bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of gastrointestinal comorbidities in patients with right & left atrial isomerism
Authors: Fotaki Anastasia , L Doughty Victoria , Banya Winston , Giuliani Stefano , Bradley Sarah , S Carvalho Julene 
Published: May 2020

ABSTRACTObjectiveHeterotaxy syndrome (HS), being right atrial isomerism (RAI) or left atrial isomerism (LAI) often presents with congenital heart disease (CHD). Intestinal abnormalities including malrotation are common. We aim to assess the impact of gut abnormalities on outcome in HS.MethodsWe reviewed cardiology records of HS patients regarding presence of CHD, time for cardiac intervention, presence of gastrointestinal (GI) abnormalities and type/time of surgery. A questionnaire about GI status was sent to patients <18 years old. Kaplan-Meier curves were derived for survival data.ResultsData were available for 195 patients (49 RAI, 146 LAI) of 247 identified. Questionnaires were sent to 77 families, 47 replied. CHD was present in all RAI and 63.7% of LAI cases. Thirty-eight patients had abdominal surgery (19.5%), similar rate in RAI and LAI (20.4% vs 19.1%, p=0.92). Ladd procedure was performed in 17 (44.7%), non-Ladd in 12 (31.5%) and both procedures in nine patients (23.7%). Ten-year freedom from Ladd procedure for all was 86% (RAI=87%; LAI=85%, p=0.82). Freedom from any GI surgery at one year was 86% (RAI=86%; LAI=86%, p=0.98) and at ten years was 80% (RAI=77%; LAI=81%, p=0.65). Ten-year freedom from cardiac surgery was 34% (RAI=7%; LAI=42%, p<0.0001).ConclusionsIn our cohort, one in five patients required abdominal surgery, mostly in their first year, similar in RAI and LAI. Between one and ten years of follow up the impact of GI abnormalities on outcome was minimal. Medium term survival was related to CHD.ARTICLE SUMMARYSTRENGTHS AND LIMITATIONS OF THIS STUDYThis study is the largest cohort study investigating the impact of gastrointestinal abnormalities in cardiology patients with heterotaxy syndrome.It is the first clinical study to show that HS patients suffer from a wider spectrum of abdominal abnormalities, other than typical malrotation, varying in severity from asymptomatic malrotation to complete non-rotation, namely atresia at multiple intestinal levels. This is relevant in prenatal family counseling but also raises questions regarding the indication of elective Ladd procedure in all heterotaxy syndrome patients, as a different procedure might be indicated.Patient morbidity was investigated from both the cardiology and gastrointestinal point 12 of view.Its main limitations in design is that is not a prospective study. Cardiology records have been reviewed with regards to GI symptomatology, screening investigations and procedures.It involved both reviewing the medical records and directly contacting the family for the subcohort that was below 18 years old and lived in the UK, in an attempt to minimise any data errors. Our records were consistent with the information provided by parents/guardians in all cases but one.
Electric Field Induced Wetting of a Hydrophobic Gate in a Model Nanopore Based on the 5-HT3Receptor Channel
Authors: Klesse Gianni , Tucker Stephen J. , Sansom Mark S.P. 
Published: May 2020

AbstractIn this study we examined the influence of a transmembrane voltage on the hydrophobic gating of nanopores using molecular dynamics simulations. We observed electric field induced wetting of a hydrophobic gate in a biologically inspired model nanopore based on the 5-HT3receptor in its closed state, with a field of at least ∼100 mV nm−1was required to hydrate the pore. We also found an unequal distribution of charged residues can generate an electric field intrinsic to the nanopore which, depending on its orientation, can alter the effect of the external field, thus making the wetting response asymmetric. This wetting response could be described by a simple model based on water surface tension, the volumetric energy contribution of the electric field, and the influence of charged amino acids lining the pore. Finally, the electric field response was used to determine time constants characterising the phase transitions of water confined within the nanopore, revealing liquid-vapour oscillations on a time scale of ~5 ns. This time scale was largely independent of the water model employed and was similar for different sized pores representative of the open and closed states of the pore. Furthermore, our finding that the threshold voltage required for hydrating a hydrophobic gate depends on the orientation of the electric field provides an attractive perspective for the design of rectifying artificial nanopores.ToC/Abstract Graphic
Characterization ofmWakeexpression in the murine brain
Authors: Bell Benjamin J. , Wang Annette A. , Kim Dong Won , Blackshaw Seth , Wu Mark N. 
Published: May 2020

