bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-modal single cell analysis reveals brain immune landscape plasticity during aging and gut microbiota dysbiosis
Authors: Golomb Samantha M. , Guldner Ian H. , Zhao Anqi , Wang Qingfei , Palakurthi Bhavana , Lopez Jacqueline , Yang Kai , Zhang Siyuan 
Published: July 2020

ABSTRACTThe brain contains a diverse array of immune cell types. The phenotypic and functional plasticity of brain immune cells collectively contribute to brain tissue homeostasis and disease progression. Immune cell plasticity is profoundly influenced by local tissue microenvironment cues and systemic factors. Yet, the transcriptional mechanism by which systemic stimuli, such as aging and gut microbiota dysbiosis, reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyzed compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. We first examined the discordance between canonical surface marker-defined immune cell types (Cell-ID) and their transcriptome signatures, which suggested transcriptional plasticity among immune cells despite sharing the same cell surface markers. Specifically, inflammatory and patrolling Ly6C+ monocytes were shifted predominantly to a pro-inflammatory transcriptional program in the aged brain, while brain ILCs shifted toward an ILC2 transcriptional profile. Finally, aging led to an increase of ILC-like cells expressing a T memory stemness (Tscm) signature in the brain. Antibiotics (ABX)-induced gut dysbiosis reduced the frequency of ILCs exhibiting Tscm-like properties in the aged mice, but not in the young mice. Enabled by high-resolution single-cell molecular phenotyping, our study revealed that systemic changes due to aging and gut dysbiosis prime the brain environment for an increased propensity for neuroinflammation, which provided insights into gut dysbiosis in age-related neurological diseases.Manuscript SummaryGolombet al.performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) on immune cells from the brains of young and aged mice with and without antibiotics-induced gut dysbiosis. High resolution, single cell immunophenotyping enabled the dissection of extensive transcriptional plasticity of canonically identified monocytes and innate lymphoid cells (ILCs) in the aged brain. Through differential gene expression and trajectory inference analyses, the authors revealed tissue microenvironment-dependent cellular responses influenced by aging and gut dysbiosis that may potentiate neuroinflammatory diseases.Graphical Abstract
Wing-pattern-specific effects of experience on mating behavior inHeliconius melpomenebutterflies
Authors: Rather Peyton A. , Herzog Abigail E. , Ernst David A. , Westerman Erica L. 
Published: July 2020

AbstractMany animals have the ability to learn, and some taxa have shown learned mate preference. This learning may be important for speciation in some species. The butterflyHeliconius melpomeneis a model system for several areas of research, including hybridization, mate selection, and speciation, partially due to its widespread diversity of wing patterns. It remains unclear whether these butterflies can learn to prefer certain mates and if social experience shapes realized mating preferences. Here we test whether previous experience with a female influences male mate preference for two differentH. melpomenesubspecies,H. m. malletiandH. m. rosina. We conducted no-choice behavioral assays to determine if latency to court and whether males courted (vs no courtship) differed between naïve males and males with previous exposure to a young, sexually mature, virgin female. To test whether assortative courtship preference is learned inH. melpomene, males were either paired with a female who shared their phenotype or one who did not. NaïveH. m. mallettimales courted assortatively, while naïveH.m. rosinamales did not. ExperiencedH. m. malletimales reduced their courting relative to naïve males, suggesting that social experience with a sexually mature female that does not result in copulation may be perceived as a negative experience. In contrast, experiencedH. m. rosinamales exhibited similar courting rates to naïveH. m. rosinamales. Our results suggest that social experience can influence male mating behavior inH. melpomeneand that behavioral plasticity may differ across populations in this species.
Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish
Authors: Holmgren Melanie , Ravicz Michael E. , Hancock Kenneth E. , Strelkova Olga , Kallogjeri Dorina , Indzhykulian Artur A. , Warchol Mark E. , Sheets Lavinia 
Published: July 2020

