bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread Cortical Thickness Reductions Following Non-medical Use of Ketamine: a Structural MRI Study of Individuals with Ketamine Dependence
Authors: Tang Jinsong , Wu Qiuxia , Qi Chang , Xie An , Liu Jianbin , Sun Yunkai , Yuan Tifei , Chen Wei , Liu Tieqiao , Hao Wei , Liao Yanhui 
Published: February 2021

AbstractBackgroundA version of ketamine, called Esketamine has been approved for treatment-resistant depression (TRD). Ketamine (“K powder”), a “dissociative” anesthetic agent, however, has been used non-medically alone or with other illicit substances. Our previous studies showed a link between non-medical ketamine use and brain structural and functional alterations. We found dorsal prefrontal gray matter reduction in chronic ketamine users. It is unknown, however, whether these observations might parallel findings of cortical thickness alterations. This study aimed at exploring cortical thickness abnormalities following non-medical, long-term use of ketamine.MethodsStructural brain images were acquired for 95 patients with ketamine dependence, and 169 drug-free healthy controls. FreeSurfer software was used to measure cortical thickness for 68 brain regions. Cortical thickness was compared between the two groups using analysis of covariance (ANCOVA) with covariates of age, gender, educational level, smoking, drinking, and whole brain mean cortical thickness. Results were considered significant if the Bonferroni corrected P-value < 0.01.ResultsCompared to healthy controls, patients with ketamine dependence have widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex, DLPFC) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed in ketamine users relative to comparison subjects. Estimated total lifetime ketamine consumption is correlated with the right inferior parietal and the right rostral middle frontal cortical thickness reductions.ConclusionsThis study provides first evidence that, compared with healthy controls, chronic ketamine users had cortical thickness reductions.
The Good, the Bad and the Stochastic: How Living in Groups Innately Supports Cooperation
Authors: Steiner Klaus F. 
Published: February 2021

AbstractBased on theoretical considerations and computer simulations, I show that living in groups brings advantages for cooperative traits through purely stochastic effects that result from the division of a population into groups. These advantages can be sufficient to compensate individual selection pressures that may be associated with the cooperative traits. In more complex agent-based simulation models, this effect combined with some migration between the groups leads to stable dynamic equilibria between cooperative and defective replicators in the population.
Excess Serum Interleukin-18 Distinguishes Patients with Pathogenic Mutations in PSTPIP1
Authors: Stone Deborah L. , Ombrello Amanda , Arostegui Juan I. , Schneider Corinne , Jesus Adriana de , Girard-Guyonvarc’h Charlotte , Gabay Cem , Lee Wonyong , Chae Jae Jin , Aksentijevich Ivona , Goldbach-Mansky Raphaela , Kastner Daniel L. , Canna Scott W. 
Published: February 2021

ABSTRACTObjectiveDominantly-inherited mutations in PSTPIP1 cause a family of monogenic autoinflammatory diseases epitomized by Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA) syndrome. The connections between PSTPIP1 and PAPA are poorly understood, although in vitro evidence suggests increased activation of the pyrin-inflammasome. We sought to identify biomarkers of potential mechanistic, diagnostic, and therapeutic utility specific to autoinflammatory diseases.MethodsClinical and genetic data and sera were obtained from patients referred with concern for PAPA syndrome, as well as relevant disease controls. Serum Interleukin-18 (IL-18) and related biomarkers were assessed by bead-based assay.ResultsSymptoms in PSTPIP1 mutation-positive PAPA patients overlapped with those of mutation-negative PAPA-like patients, but the former were younger at onset and had more arthritis. We found uniform elevation of total IL-18 in PAPA patients at a level approaching NLRC4-associated Macrophage Activation Syndrome (MAS) and well beyond Familial Mediterranean Fever. IL-18 elevation in PAPA patients’ sera persisted despite fluctuations in disease activity. IL-18 Binding Protein (IL-18BP) was modestly elevated, and as such PAPA patients had detectable free IL-18. PAPA patients did not develop MAS, and CXCL9 (an indicator of Interferon-gamma activity) was rarely elevated in their sera.ConclusionPAPA syndrome is a refractory, and often disabling monogenic autoinflammatory disease associated with chronic elevation of serum IL-18, but not risk for MAS. This finding instructs our understanding of the origins of excess IL-18, its potential spectrum of pathogenic effects, and the possible role for IL-18 blockade in refractory PAPA syndrome.
Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression
Authors: Martin Joanna , Asjadi Kimiya , Hubbard Leon , Kendall Kimberley , Pardiñas Antonio F. , Jermy Bradley , Lewis Cathryn M. , Baune Bernhard T. , Boomsma Dorret I. , Hamilton Steven P. , Lucae Susanne , Magnusson Patrik K. , Martin Nicholas G. , McIntosh Andrew M. , Mehta Divya , Mors Ole , Mullins Niamh , Penninx Brenda W. J. H. , Preisig Martin , Rietschel Marcella ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Jones Ian , Walters James T. R. , Rice Frances , Thapar Anita , O’Donovan Michael 
Published: February 2021

AbstractAnxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset.We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N=4,178, 65.5% female; mean age=41.5 years; N=1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age=45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets.In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD.These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.
Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19
Authors: Ortega Natalia , Ribes Marta , Vidal Marta , Rubio Rocío , Aguilar Ruth , Williams Sarah , Barrios Diana , Alonso Selena , Hernández-Luis Pablo , Mitchell Robert A. , Jairoce Chenjerai , Cruz Angeline , Jimenez Alfons , Santano Rebeca , Méndez Susana , Lamoglia Montserrat , Rosell Neus , Llupià Anna , Puyol Laura , Chi Jordi , Rodrigo Melero Natalia , Parras Daniel , Serra Pau , Pradenas Edwards , Trinité Benjamin , Blanco Julià , Mayor Alfredo , Barroso Sonia , Varela Pilar , Vilella Anna , Trilla Antoni , Santamaria Pere , Carolis Carlo , Tortajada Marta , Izquierdo Luis , Angulo Ana , Engel Pablo , García-Basteiro Alberto L. , Moncunill Gemma , Dobaño Carlota 
Published: February 2021

AbstractUnraveling the long-term kinetics of antibodies to SARS-CoV-2 and its determinants, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E,NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed-up for 6 months (N = 578). Seroprevalence increased over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, were stable over time, except IgG to nucleocapsid antigen and IgM levels that waned. After the peak response, anti-spike antibody levels increased from ∼150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. Pre-existing antibodies to alpha-HCoV were lower in individuals who subsequently seroconverted for SARS-CoV-2. IgG and IgA to HCoV were significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Modelling the Impact of Delaying Vaccination Against SARS-CoV-2 Assuming Unlimited Vaccines Supply
Authors: Amaku Marcos , Covas Dimas Tadeu , Bezerra Coutinho Francisco Antonio , Azevedo Raymundo Soares , Massad Eduardo 
Published: February 2021

AbstractBackgroundAt the moment we have more than 109 million cases and 2.4 million deaths around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far.MethodsWe propose a new mathematical model to estimate the impact of vaccination delay against COVID-19 on the number of cases and deaths by the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations.ResultsThe model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths until the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, that for each month of delay the number of deaths increases monotonically in a logarithm fashion, for both the State of Sao Paulo and Brazil as a whole.ConclusionsOur model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.
Lower respiratory tract sampling via bronchoscopy in COVID-19 ARDS: A focus on microbiology, cellular morphology, cytology and management impact
Authors: Bansal Sameer , Kalpakam Hariprasad , Kumar Ashwin , Thorbole Anmol , Varsha Amogha , Mehta Ravindra M 
Published: February 2021

AbstractBackgroundLower respiratory tract (LRT) sampling via bronchoscopy has been done sparingly in COVID-19 ARDS due to the high aerosol risk for the health care workers (HCW). Valuable information can be gained by detailed evaluation of bronchoscopic LRT samples.MethodsLRT samples were obtained by bedside bronchoscopy performed in suspected or confirmed severe COVID-19 ARDS patients on mechanical ventilation. Only positive cases were included in the study. Microbiological, cellular and cytological studies including LRT COVID-19 RT-PCR were performed and analysed.Results100 samples were collected from 63 patients, 53 were males (84%). 43 patients (68%) had at least 1 comorbidity. 55% cases had secondary bacterial infection as demonstrated by positive culture. Most of these infections were due to multi-drug resistant organisms (94.5%). The most common organisms were Klebsiella pneumoniae and Acinetobacter baumanii in 56.3% and 14.5% cases respectively. Fungal superinfection was observed in 9 patients (14.3%). Bronchoscopy helped confirm COVID-19 diagnosis in 1 patient and helped rule out COVID-19 in 3 patients who were eventually excluded from the study. The median BAL fluid (BALF) WBC count was 953 (IQR; 400-2717), with mean neutrophil count 85.2% (±13.9), and mean lymphocyte count 14.8% (±13.9). Repeat sampling done in some patients showed a progressive increase in the total WBC count in BALF, an increase in neutrophil percentage, and a higher chance of isolating an organism on the culture (81% repeat procedures were culture positive). The rate of super-infection increased with longer duration of illness. Patients with superinfection also had an increased WBC count (1001 vs 400), and lower lymphocyte percentage (19% vs 12% - OR - 6.8 [95%CI −14.3 − 0.7]). Bronchoscopic LRT sampling contributed significantly to modifying antibiotic coverage and discontinuing steroids in 37% cases.ConclusionThis study describes a detailed analysis of bronchoscopic LRT sampling in critically ill COVID-19 patients. This provided important basic and applied information augmenting disease understanding and contributing to clinical management when there was scant information available in the pandemic.
Vaccination efforts in Brazil: scenarios and perspectives under a mathematical modeling approach
Authors: Vilches Thomas Nogueira , Rubio Felipe Alves , Forti Perroni Rafael Augusto , de Almeida Gabriel Berg , Branco Fortaleza Carlos Magno Castelo , Ferreira Cláudia Pio 
Published: February 2021

