bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional geometry of auditory cortical resting state networks derived from intracranial electrophysiology
Authors: Banks Matthew I. , Krause Bryan M. , Berger D. Graham , Campbell Declan I. , Boes Aaron D. , Bruss Joel E. , Kovach Christopher K. , Kawasaki Hiroto , Steinschneider Mitchell , Nourski Kirill V. 
Published: February 2022

AbstractUnderstanding central auditory processing critically depends on defining underlying auditory cortical networks and their relationship to the rest of the brain. We addressed these questions using resting state functional connectivity derived from human intracranial electroencephalography. Mapping recording sites into a low-dimensional space where proximity represents functional similarity revealed a hierarchical organization. At fine scale, a group of auditory cortical regions excluded several higher order auditory areas and segregated maximally from prefrontal cortex. On mesoscale, the proximity of limbic structures to auditory cortex suggested a limbic stream that parallels the classically described ventral and dorsal auditory processing streams. Identities of global hubs in anterior temporal and cingulate cortex depended on frequency band, consistent with diverse roles in semantic and cognitive processing. On a macro scale, observed hemispheric asymmetries were not specific for speech and language networks. This approach can be applied to multivariate brain data with respect to development, behavior, and disorders.BlurbWe describe the organization of human neocortex on multiple spatial scalesbased on resting state intracranial electrophysiology. We focus on cortical regions involved in auditory processing and examine inter-regional hierarchical relationships, network topology, and hemispheric lateralization. This work introduces a powerful analytical tool to examine mechanisms of altered arousal states, brain development, and neuropsychiatric disorders.
Coupling comprehensive pesticide-wide association study to iPSC dopaminergic screening identifies and classifies Parkinson-relevant pesticides
Authors: Paul Kimberly C , Krolewski Richard C , Moreno Edinson Lucumi , Blank Jack , Holton Kris , Ahfeldt Tim , Furlong Melissa , Yu Yu , Cockburn Myles , Thompson Laura K , Bronstein Jeff , Rubin Lee L. , Khurana Vikram , Ritz Beate 
Published: February 2022

ABSTRACTParkinson’s disease (PD) is a complex, multi-factorial neurodegenerative disease, known to involve genetic, aging-related components, but also to be highly sensitive to environmental factors. In particular, ample evidence links pesticides to PD etiology. Here, establishing a field-to-bench paradigm, we have combined record-based exposure assessment in a population-based epidemiologic study of PD with testing in dopaminergic neurons produced from iPSCs to further identify and classify PD-relevant pesticides. First, agricultural pesticide-application records in California enabled us to investigate exposure to nearly 300 specific pesticides and PD risk in a comprehensive, pesticide-wide association study (PWAS). We implicated long-term exposure to 53 pesticide active ingredients in PD risk and identified their relevant co-exposure profiles. Second, to identify which of these pesticides might contribute to PD through direct effects on dopaminergic neurons, we employed a live-cell imaging screening paradigm in which neurons, definitively identified with a tyrosine hydroxylase reporter, were exposed to 43 of the high-risk pesticides. Using detailed morphometric measures, we found 10 pesticides were directly toxic to these neurons. Further, we analyzed pesticides typically used in combinations in cotton farming. Among these “cotton cluster” pesticides, co-exposures resulted in markedly greater toxicity than any single pesticide. Trifluralin was a pivotal driver of toxicity to dopaminergic neurons and led to marked mitochondrial dysfunction. Our field-to-bench paradigm may prove useful to mechanistically dissect pesticide exposure implicated in PD risk, and guide agricultural policy in the future.
A potent SARS-CoV-2 neutralizing antibody recognizing a conserved epitope with broad mutant variant and SARS-CoV activity
Authors: Pelzek Adam J. , Ebtehaj Sanam , Lulo James , Zhang Lucy , Balduf Olivia , Dolan Lindsay , Zhang Chaohua , Wan Shengqin , An Gang , Kankam Awo , Chan Eugene , Murphy Shaun P. 
Published: February 2022