AbstractStructure-function analyses of the mammalian brain have historically relied on anatomically-based approaches. In these investigations, physical, chemical, or electrolytic lesions of anatomical structures are applied, and the resulting behavioral or physiological responses assayed. An alternative approach is to focus on the expression pattern of a molecule whose function has been characterized and then use genetic intersectional methods to optogenetically or chemogenetically manipulate distinct circuits. We previously identified WIDE AWAKE (WAKE) inDrosophila, a clock output molecule that mediates the temporal regulation of sleep onset and sleep maintenance. More recently, we have studied the mouse homolog, mWAKE/ANKFN1, and found that its role in the circadian regulation of arousal is conserved. Here, we perform a systematic analysis of the expression pattern ofmWakemRNA, protein, and cells throughout the adult mouse brain. We find that mWAKE labels neurons in a restricted, but distributed manner, in multiple regions of the hypothalamus (including the suprachiasmatic nucleus), the limbic system, sensory processing nuclei, and additional specific brainstem, subcortical, and cortical areas. Interestingly, mWAKE is also observed in non-neuronal ependymal cells. In addition, to describe the molecular identities and clustering ofmWake+cells, we provide detailed analyses of single cell RNA sequencing data from the hypothalamus, a region with particularly significant mWAKE expression. These findings lay the groundwork for future studies into the potential role ofmWake+cells in the rhythmic control of diverse behaviors and physiological processes.
The impact of genetic diversity on gene essentiality within theE. colispecies
Authors: Rousset François , Caballero José Cabezas , Piastra-Facon Florence , Fernández-Rodríguez Jesús , Clermont Olivier , Denamur Erick , Rocha Eduardo P.C. , Bikard David 
Published: May 2020

AbstractBacteria from the same species can differ widely in their gene content. InE. coli, the set of genes shared by all strains, known as the core genome, represents about half the number of genes present in any strain. While recent advances in bacterial genomics have enabled to unravel genes required for fitness in various experimental conditions at the genome scale, most studies have focused on model strains. As a result, the impact of this genetic diversity on core processes of the bacterial cell largely remains to be investigated. Here, we developed a new CRISPR interference platform for high-throughput gene repression that is compatible with mostE. coliisolates and closely-related species. We applied it to assess the importance of ∼3,400 nearly ubiquitous genes in 3 growth media in 18 representativeE. colistrains spanning most common phylogroups and lifestyles of the species. Our screens highlighted extensive variations in gene essentiality between strains and conditions. Unlike variations in gene expression level, variations in gene essentiality do not recapitulate the strains’ phylogeny. Investigation of the genetic determinants for these variations highlighted the importance of epistatic interactions with mobile genetic elements. In particular, we showed how mobile genetic elements can trigger the essentiality of core genes that are usually nonessential. This study provides new insights into the evolvability of gene essentiality and argues for the importance of studying various isolates from the same species in bacterial genomics.
PA-X is an avian virulence factor in H9N2 avian influenza virus
Authors: Clements Anabel L. , Peacock Thomas P. , Sealy Joshua E. , Hussain Saira , Sadeyen Jean-Remy , Shelton Holly , Digard Paul , Iqbal Munir 
Published: May 2020

AbstractInfluenza A viruses encode several accessory proteins that have host- and strain-specific effects on virulence and replication. The accessory protein PA-X is expressed due to a ribosomal frameshift during translation of the PA gene. Depending on the particular combination of virus strain and host species, PA-X has been described as either acting to either reduce or increase virulence and/or virus replication. In this study, we set out to investigate the role PA-X plays in H9N2 avian influenza viruses, focussing particularly on the natural avian host, chickens. We found H9N2 PA-X induced robust host shutoff in both mammalian and avian cells and increased replication in mammalian, but not avian cells. We further showed that PA-X affected embryonic lethalityin ovoand led to more rapid viral shedding and widespread organ disseminationin vivoin chickens. Overall, we conclude PA-X may act as a virulence factor for H9N2 viruses in chickens, allowing faster replication and wider organ tropism.
Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils
Authors: Cao Qin , Boyer David R. , Sawaya Michael R. , Ge Peng , Eisenberg David S. 
Published: May 2020

