bluuebunny/crossref_metadata_2025 huggingface dataset:
Once upon a time in the far south: Influence of local drivers and functional traits on plant invasion in the harsh sub-Antarctic islands
Authors: Bazzichetto Manuele , Massol François , Carboni Marta , Lenoir Jonathan , Jonas J Lembrechts , Joly Rémi , Renault David
Published: July 2020

Aim

Here, we aim to: (i) investigate the local effect of environmental and human-related factors on alien plant invasion in sub-Antarctic islands; (ii) explore the relationship between alien species features and their dependence on anthropogenic propagule pressure; and (iii) unravel key traits conferring invasiveness in the sub-Antarctic.

Location

Possession Island, Crozet archipelago (French sub-Antarctic islands).

Taxon

Non-native vascular plants (Poaceae, Caryophyllaceae, Juncaceae).

Methods

Single-species distribution models were used to explore the effect of high-resolution topoclimatic and human-related variables on the occurrence of six of the most aggressive alien plants colonizing French sub-Antarctic islands. Furthermore, the interaction between alien species traits and their response to anthropogenic propagule pressure was analysed by means of a multi-species distribution model. This allowed identifying the features of species that were associated to low dependence on human-assisted introductions, and were thus potentially more invasive.

Results

We observed two main invasion patterns: low-spread species strongly dependent on anthropogenic propagule pressure and high-spread species limited mainly by harsh climatic conditions. Differences in invasiveness across species mostly related to their residence time, life history and plant height, with older introductions, perennial and low-stature species being more invasive.

Main conclusions

The availability of high-resolution data improved our understanding of the role of environmental and human-related factors in driving alien species distribution on sub-Antarctic islands. At the same time, the identification of alien species features conferring invasiveness may help anticipating future problematic invasions.
CAMSAP3 is required for mTORC1-dependent ependymal cell growth and lateral ventricle shaping in mouse brains
Authors: Kimura Toshiya , Saito Hiroko , Kawasaki Miwa , Takeichi Masatoshi
Published: July 2020

Microtubules (MTs) regulate numerous cellular processes, but their roles in brain morphogenesis are not well known. Here we show that CAMSAP3, a non-centrosomal microtubule regulator, is important for shaping the lateral ventricles. In differentiating ependymal cells, CAMSAP3 became concentrated at the apical domains, serving to generate MT networks at these sites.Camsap3-mutated mice showed abnormally narrow lateral ventricles, in which excessive stenosis or fusion was induced, leading to a decrease of neural stem cells at the ventricular and subventricular zones. This defect was ascribed at least in part to a failure of neocortical ependymal cells to broaden their apical domain, a process necessary for expanding the ventricular cavities. mTORC1 was required for ependymal cell growth but its activity was downregulated in mutant cells. Lysosomes, which mediate mTORC1 activation, tended to be reduced at the apical regions of the mutant cells, along with disorganized apical MT networks at the corresponding sites. These findings suggest that CAMSAP3 supports mTORC1 signaling required for ependymal cell growth via MT network regulation, and, in turn, shaping of the lateral ventricles.

Summary statement

CAMSAP3, which mediates non-centrosomal microtubule assembly, is required for mTORC1-dependent maturation of ependymal cells at the neocortex of developing mouse brains. Loss of CAMSAP3 causes deformation of the lateral ventricles.
BMP signalling directs a fibroblast-to-myoblast conversion at the connective tissue/muscle interface to pattern limb muscles
Authors: de Lima Joana Esteves , Blavet Cédrine , Bonnin Marie-Ange , Hirsinger Estelle , Comai Glenda , Yvernogeau Laurent , Bellenger Léa , Mella Sébastien , Nassari Sonya , Robin Catherine , Schweitzer Ronen , Fournier-Thibault Claire , Tajbakhsh Shahragim , Relaix Frédéric , Duprez Delphine
Published: July 2020

Positional information driving limb muscle patterning is contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue but not in myogenic cells themselves. The long-standing consensus is that myogenic cells originate from the somitic mesoderm, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model using cell and genetic lineage tracing experiments in birds and mice, respectively, and identified a subpopulation of myogenic cells at the muscle tips close to tendons originating from the lateral plate mesoderm and derived from connective tissue gene lineages. Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages revealed a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performedin vivoandin vitroshowed that this signalling pathway regulated a fibroblast-to-myoblast conversion. We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the muscle/tendon interface to control the muscle pattern during limb development.
The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development
Authors: Goulielmaki Evi , Tsekrekou Maria , Batsiotos Nikos , Ascensão-Ferreira Mariana , Ledaki Eleftheria , Stratigi Kalliopi , Chatzinikolaou Georgia , Topalis Pantelis , Kosteas Theodore , Altmüller Janine , Demmers Jeroen A. , Barbosa-Morais Nuno L. , Garinis George A.
Published: July 2020

RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using anin vivobiotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells andCsbm/mdeveloping livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for mammalian development and transcription-coupled DNA repair disorders.
Monitoring Autophagy: Not All LC3s Are Created Equal
Authors: Fouad Yousef A , El-Naggar Shahenda
Published: July 2020

The heightened interest in monitoring autophagy comes with discrepant results in different settings. We examined the specificity of reporting in previous studies regarding the isoforms of the most commonly monitored autophagy-related protein, LC3. An ambiguous picture emerged reflecting confusion in design and/or reporting. In light of our current understanding of the different LC3 isoforms, it has become important to specify the targeted isoform when reporting methods and results of studies attempting to monitor autophagy.
Integrative Vectors for Regulated Expression of SARS-CoV-2 Proteins Implicated in RNA Metabolism
Authors: Bresson Stefan , Robertson Nic , Sani Emanuela , Turowski Tomasz W , Shchepachev Vadim , Kompauerova Michaela , Spanos Christos , Helwak Aleksandra , Tollervey David
Published: July 2020

Infection with SARS-CoV-2 is expected to result in substantial reorganization of host cell RNA metabolism. We identified 14 proteins that were predicted to interact with host RNAs or RNA binding proteins, based on published data for SARS-CoV and SARS-CoV-2. Here, we describe a series of affinity-tagged and codon-optimized expression constructs for each of these 14 proteins. Each viral gene was separately tagged at the N-terminus with Flag-His8, the C-terminus with His8-Flag, or left untagged. The resulting constructs were stably integrated into the HEK293 Flp-In TREx genome. Each viral gene was expressed under the control of an inducible Tet-On promoter, allowing expression levels to be tuned to match physiological conditions during infection. Expression time courses were successfully generated for most of the fusion proteins and quantified by western blot. A few fusion proteins were poorly expressed, whereas others, including Nsp1, Nsp12, and N protein, were toxic unless care was taken to minimize background expression. All plasmids can be obtained from Addgene and cell lines are available. We anticipate that availability of these resources will facilitate a more detailed understanding of coronavirus molecular biology.
Integrative Modeling of Membrane-associated Protein Assemblies
Authors: Roel-Touris Jorge , Jiménez-García Brian , Bonvin Alexandre M.J.J.
Published: July 2020

Historically, membrane protein systems have been considered as one of the most challenging systems to study with experimental structural biology techniques. Over the past years, increased number of experimental structures of membrane proteins have become available thanks in particular to advances in solid-state NMR spectroscopy and cryo-electron microscopy. This has opened the route to modeling the complexes that those membrane proteins form by methods such as docking. Most approaches developed to date are, however, not capable of incorporating the topological information provided by the membrane into the modeling process. Here, we present an integrative computational protocol for the modeling of membrane-associated protein assemblies, specifically complexes consisting of a membrane-embedded protein and a soluble partner. It combines efficient, artificial intelligence-based rigid-body docking by LightDock with a flexible final refinement with HADDOCK to remove potential clashes at the interface. We make use of an equilibrated coarse-grained lipid bilayer to represent the information encoded in the membrane in the form of artificial beads, which allows to target the docking towards the binding-competent regions. We demonstrate the performance of this membrane-driven protocol on eighteen membrane-associated complexes, whose interface lies between the membrane and either the cytosolic or periplasmic regions. In addition, we evaluate how different membrane definitions impact the performance of the docking protocol and provide a comparison, in terms of success rate, to another state-of-the-art docking software, ZDOCK. Finally, we discuss the quality of the generated models and propose possible future developments. Our membrane docking protocol should allow to shed light on the still rather dark fraction of the interactome consisting of membrane proteins.
Comparative regulomics reveals pervasive selection on gene dosage following whole genome duplication
Authors: Gillard Gareth B. , Grønvold Lars , Røsæg Line L. , Holen Matilde Mengkrog , Monsen Øystein , Koop Ben F. , Rondeau Eric B. , Gundappa Manu Kumar , Mendoza John , Macqueen Daniel J. , Rohlfs Rori V. , Sandve Simen R. , Hvidsten Torgeir R.
Published: July 2020

Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80-100 million years ago. We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Although ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards pseudogenization, strong evolutionary constraints have frequently also favoured symmetric shifts in gene dosage of both copies, likely to achieve gene dose reduction while avoiding accumulation of ‘toxic mutations’. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one source of novel binding sites driving tissue-specific gains in expression. Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.
Nutrient supplementation experiments with saltern microbial communities implicate utilization of DNA as a source of phosphorus
Authors: Hua Zhengshuang , Ouellette Matthew , Makkay Andrea M. , Papke R. Thane , Zhaxybayeva Olga
Published: July 2020

