bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant nitrogen supply affects the Botrytis cinerea infection process and modulates known and novel virulence factors
Authors: Soulie Marie‐Christine , Koka Shamsuddin Mia , Floch Kévin , Vancostenoble Baptiste , Barbe Deborah , Daviere Antoine , Soubigou‐Taconnat Ludivine , Brunaud Veronique , Poussereau Nathalie , Loisel Elise , Devallee Amelie , Expert Dominique , Fagard Mathilde 
Published: September 2020

AbstractPlant nitrogen (N) fertilization is known to affect disease; however, the underlying mechanisms remain mostly unknown. We investigated the impact of N supply on the Arabidopsis thaliana–Botrytis cinerea interaction. A. thaliana plants grown in low nitrate were more tolerant to all wild‐type B. cinerea strains tested. We determined leaf nitrate concentrations and showed that they had a limited impact on B. cinerea growth in vitro. For the first time, we performed a dual RNA‐Seq of infected leaves of plants grown with different nitrate concentrations. Transcriptome analysis showed that plant and fungal transcriptomes were marginally affected by plant nitrate supply. Indeed, only a limited set of plant (182) and fungal (22) genes displayed expression profiles altered by nitrate supply. The expression of selected genes was confirmed by quantitative reverse transcription PCR at 6 hr postinfection (hpi) and analysed at a later time point (24 hpi). We selected three of the 22 B. cinerea genes identified for further analysis. B. cinerea mutants affected in these genes were less aggressive than the wild‐type strain. We also showed that plants grown in ammonium were more tolerant to B. cinerea. Furthermore, expression of the selected B. cinerea genes in planta was altered when plants were grown with ammonium instead of nitrate, demonstrating an impact of the nature of N supplied to plants on the interaction. Identification of B. cinerea genes expressed differentially in planta according to plant N supply unveils two novel virulence functions required for full virulence in A. thaliana: a secondary metabolite (SM) and an acidic protease (AP).
Pharmacologic treatment of GERD: Where we are now, and where are we going?
Authors: Scarpignato Carmelo , Hongo Michio , Wu Justin C. Y. , Lottrup Christian , Lazarescu Adriana , Stein Ellen , Hunt Richard H. 
Published: September 2020

AbstractThe introduction of acid inhibition in clinical practice has revolutionized the management of acid‐related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI‐refractoriness is common, and persistent symptoms are observed in up to 40–55% of daily PPI users. Potassium‐competitive acid blockers (P‐CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P‐CABS are used as add‐on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case‐by‐case basis.
Epigenetic regulation of adipose tissue expansion and adipogenesis by N6‐methyladenosine
Authors: Wu Ruifan , Wang Xinxia 
Published: September 2020

SummaryObesity, defined as excessive fat accumulation, is strongly associated with metabolic diseases and cancer, and its prevalence is rising worldwide. Thus, understanding the molecular mechanism of adipogenesis is of fundamental significance. Epigenetic modifications play important roles in regulating adipogenesis. N6‐methyladenosine (m6A), the most prevalent and abundant mRNA modification in eukaryotic cells, modulates multiple aspects of RNA metabolism, including mRNA stability, translation, splicing and export. Recent studies indicate that m6A methylation plays important roles in modulating gene expression and signal pathways in various physiologic processes and diseases. Notably, the significant function and regulatory mechanisms of m6A in adipogenesis are now emerging. In this review, we summarize recent studies that elucidate the vital roles of m6A modifications in regulating adipogenesis and adipose tissue expansion. Furthermore, we highlight the nutritional regulation of m6A methylation and adipogenesis, which may prove a novel therapeutic strategy to fight against obesity.
Role of the RprY response regulator in P. gingivalis community development and virulence
Authors: Shen Daonan , Perpich John D. , Stocke Kendall S. , Yakoumatos Lan , Fitzsimonds Zackary R. , Liu Chengcheng , Miller Daniel P. , Lamont Richard J. 
Published: September 2020

