bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colistin susceptibility pattern in gram negative bacilli isolated from patients of dhaka medical college hospital with distribution of antibiotic resistance genes among them
Authors: Mostofa Hasbi Ara , Shamsuzzaman S.M. , Hasan MD. Maniul 
Published: April 2020

AbstractColistin is one of the last resort of antibiotics used specifically in the treatment of multidrug resistant gram negative bacilli. Though an older class of antibiotic with no use in last four decades, resurgence of colistin use is also causing emergence of colistin resistant gram negative bacilli.The aim of this cross sectional study was to investigate the colistin susceptibility and resistant pattern along with colistin resistant genes in gram negative bacilli among different samples in Dhaka medical college hospital. Total 300 samples (wound swab, urine, endotracheal aspirate, blood and sputum) were collected from 2015 to 2016. 204 gram negative bacilli were isolated and tested for resistance to colistin by disc diffusion method. Then, the prevalence of colistin resistant genes (pmrA, pmrB, pmrC, mgrB, phoP, phoQ, lpxA, lpxC, lpxD, mcr-1) was detected by polymerase chain reaction method (PCR). Among 204 gram negative bacilli, 22 (10.78%) colistin resistance was identified. PCR analysis revealed that 50% of these isolates contained pmrA gene, followed by phoP gene (27.27%). The prevalence of pmrB, phoQ, mgrB, lpxC and lpxD were 22.72%, 13.63%, 13.63%, 13.63%, 13.63%, and 13.63% respectively among the isolates. Colistin resistance is widespread among gram negative bacilli isolated from human infections. Colistin resistance (10.78%) found in the study is quite alarming. A restricted and rational use of the colistin is the need of hour.
RefKA: A fast and efficient long-read genome assembly approach for large and complex genomes
Authors: Yuan Yuxuan , Bayer Philipp E. , Anderson Robyn , Lee HueyTyng , Chan Chon-Kit Kenneth , Zhao Ruolan , Batley Jacqueline , Edwards David 
Published: April 2020

AbstractRecent advances in long-read sequencing have the potential to produce more complete genome assemblies using sequence reads which can span repetitive regions. However, overlap based assembly methods routinely used for this data require significant computing time and resources. Here, we have developed RefKA, a reference-based approach for long read genome assembly. This approach relies on breaking up a closely related reference genome into bins, aligningk-mers unique to each bin with PacBio reads, and then assembling each bin in parallel followed by a final bin-stitching step. During benchmarking, we assembled the wheat Chinese Spring (CS) genome using publicly available PacBio reads in parallel in 168 wall hours on a 250 CPU system. The maximum RAM used was 300 Gb and the computing time was 42,000 CPU hours. The approach opens applications for the assembly of other large and complex genomes with much-reduced computing requirements. The RefKA pipeline is available athttps://github.com/AppliedBioinformatics/RefKA
Learning a tactile sequence induces selectivity to action decisions and outcomes in the mouse somatosensory cortex
Authors: Bale Michael R. , Bitzidou Malamati , Giusto Elena , Kinghorn Paul , Maravall Miguel 
Published: April 2020

AbstractSequential temporal ordering and patterning are key features of natural signals used by the brain to decode stimuli and perceive them as sensory objects. To explore how cortical neuronal activity underpins sequence recognition, we developed a task in which mice distinguished between tactile ‘words’ constructed from distinct vibrations delivered to the whiskers, assembled in different orders. Animals licked to report the presence of the target sequence. Mice could respond to the earliest possible cues allowing discrimination, effectively solving the task as a ‘detection of change’ problem, but enhanced their performance when deliberating for longer. Optogenetic inactivation showed that both primary somatosensory ‘barrel’ cortex (S1bf) and secondary somatosensory cortex were necessary for sequence recognition. Two-photon imaging of calcium activity in S1bf layer 2/3 revealed that, in well-trained animals, neurons had heterogeneous selectivity to multiple task variables including not just sensory input but also the animal’s action decision and the trial outcome (presence or absence of a predicted reward). A large proportion of neurons were activated preceding goal-directed licking, thus reflecting the animal’s learnt response to the target sequence rather than the sequence itself; these neurons were found in S1bf as soon as mice learned to associate the rewarded sequence with licking. In contrast, learning evoked smaller changes in sensory responses: neurons responding to stimulus features were already found in naïve mice, and training did not generate neurons with enhanced temporal integration or categorical responses. Therefore, in S1bf sequence learning results in neurons whose activity reflects the learnt association between the target sequence and licking, rather than a refined representation of sensory features.
Insights into the evolution of symbiosis gene copy number and distribution from a chromosome-scale Lotus japonicus Gifu genome sequence
Authors: Kamal Nadia , Mun Terry , Reid Dugald , Lin Jie-shun , Akyol Turgut Yigit , Sandal Niels , Asp Torben , Hirakawa Hideki , Stougaard Jens , Mayer Klaus F. X. , Sato Shusei , Andersen Stig Uggerhøj 
Published: April 2020

