bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic evidence for co-occurrence of antibiotic, biocide and metal resistance genes in pigs
Authors: Li Xuanji , Rensing Christopher , Vestergaard Gisle , Nesme Joseph , Gupta Shashank , Arumugam Manimozhiyan , Brejnrod Asker Daniel , Sørensen Søren Johannes 
Published: January 2021

AbstractAntibiotic-resistant pathogens constitute an escalating public health concern. Hence a better understanding of the underlying processes responsible for this expansion is urgently needed. Co-selection of heavy metals/biocides and antibiotic resistance genes (ARGs) has been suggested as one potential mechanism promoting the proliferation of antimicrobial resistance (AMR). This paper aims to elucidate this interplay and exploit differences in antibiotic usage to infer patterns of co-selection by the non-antibiotic factors metals and biocides in the context of pig farming. We examined 278 gut metagenomes from pigs with continuous antibiotic exposure, only at weaning and at no exposure. Metals as growth promoters and biocides as disinfectants are currently used with little restrictions in stock farming. The pigs under continuous antibiotic exposure displayed the highest co-occurrence of ARGs and other genetic elements while the pigs under limited use of antibiotics still showed abundant co-occurrences. Pathogens belonging toEnterobacteriaceaedisplayed increased co-occurrence phenomena, suggesting that this maintenance is not a random selection process from a mobilized pool but pertains to specific phylogenetic clades. These results suggest that metals and biocides displayed strong selective pressures on ARGs exerted by intensive farming, regardless of the current use of antibiotics.HighlightsA comprehensive gut microbiome metagenomics analysis of 278 pigsCo-selection phenomena were investigated via co-occurrence patterns as a proxyTwenty-seven types of co-occurrences involving 131 resistance genes were detectedRegardless of use of antibiotics, AMR can be maintained by co-occurrence with MRGs/BRGsMaintenance of AMR is not a random selection process but pertains to specific phylogenetic clades
Electrophysiological maturation and increased excitability of human iPSC-derived neurons inHTR2Avariant-related sleep bruxism
Authors: Sarkar Avijite Kumer , Nakamura Shiro , Nakai Kento , Shiga Takahiro , Abe Yuka , Hoashi Yurie , Inoue Tomio , Akamatsu Wado , Baba Kazuyoshi 
Published: January 2021

AbstractSleep bruxism (SB) is a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep. We previously found a significant association between SB and a single nucleotide polymorphism (SNP), rs6313, in the neuronal serotonin 2A receptor gene (HTR2A), and established human induced pluripotent stem cell (hiPSC)-derived neurons from SB patients with a genetic variant. To elucidate the electrophysiological characteristics of SB iPSC-derived neural cells bearing a SB-related genetic variant, we generated ventral hindbrain neurons from two SB patients and two unaffected controls and explored the intrinsic membrane properties of these neurons by patch-clamp technique. We found that the electrophysiological properties of the iPSC-derived neurons from the control line mature in a time-dependent manner in long-term cultures. In the early stage of neurogenesis, neurons from two SB lines tended to display shorter action potential (AP) half durations, which led to an increased cell capability of evoked firing. This is the firstin vitromodelling of SB using disease-specific hiPSCs. The revealed electrophysiological characteristics may serve as a benchmark for further investigation of pathogenic mechanisms underlying SB.Summary StatementSleep bruxism patient-specific iPSC-derived neurons with theHTR2Avariant show altered electrophysiological characteristics, providing the foremost narration of sleep bruxism neurological phenotypesin vitrofrom any species.
tTARGIT AAVs: A sensitive and flexible method to manipulate intersectional neuronal populations
Authors: Sabatini Paul V. , Wang Jine , Rupp Alan C. , Affinati Alison H. , Flak Jonathan N. , Li Chien , Olson David P. , Myers Martin G. 
Published: January 2021

