bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing topical triclosan for cutaneous leishmaniasis: Preclinical efficacy in a murine Leishmania (L.) amazonensis model
Authors: Mesquita Juliana Tonini , Romanelli Maiara Maria , de Melo Trinconi Trinconi CM Cristiana , Guerra Juliana Mariotti , Taniwaki Noemi Nosomi , Uliana Silvia Reni Bortolin , Reimão Juliana Quero , Tempone Andre Gustavo 
Published: August 2020

AbstractLeishmaniasis remains an important neglected tropical infection caused by the protozoan Leishmania and affects 12 million people in 98 countries. The treatment is limited with severe adverse effects. In the search for new therapies, the drug repositioning and combination therapy have been successfully applied to neglected diseases. The aim of the present study was to evaluate the in vitro and in vivo anti‐Leishmania (Leishmania) amazonensis potential of triclosan, an approved topical antimicrobial agent used for surgical procedures. in vitro phenotypic studies of drug‐treated parasites were performed to evaluate the lethal action of triclosan, accompanied by an isobolographic ex‐vivo analysis with the association of triclosan and miltefosine. The results showed that triclosan has activity against L. (L.) amazonensis intracellular amastigotes, with a 50% inhibitory concentration of 16 μM. By using fluorescent probes and transmission electron microscopy, a pore‐forming activity of triclosan toward the parasite plasma membrane was demonstrated, leading to depolarization of the mitochondrial membrane potential and reduction of the reactive oxygen species levels in the extracellular promastigotes. The in vitro interaction between triclosan and miltefosine in the combination therapy assay was classified as additive against intracellular amastigotes. Leishmania‐infected mice were treated with topical triclosan (1% base cream for 14 consecutive days), and showed 89% reduction in the parasite burden. The obtained results contribute to the investigation of new alternatives for the treatment of cutaneous leishmaniasis and suggest that the coadministration of triclosan and miltefosine should be investigated in animal models.
How to make methodological decisions when inferring social networks
Authors: Ferreira André C. , Covas Rita , Silva Liliana R. , Esteves Sandra C. , Duarte Inês F. , Fortuna Rita , Theron Franck , Doutrelant Claire , Farine Damien R. 
Published: August 2020

AbstractSocial network analyses allow studying the processes underlying the associations between individuals and the consequences of those associations. Constructing and analyzing social networks can be challenging, especially when designing new studies as researchers are confronted with decisions about how to collect data and construct networks, and the answers are not always straightforward. The current lack of guidance on building a social network for a new study system might lead researchers to try several different methods and risk generating false results arising from multiple hypotheses testing. Here, we suggest an approach for making decisions when starting social network research in a new study system that avoids the pitfall of multiple hypotheses testing. We argue that best edge definition for a network is a decision that can be made using a priori knowledge about the species and that is independent from the hypotheses that the network will ultimately be used to evaluate. We illustrate this approach with a study conducted on a colonial cooperatively breeding bird, the sociable weaver. We first identified two ways of collecting data using different numbers of feeders and three ways to define associations among birds. We then evaluated which combination of data collection and association definition maximized (a) the assortment of individuals into previously known “breeding groups” (birds that contribute toward the same nest and maintain cohesion when foraging) and (b) socially differentiated relationships (more strong and weak relationships than expected by chance). This evaluation of different methods based on a priori knowledge of the study species can be implemented in a diverse array of study systems and makes the case for using existing, biologically meaningful knowledge about a system to help navigate the myriad of methodological decisions about data collection and network inference.
Innate immune evasion by picornaviruses
Authors: Zhang Xiangle , Paget Max , Wang Congcong , Zhu Zixiang , Zheng Haixue 
Published: August 2020