AbstractCOVID-19 is the deadliest respiratory virus pandemic since 1918 and the latest of several coronavirus epidemics and pandemics in recent years. Despite the unprecedented response by both the government and private sectors to develop vaccines and therapies, the evolution of SARS-CoV-2 variants resistant to these interventions reveals a crucial need for therapeutics that maintain their efficacy against current and future mutant variants. Here we describe a SARS-CoV-2 neutralizing antibody, ABP-310, with potent activity against all variants tested including the Omicron variant. ABP-310 also displays potent neutralizing activity against SARS-CoV, highlighting the conserved nature of the ABP-310 epitope. By targeting a conserved epitope, we believe that ABP-310 has therapeutic promise not only against the current SARS-CoV-2 variants but would be expected to maintain efficacy against future variants and possibly even novel coronaviruses.
Rapid, High-Throughput, Cost Effective Whole Genome Sequencing of SARS-CoV-2 Using a Condensed One Hour Library Preparation of the Illumina DNA Prep Kit
Authors: Hickman Rebecca , Nguyen Jason , Lee Tracy D. , Tyson John R. , Azana Robert , Tsang Frankie , Hoang Linda , Prystajecky Natalie 
Published: February 2022

ABSTRACTThe ongoing COVID-19 pandemic necessitates cost-effective, high-throughput, and timely genomic sequencing of SARS-CoV-2 viruses for outbreak investigations, identifying variants of concern (VoC), characterizing vaccine breakthrough infections, and public health surveillance. Additionally, the enormous demand of genomic sequencing on supply chains and the resulting shortages of laboratory supplies necessitate the use of low-reagent and low-consumable methods. Here, we report an optimized library preparation method where the same protocol can be used in a STAT scenario, from sample to sequencer in as little as eight hours, and a high-throughput scenario, where one technologist can perform 576 library preparations over the course of one 8-hour shift. This new method uses Freed et al.’s 1200 bp primer sets (Biol Methods Protoc 5:bpaa014, 2020, https://doi.org/10.1093/biomethods/bpaa014) and a modified and truncated Illumina DNA Prep workflow (Illumina, CA, USA). Compared to the original, application of this new method in hundreds of clinical specimens demonstrated equivalent results to the full-length DNA Prep workflow at 45% the cost, 15% of consumables required (such as pipet tips), 25% of manual hands-on time, and 15% of on-instrument time if performing on a liquid handler, with no compromise in sequence quality. Results suggest that this new method is a rapid, simple, cost-effective, and high-quality SARS-CoV-2 whole genome sequencing protocol.
Disentangling “Bayesian brain” theories of autism spectrum disorder
Authors: Schneebeli Maya , Haker Helene , Rüesch Annia , Zahnd Nicole , Marino Stephanie , Paolini Gina , Iglesias Sandra , Petzschner Frederike H. , Stephan Klaas Enno 
Published: February 2022

AbstractBackgroundBayesian theories of perception have provided a variety of alternative mechanistic explanations for autistic symptoms, including (1) overprecise sensations, (2) imprecise priors, (3) inflexible priors, and (4) altered hierarchical learning. Here, we designed a set of experiments to systematically test predictions from each of the four hypotheses in individuals with autism spectrum disorder (ASD).MethodsTwo versions of a two-alternative forced-choice (2AFC) random dot motion task were developed to disentangle the influence of sensory inputs and prior expectations and test implications of the four Bayesian hypotheses. Using a cross-sectional observational study design, behavioural data were obtained from participants with autism spectrum disorder (N=47) and a control group (N=50). Analyses used mixed effects models and a drift diffusion model.ResultsContrary to the sensory overprecision hypothesis, individuals with ASD did not differ from controls in performance or parameter estimates during the perceptual 2AFC task. When adding cues to the task, individuals with ASD profited less from this prior information than controls, as predicted by the imprecise prior hypothesis. However, individuals with ASD were still able to update their initial priors, contradicting the inflexible prior hypothesis. Finally, in line with the hierarchical learning hypothesis, volatility differentially modulated expectation effects, exerting a significantly smaller effect in the ASD group compared to the control group.ConclusionOur findings support two mutually compatible alterations of perception in ASD (imprecise priors and, to a lesser degree, altered hierarchical learning). By contrast, they are not compatible with the notions of sensory overprecision and inflexible priors.
Effectiveness of Covid-19 Vaccines against the SARS-COV-2-Delta (B.1.617.2) in China-A Real World Study
Authors: Ma Xinge , Han Jianfeng , Li Hongxia , Liu Chang 
Published: February 2022

AbstractsBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta (B.1.617.2) variant is highly transmissible and has contributed to a surge in cases globally. This study aimed to explore the potential of vaccines against SARS-CoV-2 delta (B.1.617.2) variant in China.MethodsIn this real-world study, all data were extracted from Xi’an Chest Hospital. Confirmed cases infected with Delta VOC with exact date of positive viral testing were included for analysis. Patients meeting the study criteria were divided into unvaccinated and partially vaccinated (one dose), full vaccinated (two doses), and booster vaccination of COVID-19.ResultsA total of 455 cases were enrolled in this study. Proportion of severe and critical cases in full vaccinated cases (1.82%) and cases with booster vaccination (1.35%) of COVID-19 were much lower than that of unvaccinated and partially vaccinated cases (8.16%). In addition, cases with booster vaccination (12.78 days) and full vaccinated cases (12.59 days) showed shorter duration of viral shedding than that in unvaccinated and partially vaccinated cases (13.87 days).ConclusionThis is the first real world study indicating that Covid-19 vaccines showed much powerful effectiveness against the SARS-COV-2-Delta (B.1.617.2) in China, including lowing the proportion of severe illness and shorting the virus shedding time.
Duration of protection of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 Omicron infection in Qatar
Authors: Chemaitelly Hiam , Ayoub Houssein H. , AlMukdad Sawsan , Tang Patrick , Hasan Mohammad R. , Yassine Hadi M. , Khatib Hebah A. Al , Smatti Maria K. , Coyle Peter , Kanaani Zaina Al , Kuwari Einas Al , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Rahim Hanan F. Abdul , Nasrallah Gheyath K. , Al Kuwari Mohamed Ghaith , Butt Adeel A. , Romaihi Hamad Eid Al , Al-Thani Mohamed H. , Khal Abdullatif Al , Bertollini Roberto , Abu-Raddad Laith J. 
Published: February 2022

AbstractBACKGROUNDQatar has been experiencing a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021. We assessed duration of protection of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines after second dose and after third/booster dose against symptomatic Omicron infection and against COVID-19 hospitalization and death, between December 23, 2021 and February 2, 2022.METHODSVaccine effectiveness was estimated using the test-negative, case-control study design, applying the same methodology used earlier to assess waning of BNT162b2 and mRNA-1273 effectiveness in the same population during earlier infection waves.RESULTSBNT162b2 effectiveness against symptomatic Omicron infection was highest at 61.9% (95% CI: 49.9-71.1%) in the first month after the second dose, but then gradually declined and was at 10% or less starting from the 5th month after the second dose. After the booster, effectiveness rapidly rebounded to peak at about 55% between 2-5 weeks after the booster, but then started to decline again thereafter. Effectiveness against severe, critical, or fatal COVID-19 was maintained at >70% after the second dose and at >90% after the booster with no evidence for declining effectiveness over time. mRNA-1273 effectiveness against symptomatic Omicron infection was highest at 44.8% (95% CI: 16.0-63.8%) in the first three months after the second dose, before gradually declining to negligible levels thereafter. After the booster, effectiveness rapidly rebounded to peak at about 55% between 2-5 weeks after the booster, but then declined again thereafter. Effectiveness against severe, critical, or fatal COVID-19 was high at >60% after the second dose and at >80% after the booster, but the confidence intervals were wide owing to the small number of cases.CONCLUSIONSBNT162b2 and mRNA-1273 vaccines show a similar level and pattern of protection against symptomatic Omicron infection. Protection against Omicron is lower than that against Alpha, Beta, and Delta variants, and wanes more rapidly than against earlier variants after the second and booster doses. Meanwhile, protection against hospitalization and death appears robust and durable after both the second and booster doses.
Dopaminergic medication increases motivation to exert cognitive control by reducing subjective effort costs in Parkinson’s patients
Authors: Bogdanov Mario , LoParco Sophia , Otto A. Ross , Sharp Madeleine 
Published: February 2022

