bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low SARS-CoV-2 sero-prevalence based on anonymized residual sero-survey before and after first wave measures in British Columbia, Canada, March-May 2020
Authors: Skowronski Danuta M , Sekirov Inna , Sabaiduc Suzana , Zou Macy , Morshed Muhammad , Lawrence David , Smolina Kate , Ahmed May A , Galanis Eleni , Fraser Mieke N , Singal Mayank , Naus Monika , Patrick David M , Kaweski Samantha E , Mill Christopher , Reyes Romina C , Kelly Michael T , Levett Paul N , Petric Martin , Henry Bonnie , Krajden Mel 
Published: July 2020

AbstractBackgroundThe province of British Columbia (BC) has been recognized for successful SARS-CoV-2 control, with surveillance data showing amongst the lowest case and death rates in Canada. We estimate sero-prevalence for two periods flanking the start (March) and end (May) of first-wave mitigation measures in BC.MethodsSerial cross-sectional sampling was conducted using anonymized residual sera obtained from an outpatient laboratory network, including children and adults in the Greater Vancouver Area (population ∼3 million) where community attack rates were expected to be highest. Screening used two chemiluminescent immuno-assays for spike (S1) and nucleocapsid antibodies. Samples sero-positive on either screening assay were assessed by a third assay targeting the S1 receptor binding domain plus a neutralization assay. Age-standardized sero-prevalence estimates were based on dual-assay positivity. The May sero-prevalence estimate was extrapolated to the source population to assess surveillance under-ascertainment, quantified as the ratio of estimated infections versus reported cases.ResultsSerum collection dates spanned March 5-13 and May 15-27, 2020. In March, two of 869 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.28% (95%CI=0.03-0.95). Neither specimen had detectable neutralizing antibodies. In May, four of 885 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.55% (95%CI=0.15-1.37%). All four specimens had detectable neutralizing antibodies. We estimate ∼8 times more infections than reported cases.ConclusionsLess than 1% of British Columbians had been infected with SARS-CoV-2 when first-wave mitigation measures were relaxed in May 2020. Our findings indicate successful suppression of community transmission in BC, but also substantial residual susceptibility. Further sero-survey snapshots are planned as the pandemic unfolds.Key pointsCross-sectional sampling of anonymized residual sera at the start and end of first-wave mitigation measures in British Columbia, Canada shows SARS-CoV-2 sero-prevalence below 1% throughout the winter-spring 2020. Findings indicate successful suppression of community transmission but also substantial residual susceptibility.
Connecting in COVID 19: Neurology tele-follow-up experience
Authors: Vibha Deepti , Srivastava MV Padma , Prasad Kameshwar , Tripathi Manjari , Srivastava Achal Kumar , Bhatia Rohit , Singh Mamta Bhushan , Vishnu VY , Rajan Roopa , Singh Rajesh Kumar , Gupta Anu , Das Animesh , Elavarasi A , Divya MR , Ramanujam Bhargavi , Shariff A 
Published: July 2020

AbstractIntroductionThe lockdown due to COVID-19 pandemic led to temporary closure of routine hospital services. This prompted the initiation of teleconsult follow-up in our department. The study outlines the experience of tele-follow-up at a tertiary care teaching hospital in India, and the perspective of neurologists about this novel approach.MethodsThe tele-follow-up was started from 26th March 2020. Data of follow up appointments was provided by the medical record section. The faculty and senior residents conducted the tele-follow-up. Communication was made via voice calls. The data for initial ten days was analyzed to find the utility and experience of the new service.ResultsIn the initial ten working days, data of 968 patients was provided for tele-follow-up. A successful communication was made in 50.3% patients (contact with patients: 27.7% and family members 22.6%). The phone numbers which were not contactable/invalid/not available constituted 36.8% of the data. A total of 35 faculty and residents conducted the tele-follow-up. The utility of tele-follow-up was perceived as good by 71.4% of neurologists. Majority of neurologists (71.4%) observed that >90% of patients were continuing medications. Patients outside the city constituted 50-75% of the list. The survey revealed that all neurologists felt the need to continue tele-follow-up for far off stable patients post lock down and resumption of regular outpatient services.ConclusionThe survey established the feasibility and utility of teleconsult for follow up of patients with neurological diseases who were attending the regular outpatient services before the lock down.
Pharmacokinetics and pharmacodynamics of inhaled antipseudomonal bacteriophage therapy in mice
Authors: Chow Michael Y.T. , Chang Rachel Yoon Kyung , Li Mengyu , Wang Yuncheng , Lin Yu , Morales Sandra , McLachlan Andrew J , Kutter Elizabeth , Li Jian , Chan Hak-Kim 
Published: July 2020

