bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual effort moderates postural cascade dynamics
Authors: Mangalam Madhur , Lee I-Chieh , Newell Karl M. , Kelty-Stephen Damian G.
Published: July 2020

Standing still and focusing on a visible target in front of us is a preamble to many coordinated behaviors (e.g., reaching an object). Hiding behind its apparent simplicity is a deep layering of texture at many scales. The task of standing still laces together activities at multiple scales: from ensuring that a few photoreceptors on the retina cover the target in the visual field on an extremely fine scale to synergies spanning the limbs and joints at smaller scales to the mechanical layout of the ground underfoot and optic flow in the visual field on the coarser scales. Here, we used multiscale probability density function (PDF) analysis to show that postural fluctuations exhibit similar statistical signatures of cascade dynamics as found in fluid flow. In participants asked to stand quietly, the oculomotor strain of visually fixating at different distances moderated postural cascade dynamics. Visually fixating at a comfortable viewing distance elicited posture with a similar cascade dynamics as posture with eyes closed. Greater viewing distances known to stabilize posture showed more diminished cascade dynamics. In contrast, nearest and farthest viewing distances requiring greater oculomotor strain to focus on targets elicited a dramatic strengthening of postural cascade dynamics, reflecting active postural adjustments. Critically, these findings suggest that vision stabilizes posture by reconfiguring the prestressed poise that prepares the body to interact with different spatial layouts.
Delay-Induced Uncertainty in Physiological Systems
Authors: Karamched Bhargav , Hripcsak George , Albers Dave , Ott William
Published: July 2020

Abstract

Medical practice in the intensive care unit is based on the supposition that physiological systems such as the human glucose-insulin system arereliabile. Reliability of dynamical systems refers to response to perturbation: A dynamical system is reliable if it behaves predictably following a perturbation. Here, we demonstrate that reliability fails for an archetypal physiological model, the Ultradian glucose-insulin model. Reliability failure arises because of the presence of delay. Using the theory of rank one maps from smooth dynamical systems, we precisely explain the nature of the resulting delay-induced uncertainty (DIU). We develop a recipe one may use to diagnose DIU in a general dynamical system. Guided by this recipe, we analyze DIU emergence first in a classical linear shear flow model and then in the Ultradian model. Our results potentially apply to a broad class of physiological systems that involve delay.
Genome-wide Identification of Disease Resistance Genes (R Genes) in Wheat
Authors: Andersen Ethan J. , Lindsey Lauren E. , Nepal Madhav P.
Published: July 2020

Proteins encoded by plant resistance genes (R genes) detect pathogenic effectors and initiate immune responses. Although R genes in many plant genomes are identified, they are yet to be identified in wheat. The major objectives of this project were to conduct genome-wide identification of the NB-ARC-encoding R genes in wheat (Triticum aestivumL.) and assess their genomic architecture and potential functional divergence. Wheat protein sequences were obtained from the Ensembl Genomes database, and genes were identified using interpro program. Chromosomal locations of the R genes were determined and syntenic analyses were performed. Altogether, 2151 wheat NB-ARC-encoding genes were identified, among which 1298 genes formed 547 gene clusters. Many of these gene clusters included highly similar genes likely formed by tandem duplications. Among the NB-ARC-encoding genes, 1552 (∼72%) encode Leucine-Rich Repeats (LRRs), 802 are Coiled-Coil (CC) domain-encoding CC-NBS-LRR (CNL) genes and three are Resistance to Powdery mildew 8 (RPW8) domain-encoding RPW8-NBS-LRR (RNL) genes. Surprisingly, five of the NB-ARC-encoding genes encoded a Toll/Interleukin-1 Receptor (TIR), with no LRR, known as TN genes. CNL clades formed similar nesting patterns with a large expansion of CNL-C group like previously reported findings in wheat relatives. Comparisons of the wheat genome with barley (Hordeum vulgareL.) and Tausch’s goatgrass (Aegilops tauschiiCoss.), showed similar locations for homologous NB-ARC-encoding genes. These results showed that R genes in wheat have diversified through duplication to encode receptors that recognize rapidly evolving pathogenic effectors. Identified R genes in this study have implications in plant breeding, as a source of resistance for crop improvement.
Whole-exome sequencing analysis on products of conception: A cohort study to evaluate clinical utility and genetic etiology for pregnancy loss
Authors: Zhao Chen , Chai Hongyan , Zhou Qinghua , Wen Jiadi , Reddy Uma M. , Kastury Rama , Jiang Yonghui , Mak Winifred , Bale Allen E. , Zhang Hui , Li Peining
Published: July 2020

Purpose

Pregnancy loss ranging from spontaneous abortion (SAB) to stillbirth can result from monogenic causes of Mendelian inheritance. This study evaluated the clinical application of whole exome sequencing (WES) in identifying the genetic etiology for pregnancy loss.

Methods

A cohort of 102 specimens from products of conception (POC) with normal karyotype and absence of pathogenic copy number variants were selected for WES. Abnormality detection rate (ADR) and variants of diagnostic value correlated with SAB and stillbirth were evaluated.

Results

WES detected six pathogenic variants, 16 likely pathogenic variants, and 17 variants of uncertain significance favor pathogenic (VUSfp) from this cohort. The ADR for pathogenic and likely pathogenic variants was 22% and reached 35% with the inclusion of VUSfp. The ADRs of SAB and stillbirth were 36% and 33%, respectively. Affected genes included those associated with multi-system abnormalities, neurodevelopmental disorders, cardiac anomalies, skeletal dysplasia, metabolic disorders and renal diseases.