AbstractEngaging in demanding mental activities requires the allocation of cognitive control, which can be effortful and aversive. Individuals thus tend to avoid exerting cognitive effort if less demanding behavioral options are available. Recent accounts propose a key role for dopamine in motivating behavior by increasing the sensitivity to rewards associated with effort exertion. Whether dopamine additionally plays a specific role in modulating the sensitivity to the costs of cognitive effort, even in the absence of any incentives, is much less clear. To address this question, we assessed cognitive effort avoidance in patients (n = 38) with Parkinson’s disease, a condition characterized by loss of midbrain dopaminergic neurons, both ON and OFF dopaminergic medication and compared them to healthy controls (n = 24). Effort avoidance was assessed using the Demand Selection Task (DST), in which participants could freely choose between performing a high-demand or a low-demand version of a task-switching paradigm. Critically, participants were not offered any incentives to choose the more effortful option, nor for good performance. Healthy controls and patients OFF their dopaminergic medications preferred the low-demand option, in keeping with the tendency to avoid effort on this task previously demonstrated in young adults. In contrast, patients ON dopaminergic medications displayed significantly less effort avoidance than when they were OFF medications. This change in preference could not be explained by differences in task-switching performance or the patients’ ability to detect the different levels of cognitive demand in the DST. Our findings provide evidence that dopamine replacement in Parkinson’s patients increases the willingness to engage in cognitively demanding behavior, even in the absence of any clear benefits. These results suggest that dopamine plays a role in reducing the sensitivity to effort costs that is independent of its role in enhancing the sensitivity to the benefits of effort exertion.
Evaluation of a Rapid and Accessible RT-qPCR Approach for SARS-CoV-2 Variant of Concern Identification
Authors: Yeung Priscilla S.-W. , Wang Hannah , Sibai Mamdouh , Solis Daniel , Yamamoto Fumiko , Iwai Naomi , Jiang Becky , Hammond Nathan , Truong Bernadette , Bihon Selamawit , Santos Suzette , Mar Marilyn , Mai Claire , Mfuh Kenji O. , Miller Jacob A. , Huang ChunHong , Sahoo Malaya K. , Zehnder James L. , Pinsky Benjamin A. 
Published: February 2022

ABSTRACTThe ability to distinguish between SARS-CoV-2 variants of concern (VOCs) is of ongoing interest due to differences in transmissibility, response to vaccination, clinical prognosis, and therapy. Although detailed genetic characterization requires whole-genome sequencing (WGS), targeted nucleic acid amplification tests can serve a complementary role in clinical settings, as they are more rapid and accessible than sequencing in most laboratories.We designed and analytically validated a two-reaction multiplex reverse transcription quantitative PCR (RT-qPCR) assay targeting spike protein mutations L452R, E484K, and N501Y in Reaction 1, and del69-70, K417N, and T478K in Reaction 2. This assay had 95-100% agreement with WGS in 502 upper respiratory swabs collected between April 26 and August 1, 2021, consisting of 43 Alpha, 2 Beta, 20 Gamma, 378 Delta, and 59 non-VOC infections. Validation in a separate group of 230 WGS-confirmed Omicron variant samples collected in December 2021 and January 2022 demonstrated 100% agreement.This RT-qPCR-based approach can be implemented in clinical laboratories already performing SARS-CoV-2 nucleic acid amplification tests to assist in local epidemiological surveillance and clinical decision-making.
Antibody Evasion Properties of SARS-CoV-2 Omicron Sublineages
Authors: Iketani Sho , Liu Lihong , Guo Yicheng , Liu Liyuan , Huang Yiming , Wang Maple , Luo Yang , Yu Jian , Yin Michael T. , Sobieszczyk Magdalena E. , Huang Yaoxing , Wang Harris H. , Sheng Zizhang , Ho David D. 
Published: February 2022

