival among Users versus Nonusers of Raloxifene
Authors: Pinsky Paul F. , Miller Eric A. , Heckman-Stoddard Brandy M. , Minasian Lori 
Published: December 2019

Abstract
Raloxifene reduces breast cancer incidence. However, it is unclear whether it also reduces mortality from breast cancer. For raloxifene to reduce incidence but not mortality, breast cancer survival would have to be worse for raloxifene users than nonusers. Surveillance Epidemiology and End Results-Medicare was used to identify women with invasive breast cancer diagnosed from 2007 to 2015 at ages 65–89 who had prior Medicare Part D (prescription drug) enrollment; breast cancer characteristics and survival were assessed among raloxifene regular users (≥180 days in past year) versus nonusers. Logistic regression was used to assess cancer characteristics. Two methods utilizing proportional hazards models were employed to assess breast cancer–specific survival. In method 1, survival was assessed adjusting for demographics, mammography use, and chronic conditions in the subset with Medicare fee-for-service enrollment. In method 2, predicted survival as a function of breast cancer characteristics was modeled in nonusers and the model applied to users to predict survival. A total of 116,317 raloxifene nonusers and 1,223 regular users were identified. Users were significantly more likely to have hormone receptor (HR)-negative cancers, but less likely to have T2+, N1+, and metastatic disease. There were 10,869 and 101 breast cancer–related deaths in nonusers and regular users, respectively. The HR (users vs. nonusers) for breast cancer–specific survival in method 1 was 0.94 (95% confidence interval, 0.73–1.22). In method 2, predicted survival was higher in users than nonusers (8-year survival 84.9% vs. 83.4%). Breast cancer–specific survival in raloxifene users was not worse than in nonusers, providing indirect evidence that raloxifene reduces breast cancer–related mortality.
A clinical staging approach to improving diagnostics in anxiety disorders: Is it the way to go?
Authors: Bokma Wicher A , Batelaan Neeltje M , Hoogendoorn Adriaan W , Penninx Brenda WJH , van Balkom Anton JLM 
Published: December 2019

Background: Clinical staging is a paradigm in which stages of disease progression are identified; these, in turn, have prognostic value. A staging model that enables the prediction of long-term course in anxiety disorders is currently unavailable but much needed as course trajectories are highly heterogenic. This study therefore tailored a heuristic staging model to anxiety disorders and assessed its validity. Methods: A clinical staging model was tailored to anxiety disorders, distinguishing nine stages of disease progression varying from subclinical stages (0, 1A, 1B) to clinical stages (2A–4B). At-risk subjects and subjects with anxiety disorders ( n = 2352) from the longitudinal Netherlands Study of Depression and Anxiety were assigned to these nine stages. The model’s validity was assessed by comparing baseline (construct validity) and 2-year, 4-year and 6-year follow-up (predictive validity) differences in anxiety severity measures across stages. Differences in depression severity and disability were assessed as secondary outcome measures. Results: Results showed that the anxiety disorder staging model has construct and predictive validity. At baseline, differences in anxiety severity, social avoidance behaviors, agoraphobic avoidance behaviors, worrying, depressive symptoms and levels of disability existed across all stages (all p-values < 0.001). Over time, these differences between stages remained present until the 6-year follow-up. Differences across stages followed a linear trend in all analyses: higher stages were characterized by the worst outcomes. Regarding the stages, subjects with psychiatric comorbidity (stages 2B, 3B, 4B) showed a deteriorated course compared with those without comorbidity (stages 2A, 3A, 4A). Conclusion: A clinical staging tool would be useful in clinical practice to predict disease course in anxiety disorders.
Randomization of endovascular treatment with stent-retriever and/or thromboaspiration versus best medical therapy in acute ischemic stroke due to large vessel occlusion trial: Rationale and design
Authors: Nogueira Raul G , Lima Fabricio O , Pontes-Neto Octávio M , S Silva Gisele , José Mont’Alverne Francisco , Abud Daniel G , Frudit Michel , Passos Paulo , Haussen Diogo C , Dabus Guilherme , de Freitas Gabriel R , Oliveira-Filho Jamary , Bezerra Daniel C , Liebeskind David S , Wagner Mario B , Passos José EF , Molina Carlos A , Broderick Joseph , Saver Jeffrey L , Martins Sheila O 
Published: December 2019