AbstractInhaled bacteriophage (phage) therapy is a potential alternative to conventional antibiotic therapy to combat multidrug-resistant (MDR)Pseudomonas aeruginosainfections. However, pharmacokinetics (PK) and pharmacodynamics (PD) of phages are fundamentally different to antibiotics and the lack of understanding potentially limits optimal dosing. The aim of this study was to investigate thein vivoPK and PD profiles of antipseudomonal phage PEV31 delivered by pulmonary route in mice. BALB/c mice were administered phage PEV31 at doses of 107and 109PFU by the intratracheal route. Mice (n= 4) were sacrificed at 0, 1, 2, 4, 8 and 24 h post-treatment and various tissues (lungs, kidney, spleen and liver), bronchoalveolar lavage and blood were collected for phage quantification. In a separate study, mice (n= 4) were treated with PEV31 (109PFU) or PBS at 2 h post-inoculation with MDRP. aeruginosa. Infective PEV31 and bacteria were enumerated from the lungs. In the phage only study, PEV31 titer gradually decreased in the lungs over 24 hours with a half-life of approximately 8 h for both doses. In the presence of bacteria, PEV31 titer increased by almost 2-log10in the lungs at 16 h. Furthermore, bacterial growth was suppressed in the PEV31-treated group, while the PBS-treated group showed exponential growth. Some phage-resistant colonies were observed from the lung homogenates sampled at 24 h post-phage treatment. These colonies had a different antibiogram to the parent bacteria. This study provides evidence that pulmonary delivery of phage PEV31 in mice can reduce the MDR bacterial burden.
Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors inAcinetobacter baumannii
Authors: Martinez Jasmine , Razo-Gutierrez Chelsea , Le Casin , Courville Robert , Pimentel Camila , Liu Christine , Fuang Sammie E. , Vila Alejandro J. , Shahrestani Parvin , Jimenez Veronica , Tolmasky Marcelo E. , Becka Scott A. , Papp-Wallace Krisztina M. , Bonomo Robert A. , Soler-Bistue Alfonso , Sieira Rodrigo , Ramirez Maria Soledad 
Published: July 2020

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR)Acinetobacter baumanniiis a pathogen described as an “urgent threat”. Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, a common complication of neurosurgery caused by extensively-drug resistant (XDR)A. baumannii, is extremely challenging to manage. Therefore, it is necessary to identify signals, such as exposure to cerebrospinal fluid (CSF), that trigger expression of virulence factors that are associated with the successful establishment and progress of this infection. While a hypervirulentA. baumanniistrain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and virulence as determined in various model systems. Furthermore, although CSF’s presence did not enhance bacterial growth, it was associated with an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery. Experiments to identify the active CSF component pointed to human serum albumin (HSA).ImportanceAcinetobacter baumannii, notorious for its multidrug resistant phenotype, overcomes nutrient deprived and desiccated conditions through its metabolic flexibility, pathogenic and physiological adaptability. Although this pathogen is commonly associated with respiratory infections, there have been a considerable amount of cases ofA. baumanniibacterial meningitis. These infections are usually post-neurological surgery complications associated with high mortality rates ranging from 40 to 70%. This work describes interactions that may occur duringA. baumanniiinfection of human cerebrospinal fluid (CSF).A. baumannii’sdisplays capabilities to persist and thrive in a nutrient-limited environment, which also triggers the expression of virulence factors. This work also further exploresA. baumannii’sutilization of an essential component within CSF to trigger enhanced expression of genes associated with its pathoadaptibility in this environment.
Action Imagery and Observation in Neurorehabilitation for Parkinson’s Disease (ACTION-PD): development and pilot randomised controlled trial of a user-informed home training intervention to improve everyday functional actions
Authors: Bek Judith , Holmes Paul S. , Craig Chesney E. , Franklin Zoë C. , Sullivan Matthew , Webb Jordan , Crawford Trevor J. , Vogt Stefan , Gowen Emma , Poliakoff Ellen 
Published: July 2020