Conclusion

These results supported the clinical utility of WES for detecting monogenic etiology of pregnancy loss. The identification of disease associated variants provided information for follow-up genetic counseling of recurrence risk and management of subsequent pregnancies. Discovery of novel variants could provide insight for underlying molecular mechanisms causing fetal death.
Genome-wide Genetic Marker Analysis and Genotyping ofEscherichia fergusoniistrain OTSVEF–60
Authors: Saha Otun , Rakhi Nadira Naznin , Hoque M. Nazmul , Sultana Munawar , Hossain M. Anwar
Published: July 2020

Poultry originatedEscherichia fergusonii(POEF), an emerging bacterial pathogen, causes a wide range of intestinal and extra-intestinal infections in the poultry industry which incurred significant economic losses worldwide. Chromosomal co-existence of antibiotics and metal resistance genes has recently been the focal point of POEF isolates besides its pathogenic potentials. This study reports the complete genome analysis of POEF strain OTSVEF-60 from the poultry originated samples of Bangladesh. The assembled draft genome of the strain was 4.2 Mbp containing 4,503 coding sequences, 120 RNA (rRNA = 34, tRNA = 79, ncRNA = 7), and three intact phage signature regions. Forty one broad range antibiotic resistance genes (ARGs) includingdfrA12,qnrS1,blaTEM-1,aadA2,tet(A) andsul-2 along with multiple efflux pump genes were detected, which translated to phenotypic resistant patterns of the pathogen to trimethoprim, fluoroquinolones, β-lactams, aminoglycoside, tetracycline, and sulfonamides. Moreover, 22 metal resistance genes were found co-existing within the genome of the POEF strain, and numerous virulence genes (VGs) coding forcit(AB),feo(AB),fep(ABCG),csg(ABCDEFG),fliC,ompAgadA,ecpD etc were also identified throughout the genome. In addition, we detected a Class I integron gene cassette harboringdfrA12,ant(3″)-I andqacEΔ-sul2) genes, 42 copies of insertion sequence (IS) elements, and two CRISPR arrays. The genomic functional analysis revealed overexpression of several metabolic pathways related to motility, flagellar assembly, epithelial cell invasion, quorum sensing, biofilm formation, and biosynthesis of vitamin, co-factors, and secondary metabolites. We herein for the first time detected multiple ARGs, VGs, mobile genetic elements, and some metabolic functional genes in the complete genome of POEF strain OTSVEF-60, which might be associated with the pathogenesis, spreading of ARGs and VGs, and subsequent treatment failure against this emerging avian pathogen with currently available antimicrobials.
Quantitative mapping of membrane nanoenvironments through single-molecule imaging of solvatochromic probes
Authors: Nieves Daniel J. , Owen Dylan M.
Published: July 2020

Environmentally-sensitive fluorophores report on their local biochemical or biophysical environments through changes in their emission. We combine the solvatochromic probe di-4-ANEPPDHQ with multi-channel SMLM and quantitative analysis of the resulting marked point patterns to map biophysical environments in the mammalian cell membrane. We show that plasma membrane properties can be mapped with nanoscale resolution, and that partitioning between ordered and disordered regions is observed on length scales below 300 nm.
Theoretical analysis predicts an optimal therapeutic strategy in distinct parkinsonian landscapes of the striatum
Authors: Heltberg Mathias L. , Awada Hussein N. , Lucchetti Alessandra , Jensen Mogens H. , Dreyer Jakob K. , Rasmussen Rune N.
Published: July 2020

Parkinson’s disease (PD) results from a loss of dopaminergic neurons. The age of disease onset, its progression and symptoms vary significantly between patients, pointing to a complex relationship between neuron loss and PD etiology. Yet, our understanding of the clinical variability remains incomplete. Here, we use biophysical modelling to characterize the dopaminergic landscape in the healthy and denervated striatum. Based on currently proposed mechanisms causing PD, we model three distinct denervation patterns, and show notable differences in the dopaminergic network as denervation progresses. We find local and global differences in the activity of two types of striatal neurons depending on the denervation pattern. Finally, we identify an optimal cellular strategy for maintaining normal dopamine signaling when neurons degenerate stochastically within our model. Our results derive a conceptual framework in which the clinical variability of PD is rooted in distinct denervation patterns and forms testable predictions for future PD research.
Toward understanding thrombus fracture: Dissipative phenomena of whole blood clots
Authors: Sugerman Gabriella P. , Parekh Sapun H. , Rausch Manuel K.
Published: July 2020

When thrombus fractures and breaks off it can occlude vital vessels such as those of the heart, lung, or brain. These thromboembolic conditions are responsible for 1 in 4 deaths world-wide. This problem is also of significant current interest as 1 in 3 COVID-19 intensive care patients exhibit thromboembolic complications. Thrombus resistance to fracture is driven by its intrinsic fracture toughness as well as other, non-surface-creating dissipative mechanisms. In our current work, we identify and quantify these latter mechanisms toward future studies that aim to delineate fracture from other forms of dissipation. To this end, we use an in vitro thrombus mimic system to produce whole blood clots and explore their dissipative mechanics under simple uniaxial extension, cyclic loading, and stress-relaxation. We found that whole blood clots exhibit Mullins effect, hysteresis, permanent set, strain-rate dependence, and nonlinear stress-relaxation. Interestingly, we found that performing these tests under dry or submerged conditions did not change our results. However, performing these tests under room temperature or body temperature conditions yielded differences. Overall, we have demonstrated that whole blood clots show several dissipative phenomena - similarly to hydrogels - that will be critical to our understanding of thrombus fracture.
The Dystonia Gene THAP1 Controls DNA Double Strand Break Repair Choice
Authors: Shinoda Kenta , Zong Dali , Callen Elsa , Wu Wei , Dumitrache Lavinia C. , Belinky Frida , Wong Nancy , Ishikawa Momoko , Stanlie Andre , Ehrlich Michelle , McKinnon Peter J. , Nussenzweig Andre
Published: July 2020

The Shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and REV7, shields DNA double strand breaks (DSBs) from nucleolytic resection. The end-protecting activity of Shieldin promotes productive non-homologous end joining (NHEJ) in G1 but can threaten genome integrity during S-phase by blocking homologous recombination (HR). Curiously, the penultimate Shieldin component, SHLD1 is one of the least abundant mammalian proteins. Here, we report that the transcription factors THAP1, YY1 and HCF1 bind directly to theSHLD1promoter, where they cooperatively maintain the low basal expression ofSHLD1. Functionally, this transcriptional network ensures that SHLD1 protein levels are kept in check to enable a proper balance between end protection and end resection during physiological DSB repair. In the context of BRCA1 deficiency, loss of THAP1 dependent SHLD1 expression confers cross resistance to PARP inhibitor and cisplatin, and shorter progression free survival in ovarian cancer patients. In contrast, loss of THAP1 in BRCA2 deficient cells increases genome instability and correlates with improved responses to chemotherapy. Pathogenic THAP1 mutations are causatively linked to the adult-onset torsion dystonia type 6 (DYT6) movement disorder, but the critical disease targets are unknown. We further demonstrate that murine models ofThap1-associated dystonia show reducedShld1expression concomitant with elevated levels of unresolved DNA damage in the brain. In summary, our study provides the first example of a transcriptional network that directly controls DSB repair choice and reveals a previously unsuspected link between DNA damage and dystonia.
Sarcolambans are phospholamban- and sarcolipin-like regulators of the sarcoplasmic reticulum calcium pump SERCA
Authors: Bak Jessi J. , Aguayo-Ortiz Rodrigo , Khan Muhammad Bashir , Robia Seth L. , Lemieux M. Joanne , Espinoza-Fonseca L. Michel , Young Howard S.
Published: July 2020

From insects to humans, calcium signaling is essential for life. An important part of this process is the sarco-endoplasmic reticulum calcium pump SERCA, which maintains low cytosolic calcium levels required for intracellular calcium homeostasis. In higher organisms, this is a tightly controlled system where SERCA interacts with tissuespecific regulatory subunits such as phospholamban in cardiac muscle and sarcolipin in skeletal muscle. With the recent discovery of the sarcolambans, the family of calcium pump regulatory subunits also appears to be ancient, spanning more than 550 million years of evolutionary divergence from insects to humans. This evolutionary divergence is reflected in the peptide sequences, which vary enormously from one another and range from vaguely phospholamban-like to vaguely sarcolipin-like. Here, our goal was to investigate select sarcolamban peptides for their ability to regulate calcium pump activity. For a side-by-side comparison of diverse sarcolamban peptides, we tested them against mammalian skeletal muscle SERCA1a. This allowed us to determine if the sarcolamban peptides mimic phospholamban and sarcolipin in their regulatory activities. Four sarcolamban peptides were chosen from different invertebrate species. Of these, we were able to express and purify sarcolamban peptides from bumble bee, water flea, and tadpole shrimp. Sarcolamban peptides were co-reconstituted into proteoliposomes with mammalian SERCA1a and the effect of each peptide on the apparent calcium affinity and maximal activity of SERCA was measured. While all peptides were super-inhibitors of SERCA, they exhibited either phospholamban-like or sarcolipin-like characteristics. Molecular modeling, protein-protein docking, and molecular dynamics simulations were used to reveal novel features of insect versus mammalian calcium pumps and the sarcolamban regulatory subunits.
The state of the knowledge-based economy in the Arab world: cases of Qatar and Lebanon
Authors: Ben Hassen Tarek
Published: July 2020

Purpose

The purpose of this paper is to examine the current state of the knowledge-based economy in two distinctive case studies in the Arab World: Qatar and Lebanon. Based on five aspects of the knowledge-based economy namely: ICT, human capital and education; innovation, entrepreneurship, and economic and institutional regime, we provide a careful view of the obstacles and challenges that Qatar and Lebanon are facing and how this is hindering their transformation to a knowledge-based economy.

Design/methodology/approach

The methodology of this research is based on a literature review and information collected through semi-structured interviews with the different stakeholders of the knowledge-based economy in Qatar and Lebanon.

Findings

The research reveals that numerous factors shape the knowledge-based economy in Qatar and Lebanon. In Qatar, the main strength of the knowledge-based economy is the determination of the Qatari government to diversify the economy and the main weaknesses are the shortage of qualified human resources, the fear of failure and the low performance of the innovation system. In Lebanon, the knowledge-based economy is driven by the education system and the entrepreneurship culture, nevertheless the political instability of the country and the weak ICT infrastructure impede its development.

