bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Fetal Alcohol Spectrum Disorder (FASD) in Greater Manchester, UK: an active case ascertainment study
Authors: McCarthy Robyn , Mukherjee Raja A.S. , Fleming Kate M. , Green Jonathan , Clayton-Smith Jill , Price Alan D. , Allely Clare S. , Cook Penny A. 
Published: June 2021

AbstractBackgroundDespite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school.MethodsA two-phase active case ascertainment study was conducted in three mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8-9 years used pre-specified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen positive children were invited for detailed ascertainment of FASD using gold standard measures including medical history, facial dysmorphology, neurological impairment, executive function and behavioural difficulties.ResultsOf 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to phase-two assessment. Twenty had a developmental disorder, of which, four had FASD and four were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95%CI: 1.0%,3.4%) and when including possible cases was 3.6% (2.1%,6.3%). None of these children had previously identified with a developmental diagnosis.ConclusionsFASD was found to be common in these schools, but limitations to the sampling restrict inferences to a population prevalence. Most of these children’s needs had not previously been identified.
The impact of three progressively introduced interventions on second wave daily COVID-19 case numbers in Melbourne, Australia
Authors: Saul Allan , Scott Nick , Spelman Tim , Crabb Brendan S. , Hellard Margaret 
Published: June 2021

AbstractBackgroundThe city of Melbourne, Australia experienced two waves of the COVID-19 epidemic peaking, the first in March and a more substantial wave in July 2020. During the second wave, a series of control measure were progressively introduced that initially slowed the growth of the epidemic then resulted in decreasing cases until there was no detectable local transmission.MethodsTo determine the relative efficacy of the progressively introduced intervention measures, we modelled the second wave as a series of exponential growth and decay curves. We used a linear regression of the log of daily cases vs time, using a four-segment linear spline model corresponding to implementation of the three successive major public health measures. The primary model used all reported cases between 14 June and 15 September then compared the projection of the model with observed cases predict future case trajectory up until the 31 October to assess the use of exponential models in projecting the future course and planning future interventions. The main outcome measures were the exponential daily growth constants, analysis of residuals and estimates of the 95% confidence intervals for the expected case distributions, comparison of predicted daily cases.ResultsThe exponential growth/decay constants in the primary analysis were: 0.122 (s.e. 0.004), 0.035 (s.e. 0.005), -0.037 (s.e. 0.011), and -0.069 (s.e. 0.003) for the initial growth rate, Stage 3, stage 3 + compulsory masks and Stage 4, respectively. Extrapolation of the regression model from the 14 September to the 31 October matched the decline in observed cases over this period.ConclusionsThe four-segment exponential model provided an excellent fit of the observed reported case data and predicted the day-to-day range of expected cases. The extrapolated regression accurately predicted the decline leading to epidemic control in Melbourne.
A Systematic Review of COVID - 19 Induced Myocarditis - Symptomatology, Prognosis, and Clinical Findings
Authors: Jaiswal Vikash , Nagpal Shavy , Labitag Christine Angela E. , Tayo Janelle , Patel Abhinav , Lo Kevin Bryan , Vijayan Rupalakshmi , Matos Wanessa F , Yaqoob Sadia , Panday Priyanka , Savani Saloni , Alnahas Zeinab , Bhatnagar Arushee , Diaz Yoandra , Dylewski John R. 
Published: June 2021

AbstractObjectiveWith the advent of a novel coronavirus in December 2019, several case studies have reported its adversity on cardiac cells. We conducted a systematic review that describes the symptomatology, prognosis, and clinical findings of patients with COVID-19-related myocarditis.MethodsSearch engines including PubMed, Google Scholar, Cochrane Central, and Web of Science were queried for “SARS-CoV-2” or “COVID 19” and “myocarditis.” PRISMA guidelines were employed, and peer-reviewed journals in English related to COVID-19 were included.ResultsThis systematic review included 22 studies and 37 patients. Eight patients (36%) were confirmed myocarditis, while the rest were possible myocarditis. Most patients had elevated cardiac biomarkers, including troponin, CRP, CK, CK-MB, and NT-pro BNP. Electrocardiogram results noted tachycardia (47%), left ventricular hypertrophy (50%), ST-segment alterations (41%), and T wave inversion (18%). Echocardiography presented reduced LVEF (77%), left ventricle abnormalities (34%), right ventricle aberrations (12%), and pericardial effusion (71%). Further, CMR showed reduced myocardial edema (75%), non-ischemic patterns (50%), and hypokinesis (26%). The mortality was significant at 25%.ConclusionsMortality associated with COVID-19 myocarditis appears significant but underestimated. Further studies are warranted to evaluate and quantify patients’ actual prognosis and outcomes with COVID-19 myocarditis.
Effect of 2021 Assembly Election in India on Covid-19 Transmission
Authors: Manik Souvik , Pal Sabyasachi , Mandal Manoj , Hazra Mangal 
Published: June 2021

