bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schwann cells as underestimated, major players in human skin physiology and pathology
Authors: Bray Eric R. , Chéret Jérémy , Yosipovitch Gil , Paus Ralf 
Published: November 2019

AbstractSchwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor‐like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial‐to‐mesenchymal‐like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.
Identifying pseudoenzymes using functional annotation: pitfalls of common practice
Authors: Ribeiro Antonio J. M. , Tyzack Jonathan D. , Borkakoti Neera , Thornton Janet M. 
Published: November 2019

Pseudoenzymes are proteins that are evolutionary related to enzymes but lack relevant catalytic activity. They are usually evolved from enzymatic ancestors that have lost their catalytic activities. The loss of catalytic function is one extreme amongst the other evolutionary changes that can occur to enzymes, like the changing of substrate specificity or the reaction catalysed. However, the loss of catalytic function events remain poorly characterised, except for some notable examples, like the pseudokinases. In this review, we aim to analyse current knowledge related to pseudoenzymes across a large number of enzymes families. This aims to be a review of the data available in biological databases, rather than a more traditional literature review. In particular, we use UniProtKB as the source for functional annotation and M‐CSA (Mechanism and Catalytic Site Atlas) for information on the catalytic residues of enzymes. We show that explicit annotation of lack of activity is not exhaustive in UniProtKB and that a protocol using lack of catalytic annotation as an indication for lack of function can be an adequate alternative, after some corrections. After identifying pseudoenzymes related to enzymes in M‐CSA, we were able to comment on their prevalence across enzyme families, and on the correlation between lack of catalytic function and the mutation of catalytic residues. These analyses challenge two common ideas in the emerging literature: that pseudoenzymes are ubiquitous across enzyme families and that mutations in the catalytic residues of enzyme homologues are always a good indication of lack of activity.
Fatigue crack growth analysis of different adhesive systems: Effects of mode mixity and load level
Authors: Rocha Ana V.M. , Akhavan‐Safar Alireza , Carbas Ricardo , Marques Eduardo A.S. , Goyal Rakesh , El‐zein Mohamad , da Silva Lucas F.M. 
Published: November 2019

AbstractThe aim of this paper is to investigate the fatigue fracture behavior of three different adhesive systems (epoxy‐based, acrylic, and a rubber‐like adhesive). To achieve this, double cantilever beam specimens were manufactured with different adhesives and tested under several mode mixities and different load levels. Fatigue crack growth rate was evaluated through a Paris law equation. For postprocessing, the compliance‐based beam method was used. Results showed that the variation of the threshold energy with load level is more pronounced for the epoxy‐based adhesive. The crack propagation life is higher for the acrylic adhesive. Although, for pure mode I conditions, the normalized threshold of the rubber‐like adhesive is lower, for pure mode II, it was higher than the epoxy‐based adhesive. Due to the normalization by the static fracture energy, the slope of the Paris law was approximately constant for all the adhesive systems.
Dynamic splitting tensile properties of concrete and cement mortar
Authors: Liu Pengfei , Zhou Xiaoping , Qian Qihu , Berto Filippo , Zhou Lunshi 
Published: November 2019

AbstractTo investigate the dynamic tensile behaviours of concrete and cement mortar, a 50‐mm split Hopkinson pressure bar was applied on Brazilian disc specimens for dynamic tensile experiments, in which strain rate varied from 10−5 to 20 s−1. The high‐speed camera testing technique was used to capture the dynamic fractured process of the specimens at relative high strain rate. The experimental results revealed that the dynamic tensile strength of concrete specimens has a stronger strain rate effect than that of cement mortar specimens. Then three typical failure patterns of the specimens were confirmed in dynamic experiments. In addition, one‐parameter semi‐empirical relation between dynamic tensile strength and strain rate was established. Finally, the limitation of dynamic splitting experiments on Brazilian disc specimens was discussed in detail at high strain rate, in which the crack initiates from the contact point between the incident bar and specimens rather than the centre of the specimens.
Megacity development and the demise of coastal coral communities: Evidence from coral skeleton δ15N records in the Pearl River estuary
Authors: Duprey Nicolas N. , Wang Tony X. , Kim Taihun , Cybulski Jonathan D. , Vonhof Hubert B. , Crutzen Paul J. , Haug Gerald H. , Sigman Daniel M. , Martínez‐García Alfredo , Baker David M. 
Published: November 2019