AbstractThe family Picornaviridae comprises a large number of viruses that cause disease in broad spectrum of hosts, which have posed serious public health concerns worldwide and led to significant economic burden. A comprehensive understanding of the virus‐host interactions during picornavirus infections will help to prevent and cure these diseases. Upon picornavirus infection, host pathogen recognition receptors (PRRs) sense viral RNA to activate host innate immune responses. The activated PRRs initiate signal transduction through a series of adaptor proteins, which leads to activation of several kinases and transcription factors, and contributes to the consequent expression of interferons (IFNs), IFN‐inducible antiviral genes, as well as various inflammatory cytokines and chemokines. In contrast, to maintain viral replication and spread, picornaviruses have evolved several elegant strategies to block innate immune signaling and hinder host antiviral response. In this review, we will summarize the recent progress of how the members of family Picornaviridae counteract host immune response through evasion of PRRs detection, blocking activation of adaptor molecules and kinases, disrupting transcription factors, as well as counteraction of antiviral restriction factors. Such knowledge of immune evasion will help us better understand the pathogenesis of picornaviruses, and provide insights into developing antiviral strategies and improvement of vaccines.
A single‐view field filter device for rare tumor cell filtration and enumeration
Authors: Quan Yunlin , Chen Ke , Xiang Nan , Ni Zhonghua 
Published: August 2020

AbstractIn this work, we demonstrate a single‐view field filter (SVFF) device for the efficient filtration and enumeration of rare tumor cells in the blood. In our device, the track‐etched membrane is integrated within a low‐cost polymer‐film microfluidic chip, and multiplex microfiltration chambers are designed. Our device permits the performing of multiple sample tests on a single membrane and the dynamical observation of the entire filtration process in a single field of view. To characterize the device performance, our device is first tested using tumor cells, and three different cell behaviors are observed during the filtration process. Finally, we successfully apply our device for the separation of rare tumor cells from the lysed blood samples at various flow rates. The recovery rates of 93.3, 87.6, and 84.1% can be respectively achieved at the throughputs of 50, 100, and 150 μL/min. Our single‐view field filter (SVFF) device offers the advantages of label‐free filtration, efficient enumeration, easy integration, and low cost, and holds the potential to be used as an efficient tool for the filtration and enumeration of rare cells.
Simulating Honey Bee Large-Scale Colony Feeding Studies Using the BEEHAVE Model—Part I: Model Validation
Authors: Schmolke Amelie , Abi-Akar Farah , Roy Colleen , Galic Nika , Hinarejos Silvia 
Published: August 2020

Abstract
In pesticide risk assessments, semifield studies, such as large-scale colony feeding studies (LSCFSs), are conducted to assess potential risks at the honey bee colony level. However, such studies are very cost and time intensive, and high overwintering losses of untreated control hives have been observed in some studies. Honey bee colony models such as BEEHAVE may provide tools to systematically assess multiple factors influencing colony outcomes, to inform study design, and to estimate pesticide impacts under varying environmental conditions. Before they can be used reliably, models should be validated to demonstrate they can appropriately reproduce patterns observed in the field. Despite the recognized need for validation, methodologies to be used in the context of applied ecological models are not agreed on. For the parameterization, calibration, and validation of BEEHAVE, we used control data from multiple LSCFSs. We conducted detailed visual and quantitative performance analyses as a demonstration of validation methodologies. The BEEHAVE outputs showed good agreement with apiary-specific validation data sets representing the first year of the studies. However, the simulations of colony dynamics in the spring periods following overwintering were identified as less reliable. The comprehensive validation effort applied provides important insights that can inform the usability of BEEHAVE in applications related to higher tier risk assessments. In addition, the validation methodology applied could be used in a wider context of ecological models. Environ Toxicol Chem 2020;39:2269–2285. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Abstract
Left: Comparison plot of adult bee numbers and honey stores between data from an example large-scale colony feeding study (LSCFS, dots) and model outputs (shaded areas). Right: Quantitative performance indicators for BEEHAVE across several LSCFSs used for validation. The combination of visual and quantitative validation methods provides comprehensive insight into model performance across studies, endpoints and time periods simulated.
VWF/ADAMTS13 Imbalance, But Not Global Coagulation or Fibrinolysis, Is Associated With Outcome and Bleeding in Acute Liver Failure
Authors: Driever Ellen G. , Stravitz R. Todd , Zhang Jingwen , Adelmeijer Jelle , Durkalski Valerie , Lee William M. , Lisman Ton 
Published: August 2020

Background and Aims
Recent studies of acute liver failure (ALF) in man and animals have suggested that rebalanced hemostasis occurs, with distinct hypercoagulable features clinically evidenced by a low risk of bleeding. Rodent models have shown a link between intrahepatic microthrombus formation and progression of ALF. We sought to confirm these earlier findings in a large series of patients with well‐characterized ALF from the Acute Liver Failure Study Group.

