bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome charaterization based on the Spike-614 and NS8-84 loci of SARS-CoV-2 reveals two major onsets of the COVID-19 pandemic
Authors: Hu Xiaowen , Mu Yaojia , Deng Ruru , Yi Guohui , Yao Lei , Zhang Jiaming 
Published: December 2022

AbstractThe global COVID-19 pandemic has lasted for three years since its outbreak, however its origin is still unknown. Here, we analyzed the genotypes of 3.14 million SARS-CoV-2 genomes based on the amino acid 614 of the Spke (S) and the amino acid 48 of NS8 (nonstructural protein 8), and identified 16 linkage haplotypes. The GL haplotype (S_614G and NS8_48L) was the major haplotype driving the global pandemic and accounted for 99.2% of the sequenced genomes, while the DL haplotype (S_614D and NS8_48L) caused the pandemic in China in the spring of 2020 and accounted for approximately 60% of the genomes in China and 0.45% of the global genomes. The GS (S_614G and NS8_48S), DS (S_614D and NS8_48S) and NS (S_614N and NS8_48S) haplotypes accounted for 0.26%, 0.06%, and 0.0067% of the genomes, respectively. The main evolutionary trajectory of SARS-CoV-2 is DS→DL→GL, whereas the other haplotypes are minor byproducts in the evolution. Surprisingly, the newest haplotype GL had the oldest time of most recent common ancestor (tMRCA), which was May 1 2019 by mean, while the oldest haplotype had the newest tMRCA with a mean of October 17, indicating that the ancestral strains that gave birth to GL had been extinct and replaced by the more adapted newcomer at the place of its origin, just like the sequential rise and fall of the delta and omicron variants. However, they arrived and evolved into toxic strains and ignited a pandemic in China where the GL strains did not exist at the end of 2019. The GL strains had spread all over the world before they were discovered, and ignited the global pandemic, which had not been noticed until the pandemic was declared in China. However, the GL haplotype had little influence in China during the early phase of the pandemic due to its late arrival as well as the strict transmission controls in China. Therefore, we propose two major onsets of the COVID-19 pandemic, one was mainly driven by the haplotype DL in China, the other was driven by the haplotype GL globally.
The impact of quality control on cortical morphometry comparisons in autism
Authors: Bedford Saashi A. , Ortiz-Rosa Alfredo , Schabdach Jenna M. , Costantino Manuela , Tullo Stephanie , Piercy Tom ,   Lifespan Brain Chart Consortium, Lai Meng-Chuan , Lombardo Michael V. , Di Martino Adriana , Devenyi Gabriel A. , Chakravarty M. Mallar , Alexander-Bloch Aaron F. , Seidlitz Jakob , Baron-Cohen Simon , Bethlehem Richard A.I. 
Published: December 2022

AbstractStructural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons. However, despite this, limited work has systematically evaluated the impact of image and image-processing quality on these measures, or compared different quality control (QC) methods and metrics. The growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. Two of the most important aspects of MRI quality are motion, which is known to have a substantial impact on cortical measures in particular, and the accuracy of processed outputs, which have been shown to impact neurodevelopmental trajectories. Here, we present a tool, FSQC, that enables quick and efficient yet thorough assessment of both of these aspects in outputs of the FreeSurfer processing pipeline. We validate our method against other existing QC metrics, including the automated FreeSurfer Euler number, and two other manual ratings of raw image quality. We show strikingly similar spatial patterns in the relationship between each QC measure and cortical thickness; relationships for cortical volume and surface area are largely consistent across metrics, though with some notable differences. We next demonstrate that thresholding by QC score attenuates but does eliminate the impact of quality on cortical estimates. Finally, we explore different ways of controlling for quality when examining differences between autistic individuals and neurotypical controls in the ABIDE dataset, demonstrating that inadequate control for quality can alter results of case-control comparisons.
Plasma GFAP associates with secondary Alzheimer’s pathology in Lewy body disease
Authors: Cousins Katheryn A.Q. , Irwin David J. , Chen-Plotkin Alice , Shaw Leslie M. , Arezoumandan Sanaz , Lee Edward B. , Wolk David A. , Weintraub Daniel , Spindler Meredith , Deik Andres , Grossman Murray , Tropea Thomas F. 
Published: December 2022