Originality/value

These findings contribute to the clarification and critical analysis of the current state of the knowledge-based economy in Qatar and Lebanon, which would have several policy implications.
Green supplier integration and environmental performance: do environmental innovation and ambidextrous governance matter?
Authors: Zhang Qiansong , Pan Jieyi , Feng Taiwen
Published: July 2020

Purpose

Since firms are often puzzled with the adoption of proper governing mechanism to achieve their environmental benefits, this research examines how green supplier integration (GSI) affects environmental performance via environmental innovation and the moderating role of ambidextrous governance.

Design/methodology/approach

The authors tested the hypotheses by adopting two-waved survey data from 206 Chinese manufacturers and the hierarchical regression analysis.

Findings

The results revealed that GSI is positively linked with both incremental and radical environmental innovation, which further enhance environmental performance. Moreover, balanced ambidexterity enhanced the link between GSI and incremental environmental innovation, while combined ambidexterity alleviated the link between GSI and radical environmental innovation.

Practical implications

Firms should integrate suppliers into their activities of dealing with environmental issues to realize environmental benefits through facilitating environmental innovation. Moreover, the choice of different dimensions of ambidextrous governance can affect the environmental benefits of GSI.

Originality/value

This research enriches the authors’ understanding of how to achieve environmental benefits by engaging in GSI, and it provides a novel and insightful approach for better managing GSI from the perspective of ambidextrous governance.
Toxic epidermal necrolysis induced by human herpesvirus 7 treated with a tumor necrosis factor‐α inhibitor
Authors: Shen Meng‐Han , Liu Ming‐Tsan , Chung Wen‐Hung , Lu Chun‐Wei
Published: July 2020

Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a life‐threatening hypersensitivity reaction. Long‐term sequelae include dry eyes, visual impairment and psychological complications. TEN is mostly induced by medication; however, viral infections, such as coxsackievirus A6, are known triggers of this disease. However, how to define the role of infection in SJS/TEN is still a problem. Most patients develop SJS/TEN over the course of symptoms of the infection first, and then take medication. Therefore, virus culture and nucleic acid detection at the acute stage cannot predict that the virus itself will indeed produce such a serious reaction. Furthermore, many SJS/TEN patients who are diagnosed with an infection are afraid of receiving the drug rechallenge test. Thus, we report the first case worldwide of a patient who suffered from TEN caused by herpesvirus 7 infection, which was confirmed by both real‐time polymerase chain reaction and lymphocyte transformation test.
Interleukin (IL)‐17F and IL‐17E are related to fibrosis and vasculopathy in systemic sclerosis
Authors: Fukayama Maiko , Yoshizaki Ayumi , Fukasawa Takemichi , Ebata Satoshi , Kuzumi Ai , Yoshizaki‐Ogawa Asako , Asano Yoshihide , Oba Koji , Sato Shinichi
Published: July 2020

Systemic sclerosis (SSc) is an autoimmune disease that causes fibrosis and vasculopathy of the skin and internal organs against a background of autoimmune abnormalities. In recent years, the importance of the interleukin (IL)‐17 family for inflammatory diseases has received much attention, but autoimmune diseases have not yet been fully explored. As for SSc, there is also no unified perspective on the involvement of the IL‐17 family in its development, and few studies have been conducted linking IL‐17F and IL‐17E particularly to the disease severity. In the present study, we examined the correlation between serum IL‐17F and IL‐17E levels and disease severity in SSc patients. Moreover, the expression of the receptors for these cytokines, IL‐17RB and IL‐17RC, in skin tissues obtained by skin biopsy was examined by immunohistochemistry. Both cytokines were significantly elevated in the sera of patients with diffuse cutaneous SSc patients compared with healthy controls. Serum IL‐17F levels correlated with modified Rodnan total skin thickness score, a semiquantitative measure of skin sclerosis, percent predicted forced vital capacity, percent predicted carbon monoxide lung diffusion capacity and serum levels of Krebs von den Lungen‐6 and surfactant protein‐D, serological markers of interstitial lung disease. Serum IL‐17E levels were significantly correlated with percent predicted forced vital capacity and serum Krebs von den Lungen‐6 levels. Serum levels of IL‐17F and IL‐17E also correlated with the prevalence of digital ulcers, and serum IL‐17F levels were associated with elevated right ventricle systolic pressure values. In addition, IL‐17RC and IL‐17RB expression was increased in the skin tissues of diffuse cutaneous SSc patients. These results suggested that IL‐17F and IL‐17E could be involved in fibrosis and vasculopathy in SSc through their respective receptors in the affected organ tissues.
Addressing tagging location bias to assess space use by marine animals
Authors: Hays Graeme C. , Rattray Alex , Esteban Nicole
Published: July 2020

Estimates of space use derived from animal tracking studies are often biased by where animals are tagged, with areas distant to the tagging site, in both space and time, being under‐represented.

We develop an approach to overcome this tagging bias by quantifying the likely movements of animals after tags have failed.

We illustrate the approach using high accuracy Fastloc‐GPS tracking data for 35 adult female green turtles Chelonia mydas equipped with satellite tags within one of the world's largest marine protected areas (MPAs), the British Indian Ocean Territory (BIOT) MPA.

Individuals migrated up to 5,127 km from the tagging site, breaking migration distance records for this species. For 28 of the 35 individuals travelling to foraging locations well outside the MPA, we estimated that they spent, on average, 9.8% of their adult lives within the BIOT MPA.