All environments including hypersaline ones harbor measurable concentrations of dissolved extracellular DNA (eDNA) that can be utilized by microbes as a nutrient. However, it remains poorly understood which eDNA components are used, and who in a community utilizes it. For this study, we incubated a saltern microbial community with combinations of carbon, nitrogen, phosphorus, and DNA, and tracked the community response in each microcosm treatment via 16S rRNA andrpoBgene sequencing. We show that microbial communities used DNA only as a phosphorus source, and provision of other sources of carbon and nitrogen was needed to exhibit a substantial growth. The taxonomic composition of eDNA in the water column changed with the availability of inorganic phosphorus or supplied DNA, hinting at preferential uptake of eDNA from specific organismal sources. Especially favored for growth was eDNA from the most abundant taxa, suggesting some haloarchaea prefer eDNA from closely related taxa. Additionally, microcosms’ composition shifted substantially depending on the provided nutrient combinations. These shifts allowed us to predict supplemented nutrients from microbial composition with high accuracy, suggesting that nutrient availability in an environment could be assessed from a taxonomic survey of its microbial community.
Unique genomic features of crAss-like phages, the dominant component of the human gut virome
Authors: Yutin Natalya , Benler Sean , Shmakov Sergei A. , Wolf Yuri I. , Tolstoy Igor , Rayko Mike , Antipov Dmitry , Pevzner Pavel A. , Koonin Eugene V.
Published: July 2020

CrAssphage is the most abundant virus identified in the human gut virome and the founding member of a large group of bacteriophages that infect bacteria of the phylum Bacteroidetes and have been discovered by metagenomics of both animal-associated and environmental habitats. By analysis of circular contigs from human gut microbiomes, we identified nearly 600 genomes of crAss-like phages. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, which can be expected to become a new order of viruses, and of 5 distinct branches, likely, families within that order. Two of these putative families have not been identified previously. The phages in one of these groups have large genomes (145-192 kilobases) and contain an unprecedented high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable readthrough of UGA or UAG stop-codons, mostly, in late phage genes, which could represent a distinct anti-defense strategy. Another putative anti-defense mechanism that might target an unknown defense system in Bacteroidetes inhibiting phage DNA replication involves multiple switches of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals several unusual features of genome architecture and expression as well as phage biology that were not apparent from the previous crAssphage analyses.
Antifeedant activities of L-arabinose to caterpillars of the cotton bollwormHelicoverpa armigera(Hübner)
Authors: Sun Longlong , Hong Zhenzhen , Ma Ying , Hou Wenhua , Liu Long , Zhao Xincheng , Yan Fengming , Yin Xinming , Wang Chenzhu , Tang Qingbo
Published: July 2020

Exploring botanical biopesticide is one of the eco-friendly approaches for pest control in current crop protection. L-arabinose, a plant-specific and less absorptive pentose, is known for its selective inhibitory effect on the sucrose digestion in mammals. In this study, we investigated the effects of L-arabinose on the feeding preference, the peripheral gustatory perception, the larval development, as well as the activity of intestinal sucrase of an insect pest species, the cotton bollwormHelicoverpa armigera(Hübner) (Lepidoptera: Noctuidae), in an attempt to explore the antifeedant activities of this pentose. The results showed that L-arabinose deterred the feeding preferences ofH. armigeracaterpillars for its two host plants and two phagostimulants, the tobacco, the pepper, the sucrose and the fructose. Gustatory receptor neurons (GRNs) sensitive to L-arabinose were not found in the peripheral maxillary sensilla ofH. armigeracaterpillars, but the sensitivities of GRNs sensitive to sucrose, fructose and tobacco saps were suppressed by the additions of L-arabinose. Exposure ofH. armigeracaterpillars to dietary L-arabinose resulted in a prolonged larval developmental duration, a suppressed activity of intestinal sucrase and a reduced glucose level in midgut.In vitro, L-arabinose inhibited activities of the intestinal sucrase ofH. armigeracaterpillars in an uncompetitive manner. Taken together, these findings demonstrate that L-arabinose is a behavioral, gustatory and physiological inhibitor to caterpillars of the extremely generalist pest speciesH. armigera, suggesting the great potential of L-arabinose to be an effective antifeedant.
Impacts of supportive HR practices and organisational climate on the attitudes of HR managers towards gender diversity – a mediated model approach
Authors: Biswas Kumar , Boyle Brendan , Bhardwaj Sneh
Published: July 2020

Purpose

Using the theoretical lens of the behavioural perspective on HRM, this study examined a mediated model to understand the extent to which organisational factors such as supportive human resource management policies and practices (SHRPP) and organisational climate (OC) can influence the affective attitudes of HR managers towards promoting women into organisational leadership roles. Survey data collected from 182 human resource managers in Bangladesh were analysed using partial least squares–based structural equation modelling (PLS-SEM) and the PROCESS macro to test mediating effects. The results reveal that the adoption of SHRPP is positively associated with OC, which in turn shapes the attitudes of HR managers leading to implementing unbiased promotional practices for organisational leadership roles.