AbstractObjectiveWithin Lewy body spectrum disorders (LBSD) with α-synuclein pathology (αSyn), concomitant Alzheimer’s disease (AD) pathology is common and is predictive of clinical outcomes, including cognitive impairment and decline. Plasma phosphorylated tau 181 (p-tau181) is sensitive to AD neuropathologic change (ADNC) in clinical AD, and plasma glial fibrillary acidic protein (GFAP) is associated with the presence of β-amyloid plaques. While these plasma biomarkers are well tested in clinical and pathological AD, their diagnostic and prognostic performance for concomitant AD in LBSD is unknown.MethodsIn autopsy-confirmed αSyn-positive LBSD, we tested how plasma p-tau181and GFAP differed across αSyn with concomitant ADNC (αSyn+AD; n=19) and αSyn without AD (αSyn; n=30). Severity of burden was scored on a semi-quantitative scale for several pathologies (e.g., β-amyloid and tau), and scores were averaged across sampled brainstem, limbic, and neocortical regions.ResultsLinear models showed that plasma GFAP was significantly higher in αSyn+AD compared to αSyn (β=0.31, 95%CI=0.065 – 0.56,p=0.015), after covarying for age at plasma, plasma-to-death interval and sex; plasma p-tau181was not (p=0.37). Next, linear models tested associations of AD pathological features with both plasma analytes, covarying for plasma-to-death, age at plasma, and sex. GFAP was significantly associated with brain β-amyloid (β=15, 95%CI=6.1 – 25,p=0.0018) and tau burden (β=12, 95%CI=2.5 – 22,p=0.015); plasma p-tau181was not associated with either (bothp>0.34).InterpretationFindings indicate that plasma GFAP may be sensitive to concomitant AD pathology in LBSD, especially accumulation of β-amyloid plaques.
Adequacy of using a residual nasal swab specimen from a rapid influenza diagnostic test to perform PCR and whole genome sequencing
Authors: Temte Jonathan L. , Bell Cristalyne , Goss Maureen D. , Reisdorf Erik , Tamerius John , Reddy Sushruth , Barlow Shari , Temte Emily , Wedig Mary , Shult Peter A. 
Published: December 2022

AbstractBackgroundRapid influenza diagnostic tests (RIDT) demonstrate varying sensitivities, often necessitating reverse transcriptase polymerase chain reaction (RT-PCR) to confirm results. The two methods generally require separate specimens. Using the same anterior nasal swab for both RIDT and molecular confirmation would reduce cost and waste and increase patient comfort.ObjectiveThe aim of this study was to determine if RIDT residual nasal swab (rNS) specimens are adequate for RT-PCR and whole genome sequencing (WGS).Study designWe performed RT-PCR and WGS on paired rNS and nasopharyngeal or oropharyngeal (NP/OP) swab specimens that were collected from primary care patients across all ages. We randomly selected 199 and 40 paired specimens for RT-PCR and WGS, respectively, from the 962 paired surveillance specimens collected during the 2014-2015 influenza season.ResultsSensitivity and specificity for rNS specimens were 81.3% and 96.7%, respectively, as compared to NP/OP specimens. The mean cycle threshold (Ct) value for the NP/OP specimen was significantly lower when the paired specimens were both positive than when the NP/OP swab was positive and the nasal swab was negative (25.5 vs 29.5; p<0.001). WGS was successful in 67.5% of the rNS specimens and 55.0% of the NP/OP specimens.ConclusionIt is feasible to use a single anterior nasal swab for RIDT followed by RT-PCR or WGS. This approach may be appropriate in situations where training and supplies are limited. Additional studies are needed to determine if residual nasal swabs from other rapid diagnostic tests produce similar results.
Entrenching social norms in Community-led total sanitation for sustainability of open defecation free status: A survey of Suna West Sub-County, Migori County, Kenya
Authors: Aluoch Naomi R. , Asweto Collins O. , Onyango Patrick O. 
Published: December 2022

