bluuebunny/crossref_metadata_2025 huggingface dataset:
Holobiont Urbanism: sampling urban beehives reveals cities’ metagenomes
Authors: Hénaff Elizabeth , Najjar Devora , Perez Miguel , Flores Regina , Woebken Christopher , Mason Christopher E. , Slavin Kevin
Published: May 2020

Over half of the world’s population lives in urban areas with, according to the United Nations (UN), nearly 70% expected to live in cities by 2050 (United Nations, 2019). Our cities are built by and for humans, but are also complex, adaptive biological systems involving a diversity of other living species. The majority of these species are invisible and constitute the city’s microbiome. Our design decisions for the built environment shape these invisible populations, and we interact with them on a constant basis. A growing body of evidence shows us that our health and well-being are dependent on these interactions. Indeed, multicellular organisms owe meaningful aspects of their development and phenotype to interactions with the microorganisms—bacteria or fungi—with which they live in continual exchange and symbiosis. While the processing and sequencing of samples can be high-throughput, gathering samples is still very expensive, labor intensive, and can require mobilizing large numbers of volunteers to get a snapshot of the microbial landscape of a city, such as City Sampling Day (metasub.org). Here we postulate that honeybees may be effective collaborators in the sampling process, as they daily forage within a 2-mile radius of their hive. We describe the results of a pilot study conducted with 3 rooftop beehives in Brooklyn, NY, where we evaluated the potential of various hive materials (beeswax, honey, debris, pollen, propolis) to reveal information as to the surrounding metagenomic landscape, and where we conclude that the bee debris are the richest substrate. Based on these results, we profiled 4 additional cities in this manner: Sydney, Melbourne, Venice and Tokyo. While the molecular and computational methods used here were based on DNA analysis, it is possible they could be used to monitor RNA-based viruses such as Sars-Cov-2. Here we present the results of this study, and discuss them in terms of architectural implications, as well as the potential of this method for epidemic surveillance.
UropathogenicE. coliinduces DNA damage in the bladder
Authors: Chagneau Camille V. , Massip Clémence , Bossuet-Greif Nadège , Fremez Christophe , Motta Jean-Paul , Shima Ayaka , Besson Céline , Le Faouder Pauline , Cénac Nicolas , Roth Marie-Paule , Coppin Hélène , Fontanié Maxime , Martin Patricia , Nougayrède Jean-Philippe , Oswald Eric
Published: May 2020

Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of a metabolite released during the synthesis of colibactin, a bacterial genotoxin, in 50 of the samples examined. UropathogenicEscherichia colistrains isolated from these patients, as well as the archetypalE. colistrain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours of the infection, when intracellular bacterial communities form. We observed extensive DNA damage both in umbrella and bladder progenitor cells. To the best of our knowledge this is the first report of colibactin production in UTIs in humans and its genotoxicity in bladder cells. This bacterial genotoxin, which is increasingly suspected to promote colorectal cancer, should also be scrutinised in the context of bladder cancer.
Lack of adaptation to centriolar defects leads to p53-independent microcephaly in the absence of Cep135
Authors: González-Martínez José , Cwetsch Andrzej W , Martínez-Alonso Diego , López-Sainz Luis Rodrigo , Almagro Jorge , Megías Diego , Boskovic Jasminka , Gilabert-Juan Javier , Graña-Castro Osvaldo , Pierani Alessandra , Behrens Axel , Ortega Sagrario , Malumbres Marcos
Published: May 2020

Autosomal Recessive Primary Microcephaly (MCPH) is a rare disease associated to proteins involved in centrosomal and spindle dynamics including Cep135 (MCPH8). Although Cep135 has been associated to centriolar assembly, the mechanisms associated to the pathogenesis underlyingMCPH8mutations are unclear. By using a series of CRISPR/Cas9-edited murineCep135alleles, we report here that lack of Cep135 results in perinatal lethality accompanied by significant microcephaly in a dosis-dependent manner. Cep135 deficiency, but not that of other centrosomal microcephaly proteins such as Aspm or Cdk5rap2, induces centrosome duplication defects, and perturbed centriole structure and dynamics. Whereas other cell types are able to quickly adapt to these defects, neural progenitors display a prolonged response leading to chromosomal instability and cell death in later developmental stages. Genetic ablation ofTrp53in these mutant embryos prevents apoptotic cell death but does not rescue the microcephaly induced by Cep135 loss. These results suggest that microcephaly can arise from the lack of adaptation to centriole defects in neural progenitors of the developing neocortex in a p53-independent manner.
Machine learning with biomedical ontologies
Authors: Kulmanov Maxat , Smaili Fatima Zohra , Gao Xin , Hoehndorf Robert
Published: May 2020

Ontologies have long been employed in the life sciences to formally represent and reason over domain knowledge, and they are employed in almost every major biological database. Recently, ontologies are increasingly being used to provide background knowledge in similarity-based analysis and machine learning models. The methods employed to combine ontologies and machine learning are still novel and actively being developed. We provide an overview over the methods that use ontologies to compute similarity and incorporate them in machine learning methods; in particular, we outline how semantic similarity measures and ontology embeddings can exploit the background knowledge in biomedical ontologies, and how ontologies can provide constraints that improve machine learning models. The methods and experiments we describe are available as a set of executable notebooks, and we also provide a set of slides and additional resources athttps://github.com/bio-ontology-research-group/machine-learning-with-ontologies.