Design/methodology/approach

Quantitative survey data collected from 182 human resource managers in Bangladesh were analysed using PLS-SEM and PROCESS macro.

Findings

The results reveal that the adoption of SHRPP is positively associated with OC which in turn shapes the attitudes of HR managers leading to implementing unbiased promotional practices for organisational leadership roles.

Research limitations/implications

Self-report, cross-sectional survey data may contribute to the methodological bias such as common method bias (CMB). Harman's single-factor test revealed that no single component explained a major portion of the total variance. Furthermore, partial correlational analysis using a marker variable coupled with an assessment of social desirability indicates that common method variance is unlikely to have any CMB risks to the validity of the study results.

Practical implications

From a practical point of view, the findings of this study suggest that supportive HR practices may create a positive organisational climate that leads to creating a healthy work environment ensuring an equal opportunity for everyone to grow and excel irrespective of their socio-cultural backgrounds and gender identity; thus, facilitating the organisation to take advantage of creativity and innovation offered by their talents, a critical factor for the organisation to survive and flourish in the dynamic market.

Social implications

The study findings provide insights into why organisations should adopt fair and transparent HR policies to create a congenial work climate impacting on positive social attitudes towards acceptance of a gender-balanced empowered society.

Originality/value

To the best of author's knowledge, this is the first study that examined a mediated model to understand how organisational factors such as SHRPP and OC can impact on the affective attitudes of HR managers towards promoting women in the organisational leadership roles.
Work to family, family to work conflicts and work family balance as predictors of job satisfaction of Malaysian academic community
Authors: Rahman Md. Mizanur , Ali Noor Azman , Jantan Amer Hamzah , Mansor Zuraina Dato' , Rahaman Md. Saidur
Published: July 2020

Purpose

The purpose of this study is to confirm that work to family conflict (W to FC), family to work conflict (F to WC) and work family balance (WFB) are the predictors of job satisfaction (JS) for Malaysian academic community. To achieve the fundamental objective, the authors first test the direct (structural model) effects of W to FC and F to WC on JS. Secondly, using mediation model, the indirect effects of WFB were calculated through W to FC, F to WC and JS.

Design/methodology/approach

Using convenience sampling, the data was collected from 280 academic people who work at private universities in Malaysia. Structural equation modelling technique was applied to complete the data analyses procedures.

Findings

The findings revealed that W to FC and F to WC have negative significant effects on JS. Besides, WFB partially mediates only the relationship between W to FC and JS while no mediation effect was found for F to WC and JS.

Research limitations/implications

All the research variables in this study were individual-level variables, thus it is suggested to use some organizational and national level variables such as religion and culture as they might be good intervening variables for predicting JS.

Practical implications

Using the findings of this research, the Malaysian private universities community can take some necessary initiatives to mitigate work family conflict (W-FC) and ensure WFB and JS that might enhance the standard of higher education in Malaysia.

Originality/value

To the best of the authors’ knowledge, this is the first attempt to test the mediation effect of WFB in the relationship between both directions of W-FC and JS of employees from the perspective of Malaysia (a collectivist community).
The outcome of pregnancy in women with cystic fibrosis: a UK population‐based descriptive study
Authors: Ashcroft A , Chapman SJ , Mackillop L
Published: July 2020

Objective

To estimate the incidence of cystic fibrosis in pregnancy and to explore obstetric and neonatal outcomes.

Design

A population‐based descriptive study using the methodology of the UK Obstetric Surveillance System (UKOSS).

Setting

All consultant‐led maternity units in the UK.

Population

All pregnant women with a diagnosis of cystic fibrosis who booked for antenatal care in a UK obstetric unit between March 2015 and February 2017.

Methods

Prospective case collection identified using UKOSS monthly notification.

Main outcome measures

Incidence, maternal morbidity, maternal mortality, gestation at delivery, neonatal mortality, neonatal morbidity.

Results

We report 71 pregnancies over a 2‐year period. There was one early miscarriage, four terminations and three sets of twins, resulting in the live birth of 69 infants. There were no maternal deaths. One infant died following spontaneous preterm birth at 29 weeks’ gestation. The mean gestation at delivery was 36.2 completed weeks. The mean birthweight centile for gestational age was the 61st centile. We report a positive correlation between both maternal lung function (FEV1) and mean gestation at delivery, and between FEV1 and mean birthweight centile for gestational age.