ABSTRACTBackgroundCommunity-led total sanitation (CLTS) has been used to stir sanitation-related behaviour change and attain open defecation free (ODF) status. CLTS interventions suffer high rates of reversion such that their gains are unsustainable in most contexts including Suna West sub-County, Kenya.ObjectiveThis study aimed at determining the role of sanitation hygiene practices and social norms on open defecation free status in Suna West Sub County.MethodologySurvey study design was employed using questionnaire and observation checklist to collect data from 384 households.ResultsResults revealed that 66.1% households had partially reverted to non-ODF status. The sanitation-hygiene practices associated with maintenance of ODF includes: use of treated water (OR=3.17; CI=1.20-8.40;p=0.020), use of elevated racks (OR=2.17; CI=1.08-4.37;p=0.030), regularly clean latrines (OR=4.88; CI=1.12-21.37;p=0.035), pouring of ash over the pit of the latrine (OR=4.25; CI=4.20-8.87;p<0.001) and use of dug out pits for waste disposal (OR=4.51; CI=2.09-9.78;p<0.001). On social norms, the study found that laws/penalties (OR=0.31; CI=0.21-0.48;p<0.001), need to improve things in the family (OR=0.50; CI=0.28-0.92;P=0.025), and rewards/incentives (OR=0.21; CI=0.13-0.33;p<0.001) would reduce odds of being ODF. Moreover, odds of being ODF was less likely for households with perception that; construction/maintenance materials were expensive (OR=0.52; CI=0.33-0.80;p=0.003), most people don’t have a latrine (OR=0.40; CI=0.25-0.64; p<0.001) and it is okay to defecate in bushes/rivers/dams (OR=0.31; CI=0.19-0.51; p<0.001).ConclusionThis study findings provides evidence of ODF status reversion in previously certified villages. However, household with retained ODF status was enhanced by several sanitation hygiene practices. Interestingly, households that displayed social norms were less likely to be ODF. This reveals that the CLTS process failed to instil social norms around proper sanitation to inspire community collective action thus little influence on sustainable behaviour change. The findings of this study therefore highlight the need to enhance good hygiene sanitation practices, while instilling social norms to inspire community collective action.
Characterisation and zoonotic risk of tick viruses in public datasets
Authors: Lin Yuting , Pascall David J 
Published: December 2022

AbstractTick-borne viruses remain a substantial zoonotic risk worldwide, so knowledge of the diversity of tick viruses has potential health consequences. Despite their importance, large amounts of sequences in public datasets from tick meta-genomic and –transcriptomic projects remain unannotated, sequence data that could contain undocumented viruses. Through data mining and bioinformatic analyses of more than 37,800 public meta-genomic and -transcriptomic datasets, we found 83 unannotated contigs exhibiting high identity with known tick viruses. These putative viral contigs were classified into three RNA viral families (Alphatetraviridae,Orthomyxoviridae,Chuviridae) and one DNA viral family (Asfaviridae). After manual checking of quality and dissimilarity toward other sequences in the dataset, these 83 contigs were reduced to five putative novel Alphatetra-like viral contigs, four putative novel Orthomyxo-like viral contigs, and one Chu-like viral contig which clustered with known tick-borne viruses, forming a separate clade within the viral families. We further attempted to assess which previously known tick viruses likely represent zoonotic risks and thus deserve further investigation. We ranked the human infection potential of 136 known tick-borne viruses using a genome composition-based machine learning model. We found five high-risk tick-borne viruses (Langat virus, Lonestar tick chuvirus 1, Grotenhout virus, Taggert virus, and Johnston Atoll virus) that have not been known to infect human and two viral families (NairoviridaeandPhenuiviridae) that contain a large proportion of potential zoonotic tick-borne viruses. This adds to the knowledge of tick virus diversity and highlights the importance of surveillance of newly emerging tick-borne diseases.ImportanceTicks are important hosts of pathogens. Despite this, numerous tick-borne viruses are still unknown or poorly characterised. To overcome this, we re-examined currently known tick-borne viruses and identified putative novel viruses associated with ticks in public datasets. Using genome-based machine learning approach, we predicted five high-risk tick-borne viruses that have not yet been reported to cause human infections. Additionally, we highlighted two viral families,NairoviridaeandPhenuiviridae, which are potential public health threats. Our analysis also revealed 10 putative novel RNA viral contigs clustered with known tick-borne viruses. Our study highlights the importance of monitoring ticks and the viruses they carry in endemic areas to prevent and control zoonotic infectious disease outbreaks. To achieve this, we advocate for a multidisciplinary approach within a One Health and EcoHealth framework that considers the relationship between zoonotic disease outbreaks and their hosts, humans, and the environment.
Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves
Authors: Focosi Daniele , Quiroga Rodrigo , McConnell Scott A. , Johnson Marc C , Casadevall Arturo 
Published: December 2022

