bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multicenter Application of the 2018 Banff Classification for BK Polyomavirus-associated Nephropathy in Renal Transplantation
Authors: Bouatou Yassine , Nguyen Tri Q. , Roelofs Joris J.T.H. , Bemelman Frederike J. , Michielsen Laura , Goldschmeding Roel , Kers Jesper , Florquin Sandrine 
Published: March 2019

Background.
With current immunosuppressive regimens, BK polyomavirus-associated nephropathy (BKPyVAN) is still a matter of concern. Stratification of patients at risk for allograft loss is of uttermost importance to guide treatment choice and assess prognosis. In 2018, the Banff working group proposed a classification scheme for the prognosis of BKPyVAN, but external application on independent cohorts is yet to be performed. We investigated how the 2018 Banff classification would perform in a multicenter cohort comprising 50 cases of biopsy-proven BKPyVAN compared to previously published classification systems.

Methods.
We analyzed consecutive BKPyVAN cases from two Dutch university hospitals between 2002 and 2013, retrieved clinical data, and scored all biopsies according to the Banff 2018 classification, and as a comparison, 4 previously proposed BKPyVAN classification systems. We used estimated glomerular filtration rate trajectories and death-censored graft survival as primary endpoints.

Results.
The 2018 Banff classification did not associate with estimated glomerular filtration rate decline or graft failure and performed only slightly better than the 4 previously proposed classifiers. Anti-human leukocyte antigen donor-specific antibodies (DSAs), especially in combination with ongoing biopsy-proven BKPyVAN on follow-up, did correlate with graft function and survival. Patients who were DSA+/BKPyVAN+ on follow-up had more inflammation at the baseline biopsy, which by itself was not associated with graft outcomes.

Conclusions.
Neither the 2018 Banff BKPyVAN classification nor previously published stratification systems could be applied to our multicenter patient cohort. Our data suggest that there might be a prognostic value for follow-up biopsies and DSA measurements to improve risk stratification after BKPyVAN, although prospective multicenter efforts with protocol measurements are needed to confirm this.
Differences in Awareness of Disease Between Young-onset and Late-onset Dementia
Authors: Baptista Maria A.T. , Santos Raquel L. , Kimura Nathália , Marinho Valeska , Simões José P. , Laks Jerson , Johannenssen Aud , Barca Maria L. , Engedal Knut , Dourado Marcia C.N. 
Published: March 2019

Introduction:Awareness of disease is the ability to acknowledge changes caused by deficits related to the disease process. We aimed to investigate whether there are differences in awareness of disease between young-onset dementia (YOD) and late-onset dementia (LOD) and examined how awareness interacts with cognitive and clinical variables.Materials and Methods:Using a cross-sectional design, 49 people with YOD and 83 with LOD and their caregivers were included. We assessed awareness of disease, cognition, functionality, stage of dementia, mood, neuropsychiatric symptoms, and caregivers’ quality of life (QoL) and burden.Results:We found that people with YOD were more aware of the disease than people with LOD (P<0.005). Multivariate linear regression revealed that higher impairment in functional level was associated with unawareness in both groups (YOD=P<0.001; LOD=P<0.001). In the YOD group, preserved awareness was related to worse self-reported QoL (P<0.05), whereas, in LOD, deficits in awareness were related to caregivers’ worst perceptions about people with dementia QoL (P<0.001).Conclusions:The findings highlight the distinct nature of awareness between YOD and LOD. The YOD group had higher levels of disease awareness compared with the LOD group, even though the first group had a greater impairment in functionality.
Neurotoxicity associated with cancer immunotherapy: immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy
Authors: Perrinjaquet Claire , Desbaillets Nicolas , Hottinger Andreas F. 
Published: March 2019

Purpose of review
Immune checkpoint inhibitors (ICPI) and chimeric antigen receptor T cells (CAR-T) represent novel therapies recently approved to treat a number of human cancers. As both approaches modulate the immune system, they can generate a number of immune-related adverse events (irAEs), including a large spectrum of novel neurological toxicities. These are of special interest given their potential severity and risk of compromising further oncologic treatment. We aim to provide a comprehensive review of the literature and discuss their optimal management.

