bluuebunny/crossref_metadata_2025_split huggingface dataset:
Super-resolution imaging pinpoints ultrastructural changes at the node of Ranvier in patients with polyneuropathy
Authors: Appeltshauser Luise , Linke Janis , Heil Hannah S. , Karus Christine , Schenk Joachim , Hemmen Katherina , Sommer Claudia , Doppler Kathrin , Heinze Katrin G. 
Published: August 2022

To shed light on nanoscale pathologies in patients with polyneuropathy, we assessed human nerve biopsies by super-resolution fluorescence microscopy. We focused on both physiological protein arrangement and pathological ultrastructural changes at the node of Ranvier, a crucial region of the peripheral myelinated axon. Direct stochastic optical reconstruction microscopy (dSTORM) revealed a ∼190 nm periodic protein arrangement of cytoskeletal proteins and axoglial cell adhesion molecules. Periodic distances increased at the paranodal region of the node of Ranvier in patients with polyneuropathy, both at the axonal cytoskeleton and at the axoglial junction. In-depth image analysis of human nerve biopsies revealed a partial loss of proteins of the axoglial complex (Caspr-1, neurofascin-155) in combination with detachment from the cytoskeletal anchor protein ß2-spectrin. Super-resolution dual-color colocalization data was supported by high-content confocal imaging combined with deep learning-based analysis, indicating that paranodal elongation occurs especially in acute and severe axonal neuropathy, as a possible correlate of Wallerian degeneration and related cytoskeletal damage. Our findings show that super-resolution imaging can identify, quantify and map elongated periodic protein distances in peripheral nerve biopsies for pathophysiological studies and direct implications for diagnostic assessment.Graphical abstractPathological alterations of ultrastructural protein arrangement at the paranodal region of the node of Ranvier in polyneuropathy.Super-resolution microscopy allows for assessing ultrastructural protein arrangement and pathological alterations in patients with polyneuropathy. In human healthy nodes, axoglial and axoskeletal proteins follow a 190 nm periodic arrangement (left). In pathologically altered nodes (right), periodic protein distances of axonal ß2-spectrin elongate, in combination with elongation and partial loss of the axoglial complex of Caspr-1 and neurofascin-155. The axoglial complex itself colocalizes closely even in pathologically altered nodes. A complete loss of the axoglial complex could be the ultrastructural correlate of the detachment of paranodal myelin loops. Scale bar 2 μm.
Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19
Authors: Chen Dongxuan , Lau Yiu Chung , Xu Xiao-Ke , Wang Lin , Du Zhanwei , Tsang Tim K. , Wu Peng , Lau Eric H. Y. , Wallinga Jacco , Cowling Benjamin J. , Ali Sheikh Taslim 
Published: August 2022

AbstractBackgroundThe generation time distribution, reflecting the time between successive infections in transmission chains, is one of the fundamental epidemiological parameters for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution, reflecting the time between illness onsets of infector and infectee. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true.MethodsWe analyzed data on observed incubation period and serial interval distributions in China, during January and February 2020, under different sampling approaches, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures.ResultsWe analyzed data on a total of 2989 confirmed cases for COVID-19 during January 1 to February 29, 2020 in Mainland China. During the study period, the empirical forward serial interval decreased from a mean of 8.90 days to 2.68 days. The estimated mean backward incubation period of infectors increased from 3.77 days to 9.61 days, and the mean forward incubation period of infectees also increased from 5.39 days to 7.21 days. The estimated mean forward generation time decreased from 7.27 days (95% confidence interval: 6.42, 8.07) to 4.21 days (95% confidence interval: 3.70, 4.74) days by January 29. We used simulations to examine the sensitivity of our modelling approach to a number of assumptions and alternative dynamics.ConclusionsThe proposed method can provide more reliable estimation of the temporal variation in the generation time distribution, enabling proper assessment of transmission dynamics.
Ethnic inequalities in age-related patterns of multiple long-term conditions in England: analysis of primary care and nationally representative survey data
Authors: Hayanga Brenda , Stafford Mai , Saunders Catherine L. , Bécares Laia 
Published: August 2022

