bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cbl-b negatively regulates TLR/MyD88-mediated anti-
Toxoplasma gondii
immunity
Authors: Wei Haixia , Wu Shuizhen , Mai Liying , Yang Lili , Zou Weihao , Peng Hongjuan 
Published: November 2023

ABSTRACT

Toxoplasma gondii
is an important intracellular protozoan, which needs to exploit host nutrition for successful parasitism. We previously reported that Casitas B-lineage lymphoma-b (Cbl-b) was screened as a host dependency factor of
T. gondii
by using lentiviral CRISPR-Cas9-single guide RNA (sgRNA) libraries. Furthermore, the detailed mechanism of Cbl-b being required by
T. gondii
infection was explored in this study. The proliferation of
T. gondii
was found to be significantly inhibited in Cbl-b knockdown cell lines, and the Cbl-b expression level increased with prolonged
T. gondii
infection, while the MyD88 level was significantly decreased in the
T. gondii
infection group. Toll-like receptor (TLR)/MyD88 is a conserved innate cellular immune signaling pathway against pathogens infection. Cbl-b was found to interact with MyD88 and mediate MyD88 ubiquitination in the fluorescence resonance energy transfer and co-immunoprecipitation experiments. A Cbl-b knockout (KO) C57BL/6J lineage was then constructed and, together with the wild-type (WT) mice, was infected with the same amount of
T. gondii
tachyzoites of ME49 strain. At 13 days post infection, all the mice in the WT group died, while 80% of the mice in the Cbl-b KO group still survived, even to the end of the experiment. The parasitic burden in the liver, lung, and brain of the Cbl-b KO mice was significantly lower than that of the WT mice (
P
< 0.05). In Cbl-b KO infected mice, the percentage of B cells was higher, whereas that of macrophages was lower, and the interferon-γ and interleukin-6 levels in the serum were higher than that in the WT infected mice; the difference was significant (
P
< 0.05). Furthermore, when host cells were infected by
T. gondii
, host’s Cbl-b was found to interact with MyD88 to ubiquitinate MyD88 for ribosome-dependent degradation. Therefore, the host’s innate immunity against
T. gondii
through the TLR/MyD88 pathway was negatively regulated by Cbl-b.

IMPORTANCE

This is the first report that a human E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (Cbl-b), functions as a host dependency factor for the intracellular protozoan
Toxoplasma gondii
and the mechanism for how
T. gondii
infection inhibits the TLR/MyD88 innate immunity pathway through MyD88 degradation mediated by Cbl-b. This finding is an impactful contribution for understanding the host cell immunity against
T. gondii
infection.
Core-genome multilocus sequence typing and core-SNP analysis of
Clostridium neonatale
strains isolated in different spatio-temporal settings
Authors: Mesa Victoria , Delannoy Johanne , Ferraris Laurent , Diancourt Laure , Mazuet Christelle , Barbut Frédéric , Aires Julio 
Published: November 2023

ABSTRACT

Clostridium neonatale
was described as a new species within the
Clostridium
genus cluster I
sensu stricto
. It was recovered from the gut microbiota of infants and has been associated with necrotizing enterocolitis (NEC), a severe gastrointestinal disease affecting preterm neonates. In the absence of molecular typing methods, we developed a core (cg)-genome multilocus sequence typing (MLST) scheme based on 48 newly sequenced and 12 publicly available genomes of
C. neonatale
. Using the ChewBBACA algorithm, a stable MLST scheme consisting of 2,350 target genes (with genomes having ≥95% cgMLST targets) is proposed. The strains are distributed among five clades, and while some are clonality related within clades, the
C. neonatale
strain distribution is independent of geographic or temporal clustering. When considering strains isolated from patients with and without NEC, there were no observable differences in clustering. When compared to a core-single nucleotide polymorphism (SNP) analysis approach (31,248 positions), we showed that both cgMLST and cgSNP have comparable genetic discrimination of strains. In this study, we validated the use of cgMLST and cgSNP-based typing methods for the genetic comparison of clinical isolates of
C. neonatale
, which will allow for future surveillance and epidemiological clinical investigations of this potential opportunistic pathogen.

