bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural product biosynthetic potential reflects macroevolutionary diversification within a widely distributed bacterial taxon
Authors: Silva Sandra Godinho , Nabhan Homsi Masun , Keller-Costa Tina , Rocha Ulisses , Costa Rodrigo 
Published: November 2023

ABSTRACT

Flavobacteriaceae
spp. are key players in global biogeochemical cycling and are known for their versatile carbohydrate and peptide catabolism. However, it is currently unknown whether secondary metabolism traits underlie their broad range of occurrence across the earth’s biomes. We examined 2,680 genomes to unveil an unprecedented phylogenetic signal dictating natural product biosynthesis diversification within the
Flavobacteriaceae
family. The distribution of secondary metabolite biosynthetic gene clusters (BGCs) across genomes usually follows macroevolutionary, genus-specific patterns. Noticeably, 88.6% of the observed BGCs were inferred to lead to the biosynthesis of likely novel natural products. We found an unanticipated, large diversity of taxon-specific BGCs encoding carotenoid and flexirubin pigments, the vast majority of which awaiting formal description. In particular,
Aquimarina
and
Kordia
spp. possessed large genomes, versatile catabolic traits, and a repertoire of BGCs possibly encoding drug-inspiring polyketides, non-ribosomal peptides, or post-translationally modified peptides. Using a machine learning approach (feature selection), we reveal that marine and non-marine
Flavobacteriaceae
genomes are differentially enriched in CAZymes and peptidases with distinct functionalities and molecular targets.

IMPORTANCE

This is the most comprehensive study performed thus far on the biosynthetic potential within the
Flavobacteriaceae
family. Our findings reveal intertwined taxonomic and natural product biosynthesis diversification within the family. We posit that the carbohydrate, peptide, and secondary metabolism triad synergistically shaped the evolution of this keystone bacterial taxon, acting as major forces underpinning the broad host range and opportunistic-to-pathogenic behavior encompassed by species in the family. This study further breaks new ground for future research on select
Flavobacteriaceae
spp. as reservoirs of novel drug leads.
TRAF3 gene regulates macrophage migration and activation by lung epithelial cells infected with
Aspergillus fumigatus
Authors: Shang Shumi , He Dan , Liu Cong , Bao Xinyuan , Han Shuaishuai , Wang Li 
Published: November 2023

ABSTRACT

Aspergillus fumigatus
is an opportunistic pathogen that infects immunocompromised patients and imposes a heavy burden on global health. Searching for key genes in host resistance to
A. fumigatus
infection can help us understand the mechanisms of
A. fumigatus
-host interactions and provide new targets for the treatment of fungal infections. TRAF3 is one of the intracellular adapter proteins of the innate immune response that regulates signaling in various cellular processes, including host defense against pathogens. However, the defense mechanism of TRAF3 against
A. fumigatus
infection remains unknown. In this study, we found that TRAF3 overexpression led to the adhesion and internalization of more spores of
A. fumigatus
in lung epithelial cells and thus greater host immune surveillance evasion. Meanwhile, TRAF3 was able to regulate the expression of pro-inflammatory cytokines in lung epithelial cells infected with
A. fumigatus
through the negative regulation of NF-κB and MAPK signaling pathways. In this study, we also examined the effects of TRAF3 in the interaction between lung epithelial cells, macrophages, and
A. fumigatus
spores, and the results showed that TRAF3-overexpressing lung epithelial cells reduced the migration and activation of macrophages after
A. fumigatus
infection.
In vivo
experiments using TRAF3-overexpressing transgenic zebrafish larvae revealed that TRAF3 overexpression increased the fungal load and mortality of zebrafish infected with
A. fumigatus
. In conclusion, the TRAF3 gene can negatively regulate the resistance of lung epithelial cells to
A. fumigatus
, which plays an important role in the early infection processes of
A. fumigatus
.

IMPORTANCE

Aspergillus fumigatus
can infect immunocompromised individuals and cause chronic and fatal invasive fungal infections. A better understanding of the molecular mechanisms of
A. fumigatus
-host interactions may provide new references for disease treatment. In this study, we demonstrated that the TRAF3 gene plays an important role in the early infection of
A. fumigatus
by regulating the resistance of lung epithelial cells to
A. fumigatus
. Macrophages are the most abundant innate immune cells in the alveoli; however, few studies have reported on the interactions between lung epithelial cells and macrophages in response to
A. fumigatus
invasion. In our study, it was demonstrated that the TRAF3 gene reduces migration to macrophages and cytokine production by negatively regulating lung epithelial cell adhesion and internalization of
A. fumigatus
spores. Together, our results provide new insights into lung epithelial cell-macrophage interactions during
A. fumigatus
infection.
Marine snowstorm during the Permian–Triassic mass extinction
Authors: Grasby Stephen E. , Ardakani Omid H. , Liu Xiaojun , Bond David P.G. , Wignall Paul B. , Strachan Lorna J. 
Published: November 2023

Abstract
The Permian–Triassic mass extinction (PTME) interval is marked by major excursions in both inorganic and organic carbon (C) isotopes. Carbon cycle models predict that these trends were driven by large increases in productivity, yet organic C–rich rocks are not recorded in most PTME shelf sedimentary successions. Anomalous C-rich facies have been reported from rare abyssal plains records now exposed in Japan and New Zealand, where black shales at the PTME are extraordinarily organic-rich units. We examined organic matter at the Waiheke, New Zealand, section, and results show that these deposits are dominated by lamalginites composed of unicellar solitary or colonial phytoplankton produced during algal blooms that falls as “marine snow.” We modeled the impact of ash fall from eruptions in the Siberian Traps large igneous province and argue that they fertilized the Panthalassa Ocean with P and Fe, leading to a marine “snowstorm” and significant C drawdown marking this major biobloom during the PTME.
A Bare and Gravitationally Dressed Electron Formed from Kerr–Newman Black Hole
Authors: Burinskii A. 
Published: November 2023

Abstract
The Kerr–Newman (KN) electron model, based on the classical KN black hole solution, is modified by adding a “mirror” sheet of KN metric corresponding to a positron, that creates a heavy electron-positron vacuum core dressed by gravity, and allows us to consider the bare and dressed electron separately. The bare electron is formed as a massless relativistic ring string and is responsible for the wave properties of the electron, while the heavy supersymmetric vacuum core receives the additional mass-energy from two Wilson loops dragged by the KN gravitational field, thus creating a magnetically coupled monopole-antimonopole pair. As a result, the KN electron becomes consistent with wave nature of quantum electron and its gravitational interaction increases dramatically from Planck to Compton scale.
Nurture Early for Optimal Nutrition (NEON) participatory learning and action women’s groups to improve infant feeding and practices in South Asian infants: pilot randomised trial study protocol
Authors: Manikam Logan , Allaham Shereen , Patil Priyanka , Naman Maryan , Ong Zhen Ling , Demel Isabel-Cathérine , Batura Neha , Llewellyn Clare , Hayward Andrew , Lakshman Rajalakshmi , Gilmour Jenny , Webb-Martin Kelley , Irish Carol , Archibong Mfon , Clarkson Corinne , Delceta Daley , Islam Lily , Bajwa Seema , Malek Sabiha , Bhachu Jasvir , Pushpakanthan Geromini , Heys Michelle , Lakhanpaul Monica 
Published: November 2023

IntroductionFeeding practices developed in early life can impact a child’s nutrition, growth, dental health, cognitive development and lifetime risk of chronic diseases. Substantial evidence suggests ethnic health inequalities, and non-recommended complementary infant feeding practices among UK’s South Asian (SA) population. Nurture Early for Optimal Nutrition aims to use women’s group participatory learning and action (PLA) cycles to optimise infant feeding, care and dental hygiene practices in SA infants <2 years in East London.Methods and analysisA three-arm pilot feasibility cluster randomised controlled trial will assess feasibility, acceptability, costs and explore preliminary effectiveness for proposed primary outcome (ie, reporting on body mass index (BMI) z-score). Multilingual SA community facilitators will deliver the intervention, group PLA Cycle, to mothers/carers in respective ethnic/language groups. 12 wards are randomised to face-to-face PLA, online PLA and usual care arms in 1:1:1 ratio. Primary outcomes are feasibility and process measures (ie, BMI z-score, study records, feedback questionnaires, direct observation of intervention and sustainability) for assessment against Go/Stop criteria. Secondary outcomes are cluster-level and economic outcomes (ie, eating behaviour, parental feeding practices, network diffusion, children development performance, level of dental caries, general practitioner utilisation, costs, staff time). Outcomes are measured at baseline, every 2 weeks during intervention, 14 weeks and at 6 months by blinded outcome assessors where possible. This study will use concurrent mixed-methods evaluation. Quantitative analyses include descriptive summary with 95% CI and sample size calculation for the definitive trial. The intervention effect with CI will be estimated for child BMI z-score. Implementation will be evaluated qualitatively using thematic framework analysis.Ethics and disseminationEthics approval was obtained from University College London (UCL), National Health Service (Health Research Authority (HRA) and Health and Care Research Wales (HRCW)). Results will be published in peer-reviewed journals, presented at scientific conferences/workshops with commissioners, partners and participating communities. Plain language summaries will be disseminated through community groups, websites and social media.Trial registration numberIRAS-ID-296259 (ISRCTN10234623).
Estimating the cost and epidemiology of mild to severe chronic pain associated with osteoarthritis in England: a retrospective analysis of linked primary and secondary care data
Authors: Lohan Christoph , Coates Greg , Clewes Peter , Stevenson Hannah , Wood Robert , Tritton Theo , Massey Lucy , Knaggs Roger , Dickson Alastair J , Walsh David 
Published: November 2023

ObjectiveOsteoarthritis (OA) affects 10% of adults in the UK. Despite over one-third of people with OA experiencing chronic pain, few studies have examined the population-level impact of chronic pain associated with OA. We compared resource-use and epidemiological outcomes in patients with mild, moderate and severe chronic OA-associated pain and matched controls without known OA.DesignRetrospective, longitudinal, observational cohort study (July 2008 to June 2019).SettingElectronic records extracted from Clinical Practice Research Datalink GOLD primary care linked to Hospital Episode Statistics (HES).ParticipantsPatients (cases; n=23 016) aged ≥18 years with chronic OA-associated pain. Controls (n=23 016) without OA or chronic pain matched on age, sex, comorbidity burden, general practitioner practice and available HES data.InterventionsNone.Primary and secondary outcome measuresTotal healthcare resource use (HCRU), direct healthcare costs in 0–12, 12–24 and 24–36 months postindex. Secondary outcomes included incidence and prevalence of chronic OA-associated pain and pharmacological management.ResultsHCRU was consistently greater in cases versus controls for all resource categories during preindex and postindex periods. Across follow-up periods, resource use was greatest in patients with severe pain. In the first 12 months postindexing, mean total costs incurred by cases were four times higher versus matched controls (£256 vs £62); costs were approximately twice as high in cases vs controls for months 12–24 (£166 vs £86) and 24–36 (£150 vs £81; all p<0.0001). The incidence of new cases of chronic pain associated with OA was 2.64 per 1000 person-years; the prevalence was 1.4%.ConclusionsThis study highlights the real-world cost of chronic pain associated with OA in cases versus matched controls. We included patients with mild, moderate and severe pain associated with OA, and showed HCRU in discrete 1-year time frames. The true economic burden of pain associated with OA is likely to be considerably higher when indirect costs are considered.
Use of a rapid triage assessment tool to discriminate the need for hospitalisation in patients with severe COVID-19 infection presenting to an outpatient clinic: a single-centre, prospective cohort study
Authors: Owens Christopher , Lamb Chris , Sanchez Julio , Quintero Mariana , Lopez-Yunez Alfredo 
Published: November 2023

ObjectivesThe WHO designated individuals with low oxygen saturation, SpO2<94%, as severe SARS-CoV2 infection (COVID-19) and recommendations to seek care in a hospital setting were advised. A rapid, office-based method to select patients with severe COVID-19 who need intensive care was necessary during the peak of the pandemic.Design, setting and participantsThis is a prospective cohort study of patients with confirmed severe COVID-19 between September 2020 and April 2021.Outcome measures and analysisOxygen saturation was obtained at rest (SpO2r), following exertion from a 20 m walk test (SpO2e), and the difference was calculated (SpO2Δ). Radiographs and laboratory values were obtained and recorded. Logistic regression models were used to determine variables associated with hospitalisation. A lung injury score was used to quantify pulmonary involvement.ResultsOut of 103 patients enrolled with severe COVID-19 infection, 19 (18.4%) were admitted to the hospital (no deaths). Patients managed as outpatients had a standard treatment protocol. The SpO2Δ and SpO2e were associated with hospitalisation (p<0.005) while SpO2r was no different between non-hospitalised and hospitalised patients (90.7%±2.7% vs 90.8%±2.3%, p=0.87). By contrast, exertional SpO2e was significantly different between non-hospitalised and hospitalised (87.3%±2.6% vs 84.4%±3.4%, p=0.0005). The mean lung injury score was 11.0±3.5 (18-point scale) and did not discriminate against those who would need hospitalisation. Lower lung fields were significantly more involved than the upper (p<0.0001). All patients had elevated biomarkers of inflammation, C reactive protein (CRP) median 82.5 IQR (43–128.6) mg/L and evidence of elevated liver enzymes. A logistic regression model was constructed including SpO2Δ, CRP and alanine aminotransferase to predict hospitalisation. Only SpO2Δ was significant, p=0.012, 95% CI (1.128 to 2.704) and correctly classified 85.71% of patients who could remain at home or would need to receive treatment in the hospital.ConclusionAn office-based, 20 m walk test can help diverge patients with severe COVID-19 who need escalated care. Further, an aggressive standardised treatment protocol can be used to successfully manage patients outside of hospitals despite having severe COVID-19.
Associations between feelings of safety, concerns about firearms on campus and suicidal thoughts and behaviours among college students
Authors: Mournet Annabelle M , Kellerman John K , Kleiman Evan M 
Published: November 2023

BackgroundPerceptions of safety on campus may be related to a variety of factors such as concerns about campus violence, especially firearm violence, and mental health, particularly suicidal thoughts and behaviours (STBs). The present analyses aim to describe associations between feelings of safety, concerns about firearms on campus and STBs among college students.MethodsThis study uses data from the American College Health Association—National College Health Assessment wave III (n=24 682 participants across k=29 schools). Multilevel logistic regressions and cumulative link mixed models examine the associations between feelings of safety, concerns about firearm violence on campus and presence of STBs in the past year.ResultsParticipants who reported being concerned about firearm violence felt significantly less safe. Feeling unsafe at night was significantly associated with suicidal ideation and suicide attempts. Individuals with concerns about firearm safety on campus were up to 42% more likely to report suicidal ideation compared with those reporting they were not at all concerned about campus firearm violence.DiscussionWith associations highlighting increased risk of STBs among those with reduced safety feelings and heightened concerns about firearms, there is a need for college campuses to intervene and promote campus safety, with particular consideration for the presence of firearms on campus and the implications of allowing such weapons to be present in environments with increasing instances of firearm violence.
Characteristics and outcome of critically ill patients with systemic rheumatic diseases referred to the intensive care unit
Authors: Schneeweiss-Gleixner Mathias , Hillebrand Caroline , Jaksits Stephanie , Fries Jonathan , Zauner Michael , Heinz Gottfried , Sengölge Gürkan , Staudinger Thomas , Zauner Christian , Aletaha Daniel , Machold Klaus P , Schellongowski Peter , Bécède Manuel 
Published: November 2023

ObjectivesPatients with systemic rheumatic diseases (SRDs) are at risk of admission to the intensive care unit (ICU). Data concerning these critically ill patients are limited to few retrospective studies.MethodsThis is a single-centre retrospective study of patients with SRDs admitted to an ICU at the Vienna General Hospital between 2012 and 2020. Single-predictor and multiple logistic regression analysis was performed to identify potential outcome determinants.ResultsA total of 144 patients accounting for 192 ICU admissions were included. Connective tissue diseases (CTDs), vasculitides and rheumatoid arthritis were the most common SRDs requiring ICU admission. Leading causes for ICU admission were respiratory failure and shock, as reflected by a high number of patients requiring mechanical ventilation (60.4%) and vasopressor therapy (72.9%). Overall, 29.2% of admissions were due to SRD-related critical illness. In 70.8% patients, co-existent SRD not responsible for the acute critical illness was documented. When comparing these subgroups, CTDs and vasculitides had a higher frequency in the patients with SRD-related critical illness. In a significantly higher proportion of patients in the SRD-related subgroup, diagnosis of SRD was made at the ICU. ICU and 6-month mortality in the overall population was 20.3% and 38.5%, respectively. Age, glucocorticoid therapy prior to hospital admission and disease severity were associated with poor outcome.ConclusionsIn this study, respiratory failure was the leading cause of ICU admission as reflected by high rates of required mechanical ventilation. Despite considerable severity of critical illness, survival rates were comparable to a general ICU population.
Spatial patterns of anticoagulant rodenticides in three species of medium-sized carnivorans in Pennsylvania
Authors: Facka Aaron , Frair Jacqueline , Keller Thomas , Miller Erica , Murphy Lisa , Ellis Julie C. 
Published: November 2023

Human influences on natural environments are now ubiquitous but manifest in multiple and unique ways depending on local environments and communities. Attempts to control, or mediate, local pests to residences or to agriculture can impart important negative consequences on systems. Secondary exposure to anticoagulant rodenticides (ARs) can cause numerous adverse effects on wild carnivores including death. Few studies have quantified AR prevalence, investigated their pathway of exposure, or associations with specific location types in the northeastern U.S. We hypothesized that ARs would be found in the mesocarnivore community throughout Pennsylvania and have the greatest detection rate in highly urbanized or agricultural landscapes. From 2019 through early 2022, we collected carcasses to obtain liver samples ( n = 265) from three species of carnivores: bobcats ( Lynx rufus (Schreber, 1777)), fishers ( Pekania pennanti (Erxleben, 1777)), and river otters ( Lontra canadensis (Schreber, 1777)). We used generalized linear models to test for differences in AR detection rates among species and spatial scales including the six Pennsylvania Game Commission regions and 23 wildlife management units. We detected ARs in all species (44.2% collectively), but detection rates differed among species. Our study is the first to document ARs within North American river otters.
Greenstones as a source of hydrogen in cratonic sedimentary basins
Authors: Hutchinson Ian P. , Jackson Owain , Stocks Andrew E. , Barnicoat Andrew C. , Lawrence Stephen R. 
Published: November 2023

Abstract
A model is presented for the generation of natural hydrogen from cratonic basement rocks and its migration into the sediments of overlying cratonic basins. It is based on the ‘discovery’ of hydrogen at Bourakebougou in the Taoudeni Basin of Mali. In the ‘Cratonic Greenstone Model’, hydrogen is generated by the serpentinization of olivine-rich, ultramafic rocks contained within Precambrian ‘greenstones’. The model requires a protolith (in greenstones), a supply of water (from groundwater), connecting faults to act as a plumbing system and an indurated sediment cover to retard hydrogen movement. Hydrogen is expelled into the overlying basin sediments, which form the host for hydrogen accumulations. The model describes a continental ‘hydrogen system’, which can form the basis for petroleum-type play-based hydrogen exploration in cratonic settings. Using play elements derived from the model, the Bourakebougou play fairway can be extended across the Taoudeni Basin >700 km northwards of the discovery.