Key points

Ontologies provide background knowledge that can be exploited in machine learning models.

Ontology embeddings are structure-preserving maps from ontologies into vector spaces and provide an important method for utilizing ontologies in machine learning. Embeddings can preserve different structures in ontologies, including their graph structures, syntactic regularities, or their model-theoretic semantics.

Axioms in ontologies, in particular those involving negation, can be used as constraints in optimization and machine learning to reduce the search space.
Enhanced super-resolution microscopy by combined Airyscan and Quantum-Dot-Triexciton Imaging
Authors: Hennig Simon , Manstein Dietmar J.
Published: May 2020

Super-resolution fluorescence imaging provides critically improved information about the composition, organization and dynamics of sub-cellular structures. Quantum-Dot-Triexciton Imaging (QDTI) has been introduced as an easy-to-use sub-diffraction imaging method that achieves an almost 2-fold improvement in resolution when used with conventional confocal microscopes. Here we report an overall 3-fold increase in lateral and axial resolution compared to standard confocal microscopes by combining QDTI with the Airyscan approach.
Intrinsic defects in lymph node stromal cells underpin poor germinal center responses during aging
Authors: Denton Alice E , Silva-Cayetano Alyssa , Dooley James , Hill Danika L , Carr Edward J , Robert Philippe A , Meyer-Hermann Michael , Liston Adrian , Linterman Michelle A
Published: May 2020

The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center response, which generates long-lived antibody-secreting cells that provide protection against (re)infection. Despite intensive investigation into the effect of age on the lymphoid compartment, the primary cellular defect that causes impaired germinal centers in aging has not been identified. Herein we demonstrate that aging reduces the capacity of germinal center-associated stromal cells to respond to vaccination. Heterochronic parabiosis and mathematical modeling demonstrate that a poor stromal cell response limits the size of the germinal center. This study reveals that age-associated defects in stromal cells are a significant barrier to efficacious vaccine responses in older individuals.
The Impact of Graph Construction Scheme and Community Detection Algorithm on the Repeatability of Community and Hub Identification in Structural Brain Networks
Authors: Dimitriadis Stavros I. , Messaritaki Eirini , Jones Derek K.
Published: May 2020

A critical question in network neuroscience is how nodes cluster together to form communities, to form the mesoscale organization of the brain. Various algorithms have been proposed for identifying such communities, each identifying different communities within the same network. Here, (using test-retest data from the Human Connectome Project), the repeatability of 33 community detection algorithms, each paired with 7 different graph construction schemes was assessed.

Repeatability of community partition depended heavily on both the community detection algorithm and graph construction scheme. Hard community detection algorithms (in which each node is assigned to only one community) outperformed soft ones (in which each node can be belong to more than one community). The highest repeatability was observed for the fast multi-scale community detection algorithm paired with a graph construction scheme that combines 9 white matter metrics. This pair also gave the highest similarity between representative group community affiliation and individual community affiliation. Connector hubs had higher repeatability than provincial hubs. Our results provide a workflow for repeatable identification of structural brain networks communities, based on optimal pairing of community detection algorithm and graph construction scheme.
MEIS-WNT5A axis regulates development of 4thventricle choroid plexus
Authors: Kaiser Karol , Jang Ahram , Lun Melody P. , Procházka Jan , Machon Ondrej , Procházková Michaela , Laurent Benoit , Gyllborg Daniel , van Amerongen Renée , Kompaníková Petra , Wu Feizhen , Barker Roger A. , Uramová Ivana , Sedláček Radislav , Kozmík Zbyněk , Arenas Ernest , Lehtinen Maria K. , Bryja Vítězslav
Published: May 2020

The choroid plexus (ChP) produces cerebrospinal fluid and forms a critical barrier between the brain and the circulation. While the ChP forms in each brain ventricle, it adopts a different shape in each one and remarkably little is known about the mechanisms underlying its development. Here, we show that epithelial WNT5A is critical for determining fourth ventricle (4V) ChP morphogenesis and size. SystemicWnt5aknockout, or forced WNT5A overexpression beginning at E10.5, profoundly reduced the size and development of ChP in all ventricles. However, conditional deletion ofWnt5aexpression inFoxj1-expressing epithelial cells affected only the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical Wnt signaling via Ror1/Ror2 receptors. During 4V ChP development, MEIS1 bound to the proximalWnt5apromoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulatedWnt5aexpression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS1 and MEIS2 as upstream regulators ofWnt5ain the 4V ChP epithelium.
Cadherin-13 is a critical regulator of GABAergic modulation in human stem cell derived neuronal networks
Authors: Mossink Britt , van Rhijn Jon-Ruben , Wang Shan , van Hugte Eline J. H. , Linda Katrin , Bak Jitske , Verboven Anouk H. A. , Selten Martijn , Anania Alessia , Jansen Sophie , Keller Jason M. , Gunnewiek Teun Klein , Schoenmaker Chantal , Oudakker Astrid , Frega Monica , van Bokhoven Hans , Schubert Dirk , Kasri Nael Nadif
Published: May 2020

