bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of geographical variation in income measures on Measles-Mumps-Rubella uptake and coverage in England; a protocol for an ecological study
Authors: Ghazal Salma , Soyiri Ireneous N. 
Published: December 2022

3.ABSTRACTMeasles is a vaccine-preventable disease whose vaccine was introduced in the United Kingdom in 1988, however, Measles outbreaks are still occurring in England. Consequently, the World Health Organization (WHO) removed the UK’s elimination status of Measles in 2019.Noticeably, MMR vaccination coverage in England is below the recommended threshold with geographical variations across local authorities (LA). The research into the effect of income disparities on MMR vaccine coverage was insufficiently examined. Therefore, an ecological study will be conducted aiming at determining whether there is a relationship between income deprivation measures and MMR vaccine coverage in upper-tier local authorities in England, using 2019 publicly available data. The effect of spatial clustering of income level on vaccination coverage will also be assessed.Vaccination coverage data will be obtained from “Cover of Vaccination Evaluated Rapidly (COVER)”. Income deprivation score, Deprivation gap, and Income Deprivation Affecting Children Index will be obtained from Office for National Statistics and Moran’s Index will be generated using RStudio.Rural/urban LA classification and mothers’ education will be included as possible confounding factors. Additionally, the live births rate per mothers’ age group will be included as a proxy for the mothers’ age variation in different LA. Multiple linear regression will be used after testing the relevant assumptions, using SPSS software. Moran’s I together with income deprivation score will be analysed through regression and mediation analysis.This study will help in determining whether income level is a determinant of MMR vaccination uptake and coverage in LA in England which would help policymakers in designing targeted campaigns, thus preventing measles outbreaks in the future.
Is it possible to flatten-the-curve after the initial outbreak of Covid-19? A data-driven modeling analysis for Omicron pandemic in China
Authors: Sun Jiaqi , Li Yusi , Shao Ning-Yi , Liu Miao 
Published: December 2022

AbstractIn the current coronavirus disease 2019 (COVID-19) pandemic, the Omicron variant of severe acute respiratory syndrome coronavirus 2 has become the predominant strain circulating worldwide. In China, enormous controversies exist regarding the “dynamic zero tolerance” (DZT) and “totally no inventions” (TNI) strategies for preventing the spread of the Omicron variant. Currently, China is gradually relaxing the COVID-19 measures from DZT level. In such situations, the “flatten-the-curve” (FTC) strategy, which decreases and maintains the low rate of infection to avoid overwhelming the healthcare system by adopting relaxed nonpharmaceutical interventions (NPIs) after the initial outbreak, has been perceived as most appropriate and effective method to prevent the spread of the Omicron variant. Hence, we established a data-driven model of Omicron transmission based on the pandemic data of Macau, Hong Kong, and Singapore in 2022 to deduce the overall prevention effect throughout China. In the current immunity level without any NPI applied, more than 12.7 billion (including asymptomatic individuals) were infected with the Omicron variant within 90 days, but the daily new infections sharply declined; moreover, Omicron outbreak would result to 1.49 million deaths within 180 days. The application of FTC could decrease the deaths by 36.91% within 360 days. Age-stratified analyses showed that the NPI application among individuals aged >60 years would also result in 0.81 million deaths within 360 days, and the application of FTC strategy through treatment with anti-COVID drugs can reduce the number of deaths to 0.40 million. In a model of completed vaccination, the application of TNI strategy would also result in 0.56 million deaths and slightly decrease the infection numbers. The strict implementation of FTC policy combined with completed vaccination and drug use, which only resulted in 0.19 million deaths in an age-stratified model, will help end the pandemic within about 240 days. The pandemic would be terminated within a shorter period of time without resulting in a high fatality rate; therefore, the FTC policy could be strictly implemented through enhancement of immunity and drug use.
Antiviral treatments lead to the rapid accrual of hundreds of SARS-CoV-2 mutations in immunocompromised patients
Authors: Fountain-Jones Nicholas M. , Vanhaeften Robert , Williamson Jan , Maskell Janelle , Chua I-Ly J , Charleston Michael , Cooley Louise 
Published: December 2022