ABSTRACTBackgroundParkinson’s disease (PD) causes difficulties with everyday manual activities, but few studies have addressed these therapeutically. Training with action observation (AO) and motor imagery (MI) can significantly improve performance in healthy individuals, particularly when these techniques are applied simultaneously (AO+MI). Both AO and MI have shown promising effects in PD, but previous studies have used these separately. This article describes the development and pilot testing of an intervention combining AO+MI and physical practice to improve functional manual actions in PD.MethodsThe home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team including people with PD, and further developed through focus groups and initial testing. The intervention was then tested in a six-week randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual).Results and ConclusionsUsage and qualitative data provided preliminary evidence of acceptability and usability, indicating that a feasibility RCT is warranted. Exploratory analyses suggested potential improvements in manual actions. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. The findings also have broader relevance for AO+MI interventions in PD and other populations.
PD-1-induced T cell exhaustion is controlled by a Drp1-dependent mechanism
Authors: Simula Luca , Cancila Valeria , Antonucci Ylenia , Colamatteo Alessandra , Procaccini Claudio , Matarese Giuseppe , Tripodo Claudio , Campello Silvia 
Published: July 2020

AbstractPD-1 signalling downregulates the T cell response, promoting an exhausted state in tumor-infiltrating T cells, through mostly unveiled molecular mechanisms. Drp1-dependent mitochondrial fission plays a crucial role to sustain T cell motility, proliferation, survival and glycolytic engagement and, interestingly, such processes are exactly those inhibited by PD-1 in tumor-infiltrating T cells. Here we show that the signature of PD-1posCD8+T cells infiltrating MC38-derived murine tumor mass is having downregulated Drp1 activity and more fused mitochondria, compared to PD-1negcounterparts. Also, PD-1poslymphocytic elements infiltrating human colon cancer rarely express active Drp1. Mechanistically, PD-1 signalling directly prevents mitochondria fragmentation following T cell stimulation by downregulating Drp1 phosphorylation on Ser616, via regulation of the ERK1/2 and mTOR pathways. In addition, downregulation of Drp1 activity in tumor-infiltrating PD-1posCD8+ T cells seems to be a mechanism exploited by PD-1 signalling to reduce motility and proliferation of these cells. Overall, our data indicate that the modulation of Drp1 activity in tumor-infiltrating T cells may become a valuable target to ameliorate the anti-cancer immune response in future immunotherapy approaches.
COVID-19 infection and attributable mortality in UK care homes: Cohort study using active surveillance and electronic records (March-June 2020)
Authors: Dutey-Magni Peter F , Williams Haydn , Jhass Arnoupe , Rait Greta , Lorencatto Fabiana , Hemingway Harry , Hayward Andrew , Shallcross Laura 
Published: July 2020

AbstractBackgroundEpidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic.MethodsCohort study of 179 UK care homes with 9,339 residents and 11,604 staff.We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality, and estimate attributable mortality.Results2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff respectively. 121/179 (67.6%) care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection.217/607 residents with confirmed infection died (case-fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was two-fold higher in care homes with outbreaks versus those without (adjusted HR 2.2 [1.8; 2.6]).ConclusionsFindings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.
SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2
Authors: Clausen Thomas Mandel , Sandoval Daniel R. , Spliid Charlotte B. , Pihl Jessica , Painter Chelsea D. , Thacker Bryan E. , Glass Charles A. , Narayanan Anoop , Majowicz Sydney A. , Zhang Yang , Torres Jonathan L. , Golden Gregory J. , Porell Ryan , Garretson Aaron F. , Laubach Logan , Feldman Jared , Yin Xin , Pu Yuan , Hauser Blake , Caradonna Timothy M. , Kellman Benjamin P. , Martino Cameron , Gordts Philip L.S.M. , Leibel Sandra L. , Chanda Summit K. , Schmidt Aaron G. , Godula Kamil , Jose Joyce , Corbett Kevin D. , Ward Andrew B. , Carlin Aaron F. , Esko Jeffrey D. 
Published: July 2020