Abstract
Porphyromonas gingivalis expresses a limited number of two‐component systems, including RprY, an orphan response regulator which lacks a cognate sensor kinase. In this study, we examined cross‐phosphorylation of RprY on tyrosine residues and its importance for RprY function. We show that RprY reacts with phosphotyrosine antibodies, and found that the tyrosine (Y) residue at position 41 is predicted to be solvent accessible. Loss of RprY increased the level of heterotypic community development with Streptococcus gordonii, and the community‐suppressive function of RprY required Y41. Expression of the Mfa1 fimbrial adhesin was increased in the rprY mutant and in the mutant complemented with rprY containing a Y41F mutation. In a microscale thermophoresis assay, recombinant RprY protein bound to the promoter region of mfa1, and binding was diminished with RprY containing the Y41F substitution. RprY was required for virulence of P. gingivalis in a murine model of alveolar bone loss. Transcriptional profiling indicated that RprY can control the expression of genes encoding the type IX secretion system (T9SS) machinery and virulence factors secreted through the T9SS, including the gingipain proteases and peptidylarginine deiminase (PPAD). Collectively, these results establish the RprY response regulator as a component of the tyrosine phosphorylation regulon in P. gingivalis, which can independently control heterotypic community development through the Mfa1 fimbriae and virulence through the T9SS.
Clinical worsening due to inappropriate automatic mode switch during biventricular pacing: What is the mechanism?
Authors: Bera Debabrata , Kumawat Kapil , Majumder Suchit , Rana Saiyed , Sarkar Rakesh 
Published: September 2020

AbstractWe describe a case of a 65‐year‐old gentleman with nonischemic cardiomyopathy and left bundle branch block who underwent cardiac resynchronization therapy device. After becoming a responder initially, he experienced significant clinical worsening on follow‐up. Device interrogation revealed several long episodes of inappropriate automatic mode switch (AMS) entry due to far‐field R wave oversensing resulting in loss of atrioventricular synchrony. Moreover, pacing in VVI mode with consistent VA conduction taking place during the AMS episodes was also found to be detrimental, which helped in sustaining the episodes and produced pacemaker syndrome like phenomenon. Attempts made to resolve the issue by prolonging the post‐ventricular atrial blanking period was unsuccessful, hence we adjusted the atrial channel sensitivity to troubleshoot the problem.
NRASQ61K melanoma tumor formation is reduced by p38‐MAPK14 activation in zebrafish models and NRAS‐mutated human melanoma cells
Authors: Banik Ishani , Cheng Phil F. , Dooley Christopher M. , Travnickova Jana , Merteroglu Munise , Dummer Reinhard , Patton Elizabeth E. , Busch‐Nentwich Elisabeth M. , Levesque Mitchell P. 
Published: September 2020

AbstractOncogenic BRAF and NRAS mutations drive human melanoma initiation. We used transgenic zebrafish to model NRAS‐mutant melanoma, and the rapid tumor onset allowed us to study candidate tumor suppressors. We identified P38α‐MAPK14 as a potential tumor suppressor in The Cancer Genome Atlas melanoma cohort of NRAS‐mutant melanomas, and overexpression significantly increased the time to tumor onset in transgenic zebrafish with NRAS‐driven melanoma. Pharmacological activation of P38α‐MAPK14 using anisomycin reduced in vitro viability of melanoma cultures, which we confirmed by stable overexpression of p38α. We observed that the viability of MEK inhibitor resistant melanoma cells could be reduced by combined treatment of anisomycin and MEK inhibition. Our study demonstrates that activating the p38α‐MAPK14 pathway in the presence of oncogenic NRAS abrogates melanoma in vitro and in vivo.SignificanceThe significance of our study is in the accountability of NRAS mutations in melanoma. We demonstrate here that activation of p38α‐MAPK14 pathway can abrogate NRAS‐mutant melanoma which is contrary to the previously published role of p38α‐MAPK14 pathway in BRAF mutant melanoma. These results implicate that BRAF and NRAS‐mutant melanoma may not be identical biologically. We also demonstrate the translational benefit of our study by using a small molecule compound‐anisomycin (already in use for other diseases in clinical trials) to activate p38α‐MAPK14 pathway.
Perception, discrimination, and knowledge
Authors: Callahan Laura Frances 
Published: September 2020

