bluuebunny/crossref_metadata_2025_split huggingface dataset:
How can the public health impact of vaccination be estimated?
Authors: Londono Susy Echeverria , Li Xiang , Toor Jaspreet , Villiers Margaret J. de , Nayagam Shevanthi , Hallett Timothy B. , Abbas Kaja , Jit Mark , Klepac Petra , Jean Kévin , Garske Tini , Ferguson Neil M. , Gaythorpe Katy A. M. 
Published: January 2021

ABSTRACTDeaths due to vaccine preventable diseases cause a notable proportion of mortality worldwide. To quantify the importance of vaccination, it is necessary to estimate the burden averted through vaccination. The Vaccine Impact Modelling Consortium (VIMC) was established to estimate the health impact of vaccination. We describe the methods implemented by the VIMC to estimate impact by calendar year, birth year and year of vaccination (YoV). The calendar and birth year methods estimate impact in a particular year and over the lifetime of a particular birth cohort, respectively. The YoV method estimates the impact of a particular year’s vaccination activities through the use of impact ratios which have no stratification and stratification by activity type and/or birth cohort. Furthermore, we detail an impact extrapolation (IE) method for use between coverage scenarios. We compare the methods, focusing on YoV for hepatitis B, measles and yellow fever. We find that the YoV methods estimate similar impact with routine vaccinations but have greater yearly variation when campaigns occur with the birth cohort stratification. The IE performs well for the YoV methods, providing a time-efficient mechanism for updates to impact estimates. These methods provide a robust set of approaches to quantify vaccination impact.
Detection and surveillance of SARS-CoV-2 genomic variants in wastewater
Authors: Jahn Katharina , Dreifuss David , Topolsky Ivan , Kull Anina , Ganesanandamoorthy Pravin , Fernandez-Cassi Xavier , Bänziger Carola , Devaux Alexander J. , Stachler Elyse , Caduff Lea , Cariti Federica , Corzón Alex Tuñas , Fuhrmann Lara , Chen Chaoran , Jablonski Kim Philipp , Nadeau Sarah , Feldkamp Mirjam , Beisel Christian , Aquino Catharine , Stadler Tanja , Ort Christoph , Kohn Tamar , Julian Timothy R. , Beerenwinkel Niko 
Published: January 2021

AbstractThe emergence of SARS-CoV-2 mutants with altered transmissibility, virulence, or immunogenicity emphasizes the need for early detection and epidemiological surveillance of genomic variants. Wastewater samples provide an opportunity to assess circulating viral lineages in the community. We performed genomic sequencing of 122 wastewater samples from three locations in Switzerland to analyze the B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2 on a population level. We called variant-specific signature mutations and monitored variant prevalence in the local population over time. To enable early detection of emerging variants, we developed a bioinformatics tool that uses read pairs carrying multiple signature mutations as a robust indicator of low-frequency variants. We further devised a statistical approach to estimate the transmission fitness advantage, a key epidemiological parameter indicating the speed at which a variant spreads through the population, and compared the wastewater-based findings to those derived from clinical samples. We found that the local outbreak of the B.1.1.7 variant in two Swiss cities was observable in wastewater up to 8 days before its first detection in clinical samples. We detected a high prevalence of the B.1.1.7 variant in an alpine ski resort popular among British tourists in December 2020, a time when the variant was still very rare in Switzerland. We found no evidence of local spread of the B.1.351 and P.1 variants at the monitored locations until the end of the study (mid February) which is consistent with clinical samples. Estimation of local variant prevalence performs equally well or better for wastewater samples as for a much larger number of clinical samples. We found that the transmission fitness advantage of B.1.1.7, i.e. the relative change of its reproductive number, can be estimated earlier and based on substantially fewer wastewater samples as compared to using clinical samples. Our results show that genomic sequencing of wastewater samples can detect, monitor, and evaluate genetic variants of SARS-CoV-2 on a population level. Our methodology provides a blueprint for rapid, unbiased, and cost-efficient genomic surveillance of SARS-CoV-2 variants.
Engineered RNA biosensors enable ultrasensitive SARS-CoV-2 detection in a simple color and luminescence assay
Authors: Chakravarthy Anirudh , Anirudh KN , George Geen , Ranganathan Shyamsundar , Shettigar Nishan , Suchitta U , Palakodeti Dasaradhi , Gulyani Akash , Ramesh Arati 
Published: January 2021