AbstractWe show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template. Contrary to studies with purified components, spike protein binding to heparan sulfate and ACE2 on cells occurs codependently. Unfractionated heparin, non-anticoagulant heparin, treatment with heparin lyases, and purified lung heparan sulfate potently block spike protein binding and infection by spike protein-pseudotyped virus and SARS-CoV-2 virus. These findings support a model for SARS-CoV-2 infection in which viral attachment and infection involves formation of a complex between heparan sulfate and ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin may represent new therapeutic opportunities.
Mapping endothelial functional phenotype in cancer by unveiling the kinase and phosphatase drivers
Authors: Gadish Or , Edelman Elazer R. 
Published: July 2020

AbstractEndothelial cells (EC) are state-dependent regulators of the tumor ecosystem: quiescent ECs promote homeostasis; proliferative ECs stimulate tumor growth. Tumors, in turn, promote pro-tumorigenic EC phenotype. We studied functional and phosphorylative transformations on EC state in cancer. Quiescent HUVECs cultured in breast cancer cell-conditioned media displayed marked elongation and impaired wound healing. Quantitative mass spectrometry identified phosphorylative regulators of this dysfunctional transformation. Growth factor receptor kinases showed decreased, rather than increased activity, suggesting that EC regulation in tumors can arise other than from classic growth-factor-mediated angiogenesis alone. Of the 152 kinases and phosphatases across 62 families, six were chosen for functional validation using pharmacologic inhibitors. Inhibiting Akt and Ptp1b restored EC regulatory state, warranting further investigation as therapeutic targets; Src inhibition, however, promoted the dysfunctional phenotype, suggesting caution for Src inhibitors as EC-regulating therapies. Mapping phosphorylative drivers reveals complex relationships between EC phenotype, transformation, and regulation, and may shed light on how existing cancer-targeting inhibitors affect tumor endothelium. Data are available via ProteomeXchange with identifier PXD020333.
Ungulate Responses to Unmanned Aerial Vehicles Flying at Different Altitudes in Africa’s Arid Savanna
Authors: vanVuuren Marlice , vanVuuren Rudie , Silverberg Larry M. , Manning Joe , Pacifici Krishna , Dorgeloh Werner , Campbell Jennifer 
Published: July 2020

AbstractThis paper tests the hypothesis that ungulate-UAV interaction depends strongly on flight altitude, that there may be a lowest altitude range for which the ungulates are not exceedingly disturbed, dictating a practically achievable level of discernibility in flight observation. This question strongly influences the future viability of the UAV in the study and protection of the ungulates in Africa’s arid savanna. This paper examined the behavioral responses of a group of free ranging ungulate species (Oryx, Kudu, Springbok, Giraffe, Eland, Hartebeest, and Impala) found in an animal reserve in Namibia to the presence of different in-flight UAV models. The study included 99 flights (337 passes) at altitudes ranging from 15 to 55 meters. The ungulates were unhabituated to the UAVs and the study was conducted in the presence of stress-inducing events that occur naturally in the environment. The results suggest strong correlations between flight altitude and response across the different ungulates and anecdotal evidence suggests in some cases rapid habituation to the UAVs.
Movements of ancient human endogenous retroviruses detected in SOX2-expressing cells
Authors: Monde Kazuaki , Satou Yorifumi , Goto Mizuki , Uchiyama Yoshikazu , Ito Jumpei , Kaitsuka Taku , Terasawa Hiromi , Yamaga Shinya , Matsusako Tomoya , Wei Fan-Yan , Inoue Ituro , Tomizawa Kazuhito , Ono Akira , Era Takumi , Sawa Tomohiro , Maeda Yosuke 
Published: July 2020