Synthesis and applications. We highlight the importance of the British Indian Ocean Territory marine protected area (MPA) as a nesting sanctuary for turtles from across an ocean basin. The general approach outlined here can be applied to a broad range of taxa, including marine mammals, fish and sea turtles and will allow unbiased estimates of how important areas, such as MPAs, are used.
Characterization of a novel Pantoea symbiont allows inference of a pattern of convergent genome reduction in bacteria associated with Pentatomidae
Authors: Kashkouli Marzieh , Castelli Michele , Floriano Anna M. , Bandi Claudio , Epis Sara , Fathipour Yaghoub , Mehrabadi Mohammad , Sassera Davide
Published: July 2020

Phytophagous stink bugs typically harbor nutritional symbiotic bacteria in their midgut, to integrate their unbalanced diet. In the Pentatomidae, most symbionts are affiliated to the genus Pantoea, and are polyphyletic. This suggests a scenario of an ancestral establishment of symbiosis, followed by multiple symbiont replacement events by akin environmental bacteria in different host lineages. In this study, a novel Pantoeaspecies (‘CandidatusPantoea persica’) was characterized from the gut of the pentatomid Acrosternum arabicum, and shown to be highly abundant in a specific portion of the gut and necessary for the host development. The genome of the symbiont (2.9 Mb), while presenting putative host‐supportive metabolic pathways, including those for amino acids and vitamin synthesis, showed a high level of pseudogenization, indicating ongoing genome reduction. Comparative analyses with other free‐living and symbiotic Pantoea highlighted a convergent pattern of genome reduction in symbionts of pentatomids, putatively following the typical phases modelized in obligate nutritional symbionts of insects. Additionally, this system has distinctive traits, as hosts are closely related, and symbionts originated multiple independent times from closely related free‐living bacteria, displaying convergent and independent conspicuous genome reduction. Due to such peculiarities, this may become an ideal model to study genome evolutionary processes in insect symbionts.
Trade in fisheries services under the WTO and GATS framework
Authors: Will Emma , Pettersson Maria , Stage Jesper
Published: July 2020

This paper studies how fisheries services are classified in the World Trade Organization (WTO) framework for trade in services and discusses the potential impact of unclear classifications. The WTO plays a key role in regulation and assessment in the area of trade in services, mainly due to the General Agreement on Trade in Services (GATS), which contains the only set of multilateral rules managing such trade internationally. The purpose of GATS is to create a credible and reliable system of international trade rules that ensures fair treatment of all participants. Through negotiations, individual countries establish commitments to provide market access and limiting national treatment in various service sectors. During such negotiations, the classification of services is a prerequisite to ensure unambiguous and comparable commitments. However, the classification list used by the WTO, namely the W/120, is based on, and corresponds to, old versions of other classification lists, leading to unclear classifications. This lack of clarity in sectoral classifications makes policy analysis unnecessarily difficult and creates a risk that trade agreements may be interpreted differently by different parties.
Sulfation, structural analysis, and anticoagulant bioactivity of ginger polysaccharides
Authors: Wang Chaofan , He Yaoxuan , Tang Xiaozhen , Li Ningyang
Published: July 2020

In this study, ginger polysaccharide (GP), ginger polysaccharide 1 (GP1), and ginger polysaccharide 2 (GP2) from ginger were firstly modified by sulfation. Fourier transform infrared, and nuclear magnetic resonance spectra investigation of sulfated ginger polysaccharide (SGP), sulfated ginger polysaccharide 1 (SGP1), and sulfated ginger polysaccharide 2 (SGP2) revealed that the sulfation successfully occurred with the characteristic absorption peak of polysaccharide. Congo red experiment showed that triple helical structure existed in SGP and SGP1, but random coils existed in SGP2. SGP, SGP1, and SGP2 all showed a rough and rugged surface with plenty of small pores. The blood clotting time of SGP2 or SGP at 2 mg/mL in activated partial thromboplastin time (APTT) assay was 41.42 or 38.01 s, respectively, which were approximately 1.33‐ and 1.22‐fold longer than that of the physiological saline. Compared to the saline control group, prothrombin time (PT) was increased by 1.22‐fold with the addition of GP at 2 mg/mL. However, no clotting inhibition phenomenon was observed in thrombin time test even at the concentrations that APTT and PT were obviously prolonged. It indicated that GP2, SGP2, and SGP inhibited the intrinsic pathway of coagulation, but GP inhibited both the intrinsic and extrinsic pathways of coagulation. Hence, ginger polysaccharides might be used as anticoagulants and therapeutic reagents for thrombosis.
Salmonellagrows massively and aerobically in chicken faecal matter
Authors: Guerrero Teresa , Calderón Diana , Zapata Sonia , Trueba Gabriel
Published: July 2020

The use of wastewater for irrigation and animal manure as fertilizer can cause transmission of intestinal pathogens, conditions frequently observed in low‐ and middle‐income countries (LMICs). Here, we tested the ability ofSalmonellato grow in the faecal matter. We inoculated freshly isolatedSalmonellastrains (from chickens) in chicken faecal matter and incubated for 1 to 12 days, under aerobic and anaerobic conditions. We found that bothSalmonellaandEscherichia colimultiplied massively in faecal matter outside a host and significantly higher in aerobic conditions. Our results have critical implications in waste management, as we demonstrate that aerobic treatments may not be the best to reduce the number ofSalmonellain the environment.
Soil microbiota influences clubroot disease by modulatingPlasmodiophora brassicaeandBrassica napustranscriptomes
Authors: Daval Stéphanie , Gazengel Kévin , Belcour Arnaud , Linglin Juliette , Guillerm‐Erckelboudt Anne‐Yvonne , Sarniguet Alain , Manzanares‐Dauleux Maria J. , Lebreton Lionel , Mougel Christophe
Published: July 2020