Activity in the healthy brain relies on concerted interplay of excitation (E) and inhibition (I) via balanced synaptic communication between glutamatergic and GABAergic neurons. A growing number of studies imply that disruption of this E/I balance is a commonality in many brain disorders, however, obtaining mechanistic insight into these disruptions, with translational value for the human patient, has typically been hampered by methodological limitations.Cadherin-13(CDH13) has strongly been associated to attention-deficit/hyperactivity disorder and comorbid disorders such as autism and schizophrenia. CDH13 localises at inhibitory presynapses, specifically of parvalbumin (PV) and somatostatin (SST) expressing GABAergic neurons. However, the mechanism by which CDH13 regulates the function of inhibitory synapses in human neurons remains unknown. Starting from human induced pluripotent stem cells, we established a robust method to generate a homogenous population of SST and PV expressing GABAergic neurons (iGABA)in vitro, and co-cultured these with glutamatergic neurons at defined E/I ratios on micro-electrode arrays. We identified functional network parameters that are most reliably affected by GABAergic modulation as such, and through alterations of E/I balance by reduced expression of CDH13 in iGABAs. We found that CDH13-deficiency in iGABAs decreased E/I balance by means of increased inhibition. Moreover, CDH13 interacts with Integrin-β1 and Integrin-β3, which play opposite roles in the regulation of inhibitory synaptic strength via this interaction. Taken together, this model allows for standardized investigation of the E/I balance in a human neuronal background and can be deployed to dissect the cell-type specific contribution of disease genes to the E/I balance.
Rising through the Ranks: Seasonal and Diel Patterns of Marine Viruses
Authors: Hevroni Gur , Flores-Uribe José , Béjà Oded , Philosof Alon
Published: May 2020

Virus-microbe interactions have been studied in great molecular details for many years in cultured model systems, yielding a plethora of knowledge on how viruses use and manipulate host machinery. Since the advent of molecular techniques and high-throughput sequencing, viruses have been deemed the most abundant organisms on earth and methods such as co-occurrence, nucleotide composition and other statistical frameworks have been widely used to infer virus-microbe interactions, overcoming the limitations of culturing methods. However, their accuracy and relevance is still debatable, as co-occurrence does not necessarily mean interaction. Here, we introduce an ecological perspective of marine viral communities and potential interaction with their hosts, using analyses that make no prior assumptions on specific virus-host pairs. By size fractioning water samples into "free viruses" and "microbes" (i.e. also viruses inside or attached to their hosts) and looking at how viral groups abundance changes over time along both fractions, we show that the viral community is undergoing a change in rank abundance across seasons, suggesting a seasonal succession of viruses in the Red Sea. We use abundance patterns in the different size fractions to classify viral populations, indicating potential diverse interactions with their hosts and potential differences in life history traits between major viral groups. Finally, we show hourly resolved variations of intracellular abundance of similar viral groups, which might indicate differences in their infection cycles or metabolic capacities.
A simple RNA preparation method for SARS-CoV-2 detection by RT-qPCR
Authors: Wozniak Aniela , Cerda Ariel , Ibarra-Henriquez Catalina , Sebastian Valentina , Armijo Grace , Lamig Liliana , Miranda Carolina , Lagos Marcela , Solari Sandra , Guzmán Ana María , Quiroga Teresa , Hitschfeld Susan , Riveras Eleodoro , Ferres Marcela , Gutiérrez Rodrigo A. , García Patricia
Published: May 2020

The technique RT-qPCR for viral RNA detection is the current worldwide strategy used for early detection of the novel coronavirus SARS-CoV-2. RNA extraction is a key pre-analytical step in RT-qPCR, often achieved using commercial kits. However, the magnitude of the COVID-19 pandemic is causing disruptions to the global supply chains used by many diagnostic laboratories to procure the commercial kits required for RNA extraction. Shortage in these essential reagents is even more acute in developing countries with no means to produce kits locally. We sought to find an alternative procedure to replace commercial kits using common reagents found in molecular biology laboratories. Here we report a method for RNA extraction that takes about 40 min to complete ten samples, and is not more laborious than current commercial RNA extraction kits. We demonstrate that this method can be used to process nasopharyngeal swab samples and yields RT-qPCR results comparable to those obtained with commercial kits. Most importantly, this procedure can be easily implemented in any molecular diagnostic laboratory. Frequent testing is crucial for individual patient management as well as for public health decision making in this pandemic. Implementation of this method could maintain crucial testing going despite commercial kit shortages.
Shoot and root thermomorphogenesis are linked by a developmental trade-off
Authors: Gaillochet Christophe , Burko Yogev , Platre Matthieu Pierre , Zhang Ling , Simura Jan , Kumar Vinod , Ljung Karin , Chory Joanne , Busch Wolfgang
Published: May 2020