SummaryWhile Cre-dependent viral systems permit the manipulation of many neuron types, some cell populations cannot be targeted by a single DNA recombinase. Although the combined use of Flp and Cre recombinases can overcome this limitation, insufficient recombinase activity can reduce the efficacy of existing Cre+Flp-dependent viral systems. We developed a sensitive dual recombinase-activated viral approach: tTA-driven Recombinase-Guided Intersectional Targeting (tTARGIT) AAVs. tTARGIT AAVs utilize a Flp-dependent tetracycline transactivator (tTA) “Driver” AAV and a tetracycline response element (TRE)-driven, Cre-dependent “Payload” AAV to express the transgene of interest. We employed this system inSlc17a6FlpO;LeprCremice to manipulate LepRb neurons of the ventromedial hypothalamus (VMH; LepRbVMHneurons) while omitting neighboring LepRb populations. We defined the circuitry of LepRbVMHneurons and roles for these cells in the control of food intake and energy expenditure. Thus, the tTARGIT system mediates robust recombinase-sensitive transgene expression, permitting the precise manipulation of previously intractable neural populations.
Two NLR immune receptors acquired high-affinity binding to a fungal effector through convergent evolution of their integrated domain
Authors: Białas Aleksandra , Langner Thorsten , Harant Adeline , Contreras Mauricio P , Stevenson Clare EM , Lawson David M , Sklenar Jan , Kellner Ronny , Moscou Matthew J , Terauchi Ryohei , Banfield Mark J , Kamoun Sophien 
Published: January 2021

ABSTRACTA subset of plant NLR immune receptors carry unconventional integrated domains in addition to their canonical domain architecture. One example is rice Pik-1 that comprises an integrated heavy metal–associated (HMA) domain. Here, we reconstructed the evolutionary history of Pik-1 and its NLR partner, Pik-2, and tested hypotheses about adaptive evolution of the HMA domain. Phylogenetic analyses revealed that the HMA domain integrated into Pik-1 before Oryzinae speciation over 15 million years ago and has been under diversifying selection. Ancestral sequence reconstruction coupled with functional studies showed that two Pik-1 allelic variants independently evolved from a weakly binding ancestral state to high-affinity binding of the blast fungus effector AVR-PikD. We conclude that for most of its evolutionary history the Pik-1 HMA domain did not sense AVR-PikD, and that different Pik-1 receptors have recently evolved through distinct biochemical paths to produce similar phenotypic outcomes. These findings highlight the dynamic nature of the evolutionary mechanisms underpinning NLR adaptation to plant pathogens.
Niclosamide Inhalation Powder Made by Thin-Film Freezing: Pharmacokinetic and Toxicology Studies in Rats and Hamsters
Authors: Jara Miguel O. , Warnken Zachary N. , Sahakijpijarn Sawittree , Moon Chaeho , Maier Esther Y. , Christensen Dale J. , Koleng John J. , Peters Jay I. , Hackman Sarah D. , Williams Robert O. 
Published: January 2021

AbstractIn this work, we have developed and testedin vivoa dry powder form of niclosamide made by thin-film freezing (TFF) and administered it by inhalation to rats and hamsters. The niclosamide dry powder, suitable for inhalation, is being developed as a therapeutic agent against COVID-19 infection. Niclosamide, a poorly water-soluble drug, is an interesting drug candidate because it was approved over 60 years ago for use as an anthelmintic medication, but recent studies demonstrated its potential as a broad-spectrum antiviral with a specific pharmacological effect against SARS-CoV-2 infection. In the past, clinical trials for other indications were terminated prior to completion due to low and highly variable oral bioavailability. In order to quickly address the current pandemic, targeting niclosamide directly to the lungs is rational to address the COVID-19 main clinical complications. Thin-film freezing technology was used to develop a niclosamide inhalation powder composition that exhibited acceptable aerosol performance with a fine particle fraction (FPF) of 86.0% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 1.11 μm and 2.84, respectively. This formulation not only proved to be safe after an acute three-day, multi-dose pharmacokinetic study in rats as evidenced by histopathology analysis, but also was able to achieve lung concentrations above the required IC50and IC90levels for at least 24 h after a single administration in a Syrian hamster model. To conclude, we successfully developed a niclosamide dry powder inhalation formulation by thin-film freezing for further scale-up and clinical testing against the COVID-19 infection. This approach overcomes niclosamide’s limitation of poor oral bioavailability by targeting the drug directly to the primary site of infection, the lungs.
Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide
Authors: Daron J. , Bravo I.G. 
Published: January 2021