Approach and Results
Citrated plasma samples taken on admission from 676 patients with ALF or acute liver injury (international normalized ratio ≥2.0 without hepatic encephalopathy) were used to determine levels of von Willebrand factor (VWF), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity, thrombomodulin‐modified thrombin generation, and clot lysis time (CLT) and compared with the levels in 40 healthy controls. Patients had 3‐fold increased VWF levels, 4‐fold decreased ADAMTS13 activity, similar thrombin generating capacity, and 2.4‐fold increased CLT, compared with controls. Increasing disease severity was associated with progressively more elevated VWF levels as well as hypofibrinolysis. Patients who died or underwent liver transplantation within 21 days of admission had higher VWF levels, lower ADAMTS13 activity, but similar thrombin generation and a similar proportion of patients with severe hypofibrinolysis, when compared with transplant‐free survivors. Likewise, patients with bleeding complications had higher VWF levels and lower ADAMTS13 activity compared to those without bleeding. Thrombin generation and CLT did not differ significantly between bleeding and nonbleeding patients.

Conclusions
Rebalanced hemostatic status was confirmed in a large cohort of patients with acute liver injury/ALF, demonstrating that VWF/ADAMTS13 imbalance is associated with poor outcome and bleeding. The association between VWF/ADAMTS13 imbalance and bleeding suggests that bleeding in ALF relates more to systemic inflammation than a primary coagulopathy.
Hesperetin ameliorates lipopolysaccharide‐induced acute lung injury via the miR‐410/SOX18 axis
Authors: Dong Junying , Zhou Haiyan , Zhao Hongqin , Zhao Yanhong , Chang Can 
Published: August 2020

AbstractHesperetin (Hesp), a dihydroflavone, has a wide range of pharmacological activities, including antioxidant, anti‐inflammatory, and antitumor effects, as well as cardiovascular protection. It also has protective effects against acute lung injury (ALI); however, the exact mechanism remains unclear. In the present study, the protective effects and mechanism of Hesp in the lungs were investigated. Hematoxylin and eosin staining was used to examine pathological changes in the lungs. Enzyme‐linked immunosorbent assay was used to detect proinflammatory cytokine levels. In addition, reverse transcription‐quantitative polymerase chain reaction and Western blot analysis were used to observe the transcription and translation changes in the related genes, respectively. The results indicate that Hesp not only improves histopathological changes in the lungs but decreases the wet/dry ratio. In addition, total cell counts and the number of neutrophils and macrophages were lower in the bronchoalveolar fluid after Hesp treatment, consistent with the change in proinflammatory cytokine levels. MicroRNA‐410 (miR‐410) levels were significantly lower in the lung tissues of ALI mice and were reversed after Hesp treatment. Furthermore, miR‐410 overexpression due to injection with agomiR‐410 produced similar protective effects as Hesp. However, blocking miR‐410 inhibited the protective effects of Hesp in the lungs of ALI mice. In addition, miR‐410 has been shown to target the inhibition of sex determining region Y‐box 18 (SOX18), indicating that Hesp might alleviate inflammatory secretion by blocking the miR‐410/SOX18 axis. Thus, Hesp might be a potential agent for the treatment of ALI.
RAS mutation leading to acquired resistance to dabrafenib and trametinib therapy in a multiple myeloma patient harboring BRAF mutation
Authors: Le Calvez Baptiste , Le Bris Yannick , Herbreteau Guillaume , Jamet Bastien , Bossard Céline , Tessoulin Benoit , Gastinne Thomas , Mahé Béatrice , Dubruille Viviane , Blin Nicolas , Antier Chloé , Theisen Olivier , Kraeber‐Bodéré Françoise , Le Gouill Steven , Béné Marie C. , Moreau Philippe , Touzeau Cyrille 
Published: August 2020