AbstractAimLotus japonicus is a herbaceous perennial legume that has been used extensively as a genetically tractable model system for deciphering the molecular genetics of symbiotic nitrogen fixation. Our aim is to improve the L. japonicus reference genome sequence, which has so far been based on Sanger and Illumina sequencing reads from the L. japonicus accession MG-20 and contained a large fraction of unanchored contigs.Methods and ResultsHere, we use long PacBio reads from L. japonicus Gifu combined with Hi-C data and new high-density genetic maps to generate a high-quality chromosome-scale reference genome assembly for L. japonicus. The assembly comprises 554 megabases of which 549 were assigned to six pseudomolecules that appear complete with telomeric repeats at their extremes and large centromeric regions with low gene density.Conclusion and PerspectivesThe new L. japonicus Gifu reference genome and associated expression data represent valuable resources for legume functional and comparative genomics. Here, we provide a first example by showing that the symbiotic islands recently described in Medicago truncatula do not appear to be conserved in L. japonicus.
Perturbation ofin vivoneural activity following α-Synuclein seeding in the olfactory bulb
Authors: Kulkarni Aishwarya S. , del Mar Cortijo Maria , Roberts Elizabeth R. , Suggs Tamara L. , Stover Heather B. , Pena-Bravo José I. , Steiner Jennifer A. , Luk Kelvin C. , Brundin Patrik , Wesson Daniel W. 
Published: April 2020

AbstractBACKGROUNDParkinson’s disease (PD) neuropathology is characterized by intraneuronal protein aggregates composed of misfolded α-Synuclein (α-Syn), as well as degeneration of substantia nigra dopamine neurons. Deficits in olfactory perception and aggregation of α-Syn in the olfactory bulb (OB) are observed during early stages of PD, and have been associated with the PD prodrome, before onset of the classic motor deficits. α-Syn fibrils injected into the OB of mice cause progressive propagation of α-Syn pathology throughout the olfactory system and are coupled to olfactory perceptual deficits.OBJECTIVEWe hypothesized that accumulation of pathogenic α-Syn in the OB impairs neural activity in the olfactory system.METHODSTo address this, we monitored spontaneous and odor-evoked local field potential dynamics in awake wild type mice simultaneously in the OB and piriform cortex (PCX) one, two, and three months following injection of pathogenic preformed α-Syn fibrils in the OB.RESULTSWe detected α-Syn pathology in both the OB and PCX. We also observed that α-Syn fibril injections influenced odor-evoked activity in the OB. In particular, α-Syn fibril-injected mice displayed aberrantly high odor-evoked power in the beta spectral range. A similar change in activity was not detected in the PCX, despite high levels of α-Syn pathology.CONCLUSIONSTogether, this work provides evidence that synucleinopathy impactsin vivoneural activity in the olfactory system at the network-level.
Emergence of complex dynamics of choice due to repeated exposures to extinction learning
Authors: Donoso José R. , Packheiser Julian , Pusch Roland , Lederer Zhiyin , Walther Thomas , Uengoer Metin , Lachnit Harald , Güntürkün Onur , Cheng Sen 
Published: April 2020

AbstractExtinction learning, the process of ceasing an acquired behavior in response to altered reinforcement contingencies, is not only essential for survival in a changing environment, but also plays a fundamental role in the treatment of pathological behaviors. During therapy and other forms of training involving extinction, subjects are typically exposed to several sessions with a similar structure. The effects of this repeated exposure are not well understood. Here, we studied the behavior of pigeons across several sessions of a discrimination learning task in context A, extinction in context B, and a return to context A to test the context-dependent return of the learned responses (ABA renewal). By focusing on individual learning curves across animals, we uncovered a session-dependent variability of behavior: (1) During extinction, pigeons preferred the unrewarded alternative choice in one-third of the sessions, predominantly during the first one. (2) In later sessions, abrupt transitions of behavior at the onset of context B emerged, and (3) the renewal effect decayed as sessions progressed. We show that the observed results can be parsimoniously accounted for by a computational model based only on associative learning between stimuli and actions. Our work thus demonstrates the critical importance of studying the trial-by-trial dynamics of learning in individual sessions, and the power of “simple” associative learning processes.
Powered flight potential approached by wide range of close avian relatives but achieved selectively
Authors: Pei R. , Pittman M. , Goloboff P.A. , Dececchi T.A. , Habib M.B. , Kaye T.G. , Larsson H.C.E. , Norell M.A. , Brusatte S.L. , Xu X. 
Published: April 2020

