bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of brain endurance training on maximal oxygen uptake, time‐to‐exhaustion, and inhibitory control in runners
Authors: de Lima‐Junior Dalton , Silva Douglas Cavalcante , Ferreira Maria Elisa Caputo , de Sousa Fortes Leonardo
Published: August 2023

We aimed to analyze the effect of brain endurance training on maximum oxygen consumption (VO2máx), time‐to‐exhaustion, and inhibitory control in amateur trained runners. We employed a mixed experimental design, with the group as the between‐participant factor and time as the within‐participant factor. 45 participants attended 36 training sessions over 12 weeks. The cognitive training group (CT) performed the Stroop word‐color task [trials of each type (congruent, incongruent, and neutral) were randomly presented during each training session], the endurance training group (ET) participated in a running training program (intensity was 60%Δ of maximal aerobic velocity and performed on a motor‐driven treadmill), and the brain endurance training group (BET) make cognitive and endurance training simultaneously over 12 weeks. The total time of each session (i.e., 20–40 min) was identical in the experimental groups. VO2máx, time‐to‐exhaustion, and inhibitory control tests were measured before (baseline) and after (post‐experiment) the 12‐week intervention. A significant effect of interaction (group × time) for VO2máx (p < 0.05) was found. A post‐hoc test showed an increase in VO2máx from baseline to post‐experiment only for ET (Δ% = 2.98) and BET (Δ% = 3.78) groups (p < 0.05). Also, the analyses showed a significant interaction (group × time) for time‐to‐exhaustion (p < 0.05), and a post‐hoc test revealed an improvement in time‐to‐exhaustion for ET (Δ% = 8.81) and BET (Δ% = 11.01) (p < 0.05). No group × time interaction was found for accuracy and response time in the inhibitory control task (p > 0.05). The results conclude that BET was not superior to ET for improving VO2máx and time‐to‐exhaustion. Also, the findings conclude that BET improved inhibitory control similar to CT.
Is knowledge of racial identity development necessary? White transracial adoptive parents' intentions to promote Black adoptees’ racial‐ethnic identity
Authors: Pettis Shardé , Sonnentag Tammy L.
Published: August 2023

Adoptions of Black children by White parents in the United States are rapidly increasing and are a frequent transracial adoptee‐parent combination. With the prevalence of these adoptions, questions arise about White parents’ capability to promote the healthy racial‐ethnic identity of their adopted Black child(ren). This study examined if White parents’ knowledge of racial‐ethnic identity development impacts their intentions to promote their adopted Black children's racial‐ethnic identity in the context of the theory of planned behavior (TPB). White parents who have adopted, or were in the process of adopting, Black child(ren) (n = 199) completed measures examining their knowledge of racial‐ethnic identity development and their attitudes toward, perceived subjective norms for, perceived behavioral control of, and intentions related to engaging in racial‐ethnic socialization. Parents’ intentions to engage in racial‐ethnic socialization were positively correlated with their attitudes toward, subjective norms for, and perceived behavioral control of racial‐ethnic socialization. Knowledge did not predict parents’ intentions to engage in racial‐ethnic socialization above and beyond the components of the TPB. Finally, parents who perceived greater subjective norms for and greater behavioral control of racial‐ethnic socialization reported greater intentions to promote the racial‐ethnic identity of their adopted child(ren), and these relationships were particularly strong among parents with relatively low knowledge. Consistent with ideas in the TPB, White transracial adoptive parents’ knowledge of racial‐ethnic identity development (alone) may be neither necessary nor sufficient in predicting intentions to engage in racial‐ethnic socialization.
Characterization of the novel HLA‐DRB3*02:192 allele by sequencing‐based typing
Authors: Cargou Marine , Andreani Marco , Battarra Mariarosa , Tenchon Oceane , Visentin Jonathan
Published: August 2023

HLA‐DRB3*02:192 differs from DRB3*02:02:01:02 by one nucleotide substitution in codon 204 in exon 4.
Long‐term rain exclusion in a Mediterranean forest: response of physiological and physico‐chemical traits of Quercus pubescens across seasons
Authors: Laoué Justine , Havaux Michel , Ksas Brigitte , Tuccio Béatrice , Lecareux Caroline , Fernandez Catherine , Ormeño Elena
Published: August 2023