AbstractHuman islet amyloid polypeptide (hIAPP, or amylin) is a 37 amino acid hormone secreted by pancreatic islet β-cells. Aggregation of hIAPP into amyloid fibrils is found in more than 90% of Type-II Diabetes (T2D) patients and is considered to be associated with T2D pathology. Although different models have been proposed, the high resolution structure of hIAPP fibrils is unknown. Here we report the cryo-EM structure of recombinant full-length hIAPP fibrils. The fibril is composed of two symmetrically-related protofilaments with ordered residues 14-37 that meet at a 14-residue central hydrophobic core. Our hIAPP fibril structure (i) supports the previous hypothesis that residues 20-29, especially 23-29 are the primary amyloid core of hIAPP, (ii) suggests a molecular mechanism for the action of the hIAPP hereditary mutation S20G, (iii) explains why the 6 residue substitutions in rodent IAPP prevent aggregation, and (iv) suggests possible regions responsible for the observed hIAPP cross-seeding with β-amyloid. Furthermore, we performed structure-based inhibitor design to generate potential hIAPP aggregation inhibitors via a capping strategy. Four of the designed candidates delay hIAPP aggregation in vitro, providing a starting point for the development of T2D therapeutics and proof-of-concept that the capping strategy can be used on full-length cryo-EM fibril structures.
Role of Prefrontal Cortex during Sudoku task: fNIRS study
Authors: Ashlesh Patil , Deepak K K , Preet Kochhar Kanwal 
Published: May 2020

AbstractSudoku is a popular leisure time activity that involves no math, but is based on logic based combinatorial number placement in a matrix. Many studies have been dedicated towards finding an algorithm to solve Sudoku but investigation of the neural substrates involved in Sudoku has been challenging. It is difficult to measure the brain activity during 9×9 Sudoku using traditional fMRI technique due to the procedural constraints. 16 optodes fNIRS (functional near infrared spectroscopy) forms an excellent alternative to study the activity of prefrontal cortex (PFC) during Sudoku task. Sudoku task was divided into two steps to understand the differential function of the PFC while applying heuristic rules. Classical two-way ANOVA as well as General Linear Model based approach was used to analyze the data. 28-noise free recording from right-handed participants revealed increased activity in all 16 optode locations during step 1 (3 × 3 subgrids) and step 2 (easy level 9×9 Sudoku) as compared to rest. Contrasting the step2-step1 revealed that medial regions of PFC were preferentially activated. These findings suggest the role of these regions, while applying multiple heuristic rules to solve 9×9 Sudoku puzzle.Graphical abstractHighlightsThis is first fNIRS study that tried to unravel the role of PFC during Sudoku task.Uniquely divided the Sudoku task into two steps to understand the differential role of PFC while applying multiple heuristic rules.Both the medial and lateral regions of PFC are activated during Sudoku task.However, the medial regions of PFC play a differential role, especially when we consider the row and the column rule of Sudoku.
HSATII RNA is inducedviaa non-canonical ATM-regulated DNA-damage response pathway and facilitates tumor cell proliferation and movement
Authors: Nogalski Maciej T. , Shenk Thomas 
Published: May 2020

ABSTRACTPericentromeric human satellite II (HSATII) repeats are normally silent, but can be actively transcribed in tumor cells, where increased HSATII copy number is associated with a poor prognosis in colon cancer, and in human cytomegalovirus (HCMV)-infected cells, where the RNA facilitates viral replication. Here, we report that HCMV infection or treatment of ARPE-19 diploid epithelial cells with the DNA-damaging agents, etoposide and zeocin, induced HSATII RNA expression, and a kinase-independent function of ATM was required for the induction. Additionally, various breast cancer cell lines growing in adherent, 2-dimensional cell culture expressed HSATII RNA at different levels, and levels were markedly increased when cells were either infected with HCMV or treated with zeocin. High levels of HSATII RNA expression correlated with enhanced migration of breast cancer cells, and knockdown of HSATII RNA reduced cell migration and the rate of cell proliferation. Our investigation links high expression of HSATII RNA to the DNA damage response, centered on a non-canonical function of ATM, and demonstrates a role for the satellite RNA in tumor cell proliferation and movement.SIGNIFICANCEHSATII RNA is associated with cancer progression, immunostimulation and, as we recently reported, it plays an important role in herpesvirus infections. However, the understanding of cellular processes responsible for the expression of HSATII RNA has been limited. Our current investigation identified a non-canonical, ATM kinase-independent DNA-damage response pathway as a common cellular mechanism regulating HSATII RNA induction in virus-infected cells or cells treated with DNA-damaging agents. Additionally, our study provides a link between expression of HSATII RNA and the cellular growth and migration phenotypes of cancer cells, establishing a new paradigm to study the biological consequences of HSATII RNA expression, i.e., treatment of normal diploid and tumor cells with DNA-damaging agents.
Efficient, high-throughput ligand incorporation into protein microcrystals by on-grid soaking
Authors: Martynowycz Michael W. , Gonen Tamir 
Published: May 2020

