bluuebunny/crossref_metadata_2025_split huggingface dataset:
widgetcon: A website and program for quick conversion among common population genetic data formats
Authors: Aydın Mahmut , Kryvoruchko Igor S. , Şakiroğlu Muhammet 
Published: June 2019

AbstractOne of the most tedious steps in genetic data analyses is the reformatting data generated with one program for use with other applications. This conversion is necessary because comprehensive evaluation of the data may be based on different algorithms included in diverse software, each requiring a distinct input format. A platform‐independent and freely available program or a web‐based tool dedicated to such reformatting can save time and efforts in data processing. Here, we report widgetcon, a website and a program which has been developed to quickly and easily convert among various molecular data formats commonly used in phylogenetic analysis, population genetics, and other fields. The web‐based service is available at https://www.widgetcon.net. The program and the website convert the major data formats in four basic steps in less than a minute. The resource will be a useful tool for the research community and can be updated to include more formats and features in the future.
Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?
Authors: Castan Laure , Bøgh Katrine L. , Maryniak Natalia Z. , Epstein Michelle M. , Kazemi Sahar , O'Mahony Liam , Bodinier Marie , Smit Joost J. , van Bilsen Jolanda H. M. , Blanchard Carine , Głogowski Robert , Kozáková Hana , Schwarzer Martin , Noti Mario , de Wit Nicole , Bouchaud Grégory , Bastiaan‐Net Shanna 
Published: June 2019

AbstractSignificant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory‐to‐laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.
Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation
Authors: Krause Bernardo J. , Peñaloza Estefanía , Candia Alejandro , Cañas Daniel , Hernández Cherie , Arenas German A. , Peralta‐Scholz María José , Valenzuela Rodrigo , García‐Herrera Claudio , Herrera Emilio A. 
Published: June 2019

AbstractAimFoetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies.MethodsFemoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively.ResultsFGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO‐mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial‐NOS mRNA levels were decreased in FGR adult compared with control and FGR‐NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea‐pigs (P < .05).ConclusionAltogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.
Emerging roles of striatal dopamine D2 receptors in motivated behaviour: Implications for psychiatric disorders
Authors: Olivetti Pedro R. , Balsam Peter D. , Simpson Eleanor H. , Kellendonk Christoph 
Published: June 2019

AbstractImpaired motivation has been a long recognized negative symptom of schizophrenia, as well as a common feature of non‐psychotic psychiatric disorders, responsible for a significant share of functional burden, and with limited treatment options. The striatum and dopamine signalling system play a central role in extracting motivationally relevant information from the environment, selecting which behavioural direction the animal should follow, and the vigour with which to engage it. Much of this function relies on striatal projection neurons, known as medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs), or D2‐MSNs. However, determining the precise nature of D2‐MSNs in regulating motivated behaviour in both healthy individuals and experimental manipulations of D2‐MSN function has at times yielded a somewhat confusing picture since their activity has been linked to either enhancement or dampening of motivation in animal models. In this MiniReview, we describe the latest data from rodent studies that investigated how D2Rs exert their modulatory effect on motivated behaviour by regulating striatal indirect pathway neuronal activity. We will include a discussion about how functional selectivity of D2Rs towards G protein–dependent or β‐arrestin–dependent signalling differentially affects motivated behaviour. Lastly, we will describe a recent preclinical attempt to improve motivation by exploiting serotonin receptor–mediated modulation of dopamine transmission in the striatum.
Tweeting and Retweeting for Fight for $15: Unions as Dinosaur Opinion Leaders?
Authors: Frangi Lorenzo , Zhang Tingting , Hebdon Robert 
Published: June 2019

AbstractAdvocacy campaigns are central to unions’ efforts to impact labour rights beyond unionized workplaces. Social media and on‐the‐ground campaign dynamics are intimately related. Thus, if unions can become leaders on social media, they could have more impact on campaign framing and mobilizing. Drawing on primary data and applying a sequential mixed method, we analyse unions’ ability to emerge as opinion leaders in Twitter dialogues on the Fight for $15 (FF$15) campaign. We track FF$15‐related activities of Twitter profiles over seven months and compare union actions to those of others along three dimensions: level of activity, prevalence of tweeting versus retweeting and endorsement within FF$15 community and in the Twitter universe. Regression results show unions prefer advancing their own ideas over supporting those of others, and their messages are more endorsed than others’ messages in the Twitter universe. In‐depth interviews and a focus group reveal that while their actions are slow and conservative, unions can count on internal support and institutional reputation to gain leadership. The article concludes by noting the implications of the findings for unions’ strategies to become opinion leaders on social media.
The response of five intestinal cell lines to anoxic conditions in vitro
Authors: Vissenaekens Hanne , Grootaert Charlotte , Rajkovic Andreja , Van De Wiele Tom , Calatayud Marta 
Published: June 2019