AbstractThe antiviral Molnupiravir (Lageviro) is widely used across the world to treat SARS-CoV-2 infection. Molnupiravir reduces viral replication by inducing mutations throughout the genome, yet in patients that do not clear the infection, the longer-term impact of the drug on virus evolution is unclear. Here, we used a case-control approach to monitor SARS-CoV-2 genomes through time in nine immunocompromised -patients with five treated with Molnupiravir. Within days of treatment, we detected a large number of low-frequency mutations in patients and that these new mutations could persist and, in some cases, were fixed in the virus population. All patients treated with the drug accrued new mutations in the spike protein of the virus, including non-synonymous mutations that altered the amino acid sequence. Our study demonstrates that this commonly used antiviral can ‘supercharge’ viral evolution in immunocompromised patients, potentially generating new variants and prolonging the pandemic.
Understanding the quality of life of people living with HIV in rural and urban areas in Indonesia
Authors: Fauk Nelsensius Klau , Gesesew Hailay Abrha , Mwanri Lillian , Hawke Karen , Ward Paul Russell 
Published: December 2022

AbstractHuman Immunodeficiency Virus (HIV) is a major global public health issue that affects the quality of life (QoL) of people living with HIV (PLHIV) globally and in Indonesia. As a part of a large-scale qualitative study investigating HIV risk factors and impacts on PLHIV and facilitators of and barriers to their access to HIV care services in Yogyakarta and Belu, Indonesia, this paper describes their in-depth views and experiences of the influence of HIV on their QoL. 92 participants were recruited using the snowball sampling technique. Data were collected using in-depth interviews. In addition, the World Health Organisation Quality of Life questionnaire (WHOQOL – HIV BREF) was also distributed to each of them to fill out prior to the interviews. Chi-Square analysis was used to analyse data from the survey and qualitative data analysis was guided by a framework analysis. The findings reported several factors affecting the QoL of the participants. These included (i) environmental factors, such as living in rural areas, the unavailability of HIV care services and public transport, and long-distance travel to healthcare facilities; (ii) personal beliefs associated with HIV; (iii) sexual and social relationships and their influence of the QoL of participants; and (iv) level of independence and physical health condition following HIV diagnosis. The findings indicate the need for intervention programs that address the availability and accessibility of HIV care services to PLHIV within rural communities, and support various physical, psychological, and financial needs of PLHIV. These can be implemented through the provision of supplements and nutritious food, HIV counselling and door-to-door/community-based ART service delivery to PLHIV which may increase their engagement in and adherence to the treatment and improve their physical and psychological condition and QoL.
CIRCUST: a novel methodology for temporal order reconstruction of molecular rhythms; validation and application towards a daily rhythm gene expression atlas in humans
Authors: Larriba Yolanda , Mason Ivy C. , Saxena Richa , Scheer Frank A.J.L. , Rueda Cristina 
Published: December 2022

AbstractThe circadian system drives near-24-h oscillations in behaviors and biological processes. The underlying core molecular clock regulates the expression of other genes, and it has been shown that the expression of more than 50 percent of genes in mammals displays 24-h rhythmic patterns, with the specific genes that cycle varying from one tissue to another. Determining rhythmic gene expression patterns in human tissues sampled as single timepoints has several challenges, including the reconstruction of temporal order of highly noisy data. Previous methodologies have attempted to address these challenges in one or a small number of tissues for which clock gene evolutionary conservation is assumed to be preserved. Here we introduce CIRCUST, a novel CIRCular-robUST methodology for analyzing molecular rhythms, that relies on circular statistics, is robust against noise, and requires fewer assumptions than existing methodologies. Next, we validated the method against two controlled experiments in which sampling times were known, and finally, CIRCUST was applied to 34 tissues from the Genotype-Tissue Expression (GTEx) dataset with the aim towards building a comprehensive daily rhythm gene expression atlas in humans. The validation and application shown here indicate that CIRCUST provides a flexible framework to formulate and solve the issues related to the analysis of molecular rhythms in human tissues. CIRCUST methodology is publicly available athttps://github.com/yolandalago/CIRCUST/.
Genetic inactivation of the USP19 deubiquitinase regulates a-synuclein ubiquitination and inhibits accumulation of Lewy body like aggregates in mice
Authors: Schorova Lenka , Bedard Nathalie , Khayachi Anouar , Bolivar-Pedroso Joao , Ho Hung-Hsiang , Huynh Julie , Piccirelli Mikaela , Wang Yifei , Plourde Marie , Luo Wen , Cid-Pellitero Esther del , Shlaifer Irina , Ye Yihong , Durcan Thomas M. , Wing Simon S. 
Published: December 2022