AbstractHistorical coral skeleton (CS) δ18O and δ15N records were produced from samples recovered from sedimentary deposits, held in natural history museum collections, and cored into modern coral heads. These records were used to assess the influence of global warming and regional eutrophication, respectively, on the decline of coastal coral communities following the development of the Pearl River Delta (PRD) megacity, China. We find that, until 2007, ocean warming was not a major threat to coral communities in the Pearl River estuary; instead, nitrogen (N) inputs dominated impacts. The high but stable CS‐δ15N values (9‰–12‰ vs. air) observed from the mid‐Holocene until 1980 indicate that soil and stream denitrification reduced and modulated the hydrologic inputs of N, blunting the rise in coastal N sources during the early phase of the Pearl River estuary urbanization. However, an unprecedented CS‐δ15N peak was observed from 1987 to 1993 (>13‰ vs. air), concomitant to an increase of NH4+ concentration, consistent with the rapid Pearl River estuary urbanization as the main cause for this eutrophication event. We suggest that widespread discharge of domestic sewage entered directly into the estuary, preventing removal by natural denitrification hotspots. We argue that this event caused the dramatic decline of the Pearl River estuary coral communities reported from 1980 to 2000. Subsequently, the coral record shows that the implementation of improved wastewater management policies succeeded in bringing down both CS‐δ15N and NH4+ concentrations in the early 2000s. This study points to the potential importance of eutrophication over ocean warming in coral decline along urbanized coastlines and in particular in the vicinity of megacities.
Thresholds of fire response to moisture and fuel load differ between tropical savannas and grasslands across continents
Authors: Alvarado Swanni T. , Andela Niels , Silva Thiago S. F. , Archibald Sally 
Published: November 2019

AbstractAimAn emerging framework for tropical ecosystems states that fire activity is either “fuel build‐up limited” or “fuel moisture limited”, that is, as you move up along rainfall gradients, the major control on fire occurrence switches from being the amount of fuel, to the moisture content of the fuel. Here we used remotely sensed datasets to assess whether interannual variability of burned area is better explained by annual rainfall totals driving fuel build‐up, or by dry season rainfall driving fuel moisture.LocationPantropical savannas and grasslands.Time period2002–2016.MethodsWe explored the response of annual burned area to interannual variability in rainfall. We compared several linear models to understand how fuel moisture and fuel build‐up effect (accumulated rainfall during 6 and 24 months prior to the end of the burning season, respectively) determine the interannual variability of burned area and explore if tree cover, dry season duration and human activity modified these relationships.ResultsFuel and moisture controls on fire occurrence in tropical savannas varied across continents. Only 24% of South American savannas were fuel build‐up limited against 61% of Australian savannas and 47% of African savannas. On average, South America switched from fuel limited to moisture limited at 500 mm/year, Africa at 800 mm/year and Australia at 1,000 mm/year of mean annual rainfall.Main conclusionsIn 42% of tropical savannas (accounting for 41% of current area burned) increased drought and higher temperatures will not increase fire, but there are savannas, particularly in South America, that are likely to become more flammable with increasing temperatures. These findings highlight that we cannot transfer knowledge of fire responses to global change across ecosystems/regions—local solutions to local fire management issues are required, and different tropical savanna regions may show contrasting responses to the same drivers of global change.
Development of INSOL‐tag for proteome‐wide protein handling and its application in protein array analysis
Authors: Fukuda Eriko , Mori Masatoshi , Shiku Hiroshi , Miyahara Yoshihiro , Kawamura Yoshifumi , Ogawa Koji , Ogura Toshihiko , Goshima Naoki 
Published: November 2019