With climate change, an aggravation in summer drought is expected in the Mediterranean region. To assess the impact of such a future scenario, we compared the response of Quercus pubescens, a drought‐resistant deciduous oak species, to long‐term amplified drought (AD) (partial rain exclusion in natura for 10 years) and natural drought (ND). We studied leaf physiological and physico‐chemical trait responses to ND and AD over the seasonal cycle, with a focus on chemical traits including major groups of central (photosynthetic pigments and plastoquinones) and specialized (tocochromanols, phenolic compounds, and cuticular waxes) metabolites. Seasonality was the main driver of all leaf traits, including cuticular triterpenoids, which were highly concentrated in summer, suggesting their importance to cope with drought and thermal stress periods. Under AD, trees not only reduced CO2 assimilation (−42%) in summer and leaf concentrations of some phenolic compounds and photosynthetic pigments (carotenoids from the xanthophyll cycle) but also enhanced the levels of other photosynthetic pigments (chlorophylls, lutein, and neoxanthin) and plastochromanol‐8, an antioxidant located in chloroplasts. Overall, the metabolomic adjustments across seasons and drought conditions reinforce the idea that Q. pubescens is highly resistant to drought although significant losses of antioxidant defenses and photoprotection were identified under AD.
A retrospective analysis of haemolytic reactions to intravenous immunoglobulin using data from the Transfusion‐Transmitted Injuries Surveillance System (Ontario)
Authors: Batarfi Khalid , Liu Yang , Nixon Joanne , Webert Kathryn E. , John Melanie St. , Karunakaran Meera , Alhomsi Nour , Park Jane J. , Heddle Nancy M.
Published: August 2023

Background and Objectives

Haemolysis can occur following intravenous immunoglobulin (IVIG) infusion. Haemovigilance data were analysed using a novel approach for including two control groups with no haemolysis to IVIG. Objectives included a summary of all reactions to IVIG, rate estimates and analysis of haemolytic reactions including risk factors.

Materials and Methods

Canadian haemovigilance data from Ontario (2013–2021), IVIG distribution and transfusion data from the blood supplier, and data from a large local transfusion registry were used. An ‘other‐reactions’ control group included patients with IVIG reactions that were not haemolytic, and registry patients with no‐reaction were the ‘no‐reaction controls’. Descriptive analysis and two logistic regression models for the different control groups were performed.

Results

One thousand one hundred and seventy reactions were included. Most common were febrile non haemolytic (26.1%), minor allergic (24.5%) and IVIG headache (15.3%) followed by haemolytic 10.9% (128/1170). Haemolytic reaction rates decreased over time: rates since 2020 estimated between 1.5 and 2.9/1000 kg IVIG used. The regression model for other‐reaction controls identified two risk factors for haemolysis: non‐O blood group recipients compared with group O recipients (p value = 0.0106) and IVIG dose per 10 g increase (OR 1.359; 95% CI 1.225–1.506). The model using no‐reaction controls gave similar results and also showed no pre‐medication was associated with a higher risk of haemolysis (OR 29.084; 95% CI 1.989–425.312).

Conclusion

The frequency of haemolytic reactions has decreased over time. We confirmed non‐O blood group recipients and IVIG dose as risk factors for haemolysis and raise the hypothesis that no pre‐medication may increase the risk of haemolysis.
Molecular phylogeny of the marine snail genus Haminoea (Gastropoda, Cephalaspidea): A framework to study marine diversity and speciation
Authors: Turani Martina , Valdés Ángel , Malaquias Manuel António E.
Published: August 2023