Conclusions

Pregnancy outcomes are generally good in women with cystic fibrosis. Successful pregnancy is possible even in those women with FEV1 <60% predicted, although such women have higher chance of preterm delivery and a smaller baby.

Tweetable abstract

Pregnant women with cystic fibrosis who have poorer lung function at the beginning of pregnancy have a higher risk of having a premature or smaller baby.
Disclosing Physician Ratings: Performance Effects and the Difficulty of Altering Ratings Consensus
Authors: EYRING HENRY
Published: July 2020

I examine effects of a health care system's policy to publicly disclose patient ratings of its physicians. I find evidence that this policy leads to performance improvement by the disclosed, subjective ratings and also by undisclosed, objective measures of quality. These effects are consistent with multitasking theory, in that physicians respond to the disclosure by providing more of a shared input—time with patients—that benefits performance by ratings and underlying quality. I also find, as predicted by information cascade theory, that the ratings become jammed to some degree near initially disclosed values. Specifically, raters observe the pattern of initial ratings and follow suit by providing similar ratings. Finally, I find evidence that physicians anticipate rating jamming and so concentrate their effort on earlier performance in order to set a pattern of high ratings that later ratings follow. These results demonstrate that the disclosure of subjective ratings can benefit performance broadly but can also shift effort toward earlier performance.
Comparison of enzymatic and microwave‐assisted alkaline extraction approaches for the generation of oligosaccharides from American Cranberry (Vaccinium macrocarpon) Pomace
Authors: Spadoni Andreani Eugenio , Karboune Salwa
Published: July 2020

Cranberry pomace obtained from industrial juice production was characterized by proximate composition analysis and monosaccharide profile of the dietary fiber. Extraction of carbohydrates from pomace was investigated using microwave‐assisted alkaline method and five commercial biocatalysts (pure endo‐galactanase and four multienzyme biocatalysts). The extracts obtained from microwave‐assisted approach had average total sugars yield of 21.3% and contained mostly oligosaccharides in the degree of polymerization range of 7 to 10. All multienzyme biocatalysts led to yields similar or higher than microwave‐assisted approach (23.4% to 42.0%), but mainly generated shorter oligosaccharides with a degree of polymerization of 2 to 5. Compared to cranberry pomace dietary fiber, microwave‐assisted extracts were enriched in pectic oligosaccharides, whereas the enzymatic extracts were enriched in glucans and had less rhamnose and galactose. Pomace ground for 5 min or more by ball mill assumed a powdery consistence. Longer milling did not affect particle size but increased their roughness. Such physical changes had no effect on the efficiency of multienzymatic treatment.

Practical Application

The increased production of cranberries and cranberry products will continuously generate more pomace, a potentially valuable material for the generation of added‐value products. Up to 60% to 70% of cranberry pomace is composed of plant cell wall material. The properties of naturally occurring plant cell wall polysaccharides and their corresponding oligosaccharides have been of a great interest, and many of them find application as functional food ingredients. Despite the fact that the cranberry pomace is rich in plant cell polysaccharides, it has been mainly explored as a source of phenolic antioxidants. This study reveals the efficiency of cranberry pomace as a source of nondigestible oligosaccharides. The use of microwave‐assisted extraction and different biocatalysts for the enzymatic extraction led to oligosaccharides with well‐defined monosaccharide composition and molecular weight distribution. The study of the effects of these extraction techniques on the yield and the characteristics of generated oligosaccharides would allow the modulation of their properties. As an overall, the findings of this study would contribute to lay the scientific ground for the development of innovative process for the isolation of nondigestible oligosaccharides as functional ingredients from cranberry pomace by products.
DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC
Authors: Ogawa Hiroyuki , Sakai Yasuhiro , Nishio Wataru , Fujibayashi Yusuke , Nishikubo Megumi , Nishioka Yuki , Tane Shinya , Kitamura Yoshitaka , Sudo Tamotsu , Sakuma Toshiko , Yoshimura Masahiro
Published: July 2020

Background

The mammalian Notch family ligands delta‐like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated.

Methods

We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum‐based adjuvant chemotherapy.

Results

DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum‐based adjuvant chemotherapy. Among patients with DLL3 expression‐positive tumors, no difference was found in the five‐year overall survival (OS) or recurrence‐free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five‐year OS: 58.3% vs. 35.7% P = 0.36, five‐year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3‐negative tumors, significantly greater five‐year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five‐year OS: 90.0% vs. 26.9% P<0.01, five‐year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3‐negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01–0.41, P < 0.01), although it was not a factor among patients with DLL3‐positive tumors (HR: 0.73, 95% CI: 0.23–2.27, P = 0.58).