Temperature is one of the most impactful environmental factors to which plants adjust their growth and development. While the regulation of temperature signaling has been extensively investigated for the aerial part of plants, much less is known and understood about how roots sense and modulate their growth in response to fluctuating temperatures. Here we found that shoot and root growth responses to high ambient temperature are coordinated during early seedling development. A shoot signaling module that includes HY5, the phytochromes and the PIFs exerts a central function in coupling these growth responses and control auxin levels in the root. In addition to the HY5/PIF-dependent shoot module, a regulatory axis composed of auxin biosynthesis and auxin perception factors controls root responses to high ambient temperature. Together, our findings show that shoot and root developmental responses to temperature are tightly coupled during thermomorphogenesis and suggest that roots integrate energy signals with local hormonal inputs.
Controlling invasive plant species in ecological restoration: A global review
Authors: Weidlich Emanuela W. A. , Flórido Flávia G. , Sorrini Taísi B. , Brancalion Pedro H. S.
Published: May 2020

Invasive plant species can hinder the establishment and growth of native plants and impact several ecosystem properties, such as soil cover, nutrient cycling, fire regimes and hydrology. Controlling invasive plants is then a necessary, yet usually expensive, step towards the restoration of an ecosystem. A synthesis of literature is needed to understand variation in invasive plants' impacts and their practical control in restoration contexts, and to identify associated knowledge gaps.

We reviewed 372 articles published from 2000 to 2019 covering the control of undesirable plants (both exotic invasive and overabundant native plant species) in ecological restoration to gather information on the main plants being controlled and methods used, and considering the distribution of studies among biomes and countries grouped according to the Human Development Index (HDI).

Grasses and forbs were the most‐studied invasive plant species in restoration sites, but invasive trees were well studied in the tropics. Poaceae and Asteraceae were the most studied families of invasive plants. Non‐chemical interventions (mostly mowing and prescribed fire) were used in more than half of the reviewed studies globally, but chemical methods (mainly glyphosate spraying, used in 40% of projects using herbicides) are also common. The reviewed studies were mostly performed in countries with very high HDI. Countries with low and medium HDI used only non‐chemical methods.

Synthesis and applications. Decisions about which control method to use depend heavily on the invasive plant species' growth forms, the local economic situation where the restoration sites are located and resources available for control. More developed countries tend to use more chemical control, whereas less developed ones use mainly non‐chemical methods. Since most of the reviewed studies were performed in countries with very high HDI, we lack information from developing countries, which concentrates global hotspots for biodiversity conservation and global commitments of forest and landscape restoration.
Landscape genetic analyses reveal host association of mitochondrial haplotypes in the Asian corn borer, Ostrinia furnacalis
Authors: Dong Zhaoke , Li Chao , Zhang Qingqing , Li Lili , Lu Zengbin , Ouyang Fang , Song Yingying , Yu Yi , Men Xingyuan
Published: May 2020

Crop expansion often leads to high pest pressure. These pests may have fitness trade‐offs related to host use, and some host‐associated genotypes may benefit and increase in frequency. However, evidence concerning the effect of host availability on spatial distribution and frequency of mitochondrial haplotypes is scarce. We studied genetic variation of the Asian corn borer, Ostrinia furnacalis (Guenée), across a large area during 2 years (2016 and 2017). Mitochondrial sequence data were obtained from 530 individuals collected from 79 locations in Shandong Province, China. In total, 155 haplotypes were found based on the combined cytochrome oxidase subunit 1 (COI) and COII genes. Three haplotypes (H2, H12, and H23) were dominant, whereas most of the other haplotypes occurred in low frequency. A haplotype network showed that the 155 haplotypes can be grouped into three clusters. Haplotype clusters seemed to be randomly distributed. The frequency of H12 (in Cluster 1) was positively correlated with maize crop proportion, but negatively correlated with other crops (primarily vegetables, oilseed crops, and cotton) at all spatial scales (1‐, 3‐, and 5‐km radius). Cluster 2 had haplotype H23, and this cluster was negatively correlated with semi‐natural habitats. Cluster 3 had no dominant haplotype and was not affected by landscape factors. We conclude that H12 may be a maize‐associated haplotype. Further study is needed to verify the possibility that the carriers of this haplotype may possess some fitness trade‐offs. Our study highlights the importance of host availability in O. furnacalis haplotype distribution and frequency.
Association between serum biomarkers CEA and LDH and response in advanced non‐small cell lung cancer patients treated with platinum‐based chemotherapy
Authors: de Jong Corine , Deneer Vera H.M. , Kelder Johannes C. , Ruven Henk , Egberts Toine C.G. , Herder Gerarda J.M.
Published: May 2020

Background

In addition to radiological evaluation, biomarkers may be useful in providing early information on the response to treatment, and supporting clinical decision‐making. The objective of this study was to investigate carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) as biomarkers for early assessment of response in patients with advanced non‐small cell lung cancer (NSCLC) treated with platinum‐based chemotherapy.

Methods

A retrospective follow‐up study was conducted from 2012 to 2017 among 593 consecutive patients with advanced NSCLC treated with first‐line platinum‐based chemotherapy in a large teaching hospital in the Netherlands. Pretreatment biomarker levels and changes from pretreatment levels were studied for association with radiologic response (partial response [PR] or complete response [CR], according to RECIST 1.1) using multivariate logistic regression, and with overall survival using COX proportional hazard modeling. Patient and disease characteristics such as age and disease stage were taken into account as potential confounding factors.

Results

Decreases in CEA and LDH (≥ 20%), particularly early in treatment, were significantly associated with better radiological response. Increases in these biomarkers (≥ 20%) and high pretreatment LDH levels (≥ 247 U/L) were significantly associated with lower overall survival.