Recent findings
In contrast to irAEs involving other organs, neurological complications of ICPI are uncommon, may present throughout the course of treatment and involve the peripheral and central nervous system, including polyneuropathy, myositis, myasthenia gravis, demyelinating polyradiculopathy, myelitis, encephalitis and others. If started early, ICPI-related neurologic irAEs are usually responsive to steroids. In contrast, as many as 40% of patients undergoing CAR-T therapy will develop neurologic complications in the form of a cytokine-release-associated encephalopathy. It includes delirium, aphasia, tremor/myoclonus, seizure and seizure-like activity.

Summary
irAEs associated with CAR-T and ICPI therapy constitute new entities. Early identification and treatment are essential to optimize the functional outcome and further oncologic management of the patient.
Neuromyelitis optica spectrum disorders: still evolving and broadening
Authors: Fujihara Kazuo 
Published: March 2019

Purpose of reviewThe diagnostic criteria of neuromyelitis optica spectrum disorders (NMOSD) has been revised in the past 20 years and pathological and therapeutic data have been accumulated. This review provides an overview of evolution and broadening of the concept of NMOSD.Recent findingsNMOSD encompassing brain syndrome as well as optic neuritis and acute myelitis is now classified into aquaporine-4 (AQP)-antibody-seropositive and aquaporine-4 (AQP)-antibody-seronegative diseases, detecting more patients earlier than before. Seronegative NMOSD includes cases of myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive disease with its unique clinical spectrum somewhat different from AQP4-antibody-seropositive NMOSD. Pathologically, NMOSD includes AQP4-antibody-seropositive autoimmune astrocytopathic disease and MOG-antibody-seropositive inflammatory demyelinating disease. Double seronegative group needs further research. Therapeutic options of NMOSD has taken shape and first-ever clinical trials of monoclonal antibodies have been done. In retrospect, relapsing NMO in the studies preceding the discovery of AQP4-antibody had features of AQP4-antibody-seropositive NMO whereas monophasic NMO was similar to AQP4-antibody-seronegative/MOG-antibody-seropositive NMO.SummaryThe clinical, pathological and therapeutic concepts of NMOSD have evolved and broadened over the last two decades following the detection of AQP4 antibodies and MOG antibodies in the patients. Double seronegative NMOSD is a current research focus, but now we may need to reconsider how NMOSD should be defined.
A matter of background: DNA repair pathways as a possible cause for the sparse distribution of CRISPR-Cas systems in bacteria
Authors: Bernheim Aude , Bikard David , Touchon Marie , Rocha Eduardo P. C. 
Published: March 2019

The absence of CRISPR-Cas systems in more than half of the sequenced bacterial genomes is intriguing, because their role in adaptive immunity and their frequent transfer between species should have made them almost ubiquitous, as is the case in Archaea. Here, we investigate the possibility that the success of CRISPR-Cas acquisition by horizontal gene transfer is affected by the interactions of these systems with the host genetic background and especially with components of double-strand break repair systems (DSB-RS). We first described the distribution of systems specialized in the repair of double-strand breaks in Bacteria: homologous recombination and non-homologous end joining. This allowed us to show that such systems are more often positively or negatively correlated with the frequency of CRISPR-Cas systems than random genes of similar frequency. The detailed analysis of these co-occurrence patterns shows that our method identifies previously known cases of mechanistic interactions between these systems. It also reveals other positive and negative patterns of co-occurrence between DSB-RS and CRISPR-Cas systems. Notably, it shows that the patterns of distribution of CRISPR-Cas systems in Proteobacteria are strongly dependent on the epistatic groups including RecBCD and AddAB. Our results suggest that the genetic background plays an important role in the success of adaptive immunity in different bacterial clades and provide insights to guide further experimental research on the interactions between CRISPR-Cas and DSB-RS.
This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Diversified local CRISPR-Cas immunity to viruses ofSulfolobus islandicus
Authors: Pauly Matthew D. , Bautista Maria A. , Black Jesse A. , Whitaker Rachel J. 
Published: March 2019