IMPORTANCE

Clostridium neonatale
has been isolated from the fecal samples of asymptomatic neonates and cases of necrotizing enterocolitis (NEC). Taking advantage of a large collection of independent strains isolated from different spatio-temporal settings, we developed and established a cgMLST scheme for the molecular typing of
C. neonatale
. Both the cgMLST and cgSNP methods demonstrate comparable discrimination power. Results indicate geographic- and temporal- independent clustering of
C. neonatale
NEC-associated strains. No specific cgMLST clade of
C. neonatale
was genetically associated with NEC.
Global genomic diversity and conservation of SARS-CoV-2 since the COVID-19 outbreak
Authors: Li Heng , Ding Liping , Liao Rui , Li Nini , Hong Xiaoping , Jiang Zhenyou , Liu Dongzhou 
Published: November 2023

ABSTRACT
Global sequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has enabled researchers to monitor the genetic information of new pathogenic variants. However, the integrity and accuracy of most genomic information cannot be guaranteed due to limited sample quality and sequencing technology. This restricts researchers from tracking the latest changes in the virus genome. In this study, we aimed to characterize the diversity and conservation balance of complete SARS-CoV-2 genomes worldwide since the outbreak. To achieve this goal, we collected 5,966,490 genome sequences from various parts of the world, excluding those with incomplete or unknown/degenerate sequences. Our methodology included comparing sequences using BLASTN and BLASTP, analyzing RNA secondary structure, and calculating entropy. Our findings provide insights into the characteristics of SARS-CoV-2 and potential mechanisms of pathogenesis. We found that uracil had the highest proportion of all bases among various coronaviruses and cytosine to uracil mutations had the highest proportion among all point mutations. The consistency in the front part (1–26,599 nt) was significantly higher than that in the back part (26,600–29,903 nt) of the genome. For most genes, the similar consistency characteristics were also observed in their protein families.

IMPORTANCE
Our results indicate that most severe acute respiratory syndrome coronavirus 2 genomes sampled from patients had a mutation rate ≤1.07 ‰ and genome-tail proteins (including S protein) were the main sources of genetic polymorphism. The analysis of the virus-host interaction network of genome-tail proteins showed that they shared some antiviral signaling pathways, especially the intracellular protein transport pathway.
Paleoenvironmental and tectonic implications of an Upper Devonian glaciogenic succession from east-central West Virginia, USA
Authors: Ettensohn Frank R. , Seckinger D. Clay , Moecher David P. , Eble Cortland F. 
Published: November 2023

ABSTRACTGlaciogenic rocks are rare in the Appalachian area and occur only locally as parts of Upper Precambrian and Upper Devonian successions. This trip examines a relatively recent exposure of Upper Devonian glaciogenic diamictites and laminites along Corridor H (U.S. Highway 48) in east-central West Virginia, USA. The diamictites occur in the Rockwell Member of the Price Formation, in transition with the underlying redbeds of the Upper Devonian Hampshire Formation. Palynology indicates that all parts of the Rockwell Member exposed at the locality are present in the Retispora lepidophyta – Verrucosisporites nitidus (LN) Miospore Biozone and are, therefore, of Late Devonian, but not latest Devonian, age. This biozone occurrence indicates correlation with parts of the Oswayo Member of the Price Formation, the Finzel tongue of the Rockwell Formation, and with dropstone-bearing parts of the Cleveland Shale Member of the Ohio Shale in northeastern Kentucky. Much previous work supports a glaciogenic origin for the diamictites and associated sediments, which occur as parts of a shallow-marine incursion that ended the Hampshire/Catskill alluvial-plain/deltaic complex across much of the Central Appalachian area. The glaciogenic succession is part of nearshore, marginal-marine strata that accumulated in an embayment during the Cleveland-Oswayo-Finzel transgression, which represents a global eustatic sea-level rise and foreland subsidence related to Acadian/Neoacadian deformational loading in the adjacent orogen. Detrital-zircon-provenance data from the diamictites indicate Ordovician plutonic sources as well as reworked Neoproterozoic to Ordovician sedimentary sources that can only have been derived from nearby Inner Piedmont sources like the Potomac terrane. This provenance suggests that Acadian/Neoacadian convergence of the exotic Carolina terrane with the New York and Virginia promontories along the southeastern margin of Laurussia not only uplifted Inner Piedmont source areas into a high mountain range capable of supporting glaciation in a subtropical setting, but also, through deformational loading, enhanced regional subsidence and the incursion of shallow seas that allowed alpine glaciers access to the open sea.
Geologic setting and organic architecture of Fallingwater, Frank Lloyd Wright’s masterpiece
Authors: Zelt Fred , Shaulis Jim , Wach Grant 
Published: November 2023