ABSTRACTThe continued resurgence of the COVID-19 pandemic with multiple variants underlines the need for diagnostic strategies, that are easily adapatable to the changing virus. Here, we have designed and developed toehold RNA-based sensors across the SARS-CoV-2 genome for direct and ultrasensitive detection of the virus and its prominent variants. In our assay, isothermal amplification of a fragment of SARS-CoV-2 RNA coupled with activation of our biosensors leads to a conformational switch in the sensor. This leads to translation of a reporter-protein e.g. LacZ or Nano-lantern that is easily detected using color/luminescence. By optimizing RNA-amplification and biosensor-design, we have generated a highly-sensitive diagnostic assay; with sensitivity down to attomolar SARS-CoV-2 RNA. As low as 100 copies of viral RNA are detected with development of bright color that is easily visualized by the human eye, or a simple cell phone camera as well as quantified using a spectrophotometer. This makes our assay deployable all the way from a well equiped laboratory to a low-resource setting anywhere in the world. Finally, this PHAsed NASBA-Translation Optical Method (PHANTOM) using our engineered RNA biosensors efficiently detects the presence of viral RNA in human patient samples, correlating well with Ct values from RT-qPCR tests. This work presents a powerful and universally accessible strategy for detecting Covid-19 and its prominent variants. This strategy is easily adaptable to further viral evolution and brings RNA-based bioengineering to centerstage.
Comparison of algorithm-based versus single-item diagnostic measures of anxiety and depression disorders in the GLAD and COPING cohorts
Authors: Davies Molly R. , Buckman Joshua E. J. , Adey Brett N. , Armour Chérie , Bradley John R. , Curzons Susannah C. B. , Davis Katrina A. S. , Goldsmith Kimberley A. , Hirsch Colette R. , Hotopf Matthew , Hübel Christopher , Jones Ian R. , Kalsi Gursharan , Krebs Georgina , Lin Yuhao , Marsh Ian , McAtarsney-Kovacs Monika , McIntosh Andrew M. , Monssen Dina , Peel Alicia J. , Rogers Henry C. , Skelton Megan , Smith Daniel J. , Kuile Abigail ter , Thompson Katherine N. , Veale David , Walters James T. R. , Zahn Roland , Breen Gerome , Eley Thalia C. 
Published: January 2021

AbstractBackgroundUnderstanding and improving outcomes for people with anxiety or depression often requires large studies. To increase participation and reduce costs, such research is typically unable to utilise “gold-standard” methods to ascertain diagnoses, instead relying on remote, self-report measures.AimsTo assess the comparability of remote diagnostic methods for anxiety and depression disorders commonly used in research.MethodParticipants from the UK-based GLAD and COPING NBR cohorts (N= 58,400) completed an online questionnaire between 2018-2020. Responses to detailed symptom reports were compared to DSM-5 criteria to generate algorithm-based diagnoses of major depressive disorder (MDD), generalised anxiety disorder (GAD), specific phobia, social anxiety disorder, panic disorder, and agoraphobia. Participants also self-reported any prior diagnoses from health professionals, termed single-item diagnoses. “Any anxiety” included participants with at least one anxiety disorder. Agreement was assessed by calculating accuracy, Cohen’s kappa, McNemar’s chi-squared, sensitivity, and specificity.ResultsAgreement between diagnoses was moderate for MDD, any anxiety, and GAD, but varied by cohort. Agreement was slight to fair for the phobic disorders. Many participants with single-item GAD did not receive an algorithm-based diagnosis. In contrast, algorithm-based diagnoses of the phobic disorders were more common than single-item diagnoses.ConclusionsAgreement for MDD, any anxiety, and GAD was higher for cases in the case-enriched GLAD cohort and for controls in the general population COPING NBR cohort. For anxiety disorders, single-item diagnoses classified most participants as having GAD, whereas algorithm-based diagnoses distributed participants more evenly across the anxiety disorders. Further validation against gold standard measures is required.
Inflight Transmission of COVID-19 Based on Aerosol Dispersion Data
Authors: Wang Zhaozhi , Galea Edwin R. , Grandison Angus , Ewer John , Jia Fuchen 
Published: January 2021

