bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foodborne Outbreaks, Product Recalls, and Firm Learning
Authors: Akhundjanov Sherzod B. , Pozo Veronica F. , Thomas Briana 
Published: January 2022

AbstractFirms in the food industry may experience more than one contamination incident over time. In the context of food safety, increasing the interval between foodborne outbreaks represents a key objective for both the food industry and public health officials. We demonstrate a systematic approach to analyzing repeated recalls, specifically to evaluate factors influencing the time until the next recall and, more importantly, to identify the extent of organizational learning from inter-event times. An analysis of meat and poultry recalls issued by publicly traded firms in the United States between 1994-2015 indicates that more diversified firms face a lower risk of repeat recalls as firm size expands, compared to firms primarily producing meat and poultry products. The hazard of a recall incident decreases with the severity of the previous recall. Some evidence of firm learning is found, but there is no definitive evidence indicating that a firm’s ability to prevent recalls improves with the number of foodborne outbreaks it has experienced.
Brain perivascular space imaging across the human lifespan
Authors: Lynch Kirsten M. , Sepehrband Farshid , Toga Arthur W. , Choupan Jeiran 
Published: January 2022

AbstractEnlarged perivascular spaces (PVS) are considered a biomarker for vascular pathology and are observed in normal aging and neurological conditions; however, research on the role of PVS in health and disease are hindered by the lack of knowledge regarding the normative time course of PVS alterations with age. To this end, we characterized the influence of age, sex and cognitive performance on PVS anatomical characteristics in a large cross-sectional cohort (∼1400) of healthy subjects between 8 and 90 years of age using multimodal structural MRI data. Our results show age is associated with wider and more numerous MRI-visible PVS over the course of the lifetime with spatially-varying patterns of PVS enlargement trajectories. In particular, regions with low PVS volume fraction in childhood are associated with rapid age-related PVS enlargement (e.g., temporal regions), while regions with high PVS volume fraction in childhood are associated with minimal age-related PVS alterations (e.g., limbic regions). PVS burden was significantly elevated in males compared to females with differing morphological time courses with age. Together, these findings contribute to our understanding of perivascular physiology across the healthy lifespan and provide a normative reference for the spatial distribution of PVS enlargement patterns to which pathological alterations can be compared.
Meta-omics-aided isolation of an elusive anaerobic arsenic-methylating soil bacterium
Authors: Viacava Karen , Qiao Jiangtao , Janowczyk Andrew , Poudel Suresh , Jacquemin Nicolas , Meibom Karin Lederballe , Shrestha Him K. , Reid Matthew C. , Hettich Robert L. , Bernier-Latmani Rizlan 
Published: January 2022

AbstractSoil microbiomes harbor unparalleled functional and phylogenetic diversity and are sources of novel metabolisms. However, extracting isolates with a targeted function from complex microbiomes is not straightforward, particularly if the associated phenotype does not lend itself to high-throughput screening. Here, we tackle the methylation of arsenic (As) in anoxic soils. By analogy to mercury, As methylation was proposed to be catalyzed by sulfate-reducing bacteria. However, to date, there are no anaerobic isolates capable of As methylation, whether sulfate-reducing or otherwise. The isolation of such a microorganism has been thwarted by the fact that the anaerobic bacteria harboring a functional arsenite S-adenosylmethionine methyltransferase (ArsM) tested to date did not methylate As in pure culture. Additionally, fortuitous As methylation can result from the release of non-specific methyltransferases upon lysis. Thus, we combined metagenomics, metatranscriptomics, and metaproteomics to identify the microorganisms actively methylating As in anoxic soil-derived microbial cultures. Based on the metagenome-assembled genomes of microorganisms expressing ArsM, we isolated Paraclostridium sp. strain EML, which was confirmed to actively methylate As anaerobically. This work is an example of the application of meta-omics to the isolation of elusive microorganisms.
KLF5-regulated extracellular matrix remodeling secures biliary epithelial tissue integrity against cholestatic liver injury
Authors: Yamada Minami , Okada Hajime , Ema Masatsugu , Kikkawa Yamato , Miyajima Atsushi , Itoh Tohru 
Published: January 2022