Background informationIn vivo oxygen levels in tissues range from 1% to 15%, while mechanistic cell culture studies employ an atmospheric oxygen level of 21% to grow cells. These oxygen concentrations are therefore not representative for conditions where the cell response is dependent on oxygen partial pressure. In pathological situation, such as (colon) cancer or chronic inflammation, tissue oxygenation is severely affected, and even under physiological conditions a steep oxygen gradient is present in the large intestine, where epithelial cells co‐exist with microbial species, resulting in almost anoxia at the midpoint of the lumen. In these situations, a better characterisation of the essential cellular behaviour under hypoxia or anoxia is required.ResultsWe have characterised the cellular response of commonly used cell cultures for the study of intestinal epithelial processes and colon cancer development (Caco‐2, HT‐29, SW480, HCT 116 and LoVo) under conventional normoxic conditions (21% O2) and in an anoxic (<0.1% O2) environment generated in an anaerobic chamber. In general, anoxic conditions led to lower levels of oxidative stress, a reduction in reduced glutathione/oxidised glutathione (GSH/GSSG) ratio, the shift of the redox status to oxidised glutathione levels, reduced cell proliferation, decreased barrier function and higher glycolysis rates at the expense of oxidative respiration.ConclusionsContinuous exposure to anoxic conditions, such as occurring at the host–microbe interface in the intestine, may create an adaptive metabolic cellular response of the cells.SignificanceConsidering adequate oxygen levels is essential for creating more physiologically relevant models for the study of host–microbe interactions and colon cancer development.
Significant epitranscriptomes in heterogeneous cancer
Authors: Konno Masamitsu , Taniguchi Masateru , Ishii Hideshi 
Published: June 2019

AbstractPrecision medicine places significant emphasis on techniques for the identification of DNA mutations and gene expression by deep sequencing of gene panels to obtain medical data. However, other diverse information that is not easily readable using bioinformatics, including RNA modifications, has emerged as a novel diagnostic and innovative therapy owing to its multifunctional aspects. It is suggested that this breakthrough innovation might open new avenues for the elucidation of uncharacterized cancer cellular functions to develop more precise medical applications. The functional characteristics and regulatory mechanisms of RNA modifications, ie, the epitranscriptome (ETR), which reflects RNA metabolism, remains unclear, mainly due to detection methods being limited. Recent studies have revealed that N6‐methyl adenosine, the most common modification in mRNA in eukaryotes, is affected in various types of cancer and, in some cases, cancer stem cells, but also affects cellular responses to viral infections. The ETR can control cancer cell fate through mRNA splicing, stability, nuclear export, and translation. Here we report on the recent progress of ETR detection methods, and biological findings regarding the significance of ETR in cancer precision medicine.
Adding sorbitan sesquioleate to the European baseline series: Necessary, reasonable, or unavoidable?
Authors: de Groot Anton , Gilissen Liesbeth , Geier Johannes , Orton David , Goossens An 
Published: June 2019

AbstractPositive reactions to fragrance mix I (FM I) are frequent in consecutively patch tested patients suspected of having allergic contact dermatitis. However, the FM I test preparations contain 5% of the emulsifier sorbitan sesquioleate (SSO), and it is well known that SSO can cause contact allergic reactions in its own right. Indeed, the available data show that some patients with contact allergy to SSO react to FM I but are not allergic to fragrances. When SSO is not tested, this situation may go unnoticed, a wrong diagnosis of fragrance allergy may be given to the patient, and unjustified advice to avoid fragrances and fragranced products will be given in such cases. To avoid such suboptimal patient care, we postulate that testing with SSO in all patch tested individuals is mandatory. As it is well known that only a minority of FM I‐reactive patients will undergo a breakdown test with the ingredients and SSO, testing with SSO in all patients can only be achieved by adding it to the European baseline series. Not testing with SSO may also result in misinterpretation of patch test reactions to Myroxylon pereirae resin and 2‐hydroxyethyl methacrylate in the baseline series, as both (may) contain SSO, and, for the same reason, of reactions to several other hapten test materials.
Amlodipine and calcineurin inhibitor‐induced nephrotoxicity following allogeneic hematopoietic stem cell transplant
Authors: Jensen Ryan R. , Healy Regan M. , Ford Clyde D. , Child Berrie , Majers Jacob , Draper Brent , Hasan Yousef , Hoda Daanish 
Published: June 2019