AbstractProteomic analysis requires protein tags that enable high‐throughput handling; however, versatile tags that can be used in in vitro expression systems are currently lacking. In this study, we developed an insoluble protein tag, INSOL‐tag, derived from human transcription factor MafG. The INSOL‐tagged target protein is expressed in a eukaryotic in vitro expression system and recovered as a pellet following centrifugation at 19,000 × g for 20 min. Comparisons of the target protein recovery rates of GST‐tag and INSOL‐tag using 111 cytoplasmic proteins revealed a fourfold increase in the yield of INSOL‐tagged proteins. Using 267 cancer antigens purified with INSOL‐tag, we subsequently developed an INSOL‐CTA array method, for profiling autoantibodies in sera of cancer patients. The detection limit of the array was approximately 11.1 pg IgG, and the correlation with ELISA was high (R2 = .993, .955). Moreover, when autoantibody profiling of digestive cancer patient sera was performed, antigen spreading was observed. These data suggest that INSOL‐tag is a versatile tag that can insolubilize a wide range of target proteins. It is therefore expected to become a powerful tool in comprehensive protein preparation for protein arrays, antibody production, and mass spectrometry.
Characterization of genetic‐origin‐dependent monoallelic expression in mouse embryonic stem cells
Authors: Ohishi Hiroaki , Au Yeung Wan Kin , Unoki Motoko , Ichiyanagi Kenji , Fukuda Kei , Maenohara Shoji , Shirane Kenjiro , Chiba Hatsune , Sado Takashi , Sasaki Hiroyuki 
Published: November 2019

AbstractMonoallelic gene expression occurs in various mammalian cells and can be regulated genetically, epigenetically and/or stochastically. We identified 145 monoallelically expressed genes (MoEGs), including seven known imprinted genes, in mouse embryonic stem cells (ESCs) derived from reciprocal F1 hybrid blastocysts and cultured in 2i/LIF. As all MoEGs except for the imprinted genes were expressed in a genetic‐origin‐dependent manner, we focused on this class of MoEGs for mechanistic studies. We showed that a majority of the genetic‐origin‐dependent MoEGs identified in 2i/LIF ESCs remain monoallelically expressed in serum/LIF ESCs, but become more relaxed or even biallelically expressed upon differentiation. These MoEGs and their regulatory regions were highly enriched for single nucleotide polymorphisms. In addition, some MoEGs were associated with retrotransposon insertions/deletions, consistent with the fact that certain retrotransposons act as regulatory elements in pluripotent stem cells. Interestingly, most MoEGs showed allelic differences in enrichment of histone H3K27me and H3K4me marks, linking allelic epigenetic differences and monoallelic expression. In contrast, there was little or no allelic difference in CpG methylation or H3K9me. Taken together, our study highlights the impact of genetic variation including single nucleotide polymorphisms and retrotransposon insertions/deletions on monoallelic epigenetic marks and expression in ESCs.
Distinctive clinicopathological features and KRAS and IDH1/2 mutation status of cholangiolocellular carcinoma
Authors: Kusano Hironori , Naito Yoshiki , Mihara Yutaro , Kondo Reiichiro , Ogasawara Sachiko , Akiba Jun , Nakashima Osamu , Yano Hirohisa 
Published: November 2019