AbstractIndia is one of the countries in the world which is badly affected by the Covid-19 second wave. Assembly election in four states and a union territory of India was taken place during March-May 2021 when the Covid-19 second wave was close to its peak and affected a huge number of people. We studied the impact of assembly election on the effective contact rate and the effective reproduction number of Covid-19 using different epidemiological models like SIR, SIRD, and SEIR. We also modeled the effective reproduction number for all election-bound states using different mathematical functions. We separately studied the case of all election-bound states and found all the states shown a distinct increase in the effective contact rate and the effective reproduction number during the election-bound time and just after that compared to pre-election time. States, where elections were conducted in single-phase, showed less increase in the effective contact rate and the reproduction number. The election commission imposed extra measures from the first week of April 2021 to restrict big campaign rallies, meetings, and different political activities. The effective contact rate and the reproduction number showed a trend to decrease for few states due to the imposition of the restrictions. We also compared the effective contact rate, and the effective reproduction number of all election-bound states and the rest of India and found all the parameters related to the spread of virus for election-bound states are distinctly high compared to the rest of India.
Signatures of mast cell activation are associated with severe COVID-19
Authors: Tan Janessa , Anderson Danielle E. , Rathore Abhay P. S. , O’Neill Aled , Mantri Chinmay Kumar , Saron Wilfried A. A. , Lee Cheryl , Cui Chu Wern , Kang Adrian E. Z. , Foo Randy , Kalimuddin Shirin , Low Jenny G. , Ho Lena , Tambyah Paul , Burke Thomas W. , Woods Christopher W. , Chan Kuan Rong , Karhausen Jörn , John Ashley L. St. 
Published: June 2021

AbstractLung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype. MC activation in humans was confirmed, through detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. These results support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention.
The impact of local vaccine coverage and recent incidence on measles transmission in France between 2009 and 2018
Authors: Robert Alexis , Kucharski Adam J. , Funk Sebastian 
Published: June 2021

AbstractBackgroundDespite high levels of vaccine coverage, sub-national heterogeneity in immunity to measles can create pockets of susceptibility, which are hard to detect and may result in long-lasting outbreaks. The elimination status defined by the World Health Organization aims to identify countries where the virus is no longer circulating and can be verified after 36 months of interrupted transmission. However, since 2018, numerous countries have lost their elimination status soon after reaching it, showing that the indicators used to define elimination may not be predictive of lower risks of outbreaks.Methods and FindingsWe quantified the impact of local vaccine coverage and recent levels of incidence on the dynamics of measles in each French department between 2009 and 2018, using mathematical models based on the ‘Epidemic-Endemic’ regression framework. High values of local vaccine coverage were associated with fewer imported cases and lower risks of local transmissions. Regions that had recently reported high levels of incidence were also at a lower risk of local transmission, potentially due to additional immunity accumulated during these recent outbreaks. Therefore, all else being equal, the risk of local transmission was not lower in areas fulfilling the elimination criteria (i.e., low recent incidence). After fitting the models using daily case counts, we used the parameters’ estimates to simulate the effect of variations in the vaccine coverage and recent incidence on future transmission. A decrease of 3% in the three-year average vaccine uptake led to a five-fold increase in the number of cases simulated in a year on average.ConclusionsSpatiotemporal variation in vaccine coverage because of disruption of routine immunisation programmes, or lower trust in vaccines, can lead to large increases in both local and cross regional transmission. The association found between local vaccine coverage and incidence suggests that, although regional vaccine uptake can be hard to collect and unreliable because of population movements, it can provide insights into the risks of imminent outbreak. Periods of low local measles incidence were not indicative of a decrease in the risks of local transmission. Therefore, the incidence indicator used to define the elimination status was not consistently associated with lower risks of measles outbreak in France. More detailed models of local immunity levels or subnational seroprevalence studies may yield better estimates of local risk of measles outbreaks.
Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition
Authors: Winkler René , Mägdefrau Ann-Sophie , Piskor Eva-Maria , Kleemann Markus , Beyer Mandy , Linke Kevin , Hansen Lisa , Schaffer Anna-Maria , Hoffmann Marina E. , Poepsel Simon , Heyd Florian , Beli Petra , Möröy Tarik , Mahboobi Siavosh , Krämer Oliver H. , Kosan Christian 
Published: June 2021

AbstractOverexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching the acetylation state of HDAC6 substrates, such as tubulin. Tubulin facilitates nuclear import of MYC, and MYC-dependent B-cell lymphoma cells rely on continuous import of MYC due to its high turn-over. Acetylation of tubulin impairs this mechanism and enables proteasomal degradation of MYC. M-100 targets almost exclusively B-cell lymphoma cells with high levels of MYC whereas non-tumor cells are not affected. M-100 induces massive apoptosis in human and murine MYC-overexpressing B-cell lymphoma cells. We identified the heat-shock protein DNAJA3 as an interactor of tubulin in an acetylation-dependent manner and overexpression of DNAJA3 resulted in a pronounced degradation of MYC. We propose a mechanism by which DNAJA3 associates with hyperacetylated tubulin in the cytoplasm to control MYC turnover. Taken together, our data demonstrate a beneficial role of HDAC6 inhibition in MYC-dependent B-cell lymphoma.
Characterization of SARS2 Nsp15 Nuclease Activity Reveals it’s Mad About U
Authors: Frazier Meredith N. , Dillard Lucas B. , Krahn Juno M. , Perera Lalith , Williams Jason G. , Wilson Isha M. , Stewart Zachary D. , Pillon Monica C. , Deterding Leesa J. , Borgnia Mario J. , Stanley Robin E. 
Published: June 2021

ABSTRACTNsp15 is a uridine specific endoribonuclease that coronaviruses employ to cleave viral RNA and evade host immune defense systems. Previous structures of Nsp15 from across Coronaviridae revealed that Nsp15 assembles into a homo-hexamer and has a conserved active site similar to RNase A. Beyond a preference for cleaving RNA 3’ of uridines, it is unknown if Nsp15 has any additional substrate preferences. Here we used cryo-EM to capture structures of Nsp15 bound to RNA in pre- and post-cleavage states. The structures along with molecular dynamics and biochemical assays revealed critical residues involved in substrate specificity, nuclease activity, and oligomerization. Moreover, we determined how the sequence of the RNA substrate dictates cleavage and found that outside of polyU tracts, Nsp15 has a strong preference for purines 3’ of the cleaved uridine. This work advances our understanding of how Nsp15 recognizes and processes viral RNA and will aid in the development of new anti-viral therapeutics.
The human language system, including its inferior frontal component in ‘Broca’s area’, does not support music perception
Authors: Chen Xuanyi , Affourtit Josef , Ryskin Rachel , Regev Tamar I. , Norman-Haignere Samuel , Jouravlev Olessia , Malik-Moraleda Saima , Kean Hope , Varley Rosemary , Fedorenko Evelina 
Published: June 2021

AbstractLanguage and music are two human-unique capacities whose relationship remains debated. Some have argued for overlap in processing mechanisms, especially for structure processing. Such claims often concern the inferior frontal component of the language system located within ‘Broca’s area’. However, others have failed to find overlap. Using a robust individual-subject fMRI approach, we examined the responses of language brain regions to music stimuli, and probed the musical abilities of individuals with severe aphasia. Across four experiments, we obtained a clear answer: music perception does not engage the language system, and judgments about music structure are possible even in the presence of severe damage to the language network. In particular, the language regions’ responses to music are generally low, often below the fixation baseline, and never exceed responses elicited by non-music auditory conditions, like animal sounds. Further, the language regions are not sensitive to music structure: they show low responses to intact and structure-scrambled music, and to melodies with vs. without structural violations. Finally, in line with past patient investigations, individuals with aphasia who cannot judge sentence grammaticality perform well on melody well-formedness judgments. Thus the mechanisms that process structure in language do not appear to process music, including music syntax.
Plasticity in intrinsic excitability of hypothalamic magnocellular neurosecretory neurons in late-pregnant and lactating rats
Authors: Perkinson Michael R. , Augustine Rachael A. , Bouwer Gregory T. , Brown Emily F. , Cheong Isaiah , Seymour Alexander J. , Fronius Martin , Brown Colin H. 
Published: June 2021

