bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confusion will be my epitaph: Genome-scale discordance stifles phylogenetic resolution of Holothuroidea
Authors: Koch Nicolás Mongiardino , Tilic Ekin , Miller Allison K. , Stiller Josefin , Rouse Greg W. 
Published: December 2022

AbstractSea cucumbers (Holothuroidea) are a diverse clade of echinoderms found from intertidal waters to the bottom of the deepest trenches. Their reduced skeletons and limited number of phylogenetically-informative traits have long obfuscated morphological classifications. Sanger-sequenced molecular datasets have also failed to constrain the position of major lineages. Noteworthy, topological uncertainty has hindered a resolution for Neoholothuriida, a highly diverse clade of Permo-Triassic age. We perform the first phylogenomic analysis of Holothuroidea, combining existing datasets with twelve novel transcriptomes. Using a highly-curated dataset of 1,100 orthologues, our efforts recapitulate previous results, struggling to resolve interrelationships among neoholothuriid clades. Three approaches to phylogenetic reconstruction (concatenation under both site-homogeneous and site-heterogeneous models, and coalescent-aware inference) result in alternative resolutions, all of which are recovered with strong support, and across a range of datasets filtered for phylogenetic usefulness. We explore this intriguing result using gene-wise log-likelihood scores, and attempt to correlate these with a large set of gene properties. While presenting novel ways of exploring and visualizing support for alternative trees, we are unable to discover significant predictors of topological preference, and our efforts fail to favor one topology. Neoholothuriid genomes seem to retain an amalgam of signals derived from multiple phylogenetic histories.
Integrating defense and leaf economic spectrum traits in a tropical savanna plant
Authors: Mohanbabu Neha , Veldhuis Michiel P. , Jung Dana , Ritchie Mark E 
Published: December 2022

SummaryAllocation to plant defense traits likely depends on resource supply, herbivory, and other plant functional traits such as the leaf economic spectrum (LES) traits. Yet, attempts to integrate defense and resource acquisitive traits remains elusive.We assessed intraspecific correlations between different defense and LES traits in a widely distributed tropical savanna herb,Solanum incanum, a unique model species for studying allocations to physical, chemical, and structural defenses to mammalian herbivory.In a multivariate trait space, the structural defenses - lignin and cellulose - were positively related to the resource conservative traits - low SLA and low leaf N. Phenolic content, a chemical defense, was positively associated with resource acquisitive traits - high SLA and high leaf N - while also being associated with an independent third component axis. Both principal components 1 and 3 were not associated with resource supply and herbivory intensity. In contrast, spine density - a physical defense - was orthogonal to the LES axis and positively associated with soil P and herbivory intensity.Synthesis: These results suggest a hypothesized “pyramid” of trade-offs in allocation to defense along the LES and herbivory intensity axes. Therefore, future attempts to integrate defense traits with the broader plant functional trait framework needs a multifaceted approach that accounts for unique influences of resource acquisitive traits and herbivory intensity.
The Structural Layers of the Porcine Iris Exhibit Inherently Different Biomechanical Properties
Authors: Tan Royston K. Y. , Panda Satish K. , Braeu Fabian A. , Muralidharan Arumugam R. , Nongpiur Monisha E. , Chan Anita S. Y. , Aung Tin , Najjar Raymond P. , Girard Michaël J.A. 
Published: December 2022