Haminoea are herbivorous, coastal snails occurring in temperate and tropical waters of the Atlantic and Eastern Pacific oceans, with one species present in temperate South Africa (Indian Ocean). The genus is taxonomically difficult as several available nominal species were introduced based on shell descriptions alone, or described based on subtle differences in morpho‐anatomical features, without a phylogenetic molecular framework. Fifteen species are currently accepted as valid in recent scientific literature and field guides (eight Eastern Atlantic, one temperate Indian Ocean, four Western Atlantic and three Eastern Pacific). Here we generate the first complete phylogeny (Bayesian and Maximum Likelihood) of this genus based on multilocus molecular data (COI, 12S rRNA, 16S rRNA, 28S rRNA) using a taxon set accumulated over a period of 15 years, coupled with species delimitation analyses methods (ABGD, ASAP, bPTP) and morpho‐anatomical studies. The goal of this study is to provide insights into the taxonomy, phylogenetic relationships and geographical distributions of species while generating a framework for future systematic reviews of the genus, as well as to study speciation and historical biogeography. Our results rendered four possible hypotheses of species diversity: with 14, 15, 19 and 20 candidate species and point to the fact that several taxa presently regarded as valid might be conspecific (e.g. H. orteai–H. templadoi–H. exigua; and H. alfredensis–H. antillarum–H. orbignyana), while highlighting the existence of a complex of four or five species often identified as H. elegans. Pervasive nomenclatural problems in the genus, including with the type species H. hydatis, are highlighted and discussed.
Proteolytic markers associated with a gain and loss of leg muscle mass with resistance training followed by high‐intensity interval training
Authors: Michel J. Max , Godwin Joshua S. , Plotkin Daniel L. , Mesquita Paulo H. C. , McIntosh Mason C. , Ruple Bradley A. , Libardi Cleiton A. , Mobley C. Brooks , Kavazis Andreas N. , Roberts Michael D.
Published: August 2023

We recently reported that vastus lateralis (VL) cross‐sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high‐intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college‐aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P < 0.05). 20S proteasome core protein abundance increased at POST versus PRE (P = 0.031) and MID (P = 0.049). 20S proteasome activity, and protein levels for calpain‐2 and Beclin‐1 increased at MID and POST versus PRE (P < 0.05). Ubiquitinated proteins showed model significance (P = 0.019) with non‐significant increases at MID and POST (P > 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin‐like growth factor 1; IGF1) followed by a subsequent AMP‐activated protein kinase activator (5‐aminoimidazole‐4‐carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1‐treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1‐treated versus I+A myotubes (P < 0.001). In summary, the loss in RT‐induced VL CSA with HIIT coincided with increases in several proteolytic markers, and sustained proteolysis may have driven this response. Moreover, while not measured in humans, we interpret our in vitro data to suggest that (unlike RT) HIIT does not stimulate MPS.
Expression and function analyses of sex-lethal gene in Phytoseiulus persimilis
Authors: Li Mingxia , Wang Zhenhui , Wang Endong , Zhang Bo , Lv Jiale , Xu Xuenong
Published: August 2023

Phytoseiulus persimilis is a specialist predator of spider mites, with promising control effects. Its population generally has a stable sex ratio. Under appropriate conditions, the proportion of female offspring can reach 80%. But the mechanisms of sex determination in P. persimilis is still unclear. Sex-lethal (sxl) is an important gene in studying sex regulation mechanisms in insects. In the model organism Drosophila melanogaster, it has been proved to be a switch controlling sex determination. Herein, we screened one sex-lethal gene ortholog in the genome of P. persimilis (Ppsxl). We separated male and female offspring successfully based on the order of the egg laid, and found Ppsxl is expressed in both sexes at different stages. The expression peak was found in females 10 h after mating, and it was also highly expressed in eggs that developed into males. RNA interference was used to study the function of Ppsxl. When Ppsxl was interfered, all female individuals remained fertile. However, their cumulative fecundity decreased by 18.0%, daily fecundity decreased by 13.4%, and the proportion of female offspring decreased by 22.7%. This study showed that Ppsxl gene has a certain influence on the reproduction of P. persimilis, but its influence on sex determination may not be as critical as that in D. melanogaster. The regulation of sxl on P. persimilis was different from that in D. melanogaster.
Novel process integration flow of germanium-on-silicon FinFETs for low-power technologies
Authors: Choudhary Sumit , Yogesh Midathala , Schwarz Daniel , Funk Hannes S. , Ghosh Subrata , Sharma Satinder K. , Schulze Jörg , Gonsalves Kenneth E.
Published: August 2023