AbstractIn perception, perceivers discriminate. They distinguish or single out the objects and property instances that they see. One might hope this discriminatory nature of perception could help explain how perceptual evidence can be sufficient for knowledge, even granting some form of a relevant alternatives condition on knowledge. Indeed, there are examples of such thinking in recent epistemology literature. But I argue that discriminating actual percepts from actual surrounds is importantly different than discriminating actual states of affairs from merely possible states of affairs. A tension remains between optimism about immediate perceptual knowledge and plausible relevant alternatives or safety conditions on knowledge in general.
Habitat fragmentation and population features differently affect fruit predation, fecundity and offspring performance in a non‐specialist gypsum plant
Authors: Moncalvillo B. , Matesanz S. , Escudero A. , Sánchez A. M. 
Published: September 2020

Abstract

The effects of habitat fragmentation on plant populations are complex, as it might disrupt many ecological processes, including plant reproduction and plant–animal interactions. Gypsum specialist plants may be resilient to fragmentation due to their evolutionary history in fragmented landscapes, but the effects on non‐specialist plants occurring in gypsum are unknown.

We conducted a study focusing on different aspects of the reproductive cycle of Astragalus incanus subsp. incanus, a plant facultatively linked to gypsum soils. We focused on plant fecundity and pre‐dispersal predation, obtained from field observations, and offspring performance, assessed in a common garden. Beyond fragment size and connectivity, we also considered habitat quality, population size and density and plant size as predictors.

Fragment size and connectivity had no effect on plant fecundity, but jointly determined fruit predation, while fragment size was positively related to offspring growth. Population density, rather than population size, had a positive effect on predation but negatively affected plant fecundity and offspring performance. Habitat quality reduced both plant fecundity and predation incidence.

In this non‐specialist species, habitat fragmentation, population features and habitat quality affect different facets of plant performance. Predation was the only process clearly affected by fragmentation variables, fecundity mainly depended on population features and offspring performance and was better explained by mother plant identity. Our results show the need to consider habitat and population features together with fragment size and connectivity in order to assess the effects of fragmentation. Importantly, these effects can involve different aspects of plant reproduction, including plant–animal interactions.
Low antithrombin levels in neonates and infants undergoing congenital heart surgery result in more red blood cell and plasma transfusion on cardiopulmonary bypass
Authors: Fang Zhe Amy , Bruzdoski Karen , Kostousov Vadim , Hui Shiu‐Ki Rocky , Vener David , Gottlieb Erin , Teruya Jun 
Published: September 2020

AbstractBackgroundNeonates have lower levels of antithrombin (AT) due to immature liver synthetic function. AT deficiency may lead to inadequate anticoagulation with heparin during cardiac surgery resulting in consumption of coagulation factors and increased blood transfusion. The goal of this study is to examine the effect of AT level on the transfusion requirements of neonates and infants undergoing open heart surgery.Study Design and MethodsThis is a prospective, observational study at a tertiary pediatric referral center. Neonates and infants up to 6 months of age undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were enrolled. Demographic, intraoperative, transfusion, and complications data were collected. Preoperative AT level was measured after induction of anesthesia. Prior to separation from CPB, a second blood sample was drawn and AT, thrombin antithrombin complex (TAT), D‐dimer, and anti‐Xa levels were measured. Linear and logistic regression were performed for data analysis.ResultsPreoperative low AT level was significantly associated with increased transfusion of red blood cells (RBCs) and fresh frozen plasma (FFP) during CPB, but not after separation from CPB. The incidence of thrombosis and re‐operation were not associated with preoperative AT levels. There was no association between TAT, D‐dimer, and anti‐Xa levels at the end of CPB and preoperative AT levels.ConclusionLow preoperative AT level is associated with increased transfusion of RBC and FFP on CPB in neonates and infants undergoing congenital heart surgery. Low preoperative AT level did not result in coagulation activation after CPB and after surgery.
Extracellular histones and xenotransplantation
Authors: Li Tao , Jiang Hongtao , Liu Houqin , Cooper David K. C. , Wang Yi 
Published: September 2020