AbstractMultiple myeloma (MM) is still considered incurable and new therapeutic approaches are therefore needed. Deep‐sequencing analysis revealed the presence of BRAF mutations in up to 15% of patients. The clinical experience of BRAF‐targeted therapy in myeloma patients harboring BRAF mutation is still limited. We here report the case of a patient with penta‐refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab) MM with extramedullary BRAF‐mutated disease that achieved clinical response to dual BRAF and MEK inhibition. At the time of disease progression, gene sequencing analysis of the tumor at the time of progression demonstrated a clonal evolution with emergence of a NRAS mutation and persistence of BRAF and TP53 mutations. Backtracking of the NRAS mutation was performed by digital polymerase chain reaction on the baseline biopsy and identified the pre‐existence of the NRAS at a subclonal level. This observation is the first report of acquired NRAS mutation leading to resistance to dual BRAF/MEK inhibitors in MM. These data suggest that a systematic search for RAS mutations using highly sensitive techniques should be performed before considering targeted therapy in relapsed myeloma with BRAF mutation.
Sex and mechanism of injury influence knee joint loading symmetry during gait 6 months after ACLR
Authors: Ito Naoaki , Capin Jacob J. , Arhos Elanna K. , Khandha Ashutosh , Buchanan Thomas S. , Snyder‐Mackler Lynn 
Published: August 2020

AbstractEarly‐onset knee osteoarthritis (OA) is associated with gait asymmetries after anterior cruciate ligament reconstruction (ACLR). Women have higher risks of sustaining non‐contact injuries, and are more likely to present with aberrant movement patterns associated with the mechanism of injury (MOI). We hypothesized that sex and MOI would influence gait after ACLR. Seventy participants, grouped by sex and MOI, completed biomechanical testing during over‐ground walking when they had full knee range of motion, trace or less knee effusion, greater than 80% quadriceps strength limb symmetry index, ability to hop on each leg without pain, and initiated running. Bilateral knee kinetics, kinematics, and joint contact forces were compared using mixed‐model analysis of variance (α = .05). There was a three‐way interaction effect of sex × MOI × limb for peak medial compartment contact force (P = .002), our primary outcome measure previously associated with OA development. Men with non‐contact injuries walked with asymmetry characterized by underloading of the involved limb. Men with contact injuries walked with the most symmetrical loading. In women, no clear pattern emerged based on MOI. Targeting, and possibly prioritizing interventions for athletes who present with gait asymmetries after ACLR based on sex and MOI, may be necessary to optimize outcomes. Statement of Clinical Significance: Sex and MOI may influence walking mechanics, and could be considered in future interventions to target gait symmetry, as a response to interventions may vary based on differences in sex and MOI.
Inter‐regional survey of the New Zealand Pinot noir fermentative sulfur compounds profile
Authors: Parish‐Virtue Katie , Pilkington Lisa I , Martin Damian , Wood Jacqueline , Fedrizzi Bruno 
Published: August 2020

AbstractBACKGROUNDNew Zealand Pinot noir is gaining increasing attention both in New Zealand and internationally, becoming the second largest grape variety for both plantings and export. Despite the growing furore around this variety, the current coverage of the volatile chemical profile remains limited, with a lack of information on the fermentative sulfur compounds content in New Zealand Pinot noir wines.RESULTSThirty‐five Pinot noir wines from three different vintages (i.e. 2016, 2017 and 2018) form five different grape growing regions were analysed for their fermentative sulfur compounds contents. Six fermentative sulfur compounds (i.e. methanethiol, ethanethiol, dimethyl sulfide, carbon disulfide, methionol and benzothiazol) were detected and measured for the first time in New Zealand Pinot noir wines. Their concentrations were compared against previously measured Pinot noir wines from other countries, and some preliminary evidence about inter‐regional and ageing effects was obtained.CONCLUSIONThe present study reports the first survey of the inter‐regional differences in fermentative sulfur compounds contents in 35 New Zealand Pinot noir wines. Preliminary inter‐regional and vintage trends prompt further research on the role of these molecules on this wine variety. © 2020 Society of Chemical Industry
Purification and antioxidant and anti‐Inflammatory activity of extracellular polysaccharopeptide from sanghuang mushroom, Sanghuangporus lonicericola
Authors: Zuo Kang , Tang Kaijing , Liang Yue , Xu Yifan , Sheng Kangliang , Kong Xiaowei , Wang Jingmin , Zhu Fenfang , Zha Xiangdong , Wang Yongzhong 
Published: August 2020