AbstractBackgroundAn issue of concern to the travelling public is the possibility of in-flight transmission of COVID-19 during long- and short-haul flights. The aviation industry maintain the probability of contracting the illness is small based on reported cases, modelling and data from aerosol dispersion experiments conducted on-board aircraft.MethodsUsing experimentally derived aerosol dispersion data for a B777-200 aircraft and a modified version of the Wells-Riley equation we estimate inflight infection probability for a range of scenarios involving quanta generation rate and face mask efficiency. Quanta generation rates were selected based on COVID-19 events reported in the literature while mask efficiency was determined from the aerosol dispersion experiments.ResultsThe MID-AFT cabin exhibits the highest infection probability. The calculated maximum individual infection probability (without masks) for a 2-hour flight in this section varies from 4.5% for the “Mild Scenario” to 60.2% for the “Severe Scenario” although the corresponding average infection probability varies from 0.1% to 2.5%. For a 12-hour flight, the corresponding maximum individual infection probability varies from 24.1% to 99.6% and the average infection probability varies from 0.8% to 10.8%. If all passengers wear face masks throughout the 12-hour flight, the average infection probability can be reduced by approximately 73%/32% for high/low efficiency masks. If face masks are worn by all passengers except during a one-hour meal service, the average infection probability is increased by 59%/8% compared to the situation where the mask is not removed.ConclusionsThis analysis has demonstrated that while there is a significant reduction in aerosol concentration due to the nature of the cabin ventilation and filtration system, this does not necessarily mean that there is a low probability or risk of in-flight infection. However, mask wearing, particularly high-efficiency ones, significantly reduces this risk.
Polymorphisms affecting expression of the vaccine antigen factor H binding protein influence invasiveness of Neisseria meningitidis
Authors: Earle Sarah G. , Lobanovska Mariya , Lavender Hayley , Tang Changyan , Exley Rachel M. , Ramos-Sevillano Elisa , Browning Douglas , Kostiou Vasiliki , Harrison Odile B. , Bratcher Holly B. , Varani Gabriele , Tang Christoph M. , Wilson Daniel J. , Maiden Martin C. J. 
Published: January 2021

ABSTRACTMany bacterial diseases are caused by organisms that ordinarily are harmless components of the human microbiome. Effective interventions against these conditions requires an understanding of the processes whereby symbiosis or commensalism breaks down. Here, we performed bacterial genome-wide association studies (GWAS) of Neisseria meningitidis, a common commensal of the human respiratory tract despite being a leading cause of meningitis and sepsis. GWAS discovered single nucleotide polymorphisms (SNPs) and other bacterial genetic variants associated with invasive meningococcal disease (IMD) versus carriage in several loci across the genome, revealing the polygenic nature of this phenotype. Of note, we detected a significant peak around fHbp, which encodes factor H binding protein (fHbp); fHbp promotes bacterial immune evasion of human complement by recruiting complement factor H (CFH) to the meningococcal surface. We confirmed the association around fHbp with IMD in a validation GWAS, and found that SNPs identified in the validation affecting the 5’ region of fHbp mRNA alter secondary RNA structures, increase fHbp expression, and enhance bacterial escape from complement-mediated killing. This finding mirrors the known link between complement deficiencies and CFH variation with human susceptibility to IMD, highlighting the central importance of human and bacterial genetic variation across the fHbp:CFH interface in IMD susceptibility, virulence, and the transition from carriage to disease.
Expression of a miRNA targeting mutated SOD1 in astrocytes induces motoneuron plasticity and improves neuromuscular function in ALS mice
Authors: Rochat C. , Bernard-Marissal N. , Pradervand S. , Perrin F.E. , Raoul C. , Aebischer P. , Schneider B.L. 
Published: January 2021