ABSTRACTThe USP19 deubiquitinase is found in a locus associated with Parkinson’s Disease (PD), interacts with heat shock proteins and promotes secretion of a-synuclein (a-syn) through the misfolding associated protein secretion (MAPS) pathway. Since these processes might modulate the processing of a-syn aggregates during the progression of PD, we tested the effect of USP19 knockout (KO) in mice expressing the A53T mutation of a-syn and in whom a-syn preformed fibrils (PFF) had been injected in the striatum. Compared to WT, KO brains showed decreased accumulation of phospho-synuclein (pSyn) positive aggregates. The improved pathology was associated with less activation of microglia, higher levels of synaptic marker proteins and improved performance in a tail suspension test. Exposure of primary neurons from WT and KO mice to PFF in vitro also led to decreased accumulation of pSyn aggregates. KO did not affect uptake of PFF in the cultured neurons. It also did not affect the propagation of aggregates as assessed by exposing WT or KO neurons to PFF and measuring pSyn positive aggregates in non-exposed adjacent neurons separated using a microfluidics device. We conclude that USP19 instead modulates intracellular dynamics of aggregates. Indeed, at the early time following PFF injection when the number of pSyn positive neurons were similar in WT and KO brains, the KO neurons contained less aggregates. KO brain aggregates stained more intensely with anti-ubiquitin antibodies. Immunoprecipitation of soluble proteins from primary neurons exposed to PFF with antibodies to ubiquitin or pSyn showed higher levels of ubiquitinated a-syn oligomeric species in the KO neurons. We propose that the improved pathology in USP19 KO brains may arise from decreased formation or enhanced clearance of the more ubiquitinated aggregates and/or enhanced disassembly towards more soluble oligomeric species. USP19 inhibition may represent a novel therapeutic approach that targets the intracellular dynamics of a-syn complexes.
Hepatic mTORC2 compensates for loss of adipose mTORC2 in mediating energy storage and glucose homeostasis
Authors: Frei Irina C. , Weissenberger Diana , Müller Christoph , Hall Michael N. , Shimobayashi Mitsugu 
Published: December 2022

AbstractMammalian target of rapamycin complex 2 (mTORC2) is a protein kinase complex that plays an important role in energy homeostasis. Loss of adipose mTORC2 reduces lipogenic enzyme expression andde novolipogenesis in adipose tissue. Adipose-specific mTORC2 knockout mice also displays triglyceride accumulation in the liver. However, the mechanism and physiological role of hepatic triglyceride accumulation upon loss of adipose mTORC2 are unknown. Here, we show that loss of adipose mTORC2 increases expression ofde novolipogenic enzymes in the liver, thereby causing accumulation of hepatic triglyceride and hypertriglyceridemia. Simultaneous inhibition of lipogenic enzymes in adipose tissue and liver by ablating mTORC2 in both tissues prevented accumulation of hepatic triglycerides and hypertriglyceridemia. However, loss of adipose and hepatic mTORC2 caused severe insulin resistance and glucose intolerance. Thus, our findings suggest that increased hepatic lipogenesis is a compensatory mechanism to cope with loss of lipogenesis in adipose tissue, and further suggest that mTORC2 in adipose tissue and liver plays a crucial role in maintaining whole-body energy homeostasis.Graphical abstract
CHESS 3: an improved, comprehensive catalog of human genes and transcripts based on large-scale expression data, phylogenetic analysis, and protein structure
Authors: Varabyou Ales , Sommer Markus J. , Erdogdu Beril , Shinder Ida , Minkin Ilia , Chao Kuan-Hao , Park Sukhwan , Heinz Jakob , Pockrandt Christopher , Shumate Alaina , Rincon Natalia , Puiu Daniela , Steinegger Martin , Salzberg Steven L. , Pertea Mihaela 
Published: December 2022