AbstractAn agent-based model is proposed to access the impact of vaccination strategies to halt the COVID-19 spread. The model is parameterized using data from São Paulo State, Brazil. It was considered the two vaccines that are already approved for emergency use in Brazil, the CoronaVac vaccine developed by the Chinese bio-pharmaceutical company Sinovac and the Oxford-AstraZeneca vaccine (ChadOx1) developed by Oxford University and the British laboratory AstraZeneca. Both of them are two-dose schemes, but the efficacy and the interval between doses are different. We found that even in the worst scenario, in which the vaccine does not prevent infection either severe symptoms, the number of deaths decreases from 122 to 99 for CoronaVac application and to 80 for ChadOx1 administration. The same patterns have been seen in hospitalizations. Nevertheless, we show that when a low risk perception occurs, the reduction values decrease between 2% to 4%. Moreover, the increase of disease prevalence also jeopardizes immunization, showing the importance of the mitigation measures maintenance. On the other hand, doubling the vaccination rate would be able to significantly decrease the disease outcomes, reducing deaths by up to 74.4%. In conclusion, vaccination, along with non-pharmaceutical measures, is key to the control of COVID-19 in Brazil.
COVID-19 Spreading Dynamics in an Age-Structured Population with Selective Relaxation of Restrictions for Vaccinated Individuals : a Mathematical Modeling Study
Authors: Shayak B , Sharma Mohit M , Mishra Anand K 
Published: February 2021

AbstractBackgroundCOVID-19 vaccination of healthcare and other essential workers is underway in many countries while immunization of the general public is expected to begin in the next several weeks. We consider the question of whether people who have received the vaccine can be selectively and immediately permitted to return to normal activities.MethodsWe use a delay differential equation model to calculate the effects of vaccinee “immunity passports” on the epidemic spreading trajectories. The model incorporates age-structuring to account for children who are ineligible for vaccination, and senior citizens who are especially vulnerable to the disease. We consider consensus strains of virus as well as high-transmissibility variants such as B1.1.7 and B1.351 in our analysis.ResultsWe find that with high vaccine efficacy of 80 percent or greater, unrestricted vaccinee—vaccinee interactions do not derail the epidemic from a path towards elimination. Vaccinee—non-vaccinee interactions should however be treated with far more caution. At current vaccine administration rates, it may be the better part of a year before COVID-19 transmission is significantly reduced or ceased. With lower vaccine efficacy of approximately 60 percent, restrictions for vaccinees may need to remain in place until the elimination of the disease is achieved. In all cases, the death tolls can be reduced by vaccinating the vulnerable population first.ConclusionsDesigning high-efficacy vaccines with easily scalable manufacturing and distribution capacity should remain on the priority list in academic as well as industrial circles. Performance of all vaccines should continue to be monitored in real time during vaccination drives with a view to analysing socio-demographic determinants of efficacy, if any, and optimizing distribution accordingly. A speedy and efficacious vaccination drive augmented with selective relaxations for vaccinees will provide the smoothest path out of the pandemic with the least additional caseloads, death tolls and socio-economic cost.
An evolutionarily conserved coreceptor gene is essential for CLAVATA signaling inMarchantia polymorpha
Authors: Takahashi Go , Betsuyaku Shigeyuki , Okuzumi Natsuki , Kiyosue Tomohiro , Hirakawa Yuki 
Published: February 2021