AbstractThe Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus within theOrthocoronavirinaecausing an emergent infectious disease in humans, the ongoing coronavirus disease 2019 pandemic (COVID-19). Due to the high zoonotic potential of these viruses, it is critical to unravel their evolutionary history of host species shift, adaptation and emergence. Only such knowledge can guide virus discovery, surveillance and research efforts to identify viruses posing a pandemic risk in humans. We present a comprehensive analysis of the composition and codon usage bias of the 82Orthocoronavirinaemembers, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses and is only weakly dependent on the type of host they infect. Instead, we identify mutational bias towards AT-enrichment and selection against CpG dinucleotides as the main factors responsible of the codon usage bias variation. Further insight on the mutational equilibrium withinOrthocoronavirinaerevealed that most coronavirus genomes are close to their neutral equilibrium, the exception is the three recently-infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that while replicating in humans SARS-CoV-2 is slowly becoming AT-richer, likely until attaining a new mutational equilibrium.
Imagined speech can be decoded from low- and cross-frequency features in perceptual space
Authors: Proix Timothée , Saa Jaime Delgado , Christen Andy , Martin Stephanie , Pasley Brian N. , Knight Robert T. , Tian Xing , Poeppel David , Doyle Werner K. , Devinsky Orrin , Arnal Luc H. , Mégevand Pierre , Giraud Anne-Lise 
Published: January 2021

SummaryReconstructing intended speech from neural activity using brain-computer interfaces (BCIs) holds great promises for people with severe speech production deficits. While decodingovertspeech has progressed, decodingimaginedspeech have met limited success, mainly because the associated neural signals are weak and variable hence difficult to decode by learning algorithms. Using three electrocorticography datasets totalizing 1444 electrodes from 13 patients who performed overt and imagined speech production tasks, and based on recent theories of speech neural processing, we extracted consistent and specific neural features usable for future BCIs, and assessed their performance to discriminate speech items in articulatory, phonetic, vocalic, and semantic representation spaces. While high-frequency activity provided the best signal for overt speech, both low- and higher-frequency power and local cross-frequency contributed to successful imagined speech decoding, in particular in phonetic and vocalic, i.e. perceptual, spaces. These findings demonstrate that low-frequency power and cross-frequency dynamics contain key information for imagined speech decoding, and that exploring perceptual spaces offers a promising avenue for future imagined speech BCIs.
Does where you live influence what you are made of? Spatial correlates of chemical traits across commonly occurring boreal plants
Authors: Heckford Travis R , Leroux Shawn J. , Wal Eric Vander , Rizzuto Matteo , Balluffi-Fry Juliana , Richmond Isabella C. , Wiersma Yolanda F. 
Published: January 2021

AbstractContextSpatially explicit drivers of foliar chemical traits link plants to ecosystem processes to reveal landscape functionality. Specifically, foliar elemental, stoichiometric, and phytochemical (ESP) compositions represent key indicator traits.ObjectivesHere, we investigate the spatial drivers of foliar ESP at the species level and across species at the trait level for five commonly occurring boreal forest understory plants.MethodsOn the island of Newfoundland, Canada, we collected foliar material from four chronosequenced forest grids. Using response variables of foliar elemental (C, N, P, percent and quantity), stoichiometric (C:N, C:P, N:P), and phytochemical (terpenoids) composition, we tested multiple competing hypotheses using spatial predictors of land cover (e.g., coniferous, deciduous, mixedwood), productivity (e.g., enhanced vegetation index), biotic (e.g., stand age/height, canopy closure) and abiotic (e.g., elevation, aspect, slope) factors.ResultsWe found evidence to support spatial relationships of foliar ESP for most species (mean R2= 0.22, max = 0.65). Spatial variation in elemental quantity traits of C, N, P were related to land cover along with biotic and abiotic factors for 2 of 5 focal species. Notably, foliar C, C:P, and sesquiterpene traits between different species were related to abiotic factors. Similarly, foliar terpenoid traits between different species were related to a combination of abiotic and biotic factors (mean R2= 0.26).ConclusionsSpatial-trait relationships mainly occur at the species level, with some commonalities occurring at the trait level. By linking foliar ESP traits to spatial predictors, we can map plant chemical composition patterns that influence landscape-scale ecosystem processes.
Training with an auditory perceptual learning game transfers to speech in competition
Authors: de Larrea-Mancera E. Sebastian Lelo , Philipp Mark Allen , Stavropoulos Trevor , Carrillo Audrey Anna , Cheung Sierra , Koerner Tess , Molis Michelle R. , Gallun Frederick J. , Seitz Aaron R. 
Published: January 2021