AbstractXenotransplantation may be an alternative source of organs for patients with end‐stage organ failure, but problems remain to be overcome. Five factors that are problematic are (a) a sustained systemic inflammatory response in the xenograft recipient, (b) thrombotic microangiopathy and disseminated intravascular coagulation, (c) ischemia‐reperfusion injury, (d) complement activation, and (e) vascular endothelial cell injury. In xenotransplantation, histones, which are positively charged proteins, are released into the extracellular space from damaged and activated cells, cause cell and tissue damage, and act as danger/damage‐associated molecular patterns (DAMPs) that mediate inflammation, coagulation disorders, an immune response, and cytotoxicity. We have previously demonstrated that serum histones increase after pig‐to‐baboon organ transplantation and infection. Treatment of the recipient with tocilizumab (interleukin‐6 receptor blockade) reduces the level of serum histones and C‐reactive protein. In this review, the potential role of extracellular histones in xenotransplantation is discussed, and we briefly summarize the relationship between extracellular histones and the inflammatory response, coagulation dysfunction, ischemia‐reperfusion injury, the complement system, and vascular endothelial cell injury.
Comparison of Transverse Plane Tibial and Frontal Plane Rearfoot Motion and Movement Coordination Between Runners With Medial Tibial Stress Syndrome and Healthy Controls
Authors: Langley Ben , Knight Nick , Morrison Stewart C. 
Published: September 2020

Medial tibial stress syndrome (MTSS) is a common running-related injury. Alterations in movement patterns and movement coordination patterns have been linked to the development of overuse injuries. The aim of this study was to compare transverse plane tibial and frontal plane rearfoot motion and the coordination of these movements between runners with MTSS and healthy controls. A total of 10 recreational runners with MTSS and 10 healthy controls ran at 11 km/h on a treadmill. A 3-camera motion analysis system operating at 200 Hz was used to calculate tibia and rearfoot motion. Stance phase motion patterns were compared between groups using multivariate analysis, specifically, Hotelling T2 test with statistical parametric mapping. A modified vector coding technique was used to classify the coordination of transverse plane tibial and frontal plane rearfoot motion. The frequency of each coordination pattern displayed by each group was compared using independent samples t tests. Individuals with MTSS displayed significantly (P = .037, d = 1.00) more antiphase coordination (tibial internal rotation with rearfoot inversion) despite no significant (P > .05) differences in stance phase kinematics. The increased antiphase movement may increase the torsional stress placed upon the medial aspect of the tibia, contributing to the development of MTSS.
Validity and Intrarater Reliability Using a Smartphone Clinometer Application to Measure Active Cervical Range of Motion Including Rotation Measurements in Supine
Authors: Monreal Christanie , Luinstra Lindsay , Larkins Lindsay , May James 
Published: September 2020

Context: Technological advances have given smartphones the capabilities of sensitive clinical measurement equipment at lesser cost and higher availability. The Clinometer is a smartphone application that can be used to measure the joint range of motion in a clinical setting, but psychometric properties of the tool’s use measuring cervical range of motion (CROM) are not established. Objectives: The purpose of this study was to examine the validity and intrarater reliability of the Clinometer application for the measurement of CROM (ie, flexion, extension, rotation, lateral flexion) and to determine the minimal detectable change and SEM. Design: A blinded, repeated-measures correlational design was employed. Setting: The study was conducted collaboratively between 2 athletic training clinics. Participants: A convenience sample of healthy adults ages 18–30 years were recruited. Participants with any history in the last 3 months of cervical or thoracic pathology, pain, or any musculoskeletal injury were excluded. Main Outcome Measures: Three repetitions of each motion were measured by a primary researcher with a goniometer. The same researcher then conducted 3 blinded measurements with the Clinometer application following the same procedure. A second researcher, blinded to the goniometer measurements, recorded the results. Thirty minutes later, testing was repeated with the application. The Pearson correlation was calculated to determine validity of the application compared with goniometry. Results: The measurements between devices had moderate to excellent concurrent validity, with the coefficients ranging between 0.544 and 0.888, P < .01. Test–retest reliability of the CROM measurement using the application was moderate to excellent, with intraclass correlation coefficients ranging between .774 and .928. Across all movements, the SEM ranged from 1.17° to 2.01°, and the minimal detectable change ranged from 1.18° to 2.02°. Conclusion: The Clinometer application is a valid and reliable instrument for measuring active CROM. Level of evidence: clinical measurement, level 1b.
Breast cancer prognosis and P-cadherin expression: systematic review and study-level meta-analysis
Authors: Qi Runzhi , Lin Jinyin , Chen Shuntai , Jiang Juling , Zhang Xing , Yao Bo , Zheng Honggang , Jin Zhichao , Yuan Yuan , Hou Wei , Hua Baojin , Guo Qiujun 
Published: September 2020