Conclusions

Our results revealed that DLL3 is a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC.

Key points

Significant findings of the study

DLL3 was a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression‐negative LCNEC, platinum‐based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression‐positive LCNEC.

What this study adds

Our results suggest that DLL3 expression‐positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti‐DLL3 therapies if these effects are confirmed by ongoing clinical research.
Growth differentiation factor 15 protects against the aging‐mediated systemic inflammatory response in humans and mice
Authors: Moon Ji Sun , Goeminne Ludger J. E. , Kim Jung Tae , Tian Jing Wen , Kim Seok‐Hwan , Nga Ha Thi , Kang Seul Gi , Kang Baeki E. , Byun Jin‐Seok , Lee Young‐Sun , Jeon Jae‐Han , Shong Minho , Auwerx Johan , Ryu Dongryeol , Yi Hyon‐Seung
Published: July 2020

Mitochondrial dysfunction is associated with aging‐mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an important mitokine generated in response to mitochondrial stress and dysfunction; however, the implications of GDF15 to the aging process are poorly understood in mammals. In this study, we identified a link between mitochondrial stress‐induced GDF15 production and protection from tissue inflammation on aging in humans and mice. We observed an increase in serum levels and hepatic expression of GDF15 as well as pro‐inflammatory cytokines in elderly subjects. Circulating levels of cell‐free mitochondrial DNA were significantly higher in elderly subjects with elevated serum levels of GDF15. In the BXD mouse reference population, mice with metabolic impairments and shorter survival were found to exhibit higher hepatic Gdf15 expression. Mendelian randomization links reduced GDF15 expression in human blood to increased body weight and inflammation. GDF15 deficiency promotes tissue inflammation by increasing the activation of resident immune cells in metabolic organs, such as in the liver and adipose tissues of 20‐month‐old mice. Aging also results in more severe liver injury and hepatic fat deposition in Gdf15‐deficient mice. Although GDF15 is not required for Th17 cell differentiation and IL‐17 production in Th17 cells, GDF15 contributes to regulatory T‐cell‐mediated suppression of conventional T‐cell activation and inflammatory cytokines. Taken together, these data reveal that GDF15 is indispensable for attenuating aging‐mediated local and systemic inflammation, thereby maintaining glucose homeostasis and insulin sensitivity in humans and mice.
Association of TNF‐α gene T‐1031C polymorphism with endometriosis: A meta‐analysis
Authors: Cao Xian‐Ling , Chai Jie , Yu Yang‐Yang , Tian Xiao , Zhao Jian‐Yun , Yu Ling‐Yu , Sun Zhen‐Gao
Published: July 2020

The single nucleotide polymorphism T‐1031C has shown to have an important role in the regulation and transcription efficiency of TNF‐α gene. Yet, the relationship between TNF‐α T‐1031C gene polymorphism and the development of endometriosis (EM) still remains unclear. The aim of this meta‐analysis was to summarize the effects of TNF‐α T‐1031C gene polymorphism and clarify their possible association with EM. A comprehensive literature search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (up to August 10, 2019). A fixed‐ or random‐effects model was employed according to the heterogeneity among studies. The log odds ratios and 95% confidence intervals (CIs) were estimated in the models of allele comparison (T vs C), homozygote comparison (TT vs CC) and (TC vs CC), dominant (TT vs TC + CC), hyperdominant (TT + CC vs TC), and recessive (TT + TC vs CC) to estimate the strength of the associations. A total of 7 case‐control studies were included in this meta‐analysis. Overall, significant associations between TNF‐α T‐1031C and EM were identified from (T vs C: log OR [95% CI] = 0.31 [−0.09, 0.71]; TT + CC vs TC: 0.27 [0.04, 0.50]; TC + CC vs TT: −0.83 [−1.19, −0.47]). On the other hand, no significant correlation was found in other gene models (TT vs TC: log OR [95% CI] = 0.89 [0.64, 1.13]; TT vs CC: 0.3 [−0.74, 1.36]; TT + TC vs CC: 0.17 [−0.81, 1.15]). In subgroup analyses by ethnicity or HWE P‐value, there was a statistically significant association between TNF‐α T‐1031C polymorphisms and EM in the dominant model (TT vs TC + CC: log OR [95%] = −0.84 [−1.60, −0.09]) for the European population, and in hyperdominant model (TT + CC vs TC: log OR [95%] = 0.24 [0.001, 0.49]) for Asian population. To sum up, this meta‐analysis showed that TNF‐α T‐1031C polymorphism was associated with EM susceptibility and has a protective effect in Asian and European populations.
Efficacy and safety of dupilumab for moderate‐to‐severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines
Authors: Agache Ioana , Song Yang , Posso Margarita , Alonso‐Coello Pablo , Rocha Claudio , Solà Ivan , Beltran Jessica , Akdis Cezmi A. , Akdis Mubeccel , Brockow Knut , Chivato Tomas , del Giacco Stefano , Eiwegger Thomas , Eyerich Kilian , Giménez‐Arnau Ana , Gutermuth Jan , Guttman‐Yassky Emma , Maurer Marcus , Ogg Graham , Ong Peck Y. , O’Mahony Liam , Schwarze Jürgen , Werfel Thomas , Canelo‐Aybar Carlos , Palomares Oscar , Jutel Marek
Published: July 2020