AbstractA method for soaking ligands into protein microcrystals on TEM grids is presented. Every crystal on the grid is soaked simultaneously using only standard cryoEM vitrification equipment. The method is demonstrated using proteinase K microcrystals soaked with the 5-amino-2,4,6-triodoisophthalic acid (I3C) magic triangle. A soaked microcrystal is milled to a thickness of 200nm using a focused ion-beam, and microcrystal electron diffraction (MicroED) data are collected. A high-resolution structure of the protein with four ligands at high occupancy is determined. Compared to much larger crystals investigated by X-ray crystallography, both the number of ligands bound and their occupancy was higher in MicroED. These results indicate that soaking ligands into microcrystals in this way results in a more efficient uptake than in larger crystals that are typically used in drug discovery pipelines by X-ray crystallography.
Bayesian Network Analysis of Covid-19 data reveals higher Infection Prevalence Rates and lower Fatality Rates than widely reported
Authors: Neil Martin , Fenton Norman , Osman Magda , McLachlan Scott 
Published: May 2020

AbstractWidely reported statistics on Covid-19 across the globe fail to take account of both the uncertainty of the data and possible explanations for this uncertainty. In this paper we use a Bayesian Network (BN) model to estimate the Covid-19 infection prevalence rate (IPR) and infection fatality rate (IFR) for different countries and regions, where relevant data are available. This combines multiple sources of data in a single model. The results show that Chelsea Mass. USA and Gangelt Germany have relatively higher infection prevalence rates (IPR) than Santa Clara USA, Kobe, Japan and England and Wales. In all cases the infection prevalence is significantly higher than what has been widely reported, with much higher community infection rates in all locations. For Santa Clara and Chelsea, both in the USA, the most likely IFR values are 0.3-0.4%. Kobe, Japan is very unusual in comparison with the others with values an order of magnitude less than the others at, 0.001%. The IFR for Spain is centred around 1%. England and Wales lie between Spain and the USA/German values with an IFR around 0.8%. There remains some uncertainty around these estimates but an IFR greater than 1% looks remote for all regions/countries. We use a Bayesian technique called ‘virtual evidence’ to test the sensitivity of the IFR to two significant sources of uncertainty: survey quality and uncertainty about Covid-19 death counts. In response the adjusted estimates for IFR are most likely to be in the range 0.3%-0.5%.
A virtual educational model on a CNC milling machine including and excluding two methods of fuzzy controllers
Authors: Osman Bashir , Zhu Haitao 
Published: May 2020

Purpose
Training centers and labs offer many applications suitable for beginners who want to know how to set and operate a computer numerical control (CNC) milling machine. However, few applications address a basic understanding of the machining process founded on mathematical principals in line with new high-speed and high-precision machining technologies. The purpose of this paper is to present a complex mechanism in a simplified way, explaining the subject at an elementary level.

Design/methodology/approach
The authors have developed an application of the CNC milling machine in a Matlab/Simulink package, obtaining the appropriate parameters mathematically. The project developed an analytical method using Matlab code to test the step response (the actual cutting force) under various parameters to ensure comparability of the designed model. The analytical results are in line with the developed model. The Matlab/Simulink user interface allows the application to better explain machining for educational purposes. Furthermore, by combining this mathematical model and the fuzzy controller, the high-speed constant-force milling control model has a user interface for data entry. The addition of two kinds of fuzzy controllers (look-up table and Mamdani) achieve a more educational environment compared with existing models.

