bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separate to operate: the centriole-free inner core of the centrosome regulates the assembly of the intranuclear spindle in Toxoplasma gondii
Authors: Tomasina Ramiro , Martins-Duarte Érica S. , Bastin Philippe , Gissot Mathieu , Francia María E. 
Published: January 2022

ABSTRACTCentrosomes are the main microtubule-organizing center of the cell. They are normally formed by two centrioles, embedded in a cloud of proteins known as pericentriolar material (PCM). The PCM ascribes centrioles with their microtubule nucleation capacity. Toxoplasma gondii, the causative agent of toxoplasmosis, divides by endodyogeny. Successful cell division is critical for pathogenesis. The centrosome, one of the microtubule organizing centers of the cell, plays central roles in orchestrating the temporal and physical coordination of major organelle segregation and daughter cell formation. The Toxoplasma centrosome is constituted by two domains; an outer core, distal from the nucleus, and an inner core, proximal to the nucleus. This dual organization has been proposed to underlie T. gondii’s cell division plasticity. Homeostasis of the outer core has been shown to be critical for the proper assembly of the daughter cells. However, the role of the inner core remains undeciphered. Here, we focus on understanding the function of the inner core by studying the dynamics and role of its only known molecular marker; TgCEP250L1. We show that upon conditional degradation of TgCEP250L1, parasites are unable to survive. Mutants exhibit nuclear segregation defects, whilst normally forming daughter cells. In addition, the rest of the centrosome, defined by the position of the centrioles, disconnects from the nucleus. We explore the structural defects underlying these phenotypes by high resolution microscopy. We show that TgCEP250L1’s location is dynamic and encompasses the formation of the mitotic spindle. Moreover, we show that in the absence of TgCEP250L1, the microtubule binding protein TgEB1, fails to translocate from the nucleus to the mitotic spindle, while polyploid nuclei accumulate. Overall, our data supports a model in which the inner core of the T. gondii centrosome critically participates in cell division by directly impacting the formation or stability of the mitotic spindle.
Molecular surveillance reveals widespread colonisation by carbapenemase and extended spectrum beta-lactamase producing organisms in neonatal units in Kenya and Nigeria
Authors: Edwards Thomas , Williams Christopher T , Olwala Macrine , Andang’o Pauline , Otieno Walter , Nalwa Grace N , Akindolire Abimbola , Cubas-Atienzar Ana I , Ross Toby , Tongo Kemi , Adams Emily R , Nabwera Helen , Allen Stephen 
Published: January 2022

AbstractObjectivesNeonatal sepsis, a major cause of death amongst infants in sub-Saharan Africa, is often gut derived. Impairments in immunity and the gut barrier in sick neonates allow colonisation by opportunistic pathogens such as Enterobacteriaceae to progress to blood stream infection. Colonisation by Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) or carbapenemase enzymes is particularly problematic and can lead to antimicrobial-resistant (AMR) or untreatable infections. We sought to explore the rates of colonisation by ESBL or carbapenemase producers and their genotypes in two neonatal units (NNUs) in West and East Africa.MethodsStool and rectal swab samples were taken at multiple timepoints from newborns admitted to the NNUs at the University College Hospital, Ibadan, Nigeria and the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, western Kenya. Samples were tested for ESBL and carbapenemase genes using a previously validated qPCR assay with high resolution melt analysis. Kaplan-Meier survival analysis was used to examine colonisation rates at both sites.ResultsA total of 119 stool and rectal swab samples were taken from 42 infants admitted to the two NNUs. Six (14.3%) infants were extremely preterm (gestation <28 weeks), 19 (45.2%) were born by Caesarean section and 3 (8.6%) mothers were HIV positive. Median (IQR) duration of admission was 12.5 (5-26) days and 12 (28.6%) infants died. Overall, colonisation with ESBL (37 infants, 89%) was more common than with carbapenemase producers (26, 62.4%; P = 0.093). Median survival time before colonisation with ESBL organisms was 7 days and with carbapenemase producers 16 days (P=0.035). The majority of ESBL genes detected belonged to the CTX-M-1 (36/38; 95%), and CTX-M-9 (2/36; 5%) groups. The most prevalent carbapenemase was blaNDM (27/29, 93%). Single blaVIM (1/32, 3%) and blaOXA-48 genes (1/32, 3%) were also detected.ConclusionsGut colonisation of neonates by AMR organisms was common and occurred rapidly in NNUs in Kenya and Nigeria. Active surveillance of colonisation will improve the understanding of AMR in these settings and guide infection control and antibiotic prescribing practice to improve clinical outcomes.HighlightsColonisation with extended spectrum beta-lactamase (ESBL) or carbapenemase producing bacteria was common in two neonatal units in Kenya and NigeriaESBL colonisation occurred in 89% of neonates, with a median colonisation time of 7 daysColonisation with carbapenemase producers occurred in 62% of neonates, with a median time to colonisation of 16 daysThe most common ESBL genes detected were of the CTX-M-1 family, whilst the most common carbapenemase detected was blaNDM
Barley stripe mosaic virusγb protein targets thioredoxin h-type 1 to dampen SA-mediated antiviral defenses
Authors: Jiang Zhihao , Jin Xuejiao , Yang Meng , Pi Qinglin , Cao Qing , Li Zhenggang , Zhang Yongliang , Wang Xian-Bing , Han Chenggui , Yu Jialin , Li Dawei 
Published: January 2022