The population diversity and structure of CRISPR-Cas immunity provides key insights into virus–host interactions. Here, we examined two geographically and genetically distinct natural populations of the thermophilic crenarchaeonSulfolobus islandicusand their interactions withSulfolobusspindle-shaped viruses (SSVs) andS. islandicusrod-shaped viruses (SIRVs). We found that both virus families can be targeted with high population distributed immunity, whereby most immune strains target a virus using unique unshared CRISPR spacers. In Kamchatka, Russia, we observed high immunity to chronic SSVs that increases over time. In this context, we found that some SSVs had shortened genomes lacking genes that are highly targeted by theS. islandicuspopulation, indicating a potential mechanism of immune evasion. By contrast, in Yellowstone National Park, we found high inter- and intra-strain immune diversity targeting lytic SIRVs and low immunity to chronic SSVs. In this population, we observed evidence of SIRVs evolving immunity through mutations concentrated in the first five bases of protospacers. These results indicate that diversity and structure of antiviral CRISPR-Cas immunity for a single microbial species can differ by both the population and virus type, and suggest that different virus families use different mechanisms to evade CRISPR-Cas immunity.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
The effect of bacterial mutation rate on the evolution of CRISPR-Cas adaptive immunity
Authors: Chevallereau Anne , Meaden Sean , van Houte Stineke , Westra Edze R. , Rollie Clare 
Published: March 2019

CRISPR-Cas immune systems are present in around half of bacterial genomes. Given the specificity and adaptability of this immune mechanism, it is perhaps surprising that they are not more widespread. Recent insights into the requirement for specific host factors for the function of some CRISPR-Cas subtypes, as well as the negative epistasis between CRISPR-Cas and other host genes, have shed light on potential reasons for the partial distribution of this immune strategy in bacteria. In this study, we examined how mutations in the bacterial mismatch repair system, which are frequently observed in natural and clinical isolates and cause elevated host mutation rates, influence the evolution of CRISPR-Cas–mediated immunity. We found that hosts with a high mutation rate very rarely evolved CRISPR-based immunity to phage compared to wild-type hosts. We explored the reason for this effect and found that the higher frequency at which surface mutants pre-exist in the mutator host background causes them to rapidly become the dominant phenotype under phage infection. These findings suggest that natural variation in bacterial mutation rates may, therefore, influence the distribution of CRISPR-Cas adaptive immune systems.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Cost and benefits of clustered regularly interspaced short palindromic repeats spacer acquisition
Authors: Bradde Serena , Mora Thierry , Walczak Aleksandra M. 
Published: March 2019

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-mediated immunity in bacteria allows bacterial populations to protect themselves against pathogens. However, it also exposes them to the dangers of auto-immunity by developing protection that targets its own genome. Using a simple model of the coupled dynamics of phage and bacterial populations, we explore how acquisition rates affect the probability of the bacterial colony going extinct. We find that the optimal strategy depends on the initial population sizes of both viruses and bacteria. Additionally, certain combinations of acquisition and dynamical rates and initial population sizes guarantee protection, owing to a dynamical balance between the evolving population sizes, without relying on acquisition of viral spacers. Outside this regime, the high cost of auto-immunity limits the acquisition rate. We discuss these optimal strategies that minimize the probability of the colony going extinct in terms of recent experiments.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B
Authors: Vögtle Timo , Sharma Sumana , Mori Jun , Nagy Zoltan , Semeniak Daniela , Geer Mitchell J. , Smith Christopher W. , Lane Jordan , Pollack Scott , Lassila Riitta , Jouppila Annukka , Barr Alastair J. , Ogg Derek J. , Howard Tina D. , McMiken Helen J. , Warwicker Juli , Geh Catherine , Rowlinson Rachel , Mark Abbott W. , Schulze Harald , Wright Gavin J. , Mazharian Alexandra , Fütterer Klaus , Rajesh Sundaresan , Douglas Michael R. , Senis Yotis A. 
Published: March 2019