AbstractThe first 2 years of the COVID-19 pandemic were mainly characterized by convergent evolution of mutations of SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 across different variants of concern (Alpha, Beta, Gamma, and Delta). Since Spring 2022 and the third year of the pandemic, with the advent of Omicron and its sublineages, convergent evolution has led to the observation of different lineages acquiring an additional group of mutations at different amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, and S494. Mutations at these residues have become increasingly prevalent during Summer and Autumn 2022, with combinations showing increased fitness. The most likely reason for this convergence is the selective pressure exerted by previous infection- or vaccine-elicited immunity. Such accelerated evolution has caused failure of all anti-Spike monoclonal antibodies, including bebtelovimab and cilgavimab. While we are learning how fast coronaviruses can mutate and recombine, we should reconsider opportunities for economically sustainable escape-proof combination therapies, and refocus antibody-mediated therapeutic efforts on polyclonal preparations that are less likely to allow for viral immune escape.
Superiority of intranasal over systemic administration of bioengineered soluble ACE2 for survival and brain protection against SARS-CoV-2 infection
Authors: Hassler Luise , Wysocki Jan , Ahrendsen Jared T. , Ye Minghao , Gelarden Ian , Nicolaescu Vlad , Tomatsidou Anastasia , Gula Haley , Cianfarini Cosimo , Khurram Nigar , Kanwar Yashpal , Singer Benjamin D. , Randall Glenn , Missiakas Dominique , Henkin Jack , Batlle Daniel 
Published: December 2022

ABSTRACTThe present study was designed to investigate the effects of a soluble ACE2 protein termed ACE2 618-DDC-ABD, bioengineered to have long duration of action and high binding affinity to SARS-CoV-2, when administered either intranasally (IN) or intraperitoneally (IP) and before or after SARS-CoV-2 inoculation.K18hACE2 mice permissive for SARS-CoV-2 infection were inoculated with 2×104PFU wildtype SARS-CoV-2. In one protocol, ACE2 618-DDC-ABD was given either IN or IP, pre- and post-viral inoculation. In a second protocol, ACE2 618-DDC-ABD was given either IN, IP or IN+IP but only post-viral inoculation. In addition, A549 and Vero E6 cells were used to test neutralization of SARS-CoV-2 variants by ACE2 618-DDC-ABD at different concentrations.Survival by day 5 was 0% in infected untreated mice, and 40% in mice from the ACE2 618-DDC-ABD IP-pre treated group. By contrast, in the IN-pre group survival was 90%, histopathology of brain and kidney was essentially normal and markedly improved in the lungs. When ACE2 618-DDC-ABD was administered only post viral inoculation, survival was 30% in the IN+IP group, 20% in the IN and 0% in the IP group. Brain SARS-CoV-2 titers were high in all groups except for the IN-pre group where titers were undetectable in all mice. In cells permissive for SARS-CoV-2 infection, ACE2 618-DDC-ABD neutralized wildtype SARS-CoV-2 at high concentrations, whereas much lower concentrations neutralized omicron BA. 1.We conclude that ACE2 618-DDC-ABD provides much better survival and organ protection when administered intranasally than when given systemically or after viral inoculation and that lowering brain titers is a critical determinant of survival and organ protection.
Structural basis for CaVα2δ:gabapentin binding
Authors: Chen Zhou , Mondal Abhisek , Minor Daniel L. 
Published: December 2022

AbstractGabapentinoid drugs for pain and anxiety act on the CaVα2δ-1 and CaVα2δ-2 subunits of high-voltage activated calcium channels (CaV1s and CaV2s). Here, we present the cryo-EM structure of the gabapentin-bound brain and cardiac CaV1.2/CaVβ3/CaVα2δ-1 channel. The data reveal a binding pocket in the CaVα2δ-1 dCache1 domain that completely encapsulates gabapentin and define CaVα2δ isoform sequence variations that explain gabapentin binding selectivity of CaVα2δ-1 and CaVα2δ-2.
Characterization of adult human skeletal cells in different tissues reveals a CD90+CD34+ periosteal stem cell population
Authors: Cao Ye , Bolam Scott M. , Boss Anna L. , Murray Helen C. , Dalbeth Nicola , Brooks Anna E.S. , Matthews Brya G. 
Published: December 2022