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate‐to‐severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD −30,72; 95% CI −34,65% to −26,79%) and EASI‐75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD −7.29; 95% CI −8.23 to −6.35) and anxiety/depression (MD −3.08; 95% CI −4.41 to −1.75) and improves quality of life (MD −4.80; 95% CI −5.55 to −4.06). The efficacy for adolescents is similar. Dupilumab‐related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab‐related serious AE is uncertain. The incremental cost‐effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645).
Short anogenital distance is associated with testicular germ cell tumour development
Authors: Moreno‐Mendoza Daniel , Casamonti Elena , Riera‐Escamilla Antoni , Pietroforte Sara , Corona Giovanni , Ruiz‐Castañe Eduardo , Krausz Csilla
Published: July 2020

Background

Testicular germ cell tumour is a multifactorial disease in which various genetic and environmental factors play a role. Testicular germ cell tumour is part of the testicular dysgenesis syndrome which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance.

Objectives

The primary objective was to examine anogenital distance in testicular germ cell tumour cases and healthy fertile controls. The secondary objective was to assess the (CAG)n polymorphism of the Androgen Receptor gene in relationship with anogenital distances and testicular germ cell tumour development.

Material and Methods

156 testicular germ cell tumour patients and 110 tumour‐free normozoospermic controls of Spanish origin. All subjects underwent full andrological workup (including semen and hormone analysis) and genetic analysis (Androgen Receptor (CAG)n). The main outcome measures were the anopenile distance (AGDap), the anoscrotal distance (AGDas) and AR(CAG)n.

Result

We observed significantly shorter anogenital distances in the group of testicular germ cell tumour patients in respect to controls (P < .001) independently from sperm count and testis histology. Threshold values, applicable only to our cohort, were calculated for anogenital distances with the best sensitivity and specificity. Subjects with AGDap and AGDas below threshold showed a significantly increased risk for testicular germ cell tumour (OR = 4.97, 95% CI = 2.01‐12.33, P = .001 and OR = 4.11, 95% CI = 1.89‐8.92, P ≤ .001, respectively). No significant correlation was observed between AR(CAG)n polymorphism and anogenital distances. The median values of the AR(CAG)n were similar between cases and controls, excluding a major role for this polymorphism in the etiopathogenesis of these testicular dysgenesis syndrome components.

Conclusions

Ours is the first study focusing on anogenital distances in testicular germ cell tumour patients. We identified short anogenital distances (which is a surrogate biomarker of androgen action during foetal life) as a significant risk factor for this disease. After further validation of our preliminary data, anogenital distance measurement could become part of testicular germ cell tumour screening in order to better define those individuals who would benefit from long‐term active follow‐up.
Results of the endovascular treatment system for occluded native arteriovenous fistula
Authors: Leo Christopher Cheang Han , Cassorla Gabriel , Swinnen Jan
Published: July 2020

Background

Arteriovenous fistula is the definitive vascular access for patients on long‐term haemodialysis. The aim of this study is to present the techniques and results of the Endovascular Treatment System that we have developed for managing the occluded native arteriovenous fistula.

Methods

The current study is a retrospective chart review on all patients who presented with an occluded native arteriovenous fistula and underwent attempted recanalization between 1 January 2005 and 31 December 2014.

Results

A total of 130 patients were included in the study. Post‐intervention primary access patency was 83.8% at 6 months, 78.7% at 12 months, 64.6% at 2 years and 59.6% at 3 years. Post‐intervention assisted access patency in fistulas‐in‐use was 86.5% at 6 months, 81% at 12 months, 66.8% at 2 years and 61.2% at 3 years. Post‐intervention secondary patency for all cases was 84.7% at 6 months, 80.2% at 12 months, 66.1% at 2 years and 62% at 3 years. Post‐intervention secondary patency in fistula‐in‐use was 91.1% at 6 months, 90% at 12 months, 85% at 2 years and 74.6% at 3 years. Access survival nor patency differed significantly when incisional thrombectomy was compared to angioplasty with or without stenting with access survival of 91.2% and 92.5% at 12 months and access patency of 82.9% and 89.7% at 12 months (P = 0.834 and P = 0.898, respectively).