AbstractSalicylic acid (SA) acts as a signaling molecule to perceive and defend against pathogen infections. Accordingly, pathogens evolve versatile strategies to disrupt the SA-mediated signal transduction. However, it is necessary to further characterize how plant viruses manipulate the SA-dependent defense responses. Here, we show thatBarley stripe mosaic virus(BSMV) infection activates SA-mediated defense signaling pathway and upregulates the expression ofNicotiana benthamianathioredoxin h-type 1 (NbTRXh1). The γb protein interacts directly with NbTRXh1in vivoandin vitro. Overexpression of NbTRXh1, but not a reductase-defective mutant, impedes BSMV infection, whereas lowNbTRXh1expression level results in increased viral accumulation. Similar with its orthologues inArabidopsis, NbTRXh1 also plays an essential role in SA signaling transduction inN. benthamiana. To counteract NbTRXh1-mediated defenses, the BSMV γb protein targets NbTRXh1 to dampen its reductase activity and thereby impairing downstream SA defense genes expression to optimize viral cell-to-cell movement. We also found that NbTRXh1-mediated resistance defends againstLychnis ringspot virus,Beet black scorch virus, andBeet necrotic yellow vein virus. Taken together, our results reveal a novel role for the multifunctional γb protein in counteracting plant defense responses, and broadens the broad-spectrum antibiotic role of SA signaling pathway.One sentence summaryBSMV γb protein impairs NbTRXh1 reductase activity and dampen downstream SA-related genes expression to facilitate viral cell-to-cell movement.
Functional oscillation of a multienzyme glucosome assembly during cell cycle progression
Authors: Jeon Miji , Schmitt Danielle L. , Kyoung Minjoung , An Songon 
Published: January 2022

AbstractGlucose metabolism has been studied extensively to understand functional interplays between metabolism and a cell cycle. However, our understanding of cell cycle-dependent metabolic adaptation particularly in human cells remains largely elusive. Meanwhile, human enzymes in glucose metabolism are shown to functionally organize into three different sizes of a multienzyme metabolic assembly, the glucosome, to regulate glucose flux in a size-dependent manner. Here, using fluorescence single-cell imaging techniques, we discover that glucosomes spatiotemporally oscillate during a cell cycle in an assembly size-dependent manner. Importantly, their oscillation at single-cell levels is in accordance with functional contributions of glucose metabolism to cell cycle progression at a population level. Collectively, we demonstrate functional oscillation of glucosomes during cell cycle progression and thus their biological significance to human cell biology.
COVID-19-related school disruptions and well-being of children and adolescents in Geneva
Authors: Richard Viviane , Dumont Roxane , Lorthe Elsa , Baysson Hélène , Zaballa María-Eugenia , Barbe Rémy P. , Posfay-Barbe Klara M. , Guessous Idris , Stringhini Silvia 
Published: January 2022