SummaryHuman endogenous retroviruses (HERVs) occupy approximately 8% of human genome. HERVs, which are transcribed in early embryos, are epigenetically silenced in somatic cells, except in pathological contexts. HERV-K is thought to protect the embryo from exogenous viral infection. However, uncontrollable HERV-K expression in somatic cells has been implicated in several diseases. Here, we show that SOX2, which plays a key role in maintaining pluripotency of stem cells, is critical for the transcription of HERV-K LTR5Hs. HERV-K can undergo retrotransposition within producer cells in the absence of Env expression. Furthermore, new HERV-K integration sites were identified in a long-term culture of induced pluripotent stem cells, which express SOX2. Together, these results suggest the possibility that the strict dependence of HERV-K on SOX2 have allowed contribution of HERV-K to the protection of early embryos during evolution while limiting potentially harmful effects of HERV-K retrotransposition on host genome integrity to these early embryos.
Limits to the cellular control of sequestered cryptophyte prey in the marine ciliateMesodinium rubrum
Authors: Altenburger Andreas , Cai Huimin , Li Qiye , Drumm Kirstine , Kim Miran , Zhu Yuanzhen , Garcia-Cuetos Lydia , Zhan Xiaoyu , Hansen Per Juel , John Uwe , Li Shuaicheng , Lundholm Nina 
Published: July 2020

AbstractThe marine ciliateMesodinium rubrumis famous for its ability to acquire and exploit chloroplasts and other cell organelles from some cryptophyte algal species. We sequenced genomes and transcriptomes of free-swimmingTeleaulax amphioxeia, as well as well-fed and starvedM. rubrumin order to understand cellular processes upon sequestration under different prey and light conditions. From its prey, the ciliate acquires the ability to photosynthesize as well as the potential to metabolize several essential compounds including lysine, glycan, and vitamins that elucidate its specific prey dependency.M. rubrumdoes not express photosynthesis related genes itself, but elicits considerable transcriptional control of the acquired cryptophyte organelles. This control is limited as light dependent transcriptional changes found in free-swimmingT. amphioxeiagot lost after sequestration. We found strong transcriptional rewiring of the cryptophyte nucleus upon sequestration, where 35% of theT. amphioxeiagenes were significantly differentially expressed within well-fedM. rubrum. Qualitatively, 68% of all genes expressed within well-fedM. rubrumoriginated fromT. amphioxeia. Quantitatively, these genes contributed up to 48% to the global transcriptome in well-fedM. rubrumand down to 11% in starvedM. rubrum. This tertiary endosymbiosis system functions for several weeks, when deprived of prey. After this point in time, the ciliate dies if not supplied with fresh prey cells.M. rubrumrepresents one evolutionary way of acquiring photosystems from its algal prey, and might represent a step on the evolutionary way towards a permanent tertiary endosymbiosis.
Multi-batch cytometry data integration for optimal immunophenotyping
Authors: Ogishi Masato , Yang Rui , Gruber Conor , Pelham Simon , Spaan András N. , Rosain Jérémie , Chbihi Marwa , Han Ji Eun , Rao V Koneti , Kainulainen Leena , Bustamante Jacinta , Boisson Bertrand , Bogunovic Dusan , Boisson-Dupuis Stéphanie , Casanova Jean-Laurent 
Published: July 2020

AbstractWe describe the integration of multi-batch cytometry datasets (iMUBAC), a flexible, robust, and scalable computational framework for unsupervised cell-type identification across multiple batches of high-dimensional cytometry datasets. After overlaying cells from healthy controls across multiple batches, iMUBAC learns batch-specific cell-type classification boundaries and identifies aberrant immunophenotypes in patient samples. We illustrate unbiased and streamlined immunophenotyping, using both in-house and public mass and flow cytometry datasets.