AbstractThe original CHESS database of human genes was assembled from nearly 10,000 RNA sequencing experiments in 53 human body sites produced by the Genotype-Tissue Expression (GTEx) project, and then augmented with genes from other databases to yield a comprehensive collection of protein-coding and noncoding transcripts. The construction of the new CHESS 3 database employed improved transcript assembly algorithms, a new machine learning classifier, and protein structure predictions to identify genes and transcripts likely to be functional and to eliminate those that appeared more likely to represent noise. The new catalog contains 41,356 genes on the GRCh38 reference human genome, of which 19,839 are protein-coding, and a total of 158,377 transcripts. These include 14,863 novel protein-coding transcripts. The total number of transcripts is substantially smaller than earlier versions due to improved transcriptome assembly methods and to a stricter protocol for filtering out noisy transcripts. Notably, CHESS 3 contains all of the transcripts in the MANE database, and at least one transcript corresponding to the vast majority of protein-coding genes in the RefSeq and GENCODE databases. CHESS 3 has also been mapped onto the complete CHM13 human genome, which gives a more-complete gene count of 43,773 genes and 19,968 protein-coding genes. The CHESS database is available athttp://ccb.jhu.edu/chess.
Whole genome assemblies ofZophobas morioandTenebrio molitor
Authors: Kaur Sabhjeet , Stinson Sydnie A , diCenzo George C 
Published: December 2022

ABSTRACTZophobas morio(=Zophobas atratus) andTenebrio molitorare darkling beetles with industrial importance due to their use as feeder insects, their potential for use in aquafeed and human food products, and their apparent ability to biodegrade various plastic polymers. We report draft genome assemblies forZ. morioandT. molitorgenerated from Nanopore and Illumina data. Following scaffolding against published genomes, haploid assemblies of 462 Mb (scaffold N90 of 16.8 Mb) and 258 Mb (scaffold N90 of 5.9 Mb) were produced forZ. morioandT. molitor, respectively. Gene prediction led to the prediction of 28,544 and 19,830 genes forZ. morioandT. molitor, respectively. BUSCO analyses suggested both assemblies have a high level of completeness; 91.5% and 89.0% of the BUSCO endopterygota marker genes were complete in theZ. morioassembly and proteome, respectively, while 99.1% and 92.8% were complete in theT. molitorassembly and proteome, respectively. Phylogenomic analyses of four genera from the family Tenebrionidae yielded phylogenies consistent with those previously constructed based on mitochondrial genomes. Synteny analyses revealed large stretches of macrosynteny across the family Tenebrionidae, as well as numerous within-chromosome rearrangements. Finally, orthogroup analysis identified ∼28,000 gene families across the family Tenebrionidae, of which 8,185 were identified in all five of the analyzed species, and 10,837 were conserved betweenZ. morioandT. molitor. We expect that the availability of multiple whole genome sequences forZ. morioandT. molitorwill facilitate population genetics studies to identify genetic variation associated with industrially relevant phenotypes.
Mean amplitude of low frequency fluctuations measured by fMRI at 11.7T in the aging brain of mouse lemur primate
Authors: Garin Clément M. , Dhenain Marc 
Published: December 2022