ABSTRACTThe immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor G6b-B is critical for platelet production and activation, loss of which results in severe macrothrombocytopenia and aberrant platelet function in mice and humans. Using a combination of immunohistochemistry, affinity chromatography and proteomics, we identified the extracellular matrix heparan sulfate (HS) proteoglycan perlecan as a G6b-B binding partner. Subsequentin vitrobiochemical studies and a cell-based genetic screen demonstrated that the interaction is specifically mediated by the HS chains of perlecan. Biophysical analysis revealed that heparin forms a high-affinity complex with G6b-B and mediates dimerization. Using platelets from humans and genetically-modified mice, we demonstrate that binding of G6b-B to HS and multivalent heparin inhibits platelet and megakaryocyte function by inducing downstream signaling via the tyrosine phosphatases Shp1 and Shp2. Our findings provide novel insights into how G6b-B is regulated and contribute to our understanding of the interaction of megakaryocytes and platelets with glycans.
Linalool acts as a fast and reversible anesthetic inHydra
Authors: Goel Tapan , Wang Rui , Martin Sara , Lanphear Elizabeth , Collins Eva-Maria S. 
Published: March 2019

AbstractThe ability to make transgenicHydralines has opened the door for quantitativein vivostudies ofHydraregeneration and physiology. These studies commonly include excision, grafting and transplantation experiments along with high-resolution imaging of live animals, which can be challenging due to the animal’s response to touch and light stimuli. While various anesthetics have been used inHydrastudies over the years, they tend to be toxic over the course of a few hours or their long-term effects on animal health have not been studied. Here we show that the monoterpenoid linalool is a useful anesthetic forHydra. Linalool is easy to use, non-toxic, fast acting, and reversible. It has no detectable long-term effects on cell viability or cell proliferation. We demonstrate that the same animal can be immobilized in linalool multiple times at intervals of several hours for repeated imaging over 2-3 days. This uniquely allows forin vivoimaging of dynamic processes such as head regeneration. We further directly compare linalool to currently used anesthetics and show its superior performance. Because linalool, which is frequently utilized in perfumes and cosmetic products, is also non-hazardous to humans, it will be a useful tool forHydraresearch in both research and teaching contexts.
Molecular dissection of the structural and nonstructural proteins of spanish-1918 Influenza, pandemic-2009, and bird flu viruses
Authors: Mahardika Gusti Ngurah , Suartha Nyoman , Kencana Gusti Ayu Yuniati , Suardana Ida Bagus Kade , Budayanti Nyoman Sri 
Published: March 2019

AbstractThe potential emergence of deadly pandemic influenza viruses is unpredictable and most have emerged with no forewarning. The distinct epidemiological and pathological patterns of the Spanish (H1N1), pandemic-2009 (H1N1), and avian influenza (H5N1), known as bird flu, viruses may allow us to develop a ‘template’ for possible emergence of devastating pandemic strains. Here, we provide a detailed molecular dissection of the structural and nonstructural proteins of this triad of viruses. GenBank data for three representative strains were analyzed to determine the polymorphic amino acids, genetic distances, and isoelectric points, hydrophobicity plot, and protein modeling of various proteins. We propose that the most devastating pandemic strains may have full-length PB1-F2 protein with unique residues, highly cleavable HA, and a basic NS1. Any newly emerging strain should be compared with these three strains, so that resources can be directed appropriately.
A generic multivariate framework for the integration of microbiome longitudinal studies with other data types
Authors: Bodein Antoine , Chapleur Olivier , Droit Arnaud , Lê Cao Kim-Anh 
Published: March 2019