AbstractExcess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.
IGT/LAZY family genes are differentially influenced by light signals and collectively required for light-induced changes to branch angle
Authors: Waite Jessica Marie , Dardick Christopher 
Published: July 2020

AbstractPlants adjust their growth orientations in response to environmental signals such as light and gravity in order to optimize photosynthesis and access to nutrients. However, given the fixed nature of gravity, understanding how light and gravity signals are integrated is challenging. Branch orientation, or gravitropic set point angle, is a key aspect of plant architecture, set with respect to gravity and shown to be altered by changes in light conditions. The IGT gene family, also known as theLAZYfamily, contains important components for branch angle and gravity responses, including three gene clades:LAZY, DEEPER ROOTING (DRO), andTILLER ANGLE CONTROL (TAC). LAZYandDROgenes promote upward branch orientations downstream of amyloplast sedimentation, and upstream of auxin redistribution in response to gravity. In contrast,TAC1promotes downward branch angles in response to photosynthetic signals. Here, we investigated the influence of different light signaling pathways onLAZYandDROgene expression, and their role in light regulation of branch angle responses. We found differential effects of continuous light and dark, circadian clock, photoreceptor-mediated signaling, and photosynthetic signals onLAZYandDROgene expression. Phenotypic analysis revealed thatLAZYandDROgenes are collectively required for branch angle responses to light.HighlightLAZYandDROgene expression responds differentially to changes in light regime and signaling. Loss of multipleLAZYandDROgenes leads to loss of branch angle response to light.
Seasonal prevalence and characterization of Shiga toxin-producingEscherichia colion pork carcasses at three steps of the harvest process at two commercial processing plants in the US
Authors: Nastasijevic Ivan , Schmidt John W. , Boskovic Marija , Glisic Milica , Kalchayanand Norasak , Shackelford Steven D. , Wheeler Tommy L. , Koohmaraie Mohammad , Bosilevac Joseph M. 
Published: July 2020

ABSTRACTShiga toxin (stx) -producingEscherichia coli(STEC) are foodborne pathogens that have a significant impact on public health, with those possessing the attachment factor intimin (eae) referred to as enterohemorrhagicE. coli(EHEC) associated with life threatening illnesses. Cattle and beef are considered typical sources of STEC, but their presence in pork products is a growing concern. Therefore, carcasses (n=1536) at two U.S. pork processors were sampled once per season at three stages of harvest (post-stunning skins; post-scald carcasses; chilled carcasses) then examined using PCR forstxandeae, aerobic plate count (APC) andEnterobacteriaceaecounts (EBC). Skins, post-scald, and chilled carcasses had prevalence ofstx(85.3, 17.5, and 5.4%, respectively), with 82.3, 7.8, and 1.7% respectively, havingstxandeaepresent. Allstxpositive samples were subjected to culture isolation that resulted in 368 STEC and 46 EHEC isolates. The most frequently identified STEC were serogroup O121, O8, and O91(63, 6.7, and 6.0% of total STEC, respectively). The most frequently isolated EHEC was serotype O157:H7 (63% of total EHEC). Results showed that scalding significantly reduced (P< 0.05) carcass APC and EBC by 3.00 and 2.50 log10CFU/100 cm2respectively. A seasonal effect was observed with STEC prevalence lower (P< 0.05) in winter. The data from this study shows significant (P< 0.05) reduction in the incidence of STEC (stx) from 85.3% to 5.4% and of EHEC (stx+eae) from 82.3% to 1.7% within slaughter-to-chilling continuum, respectively, and that potential EHEC can be confirmed present throughout using culture isolation.IMPORTANCESeven serogroups of Shiga toxin-producingEscherichia coli(STEC) are responsible for most (>75%) cases of severe illnesses caused by STEC and are considered adulterants of beef. However, some STEC outbreaks have been attributed to pork products although the sameE. coliare not considered adulterants in pork because little is known of their prevalence along the pork chain. The significance of the work presented here is that it identifies disease causing STEC, enterohemorrhagicE. coli(EHEC), demonstrating that these same organisms are a food safety hazard in pork as well as beef. The results show that most STEC isolated from pork are not likely to cause severe disease in humans and that processes used in pork harvest, such as scalding, offer a significant control point to reduce contamination. The results will assist the pork processing industry and regulatory agencies to optimize interventions to improve the safety of pork products.
Joint CBC-ICT Interpretation for the pre-surgical screening of COVID 19 asymptomatic cases: A cross-sectional study
Authors: Imran Tanzeel , Naz Humera Altaf , Khan Hamza , Bangash Ali Haider , Khan Laraib Bakhtiar , Khan Haroon 
Published: July 2020