AbstractHearing speech in competition is a major complaint in those who suffer from hearing loss. Here we investigate a novel perceptual learning game that is designed to train perceptual skills thought to underlie speech in competition, such as spectral-temporal processing and sound localization, under conditions of quiet and in noise. Thirty young normal hearing participants were assigned either to this mixed-training condition or an active control consisting of frequency discrimination training within the same gamified setting. To assess training outcomes, we examine tests of basic central auditory processing, speech in competition, and cognitive processing abilities before and after training. Results suggest modest improvements on speech in competition tests in the mixed-training but not the frequency-discrimination control condition. This data show promise for future applications in populations with hearing difficulties.
Enhancing motor learning by increasing stability of newly formed dendritic spines in motor cortex
Authors: Albarran Eddy , Raissi Aram , Jáidar Omar , Shatz Carla J. , Ding Jun B. 
Published: January 2021

SUMMARYDendritic spine dynamics of Layer 5 Pyramidal neurons (L5PNs) are thought to be physical substrates for motor learning and memory of motor skills and altered spine dynamics are frequently correlated with poor motor performance. Here we describe an exception to this rule by studying mice lacking Paired immunoglobulin receptor B (PirB−/−). Using chronic two-photon imaging of primary motor cortex (M1) of PirB−/−;Thy1-YFP-H mice, we found a significant increase in the survival of spines on apical dendritic tufts of L5PNs, as well as increased spine formation rates and spine density. Surprisingly and contrary to expectations, adult PirB−/− mice learn a skilled reaching task more rapidly compared to wild type (WT) littermate controls. Conditional excision of PirB from forebrain pyramidal neurons in adult mice replicated these results. Furthermore, chronic imaging of L5PN dendrites throughout the learning period revealed that the stabilization of learning-induced newly formed spines is significantly elevated in PirB−/− mice. The degree of survival of newly formed spines in M1 yielded the strongest correlation with task performance, suggesting that this increased spine stability is advantageous and can translate into enhanced acquisition and maintenance of motor skills. Notably, inhibiting PirB function acutely in M1 of adult WT mice throughout training increases the survival of spines formed during early training and enhances motor learning. These results suggest that increasing the stability of newly formed spines is sufficient to improve long-lasting learning and motor performance and demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.
Mapping South Africaʼs nationally determined contributions to the targets of the sustainable development goals
Authors: Mantlana Khanyisa B. , Maoela Malebajoa A. , Nhamo Godwell 
Published: January 2021

AbstractThe Paris Agreementʼs nationally determined contributions (NDCs) provide an excellent point of entry to simultaneously address climate change and the 2030 Agenda for Sustainable Development and its Sustainable Development Goals (SDGs). This study sets out to explore the connections between climate action plans (NDCs) and each of the 17 Sustainable Development Goals (SDGs). In this study, we used four levels of visibility, that is, present, generic, implied and absent to provide a broad perspective of the extent to which South Africaʼs NDC is aligned with the targets of the SDGs. Our results revealed that South Africaʼs NDC has 12% present level of visibility to the SDG targets, with SDG 7 Affordable and Clean Energy and SDG 13 Climate Action showing the highest representation of present level of visibility. By contrast, the absent level of visibility NDC showed 53% in the SDG targets, with SDG 5 Gender Equity, SDG 16 Peace, Justice and Strong Institutions and SDG 3 Good Health and Well‐Being, showing the highest representation of absent level of visibility. These results indicate that there is scope to improve the alignment of South Africaʼs NDCs with the SDG targets. To this end, we have identified areas that may benefit with further elaboration in the countryʼs second NDC.
Overcoming the impact of the COVID‐19 pandemic on oncology early phase trials and drug development in Asia—Experiences and perspectives of the Asian Oncology Early Phase 1 Consortium
Authors: Shimizu Toshio , Kim Dong‐Wan , Loong Herbert H. , Lin Chia‐Chi , Ng Matthew CH , Yamamoto Noboru , Ma Brigette , Tan Daniel SW 
Published: January 2021