Abstract / Introductory paragraphTubular epithelial tissues in the body play fundamental roles as infrastructure constituting conduits to transport various types of biological fluids, for which contiguous and integrated epithelial tissue structures should be maintained continuously and even under stressed conditions. Compared to tissue morphological processes that take place during ontogeny, the mechanisms whereby tubular epithelial tissues maintain their structural integrity in adulthood remains largely unclear. Here, we show that the transcription factor Klf5 is crucial for maintaining the biliary epithelial integrity in tissue remodeling processes induced under cholestatic injury conditions in the adult liver. Loss of Klf5 in the biliary epithelia led to tissue collapse in vivo in injured mouse livers, as well as in vitro in bile ductular organoids in a tissue-autonomous manner and independent of cell proliferation. Klf5 regulated cell junction organization and cell adhesion, along with extracellular matrix remodeling around the expanding biliary epithelia through deposition of Lamb3-containing laminin complexes. Targeting the Lamb3 expression in biliary epithelia in mice recapitulated the tissue collapse phenotype. Together, our results highlight a novel mechanism whereby the epithelial tissue maintains its integrity while undergoing unstable structural transformation.
Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+T cell response during acute and chronic toxoplasmosis
Authors: Shallberg Lindsey A , Phan Anthony T , Christian David A , Perry Joseph A , Haskins Breanne E , Beiting Daniel P , Harris Tajie H , Koshy Anita A , Hunter Christopher A 
Published: January 2022

AbstractInitial TCR engagement of CD8+T cells results in T cell expansion, and these early events influence the generation of diverse effector and memory populations. During infection, some activated T cells re-encounter cognate antigen, but how these events influence local effector responses or formation of memory populations is unclear. To address this issue, OT-I T cells which express the Nur77-GFP reporter of TCR activation were paired withT. gondiithat express OVA to assess the impact of TCR activation on CD8+T cell responses. During acute infection, TCR stimulation in affected tissues correlated with parasite burden and was associated with markers of effector cells while Nur77-GFP-OT-I showed signs of effector memory potential. However, adoptive transfer of Nur77-GFP negative or positive OT-I from infected mice into naive recipients resulted in formation of similar memory populations. During the chronic stage of infection in the CNS, TCR activation was associated with large scale transcriptional changes and the acquisition of an effector T cell phenotype as well as the generation of a population of CD103+CD69+Trm like cells. However, while inhibition of parasite replication resulted in reduced effector responses it did not alter the Trm population. These data sets highlight the contribution of recent TCR activation on the phenotypic heterogeneity of the CD8+T cell response but suggest that this process has a limited impact on memory populations at acute and chronic stages of infection.Author SummaryCD8+T cells are important to control many acute and chronic infections, however the role that recent T cell receptor stimulation plays in the formation of ongoing T cell responses is unclear. Here, we utilize a genetic reporter of TCR stimulation and high parameter flow cytometry to characterize TCR-driven phenotypes of pathogen specific T cell responses to the parasiteToxoplasma gondiiduring acute and chronic infection in the periphery and central nervous system. This work demonstrates the importance of recent TCR stimulation in driving local effector CD8+T cell responses in peripheral tissues during infection, as well as the plasticity of the formation of memory T cells. Additionally, we utilize static and live imaging to investigate howToxoplasma gondiilife cycle impacts the ability to present antigen to CD8+T cells. These studies aid in our understanding of how effector and memory CD8+T cell responses are generated and maintained during an infection.
Weighting of celestial and terrestrial cues in the monarch butterfly central complex
Authors: Nguyen Tu Anh Thi , Beetz M. Jerome , Merlin Christine , Pfeiffer Keram , Jundi Basil el 
Published: January 2022

AbstractMonarch butterflies rely on external cues for orientation during their annual long-distance migration from Northern US and Canada to Central Mexico. These external cues can be celestial cues, such as the sun or polarized light, which are processed in the internal compass of the brain, termed the central complex (CX). Previous research typically focused on how individual simulated celestial cues are encoded in the butterfly’s CX. However, in nature, the butterflies perceive several celestial cues at the same time and need to integrate them to effectively use the compound of all cues for orientation. In addition, a recent behavioral study revealed that monarch butterflies can rely on terrestrial cues, such as the panoramic skyline, for orientation and use them in combination with the sun to maintain a directed flight course. How the CX encodes a combination of celestial and terrestrial cues and how they are weighted in the butterfly’s CX is still unknown. Here, we examined how input neurons of the CX, termed TL neurons, combine celestial and terrestrial information. While recording intracellularly from the neurons, we presented a sun stimulus and polarized light to the butterflies as well as a simulated sun and a panoramic scene simultaneously. Our results show that celestial cues are integrated linearly in these cells, while the combination of the sun and a panoramic skyline did not always follow a linear integration of action potential rates. Interestingly, while the weighting between the sun and polarized light was invariant between individual input neurons, it varied strongly when the sun stimulus and the panoramic skyline were presented simultaneously. Taken together, this dynamic weighting between celestial and terrestrial cues may allow the butterflies to flexibly set their cue preference during navigation.
The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses
Authors: Serrero Manutea C. , Girault Virginie , Weigang Sebastian , Greco Todd M. , Ramos-Nascimento Ana , Anderson Fenja , Piras Antonio , Martinez Ana Hickford , Hertzog Jonny , Binz Anne , Pohlmann Anja , Prank Ute , Rehwinkel Jan , Bauerfeind Rudolf , Cristea Ileana M. , Pichlmair Andreas , Kochs Georg , Sodeik Beate 
Published: January 2022