AbstractEvolution of birds from non-flying theropod dinosaurs is a classic evolutionary transition, but a deeper understanding of early flight has been frustrated by disagreement on the relationships between birds (Avialae) and their closest theropod relatives. We address this through a larger, more resolved evolutionary hypothesis produced by a novel automated analysis pipeline tailored for large morphological datasets. We corroborate the grouping of dromaeosaurids + troodontids (Deinonychosauria) as the sister taxon to birds (Paraves), as well as the recovery of Anchiornithidae as basalmost avialans. Using these phylogenetic results and available data for vaned feathered paravians, maximum and minimum estimates of wing loading and specific lift calculated using ancestral state reconstruction analysis are used as proxies for the potential for powered flight through this transition. We found a broad range of paravian ancestors with estimates approaching values that are indicative of powered flight potential. This suggests that prior to the evolution of flight there was a wider extent of experimentation with wing-assisted locomotion among paravians than previously appreciated. We recovered wing loading and specific lift estimates indicating the potential for powered flight among fossil birds as well as unenlagiine and microraptorine dromaeosaurids. In the context of our phylogeny and of Mesozoic palaeogeography, our results suggest that the potential for powered flight originated three or more times from a broad range of ancestors already nearing this potential, providing a well-supported scenario for the origin of theropod flight to further explore.
Shotgun proteomics of SARS-CoV-2 infected cells and its application to the optimisation of whole viral particle antigen production for vaccines
Authors: Grenga Lucia , Gallais Fabrice , Pible Olivier , Gaillard Jean-Charles , Gouveia Duarte , Batina Hélène , Bazaline Niza , Ruat Sylvie , Culotta Karen , Miotello Guylaine , Debroas Stéphanie , Roncato Marie-Anne , Steinmetz Gérard , Foissard Charlotte , Desplan Anne , Alpha-Bazin Béatrice , Almunia Christine , Gas Fabienne , Bellanger Laurent , Armengaud Jean 
Published: April 2020

AbstractSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread quickly around the globe. Currently, no effective vaccine is available to prevent COVID-19 and an intense global development activity is in progress. In this context, the different technology platforms face several challenges resulting from the involvement of a new virus still not fully characterised. Finding of the right conditions for virus amplification for the development of vaccines based on inactivated or attenuated whole viral particles is among them. Here, we describe the establishment of a workflow based on shotgun tandem mass spectrometry data to guide the optimisation of the conditions for viral amplification. In parallel, we analysed the dynamic of the host cell proteome following SARS-CoV-2 infection providing a global overview of biological processes modulated by the virus and that could be further explored to identify drug targets to address the pandemic.
Obstructed tear duct causes epiphora and precocious eyelid opening due to disruption of Prickle 1-mediated Wnt/PCP signaling
Authors: Guo Dianlei , Ru Jiali , Fan Jiaying , Ju Rong , Jin Kangxin , Ouyang Hong , Wei Lai , Liu Yizhi , Liu Chunqiao 
Published: April 2020

AbstractThe tear drainage apparatus evolved in terrestrial animals serving as conduits for tear flow. Obstruction of tear drainage causes a range of ocular surface disorders. Hitherto, genetics of tear duct development and obstruction has been scarcely explored. Here we report that a severePrickle 1hypomorph mouse line exhibited epiphora. This phenotype was due to blockage of the tear drainage by the incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (CL). Further analysis revealed that the precocious eyelid opening, previously observed in the same type ofPrickle 1mutants, is also caused by tear duct dysplasia. A comparison of wild type, thePrickle 1hypomorph and null mutants revealed a dose-dependent requirement ofPrickle 1for tear duct outgrowth. As a key component of a set of six Wnt/PCP core proteins, Prickle 1 usually works together with other PCP components. An investigation of expression of Wnt/PCP core genes demonstrated three of the six PCP components in tear duct, supporting the notion of context-dependent organization of PCP protein complexes. Furthermore, expression ofFgfr2/Fgf10andp63genes, mutations of which are associated with NLD and CL hypoplasia in human, were not altered inPrickle 1mutant mice. Lastly, we showed thatPrickle 1expression in developing tear drainage system is conserved between mouse and human despite anatomical differences. Altogether, the study uncovered how obstruction of the tear drainage could lead to a complex ocular surface disorder, which may have genetic implications in human ocular health.
Correlation between cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis
Authors: Wu Chun-Chieh , Lin Chien-Ju , Kuo Kong-Kai , Chen Wan-Tzu , Ker Chen-Guo , Chai Chee-Yin , Tsai Hung-Pei , Yang Sheau-Fang 
Published: April 2020

AbstractAimsChronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process characterised by chronic inflammation and hepatocyte damage but the correlation between HCC, inflammation and cancer stem cell remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells.Methods and resultsWe used diethylnitrosamine (DEN) to induce liver tumour and scored for H&E and reticulin staining, and also immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between each other. DEN progressively induced inflammation at 7 week 7 (40%, 2/5), week 27 (75%, 6/8), week 33 (62.5%, 5/8) and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5), week 27 (87.5%, 7/8), week 33 (100%, 8/8) and week 50 (100%, 12/12). Data obtained showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5), week 27 (37.5%, 3/8), week 33 (50%, 4/8) and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver as shown above and applying Spearman’s correlation to the data showed that expression of OV-6 was significantly correlated to inflammation (p= 0.001) and malignant transformation (p< 0.001)ConclusionsThere was a significant correlation between number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.
First-generation EGFR-TKI plus chemotherapy versus EGFR-TKI alone as first-line treatment in advanced NSCLC with EGFR activating mutation: a systematic review and meta-analysis of randomized controlled trials
Authors: Wu Qiang , Luo Wuxia , Li Wen , Wang Ting , Huang Lin , Xu Feng 
Published: April 2020

AbstractThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation. A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. A total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI=0.50-0.64; P < 0.00001) and 0.70 (95% CI=0.54-0.90; P=0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P=0.02) and concurrent therapy (P=0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10–1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia. In conclusion, compared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC, yet at the price of increasing incidence of chemotherapy-induced toxicities that is well tolerated and clinically manageable.
Systematic review of the validity of the hepatitis B virus detection tests in blood banks from 2000 to 2018
Authors: Orrego-Marín Claudia Patricia , Cardona-Arias Jaiberth Antonio , Medina-Moreno Sandra , Zapata Juan Carlos 
Published: April 2020

AbstractBackgroundHepatitis B Virus (HBV) is a public health problem that causes chronic hepatitis, eventually evolving to cirrhosis and hepatocellular carcinoma. Given the low frequency of screening in the general population, blood banks represent a key element for monitoring and controlling HBV transmission. The objective of this work was to evaluate the validity of the diagnosis of HBV in blood banks, based on studies published in the world scientific literature from 2000 to 2018.MethodsWe used a Meta-analysis of random effects with application of a search and selection protocol according to Cochrane and PRISMA guidelines. Reproducibility, completeness and quality assessment were affirmed with QUADAS, a tool for assessing diagnostics. The parameters of sensitivity, specificity, likelihood ratios, odds ratio and ROC curve were analyzed in MetaDisc with 95% confidence.ResultsFrom 4,061 studies screened, only 12 complied with the protocol, and the compliant studies included a population of 17,391 healthy people and 1,229 infected. The compliant studies evaluated mainly immunodiagnostics (ELISA) using HB surface antigen (HBsAg) and less frequently anti-HBc (HB core antigen) and PCR. The tests for HBsAg presented sensitivity of 94.1% (95% CI = 92.9% - 95.1%), specificity 98.2% (95% CI = 97.8% - 98.6%), diagnostic OR of 1721 (95% CI = 607.18 - 4418.8) and Area Under the Curve of 99.7%.ConclusionWith a large sample size and with the high quality of the studies evaluated in this review, we confirm that HBsAg for HBV immunodiagnostics has excellent validity, which supports its use in clinical screening, blood banks and population surveillance programs.
Evolution of immune escape mechanisms in the progression from preinvasive to invasive human lung adenocarcinoma
Authors: Altorki Nasser K. , Borczuk Alain C. , Mittal Vivek , Elemento Olivier , McGraw Timothy E. 
Published: April 2020

SummaryThe tumor microenvironment (TME) of lung adenocarcinoma (LUAD) precursor lesions has not been described. We interrogated by multiplex immunofluorescence the TME of preinvasive and invasive Stage 1A LUADs selected by computer tomography (CT) scan-density. Pure non-solid (p-NS) CT density nodules are preinvasive/minimally invasive, whereas solid CT density nodules are frankly invasive cancers. Our data reveal an intensely immune-suppressive immune TME in p-NS tumors characterized by an increase in Treg cells and a decrease in cytotoxic T cells relative to normal lung. The TME of the solid tumor group, more advanced lesions than the p-NS yet still early in disease development, were increasingly more immune-suppressive. Provocatively, there was a further increase in both Treg cells and cytotoxic T cells, establishing a nascent albeit ineffective anti-tumor immune response in transition from preinvasive p-NS to invasive solid tumors. Regulatory T cells play a dominant role throughout progression, while additional immune evasive mechanisms are employed at different stages of disease progression, including T cell exclusion from cancer cell nests early and activation of immune checkpoints later. Our study establishes that different immune-targeted strategies are required to intercept disease progression at these two distinct early points of lung cancer development.Statement of SignificanceUsing multiplexed IF, we compared the cellular composition and activation state of the tumor immune microenvironment between pre/minimally invasive and frankly invasive adenocarcinoma. We found a progressive increase in immunosuppressive mechanisms in association with disease progression suggesting that Interception strategies should be specifically tailored based on underlying immune escape mechanisms