AbstractSimultaneous profiling of biospecimens using different technological platforms enables the study of many data types, encompassing microbial communities, omics and meta-omics as well as clinical or chemistry variables. Reduction in costs now enables longitudinal or time course studies on the same biological material or system. The overall aim of such studies is to investigate relationships between these longitudinal measures in a holistic manner to further decipher the link between molecular mechanisms and microbial community structures, or host-microbiota interactions. However, analytical frameworks enabling an integrated analysis between microbial communities and other types of biological, clinical or phenotypic data are still in their infancy. The challenges include few time points that may be unevenly spaced and unmatched between different data types, a small number of unique individual biospecimens and high individual variability. Those challenges are further exacerbated by the inherent characteristics of microbial communities-derived data (e.g. sparsity, compositional).We propose a generic data-driven framework to integrate different types of longitudinal data measured on the same biological specimens with microbial communities data, and select key temporal features with strong associations within the same sample group. The framework ranges from filtering and modelling, to integration using smoothing splines and multivariate dimension reduction methods to address some of the analytical challenges of microbiome-derived data. We illustrate our framework on different types of multi-omics case studies in bioreactor experiments as well as human studies.
Identification of blaGIM-1 in Acinetobacter variabilis isolated from the hospital environment in Tamil Nadu, India
Authors: Manohar Prasanth , Ragavi Murugavel , Augustine Ashby , MV Hrishikesh , Ramesh Nachimuthu 
Published: March 2019

AbstractBackgroundEmergence of carbapenem resistance mechanisms among Gram-negative bacteria is a worrisome health problem. Here, we focused on to identify the presence of carbapenem-resistant bacteria among the samples collected from hospital environments in Tamil Nadu.MethodsA total of 30 hospital environmental samples were collected between August 2017 and January 2018 from hospitals located in Chennai and Vellore such as lift switches, stair rails, switchboards, nursing desks, used nursing gloves, door handles, wheelchairs, touch screens, chairs and from pillars inside the hospitals.Results and discussionA total of 22 carbapenem-resistant Gram-negative bacteria were isolated that included Escherichia coli, Klebsiella sp., Enterobacter sp., Salmonella sp., Pseudomonas aeruginosa and Acinetobacter sp. Interestingly, blaGIM-1 was detected in Acinetobacter variabilis strain isolated in samples collected from hospitals. Unlike other studies, the identified GIM-1 was not plasmid encoded, and this is the first report for the presence of GIM-1 (German imipenemase) in India.ConclusionExtensive surveillance programs are necessary to trace the uncontrolled spread of carbapenem-resistance genes in order to reduce the rapid spread of resistance.
The developmental cycle ofDictyostelium discoideumensures curing of a mycobacterial infection at both cell-autonomous level and by collaborative exclusion
Authors: López-Jiménez Ana Teresa , Hagedorn Monica , Delincé Matthieu J. , McKinney John , Soldati Thierry 
Published: March 2019

ABSTRACTDuring its life cycle, the social amoebaDictyostelium discoideumalternates between a predatory amoeba and a facultative multicellular form. The single-celled amoeba is a well-established model system to study cell-autonomous mechanisms of phagocytosis and defence against intracellular bacterial pathogens, whereas the multicellular forms are arising as models to study the emergence of innate immune defence strategies. Importantly, during evolution, prokaryotes have also evolved their own strategies to resist predation. Considering these complex ecological relationships, we wondered whetherD. discoideumcells infected with intracellular pathogenic mycobacteria would be able to undergo their developmental cycle and what would be the fate of the infection. We show that the combination of cell-autonomous mechanisms and the organisation into a multicellular organism leads to the efficient multistep-curing of a mycobacteria-infected population, thereby ensuring germ-free spores and progeny. Specifically, using a microfluidic device to trap single infected cells, we revealed that in the first curing phase, individual cells rely on three mechanisms to release intracellular bacteria: exocytic release, ejection and lytic release. The second phase occurs at the collective level, when remaining infected cells are excluded from the forming cell aggregates.