ObjectiveP-cadherin can act both as a tumour suppressor and an oncogene. The clinical prognostic value of P-cadherin overexpression in breast cancer (BC) remains unclear. We conducted a study-level meta-analysis to determine whether P-cadherin expression can help predict prognosis in BC.MethodsA systematic literature search was performed to review eligible studies and clarify the relationship between P-cadherin overexpression and overall survival (OS), disease-free survival (DFS), pathological features, molecular subtypes and molecular phenotypes in BC.ResultsThirty-one studies including 12 332 patients were included. P-cadherin overexpression was correlated with significantly worse OS (HR=1.77, p<0.00001) and DFS (HR=1.96, p<0.00001) than P-cadherin-negative. P-cadherin overexpression could lead to high histological grade (OR=3.33, p<0.00001) and lymph node metastasis (OR=1.62, p<0.00001). Moreover, P-cadherin overexpression was associated with low odds of the luminal A subtype and high odds of the human epidermal growth factor receptor-2 (HER2)-positive and triple-negative subtypes. P-cadherin expression led to low expression of oestrogen and progesterone receptor (OR=0.37 and OR=0.36, respectively, both p<0.00001) and high expression of HER2 (OR=2.31, p<0.00001), Ki-67 (OR=2.79, p<0.00001), epidermal growth factor receptor (OR=5.85, p<0.00001) and cytokeratin 5/6 (OR=6.79, p<0.00001).ConclusionsP-cadherin was found to be associated with invasiveness and metastasis. P-cadherin expression can probably be a useful biomarker for predicting poor survival and may act as an independent prognostic predictor.
The impact of routine Edmonton symptom assessment system use on receiving palliative care services: results of a population-based retrospective-matched cohort analysis
Authors: Barbera Lisa , Sutradhar Rinku , Earle Craig C , Howell Doris , Mittman Nicole , Li Qing , Thiruchelvam Deva , Seow Hsien 
Published: September 2020

BackgroundIn 2007, Cancer Care Ontario began standardised symptom assessment as part of routine care using the Edmonton Symptom Assessment System (ESAS).AimThe purpose of this study was to evaluate the impact of ESAS on receipt of palliative care when compared with a matched group of unexposed patients.DesignA retrospective-matched cohort study examined the impact of ESAS screening on initiation of palliative care services provided by physicians or homecare nurses. The study included adult patients diagnosed with cancer between 2007 and 2015. Exposure was defined as completing ≥1 ESAS during the study period. Using 4 hard and 14 propensity score-matched variables, patients with cancer exposed to ESAS were matched 1:1 to those who were not. Matched patients were followed from first ESAS until initiation of palliative care, death or end of study.ResultsThe final cohort consisted of 204 688 matched patients with no prior palliative care consult. The pairs were well matched. The cumulative incidence of receiving palliative care within the first 5 years was higher among those exposed to ESAS compared with those who were not (27.9% (95% CI: 27.5% to 28.2%) versus 27.9% (95% CI: 27.5% to 28.2%)), when death is considered as a competing event. In the adjusted cause-specific Cox proportional hazards model, ESAS assessment was associated with a 6% increase in palliative care services (HR: 1.06, 95% CI: 1.04 to 1.08).ConclusionWe have demonstrated that patients exposed to ESAS were more likely to receive palliative care services compared with patients who were not exposed. This observation provides real-world data of the impact of routine assessment with a patient-reported outcome.