Background RESILIENT is a prospective, multicenter, randomized phase III trial to test the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. Methods Subjects must fulfill the following main inclusion criteria: symptom onset ≤8 h, age ≥18 years, baseline NIHSS ≥8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS ≥6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. Randomization Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. Design The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0–2 at 90 days) common odds ratio of 1.615. Primary outcome Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. Secondary outcomes Secondary end-points include: 90-day functional independence (mRS ≤2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0–2 or improvement ≥8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.
Residential greenness and increased physical activity in patients after coronary artery bypass graft surgery
Authors: Sadeh Maya , Brauer Michael , Chudnovsky Alexandra , Ziv Arnona , Dankner Rachel 
Published: December 2019

Abstract

Aims
Physical activity is a fundamental component of rehabilitation following coronary artery bypass (CABG) surgery. Proximity to neighbourhood green spaces may encourage physical activity. We investigated the association between residential greenness and exercise-related physical activity post-CABG surgery.

Methods
Participants in a prospective cohort study of 846 patients (78% men) who underwent CABG surgery at seven cardiothoracic units during the time period 2004–2007 were interviewed regarding their physical activity habits one day before and one year after surgery. Exposure to residential neighbourhood greenness (within a 300 m buffer around their place of residence) was measured using the Normalized Difference Vegetative Index. Participation in exercise-related physical activity (yes/no), weekly duration of exercise-related physical activity and the change in exercise-related physical activity between baseline and follow-up were examined for associations with residential greenness, adjusting for socio-demographic factors, propensity score adjusted participation in cardiac rehabilitation and health-related covariates after multiple imputation for missing variables.

Results
Living in a higher quartile of residential greenness was associated with a 52% greater odds of being physically active (OR 1.52, 95% CI 1.22–1.90). This association persisted only (OR 1.75, 95% CI 1.35–2.27) among patients who did not participate in cardiac rehabilitation following surgery and was stronger in women (OR 2.38, 95% CI 1.40–4.07) than in men (OR 1.37, 95% CI 1.07–1.75). Participants who lived in greener areas were more likely to increase their post-surgical physical activity than those who lived in less green areas (OR 1.59, 95% CI 1.25–2.01).

Conclusions
Residential greenness appears to be beneficial in increasing exercise-related physical activity in cardiac patients, especially those not particpating in cardiac rehabilitation after CABG surgery.
Seed interior microbiome of rice genotypes indigenous to three agroecosystems of Indo-Burma biodiversity hotspot
Authors: Raj Garima , Shadab Mohammad , Deka Sujata , Das Manashi , Baruah Jilmil , Bharali Rupjyoti , Talukdar Narayan C. 
Published: December 2019

Abstract
Background
Seeds of plants are a confirmation of their next generation and come associated with a unique microbia community. Vertical transmission of this microbiota signifies the importance of these organisms for a healthy seedling and thus a healthier next generation for both symbionts. Seed endophytic bacterial community composition is guided by plant genotype and many environmental factors. In north-east India, within a narrow geographical region, several indigenous rice genotypes are cultivated across broad agroecosystems having standing water in fields ranging from 0-2 m during their peak growth stage. Here we tried to trap the effect of rice genotypes and agroecosystems where they are cultivated on the rice seed microbiota. We used culturable and metagenomics approaches to explore the seed endophytic bacterial diversity of seven rice genotypes (8 replicate hills) grown across three agroecosystems.

Results
From seven growth media, 16 different species of culturable EB were isolated. A predictive metabolic pathway analysis of the EB showed the presence of many plant growth promoting traits such as siroheme synthesis, nitrate reduction, phosphate acquisition, etc. Vitamin B12 biosynthesis restricted to bacteria and archaea; pathways were also detected in the EB of two landraces. Analysis of 522,134 filtered metagenomic sequencing reads obtained from seed samples (n=56) gave 4061 OTUs. Alpha diversity indices showed significant differences in observed OTU richness (P≤0.05) across genotypes. Significant differences were also found between the individual hills of a rice genotype. PCoA analysis exhibited three separate clusters and revealed the clusters separated based on genotype, while agroecosystem showed a minimal effect on the variation of seed microbiota (adonis, R2=0.07, P=0.024). Interestingly, animal gut resident bacteria such as Bifidobacterium, Faecalibacterium, Lactobacillus, etc. were found in abundance as members of the seed microbiota.