Conclusions

Our results support determination of CEA and LDH levels for earlier assessment of response to platinum‐based chemotherapy in patients with advanced NSCLC. Hence, routine determination and evaluation of CEA and LDH levels, prior to each cycle of platinum‐based chemotherapy in advanced NSCLC, should be considered as part of daily clinical practice.

Key points

Significant findings of the study

Serum biomarkers in monitoring of treatment in advanced NSCLC would be useful.

CEA and LDH decrease (≥ 20%) is favorable for achieving radiological response.

High LDH levels and CEA/LDH increase (≥ 20%) is associated with reduced survival.

What this study adds

Monitoring of CEA seems to be particularly relevant in early stage of treatment.

CEA and LDH determination should be considered as part of daily clinical practice.
Testosterone replacement therapy: Pre‐treatment sex hormone‐binding globulin levels and age may identify clinical subgroups
Authors: Ramachandran Sudarshan , Hackett Geoffrey I. , Strange Richard C.
Published: May 2020

Background

Testosterone replacement therapy (TRT) improves health in some but not all men with type 2 diabetes (T2DM) and adult‐onset testosterone deficiency (TD). Such heterogeneity is compatible with the concept of patient subgroups that respond differently to therapy.

Objectives

Use baseline SHBG and age to identify putative subgroups that demonstrate different responses in variables such as waist circumference and HbA1c following TRT.

Materials and methods

A randomized double‐blind trial approach was used to recruit and randomize men with T2DM and adult‐onset TD into placebo and TRT‐treated groups. Multiple regression was used to study differences between groups.

Results

Baseline SHBG and change in SHBG (∆SHBG) were inversely related in the TRT group. Both median values of SHBG and age mediated the effect of TRT on ∆SHBG depending on whether baseline values were ≤ or>median (28.1 nmol/L, 63 years, respectively). In men with both SHBG ≤ 28.1 nmol/L and age ≤ 63 years (subgroup 1), TRT was positively associated with ∆SHBG (c = 4.67, 95%CI 1.17‐8.16, P = .010) while in those with SHBG > 28.1 nmol/L and age > 63.1 years (subgroup 4) the association was inverse (c = −7.07, 95%CI −11.64 to −2.49, P = .003). The association between TRT and change (∆) in waist circumference, HbA1c and International Index of Erectile Function (IIEF) score differed between subgroups; in subgroup 4 but not subgroup 1, the therapy was significantly associated with ∆waist circumference, ∆HbA1c and ∆IIEF.

Discussion

Though the mechanism remains unclear, our finding of different responses to TRT in terms of change in waist circumference, HbA1c and IIEF score supports the concept of subgroups in men with T2DM and adult‐onset TD.

Conclusion

Our approach may provide a basis for identifying men who will or will not derive benefit from TRT though a larger study is required.
A disease‐specific decline of the relative abundance of Bifidobacterium in patients with autoimmune hepatitis
Authors: Liwinski Timur , Casar Christian , Ruehlemann Malte C. , Bang Corinna , Sebode Marcial , Hohenester Simon , Denk Gerald , Lieb Wolfgang , Lohse Ansgar W. , Franke Andre , Schramm Christoph
Published: May 2020

Background

The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH.

Aim

To investigate disease‐specific microbiome alterations in AIH.

Methods

The V1‐V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy controls (HC) n = 95, primary biliary cholangitis (PBC) n = 99 and ulcerative colitis (UC) n = 81).

Results

Biodiversity (Shannon entropy) was decreased in AIH patients compared to HC (P = 0.016), which was partially reversed by azathioprine (P = 0.011). Regarding between‐sample diversity, AIH patients separated from HC, PBC and UC individuals (all P = 0.001). Compared to HC, decreased relative abundance of anaerobic genera such as Faecalibacterium and an increase of Veillonella and the facultative anaerobic genera Streptococcus and Lactobacillus were detected. Importantly, a disease‐specific decline of relative abundance of Bifidobacterium was observed in AIH patients. Lack of Bifidobacterium was associated with failure to achieve remission of AIH (P < 0.001). Of potential therapeutic implication, Bifidobacterium abundance correlated with average protein intake (P < 0.001). Random forests classification between AIH and PBC on the microbiome signature yielded an area under receiver operating characteristic curve (AUC) of 0.787 in the training cohort, and an AUC of 0.849 in an external validation cohort.

Conclusion

Disease‐specific faecal microbial alterations were identified in patients with AIH. Intestinal dysbiosis in AIH was characterised by a decline of Bifidobacterium, which was associated with increased disease activity. These results point to the contribution of intestinal microbiota to AIH pathogenesis and to novel therapeutic targets.
‘I Don't Want to See that the People Are Suffering’: Nurses in an Impoverished Community Talk About Caring for Women Following Stillbirths
Authors: Lappeman Maura , Swartz Leslie
Published: May 2020