The contribution of surrounding plant microbiota to disease development has led to the ‘pathobiome’ concept, which represents the interaction between the pathogen, the host plant and the associated biotic microbial community, resulting or not in plant disease. The aim herein is to understand how the soil microbial environment may influence the functions of a pathogen and its pathogenesis, and the molecular response of the plant to the infection, with a dual‐RNAseq transcriptomics approach. We address this question usingBrassica napusandPlasmodiophora brassicae, the pathogen responsible for clubroot. A time‐course experiment was conducted to study interactions betweenP. brassicae, twoB. napusgenotypes and three soils harbouring high, medium or low microbiota diversities and levels of richness. The soil microbial diversity levels had an impact on disease development (symptom levels and pathogen quantity). TheP. brassicaeandB. napustranscriptional patterns were modulated by these microbial diversities, these modulations being dependent on the host genotype plant and the kinetic time. The functional analysis of gene expressions allowed the identification of pathogen and plant host functions potentially involved in the change of plant disease level, such as pathogenicity‐related genes (NUDIX effector) inP. brassicaeand plant defence‐related genes (glucosinolate metabolism) inB. napus.
Three‐dimensional printed navigational template for localizing small pulmonary nodules: A case‐controlled study
Authors: Fu Rui , Chai Yun‐Fei , Zhang Jia‐Tao , Zhang Tao , Chen Xiao‐Kun , Dong Song , Yan Hong‐Hong , Yang Xue‐Ning , Huang Mei‐Ping , Wu Yi‐Long , Zhuang Jian , Zhong Wen‐Zhao
Published: July 2020

Background

Localization of small pulmonary nodules is an inevitable challenge for the thoracic surgeon. This study aimed to investigate the accuracy of three‐dimensional (3D) printing technology for localizing small pulmonary nodules, especially ground‐glass nodules (GGNs).

Methods

This study enrolled patients with peripheral small pulmonary nodules (≤ 2 cm) who required preoperative localization. In the comparison period, patients underwent both computed tomography‐guided (CT‐G) and 3D‐printing template guided (3D‐G) localization to compare the accuracies of the two methods. In the testing period, the 3D‐printing technique was implemented alone. The 3D‐printing physical navigational template was designed based on data from perioperative CT images. Clinical data, imaging data, surgical data, and evaluation index were collected for further analysis. The learning curve of the 3D‐printing localization technique was assessed using cumulative sum (CUSUM) analysis and multiple linear regression analysis.

Results

In the comparison period (n = 14), the success rates of CT‐G and 3D‐G were 100% and 92.9% (P = 0.31), respectively; in the testing period (n = 23), the success rate of 3D‐G was 95.6%. The localization times of CT‐G, 3D‐G (comparison), and 3D‐G (testing) were 23.6 ± 5.3, 19.3 ± 6.8, and 9.8 ± 4.6 minutes, respectively. The CUSUM learning curve was modeled using the equation: Y = 0.48X2 − 0.013X − 0.454 (R2 = 0.89). The learning curve was composed of two phases, phase 1 (the initial 20 patients) and phase 2 (the remaining 17 patients).

Conclusions

3D printing localization has adequate accuracy and is a feasible and accessible strategy for use in localizing small pulmonary nodules, especially in right upper lobe. The use of this technique could facilitate lung nodule localization prior to surgery.
Clinical and exome sequencing findings in seven children with Bardet–Biedl syndrome from Turkey
Authors: Gumus Evren , Tuncez Ebru , Oz Ozlem , Saka Guvenc Merve
Published: July 2020

Background

Bardet–Biedl syndrome (BBS) is a very‐rare autosomal recessive genetic disorder with severe multisystem manifestations. Genetic testing plays an important role in the early diagnosis of the disease. In this study, while trying to elucidate the genetic etiology of seven individuals with clinical BBS diagnosis from six different families, we also aimed to examine the distribution of BBS variations in this region of Turkey.

Methods and materials

Exome sequencing analysis is performed for clinically diagnosed patients with BBS in the present study followed by parental segregation. The unreported and previously described clinical features are presented.

Results

Homozygous variants, four of which are unreported, in BBS‐related genes (BBS5 [c.682‐2A > G], MKKS [c.775del], BBS7 [c.849+1G > T], BBS9 [c.965G > A], BBS10 [c.145C > T], LZTFL1[c.384G > A]) are detected for all the seven individuals included in the study. The most common clinical finding is polydactyly followed by renal anomalies. The clinical features not previously described are correlated to the unreported variant.