AbstractNon-human primates are a critical species for the identification of key biological mechanisms in normal and pathological aging. One of these primates, the mouse lemur, has been widely studied as a model of cerebral aging or Alzheimer’s disease. The amplitude of low-frequency fluctuations of blood oxygenation level-dependent (BOLD) can be measured with functional MRI. Within specific frequency bands (e.g. the 0.01–0.1 Hz), these amplitudes were proposed to indirectly reflect neuronal activity as well as glucose metabolism. Here, we first created whole brain maps of the mean amplitude of low frequency fluctuations (mALFF) in middle-aged mouse lemurs. Then, we extracted mALFF in old lemurs to identify age-related changes. A high level of mALFF was detected in the temporal cortex (Brodmann area 20), somatosensory areas (Brodmann area 5), insula (Brodmann area 13-6) and the parietal cortex (Brodmann area 7) of healthy middle-aged mouse lemurs. Aging was associated with alteration of mALFF in somatosensory areas (area 5) and the parietal cortex (area 7).Graphical abstractHighlightsWe characterized mean amplitude of fluctuation at low frequencies (mALFF) in mouse lemurs.mALFF was the highest in regions involved in visuo-somatosensory-motor function (Brodmann areas 5, 7, 20) and in more integrative functions (area 13-16).mALFF was affected by aging in regions involved in visuo-somatosensory-motor function (parietal areas 5 and 7).mALFF is a useful marker to investigate age-related cerebral dysfunction in animals.Significance StatementThe amplitude of low-frequency fluctuations (ALFF) is expected to reflect neuronal activity. It has been proposed as an MRI-based method to evaluate brain function.ALFF has been used to investigate different cerebral pathologies in animal models but the regional differences of ALFF signal and the impact of cerebral aging on ALFF has never been characterized.Here, we highlight for the first time regional difference of ALFF. High signal was detected in regions involved in visuo-somatosensory-motor function as well as in more integrative functions. ALFF was reduced in regions involved in visuo-somatosensory-motor function during aging. ALFF is thus a useful marker to investigate age-related cerebral dysfunction.
O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors
Authors: Zhang Zengdi , Huang Zan , Awad Mohamed , Elsalanty Mohammed , Cray James , Ball Lauren E. , Maynard Jason C. , Burlingame Alma L. , Zeng Hu , Mansky Kim C. , Ruan Hai-Bin 
Published: December 2022

SUMMARYIn mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.
ROCK and the actomyosin network control biomineral growth and morphology during sea urchin skeletogenesis
Authors: Hijaze Eman , Gildor Tsvia , Seidel Ronald , Layous Majed , Winter Mark , Bertinetti Luca , Politi Yael , de-Leon Smadar Ben-Tabou 
Published: December 2022

AbstractBiomineralization had apparently evolved independently in different phyla, using distinct minerals, organic scaffolds and gene regulatory networks (GRNs). However, diverse eukaryotes from unicellular organisms, through echinoderms to vertebrates, use the actomyosin network during biomineralization. Specifically, the actomyosin remodeling protein, Rho-associated coiled-coil kinase (ROCK) regulates cell differentiation and gene expression in vertebrates’ biomineralizing cells, yet, little is known on ROCK’s role in invertebrates’ biomineralization. Here we reveal that ROCK controls the formation, growth and morphology of the calcite spicules in the sea urchin larva. ROCK expression is elevated in the sea urchin skeletogenic cells downstream of the Vascular Endothelial Growth Factor (VEGF) signaling. ROCK inhibition leads to skeletal loss and disrupts skeletogenic gene expression. ROCK inhibition after spicule formation reduces spicule elongation rate and induces ectopic spicule branching. Similar skeletogenic phenotypes are observed when ROCK is inhibited in a skeletogenic cell culture, indicating that these phenotypes are due to ROCK activity specifically in the skeletogenic cells. Reduced skeletal growth and enhanced branching are also observed under direct perturbations of the actomyosin network. We propose that ROCK and the actomyosin machinery were employed independently, downstream of distinct GRNs, to regulate biomineral growth and morphology in Eukaryotes.