This article explores the way in which nurses working in a high‐risk and dangerous environment understand and speak about their work caring for mothers following stillbirths. As far as we are aware, it is the first study of its kind from a low‐ or middle‐income country, and the first on this topic to apply the theoretical insights of Menzies Lyth in such contexts. In order to obtain rich exploratory data, a qualitative research methodology was used. The primary data source was interviews with nurses about their practices with women who have stillbirths. Reflecting on the findings from these interviews, we believe that the nurses’ disclosures followed an overarching narrative that connected their cultural identity and personal suffering to the care that they administer. These connections between identity and profession perpetuate a healthcare system where the nurse often gives, not only out of duty and selflessness, but also out of her own sense of vulnerability. As hospitals in low‐income countries seek to improve their capacity to heal and support those in need of medical attention, nurses should be a focus of research. While their role is generally seen as a support to the doctors, in the case of stillbirths, they are far more central and often ill‐equipped for their role as grieving partner. Nurses need to be acknowledged and adequately supported.
Association between dental pain and oral health‐related quality of life in children and adolescents: A systematic review and meta‐analysis
Authors: Barasuol Jéssica Copetti , Santos Pablo Silveira , Moccelini Bárbara Suelen , Magno Marcela Baraúna , Bolan Michele , Martins‐Júnior Paulo Antônio , Maia Lucianne Cople , Cardoso Mariane
Published: May 2020

Objective

The aim of this systematic review and meta‐analysis was to determine the impact of dental pain on oral health‐related quality of life (OHRQoL) in children and adolescents.

Methods

Electronic and manual searches were performed with no restrictions of language or year of publication. The PECO strategy was used to identify observational studies involving participants up to 19 years of age with dental pain and to those without dental pain to determine the impact of this condition on OHRQoL. The methodological quality of the studies was appraised using the Fowkes and Fulton checklist. Meta‐analysis was conducted by subgroups, based on OHRQoL questionnaires and effect measures. The quality of evidence was evaluated using the GRADE approach.

Results

Sixteen studies were included in the systematic review and fourteen in the meta‐analysis. The methodological quality of four of these studies was considered poor. The pooled results of the subgroup analysis (SOHO‐5, B‐ECOHIS and Child‐OIDP) showed that children with dental pain had a 3.64‐fold greater chance of a negative impact on OHRQoL ([log] 95% CI: 2.80‐4.72; I20%; P < .001). The second meta‐analysis (Child‐OIDP, SOHO‐5 and CPQ8‐10) demonstrated statistical significance (SMD 0.79; 95% CI: 0.43‐1.16; I292%; P < .001), as did the pooled results considering the B‐ECOHIS ([log] OR 7.75; 95% CI: 4.59‐13.11; I284%; P < .001). The certainty of evidence in all meta‐analyses was low.

Conclusions

Although the quality of the evidence is low, dental pain has a negative impact on OHRQoL.
Framing consumer food demand responses in a viral pandemic
Authors: Cranfield John A. L.
Published: May 2020

In this paper I explore several issues related to how the COVID‐19 pandemic might impact consumer demand for food. These impacts relate to the structure of preferences in the context of a pandemic, income and time constraints, and price effects. Discussion includes accounting for differential impacts of COVID‐19 on demand for food across sociodemographic characteristics, and several high‐level issues and observations related to where and how consumers shop and what they buy. My own thinking leads me to conclude that demand‐side factors will account for most of the changes we see in retail food market. These demand‐side effects will be dominated by income effects, the opportunity cost of time, and longer planning horizons on the part of consumers.
Linking data from a large clinical trial with the Australian Cerebral Palsy Register
Authors: Shepherd Emily , Mcintyre Sarah , Smithers‐Sheedy Hayley , Ashwood Pat , Sullivan Thomas R , te Velde Anna , Doyle Lex W , Makrides Maria , Middleton Philippa , Crowther Caroline A
Published: May 2020

Aim

To link data from a large maternal perinatal trial with the Australian Cerebral Palsy Register (ACPR) to identify children with cerebral palsy (CP).

Method

Deidentified data from the Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) and the ACPR were linked. Children born from 1996 to 2000 at Australian hospitals who survived and had 2‐year paediatric assessments were included. Children identified with CP in: (1) both the ACTOMgSO4 (2y) and the ACPR (5y), (2) the ACTOMgSO4 only, and (3) the ACPR only were compared.

Results

We included 913 children (492 males, 421 females; mean gestational age at birth 27.8wks [standard deviation 2.1wks]; range 23.0–40.0wks). Eighty‐four children received a CP diagnosis: 35 by the ACTOMgSO4 and the ACPR, 29 by the ACTOMgSO4 only, and 20 by the ACPR only. The ACTOMgSO4 diagnosed 76.2% (95% confidence interval [CI] 65.9–84.1) and the ACPR identified 65.5% (95% CI 54.7–74.9). Children born in states/territories with long‐standing versus more recently established registers were more likely to be included on the ACPR (p<0.05).

Interpretation

Linking deidentified perinatal trial data with the ACPR was achieved. Limitations of both strategies for identifying children with CP in this era (late 1990s and early 2000s) probably explain many of the differences observed, and inform future linkage studies and evaluations of CP‐preventive interventions.

What this paper adds

Randomized trial data were linked with the Australian Cerebral Palsy Register.

Trial (2y) and register (up to 5y) diagnoses of cerebral palsy (CP) differed.