AbstractIn amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and non-cell-autonomous mechanisms lead to the selective degeneration of motoneurons. Here, we evaluate the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes using mice expressing the mutated SOD1G93A protein. An AAV-gfaABC1D vector encoding an artificial microRNA is used to deliver RNA interference against mutated SOD1 selectively in astrocytes. The treatment leads to the progressive rescue of neuromuscular junction occupancy, to the recovery of the compound muscle action potential in the gastrocnemius muscle, and significantly improves neuromuscular function. In the spinal cord, gene therapy targeting astrocytes protects a small pool of fast-fatigable motoneurons until disease end stage. In the gastrocnemius muscle of the treated SOD1G93A mice, the fast-twitch type IIb muscle fibers are preserved from atrophy. Axon collateral sprouting is observed together with muscle fiber type grouping indicative of denervation/re-innervation events. The transcriptome profiling of spinal cord motoneurons shows changes in the expression levels of factors regulating the dynamics of microtubules. Gene therapy delivering RNA interference against mutated SOD1 in astrocytes provides therapeutic effects enhancing motoneuron plasticity and improving neuromuscular function in ALS mice.
Distinct regulation of dopamine D3 receptor in the basolateral amygdala and dentate gyrus during the reinstatement of cocaine CPP induced by drug priming and social stress
Authors: Guerrero-Bautista Rocío , Franco-García Aurelio , Hidalgo Juana M. , Fernández-Gómez Francisco José , Ribeiro Do Couto Bruno , Núñez Cristina , Milanés M. Victoria 
Published: January 2021

AbstractRelapse in cocaine seeking and intake is one of the main challenges when treating its addiction. Among the triggering factors for recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Besides, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and in the activity of the mTOR pathway, that is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced CPP evoked by drug priming and social stress. Reinstatement of cocaine-CPP paralleled with a trend to increase of D3R and dopamine transporter (DAT) levels in the BLA. Social stress-but not drug-induced reactivation of cocaine memories was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), that was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitantly with cocaine-CPP reactivation occurred a diminution of mTOR phosphorylation (activation) in the BLA and DG that was inhibited by D3R blockade in both nuclei before the social stress episode, and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while support a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicates that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli.
Mitochondrial fusion regulates proliferation and differentiation in the type II neuroblast lineage inDrosophila
Authors: Dubal Dnyanesh , Moghe Prachiti , Uttekar Bhavin , Rikhy Richa 
Published: January 2021

AbstractOptimal mitochondrial function determined by mitochondrial dynamics, morphology and activity is coupled to stem cell differentiation and organism development. However, the mechanisms of interaction of signaling pathways with mitochondrial morphology and activity are not completely understood. We assessed the role of mitochondrial fusion and fission in differentiation of neural stem cells called neuroblasts (NB) in theDrosophilabrain. Depletion of mitochondrial inner membrane fusion protein Opa1 and mitochondrial outer membrane protein Marf in theDrosophilatype II neuroblast lineage led to mitochondrial fragmentation and loss of activity. Opa1 and Marf depletion did not affect the numbers and polarity of type II neuroblasts but led to a decrease in proliferation and differentiation of cells in the lineage. On the contrary, loss of mitochondrial fission protein Drp1 led to mitochondrial fusion but did not show defects in proliferation and differentiation. Depletion of Drp1 along with Opa1 or Marf also led to mitochondrial fusion and suppressed fragmentation, loss of mitochondrial activity, proliferation and differentiation in the type II NB lineage. We found that Notch signaling depletion via the canonical pathway showed mitochondrial fragmentation and loss of differentiation similar to Opa1 mutants. An increase in Notch signaling required mitochondrial fusion for NB proliferation. Further, Drp1 mutants in combination with Notch depletion showed mitochondrial fusion and drove differentiation in the lineage suggesting that fused mitochondria can influence Notch signaling driven differentiation in the type II NB lineage. Our results implicate a crosstalk between Notch signalling, mitochondrial activity and mitochondrial fusion as an essential step in type II NB differentiation.
Design-of-Experiments In Vitro Transcription Yield Optimization of Self-Amplifying RNA
Authors: Samnuan Karnyart , Blakney Anna K. , McKay Paul F. , Shattock Robin J. 
Published: January 2021