ABSTRACTBackgroundHaving multiple long-term conditions has been associated with a higher treatment burden, reduced quality of life and a higher risk of mortality. Epidemiological evidence suggests that people from minoritised ethnic groups have a higher prevalence of multiple long-term conditions (MLTCs) but questions remain regarding the patterning of MLTCs by age, how this varies for different ethnic group populations, and across conceptualisations of MLTCs (for example, MLTCs with and without mental health conditions). The aim of this study is to examine ethnic inequalities in age-related patterns of MLTCs, and combinations of physical and mental health conditions.MethodsWe analysed data from the English GP Patient Survey (GPPS) 2015-2017, and Clinical Practice Research Datalink (CPRD) Aurum from 2016, to give us insight into self-reported and primary care recorded long-term conditions in people aged 18 years and above. We described the association between two or more long-term conditions and age using multilevel regression models adjusting for sex and area-level deprivation with patients nested within GP practices. Similar analyses were repeated for MLTCs that included a mental health condition.FindingsFor both self-reported and primary care recorded LTCs, people from most minoritised ethnic groups had a lower prevalence of MLTCs at younger ages compared to their white counterparts. We observed ethnic inequalities from middle age onwards such that in later life, Pakistani, Indian, Black Caribbean and people of Other ethnicity were at an increased risk of having MLTCs compared to white British people. These trends remained after adjusting for area-level deprivation. Compared to white British people, Gypsy and Irish Travellers had higher levels of MLTCs across the age groups, and Chinese people had lower levels. Pakistani and Bangladeshi people aged 50-74 years were more likely than white British people to report two or more LTCs that included a mental health condition. People from other minoritised ethnic groups were less likely to report this compared to white British people.ConclusionWe find clear evidence of ethnic inequalities in MLTCs. It is imperative for health systems to recognise and respond to the higher prevalence of MLTCs that develop by middle age for many minoritised ethnic group people. The lower prevalence of MLTCs that include a mental health condition among some minoritised ethnic group people may be an underestimation due to underdiagnosis and/or inadequate care in primary care and requires further scrutiny.
The distribution of antimicrobial resistance genes across phylogroup, host species and geography in 16,000 publicly-availableE. coligenomes
Authors: Pursey Elizabeth , Dimitriu Tatiana , Gaze William H. , Westra Edze R. , van Houte Stineke 
Published: August 2022

AbstractE. coliis a highly diverse bacterial species that generates a huge global burden of antimicrobial-resistant infections. A wealth of whole genome sequence data is available on public databases for this species, presenting new opportunities to analyse the distribution of antimicrobial resistance (AMR) genes across its genetic and ecological diversity. We extracted and categorised metadata on host species and geographic location and combined this within silicophylogrouping to describe the characteristics of ∼16,000 assembledE. coligenomes from the NCBI RefSeq database. We estimated AMR carriage using various metrics: counts of overall genes, multidrug- and extensively drug-resistant categories, and selected β-lactamases of current global concern –blaCTX-Mand carbapenemase genes. We present estimates of AMR carriage for these metrics by species type (human, agricultural/domestic animal, wild birds and other wild animals), geographic subregion, and across phylogroups. In addition, we describe the distribution of phylogroups within host types and geographic subregions. Our findings show high AMR carriage in commensal-associated phylogroups, agricultural and wild animal hosts and in many subregions. However, we also quantify large biases in sequencing data, the substantial gaps in our knowledge of AMR in many hosts, regions and environmental settings, and the need for systematic sampling to gain a more accurate picture.
Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection
Authors: Soni Apurv , Herbert Carly , Lin Honghuang , Yan Yi , Pretz Caitlin , Stamegna Pamela , Wang Biqi , Orwig Taylor , Wright Colton , Tarrant Seanan , Behar Stephanie , Suvarna Thejas , Schrader Summer , Harman Emma , Nowak Chris , Kheterpal Vik , Rao Lokinendi V , Cashman Lisa , Orvek Elizabeth , Ayturk Didem , Gibson Laura , Zai Adrian , Wong Steven , Lazar Peter , Wang Ziyue , Filippaios Andreas , Barton Bruce , Achenbach Chad J. , Murphy Robert L. , Robinson Matthew , Manabe Yukari C. , Pandey Shishir , Colubri Andres , O’Connor Laurel , Lemon Stephenie C. , Fahey Nisha , Luzuriaga Katherine L , Hafer Nathaniel , Roth Kristian , Lowe Toby , Stenzel Timothy , Heetderks William , Broach John , McManus David D 
Published: August 2022

AbstractBackgroundPerformance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance in screening for SARS-CoV-2 is not well established. We aimed to evaluate performance of Ag-RDT for detection of SARS-CoV-2 for symptomatic and asymptomatic participants.MethodsParticipants >2 years old across the United States enrolled in the study between October 2021 and February 2022. Participants completed Ag-RDT and molecular testing (RT-PCR) for SARS-CoV-2 every 48 hours for 15 days. This analysis was limited to participants who were asymptomatic and tested negative on their first day of study participation. Onset of infection was defined as the day of first positive RT-PCR result. Sensitivity of Ag-RDT was measured based on testing once, twice (after 48-hours), and thrice (after 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status.ResultsIn total, 5,609 of 7,361 participants were eligible for this analysis. Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDT twice 48-hours apart resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Excluding singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower at 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with testing three times at 48-hour intervals.DiscussionPerformance of Ag-RDT was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.
Effect of Adjunctive Prefronto-Cerebellar Transcranial Direct Current Stimulation(tDCS) on Craving and Relapse Prevention in Patients with Alcohol Dependence Syndrome (ADS): A Randomized Sham Controlled Study Protocol
Authors: Sarkar Susmita , Singh Lokesh Kumar , Kumar Ajay , Tikka Sai Krishna 
Published: August 2022