AbstractGrowth and development of land plants are controlled by CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) family of peptide hormones. In contrast to the genetic diversity of CLE family in flowering plants, the liverwortMarchantia polymorphapossesses a minimal set of CLE, MpCLE1(TDIF homolog) and MpCLE2 (CLV3 homolog). MpCLE1 and MpCLE2 peptides exert distinct function at the apical meristem ofM. polymorphagametophyte via specific receptors, MpTDIF RECEPTOR (MpTDR) and MpCLAVATA1 (MpCLV1), respectively, both belonging to the subclass XI of leucine-rich repeat receptor-like kinases (LRR-RLKs). Biochemical and genetic studies in Arabidopsis have shown that TDR/PXY family and CLV1/BAM family recognize the CLE peptide ligand in a heterodimeric complex with a member of subclass-II coreceptors. Here we show that three LRR-RLK genes ofM. polymorphaare classified into subclass II, representing three distinct subgroups evolutionarily conserved in land plants. To address the involvement of subclass-II coreceptors inM. polymorphaCLE signaling, we performed molecular genetic analysis on one of them, MpCLAVATA3 INSENSITIVE RECEPTOR KINASE(MpCIK). Two knockout alleles for MpCIKformed narrow apical meristems marked bypromMpYUC2:GUSmarker, which were not expanded by MpCLE2 peptide treatment, phenocopying Mpclv1. Loss of sensitivity to MpCLE2 peptide was also observed in gemma cup formation in both Mpclv1and Mpcik. Biochemical analysis using aNicotiana benthamianatransient expression system revealed weak association between MpCIK and MpCLV1, as well as MpCIK and MpTDR. While MpCIK may also participate in MpCLE1 signaling, our data show that the conserved CLV3-CLV1-CIK module functions inM. polymorpha, controlling meristem activity for development and organ formation for asexual reproduction.
A Comprehensive Phylogenomic Platform for Exploring the Angiosperm Tree of Life
Authors: Baker William J. , Bailey Paul , Barber Vanessa , Barker Abigail , Bellot Sidonie , Bishop David , Botigué Laura R. , Brewer Grace , Carruthers Tom , Clarkson James J. , Cook Jeffrey , Cowan Robyn S. , Dodsworth Steven , Epitawalage Niroshini , Françoso Elaine , Gallego Berta , Johnson Matthew G. , Kim Jan T. , Leempoel Kevin , Maurin Olivier , McGinnie Catherine , Pokorny Lisa , Roy Shyamali , Stone Malcolm , Toledo Eduardo , Wickett Norman J. , Zuntini Alexandre R. , Eiserhardt Wolf L. , Kersey Paul J. , Leitch Ilia J. , Forest Félix 
Published: February 2021

AbstractThe tree of life is the fundamental biological roadmap for navigating the evolution and properties of life on Earth, and yet remains largely unknown. Even angiosperms (flowering plants) are fraught with data gaps, despite their critical role in sustaining terrestrial life. Today, high-throughput sequencing promises to significantly deepen our understanding of evolutionary relationships. Here, we describe a comprehensive phylogenomic platform for exploring the angiosperm tree of life, comprising a set of open tools and data based on the 353 nuclear genes targeted by the universal Angiosperms353 sequence capture probes. This paper (i) documents our methods, (ii) describes our first data release and (iii) presents a novel open data portal, the Kew Tree of Life Explorer (https://treeoflife.kew.org). We aim to generate novel target sequence capture data for all genera of flowering plants, exploiting natural history collections such as herbarium specimens, and augment it with mined public data. Our first data release, described here, is the most extensive nuclear phylogenomic dataset for angiosperms to date, comprising 3,099 samples validated by DNA barcode and phylogenetic tests, representing all 64 orders, 404 families (96%) and 2,333 genera (17%). Using the multi-species coalescent, we inferred a “first pass” angiosperm tree of life from the data, which totalled 824,878 sequences, 489,086,049 base pairs, and 532,260 alignment columns. The tree is strongly supported and highly congruent with existing taxonomy, while challenging numerous hypothesized relationships among orders and placing many genera for the first time. The validated dataset, species tree and all intermediates are openly accessible via the Kew Tree of Life Explorer. This major milestone towards a complete tree of life for all flowering plant species opens doors to a highly integrated future for angiosperm phylogenomics through the systematic sequencing of standardised nuclear markers. Our approach has the potential to serve as a much-needed bridge between the growing movement to sequence the genomes of all life on Earth and the vast phylogenomic potential of the world’s natural history collections.