AimCholangiolocellular carcinoma (CLC) is classified as a subtype of combined hepatocellular cholangiocarcinoma with stem‐cell features (CHC‐SC) in the latest World Health Organization classification. This subclassification of CHC‐SCs is controversial and the relevance of such classification is unclear.MethodsWe analyzed a series of CHC‐SCs and intrahepatic cholangiocarcinoma (iCCA) to clarify the clinicopathological features and mutational status of each tumor.ResultsBackground liver disease, fibrosis stage, microvascular invasion, nodal metastasis, and IDH1/2 mutation status were associated with their histology. Compared with the intermediate cell subtype of CHC‐SC (CHCs‐SC‐int), CLCs were less frequently associated with chronic viral hepatitis, and showed lower levels of serum alpha‐fetoprotein. Compared with iCCAs, CLCs showed lower levels of serum carbohydrate antigen 19‐9 (CA19‐9) and a lower frequency of expression of S100P. Patients with iCCA showed worse overall survival than those with CLC or CHC‐SC‐int. In patients with iCCA, CLC, or CHC‐SC‐int, a histology of iCCA, microvascular invasion, and serum CA19‐9 value of >100 U/mL were significant poor prognostic factors for overall survival in univariate analysis. Multivariate analysis showed that a high serum CA19‐9 value was an independent poor prognostic factor for overall survival.ConclusionsPatients with CLC are likely to have a different etiology and mutational background from those with CHC‐SC‐int. Their clinicopathological manifestations are also different from those with classic iCCA. Our results suggest that CLC might be a distinct entity among primary liver carcinomas.
Patients’ and providers’ perspectives on medication relatedness and potential preventability of hospital readmissions within 30 days of discharge
Authors: Uitvlugt Elien B. , Janssen Marjo J. A. , Siegert Carl E. H. , Leenders Anna J. A. , van den Bemt Bart J. F. , van den Bemt Patricia M. L. A. , Karapinar‐Çarkit Fatma 
Published: November 2019

AbstractBackgroundHospital readmissions are increasingly used as an indicator of quality in health care. One potential risk factor of readmissions is polypharmacy. No studies have explored the patients’ perspectives on the medication relatedness and potential preventability of their readmissions.ObjectiveTo compare the patients’ perspectives on the medication relatedness and potential preventability of their readmissions with the providers’ perspectives.MethodsPatients unplanned readmitted within 30 days after discharge at one of the participating departments of OLVG Hospital in Amsterdam were interviewed during their readmission. Patients’ perspectives regarding medication relatedness of their readmissions, the potential preventability, possible preventable interventions, and satisfaction with medication information were examined. Health‐care providers also reviewed files of these readmitted patients. Primary outcome was the percentage of medication‐related and potentially preventable readmissions according to the patient vs the provider. Descriptive data analysis was used.ResultsAccording to patients, 36 of 172 (21%) readmissions were medication‐related, and of these, 21 (58%) were potentially preventable. According to providers, 26 (15%) readmissions were medication‐related and 6 (23%) of these were potentially preventable. Patients and providers agreed on the medication relatedness in 11 of the 172 readmissions, and in two of these, agreement on the potential preventability existed. According to patients, preventive interventions belonged mostly to the hospital level, followed by the primary care level and patient level.ConclusionPatients and providers differ substantially on their perspectives regarding the medication relatedness and preventability of readmissions. Patients were more likely to view medication‐related readmissions as preventable.
Comparison of Lupinus angustifolius protein digestibility in dependence on protein, amino acids, trypsin inhibitors and polyphenolic compounds content
Authors: Zielińska‐Dawidziak Magdalena , Tomczak Aneta , Burzyńska Marta , Rokosik Ewa , Dwiecki Krzysztof , Piasecka‐Kwiatkowska Dorota 
Published: November 2019

SummaryLupine seeds are proposed as a source of valuable protein in human and animal nutrition. However, not only protein content but its bioavailability is important. Thus, the protein digestibility of twenty Lupinus angustifolius varieties seeds and the impact of some factors (protein and polyphenols content, trypsin inhibition and amino acids composition) on the protein digestion were discussed. Composition as well as the digestibility of these seeds was influenced by variety, weather conditions (precipitations) and place of cultivation (soil quality). The average digestibility of the seeds was 46%. The positive impact on the digestibility had the extractivity of the protein. Higher than it was expected activity of trypsin inhibitors (even up to ~32%) in some varieties influenced the protein availability, while the lysine and phenolic compounds content did not affect digestibility. The content of compounds influencing protein digestibility depends both on variety as well as on agronomical conditions.
Nondestructive determination of salmon fillet freshness during storage at different temperatures by electronic nose system combined with radial basis function neural networks
Authors: Jia Zhixin , Shi Ce , Wang Yanbo , Yang Xinting , Zhang Jiaran , Ji Zengtao 
Published: November 2019