ABSTRACTBACKGROUNDThere is growing evidence that tDCS in the Dorsolateral Prefrontal Cortex (DLPFC) technique is effective in controlling craving and relapse in ADS patients. Till now the results are inconclusive. Interestingly, the cerebellum is related to impulsive and compulsive behavior which is supported by both structural and functional neuroimaging findings. There are few clinical trials regarding the effect of cerebellar tDCS in ADS.OBJECTIVETo assess the effect of Prefronto-cerebellar tDCS in reducing craving and relapses in ADS patients.METHODSThe study population will be randomly assigned to either of two groups i.e. Active and Sham tDCS group. The active group will receive 10 sessions over 5 days; 2mA current for 15 minutes. The site of anodal stimulation is 2cm below the Iz (inion) and cathodal stimulation at F3 (left prefrontal) and in the sham group will receive the same except that intensity of the current is 0.2mA. Patients will be assessed for craving at 3-time points.CONCLUSIONIt will be helpful in analyzing the effect of stimulating DLPFC as well as the cerebellum which is a potential novel site in reducing craving and relapse in ADS.HIGHLIGHTStDCS in ADS is being tried for the last decade mainly focusing on the frontal area. With the current understanding of the role of the cerebellum in regulating impulsive and compulsive behavior, we intend to add the cerebellum as a potential site for neuromodulation in reducing craving and relapse in ADS patients.
BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection
Authors: Aggarwal Surya D. , Lees John A. , Jacobs Nathan T. , Bee Gavyn Chern Wei , Abruzzo Annie R. , Weiser Jeffrey N. 
Published: August 2022

SUMMARYChromosomal barcoding and high-throughput sequencing were used to investigate the population dynamics of Streptococcus pneumoniae. During infant mouse colonization, >35-fold reduction in diversity and expansion of a single clonal lineage was observed within 1 day post-inoculation. This loss of diversity was not due to immune factors, host microbiota or exclusively because of genetic drift. Rather, it required the expression of blp bacteriocins induced by the BlpC-quorum sensing pheromone. This points towards the role of intra-strain competition whereby the subpopulation reaching a quorum eliminates others that have yet to activate the blp locus. We show that this loss of diversity also restricts the number of unique clones that could establish colonization during transmission between hosts. Moreover, we show that genetic variation in the blp locus is associated with transmissibility in the human population. We posit this is due to its importance in clonal selection and its role as a selfish element.
Structure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120
Authors: Nagao Ryo , Kato Koji , Hamaguchi Tasuku , Ueno Yoshifumi , Tsuboshita Naoki , Shimizu Shota , Furutani Miyu , Ehira Shigeki , Nakajima Yoshiki , Kawakami Keisuke , Suzuki Takehiro , Dohmae Naoshi , Akimoto Seiji , Yonekura Koji , Shen Jian-Ren 
Published: August 2022

AbstractIron-stress-induced-A proteins (IsiAs) are expressed in cyanobacteria under iron-deficient conditions. The cyanobacterium Anabaena sp. PCC 7120 has four isiA genes; however, their binding property and functional roles in PSI are still missing. We analyzed a cryo-electron microscopy structure of a PSI-IsiA supercomplex isolated from Anabaena grown under an iron-deficient condition. The PSI-IsiA structure contains six IsiA subunits associated with the PsaA side of a PSI core monomer. Three of the six IsiA subunits are identified as IsiA1 and IsiA2. The PSI-IsiA structure lacks a PsaL subunit; instead, a C-terminal domain of IsiA2 is inserted at the position of PsaL, which inhibits the oligomerization of PSI, leading to the formation of a monomer. Furthermore, excitation-energy transfer from IsiAs to PSI appeared with a time constant of 55 ps. These findings provide novel insights into both the molecular assembly of the Anabaena IsiA family and the functional roles of IsiAs.
A fear conditioned cue orchestrates a suite of behaviors
Authors: Chu Amanda , Michel Christa B. , Gordon Nicholas T. , Hanrahan Katherine E. , DuBois Aleah M. , Williams David C. , McDannald Michael A. 
Published: August 2022

AbstractPavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave 24 rats (12 female) Pavlovian fear discrimination over a baseline of reward seeking. The within-subjects procedure had full controls for associative learning, consisting of three cues predicting unique foot shock probabilities: danger (p=1), uncertainty (p=0.25), and safety (p=0). TTL-triggered cameras captured 5 behavior frames/s prior to and during cue presentation. We scored 86,400 frames for nine discrete behaviors spanning reward, passive fear, and active fear. Temporal ethograms show that a fear conditioned cue elicits locomotion, jumping, and rearing that is maximal towards cue offset, when foot shock is imminent. A fear conditioned cue further suppresses reward-related behavior, and elicits freezing in a sex-specific manner. The differing temporal profiles and independent expression of these behaviors reveal a fear conditioned cue to orchestrate a rich and intricate suite of behaviors.
Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus
Authors: Flowers Laurice , Wei Monica , Knight Simon A. B. , Zheng Qi , Uberoi Aayushi , Campbell Amy , Pan Ting-Chun Jamie , Walsh Jasmine , Schroeder Erin , Chu Emily W. , Bradley Charles W. , Duran-Struuck Raimon , Grice Elizabeth A. 
Published: August 2022

ABSTRACTThe microbiota mediates multiple aspects of skin barrier function, including colonization resistance to pathogens such as Staphylococcus aureus. The endogenous skin microbiota limits S. aureus colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant S. aureus (MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had little discernable effect on community diversity though the overall microbial load was sensitive to any type of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. Using genomic and phenotypic criteria, we curated 3 isolates to investigate whether prophylactic colonization would inhibit MRSA colonization in vivo. The 3-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection.
Sequence features do not drive karyotypic evolution: what are the missing correlates of genome evolution?
Authors: Brekke Thomas D. , Papadopulos Alexander S. T. , Swain Martin T. , Mulley John F. 
Published: August 2022

AbstractGenome rearrangements are prevalent across the tree of life and even within species. After two decades of research, various suggestions have been proposed to explain which features of the genome are associated with rearrangements and the breakpoints between rearranged regions. These include: recombination rate, GC content, repetitive DNA content, gene density, and markers of chromatin conformation. Here, we use a set of six aligned rodent genomes to identify regions that have not been rearranged and characterize the breakpoint regions where rearrangements have occurred. We found no strong support for any of the expected correlations between breakpoint regions and a variety of genomic features previously identified. These results call into question the utility and repeatability of identifying chromatin characteristics associated with rearranged regions of the genome and suggest that perhaps a different explanation is in order. We analyzed rates of karyotypic evolution in each of the six lineages and found that the Mongolian gerbil genome has had the most rearrangements. That gerbils exhibit very rapid sequence evolution at a number of key DNA repair genes suggests an alternative hypothesis for patterns of genome rearrangement: karyotypic evolution may be driven by variation at a few genes that control the repair pathway used to fix double-stranded DNA breaks. Such variation may explain the heterogeneity in the rates of karyotypic evolution across species. While currently only supported by circumstantial evidence, a systematic survey of this hypothesis is now warranted.
Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5
Authors: Tamura Tomokazu , Yamasoba Daichi , Oda Yoshitaka , Ito Jumpei , Kamasaki Tomoko , Nao Naganori , Hashimoto Rina , Fujioka Yoichiro , Suzuki Rigel , Wang Lei , Ito Hayato , Kimura Izumi , Yokota Isao , Kishimoto Mai , Tsuda Masumi , Sawa Hirofumi , Yoshimatsu Kumiko , Ohba Yusuke , Yamamoto Yuki , Nagamoto Tetsuharu , Kanamune Jun ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Matsuno Keita , Takayama Kazuo , Tanaka Shinya , Sato Kei , Fukuhara Takasuke 
Published: August 2022

AbstractUnremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants imposes us to continuous control measurement. Given the rapid spread, new Omicron subvariant named BA.5 is urgently required for characterization. Here we analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1 comprehensively. Although in vitro growth kinetics of BA.5 is comparable among the Omicron subvariants, BA.5 become much more fusogenic than BA.1 and BA.2. The airway-on-a-chip analysis showed that the ability of BA.5 to disrupt the respiratory epithelial and endothelial barriers is enhanced among Omicron subvariants. Furthermore, in our hamster model, in vivo replication of BA.5 is comparable with that of the other Omicrons and less than that of the ancestral B.1.1. Importantly, inflammatory response against BA.5 is strong compared with BA.1 and BA.2. Our data suggest that BA.5 is still low pathogenic compared to ancestral strain but evolved to induce enhanced inflammation when compared to prior Omicron subvariants.