ABSTRACT
Fallingwater is a UNESCO World Heritage Site that showcases a unique organic architectural design by Frank Lloyd Wright. Rising from bedrock in Mill Run, Pennsylvania, USA, Fallingwater incorporates large boulders into interior living spaces and is oriented with the geometry of a landscape created by the interplay of mountain and climate. Built to showcase local sandstone, Fallingwater is of the terrain. Building stone was quarried near the house from a 2-m-thick zone of quartzose medium to thin-bedded, fine- to very fine-grained sandstones in the Pennsylvanian upper Pottsville Formation. The building stone has abundant trace fossils and ripple marks, and is interpreted to have been deposited in shoreface environments with some tidal influence, or possibly in tidal flat environments. The house rests on sandstone bedrock of the Homewood sandstone, a Middle Pennsylvanian unit within the upper Pottsville Formation. At Fallingwater, the Homewood sandstone is interpreted to fill an incised valley with coarse, fluvial sandstones common in the lower part of the valley fill and finer-grained fluvial sandstones with possible evidence of marine or brackish influence in the upper fill. The Fallingwater building stone unit overlies the Homewood sandstone, above an interpreted marine flooding surface. Thickening of the Homewood sandstone in synclines suggests that deposition was influenced by Alleghanian deformation. Natural fractures in competent bedrock controlled the orientation of Bear Run at Fallingwater, and the fit of the house within the three-dimensional landscape of the valley, stream, and waterfall. Variation in natural fractures in bedded versus massive sandstone layers appears to have controlled the azimuths of the edges of the waterfalls at Fallingwater. Creation of the Fallingwater sandstone member of the Pottsville Formation is proposed.
Special geologic features of the Erie lakeshore, northwestern Pennsylvania, USA
Authors: Zelt Fred , Fleeger Gary M. 
Published: November 2023

ABSTRACT
The Erie lakeshore in Pennsylvania, west of the city of Erie, has many geological features that are ripe for study, teaching, and use as a vehicle for public science outreach. Features and processes on display include rapid slope failure and erosion of lakeshore bluffs, Pleistocene till in the bluffs, well-developed ancient sandy beach ridges atop till, and thin Upper Devonian sandstones that were deposited by storms. A wide variety of sedimentary, igneous, and metamorphic rocks can be found among cobbles eroded from till and rounded on lakeshore beaches, providing opportunities for teaching the identification of rocks, minerals, and Paleozoic marine fossils. Small fans at the bases of lakeshore bluffs have morphologies derived from distinct modes of sediment transport and deposition, with the potential to serve as analogs in better understanding large submarine fans. In winter, ice volcanoes can occur on the shoreline. Opportunities for teaching about geologic time are provided by localities where recent sedimentary processes, Pleistocene deposits, Paleozoic sedimentary rocks, and Precambrian igneous and metamorphic rocks can all be seen.
Occupational physical activity and risk of mortality in women and men: the Tromsø Study 1986–2021
Authors: Sagelv Edvard H , Dalene Knut Eirik , Eggen Anne Elise , Ekelund Ulf , Fimland Marius Steiro , Heitmann Kim Arne , Holtermann Andreas , Johansen Kristoffer Robin , Løchen Maja-Lisa , Morseth Bente , Wilsgaard Tom 
Published: November 2023

Objective
Associations between occupational physical activity (OPA) and mortality risks are inconclusive. We aimed to examine associations between (1) OPA separately and (2) jointly with leisure time physical activity (LTPA), and risk of all-cause, cardiovascular disease (CVD) and cancer mortality, over four decades with updated exposure and covariates every 6–8 years.

Methods
Adults aged 20–65 years from the Tromsø Study surveys Tromsø3-Tromsø7 (1986–2016) were included. We categorised OPA as low (sedentary), moderate (walking work), high (walking+lifting work) or very high (heavy manual labour) and LTPA as inactive, moderate and vigorous. We used Cox/Fine and Gray regressions to examine associations, adjusted for age, body mass index, smoking, education, diet, alcohol and LTPA (aim 1 only).

Results
Of 29 605 participants with 44 140 total observations, 4131 (14.0%) died, 1057 (25.6%) from CVD and 1660 (40.4%) from cancer, during follow-up (median: 29.1 years, 25th–75th: 16.5.1–35.3). In men, compared with low OPA, high OPA was associated with lower all-cause (HR 0.83, 95% CI 0.74 to 0.92) and CVD (subdistributed HR (SHR) 0.68, 95% CI 0.54 to 0.84) but not cancer mortality (SHR 0.99, 95% CI 0.84 to 1.19), while no association was observed for moderate or very high OPA. In joint analyses using inactive LTPA and low OPA as reference, vigorous LTPA was associated with lower all-cause mortality combined with low (HR 0.75, 95% CI 0.64 to 0.89), high (HR 0.67, 95% CI 0.54 to 0.82) and very high OPA (HR 0.74, 95% CI 0.58 to 0.94), but not with moderate OPA. In women, there were no associations between OPA, or combined OPA and LTPA, with mortality.