SummaryThis study develops a predictive model for determining freshness of salmon fillets during cold storage at different temperatures using electronic nose combined with principal component analysis (PCA) and radial basis function neural networks (RBFNNs). The electronic nose sensed ammonia/amines, hydrocarbons, solvents and aromatics that increased during storage. The concentrations of the volatiles were compared with the increased thiobarbituric acid (TBA), total volatile basic nitrogen (TVB‐N), total aerobic bacteria count (TAC) and decreased of sensory assessments (SA). Gas chromatograph–ion mobility spectrometry analysis confirmed the changes in gas species. RBFNNs and PCA were used to establish predictive models and the relative errors of TBA, TVB‐N and TAC by the PCA‐RBFNNs model were all within ±10% and SA was within ±15%. These results suggest that the PCA‐RBFNNs model can be used to predict changes in the freshness of salmon fillets stored at −2 to 10 °C.
B‐cell memory in malaria: Myths and realities
Authors: Pérez‐Mazliah Damián , Ndungu Francis M. , Aye Racheal , Langhorne Jean 
Published: November 2019

SummaryB‐cell and antibody responses to Plasmodium spp., the parasite that causes malaria, are critical for control of parasitemia and associated immunopathology. Antibodies also provide protection to reinfection. Long‐lasting B‐cell memory has been shown to occur in response to Plasmodium spp. in experimental model infections, and in human malaria. However, there are reports that antibody responses to several malaria antigens in young children living with malaria are not similarly long‐lived, suggesting a dysfunction in the maintenance of circulating antibodies. Some studies attribute this to the expansion of atypical memory B cells (AMB), which express multiple inhibitory receptors and activation markers, and are hyporesponsive to B‐cell receptor (BCR) restimulation in vitro. AMB are also expanded in other chronic infections such as tuberculosis, hepatitis B and C, and HIV, as well as in autoimmunity and old age, highlighting the importance of understanding their role in immunity. Whether AMB are dysfunctional remains controversial, as there are also studies in other infections showing that AMB can produce isotype‐switched antibodies and in mouse can contribute to protection against infection. In light of these controversies, we review the most recent literature on either side of the debate and challenge some of the currently held views regarding B‐cell responses to Plasmodium infections.
Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta‐analysis
Authors: Lim Vanessa W. , Tudor Car Lorainne , Leo Yee‐Sin , Chen Mark I‐Cheng , Young Barnaby 
Published: November 2019

AbstractBackgroundA range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non‐corticosteroid immunomodulatory therapy and potential adverse effects.MethodWe searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of included articles. We included RCTs, quasi‐RCTs and observational studies of virologically confirmed influenza infections in hospitalised patients. We did not restrict studies by language of publication, influenza type/subtype or age of participants. Where possible, we pooled estimates of effect using random‐effects meta‐analysis models.ResultsWe identified 11 eligible studies for inclusion: five studies (4 RCTs and 1 observational; 693 individuals) of passive immune therapy; four studies (3 RCTs and 1 observational; 1120 individuals) of macrolides and/or non‐steroidal anti‐inflammatory drugs (NSAIDs), one RCT of mTOR inhibitors (38 individuals), and one RCT of statin therapy (116 individuals). Meta‐analysis of RCTs of passive immune therapy indicated no significant reduction in mortality (OR 0.84, 0.37‐1.90), but better clinical outcomes at Day 7 (OR 1.42, 1.05‐1.92). There was a significant reduction in mortality associated with macrolides and/or NSAIDs (OR 0.28; 0.10‐0.77).ConclusionsPassive immune therapy is unlikely to offer substantial mortality benefit in treatment of severe seasonal influenza, but may improve clinical outcomes. The effect of other immunomodulatory agents is uncertain, but promising. There is a need for high‐quality RCTs with sufficient statistical power to address this evidence gap.