Findings
The developed technique can be used in CNC milling machine centers and laboratories. For virtual training purposes, this paper provides a two-stage educational model, giving students the necessary feedback on what they have learned at each stage from the beginning use of the CNC milling machine, with and without the controller. The system also offers to track the step-response analysis method. This method overcomes the shortage of milling processes modeled by the traditional transfer function, which more accurately establishes the relationship between cutting force and cutting parameters.

Practical implications
This technique can be used in the CNC machine centers and laboratory for teaching beginner students and trainees. Real data from the workshop had been used.

Originality/value
The earlier versions of this manuscript were presented in: JVE International LTD. Vibroengineering Procedia. +2017. 14.; IEEE 4th International Conference on Information Science and Control Engineering (ICISCE) +2017.
Skin seeding technique with 0.5‐mm micropunch grafting for vitiligo irrespective of the epidermal–dermal orientation: Animal and clinical studies
Authors: Kim Dong Seok , Ju Hyun Jeong , Lee Han Na , Choi In Hye , Eun Sung Hye , Kim Jiehoon , Bae Jung Min 
Published: May 2020

AbstractMicropunch grafting is the simplest surgical intervention for refractory vitiligo but is tedious and time‐consuming. Therefore, we aimed to verify the efficacy and safety of dermal orientation grafting using motorized 0.5‐mm micropunch grafting for vitiligo. In a preliminary animal study, 12‐week‐old rats were used to observe the healing process after the transplantation of dermal orientation grafts with various punch sizes. In a clinical trial, a total of 100 vitiligo patches in 50 patients with stable vitiligo were randomly allocated to motorized 0.5‐mm micropunch grafting in epidermal and dermal orientations, respectively. The grafts were implanted at intervals of 5 mm at the recipient site. Treatment success was defined as greater than 75% repigmentation. In the animal study, all grafts were shown to be well integrated into the recipient site within 3 weeks. In the clinical trial, treatment success was achieved in 72% and 76% of the epidermal and dermal orientation groups, respectively; a cobblestone appearance was observed in 4% and 2%, respectively. In conclusion, we demonstrated that this new grafting method irrespective of epidermal–dermal orientation using motorized 0.5‐mm micropunch grafting was effective and safe. We have named this the “skin seeding technique” and it differs from traditional punch grafting in that it can be performed regardless of the graft orientation.
Local‐scale tree and shrub diversity improves pollination services to shea trees in tropical West African parklands
Authors: Delaney Aoife , Dembele Assita , Nombré Issa , Gnane Lirasse Franck , Marshall Elaine , Nana Adama , Vickery Juliet , Tayleur Catherine , Stout Jane C. 
Published: May 2020

Abstract

Shea Vitellaria paradoxa trees bear fruit and seeds of considerable economic, nutritional and cultural value in the African Sudano‐Sahelian zone. In much of West Africa, shea exists within an agroforestry system referred to as ‘parkland’, where social changes, including migration, have resulted in expanding areas of crop cultivation, reductions in both the area of fallow land and the duration of fallow periods, and reduced diversity of habitats and woody species. Shea benefits strongly from pollination by bees and the loss of Parkland biodiversity may reduce the availability of pollinators, leading to pollen limitation and reductions in fruit yields.

We investigated whether shea trees in southern Burkina Faso experienced pollination limitation, and whether local‐ and landscape‐scale diversity were linked to visitation by bees, the degree of limitation observed and the weight of fruit produced.

Honeybees Apis mellifera were observed more frequently in diverse sites, whereas non‐Apis species were generally widespread but visited trees in greater numbers at diverse sites.

We found that shea fruit production was significantly limited due to lack of pollination and that the degree of pollination limitation was greater in sites with lower levels of tree and shrub diversity.

Synthesis and applications. Sites with greater diversity of tree and shrub species had more bee visits and less extreme pollination limitation than less diverse sites, indicating that small‐scale diversity is associated with more efficient pollination services. Consequently, shea yields are likely to benefit from retention of a range of different tree and shrub species in parklands. We recommend that when fallows are cleared for cultivation, such beneficial plants are retained within cultivated fields, and that measures to conserve pollinators in the region should target both A. mellifera and non‐Apis bee species.