Conclusion
Overall, our study demonstrates, indigenous rice genotypes of north-east India have a unique blend of endophytic bacteria in their mature seeds. While there are notable variations among plants of the same genotype, we found similarities among genotypes cultivated in completely different environmental conditions. The beta diversity variations across the seven rice genotypes were significantly shaped by their genotype rather than their agroecosystems.
Awareness, knowledge, attitude and practice of adverse drug reaction reporting among health workers and patients in selected primary healthcare centres in Ibadan, southwestern Nigeria
Authors: Adisa Rasaq , Omitogun Tomilayo I. 
Published: December 2019

AbstractBackgroundHigher incidence of adverse drug reactions (ADRs) is a global health problem requiring attention of all stakeholders regardless of the practice settings. This study therefore aimed to evaluate awareness, knowledge, attitude and practice of ADR reporting among health workers and patients in 10 primary healthcare centres (PHCs) in Ibadan, southwestern Nigeria.MethodsQuestionnaire-guided cross-sectional survey among 80 health workers and 360 patients enrolled from the selected PHCs between October and December 2018. The semi-structured questionnaires generally comprised open-ended and closed-ended questions to explore general knowledge and awareness of ADRs and pharmacovigilance, while other question-items evaluated attitude towards ADR reporting and ADR reporting practice. Overall percent score in the knowledge and attitude domains for the health workers was developed into binary categories of > 80 versus ≤80% for “adequate” and “inadequate” knowledge, as well as “positive” and “negative” attitude, respectively. Data were summarised using descriptive statistics, while Chi-square test was used to evaluate categorical variables atp < 0.05.ResultsOverall, 58(72.5%) health workers had heard of pharmacovigilance,but only 3(5.2%) correctly understood the pharmacovigilance concept. Twelve (15.0%) showed adequate knowledge of ADRs, while 37(46.2%) demonstrated positive attitude towards ADR reporting. Thirty (37.5%) health workers had come across ADR reporting form, while 79(98.8%) expressed willingness to report all ADRs encountered. Of the patients, 31(8.6%) had heard of pharmacovigilance, 143(39.7%) correctly cited ADR definition, while 67(18.6%) reported the previously experienced ADRs. Informing healthcare professional (38; 38.8%) was the most common measure taken by patients when they experienced reaction(s). Nurses significantly had adequate knowledge of ADRs (p < 0.001) compared to other cadres.ConclusionsHealth workers in the selected PHCs were largely aware of pharmacovigilance but show low level of knowledge about ADRs and pharmacovigilance concept, with moderately positive attitude towards ADR reporting. Patients on the other hand demonstrate low level of awareness of pharmacovigilance and ADR reporting, with less than one-fifth who reported the previously experienced ADRs. This perhaps underscores a need for regular mandatory education and training on ADRs/pharmacovigilance concept among the PHC health workers, while continuous public enlightenment and awareness campaign on spontaneous reporting of ADRs is advocated in order to enhance reporting rate.
A cross-sectional study on feather cover damage in Canadian laying hens in non-cage housing systems
Authors: Decina Caitlin , Berke Olaf , van Staaveren Nienke , Baes Christine F. , Widowski Tina M. , Harlander-Matauschek Alexandra 
Published: December 2019

AbstractBackgroundFeather damage (FD) resulting from feather pecking remains a concern in non-cage housing systems for laying hens worldwide. This study aimed to identify bird-, housing-, and management-related factors associated with FD in non-cage housing systems as the egg production sector phases out the conventional cage system in Canada. A survey on housing and management practices was developed and distributed to 122 laying hen farms where 39 respondents provided information on non-cage flocks. Farmers visually assessed 50 birds throughout the barn for FD using a 0–2 scoring scale according to severity. Prevalence of FD was calculated as the percentage of birds with any form of FD (score > 0). Multivariable linear regression modeling was used to identify factors associated with FD prevalence.ResultsSix variables were included in the final model and accounted for 64% of the variation in FD between farms. FD prevalence was higher with increasing flock age (0.9% ± 0.29) and when birds were housed in all wire/slatted barns compared with all litter barns (37.6% ± 13.1). Additionally, FD prevalence tended to be higher in barns with manure removal only after depopulation (20.1% ± 10.70). Enrichment also tended to be associated with higher FD (19.1% ± 8.04), possibly indicating that it was provided after FD was observed as a control measure, or, was not efficient in reducing the development of FD.ConclusionsThese findings emphasize the role of litter provision and management (e.g., manure removal effects on air quality), and its potential impact on FD among laying hens in non-cage housing systems in Canada. Further longitudinal and/or intervention studies are needed to assess the potential of the identified factors to function as a management strategy to prevent or reduce FD in non-cage housed laying hens.
Risk factors associated with progressive myelomalacia in dogs with complete sensorimotor loss following intervertebral disc extrusion: a retrospective case-control study
Authors: Castel Aude , Olby Natasha J. , Ru Hongyu , Mariani Christopher L. , Muñana Karen R. , Early Peter J. 
Published: December 2019