AbstractThe identification of the Omicron variant (B.1.1.529.1 or BA.1) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in Botswana in November 20211 immediately raised alarms due to the sheer number of mutations in the spike glycoprotein that could lead to striking antibody evasion. We2 and others3–6 recently reported results in this Journal confirming such a concern. Continuing surveillance of Omicron evolution has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K mutation (BA.1+R346K) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike mutations while lacking 13 spike mutations found in BA.1. We therefore extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.12,3,5,6. These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K2–4,6. This new finding shows that no presently approved or authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant.
Transcriptome Mining Reveals a Spectrum of RNA Viruses in Primitive Plants
Authors: Mifsud Jonathon C.O. , Gallagher Rachael V. , Holmes Edward C. , Geoghegan Jemma L. 
Published: February 2022

AbstractCurrent knowledge of plant viruses stems largely from those affecting economically important plants. Yet, plant species in cultivation represent a small and bias subset of the plant kingdom. Here, we describe virus diversity and abundance from a survey of 1079 transcriptomes from species across the breadth of the plant kingdom (Archaeplastida) by analysing open-source data from the One Thousand Plant Transcriptomes Initiative (1KP). We identified 104 potentially novel viruses, of which 40% comprised single-stranded positive-sense RNA viruses across eight orders, including members of the Hepelivirales, Tymovirales, Cryppavirales, Martellivirales and Picornavirales. One-third of the newly described viruses comprised double-stranded RNA viruses from the orders Durnavirales and Ghabrivirales. The remaining were negative-sense RNA viruses from the Rhabdoviridae, Aspiviridae, Yueviridae, Phenuiviridae and the newly proposed Viridisbunyaviridae. Our analysis considerably expands the known host range of 13 virus families to include lower plants (e.g., Benyviridae and Secoviridae) and four virus families to include algae hosts (e.g., Tymoviridae and Chrysoviridae). The discovery of the first 30 kDa movement protein in a non-vascular plant, suggests that the acquisition of plant virus movement proteins occurred prior to the emergence of the plant vascular system. More broadly, however, a co-phylogeny analysis revealed that the evolutionary history of these families is largely driven by cross-species transmission events. Together, these data highlight that numerous RNA virus families are associated with older evolutionary plant lineages than previously thought and that the scarcity of RNA viruses found in lower plants to date likely reflects a lack of investigation rather than their absence.ImportanceOur knowledge of plant viruses is mainly limited to those infecting economically important host species. In particular, we know little about those viruses infecting primitive plant lineages such as the ferns, lycophytes, bryophytes and charophytes. To expand this understanding, we conducted a broad-scale viral survey of species across the breadth of the plant kingdom. We find that primitive plants harbour a wide diversity of RNA viruses including some that are sufficiently divergent to comprise a new virus family. The primitive plant virome we reveal offers key insights into the evolutionary history of core plant virus gene modules and genome segments. More broadly, this work emphasises that the scarcity of viruses found in these species to date likely reflects the absence of research in this area.
Optimal pathways control fixation of multiple mutations during cancer initiation
Authors: Teimouri Hamid , Spaulding Cade , Kolomeisky Anatoly B. 
Published: February 2022

AbstractCancer starts after initially healthy tissue cells accumulate several specific mutations or other genetic alterations. The dynamics of tumor formation is a very complex phenomenon due to multiple involved biochemical and biophysical processes. It leads to a very large number of possible pathways on the road to final fixation of all mutations that marks the beginning of the cancer, complicating the understanding of microscopic mechanisms of tumor formation. We present a new theoretical framework of analyzing the cancer initiation dynamics by exploring the properties of effective free-energy landscape of the process. It is argued that although there are many possible pathways for the fixation of all mutations in the system, there are only few dominating pathways on the road to tumor formation. The theoretical approach is explicitly tested in the system with only two mutations using analytical calculations and Monte Carlo computer simulations. Excellent agreement with theoretical predictions is found for a large range of parameters, supporting our hypothesis and allowing us to better understand the mechanisms of cancer initiation. Our theoretical approach clarifies some important aspects of microscopic processes that lead to tumor formation.