Conclusion
High OPA, but not moderate and very high OPA, was associated with lower all-cause and CVD mortality risk in men but not in women. Vigorous LTPA was associated with lower mortality risk in men with low, high and very high OPA, but not moderate OPA.
Responses to the Strengths and Difficulties Questionnaire predict HbA1c trajectories in children and adolescents with type 1 diabetes: a population-based study
Authors: Marks Kevin P , Pouwer Frans , Jensen Morten B , Ibfelt Else H , Kristensen Lene J , Thastum Mikael , Birkebæk Niels H 
Published: November 2023

IntroductionWe aimed to determine whether caregiver responses to the Strengths and Difficulties Questionnaire (SDQ) are predictive of HbA1c trajectory membership in children and adolescents with type 1 diabetes, when adjusting for covariates.Research design and methodsFor a Danish 2009 national cohort of children and adolescents with type 1 diabetes, we analyzed yearly HbA1c follow-up data during 2010–2020 including sociodemographic data from Danish national registries. Using group-based trajectory modeling and multinomial logistic regression, we tested whether caregiver SDQ scores predicted HbA1c trajectory membership when adjusting for sex, age at diabetes diagnosis, diabetes duration, family structure, and caregiver education.ResultsIn total, 835 children and adolescents (52% females) with a mean (SD) age of 12.5 (3.3) years, and a mean diabetes duration of 5.2 (3.1) years, were included. Based on 7247 HbA1c observations, four HbA1c trajectories were identified: (1) ‘on target, gradual decrease’ (26%), (2) ‘above target, mild increase then decrease’ (41%), (3) ‘above target, moderate increase then decrease’ (24%), and (4) ‘well above target, large increase then decrease’ (9%). Higher SDQ total difficulties scores predicted trajectories 3 and 4 (p=0.0002 and p<0.0001, respectively). Regarding the SDQ subscale scores, emotional symptoms predicted trajectories 3 and 4, and conduct problems and hyperactivity/inattention predicted trajectories 2, 3, and 4. Single-parent family and low caregiver education level both predicted trajectories 3 and 4.ConclusionsCaregiver SDQ responses and sociodemographic information may help detect children and adolescents with type 1 diabetes, who need intensive multidisciplinary medical and psychological interventions.
Health impacts in pathology workforce during mergers and acquisitions (M&A)
Authors: Chiou Paul Zone , Herring R Patti , Oh Jisoo , Medina Ernest 
Published: November 2023

AimsTo compare burn-out in laboratory professionals (LPs) with exposure to consolidation to those without, and to investigate the role of social support as a moderator in the exposure to mergers and acquisitions (M&A).MethodsSurveys were sent to the clinical LPs, including 732 with exposure to M&A and 819 without. The dependent variable was burn-out, and the independent variable was exposure to M&A. In investigating the role of social support in exposure group, a logistic regression was used with education, time since M&A, gender, merger types, practice setting, lab hierarchy and race as covariates.ResultsExposure to M&A was associated with higher levels of burn-out (p<0.05). In logistic regression of the workforce exposed to M&A, the odds for LP developing a high level of burn-out are lowered by 7.1% for every unit of increase in social support (OR 0.93; 95% CI 0.88 to 0.98; p=0.004).ConclusionLPs exposed to M&A are more likely to experience higher levels of burn-out but having social support can protect against burn-out, which has policy implications for leadership managing laboratories in times of M&A.
Suboptimal management of rheumatoid arthritis in France: a real-world study based on data from the French National Health Data System
Authors: Gaujoux-Viala Cécile , Bergmann Jean-Francois , Goguillot Mélanie , Mélaine Asma , Guérin Marie , Edouard Alban , Bénard Stève , Fautrel Bruno 
Published: November 2023