AbstractAimThe significance and prioritization of early phase oncology trial continuation during a global pandemic is unknown. This study reported the outcomes, multiple challenges, and broad recommendations associated with the impact of the novel coronavirus disease 2019 (COVID‐19) on oncology early phase 1 trials—and on drug development in Asia—based on the experiences and perspectives of Asian oncology phase 1 centers.MethodsBetween March and April 2020 during the initial period of outbreak, the impact of COVID‐19 across oncology phase 1 sites in five Asian countries—China (Hong Kong), Japan, South Korea, Taiwan, and Singapore—was retrospectively analyzed.ResultsThere was no trial termination or treatment discontinuation in all five countries. Although the most common impact was new patient enrollment being placed on hold, which was based on pharmaceutical sponsors’ decision‐making, the situation varied per site. Most sites had no restrictions in place that would limit their ability to fully comply with the requirements of conducting the early phase studies. The number of protocol deviations during the pandemic was largely dependent on domestic transportation status during the outbreak rather than the ability of the clinical trial centers.ConclusionDetermining the risk to benefits ratio of patients with cancer who are enrolled in early phase 1 clinical trials under the unusual circumstances of a global pandemic is important. Specific guidance or guidelines on the conduct of early phase 1 clinical trials during public health emergencies that are based on the recent lessons learned is urgently required.
Addressing surgical inequity for Aboriginal and Torres Strait Islander people in Australia's universal health care system: a call to action
Authors: O'Brien Penny , Bunzli Samantha , Lin Ivan , Bessarab Dawn , Coffin Juli , Dowsey Michelle M. , Choong Peter F. M. 
Published: January 2021

AbstractAboriginal and Torres Strait Islander people continue to experience health inequity within the Australian health care system. Little research has examined how disparities in surgical care access and outcomes contribute to Aboriginal health. In this narrative review and call to action, we discuss five care points along the journey to high‐quality surgical care: health care seeking, primary health care services, specialist services, surgery and surgical outcomes. We highlight barriers and disparities that exist along this journey, drawing examples from the field of joint replacement surgery. Finally, we present opportunities for change at the health system, health service and clinician level, calling upon researchers, clinicians and policy makers to confront the surgical disparities experienced by Aboriginal and Torres Strait Islander people.
New Zealand and Australia emergency laparotomy mortality rates compare favourably to international outcomes: a systematic review
Authors: Fagan Georgina , Barazanchi Ahmed , Coulter Grant , Leeman Matthew , Hill Andrew G. , Eglinton Tim W. 
Published: January 2021

AbstractBackgroundAlmost 20 000 people undergo an emergency laparotomy each year in New Zealand and Australia. Common indications include small and large bowel obstruction, and intestinal perforation. Considered a high‐risk procedure, emergency laparotomy is associated with significantly high morbidity and mortality. The aim of this review was to identify and compare 30‐day, 90‐day and 1‐year mortality rates following emergency laparotomy in New Zealand and Australia.MethodsA systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Electronic searches were performed in Medline, Embase, PubMed and Scopus in April 2020.ResultsThirty‐three papers met the inclusion criteria. Studies ranged in size from 58 to 75 280 patients. Weighted mean 30‐day mortality was 8.40% (8.39–8.41). Mortality rates increased with longer postoperative follow up with 90‐day weighted mortality rate of 14.14% (14.13–14.15) and the weighted mortality rate at 1 year of 24.60% (24.56–24.66). There was significant variability in mortality rates between countries.ConclusionThere is a wide variability of 30‐day, 90‐day and 1‐year mortality rates internationally. Lowering postoperative mortality rates following emergency laparotomy through quality improvement initiatives could result in up to 120 lives in New Zealand and over 250 lives in Australia being saved each year. The continued work of the Australian and New Zealand Emergency Laparotomy Audit – Quality Improvement is crucial to improving emergency laparotomy mortality rates further in New Zealand and Australia.