AbstractPurposeTo isolate the structural components of theex vivoporcine iris tissue and to determine their biomechanical properties.MethodsThe porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n= 32) to evaluate for permeability using Darcy’s Law (ΔP= 2000 Pa,A= 0.0391 mm2), and both tissues underwent stress relaxation experiments (ε = 0.5 with initial ramp of δε = 0.1) to evaluate for their viscoelastic behaviours (n= 28). Viscoelasticity was characterised by the parametersβ(half width of the Gaussian distribution), τm(mean relaxation time constant),E0(instantaneous modulus) andE∞(equilibrium modulus).ResultsFor the stroma, the hydraulic permeability was 9.49 ± 3.05 × 10-6mm2/Pa·s, and the viscoelastic parameters wereβ= 2.50 ± 1.40, and τm= 7.43 ± 4.96 s, with the two moduli calculated to beE0= 14.14 ± 6.44 kPa andE∞= 6.08 ± 2.74 kPa. For the dilator tissue, the viscoelastic parameters wereβ= 2.06 ± 1.33 and τm= 1.28 ± 1.27 s, with the two moduli calculated to beE0= 9.16 ± 3.03 kPa andE∞= 5.54 ± 1.98 kPa.ConclusionWe have established a new protocol to evaluate the biomechanical properties of the structural layers of the iris. Overall, the stroma was permeable and exhibited smaller moduli than those of the dilator muscle. An improved characterisation of iris biomechanics may form the basis to further our understanding of angle closure glaucoma.
BCG vaccination of healthcare workers does not reduce SARS-CoV-2 infections nor infection severity or duration: a randomised placebo-controlled trial
Authors: Claus Juana , Doesschate Thijs ten , Gumbs Cheyenne , van Werkhoven Cornelis H. , van der Vaart Thomas W. , Janssen Axel B. , Smits Gaby , van Binnendijk Rob , van der Klis Fiona , van Baarle Debbie , Paganelli Fernanda L. , Leavis Helen , Verhagen Lilly M. , Joosten Simone A. , Bonten Marc J.M. , Netea Mihai G. , van de Wijgert Janneke H. H. M. 
Published: December 2022

AbstractBackgroundBacillus Calmette-Guerin (BCG) vaccination has been hypothesised to reduce SARS-CoV-2 infection, severity, and/or duration via trained immunity induction.MethodsHealthcare workers (HCWs) in 9 Dutch hospitals were randomised to BCG or placebo vaccination (1:1) in March/April 2020 and followed for one year. They reported daily symptoms, SARS-CoV-2 test results, and healthcare-seeking behaviour via a smartphone application, and donated blood for SARS-CoV-2 serology at two time points.Results1,511 HCWs were randomised and 1,309 analysed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio=0.95; 95% confidence interval 0.76-1.21; p=0.732). Only three participants required hospitalisation for COVID-19. The proportions of participants with asymptomatic, mild, or mild-to-moderate infections, and the mean infection durations, did not differ between randomisation groups. Unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes either. The percentage of participants with seroconversion (7.8% versus 2.8%; p=0.006) and mean anti-S1 antibody concentration (13.1 versus 4.3 IU/ml; p=0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months post-vaccination.ConclusionsBCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (on a scale from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection.
Suicide after leaving the UK Armed Forces 1996-2018: a cohort study
Authors: Rodway Cathryn , Ibrahim Saied , Westhead Jodie , Bojanić Lana , Turnbull Pauline , Appleby Louis , Bacon Andy , Dale Harriet , Harrison Kate , Kapur Nav 
Published: December 2022

ABSTRACTBackgroundThere are comparatively few international studies investigating suicide in military veterans and no recent UK studies. We aimed to investigate the rate, timing, and risk factors for suicide in personnel who left the UK Armed Forces (UKAF) over a 22-year period.Methods and findingsWe conducted a retrospective cohort study of suicide in personnel who left the regular UKAF between 1996 and 2018 by linking national databases of discharged personnel and suicide deaths. Of the 458,058 individuals who left the UKAF, 1,086 (0.2%) died by suicide. The overall rate of suicide in veterans was not greater than the general population (SMR [95% CI] 94 [88-99]). However, suicide risk was two to four times higher in male and female veterans aged under 25 years than in the same age groups in the general population (age-specific mortality ratios ranging from 160 to 409). Male veterans aged 35 years and older were at reduced risk of suicide (age-specific mortality ratios 47 to 80). Male sex, Army service, discharge between the ages of 16 and 34 years, being untrained on discharge, and length of service under 10 years were associated with increased suicide risk. Factors associated with reduced risk included being married, a higher rank and deployment on combat operations. The rate of contact with specialist NHS mental health services (273/1,086, 25%) was lowest in the youngest age groups (10% for 16–19-year-olds; 23% for 20–24-year-olds).ConclusionsSuicide risk in veterans is not high but there are important differences according to age, with higher risk in young men and women. We found a number of factors which increased the risk of suicide but deployment was associated with reduced risk. Our focus should be on improving and maintaining access to mental health care and social supports for young service leavers, as well as implementing general suicide prevention measures for all veterans.
Mental Health in Ireland During the Covid Pandemic: Evidence from Two Longitudinal Surveys
Authors: Madden David 
Published: December 2022

AbstractUsing data from the Growing Up in Ireland Covid survey, this study examines the evolution of mental health as measured in December 2020, nine months into the pandemic, compared to observations pre pandemic for two cohorts of people. A deterioration in mental health was observed for both cohorts and particularly for younger women of the 1998 cohort. The increase in the rate of depression predominantly occurred due to an overall decline in mental health rather than being concentrated amongst those already vulnerable (in the sense of being near the depression threshold). There was little, if any, change in the socioeconomic gradient associated with mental health and virtually no gradient at all was observed pre or post pandemic for the 1998 cohort. Mobility analysis revealed that not only did females from the 1998 cohort show greater transitions into depression, they also appeared to transition into more extreme levels of depression.JEL CodesI14, I31.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.AbstractBackgroundThe Covid pandemic arrived in Ireland on February 29, 2020. In the following weeks various restrictions were introduced to stem the spread of the disease. Anxiety over the spread of the disease and over the restrictions introduced had an adverse effect upon mental health. This study examines the change in mental health for two groups: young adults aged around 23 at the time of onset of Covid (the 1998 cohort) and a sample of principal carers (PCs) of children who were aged 13 at the onset of Covid (the 2008 cohort).MethodsData were obtained from the two cohorts of the longitudinal Growing Up In Ireland (GUI) survey. The sample included 1953 young adults (from the 1998 cohort) and 3547 principal carers (from the 2008 cohort). Mental health as measured by the Centre for Epidemiological Studies Depression - 8 scale was obtained for the last pre-Covid wave and for the Covid wave (surveyed in December 2020). Observations for which CES-D8 was not available in either pre or post Covid waves were excluded. Post-Covid sampling weights were applied.ResultsRelative to the last pre-Covid survey, mental health, as measured by CES-D8 deteriorated for both the young adults of the 1998 cohort and the PCs of the 2008 cohort. For young adults, the deterioration was more pronounced for females. There was no observable socioeconomic gradient for poor mental health amongst young adults, both pre and post Covid. For mothers from the 2008 cohort, a gradient was observed pre-Covid with poorer mental health for lower-income, less well-educated mothers. This gradient was less pronounced post-Covid, the levelling-off arising from a greater deterioration in mental health for higher-income and better-educated PCs.ConclusionBoth observed cohorts showed a significant deterioration in mental health post Covid. For young adults the effect was more pronounced among females.
Laboratory-Developed Test Orders in an Academic Health System
Authors: Rychert Jenna , Schmidt Robert L. , Genzen Jonathan R 
Published: December 2022

ABSTRACTImportanceThe Verifying Accurate Leading-edge IVCT Development Act, if enacted, would create a unified regulatory oversight system for all in vitro clinical tests, including laboratory-developed tests.ObjectiveTo determine the frequency of use of laboratory-developed tests in an academic medical center system.DesignQuality improvement study analyzing 2021 test order data.SettingAcademic medical center (hospital, outpatient clinics, and cancer center) and non-profit national reference laboratory.Main Outcome(s) and Measure(s)Main outcome, not applicable; non-interventional study of retrospective data. Measures include assay type, assay methodology, compliance status (i.e., Food and Drug Administration cleared, approved, and/or authorized assay, laboratory-developed test, and standard method), test order volume, inpatient versus outpatient setting, and provider medical specialty.ResultsOf the 3,016,928 tests ordered in 2021, 2,831,489 (93.9%) were Food and Drug Administration cleared, approved, and/or authorized assays, 116,583 (3.9%) were laboratory-developed tests, and 68,856 (2.3%) were standard methods. Laboratory-developed tests were more commonly ordered in the outpatient versus inpatient setting and represented a higher proportion of the test volume at the cancer center compared to University Hospital (5.6% vs 3.6% respectively). The top 167 laboratory-developed test assays accounted for 90% of the laboratory-developed test volume (104,996 orders). Among the 20 most frequently ordered laboratory-developed tests were mass spectrometry assays and tests used in the care of immunocompromised patients. Internal/family medicine placed the greatest number of orders (1,044,642) and ordered one of the lowest proportions of laboratory-developed tests (3.2%). Non-infectious disease molecular testing made up 8.8% of laboratory-developed tests ordered.ConclusionsLaboratory-developed tests made up a small percentage of the total laboratory tests ordered within the academic health system studied. Regulatory reform proposals should consider the need for both safety and availability of laboratory-developed tests in clinical laboratory settings.KEY POINTSQuestionHow frequently are laboratory developed tests (LDTs) used in an academic medical center (AMC) setting?FindingsIn this quality improvement study looking at test orders in 2021, 93.9% of test orders were for FDA cleared, approved, or authorized assays, 3.9% were for LDTs, and 2.3% were for standard methods. The top 167 LDT assays accounted for 90% of the LTD volume.MeaningIn vitro diagnostic reform efforts will impact many LDTs assays with relatively low order volumes in AMC settings.
Distribution of mutation rates challenges evolutionary predictability
Authors: Sun T. Anthony , Lind Peter A. 
Published: December 2022

AbstractNatural selection is commonly assumed to act on extensive standing genetic variation. Yet, accumulating evidence highlights the role of mutational processes creating this genetic variation: to become evolutionarily successful, adaptive mutants must not only reach fixation, but also emerge in the first place,i.e.have a high enough mutation rate relative to the population size.Here, we use numerical simulations to investigate how mutational biases impact our ability to observe rare mutational pathways in the laboratory and to predict outcomes in experimental evolution. We find the number of available mutations and the unevenness of their mutation rates to increase, sometimes impractically, the experimental effort required to discover all of them. Thus, most experimental studies lack power to directly observe the full range of adaptive mutations.Modelling mutation rates as a distribution, we show that a substantially larger target size ensures that a pathway mutates more commonly. Therefore, we predict that commonly mutated pathways are conserved between closely related species, contrary to rare pathways. This approach formalizes our proposal that most mutations have a lower mutation rate than the average mutation rate measured experimentally. We suggest that the extent of genetic variation is overestimated when based on the average mutation rate.
Characterization of the mIF4G domains in the RNA surveillance protein Upf2
Authors: Colón Edgardo M. , Haddock Luis A. , Lasalde Clarivel , Lin Qishan , Ramírez-Lugo Juan S. , González Carlos I. 
Published: December 2022

AbstractThirty percent of all mutations causing human diseases generate mRNAs with premature termination codons (PTCs). Recognition and degradation of these PTC-containing mRNAs is carried out by the mechanism known as nonsense-mediated mRNA decay (NMD). Upf2 is a scaffold protein known to be a central component of the NMD surveillance pathway. It harbors three middle domain of eukaryotic initiation factor 4G (mIF4G) domains in its N-terminal potentially important in regulating the surveillance pathway. In this study, we defined regions within the mIF4G-1 and mIF4G-2 that are required for proper function of NMD and translation termination inSaccharomyces cerevisiaeUpf2. In addition, we narrowed down the activity of these regions to an aspartic acid (D59) in mIF4G-1 which is important for NMD activity and translation termination accuracy. Taken together, these studies suggest that inherent charged residues within mIF4G-1 of Upf2 play a role in the regulation of the NMD surveillance mechanism inS. cerevisiae.
SARS-CoV-2 vaccine-breakthrough infections (VBIs) by Omicron (B.1.1.529) variant and consequences in structural and functional impact
Authors: Abduljaleel Zainularifeen , Melebari Sami , Dehlawi Saied , Udhaya Kumar S , Aziz Syed A. , Dannoun Anas Ibrahim , Malik Shaheer M. , George Priya Doss C 
Published: December 2022

AbstractThis study investigated the efficacy of existing vaccinations against hospitalization and infection due to the Omicron variant of COVID-19, particularly for those who received two doses of Moderna or Pfizer vaccines and one dose of a vaccine by Johnson & Johnson or who were vaccinated more than five months previously. A total of 36 variants in Omicron’s spike protein, targeted by all three vaccinations, have made antibodies less effective at neutralizing the virus. Genotyping of SARS-CoV-2 viral sequencing revealed clinically significant variants such as E484K in three genetic mutations (T95I, D614G, and del142-144). One woman displayed two of these mutations, indicating a potential risk of infection following successful immunization, as recently reported by Hacisuleyman (2021). We examined the effects of mutations on domains (NID, RBM, and SD2) found at the interfaces of spike domains Omicron B.1.1529, Delta/B.1.1529, Alpha/B.1.1.7, VUM B.1.526, B.1.575.2, and B.1.1214 (formerly VOI Iota). We tested the affinity of Omicron for hACE2 and found that the wild and mutant spike proteins were using atomistic molecular dynamics simulations. According to binding free energies calculated during mutagenesis, hACE2 bound Omicron spike more strongly than SARS-CoV-2 wild strain. T95I, D614G, and E484K are three substitutions that significantly contribute to the RBD, corresponding to hACE2 binding energies and a doubling of Omicron spike proteins’ electrostatic potential. Omicron appears to bind hACE2 with greater affinity, increasing its infectivity and transmissibility. The spike virus was designed to strengthen antibody immune evasion through binding while boosting receptor binding by enhancing IgG and IgM antibodies that stimulate humanβ-cell, as opposed to the wild strain, which has more vital stimulation of both antibodies.
Genetic analysis of the rice jasmonate receptors reveals specialized function forOsCOI2
Authors: Nguyen Hieu Trang , Cheaib Mohamad , Fournel Marie , Rios Maelle , Gantet Pascal , Laplaze Laurent , Guyomarc’h Soazig , Riemann Michael , Heitz Thierry , Petitot Anne-Sophie , Champion Antony 
Published: December 2022

SummaryCOI1-mediated perception of jasmonate is critical for plant development and responses to environmental stresses. Monocots such as rice have two groups ofCOIgenes due to gene duplication:OsCOI1aandOsCOI1bthat are functionally equivalent to the dicotyledonsCOI1on one hand andOsCOI2whose function remains unclear.In order to assess the function ofOsCOI2and its functional redundancy withCOI1genes, we developed a series of rice mutants in the 3 genesOsCOI1a, OsCOI1bandOsCOI2by CRISPR Cas9 and characterized their phenotype and responses to jasmonate.Characterization ofOsCOI2uncovered important roles in root, leaf and flower development. In particular, we show that crown root growth inhibition by jasmonate relies onOsCOI2and notOsCOI1aorOsCOI1bin rice, revealing a major function for the non-canonicalOsCOI2in jasmonate-dependent control of rice root growth.Collectively, these results point to a specialized function ofOsCOI2in the regulation of plant development in rice and indicate that sub-functionalisation of jasmonate receptors has occurred in the monocot phylum.
Mean Dimension of Generative Models for Protein Sequences
Authors: Feinauer Christoph , Borgonovo Emanuele 
Published: December 2022

AbstractGenerative models for protein sequences are important for protein design, mutational effect prediction and structure prediction. In all of these tasks, the introduction of models which include interactions between pairs of positions has had a major impact over the last decade. More recently, many methods going beyond pairwise models have been developed, for example by using neural networks that are in principle able to capture interactions between more than two positions from multiple sequence alignments. However, not much is known about the inter-dependency patterns between positions in these models, and how important higher-order interactions involving more than two positions are for their performance. In this work, we introduce the notion of mean dimension for generative models for protein sequences, which measures the average number of positions involved in interactions when weighted by their contribution to the total variance in log probability of the model. We estimate the mean dimension for different model classes trained on different protein families, relate it to the performance of the models on mutational effect prediction tasks and also trace its evolution during training. The mean dimension is related to the performance of models in biological prediction tasks and can highlight differences between model classes even if their performance in the prediction task is similar. The overall low mean dimension indicates that well-performing models are not necessarily of high complexity and encourages further work in interpreting their performance in biological terms.