ObjectivesThe emergence of targeted therapy is changing rheumatoid arthritis (RA) management, but real-world data remain limited. This study aimed to describe real-world RA treatment patterns using data from a French national claims database.MethodsThis longitudinal study used the French Permanent Representative Sample (Echantillon Généraliste des Bénéficiaires) claims database. Patients with RA were identified between 2013 and 2017, with treatment patterns, persistence and adherence described.ResultsThe study population included 2553 patients with RA. Disease-modifying antirheumatic drugs (DMARDs) were prescribed for 1512 (59.2%) patients, of whom 721 (47.6%) did not require discontinuation or treatment switch. There were 377 (24.9%) treatment discontinuations and 114 patients (7.5%) switched to a targeted DMARD (biological and synthetic (Janus kinase inhibitor) DMARDs). Among the 2315 patients with RA in 2017, almost half (n=1102, 47.6%) were not treated with a DMARD. Most (85.7%) received symptomatic treatment (analgesics (81.0%), steroids (49.2%), non-steroidal anti-inflammatory drugs (39.5%)). Of the 1142 treatment initiations identified, 713 (62.4%) were conventional synthetic DMARDs (csDMARDs), with methotrexate being the most frequent (n=553, 48.45%). One-year persistence rates varied between 55.9% (49.2–62.0%) for tumour necrosis factor inhibitors, and 63.4% (59.6–67.0%) for csDMARDs. Treatment adherence, assessed through medication possession ratio, varied between 71.9% and 90.8%, with ≥80% being the adherence cut-off. Almost half of DMARD initiations were associated with long-term (>6 months), high-dose oral steroid use (~7 mg/day prednisone equivalent).ConclusionDespite a diverse therapeutic arsenal, there remains a medical need that is not covered by current RA management, which is frequently compensated for by overprescription of steroids.
Actovegin improves skeletal muscle mitochondrial respiration and functional aerobic capacity in a type 1 diabetic male murine model
Authors: Kosik Brandon , Larsen Steen , Bergdahl Andreas 
Published: November 2023

Insulin deficiency in type 1 diabetes (T1D) leads to an impairment of glucose metabolism and mitochondrial function. Actovegin is a hemodialysate of calf blood, which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effects of Actovegin on skeletal muscle mitochondrial respiration and functional aerobic capacity in a T1D mouse model. Effects on the expression of mitochondrial proteins, body mass, and food and water consumption were also investigated. Streptozotocin-induced T1D male C57B1/6 mice (aged 3–4 months) were randomized to an Actovegin group and a control group. Every third day, the Actovegin and control groups were injected intraperitoneally with (0.1 mL) Actovegin and (0.1 mL) physiological salt solution, respectively. Oxidative phosphorylation (OXPHOS) capacity of the vastus lateralis muscle was measured by high resolution respirometry in addition to the expression levels of the mitochondrial complexes as well as voltage-dependent anion channel. Functional aerobic capacity was measured using a rodent treadmill protocol. Body mass and food and water consumption were also measured. After 13 days, in comparison to the control group, the Actovegin group demonstrated a significantly higher skeletal muscle mitochondrial respiratory capacity in an ADP-restricted and ADP-stimulated environment. The Actovegin group displayed a significantly lesser decline in functional aerobic capacity and baseline body mass after 13 days. There were no significant differences in food or water consumption between groups. Actovegin could act as an effective agent for facilitating glucose metabolism and improving OXPHOS capacity and functional aerobic capacity in T1D. Further investigation is warranted to establish Actovegin’s potential as an alternative therapeutic drug for T1D.
Constraints on dark energy from the gravitational wave background
Authors: Khodagholizadeh Jafar 
Published: November 2023

AbstractCurrent observational data indicate that dark energy (DE) is a cosmological constant without considering its conclusiveness evidence. Considering the dynamic nature of $$\Lambda $$
Λ
individually as a function of time and the scale factor, we review their effects on the gravitational waves. This article is a continuation of the previous work (Khodagholizadeh in JHEAp 36:48–54, 2022), in which DE only was based on Hubble’s parameter and/or its derivatives. For the DE model based on the scale factor ($$a^{-m}$$

a

-
m

), the results showed that the parameter m is more limited as $$ 2 < m \leqslant 3$$

2
<
m
⩽
3

compared with the other models and due to the small value of DE density at the early universe. It is only in the mode $$m=3$$

m
=
3

that DE affects the low-frequency gravitational waves when its frequency is less than the $$10^{-3}$$

10

-
3

Hz in a matter-dominated epoch. The broad bound on reducing the amplitude and the B-B polarization multipole coefficients, from maximum to minimum, is for the models developed based on the Hubble parameter function. There are primary sources of low- and very low-frequency GWs, such as the coalescence of massive black hole binaries with $$M_{bh} > 10^{3} M_{sun}$$

M

bh

>

10
3

M

sun

, to determine the type of DE by mHz frequency space experiments (e.g., LISA) and by nHz-range NANOGrav 15-year data.