AbstractSelf-amplifying RNA (saRNA) vaccines are able to induce a higher antigen-specific immune response with a more cost-effective and rapid production process compared to plasmid DNA vaccines. saRNAs are synthesized through in vitro transcription (IVT) however; this process has mainly been optimized for relatively short mRNAs. Here, we optimized the IVT process for long saRNAs, approximately 9.4 kb through a design of experiment (DoE) approach to produce a maximal RNA yield and validated the optimal IVT method on various sizes of RNA. We found that magnesium has the highest impact on RNA yield with acetate ions enabling a higher yield than chloride ions. In addition, the interaction between magnesium and nucleoside triphosphates (NTPs) is highly essential for IVT. Further addition of sodium acetate (NaOAc) during IVT provided no added benefit in RNA yield. Moreover, pyrophosphatase was not essential for productive IVT. The optimal IVT method can be used to synthesize different lengths of RNA. These findings emphasize the ability to synthesize high quality and quantity of saRNA through IVT and that the optimal amount of each component is essential for their interactions to produce a high RNA yield.
No evidence for general intelligence in a fish
Authors: Aellen Mélisande , Burkart Judith M. , Bshary Redouan 
Published: January 2021

AbstractDifferences in human general intelligence or reasoning ability can be quantified with the psychometric factorg, because individual performance across cognitive tasks is positively correlated.galso emerges in mammals and birds, is correlated with brain size and may similarly reflect general reasoning ability and behavioural flexibility in these species. To exclude the alternative that these positive cross-correlations may merely reflect the general biological quality of an organism or an inevitable by-product of having brains it is paramount to provide solid evidence for the absence ofgin at least some species. Here, we show that wild-caught cleaner fishLabroides dimidiatus, a fish species otherwise known for its highly sophisticated social behaviour, completely lacksgwhen tested on ecologically non-relevant tasks. Moreover, performance in these experiments was not or negatively correlated with an ecologically relevant task, and in none of the tasks did fish caught from a high population density site outperform fish from a low-density site.gis thus unlikely a default result of how brains are designed, and not an automatic consequence of variation in social complexity. Rather, the results may reflect thatgrequires a minimal brain size, and thus explain the conundrum why the average mammal or bird has a roughly 10 times larger brain relative to body size than ectotherms. Ectotherm brains and cognition may therefore be organized in fundamentally different ways compared to endotherms.
Novel functional sequences uncovered through a bovine multi-assembly graph
Authors: Crysnanto Danang , Leonard Alexander S. , Fang Zih-Hua , Pausch Hubert 
Published: January 2021

AbstractLinear reference genomes are typically assembled from single individuals. They are unable to reflect the genetic diversity of populations and lack millions of bases. To overcome such limitations and make non-reference sequences amenable to genetic investigations, we build a multi-assembly graph from six reference-quality assemblies from taurine cattle and their close relatives. We uncover 70,329,827 bases that are missing in the bovine linear reference genome. The missing sequences encode novel transcripts that are differentially expressed between individual animals. Reads which were previously poorly or unmapped against the bovine reference genome now align accurately to the non-reference sequences. We show that the non-reference sequences contain polymorphic sites that segregate within and between breeds of cattle. Our efforts to uncover novel functional sequences from a multi-assembly graph pave the way towards the transition to a more representative bovine reference genome.