AbstractBackgroundOn 26th, February 2020, first cases of COVID 19 were confirmed in Pakistan. Since then, surgeries were halted in a bid to prevent transmission. However, since such a long halt is infeasible, a general protocol of screening the carriers, especially asymptomatic carries, is a dire need of time. The objective of our study is to propose an economically feasible protocol of COVID 19 screening. Simple but effective screening strategies can help to restore the workings of hospital surgical departments.MethodsWe analyzed the clinical data of patients turning up for elective surgeries at the Rawal General Hospital (RGH), Islamabad from the 24thof March to the 15thof May, 2020. Asymptomatic patients with negative COVID 19 contact and travel histories were screened with COVID 19 Immunochromatography (ICT) IgM / IgG Ab Test. Complete blood count (CBC) was done and interpreted in conjunction with the ICT results.Results39 patients with a mean age of 49 years were studied. The result of ICT for COVID-19 was positive in 9 cases (23%). The entire positive ICT patients population expressed significantly lower lymphocyte count (p<0.01); 8 patients had high monocyte count (p<0.05) whereas only 4 patients had a combined high neutrophil and monocyte count (P<0.05). All of these four patients with high neutrophil count were females. The combined interpretation of CBC and ICT IgM / IgG Ab Test had a high accuracy in diagnosing asymptomatic COVID-19 carriers that were later confirmed by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR).ConclusionWe propose that joint CBC-ICT interpretation should be adopted on a large scale to help in the diagnoses of asymptomatic carriers as both tests are simple and inexpensive and thus suit the developing countries’ limited health budget. Future research projects should be adopted in order to assess the accuracy of the proposed protocol on a large scale.
Implementing Primary Care Mediated Population Genetic Screening within an Integrated Health System
Authors: David Sean P , Dunnenberger Henry M , Ali Raabiah , Matsil Adam , Lemke Amy A , Singh Lavisha , Zimmer Anjali , Hulick Peter J 
Published: July 2020

AbstractIntroductionGenetic screenings can have a large impact on enabling personalized preventative care. However, this can be limited by the primary use of medical history-based screenings in determining care. The purpose of this study was to understand the impact of DNA10K, a population-based genetic screening program mediated by primary care physicians (PCPs) within an integrated health system to emphasize its contribution to preventative healthcare.MethodsConstruction of the patient experience as part of DNA10K shaped the context for PCP engagement within the program. A cross-sectional analysis of patient consents, orders, tests, and results of nearly 10,000 patients within the primary care specialties of family medicine, internal medicine or obstetrics/gynecology between April 1, 2019 and January 22, 2020 was conducted.ResultsAcross all specialties, a median number of 7.5 cancer and cardiovascular disease variants per PCP was found. The average age of the study population was 49.6 years. Over 8% of these patients had at least one actionable genetic risk variant and almost 2% of patients had at least one CDC Tier 1 variant. The median number of patients per PCP with either hereditary breast and ovarian cancer, Lynch Syndrome, or Familial Hypercholesterolemia was 1 (Interquartile Range 0-2).DiscussionThe analysis of test results and the engagement of an integrated healthcare system in the implementation of a genetic screening program suggests that it can have a large impact on population health outcomes and minimal referral burden to PCPs if identified risks can lead to preventative care.
Genetic risk for Alzheimer’s disease influences neuropathology and cognition via multiple biological pathways
Authors: Hannon Eilis , Shireby Gemma L , Brookes Keeley , Attems Johannes , Sims Rebecca , Cairns Nigel J , Love Seth , Thomas Alan J , Morgan Kevin , Francis Paul T , Mill Jonathan 
Published: July 2020