AbstractSkeletal stem and progenitor cells are critical for bone homeostasis and healing, but their identity and diversity in humans are not well understood. In this study, we compared stromal populations in matched tissues from the femoral head and neck of 21 human participants using spectral flow cytometry of freshly isolated cells. High-level analysis indicated significant differences in marker distribution between periosteum, articular cartilage, endosteum and bone marrow stromal populations, and identified populations that were highly enriched or unique to specific tissues. Periosteum-enriched markers included CD90 and CD34. Articular cartilage, which has very poor regenerative potential, showed enrichment of multiple markers, including the PDPN+CD73+CD164+ population previously reported to represent human skeletal stem cells. We further characterized periosteal populations by combining CD90 with other strongly expressed markers. CD90+CD34+ cells sorted directly from periosteum showed significant colony-forming unit fibroblasts (CFU-F) enrichment, rapid expansion, and consistent multi-lineage differentiation of clonal populations. In situ, CD90+CD34+ cells include a perivascular population in the outer layer of the periosteum and non-perivascular cells closer to the bone surface. In conclusion, our study indicates considerable diversity in the stromal cell populations in different tissue compartments within the adult human skeleton, and suggests that periosteal stem cells reside within the CD90+CD34+ population.
Spontaneous and multifaceted ATP release from astrocytes at the scale of hundreds of synapses
Authors: Hatashita Yoshiki , Wu Zhaofa , Fujita Hirotaka , Kumamoto Takuma , Livet Jean , Li Yulong , Tanifuji Manabu , Inoue Takafumi 
Published: December 2022

AbstractAstrocytes participate in information processing by releasing neuroactive substances termed gliotransmitters, including ATP. Individual astrocytes come into contact with thousands of synapses with their ramified structure, but the spatiotemporal dynamics of ATP gliotransmission remain unclear, especially in physiological brain tissue. Using a genetically encoded fluorescent sensor, GRABATP1.0, we discovered that extracellular ATP increased locally and transiently in absence of stimuli in neuron-glia co-cultures, cortical slices, and the anesthetized mouse brain. Spontaneous ATP release events were tetrodotoxin-insensitive but suppressed by gliotoxin, fluorocitrate, and typically spread over 50–250 μm2area at concentrations capable of activating purinergic receptors. Besides, most ATP events did not coincide with Ca2+transients. Clustering analysis revealed that these events followed multiple distinct kinetics, and blockade of exocytosis only decreased a minor group of slow events. Overall, astrocytes spontaneously release ATP through multiple mechanisms, mainly in non-vesicular and Ca2+-independent manners, thus potentially regulating hundreds of synapses all together.
Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant
Authors: Ito Jumpei , Suzuki Rigel , Uriu Keiya , Itakura Yukari , Zahradnik Jiri , Deguchi Sayaka , Wang Lei , Lytras Spyros , Tamura Tomokazu , Kida Izumi , Nasser Hesham , Shofa Maya , Begum MST Monira , Tsuda Masumi , Oda Yoshitaka , Fujita Shigeru , Yoshimatsu Kumiko , Ito Hayato , Nao Naganori , Asakura Hiroyuki , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa , Yamamoto Yuki , Nagamoto Tetsuharu , Schreiber Gideon ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Saito Akatsuki , Matsuno Keita , Takayama Kazuo , Tanaka Shinya , Fukuhara Takasuke , Ikeda Terumasa , Sato Kei 
Published: December 2022

AbstractIn late 2022, although the SARS-CoV-2 Omicron subvariants have highly diversified, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein. Here, we illuminated the evolutionary rules underlying the convergent evolution of Omicron subvariants and the properties of one of the latest lineages of concern, BQ.1.1. Our phylogenetic and epidemic dynamics analyses suggest that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. Particularly, BQ.1.1, which harbors all five convergent substitutions, shows the highest fitness among the viruses investigated. Neutralization assays show that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. The BQ.1.1 spike exhibits enhanced binding affinity to human ACE2 receptor and greater fusogenicity than the BA.5 spike. However, the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5. Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants.