bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the classical paradigm: what we have learnt from vertebrates about sex chromosome evolution
Authors: Kratochvíl Lukáš , Stöck Matthias , Rovatsos Michail , Bullejos Mónica , Herpin Amaury , Jeffries Daniel L. , Peichel Catherine L. , Perrin Nicolas , Valenzuela Nicole , Pokorná Martina Johnson 
Published: July 2021

Until recently, the field of sex chromosome evolution has been dominated by the canonical unidirectional scenario, first developed by Muller in 1918. This model postulates that sex chromosomes emerge from autosomes by acquiring a sex-determining locus. Recombination reduction then expands outwards from this locus, to maintain its linkage with sexually antagonistic/advantageous alleles, resulting in Y or W degeneration and potentially culminating in their disappearance. Based mostly on empirical vertebrate research, we challenge and expand each conceptual step of this canonical model and present observations by numerous experts in two parts of a theme issue ofPhil. Trans. R. Soc. B.We suggest that greater theoretical and empirical insights into the events at the origins of sex-determining genes (rewiring of the gonadal differentiation networks), and a better understanding of the evolutionary forces responsible for recombination suppression are required. Among others, crucial questions are: Why do sex chromosome differentiation rates and the evolution of gene dose regulatory mechanisms between male versus female heterogametic systems not follow earlier theory? Why do several lineages not have sex chromosomes? And: What are the consequences of the presence of (differentiated) sex chromosomes for individual fitness, evolvability, hybridization and diversification? We conclude that the classical scenario appears too reductionistic. Instead of being unidirectional, we show that sex chromosome evolution is more complex than previously anticipated and principally forms networks, interconnected to potentially endless outcomes with restarts, deletions and additions of new genomic material.This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Whole-chromosome fusions in the karyotype evolution ofSceloporus(Iguania, Reptilia) are more frequent in sex chromosomes than autosomes
Authors: Lisachov Artem P. , Tishakova Katerina V. , Romanenko Svetlana A. , Molodtseva Anna S. , Prokopov Dmitry Yu. , Pereira Jorge C. , Ferguson-Smith Malcolm A. , Borodin Pavel M. , Trifonov Vladimir A. 
Published: July 2021

Whole-chromosome fusions play a major role in the karyotypic evolution of reptiles. It has been suggested that certain chromosomes tend to fuse with sex chromosomes more frequently than others. However, the comparative genomic synteny data are too scarce to draw strong conclusions. We obtained and sequenced chromosome-specific DNA pools ofSceloporus malachiticus, an iguanian species which has experienced many chromosome fusions. We found that four of seven lineage-specific fusions involved sex chromosomes, and that certain syntenic blocks which constitute the sex chromosomes, such as the homologues of theAnolis carolinensischromosomes 11 and 16, are repeatedly involved in sex chromosome formation in different squamate species. To test the hypothesis that the karyotypic shift could be associated with changes in recombination patterns, we performed a synaptonemal complex analysis in this species and inSceloporus variabilis(2n= 34). It revealed that the sex chromosomes inS. malachiticushad two distal pseudoautosomal regions and a medial differentiated region. We found that multiple fusions little affected the recombination rate inS. malachiticus. Our data confirm more frequent involvement of certain chromosomes in sex chromosome formation, but do not reveal a connection between the gonosome–autosome fusions and the evolution of recombination rate.This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Sex chromosome evolution among amniotes: is the origin of sex chromosomes non-random?
Authors: Kratochvíl Lukáš , Gamble Tony , Rovatsos Michail 
Published: July 2021

Sex chromosomes are a great example of a convergent evolution at the genomic level, having evolved dozens of times just within amniotes. An intriguing question is whether this repeated evolution was random, or whether some ancestral syntenic blocks have significantly higher chance to be co-opted for the role of sex chromosomes owing to their gene content related to gonad development. Here, we summarize current knowledge on the evolutionary history of sex determination and sex chromosomes in amniotes and evaluate the hypothesis of non-random emergence of sex chromosomes. The current data on the origin of sex chromosomes in amniotes suggest that their evolution is indeed non-random. However, this non-random pattern is not very strong, and many syntenic blocks representing putatively independently evolved sex chromosomes are unique. Still, repeatedly co-opted chromosomes are an excellent model system, as independent co-option of the same genomic region for the role of sex chromosome offers a great opportunity for testing evolutionary scenarios on the sex chromosome evolution under the explicit control for the genomic background and gene identity. Future studies should use these systems more to explore the convergent/divergent evolution of sex chromosomes.
This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Chitinophaga oryzae sp. nov., an epiphytic bacterium isolated from rice root surfaces
Authors: Niemhom Nantawan , Suriyachadkun Chanwit , Kittiwongwattana Chokchai 
Published: July 2021

Two Gram-stain-negative, non-motile, rod-shaped bacterial strains were isolated from the surfaces of rice roots. They were designated as strains 1303T and 1310. Their colonies were circular, entire, opaque, convex and yellow. They were chitinase- and catalase-positive, reduced nitrate and grew at 16–37 °C (optimum, 30 °C), pH 5.0–10.0 (optimum, pH 7.0) and 0–2.0% NaCl (optimum, 1.0 %). Based on the 16S rRNA gene sequence analysis, they were classified as members of the genus

Chitinophaga

. Results of phylogenetic and phylogenomic analyses indicated that they formed a cluster with

Chitinophaga eiseniae

YC6729T,

Chitinophaga qingshengii

JN246T,

Chitinophaga varians

10-7 W-9003T and

Chitinophaga fulva

G-6-1-13T. When the genomic sequences of strains 1303T and 1310 were compared with their close relatives, the average nucleotide identity and digital DNA–DNA hybridization values were below the cut-off levels. Phosphatidylethanolamine was the major polar lipid. MK-7 was the major respiratory quinone. iso-C15 : 0, C16 : 1
ω5c, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1
ω7c/C16 : 1
ω6c) were the predominant fatty acids. Differential characteristics between both strains and their close relatives were also observed. Based on the distinctions in genotypic, phenotypic and chemotypic features, strains 1303T and 1310 represent members of a novel species of the genus

Chitinophaga

, for which the name Chitinophaga oryzae sp. nov. is proposed. The type strain is 1303T (=KACC 22075T=TBRC 12926T).
Assessment of Ankle Fractures using Deep Learning Algorithms and Convolutional Neural Network
Authors: Ashkani-Esfahani Soheil , Mojahed Yazdi Reza , Bhimani Rohan , Kerkhoffs Gino M. , Maas Mario , Guss Daniel , DiGiovanni Christopher W. , Lubberts Bart 
Published: July 2021

AbstractEarly and accurate detection of ankle fractures is crucial for reducing future complications. Radiographs are the most abundant imaging techniques for assessing fractures. We believe deep learning (DL) methods, through adequately trained deep convolutional neural networks (DCNNs), can assess radiographic images fast and accurate without human intervention. Herein, we aimed to assess the performance of two different DCNNs in detecting ankle fractures using radiographs compared to the ground truth.In this retrospective study, our DCNNs were trained using radiographs obtained from 1050 patients with ankle fracture and the same number of individuals with otherwise healthy ankles. Inception V3 and Renet50 pretrained models were used in our algorithms. Danis-Weber classification method was used. Out of 1050, 72 individuals were labeled as occult fractures as they were not detected in the primary radiographic assessment. Using single-view radiographs was compared with 3-views (anteroposterior, mortise, lateral) for training the DCNNs.Our DCNNs showed a better performance using 3-views images versus single-view based on greater values for accuracy, F-score, and area under the curve (AUC). The sensitivity and specificity in detection of ankle fractures using 3-views were 97.5% and 93.9% using Resnet50 compared to 98.7% and 98.6 using inception V3, respectively. Resnet50 missed 3 occult fractures while Inception V3 missed only one case.Clinical SignificanceThe performance of our DCNNs showed a promising potential that can be considered in developing the currently used image interpretation programs or as a separate assistant to the clinicians to detect ankle fractures faster and more precisely.Level of evidenceIII
Development of a federated learning approach to predict acute kidney injury in adult hospitalized patients with COVID-19 in New York City
Authors: Jaladanki Suraj K , Vaid Akhil , Sawant Ashwin S , Xu Jie , Shah Kush , Dellepiane Sergio , Paranjpe Ishan , Chan Lili , Kovatch Patricia , Charney Alexander W , Wang Fei , Glicksberg Benjamin S , Singh Karandeep , Nadkarni Girish N 
Published: July 2021

ABSTRACTFederated learning is a technique for training predictive models without sharing patient-level data, thus maintaining data security while allowing inter-institutional collaboration. We used federated learning to predict acute kidney injury within three and seven days of admission, using demographics, comorbidities, vital signs, and laboratory values, in 4029 adults hospitalized with COVID-19 at five sociodemographically diverse New York City hospitals, between March-October 2020. Prediction performance of federated models was generally higher than single-hospital models and was comparable to pooled-data models. In the first use-case in kidney disease, federated learning improved prediction of a common complication of COVID-19, while preserving data privacy.
The effective family size of immigrant founders predicts their long-term demographic outcome: from Québec settlers to their 20th-century descendants
Authors: Labuda Damian , Harding Tommy , Milot Emmanuel , Vézina Hélène 
Published: July 2021

AbstractHuman evolution involves population splits, size fluctuations, founder effects, and admixture. Population history reconstruction based on genetic diversity data routinely relies on simple demographic models while projecting the past. No specific demographic assumptions are needed to understand the genetic structure of the founder population of Québec. Because genealogy and genetics are intimately related, we used descending genealogies of this population to pursue the fate of its founder lineages. Maternal and paternal lines reflect the transmission of mtDNA and the Y-chromosome, respectively. We followed their transmission in real-time, from the 17thcentury down to its 20th-century population. We counted the number of married children of immigrants (i.e., their effective family size, EFS), estimated the proportion of successful immigrants in terms of their survival ratio, and assessed net growth rates and extinction. Likewise, we evaluated the same parameters for their Québec-born descendants. The survival ratio of the first immigrants was the highest and declined over time in association with the decreasing immigrants’ EFS. Parents with high EFS left plentiful married progeny, putting EFS as the most important variable determining the parental demographic success throughout time for generations ahead. The 17thand 18th-century immigrants bear the most remarkable demographic and genetic impact on the 20th-century population of Québec. Lessons learned from Québec genealogies can teach us about the consequences of founder effects and migrations through real people’s history. The effective family size of immigrant founders predicts their long-term demographic outcome.
Prospective validation of host transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR
Authors: Mendelsohn Simon C. , Mbandi Stanley Kimbung , Fiore-Gartland Andrew , Penn-Nicholson Adam , Musvosvi Munyaradzi , Mulenga Humphrey , Fisher Michelle , Hadley Katie , Erasmus Mzwandile , Nombida Onke , Tameris Michèle , Walzl Gerhard , Naidoo Kogieleum , Churchyard Gavin , Hatherill Mark , Scriba Thomas J. ,   The Cross-sectional TB Cohort Study Team,   The CORTIS Study Team
Published: July 2021

AbstractWe tested performance of host-blood transcriptomic tuberculosis (TB) signatures for active case-finding. Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2,923 and 861 were enrolled from five South African communities. Eight signatures were measured by microfluidic RT-qPCR and participants were microbiologically-investigated for pulmonary TB at baseline, and actively surveilled for incident disease through 15 months. Diagnostic AUCs for 61 HIV-uninfected (weighted-prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) prevalent TB cases for the 8 signatures were 0.63–0.79 and 0.65–0.88, respectively. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident TB (1.1 and 1.0 per 100 person-years, respectively). Prognostic AUCs through 15-months follow-up were 0.49–0.66 and 0.54–0.81, respectively. Prognostic performance for incident TB occurring within 6-12 months in HIV-negative participants was higher for all signatures. None of the signatures met WHO Target Product Profile criteria for a triage test to diagnose asymptomatic TB; most signatures met the criteria for symptomatic TB. Prognostic accuracy of most signatures for incident TB within six months of testing met the criteria for an incipient TB test.
COVID-19 Disease Severity among People with HIV Infection or Solid Organ Transplant in the United States: A Nationally-representative, Multicenter, Observational Cohort Study
Authors: Sun Jing , Patel Rena C. , Zheng Qulu , Madhira Vithal , Olex Amy L. , Islam Jessica Y. , French Evan , Chiang Teresa Po-Yu , Akselrod Hana , Moffitt Richard , Alexander G. Caleb , Andersen Kathleen M. , Vinson Amanda J. , Brown Todd T. , Chute Christopher G. , Crandall Keith A. , Franceschini Nora , Mannon Roslyn B. , Kirk Gregory D. ,   National COVID Cohort Collaborative (N3C) Consortium
Published: July 2021

ABSTRACTBackgroundIndividuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction.MethodsWe evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction.FindingsCompared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm3, PWH with CD4<350 cells/mm3 were independently at 4.4-, 5.4-, and 7.6-times higher odds for hospitalization, requiring ventilation, and death, respectively. Increased COVID-19 severity was associated with higher levels of HIV viremia.InterpretationIndividuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.
The Achilles’ heel of coronaviruses: targeting the 5’ Polyuridines tract of the antigenome to inhibit Mouse coronavirus-induced cell death
Authors: Ullah Hemayet , Averick Saadyah , Tang Qiyi 
Published: July 2021

AbstractThe current coronavirus pandemic situation is worsened by the rapidly-spreading SARS-CoV-2 virus variants. Identification of viral targets that are indispensable for the virus can be targeted to inhibit mutation-based new escape variant development. The 5’-polyU tract of the antigenome offers such a target. Host cells do not harbor 5’-polyU tracts on any of their transcripts, making the tract an attractive, virus-specific target. Inhibiting the 5’-polyU can limit the use of the tract as template to generate 3’ polyA tails of +RNAs of coronaviruses. Here, a modified DNA oligo with 3’ polyAs is used to target the 5-polyU tract in mouse coronavirus (MHV-A59). The oligo treatment in mouse 17CL-1 cells infected with MHV-A59 significantly prevented virus-induced cell deaths. This proof-of-concept result shows a unique mode of action against mouse coronavirus without affecting host cells, and can be used for the development of novel classes of drugs that inhibit coronavirus infection in host cells, specifically by the COVID-19-causing virus SARS-CoV-2. In addition, as the 5’-polyU tract is immediately generated upon infection, the tag can also be targeted for reliable early detection of viral infection.
Bacterial and metabolic factors of staphylococcal planktonic and biofilm environments differentially regulate macrophage immune activation
Authors: Seebach Elisabeth , Elschner Tabea , Kraus Franziska V. , Souto-Carneiro Margarida , Kubatzky Katharina F. 
Published: July 2021

AbstractBiofilm formation is a leading cause for chronic implant-related bone infections as biofilms shield bacteria against the immune system and antibiotics. Additionally, biofilms generate a metabolic microenvironment that shifts the immune response towards tolerance. Here, we compared the impact of the metabolite profile of bacterial environments on macrophage immune activation usingStaphylococcus aureus(SA) andepidermidis(SE) conditioned media (CM) of planktonic and biofilm cultures. The biofilm environment had reduced glucose and increased lactate concentrations. Moreover, the expression of typical immune activation markers on macrophages was reduced in the biofilm environment compared to the respective planktonic CM. However, all CM caused a predominantly pro-inflammatory macrophage cytokine response with a comparable induction ofTnfaexpression. In biofilm CM this was accompanied by higher levels of anti-inflammatoryIl10. Planktonic CM on the other hand, induced an IRF-7 mediatedIfnbexpression which was absent in the biofilm environments. For SA but not for SE planktonic CM, this was accompanied by IRF3 activation. Stimulation of macrophages with TLR-2/-9 ligands under varying metabolic conditions revealed that, like in the biofilm setting, low glucose concentration reduced theTnfatoIl10mRNA ratio. However, addition of extracellular L-lactate but not D-lactate increased theTnfatoIl10mRNA ratio upon TLR-2/-9 stimulation. In summary, our data indicate that the mechanisms behind the activation of macrophages differs between planktonic and biofilm environments. These differences are independent of the metabolite profiles, suggesting that the production of different bacterial factors is ultimately more important than the concentrations of glucose and lactate in the environment.
Tolerability, safety and immunogenicity of intradermal delivery of a fractional dose mRNA-1273 SARS-CoV-2 vaccine in healthy adults as a dose sparing strategy
Authors: Roozen Geert V.T. , Prins Margaretha L.M. , van Binnendijk Rob , Hartog Gerco den , Kuiper Vincent P. , Prins Corine , Janse Jacqueline J. , Kruithof Annelieke C. , Feltkamp Mariet C.W. , Kuijer Marjan , Rosendaal Frits R. , Roestenberg Meta , Visser Leo G. , Roukens Anna H.E. 
Published: July 2021

AbstractBackgroundThere is an urgent need for fair and equitable access to safe and effective vaccines to end the COVID-19 pandemic. Shortages in reagents and vaccines are a major challenge, as well as limited knowledge on dose response relationship with mRNA COVID-19 vaccines. We explored intradermal fractional dose administration of a mRNA SARS-CoV-2/COVID-19 vaccine as a potential dose-sparing strategy.MethodsWe conducted a proof-of-concept, dose-escalation, open-label, randomised-controlled vaccine trial (IDSCOVA) in healthy adults aged 18-30 years. To test initial safety, ten participants received 10 µg mRNA-1273 vaccine through intradermal injection at day 1 and 29. Following a favourable safety review, thirty participants were 1:1 randomised to receive 20 µg mRNA-1273 either intradermally or intramuscularly. The primary endpoint was tolerability and safety. The secondary endpoint was seroconversion and specific IgG concentration against SARS-CoV-2 spike S1 and Receptor Binding Domain (RBD) after the second dose at day 43. We compared results to two historical cohorts of non-hospitalised COVID-19 patients and vaccinated individuals.FindingsThirty-eight of forty included participants (median age 25 years) completed the study. There were no serious adverse events. Self-reported local adverse reactions after intradermal delivery were mild, both in the 10 µg and the 20 µg group. In the higher dose group, systemic adverse reactions were more common, but still well tolerated. All 38 participants mounted substantially higher IgG-anti-S1 and IgG-anti-RBD concentrations at day 43 than COVID-19 controls. At day 43, anti-S1 (95% CI) was 1,696 (1,309-2,198) BAU/mL for the 10 µg intradermal group, 1,406 (953·5-2,074) BAU/mL for the 20 µg intramuscular group and 2,057 (1,421-2,975) BAU/mL for the 20 µg intradermal group. Anti-S1 was 107·2 (63-182·2) BAU/mL for the convalescent plasma control group and 1,558 (547·8-4,433) BAU/mL for the individuals vaccinated with 100 µg mRNA-1273.InterpretationIntradermal administration of 10 µg and 20 µg mRNA-1273 vaccine was well tolerated and safe, and resulted in a robust antibody response. Intradermal vaccination has the potential to be deployed for vaccine dose-sparing.FundingThe trial was supported by crowdfunding (Wake Up to Corona).