AbstractAlzheimer’s disease is a highly heritable, common neurodegenerative disease characterised neuropathologically by the accumulation of β-amyloid plaques and tau-containing neurofibrillary tangles. In addition to the well-established risk associated with the APOE locus, there has been considerable success in identifying additional genetic variants associated with Alzheimer’s disease. Major challenges in understanding how genetic risk influences the development of Alzheimer’s disease are clinical and neuropathological heterogeneity, and the high level of accompanying comorbidities. We report a multimodal analysis integrating longitudinal clinical and cognitive assessment with neuropathological data collected as part of the Brains for Dementia Research (BDR) study to understand how genetic risk factors for Alzheimer’s disease influence the development of neuropathology and clinical performance. 693 donors in the BDR cohort with genetic data, semi-quantitative neuropathology measurements, cognitive assessments and established diagnostic criteria were included in this study. We tested the association of APOE genotype and Alzheimer’s disease polygenic risk score - a quantitative measure of genetic burden - with survival, four common neuropathological features in Alzheimer’s disease brains (neurofibrillary tangles, β-amyloid plaques, Lewy bodies and TDP-43 proteinopathy), clinical status (clinical dementia rating) and cognitive performance (Mini-Mental State Exam, Montreal Cognitive Assessment). The APOE ε4 allele was significantly associated with younger age of death in the BDR cohort. Our analyses of neuropathology highlighted two independent pathways from APOE ε4, one where β-amyloid accumulation mediates the development of tauopathy, and a second characterized by direct effects on tauopathy independent of β-amyloidosis. Although we also detected association between APOE ε4 and dementia status and cognitive performance, these were all mediated by tauopathy, highlighting that they are a consequence of the neuropathological changes. Analyses of polygenic risk score identified associations with tauopathy and β-amyloidosis, which appeared to have both shared and unique contributions, suggesting that different genetic variants associated with Alzheimer’s disease affect different features of neuropathology to different degrees. Taken together, our results provide insight into how genetic risk for Alzheimer’s disease influences both the clinical and pathological features of dementia, increasing our understanding about the interplay between APOE genotype and other genetic risk factors.
Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19
Authors: Unterman Avraham , Sumida Tomokazu S. , Nouri Nima , Yan Xiting , Zhao Amy Y. , Gasque Victor , Schupp Jonas C. , Asashima Hiromitsu , Liu Yunqing , Cosme Carlos , Deng Wenxuan , Chen Ming , Raredon Micha Sam Brickman , Hoehn Kenneth , Wang Guilin , Wang Zuoheng , DeIuliis Giuseppe , Ravindra Neal G. , Li Ningshan , Castaldi Christopher , Wong Patrick , Fournier John , Bermejo Santos , Sharma Lokesh , Casanovas-Massana Arnau , Vogels Chantal B.F. , Wyllie Anne L. , Grubaugh Nathan D. , Melillo Anthony , Meng Hailong , Minasyan Maksym ,   the Yale IMPACT research team, Niklason Laura E. , Ko Albert I. , Montgomery Ruth R. , Farhadian Shelli F. , Iwasaki Akiko , Shaw Albert C. , van Dijk David , Zhao Hongyu , Kleinstein Steven H. , Hafler David A. , Kaminski Naftali , Dela Cruz Charles S. 
Published: July 2020