ABSTRACTHost proteins sense viral products and induce defence mechanisms, particularly in immune cells. Using cell-free assays and quantitative mass spectrometry, we determined the interactome of capsid- host protein complexes of herpes simplex virus and identified the large dynamin-like GTPase myxovirus resistance protein B (MxB) as an interferon-inducible protein interacting with capsids. Electron microscopy analyses showed that cytosols containing MxB had the remarkable capability to disassemble the icosahedral capsids of herpes simplex viruses and varicella zoster virus into flat sheets of connected triangular faces. In contrast, capsids remained intact in cytosols with MxB mutants unable to hydrolyse GTP or to dimerize. Our data suggest that MxB senses herpesviral capsids, mediates their disassembly, and thereby restricts the efficiency of nuclear targeting of incoming capsids and/or the assembly of progeny capsids. The resulting premature release of viral genomes from capsids may enhance the activation of DNA sensors, and thereby amplify the innate immune responses.
Divergent Golgi Trafficking Limits B cell-Mediated IgG Sialylation
Authors: Glendenning Leandre M. , Zhou Julie Y. , Reynero Kalob M. , Cobb Brian A. 
Published: January 2022

AbstractThe degree of α2,6-linked sialylation on IgG glycans is associated with a variety of inflammatory conditions and is thought to drive IgG anti-inflammatory activity. Previous findings revealed that ablation of β-galactoside α2,6-sialyltransferase 1 (ST6Gal1) in B cells failed to alter IgG sialylation in vivo, yet resulted in the loss of B cell surface α2,6 sialylation, suggesting divergent pathways for IgG and cell surface glycoprotein glycosylation and trafficking. Employing both B cell hybridomas and ex vivo murine B cells, we discovered that IgG was poorly sialylated by ST6Gal1 and highly core fucosylated by α1,6-fucosyltransferase 8 (Fut8) in cell culture. In contrast, IgG-producing cells showed the opposite pattern by flow cytometry, with high cell surface α2,6 sialylation and low α1,6 fucosylation. Paired studies further revealed that ex vivo B cell-produced IgG carried significantly less sialylation compared to IgG isolated from the plasma of matched animals, providing evidence that sialylation increases after release in vivo. Finally, confocal analyses demonstrated that IgG poorly localized to subcellular compartments rich in sialylation and ST6Gal1, and strongly to regions rich in fucosylation and Fut8. These findings support a model in which IgG subcellular trafficking diverges from the canonical secretory pathway by promoting Fut8-mediated core fucosylation and limiting exposure to and modification by ST6Gal1, providing a mechanism for why B cell-expressed ST6Gal1 is dispensable for IgG sialylation in vivo.
The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate
Authors: Hirano Minato , Galarza-Muñoz Gaddiel , Schott Geraldine , Wang Liuyang , Nagasawa Chloe , Antonia Alejandro L. , Jain Vaibhav , Yu Xiaoying , Widen Steven G. , Briggs Farren B.S. , Gregory Simon G. , Ko Dennis C. , Samuel Fagg W. , Bradrick Shelton S. , Garcia-Blanco Mariano A. 
Published: January 2022

SummaryGenes associated with increased susceptibility to multiple sclerosis (MS) have been identified, but their functions are incompletely understood. One of these genes codes for the RNA helicase DExD/H-Box Polypeptide 39B (DDX39B), which shows genetic and functional epistasis with interleukin-7 receptor-α gene (IL7R) in MS-risk. Based on evolutionary and functional arguments we postulated that DDX39B enhances immune tolerance decreasing MS risk. Consistent with such a role we show that DDX39B controls the expression of many MS susceptibility genes and important immune-related genes. Among these we identified ForkheadBox P3 (FOXP3), which codes for the master transcriptional factor in CD4+/CD25+ T regulatory cells. DDX39B knockdown led to loss of immune-regulatory and gain of immune-effector expression signatures. Splicing of FOXP3 introns, which belong to a previously unrecognized subclass of introns with C-rich polypyrimidine tracts, was exquisitely sensitive to DDX39B levels. Given the importance of FOXP3 in autoimmunity, this work cements DDX39B as an important guardian of immune tolerance.
Deep Learning Approaches to Identify Patients within the Thrombolytic Treatment Window
Authors: Polson Jennifer S , Zhang Haoyue , Nael Kambiz , Salamon Noriko , Yoo Bryan Y , El-Saden Suzie , Starkman Sidney , Kim Namkug , Kang Dong-Wha , Speier William F , Arnold Corey W 
Published: January 2022