AbstractStudies in the renal transplant population have suggested calcium‐channel blockers (CCBs) may protect against calcineurin inhibitor (CNI)‐induced nephrotoxicity. However, this has not been evaluated in the hematopoietic stem cell transplant (HSCT) population. This retrospective study reviews data from 350 consecutive patients who underwent allogeneic HSCT to determine whether amlodipine improved renal outcomes. Subject data included up to one year from CNI initiation. Patients in the amlodipine group (n = 130) received an average of 143 days treatment with amlodipine and experienced a smaller decrease in creatinine clearance (CrCl) through day 180. At day 30, change in CrCl was −17.4 mL/min in the amlodipine cohort and −33.8 mL/min in the control (P < 0.001). At day 180, change in CrCl was −40.9 and −50.6 mL/min, respectively (P = 0.005). Incidence of hospitalization with acute kidney injury (AKI) was significantly lower in patients receiving amlodipine, 7.7% (10/132) vs 16.4% (36/220) (hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.22‐0.89). Median blood pressure in the amlodipine group remained <132/78 through day 360. Our data support the use of amlodipine for hypertension in the allogeneic HSCT population and provide evidence suggesting that CCBs protect against CNI‐induced nephrotoxicity.
Evaluation and diagnosis of the traumatized dentition
Authors: Myers Garry L. 
Published: June 2019

AbstractTraumatic dental injuries comprise a number of the dental emergency patients who are often seen after hours or on an unscheduled basis in a dental practice environment. Although there are a variety of traumatic dental injuries that can occur, each with their own recommended treatment protocols, the initial evaluation and diagnosis of the traumatized dentition make up a critical aspect of the management of these cases. This article will highlight the key components of a thorough and efficient examination process of the traumatized dentition to include (a) documenting an accurate history of the events causing the injury, (b) performing a systematic clinical examination to include the use of clinical photographs and pulp sensibility tests, (c) obtaining appropriate radiographic images and scans, (d) understanding some considerations unique to evaluating young patients with traumatic injuries, and (e) recognizing the importance of having accurate and thorough documentation of these types of cases. Once the evaluation and diagnosis phase has been completed, the necessary treatment protocols can be initiated in an appropriate manner.
Implementation of an NGS‐based sequencing and gene fusion panel for clinical screening of patients with suspected hematologic malignancies
Authors: Levy Michael A. , Santos Stephanie , Kerkhof Jennifer , Stuart Alan , Aref‐Eshghi Erfan , Guo Fen , Hedley Ben , Wong Henry , Rauh Michael , Feilotter Harriet , Berardi Philip , Semenuk Laura , Yang Ping , Knoll Joan , Ainsworth Peter , McLachlin Catherine Meg , Chin‐Yee Ian , Kovacs Michael , Deotare Uday , Lazo‐Langner Alejandro , Hsia Cyrus , Keeney Mike , Xenocostas Anargyros , Howlett Christopher , Lin Hanxin , Sadikovic Bekim 
Published: June 2019

AbstractObjectivesThe diagnosis of hematologic malignancies integrates multiple diagnostic and clinical disciplines. Historically, targeted (single‐analyte) genetic testing has been used as reflex to initial prescreening by other diagnostic modalities including flow cytometry, anatomic pathology, and clinical cytogenetics. Given the wide range of mutations associated with hematologic malignancies a DNA/RNA‐based NGS panel can provide a more effective and economical approach to comprehensive testing of patients as an initial, tier‐1 screen.MethodsUsing a cohort of 380 patients, we performed clinical validation of a gene panel designed to assess 40 genes (DNA), and 29 fusion driver genes with over 600 gene fusion partners (RNA), including sample exchange data across three clinical laboratories, and correlation with cytogenetic testing results.ResultsThe clinical validation of this technology demonstrated that its accuracy, sensitivity, and specificity are comparable to the majority of targeted single‐gene approaches, while assessment of the initial patient cohort data demonstrated a high diagnostic yield of 50.5%.ConclusionsImplementation of a tier‐1 NGS‐based protocol for gene panel screening provides a comprehensive alternative to targeted molecular testing in patients with suspected hematologic malignancies, with increased diagnostic yield, scalability, reproducibility, and cost effectiveness, making it ideally suited for implementation in clinical laboratories.
Semi‐rational evolution of the 3‐(3‐hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA to improve rhamnolipid production in Pseudomonas aeruginosa and Burkholderia glumae
Authors: Dulcey Carlos Eduardo , López de los Santos Yossef , Létourneau Myriam , Déziel Eric , Doucet Nicolas 
Published: June 2019