Conclusions

In this study, exome sequencing findings are discussed and four previously unreported disease‐associated variants are described including the fifth BBS‐implicated LZTFL1 change and possible genotype–phenotype correlation is described.
Predator naïve minnows respond to their conspecific alarm substance but not the odour from a non‐native predator
Authors: Kadye Wilbert T. , Leigh Simon , Booth Anthony J.
Published: July 2020

When exposed to predator cues, ostariophysan fishes exhibit short‐term anti‐predator behavioural responses in order to minimise predation risk. Non‐native predator cues are, however, likely to elicit poor behavioural responses in native prey fishes. This study investigated whether chubbyhead barb Enteromius anoplus, a native freshwater minnow in South Africa, had the innate ability to recognise and respond to largemouth bass Micropterus salmoides, a non‐native piscivore. This was experimentally evaluated by investigating behavioural responses to both the non‐native predator's odour and damage‐released conspecific alarm substance (CAS). Chubbyhead barbs did not exhibit any behavioural response to largemouth bass odour both before and after exposure to CAS. This suggests that the chubbyhead barbs likely lacked the innate ability to recognise the non‐native largemouth bass predator kairomones. By comparison, exposure to CAS was associated with significant behavioural responses, with chubbyhead barbs shifting from free‐swimming to hovering, and frequent use of refugia. This suggests that despite ineffective response to non‐native largemouth bass odour, chubbyhead barbs responded to general predator attack. Overall, this study suggests the potential for non‐native largemouth bass to induce negative consumptive effects on chubbyhead barbs due to their inability to identify non‐native predator's odour. In addition, nonconsumptive effects are likely due to altered activities in response to predator attack.
The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota
Authors: Misawa Noboru , Higurashi Takuma , Takatsu Tomohiro , Iwaki Michihiro , Kobayashi Takashi , Yoshihara Tsutomu , Ashikari Keiichi , Kessoku Takaomi , Fuyuki Akiko , Matsuura Tetsuya , Ohkubo Hidenori , Usuda Haruki , Wada Koichiro , Naritaka Nakayuki , Takei Hajime , Nittono Hiroshi , Matsumoto Mitsuharu , Honda Akira , Nakajima Atsushi , Camilleri Michael
Published: July 2020

Background

Elobixibat, a novel inhibitor of apical sodium‐dependent bile acid transporter for treating chronic constipation, increases colonic bile acid concentrations, stimulating bowel function. However, it is not clear which bile acids are altered, or whether altered gut microbiota are associated with functional effects that may alter bowel function.

Aims

To investigate the effects of elobixibat on changes in the faecal concentrations of total and individual bile acids and in faecal microbiota.

Methods

This was a prospective, single‐centre study. After baseline period, patients received 10 mg daily of elobixibat for 2 weeks. We evaluated the effects on bowel function, changes in faecal bile acid concentrations and composition of gut bacteria, before and after elobixibat administration.

Results

In the 30 patients analysed, the frequency of pre‐ and post‐treatment bowel movements per fortnight was 7 and 10 (P < 0.001), respectively. The pre‐treatment faecal bile acid concentration increased significantly from 10.9 to 15.0 µg/g stool post‐treatment (P = 0.030), with a significant increase in faecal deoxycholic acid (pre‐treatment 3.94 µg/g stool to post‐treatment 5.02 µg/g stool, P = 0.036) and in glycine‐conjugated deoxycholic and chenodeoxycholic acids. Shannon index was significantly decreased, but there were no significant changes at the genus and phylum levels.

Conclusions

Short term treatment with elobixibat increased the concentrations of total bile acids and deoxycholic acid and decreased the diversity of faecal microbiota. The biological effects of elobixibat are associated with its effects on secretory bile acids, rather than the structural changes of an altered faecal microbiota.
What next for courtroom special measures? Embodying legal geographies through “appreciative‐assemblage” methodology
Authors: Traynor Catherine , Tomczak Philippa
Published: July 2020

Courtrooms globally are being reshaped by (1) (legal) special measures, and (2) increasing voluntary sector involvement. We examine multisectoral efforts to change conditions under which vulnerable people give evidence in Scotland. Vulnerable complainers (in Scotland)/complainants and witnesses are now often shielded by screens and accompanied by volunteer witness supporters when testifying. These developments have important (geo)political implications. However, little scholarship examines the spatiality, materiality, and discursivity of the special measures themselves and/or the relationships between special measures, courts, and the voluntary sector. Addressing this gap, we fuse assemblage methodologies and appreciative inquiry, providing a novel methodological hybrid to underpin forthcoming research examining what constitutes these measures and their relationships with the court voluntary sector. Our “playful experimentation” increases the political momentum of assemblages and adds spatial, material, and discursive perspectives to narrative‐focused appreciative inquiry, to facilitate best evidence and organisational development. Our methodological hybrid increases interdisciplinary possibilities: for embodied legal geography, seeing law as enacted through the spatial, material, and discursive body of a volunteer; and for criminal justice voluntary sector studies, creating a more materially and spatially aware public criminology. This is relevant across interest groups, including those supporting (vulnerable) populations involved in criminal justice; evaluating court reforms; and doing research involving the representational, emotional, and affective body.
Efficacy of pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms—A bayesian network meta‐analysis
Authors: Li Jiande , Wang Hongxuan , Li Mei , Shen Qingyu , Li Xiangpen , Rong Xiaoming , Peng Ying
Published: July 2020

Background

We aimed to compare and rank the efficacy of different pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms.

Method

Bayesian network meta‐analysis was performed for three different outcome parameters: alcohol use disorders (AUD) remission rate, percent abstinent days, and scores of depression scales. The surface under the cumulative ranking curves (SUCRA) was used for ranking the efficacy of interventions. Sensitivity analysis and direct pairwise analysis were conducted to validate the main results.