AbstractBackgroundVarious studies showed the negative impact of COVID-19-related lockdowns and school closures on the well-being of children and adolescents. However, the prevalence and consequences of occasional short-term school disruptions due to COVID-19-related quarantine or isolation remain unknown. This study evaluated their impact on the well-being and stress level of children and adolescents.MethodsIn June/July 2021, we conducted a survey selecting a representative sample of children and adolescents of a Swiss canton population. Parents of school-aged children reported information about them missing school because of COVID-19, from August 2020 to June 2021, as well as about their health-related quality of life (HRQoL) measured with the KINDL® scale and their stress level.ResultsAmong the 538 participants, 216/538 (40.1%) pupils missed school at least once for COVID-19-related causes, with a total of 272 absences. We observed no relationship between the frequency of COVID-19-related absences and the HRQoL or stress level, even when stratifying by the type of absence or socio-demographic factors.DiscussionOverall, these findings are reassuring in that quarantines and related school disruptions, which we know are a common and effective way of controlling SARS-CoV-2 transmission, did not seem to meaningfully impact children and adolescent’s wellbeing and stress. Finding the right balance between SARS-CoV-2 control and young populations’ well-being is challenging, and the current results provide additional information for decision makers.
Reconstructing transmission chains of SARS-CoV-2 amid multiple outbreaks in a geriatric acute-care hospital
Authors: Abbas Mohamed , Cori Anne , Cordey Samuel , Laubscher Florian , Robalo Nunes Tomás , Myall Ashleigh , Salamun Julien , Huber Philippe , Zekry Dina , Prendki Virginie , Iten Anne , Vieux Laure , Sauvan Valérie , Graf Christophe E. , Harbarth Stephan 
Published: January 2022

AbstractBackgroundThere is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings.MethodsWe performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, in order to determine who infected whom. We evaluated general transmission patterns according to type of case (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each type of case across all posterior trees and comparing them to random expectations.ResultsDuring the study period (March 1 to May 7, 2020) we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10-19% for patients, and 21% for HCWs. We estimated that there were 16 importation events (3 patients, 13 HCWs) that jointly led to 16 secondary cases. Most patient-to-patient transmission events involved patients having shared a ward (97.6%, 95% credible interval [CrI] 90.4-100%), in contrast to those having shared a room (44.4%, 95%CrI 27.8-62.5%). Transmission events tended to cluster by type of case: patientnosowere almost twice as likely to be infected by other patientnosothan expected (observed:expected ratio 1.91, 95%CrI 1.08 – 4.00,p= 0.02); similarly, HCWoutbreakwere more than twice as likely to be infected by other HCWoutbreakthan expected (2.25, 95%CrI 1.00-8.00,p= 0.04). The proportion of infectors of HCWcovidwere as expected as random. The proportions of high transmitters (≥2 secondary cases) were significantly higher among HCWoutbreakthan patientnosoin the late phases (26.2% vs. 13.4%, p<2.2e-16) of the outbreak.ConclusionsMost importation events were linked to HCW. Unexpectedly, transmission between HCWcovidwas more limited than transmission between patients and HCWoutbreak. This highlights gaps in infection control and suggests possible areas of improvements to limit the extent of nosocomial transmission.
Amyloid-associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer
Authors: Binette Alexa Pichet , Franzmeier Nicolai , Spotorno Nicola , Ewers Michael , Brendel Matthias , Biel Davina ,   ADNI, Strandberg Olof , Janelidze Shorena , Palmqvist Sebastian , Mattsson-Carlgren Niklas , Smith Ruben , Stomrud Erik , Ossenkoppele Rik , Hansson Oskar 
Published: January 2022

ABSTRACTFor optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer’s disease (AD) continuum. In early stages of AD, increased concentration of soluble CSF p-tau was the main driver of accumulation of insoluble tau aggregates across the brain, and mediated the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations were mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations were associated with cognitive decline, which was mediated by faster increase of tau aggregates. In AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline was driven by the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD.
Two schizophrenia imaging signatures and their associations with cognition, psychopathology, and genetics in the general population
Authors: Chand Ganesh B. , Singhal Pankhuri , Dwyer Dominic B. , Wen Junhao , Erus Guray , Doshi Jimit , Srinivasan Dhivya , Mamourian Elizabeth , Varol Erdem , Sotiras Aristeidis , Hwang Gyujoon , Dazzan Paola , Kahn Rene S. , Schnack Hugo G. , Zanetti Marcus V. , Meisenzahl Eva , Busatto Geraldo F. , Crespo-Facorro Benedicto , Pantelis Christos , Wood Stephen J. , Zhuo Chuanjun , Shinohara Russell T. , Shou Haochang , Fan Yong , Koutsouleris Nikolaos , Kaczkurkin Antonia N. , Moore Tyler M. , Verma Anurag , Calkins Monica E. , Gur Raquel E. , Gur Ruben C. , Ritchie Marylyn D. , Satterthwaite Theodore D. , Wolf Daniel H. , Davatzikos Christos 
Published: January 2022

ABSTRACTThe prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume, and signature 2 with increased striatal volume, could be replicated in an independent schizophrenia sample, and investigate whether expression of these signatures can be detected at the population-level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. This cross-sectional study used an independent schizophrenia-control sample (n=347; age 16-57 years) for replication of imaging signatures, and then examined two independent population-level datasets: Philadelphia Neurodevelopmental Cohort [PNC; n=359 typically developing (TD) and psychosis-spectrum symptoms (PS) youth] and UK Biobank (UKBB; n=836; age 44-50 years) adults. We quantified signature expression using support-vector machine learning, and compared cognition, psychopathology, and polygenic risk between signatures. Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youth with PS than TD youth, whereas signature 2 frequency was similar. In both youth and adults, signature 1 had worse cognitive performance than signature 2. Compared to adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. We successfully replicate two neuroanatomical signatures of schizophrenia, and describe their prevalence in population-based samples of youth and adults. We further demonstrate distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.
Clinical Performance of the cobas Liat SARS-CoV-2 & Influenza AB for the Detection of SARS-CoV-2 in Nasal Samples
Authors: Akashi Yusaku , Horie Michiko , Kiyotaki Junichi , Takeuchi Yuto , Togashi Kenichi , Adachi Yuki , Ueda Atsuo , Notake Shigeyuki , Nakamura Koji , Terada Norihiko , Kurihara Yoko , Kiyasu Yoshihiko , Suzuki Hiromichi 
Published: January 2022

AbstractBackground and ObjectivePoint-of-care type molecular diagnostic tests have been used for detecting SARS-CoV-2, although their clinical utility with nasal samples has yet to be established. This study evaluated the clinical performance of the cobas Liat SARS-CoV-2 & Influenza AB (Liat) in nasal samples.MethodsNasal and nasopharyngeal samples were collected and were tested using the Liat, the cobas 6800 system and the cobas SARS-CoV-2 & Influenza AB (cobas), and a method developed by National Institute of Infectious Diseases, Japan (NIID).ResultsA total of 814 nasal samples were collected. The Liat assay was positive for SARS-CoV-2 in 113 (13.9%). The total, positive, and negative concordance rate between the Liat and cobas/NIID assays were 99.3%/98.4%, 99.1%/100%, and 99.3%/98.2%, respectively. Five samples were positive only using the Liat assay. Their Ct values ranged from 31.9 to 37.2. The Ct values of the Liat assay were significantly lower (p < 0.001) but were correlated (p < 0.001) with those of other molecular assays. In the participants who tested positive for SARS-CoV-2 on the Liat assay using nasopharyngeal samples, 88.2% of their nasal samples also tested positive using the Liat assay.ConclusionThe Liat assay showed high concordance with other molecular assays in nasal samples. Some discordance occurred in samples with Ct values > 30 on the Liat assay.Key PointsThe cobas Liat SARS-CoV-2 & Influenza AB assay showed high concordance with other molecular assays in nasal and nasopharyngeal samples, providing results within 20 minutes.Some discordance occurred in samples with Ct values > 30 on the Liat assay.The Liat assay may be suitable for use in a variety of clinical situations, primarily where accurate detection of SARS-CoV-2 is necessary.
Safety and immunogenicity of the BBIBP-CorV vaccine in adolescents aged 12-17 years in Thai population, prospective cohort study
Authors: Tawinprai Kriangkrai , Siripongboonsitti Taweegrit , Porntharukchareon Thachanun , Vanichsetakul Preeda , Thonginnetra Saraiorn , Niemsorn Krongkwan , Promsena Pathariya , Tandhansakul Manunya , Kasemlawan Naruporn , Ruangkijpaisal Natthanan , Banomyong Narin , Phattraprayoon Nanthida , Ungtrakul Teerapat , Wittayasak Kasiruck , Thonwirak Nawarat , Soonklang Kamonwan , Sornsamdang Gaidganok , Mahanonda Nithi 
Published: January 2022