AbstractOxytocin and vasopressin secretion from the posterior pituitary gland are required for normal pregnancy and lactation. Oxytocin secretion is relatively low and constant under basal conditions but becomes pulsatile during birth and lactation to stimulate episodic contraction of the uterus for delivery of the fetus and milk ejection during suckling. Vasopressin secretion is maintained in pregnancy and lactation despite reduced osmolality (the principal stimulus for vasopressin secretion) to increase water retention to cope with the cardiovascular demands of pregnancy and lactation. Oxytocin and vasopressin secretion are determined by the action potential (spike) firing of magnocellular neurosecretory neurons of the hypothalamic supraoptic and paraventricular nucleus. In addition to synaptic input activity, spike firing depends on intrinsic excitability conferred by the suite of channels expressed by the neurons. Therefore, we analysed oxytocin and vasopressin neuron activity in anaesthetised non-pregnant, late-pregnant and lactating rats to test the hypothesis that intrinsic excitability of oxytocin and vasopressin neurons is increased in late pregnancy and lactation to promote oxytocin and vasopressin secretion required for successful pregnancy and lactation. Hazard analysis of spike firing revealed a higher incidence of post-spike hyperexcitability immediately following each spike in oxytocin neurons, but not in vasopressin neurons, in late pregnancy and lactation, which is expected to facilitate high frequency firing during bursts. Despite lower osmolality in late-pregnant and lactating rats, vasopressin neuron activity was not different between non-pregnant, late-pregnant and lactating rats, and blockade of osmosensitive ΔN-TRPV1 channels inhibited vasopressin neurons to a similar extent in non-pregnant, late-pregnant and lactating rats. Furthermore, supraoptic nucleus ΔN-TRPV1 mRNA expression was not different between non-pregnant and late-pregnant rats, suggesting that enhanced activity of ΔN-TRPV1 channels might maintain vasopressin neuron activity to increase water retention during pregnancy and lactation.
SARS-CoV-2 cell-to-cell spread occurs rapidly and is insensitive to antibody neutralization
Authors: Jackson Laurelle , Rodel Hylton , Hwa Shi-Hsia , Cele Sandile , Ganga Yashica , Tegally Houriiyah , Bernstein Mallory , Giandhari Jennifer ,   COMMIT-KZN Team, Gosnell Bernadett I. , Khan Khadija , Hanekom Willem , Karim Farina , de Oliveira Tulio , Moosa Mahomed-Yunus S. , Sigal Alex 
Published: June 2021

AbstractViruses increase the efficiency of close-range transmission between cells by manipulating cellular physiology and behavior, and SARS-CoV-2 uses cell fusion as one mechanism for cell-to-cell spread. Here we visualized infection using time-lapse microscopy of a human lung cell line and used live virus neutralization to determine the sensitivity of SARS-CoV-2 cell-to-cell spread to neutralizing antibodies. SARS-CoV-2 infection rapidly led to cell fusion, forming multinucleated cells with clustered nuclei which started to be detected at 6h post-infection. To compare sensitivity of cell-to-cell spread to neutralization, we infected either with cell-free virus or with single infected cells expressing on their surface the SARS-CoV-2 spike protein. We tested two variants of SARS-CoV-2: B.1.117 containing only the D614G substitution, and the escape variant B.1.351. We used the much smaller area of single infected cells relative to infection foci to exclude any input infected cells which did not lead to transmission. The monoclonal antibody and convalescent plasma we tested neutralized cell-free SARS-CoV-2, with the exception of B.1.351 virus, which was poorly neutralized with plasma from non-B.1.351 infections. In contrast, cell-to-cell spread of SARS-CoV-2 showed no sensitivity to monoclonal antibody or convalescent plasma neutralization. These observations suggest that, once cells are infected, SARS-CoV-2 may be more difficult to neutralize in cell types and anatomical compartments permissive for cell-to-cell spread.
Transcriptome analysis of developmental stages of cocoa pod borer, Conopomorpha cramerella: A polyphagous insect pest of economic importance in Southeast Asia
Authors: Tan Chia Lock , Kasran Rosmin , Lee Wei Wei , Leong Wai Mun 
Published: June 2021

AbstractThe cocoa pod borer, Conopomorpha cramerella (Snellen) is a serious pest in cocoa plantations in Southeast Asia. It causes significant losses in the crop. Unfortunately, genetic resources for this insect is extremely scarce. To improve these resources, we sequenced the transcriptome of C. cramerella representing the three stages of development, larva, pupa and adult moth using Illumina NovaSeq6000. Transcriptome assembly was performed by Trinity for all the samples. A total number of 147,356,088 high quality reads were obtained. Of these, 285,882 contigs were assembled. The mean contig size was 374 bp. Protein coding sequence (CDS) was extracted from the reconstructed transcripts by TransDecoder. Subsequently, BlastX and InterProScan were applied for homology search to make a prediction of the function of CDS in unigene. Additionally, we identified a number of genes that are involved in reproduction and development such as genes involved in general function processes in the insect. Genes found to be involved in reproduction such as porin, dsx, bol and fruitless were associated with sex determination, spermatogenesis and pheromone binding. Furthermore, transcriptome changes during development were analysed. There were 2,843 differentially expressed genes (DEG) detected between the larva and pupa samples. A total of 2,861 DEG were detected between adult and larva stage whereas between adult and pupa stage, 1,953 DEG were found. In conclusion, the transcriptomes could be a valuable genetic resource for identification of genes in C. cramerella and the study will provide putative targets for RNAi pest control.