The 3‐(3‐hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA is an essential enzyme involved in the biosynthesis of HAAs in Pseudomonas and Burkholderia species. RhlA modulates the aliphatic chain length in rhamnolipids, conferring distinct physicochemical properties to these biosurfactants exhibiting promising industrial and pharmaceutical value. A detailed molecular understanding of substrate specificity and catalytic performance in RhlA could offer protein engineering tools to develop designer variants involved in the synthesis of novel rhamnolipid mixtures for tailored eco‐friendly products. However, current directed evolution progress remains limited due to the absence of high‐throughput screening methodologies and lack of an experimentally resolved RhlA structure. In the present work, we used comparative modeling and chimeric‐based approaches to perform a comprehensive semi‐rational mutagenesis of RhlA from Pseudomonas aeruginosa. Our extensive RhlA mutational variants and chimeric hybrids between the Pseudomonas and Burkholderia homologs illustrate selective modulation of rhamnolipid alkyl chain length in both Pseudomonas aeruginosa and Burkholderia glumae. Our results also demonstrate the implication of a putative cap‐domain motif that covers the catalytic site of the enzyme and provides substrate specificity to RhlA. This semi‐rational mutant‐based survey reveals promising ‘hot‐spots’ for the modulation of RL congener patterns and potential control of enzyme activity, in addition to uncovering residue positions that modulate substrate selectivity between the Pseudomonas and Burkholderia functional homologs.DatabaseModel data are available in the PMDB database under the accession number PM0081867.
Combined effect of a farnesoid X receptor agonist and dipeptidyl peptidase‐4 inhibitor on hepatic fibrosis
Authors: Shimozato Naotaka , Namisaki Tadashi , Kaji Kosuke , Kitade Mitsuteru , Okura Yasushi , Sato Shinya , Moriya Kei , Seki Kenichiro , Kawaratani Hideto , Takaya Hiroaki , Sawada Yasuhiko , Saikawa Soichiro , Nakanishi Keisuke , Furukawa Masanori , Fujinaga Yukihisa , Kubo Takuya , Asada Kiyoshi , Kitagawa Koh , Tsuji Yuki , Kaya Daisuke , Ozutsumi Takahiro , Akahane Takemi , Mitoro Akira , Yoshiji Hitoshi 
Published: June 2019

AimNon‐alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase‐4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH.MethodsFifty Fischer 344 rats were fed a choline‐deficient L‐amino‐acid‐defined (CDAA) diet for 12 weeks. The in vitro and in vivo effects of OCA + sitagliptin were assessed along with hepatic fibrogenesis, lipopolysaccharide–Toll‐like receptor 4 (TLR4) regulatory cascade and intestinal barrier function. Direct inhibitory effects of OCA + sitagliptin on activated hepatic stellate cells (Ac‐HSCs) were assessed in vitro.ResultsTreatment with OCA + sitagliptin potentially inhibited hepatic fibrogenesis along with Ac‐HSC proliferation and hepatic transforming growth factor (TGF)‐β1, α1(I)‐procollagen, and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) mRNA expression and hydroxyproline levels. Obeticholic acid inhibited hepatic TLR4 expression and increased hepatic matrix metalloproteinase‐2 expression. Obeticholic acid decreased intestinal permeability by ameliorating CDAA diet‐induced zonula occludens‐1 disruption, whereas sitagliptin directly inhibited Ac‐HSC proliferation. The in vitro suppressive effects of OCA + sitagliptin on TGF‐β1 and α1(I)‐procollagen mRNA expression and p38 phosphorylation in Ac‐HSCs were almost consistent. Sitagliptin directly inhibited the regulation of Ac‐HSC.ConclusionsTreatment with OCA + sitagliptin synergistically affected hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing Ac‐HSC proliferation. Thus, OCA + sitagliptin could be a promising therapeutic strategy for NASH.