1.AbstractBackgroundTreatment of acute ischemic stroke is heavily contingent upon time, as there is a strong relationship between time clock and tissue progression. We sought to a develop a deep learning algorithm for classifying time since stroke (TSS) from MR images by comparison to neuroradiologist assessments of imaging signal mismatch and evaluation on external data.MethodsThis retrospective study involved patients who underwent MRI from 2011-2019. Models were trained to classify TSS within 4.5 hours; performance metrics with confidence intervals were reported on both internal and external evaluation sets.ResultsA total of 772 patients (66 ± 9 years, 319 women) were used for model development and evaluation. Three board-certified neuroradiologists’ assessments, based on majority vote, yielded a sensitivity of 0.62, a specificity of 0.86, and a Fleiss’ kappa of 0.46. The deep learning method performed similarly to radiologists and outperformed previously reported methods, with the best model achieving an average evaluation accuracy, sensitivity, and specificity of 0.726, 0.712, and 0.741, on an internal cohort and 0.724, 0.757, and 0.679, respectively, on an external, unseen evaluation cohort from another institution.ConclusionThis model achieved higher generalization performance on external evaluation datasets than the current state of the art for TSS classification.
Impact of voluntary risk-mitigation behaviour on transmission of the Omicron SARS-CoV-2 variant in England
Authors: Brooks-Pollock Ellen , Northstone Kate , Pellis Lorenzo , Scarabel Francesca , Thomas Amy , Nixon Emily , Matthews David A. , Bowyer Vicky , Garcia Maria Paz , Steves Claire J. , Timpson Nicholas J. , Danon Leon 
Published: January 2022

AbstractBackgroundThe Omicron variant of SARS-CoV-2 infection poses substantial challenges to public health. In England, “plan B” mitigation measures were introduced in December 2021 including increased home working and face coverings in shops, but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown.MethodsWe developed a rapid online survey of risk mitigation behaviours during the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/Covid Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we describe the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave.ResultsOver 95% of survey respondents (NALSPAC=2,686 and NTwins=6,155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to “plan B”. We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 15,000 and 46,000 cumulative deaths, depending on assumptions about vaccine effectiveness. We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%.ConclusionsWe conclude that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant, but that voluntary measures alone would be unlikely to completely control transmission.
Patterns of treatment and outcome in patients with unresectable or inoperable esophageal cancer: A real world data
Authors: Chauhan Richa , Trivedi Vinita , Rani Rita , Singh Usha 
Published: January 2022

AbstractBackgroundEsophageal cancer is the eighth most common cancer in the world with a high mortality rate. Surgery, radiation and chemotherapy have been tried in various combinations to improve on the survival rates. Our study provides real world data from a South Asian country on patterns of treatment and outcome in patients with unresectable or inoperable esophageal cancer.Materials and MethodsThis study is a retrospective analysis of all consecutive esophageal cancer patients, with medically inoperable or unresectable disease, and treated with conformal radical radiotherapy at a tertiary cancer center from January, 2016 to December, 2017. Data regarding patients’ age, histology, location, pre-treatment imaging, disease stage, treatment details, compliance and response to treatment and status at last follow-up were retrieved from their file. Continuous and categorical variables were summarized by descriptive statistics.ResultsA total of 100 esophageal cancer patients with a mean age of 60.24 years were included in the study. 60% of the patients were male and upper one-third was the most common site involved. Squamous cell carcinoma was reported in 83% of the patients. About 70% of the patients had a T3/T4 disease and 44% also had nodal metastasis. The radiation dose ranged from 45Gy – 63Gy (median = 59.4Gy). Further, 15% and 54% of the patients received neoadjuvant and concurrent chemotherapy respectively. Radiation compliance was seen in 90% of the patients. With a median follow-up of 7 months (range 3-58 months), 80% of the patients were alive with 32.22% having no evidence of disease. Distant metastases and loco regional failure was seen in 32.22% and 28% of the patients respectively.ConclusionOur study showed that esophageal cancer is more common in elderly males. Adherence to a uniform treatment protocol using concurrent chemo radiation is difficult in clinical practice especially in resource constrained set up. Both distant metastases and loco regional failure continues to be a matter of concern. Further improvement in local control must be evaluated by either radiation dose escalation or novel combinations with chemotherapy and immunotherapy in large, multi centric trial settings.