AbstractBACKGROUNDSanghuang mushrooms are medicinal fungi widely used in eastern Asia. In this study, the antioxidant and anti‐inflammatory activity of a novel extracellular polysaccharopeptide, sanghuang extracellular polysaccharopeptide (SePSP) was investigated. The SePSP was purified from the submerged fermentation broth of a sanghuang mycelium, Sanghuangporus lonicericola strain CBS17, which was isolated from a wild sanghuang fruiting body.RESULTSThe SePSP was extracted using an ethanol precipitation procedure, followed by diethylaminoethanol (DEAE) anion‐exchange and size‐exclusion chromatography. The mass ratio of the polysaccharide and peptide components in the purified SePSP was approximately 4.87:1. By determining its free radical scavenging abilities using 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), the hydroxyl free radical, and the superoxide anion free radical, as well as its total reducing power, SePSP was shown to have strong concentration‐dependent antioxidant activity in vitro. Further, SePSP effectively alleviated dextran sodium sulfate (DSS)‐induced ulcerative colitis (UC) in mice. Administration of 200 mg kg−1 SePSP by gavage for 7 days prevented body weight loss; significantly reduced the mRNA levels of proinflammatory cytokines, including TNF‐α and IL‐1β; increased mRNA level of the anti‐inflammatory cytokine IL‐10 in the colon, and decreased the malondialdehyde concentration from 6.42 to 4.82 μmol L−1 in the blood in UC mice.CONCLUSIONThe SePSP had strong concentration‐dependent antioxidant activity in vitro and effectively alleviated DSS‐induced UC in mice. The in vivo therapeutic efficacy in DSS‐induced UC may be mediated by modulating the expression of inflammatory cytokines and inhibiting oxidative stress. The findings provide a scientific rationale for the use of bioactive nutraceuticals from sanghuang mushrooms to develop functional foods for the prevention and treatment of UC. © 2020 Society of Chemical Industry
Identification of a novel pathogenic variant in the MYH3 gene in a five‐generation family with CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A)
Authors: Zhang Jing , Chen Wen‐Qi , Wang Si‐Wen , Wang Shao‐Xiong , Yu Mei , Guo Qing , Yu Ya‐Dong 
Published: August 2020

AbstractBackgroundDistal arthrogryposis (DA) is a group of rare Mendelian conditions that demonstrate heterogeneity with respect to genetics and phenotypes. Ten types of DAs, which collectively involve six genes, have been reported. Among them, the MYH3 gene causes several types of arthrogryposis conditions and therefore has a pivotal role in the skeletal and muscle development of the fetus. For this study, we recruited a five‐generation Chinese family with members presenting DA features and phenotypic variability. Further clinical study characterized it as CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A).MethodsGenomic DNA was extracted from eight family members, including one fetus. Whole‐exome sequencing (WES) was then conducted on the proband's sample, followed by Sanger sequencing as validation for each of the participants. In silico analysis was performed. Western blotting (WB) detection and pathological staining were conducted on skeletal muscle tissue of the induced fetus after prenatal diagnosis.ResultsA novel heterozygous pathogenic variant, namely NM_002470.3: c.3044_3047delinsTCAATTTGTT: p.E1015_D1016delinsVNLF in the MYH3 gene, was identified and shown to be cosegregated with the condition in the subject family. This variant resulted in the replacement of amino‐acid residues E1015 and D1016 by a string of VNLFs. The pregnancy was selectively terminated because the fetus was genetically affected. However, the WB and pathological results did not indicate a significant change in the norm.ConclusionsOur study expanded the variant spectrum of CPSFS1A, in addition to which it provided solid evidence for the appropriateness of genetic counseling and pregnancy management for the family. The results may also provide further insight into the molecular mechanism of MYH3.