ABSTRACTIntroductionCOVID-19 pandemic affects all populations worldwide, including adolescents. Adolescents can develop a severe form of COVID-19, especially with comorbidity underlying. The prior studies of the mRNA COVID-19 vaccine showed excellent effectiveness in adolescents. Therefore, this study aimed to evaluate the safety and effectiveness of the BBIBP-CorV vaccine with the immunobridging approach in Thai adolescents.MethodsThis single-center, prospective cohort study compared the immunogenicity after 2 doses of the BBIBO-CorV vaccine with 21 days interval of participants aged 12-17 years with 18-30 years at Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand. The key eligible criteria were healthy or had stable pre-existing comorbidity participants, aged 12-17 years. The primary endpoint was the anti-receptor binding domain antibody concentration at 4 weeks after dose 2 of the vaccine. In addition, safety profiles were solicited adverse events within 7 days after each dose of vaccine and any adverse events through 1 month after dose 2 of the vaccine.ResultsFour weeks after the second vaccination, the GMC of anti-RBD antibody in the adolescent cohort was 102.9 BAU/mL (95%CI; 91.0-116.4) and 36.9 BAU/mL (95%CI; 30.9-44.0) in the adult cohort. The GMR of the adolescent cohort was 2.79 (95%CI; 2.25-3.46, p-value; <0.0001) compared with the adult cohort which met non-inferiority criteria. The reactogenicity was slightly less reported in the adolescent cohort compared with the adult cohort. No serious adverse events were reported in both cohorts.ConclusionVaccination with the BBIBP-CorV vaccine in the adolescent participants was safe and effective.
Mobile Phone Virtual Reality Game for Pediatric Home Burn Dressing Pain Management, a Randomized Clinical Trial
Authors: Armstrong Megan , Lun Jonathan , Groner Jonathan I. , Thakkar Rajan K. , Fabia Renata , Noffsinger Dana , Xiang Henry 
Published: January 2022

AbstractImportanceVirtual Reality (VR) gaming is considered a safe and effective alternative to standard pain alleviation in the hospital, we advocate for its use during repeated redressing at home.ObjectiveThis study will address the effectiveness and feasibility of the Virtual Reality Pain Alleviation Tool (VR-PAT) that was developed by the research team at the Nationwide Children’s Hospital for repeated at-home burn dressing changes.Design, Setting and ParticipantsRandomized clinical trial among patients recruited at the Nationwide Children’s Hospital (NCH) outpatient burn clinic between September 2019 and June 2021. We included English-speaking burn patients 5-17 years old requiring daily dressing changes for at least one week after first outpatient dressing change.InterventionsOne group played an interactive VR-PAT game during dressing changes, while the other utilized standard distraction techniques available in the home for a week. Both child and caretaker were later asked to assess perceived pain. Those in the intervention group were asked to evaluate convenience and enjoyment of the VR-PAT game.OutcomesPatients were asked to rate perceived pain on a scale of 1-10, and caregivers were asked to rate observed pain on a scale of 1-10. For the VR-PAT group, patients were also asked to rate various aspects of the VR game on a scale of 1-10 and caregivers were asked questions assessing ease of use.ConclusionsSubjects found the VR-PAT to be a useful distraction during home dressing changes and reported it be easy to implement. In the VR-PAT group, child and caregiver reported pain decreased as the week of dressing changes progressed and was lower than those in the control group after the fourth dressing change. Children playing the VR-PAT reported consistent happiness and fun as the week went on and increased realism and engagement, which means our results weren’t just due to the novel experience of VR-PAT.Trial RegistrationClinicalTrials.gov Identifier: NCT04548635