States with long‐standing registers were more likely to include children with CP.
In‐hospital management of persons with haemophilia and COVID‐19: Practical guidance
Authors: Hermans Cedric , Lambert Catherine , Sogorb Amaury , Wittebole Xavier , Belkhir Leila , Yombi Jean Cyr
Published: May 2020

A new disease (COVID‐19) caused by a coronavirus (SARS‐CoV‐2) that appeared in China at the end of 2019 is currently spreading globally. This emerging virus is mainly responsible for respiratory tract infections and potentially fatal pneumonia, mainly in more frail patients. Persons with haemophilia of variable severity and from all parts of the world will likely be infected and develop COVID‐19.

We here propose practical guidance for the in‐hospital specific management of haemophilia persons with COVID‐19 including their possible transfer to the intensive care unit.

Rapid identification of the haemophilia status, undelayed and regular liaison with the haemophilia team, proper therapy with factor concentrates or alternative treatments appear instrumental to prevent haemophilia‐related complications in this setting. Information of patients and their families about COVID‐19, psychological support and good appreciation of the impact of haemophilia on therapeutic decisions including end‐of‐life directives are also addressed.
Increased heart rate due to supra‐ventricular tachycardia triggering premature ventricular contraction
Authors: Nakashima Takashi , Vlachos Konstantinos , Krisai Philipp , Jaïs Pierre
Published: May 2020

We describe a case wherein the presence of premature ventricular contractions was related to an increased heart rate that occurred due to supra‐ventricular tachycardia: atrial tachycardia or atrioventricular nodal reentry tachycardia.
Cardiac metabolism as a driver and therapeutic target of myocardial infarction
Authors: Zuurbier Coert J. , Bertrand Luc , Beauloye Christoph R. , Andreadou Ioanna , Ruiz‐Meana Marisol , Jespersen Nichlas R. , Kula‐Alwar Duvaraka , Prag Hiran A. , Eric Botker Hans , Dambrova Maija , Montessuit Christophe , Kaambre Tuuli , Liepinsh Edgars , Brookes Paul S. , Krieg Thomas
Published: May 2020

Reducing infarct size during a cardiac ischaemic‐reperfusion episode is still of paramount importance, because the extension of myocardial necrosis is an important risk factor for developing heart failure. Cardiac ischaemia‐reperfusion injury (IRI) is in principle a metabolic pathology as it is caused by abruptly halted metabolism during the ischaemic episode and exacerbated by sudden restart of specific metabolic pathways at reperfusion. It should therefore not come as a surprise that therapy directed at metabolic pathways can modulate IRI. Here, we summarize the current knowledge of important metabolic pathways as therapeutic targets to combat cardiac IRI. Activating metabolic pathways such as glycolysis (eg AMPK activators), glucose oxidation (activating pyruvate dehydrogenase complex), ketone oxidation (increasing ketone plasma levels), hexosamine biosynthesis pathway (O‐GlcNAcylation; administration of glucosamine/glutamine) and deacetylation (activating sirtuins 1 or 3; administration of NAD+‐boosting compounds) all seem to hold promise to reduce acute IRI. In contrast, some metabolic pathways may offer protection through diminished activity. These pathways comprise the malate‐aspartate shuttle (in need of novel specific reversible inhibitors), mitochondrial oxygen consumption, fatty acid oxidation (CD36 inhibitors, malonyl‐CoA decarboxylase inhibitors) and mitochondrial succinate metabolism (malonate). Additionally, protecting the cristae structure of the mitochondria during IR, by maintaining the association of hexokinase II or creatine kinase with mitochondria, or inhibiting destabilization of FOF1‐ATPase dimers, prevents mitochondrial damage and thereby reduces cardiac IRI. Currently, the most promising and druggable metabolic therapy against cardiac IRI seems to be the singular or combined targeting of glycolysis, O‐GlcNAcylation and metabolism of ketones, fatty acids and succinate.
Lamina feedback neurons regulate the bandpass property of the flicker‐induced orientation response in Drosophila
Authors: Yuan Deliang , Ji Xiaoxiao , Hao Shun , Gestrich Julia Yvonne , Duan Wenlan , Wang Xinwei , Xiang Yuanhang , Yang Jihua , Hu Pengbo , Xu Mengbo , Liu Li , Wei Hongying
Published: May 2020

Natural scenes contain complex visual cues with specific features, including color, motion, flicker, and position. It is critical to understand how different visual features are processed at the early stages of visual perception to elicit appropriate cellular responses, and even behavioral output. Here, we studied the visual orientation response induced by flickering stripes in a novel behavioral paradigm in Drosophila melanogaster. We found that free walking flies exhibited bandpass orientation response to flickering stripes of different frequencies. The most sensitive frequency spectrum was confined to low frequencies of 2–4 Hz. Through genetic silencing, we showed that lamina L1 and L2 neurons, which receive visual inputs from R1 to R6 neurons, were the main components in mediating flicker‐induced orientation behavior. Moreover, specific blocking of different types of lamina feedback neurons Lawf1, Lawf2, C2, C3, and T1 modulated orientation responses to flickering stripes of particular frequencies, suggesting that bandpass orientation response was generated through cooperative modulation of lamina feedback neurons. Furthermore, we found that lamina feedback neurons Lawf1 were glutamatergic. Thermal activation of Lawf1 neurons could suppress neural activities in L1 and L2 neurons, which could be blocked by the glutamate‐gated chloride channel inhibitor picrotoxin (PTX). In summary, lamina monopolar neurons L1 and L2 are the primary components in mediating flicker‐induced orientation response. Meanwhile, lamina feedback neurons cooperatively modulate the orientation response in a frequency‐dependent way, which might be achieved through modulating neural activities of L1 and L2 neurons.