AbstractBackgroundProgressive myelomalacia (PMM) is a usually fatal complication of acute intervertebral disc extrusion (IVDE) in dogs but its risk factors are poorly understood. The objective of this retrospective case-control study was to identify risk factors for PMM by comparing dogs with complete sensorimotor loss following IVDE that did and did not develop the disease after surgery. We also investigated whether any risk factors for PMM influenced return of ambulation. Medical records of client-owned dogs with paraplegia and loss of pain perception that underwent surgery for IVDE from 1998 to 2016, were reviewed. Dogs were categorized as PMM yes or no based on clinical progression or histopathology. Walking outcome at 6 months was established. Signalment, onset and duration of signs (categorized), steroids, non-steroidal anti-inflammatory drugs (yes or no), site of IVDE (lumbar intumescence or thoracolumbar) and longitudinal extent of IVDE were retrieved and their associations with PMM and walking outcome were examined using logistic regression.ResultsOne hundred and ninety seven dogs were included, 45 with and 152 without PMM. A 6-month-outcome was available in 178 dogs (all 45 PMM dogs and 133 control dogs); 86 recovered walking (all in the control group). Disc extrusions at the lumbar intumescence were associated with PMM (p = 0.01, OR: 3.02, CI: 1.3–7.2). Surgery performed more than 12 h after loss of ambulation was associated with PMM (OR = 3.4; CI = 1.1–10.5,p = 0.03 for 12-24 h and OR = 4.6; CI = 1.3–16.6,p = 0.02 for the > 24 h categories when compared with the ≤12 h category). Treatment with corticosteroids was negatively associated with PMM (OR: 3.1; CI: 1.3–7.6,p = 0.01). The only variable to affect walking outcome was longitudinal extent of IVDE (OR = 2.6; CI = 1.3–5.3,p = 0.006).ConclusionDogs with lumbar intumescence IVDE are at increased risk of PMM. Timing of surgery and corticosteroid use warrant further investigations. PMM and recovery of walking are influenced by different factors.
Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts
Authors: Kong Jing , Tian Hongzhu , Zhang Fuyin , Zhang Zebing , Li Jiao , Liu Xue , Li Xiancheng , Liu Jing , Li Xiaojie , Jin Dong , Yang Xuesong , Sun Bo , Guo Tao , Luo Yong , Lu Yao , Lin Bingcheng , Liu Tingjiao 
Published: December 2019

Abstract
Objectives
Carcinoma-associated fibroblasts (CAFs) have been known to promote cancer progression by modifying the primary tumor microenvironment. We aimed to elucidate the intercellular communication between CAFs and secondary organs in salivary adenoid cystic carcinoma (SACC) metastasis.

Methods
Pre-metastatic and metastatic animal models of SACC were established using extracellular vesicles (EVs) from CAFs and SACC cells. Lung fibroblasts (LFs) were treated with EVs and their transcriptomic alterations were identified by RNA sequencing. ITRAQ were performed to analyze EV cargos. TC I-15 was used to inhibit EV uptake by LFs and SACC lung metastasis in vivo.

Results
Here, we show that CAF EVs induced lung pre-metastatic niche formation in mice and consequently increased SACC lung metastasis. The pre-metastatic niche induced by CAF EVs was different from that induced by SACC EVs. CAF EVs presented a great ability for matrix remodeling and periostin is a potential biomarker characterizing the CAF EV-induced pre-metastatic niche. We found that lung fibroblast activation promoted by CAF EVs was a critical event at the pre-metastatic niche. Integrin α2β1 mediated CAF EV uptake by lung fibroblasts, and its blockage by TC I-15 prevented lung pre-metastatic niche formation and subsequent metastasis. Plasma EV integrin β1 was considerably upregulated in the mice bearing xenografts with high risk of lung metastasis.

Conclusions
We demonstrated that CAF EVs participated in the pre-metastatic niche formation in the lung. Plasma EV integrin β1 might be a promising biomarker to predict SACC metastasis at an early stage. An integrated strategy targeting both tumor and stromal cells is necessary to prevent SACC metastasis.