Results

A total of 68 RCTs consisting of 5890 patients were included. Disulfiram could significantly increase the AUD remission rates (OR 5.02, 1.97‐12.95) and the percent abstinent days (MD 17.08, 3.48‐30.93). Disulfiram was associated with the best efficacy in achieving remission (SUCRA 95.1%) and increasing abstinent days (SUCRA 87.6%). Noradrenaline reuptake inhibitor was significantly more efficacious than controls (SMD −2.44, −3.53 to −1.36) and have the first rank (SUCRA 99.0%) in reducing the scores of depression scales. Antiepileptics have relatively higher ranks in efficacy for both AUD and depressive symptoms.

Conclusions

Disulfiram was associated with the best efficacy in achieving abstinence for comorbidity patients. Noradrenaline reuptake inhibitor was demonstrated to be associated with the best efficacy in reducing scores of depression scales. Antiepileptics might be beneficial to both alcohol‐related and depressive symptoms.
Early‐ and long‐term outcomes of liver transplantation with rescue allocation grafts
Authors: Kitano Yuki , Allard Marc‐Antoine , Nakada Shinichiro , Beghdadi Nassiba , Karam Vincent , Vibert Eric , Sa Cunha Antonio , Castaing Denis , Cherqui Daniel , Baba Hideo , Adam René
Published: July 2020

In France, liver grafts which have been refused by at least five centers are proposed as rescue allocation (RA). The aim of this study is to clarify the feasibility and safety of RA grafts in liver transplantation (LT). Short‐ and long‐term outcomes of patients who received RA grafts (RA group) were compared with those of patients who received standard allocation (SA) grafts (SA group). From a total of 1635 patients, 102 patients received RA grafts. Before matching, the RA group was characterized primarily by less severe liver disease, but the quality of graft was worse. After matching recipients' characteristics of 102 patients who used RA grafts with 306 patients who used SA grafts, recipients' characteristics were well balanced (1:3 matching). Although the rate of primary dysfunction was significantly higher in the RA group, there is no significant difference in the occurrence of major complications, length of hospitalization, and mortality between two groups. Graft survival (GS) and overall survival (OS) in the RA group were not significantly different from the SA group (GS; HR = 1.03 P = .89, OS; HR = 1.03 P = .90). In the French allocation system, the feasibility and safety of RA grafts might be comparable to SA grafts for carefully selected patients.
Aberrant Cerebellar Resting‐State Functional Connectivity Related to Reading Performance in Struggling Readers
Authors: Greeley Brian , Weber Rachel C. , Denyer Ronan , Ferris Jennifer K. , Rubino Cristina , White Katherine , Boyd Lara A.
Published: July 2020

Reading is a critical neurodevelopmental skill for school‐aged children, which requires a distributed network of brain regions including the cerebellum. However, we do not know how functional connectivity between the cerebellum and other brain regions contributes to reading. Here we used resting‐state functional connectivity to understand the cerebellum's role in decoding, reading speed, and comprehension in a group of struggling readers (RD) and a group of adolescents and children with typical reading abilities (TD). We observed an increase in functional connectivity between the sensorimotor network and the left angular gyrus, left lateral occipital cortex, and right inferior frontal gyrus in the RD group relative to the TD group. Additionally, functional connectivity between the cerebellum network and the precentral gyrus was decreased and was related to reading fluency in the RD group. Seed‐based analysis revealed increased functional connectivity between crus 1, lobule 6, and lobule 8 of the cerebellum and brain regions related to the default mode network and the motor system for the RD group. We also found associations between reading performance and the functional connectivity between lobule 8 of the cerebellum and the left angular gyrus for both groups, with stronger relationships in the TD group. Specifically, the RD group displayed a positive relationship between functional connectivity, whereas the TD group displayed the opposite relationship. These results suggest that the cerebellum is involved in multiple components of reading performance and that functional connectivity differences observed in the RD group may contribute to poor reading performance.
Phenotypic spectrum of patients with GABRB2 variants: from mild febrile seizures to severe epileptic encephalopathy
Authors: Yang Ying , Xiangwei Wenshu , Zhang Xiaoli , Xiao Jiangxi , Chen Jiaoyang , Yang Xiaoling , Jia Tianming , Yang Zhixian , Jiang Yuwu , Zhang Yuehua
Published: July 2020

Aim

To characterize the different phenotypes of GABRB2‐related epilepsy and to establish a genotype–phenotype correlation.

Method

We used next‐generation sequencing to identify GABRB2 variants in 15 patients.

Results

Eleven GABRB2 variants were novel and 12 were de novo. The age at the onset of seizures ranged from 1 day to 26 months. Nine patients had multiple seizure types, including focal seizures, generalized tonic–clonic seizures, myoclonic seizures, epileptic spasms, and atonic seizures. Seizures were fever‐sensitive in 13 out of the 15 patients. Eleven patients displayed developmental delay, while 11 had abnormal video electroencephalography. Abnormalities in the brain images included dysplasia of the frontal and temporal cortex, dysplasia of the corpus callosum, and delayed myelination in four patients. One patient was diagnosed with febrile seizures, three with febrile seizures plus, three with Dravet syndrome, three with West syndrome, one with Ohtahara syndrome, three with developmental delays and epilepsy, and one with non‐specific early‐onset epileptic encephalopathy.

Interpretation

The most common phenotypes of patients with GABRB2 variants include early onset of seizure and fever sensitivity. Febrile seizures and febrile seizures plus are new phenotypes of GABRB2 variants. The phenotypic spectrum of GABRB2 variants ranges from mild febrile seizures to severe epileptic encephalopathy.