AbstractA dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, the molecular and cellular mechanisms by which the virus causes lethal immunopathology are poorly understood. Here, we utilize multiomics single-cell analysis to probe dynamic immune responses in patients with stable or progressive manifestations of COVID-19, and assess the effects of tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling of gene expression and cell lineage protein markers reveals a prominent type-1 interferon response across all immune cells, especially in progressive patients. An anti-inflammatory innate immune response and a pre-exhaustion phenotype in activated T cells are hallmarks of progressive disease. Skewed T cell receptor repertoires in CD8+ T cells and uniquely enriched V(D)J sequences are also identified in COVID-19 patients. B cell repertoire and somatic hypermutation analysis are consistent with a primary immune response, with possible contribution from memory B cells. Our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19, which may contribute to delayed virus clearance and has implications for therapeutic intervention.
Hospital mortality and resource implications of hospitalisation with COVID-19 in London, UK: a prospective cohort study
Authors: Vlachos Savvas , Wong Adrian , Metaxa Victoria , Canestrini Sergio , Soto Carmen Lopez , Periselneris Jimstan , Lee Kai , Patrick Tanya , Stovin Christopher , Abernethy Katrina , Albudoor Budoor , Banerjee Rishi , Juma Fatima , Al-Hashimi Sara , Bernal William , Maharaj Ritesh 
Published: July 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 33 000 cases reported in London by July 6, 2020. Detailed hospital-level information on patient characteristics, outcomes and capacity strain are currently scarce but would guide clinical decision-making and inform prioritisation and planning.MethodsWe aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK. We included adult patients admitted to hospital with laboratory-confirmed COVID-19 and followed them up until hospital discharge or 30 days. Baseline factors that are associated with hospital mortality were identified via semi-parametric and parametric survival analyses.ResultsOur study included 429 patients; 18% of them were admitted to ICU, 52% met criteria for ICU outreach team activation and 61% had treatment limitations placed during their admission. Hospital mortality was 26% and ICU mortality was 34%. Hospital mortality was independently associated with increasing age, male sex, history of chronic kidney disease, increasing baseline C-reactive protein level and dyspnoea at presentation. COVID-19 resulted in substantial ICU and hospital strain, with up to 9 daily ICU admissions and 41 daily hospital admissions, to a peak census of 80 infected patients admitted in ICU and 250 in the hospital. Management of such a surge required extensive reorganisation of critical care services with expansion of ICU capacity from 69 to 129 beds, redeployment of staff from other hospital areas and coordinated hospital-level effort.ConclusionsCOVID-19 is associated with a high burden of mortality for patients treated on the ward and the ICU and required substantial reconfiguration of critical care services. This has significant implications for planning and resource utilization.
Computer-aided covid-19 patient screening using chest images (X-Ray and CT scans)
Authors: Burgos-Artizzu Xavier P. 
Published: July 2020

ABSTRACTObjectivesto evaluate the performance of Artificial Intelligence (AI) methods to detect covid-19 from chest images (X-Ray and CT scans).MethodsChest CT scans and X-Ray images collected from different centers and institutions were downloaded and combined together. Images were separated by patient and 66% of the patients were used to develop and train AI image-based classifiers. Then, the AI automated classifiers were evaluated on a separate set of patients (the remaining 33% patients).Results (Chest X-Ray)Five different data sources were combined for a total of N=9,841 patients (1,733 with covid-19, 810 with bacterial tuberculosis and 7,298 healthy patients). The test sample size was N=3,528 patients. The best AI method reached an Area Under the Curve (AUC) for covid-19 detection of 99%, with a detection rate of 96.4% at 1.0% false positive rate.Results (Chest CT scans)Two different data sources were combined for a total of N=363 patients (191 having covid-19 and 172 healthy patients). The test sample size was N=121 patients. The best AI method reached an AUC for covid-19 detection of 90.9%, with a detection rate of 90.6% at 24.6% false positive rate.ConclusionsComputer aided automatic covid-19 detection from chest X-ray images showed promising results to be used as screening tool during the covid-19 outbreak. The developed method may help to manage patients better in case access to PCR testing is not possible or to detect patients with symptoms missed in a first round of PCR testing. The method will be made available online (www.quantuscovid19.org). These results merit further evaluation collecting more images. We hope this study will allow us to start such collaborations.