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Epigenomic control of gonadotrophin‐releasing hormone neurone development and hypogonadotrophic hypogonadism
Authors: Linscott Megan L. , Chung Wilson C. J.
Published: May 2020

Mammalian reproductive success depends on gonadotrophin‐releasing hormone (GnRH) neurones to stimulate gonadotrophin secretion from the anterior pituitary and activate gonadal steroidogenesis and gametogenesis. Genetic screening studies in patients diagnosed with Kallmann syndrome (KS), a congenital form of hypogonadotrophic hypogonadism (CHH), identified several causal mutations, including those in the fibroblast growth factor (FGF) system. This signalling pathway regulates neuroendocrine progenitor cell proliferation, fate specification and cell survival. Indeed, the GnRH neurone system was absent or abrogated in transgenic mice with reduced (ie, hypomorphic) Fgf8 and/or Fgf receptor (Fgfr) 1 expression, respectively. Moreover, we found that GnRH neurones were absent in the embryonic olfactory placode of Fgf8 hypomorphic mice, the putative birthplace of GnRH neurones. These observations, together with those made in human KS/CHH patients, indicate that the FGF8/FGFR1 signalling system is a requirement for the ontogenesis of the GnRH neuronal system and function. In this review, we discuss how epigenetic factors control the expression of genes such as Fgf8 that are known to be critical for GnRH neurone ontogenesis, fate specification, and the pathogenesis of KS/CHH.
Making Sense of an Interconnected World: How Innovation Champions Drive Social Innovation in the Not‐for‐Profit Context
Authors: Molloy Courtney , Bankins Sarah , Kriz Anton , Barnes Lisa
Published: May 2020

Social innovation is critical for supporting the economic and social fabric of communities globally. Yet little is known about the processes through which social innovation occurs and how context shapes them. To date, scholarship has focused primarily on social entrepreneurs and social enterprise creation, while the role of established not‐for‐profits (NFPs) as agents of social innovation has received surprisingly little attention given their importance to communities. It is expected that innovation will be increasingly important for NFPs as shifts in their funding models create greater complexity in maintaining sustainability and continuity in social service delivery. This research generates a deeper understanding of the processes of social innovation within NFPs by examining how multiple levels of context influence the behaviors of a key set of agents: innovation champions. Adopting an interactionist lens, the study explores how shifts in funding policy at the macro level, and the role of leaders (CEOs and Boards) and organizational institutional logics at the meso level, influence champion behavior at the micro level. To do this, we draw on sensemaking as an important cognitive and action‐enabling mechanism. A qualitative, multicase study design with 46 interviews across six case organizations allows an in‐depth exploration of this under‐investigated area. The findings indicate that bricolage activity can facilitate championing that supports social innovation within NFPs and that organizational context guides the direction and content of champion behavior. The findings further uncover a broader range of behaviors and outcomes than have been previously attributed to champions, while highlighting the critical role that bricolage‐enabled championing can play in driving social innovation that is both directly impactful and offers significant longer‐term social impact. The important roles that sensebreaking, sensegiving, and sensemaking play in connecting champions’ interpretations of their contexts to their behaviors are also outlined.
RHDV2 epidemic in UK pet rabbits. Part 1: clinical features, gross post mortem and histopathological findings
Authors: Harcourt‐Brown N. , Silkstone M. , Whitbread T. J. , Harcourt‐Brown F. M.
Published: May 2020

Objectives

To report clinical features, gross post mortem and histopathological findings from an investigation into sudden or unexpected death in rabbits that was undertaken during an outbreak of rabbit haemorrhagic disease.

Materials and Methods

Using a standard protocol, veterinarians were invited to submit case histories and results of their post mortem examination of pet rabbits that died unexpectedly. Histopathological examination of heart, lungs, liver, spleen and kidney samples was collated with macroscopic appearance and clinical details.

Results

Hepatocellular necrosis, characteristic of rabbit haemorrhagic disease, was observed in 185 of 300 (62%) submissions, often accompanied by glomerular thrombosis and changes in other organs. Evidence of rabbit haemorrhagic disease was not apparent on histopathology in 113 of 300 (38%) rabbits. Gross post mortem examination by veterinary practitioners did not always reflect reported histopathological changes. No macroscopic abnormalities were seen in 78/185 (42%) of rabbit haemorrhagic disease cases. Rapid death and death of other rabbits in the household were common features of rabbit haemorrhagic disease. Ante mortem clinical signs included anorexia, collapse, lethargy, seizures, icterus, bleeding from the mouth, dyspnoea, hypothermia, pyrexia, bradycardia or poor blood clotting.

Clinical Importance

Rabbit haemorrhagic disease can be suspected from a history of sudden death, especially if multiple rabbits are affected. There is not always macroscopic evidence of the disease but histopathology is useful to support or refute a diagnosis of rabbit haemorrhagic disease and provide information about other causes of death.