Conclusions

In autologous arteriovenous thrombosed fistulae, the use of endovascular techniques to revive the access is a viable and safe technique to employ in most cases.
Systematic review and meta‐analysis suggest that the duration of Kangaroo mother care has a direct impact on neonatal growth
Authors: Charpak Nathalie , Montealegre‐Pomar Adriana , Bohorquez Adriana
Published: July 2020

Aim

A 2016 Cochrane review showed that Kangaroo mother care (KMC) had a moderate impact on preterm growth, with high heterogeneity among studies. This systematic review and meta‐analysis considered new evidence on KMC, particularly the duration.

Method

Databases were searched for papers published in English, French, Spanish and Portuguese up to 2017. Randomised controlled trials (RCT) of preterm or low birth weight infants were included if they compared growth between KMC and conventional care. Anthropometric measures were related to duration.

Results

We identified 1368 papers, and 13 RCTs covering 743 KMC infants and 718 controls met the selection criteria. Infants held in KMC for at least 6 h/d gained more weight than the controls, with a mean difference of 8.99 g/d (95% confidence interval 8.14‐9.84, I2 = 0%). This difference persisted between 2 and 6 h/d and disappeared with 2 hours or less. When we used g/kg/d, the weight gain was higher when the duration was at least 8 h/d. Only babies who received 6 h/d gained more length and head circumference.

Conclusions

The effect of the KMC on growth was directly related to the duration.
Correlation between skeletal muscle fiber type and responses of a taste sensing system in various beef samples
Authors: Komiya Yusuke , Mizunoya Wataru , Kajiwara Kurumi , Yokoyama Issei , Ogasawara Hideki , Arihara Keizo
Published: July 2020

The difference of muscle fiber type composition affects several parameters related to meat quality; however, the relationship between muscle fiber types and meat taste is unclear. To elucidate this relationship, we determined the taste of various beef samples using a taste sensor (INSENT SA402B) and analyzed its correlation with different muscle fiber type composition. We used 22 kinds of beef samples and measured nine tastes, including the relative and change of membrane potential caused by adsorption (CPA) values, using six sensors (GL1, CT0, CA0, AAE, C00, and AE1). The taste sensor analysis indicated positive value outputs for the relative C00, AAE, and GL1 values as well as for the CPA value of AAE, which corresponded to bitterness, umami, sweetness, and richness, respectively. We found significant positive correlations of the myosin heavy chain 1 (MyHC1) composition with umami taste, and with richness. This result suggests that high levels of slow MyHC1 can induce strong umami taste and richness in beef. We expect that our results will contribute to the elucidation of the relationship between muscle fiber types and meat palatability.
Poststratification fusion learning in longitudinal data analysis
Authors: Tang Lu , Song Peter X.‐K.
Published: July 2020

Stratification is a very commonly used approach in biomedical studies to handle sample heterogeneity arising from, for examples, clinical units, patient subgroups, or missing‐data. A key rationale behind such approach is to overcome potential sampling biases in statistical inference. Two issues of such stratification‐based strategy are (i) whether individual strata are sufficiently distinctive to warrant stratification, and (ii) sample size attrition resulted from the stratification may potentially lead to loss of statistical power. To address these issues, we propose a penalized generalized estimating equations approach to reducing the complexity of parametric model structures due to excessive stratification. Specifically, we develop a data‐driven fusion learning approach for longitudinal data that improves estimation efficiency by integrating information across similar strata, yet still allows necessary separation for stratum‐specific conclusions. The proposed method is evaluated by simulation studies and applied to a motivating example of psychiatric study to demonstrate its usefulness in real world settings.
Refinement and augmentation for data in micro open learning activities with an evolutionary rule generator
Authors: Sun Geng , Lin Jiayin , Shen Jun , Cui Tingru , Xu Dongming , Kayastha Mahesh
Published: July 2020

Improving both the quantity and quality of existing data are placed at the center of research for adaptive micro open learning. To cover this research gap, our work targets on the current scarcity of both data and rules that represent open learning activities. An evolutionary rule generator is constructed, which consists of an outer loop and an inner loop. The outer loop runs a genetic algorithm (GA) to produce association rules that can be effective in the micro open learning scenario from a small amount of available data sources; while the inner loop optimizes generated candidates by taking into account both rare and negative association rules (NARs). These optimized rules are further applied in refining and augmenting data denoting learners’ behaviors in open learning into a low‐dimensional, descriptive and interpretable form. The performance of rule discovery and data processing have been empirically evaluated using genuine open learning data.