Germanium channel FinFET transistors process integration on a silicon substrate is a promising candidate to extend the complementary metal–oxide–semiconductor semiconductor roadmap. This process has utilized the legacy of state-of-art silicon fabrication process technology and can be an immediate solution to integrate beyond Si channel materials over standard Si wafers. The fabrication of such devices involves several complicated technological steps, such as strain-free epi layers over the Si substrate to limit the substrate leakage and patterning of narrow and sharp fins over germanium (Ge). To overcome these issues, the active p-type germanium layers were grown over n-type germanium and virtual substrates. The poly ((4-(methacryloyloxy) phenyl) dimethyl sulfoniumtriflate) was utilized as a polymeric negative tone e-beam resist for sub-20 nm critical dimensions with low line edge roughness, line width roughness, and high etch resistance to pattern p-Ge fins to meet these concerns. Here, the devices use the mesa architecture that will allow low bandgap materials only at the active regions and raised fins to reduce the active area interaction with the substrate to suppress leakage currents. This paper discusses the simple five-layer process flow to fabricate FinFET devices with critical optimizations like resist prerequisite optimization conditions before exposure, alignment of various layers by electron beam alignment, pattern transfer optimizations using reactive ion etching, and bilayer resist for desired lift-off. The Ge-on-Si FinFET devices are fabricated with a width and gate length of 15/90 nm, respectively. The devices exhibit the improved ION/IOFF in order of ∼105, transconductance Gm ∼86 μS/μm, and subthreshold slope close to ∼90 mV/dec.
A Resource for Promoting Personal and Social Responsibility in Higher Education: A Call to Action for Kinesiology Departments
Authors: Kuipers Karisa L. , Jacobs Jennifer M. , Wright Paul M. , Richards Kevin Andrew
Published: August 2023

In recent decades, emphasis on helping postsecondary students develop personal and social responsibility has increased in higher education. The purpose of this conceptual paper is to propose a kinesiology-based model to assist in defining, implementing, and evaluating personal and social responsibility education with postsecondary students. In the paper, a general overview of the higher education landscape as it relates to personal and social responsibility is presented. Then, the teaching personal and social responsibility model is presented as a model that is already familiar in kinesiology and may assist in defining, implementing, and evaluating structures and strategies for promoting personal and social responsibility in higher education. The alignment of this model and the personal and social responsibility priorities of higher education are analyzed. Recommendations for implementing specific strategies and resources associated with the teaching personal and social responsibility model into higher education are shared, and next steps for integrating these resources are acknowledged.
Complete genome sequence of the
Microbacterium
sp. strain BDGP8
Authors: Wan Kenneth H. , Park Soo , Booth Benjamin W. , Brydon Ella C. , Eichenberger Joanne , Inman Jamie L. , Mao Jian-Hua , Snijders Antoine M. , Celniker Susan E.
Published: August 2023

Microbacterium
sp. BDGP8 is a species of facultative anaerobic gram-positive bacterium of the family Microbacteriaceae. The complete genome consists of a single circular chromosome of 3,293,567 bp with a G + C content of 69.84% and two plasmids of 49,365 bp and 32,884 bp.
Phyllosphere microbial diversity and specific taxa mediate within-cultivar resistance to
Phytophthora palmivora
in cacao
Authors: Schmidt Jennifer E. , Puig Alina S. , DuVal Ashley E. , Pfeufer Emily E.
Published: August 2023

The oomycete pathogen
Phytophthora palmivora
, which causes black pod rot (BPR) on cacao (
Theobroma cacao
L.), is responsible for devastating yield losses worldwide. Genetic variation in resistance to
Phytophthora
spp. is well documented among cacao cultivars, but variation has also been observed in the incidence of BPR even among trees of the same cultivar. In light of evidence that the naturally occurring phyllosphere microbiome can influence foliar disease resistance in other host-pathogen systems, it was hypothesized that differences in the phyllosphere microbiome between two field accessions of the cultivar Gainesville II 164 could be responsible for their contrasting resistance to
P. palmivora
. Bacterial alpha diversity was higher but fungal alpha diversity was lower in the more resistant accession MITC-331, and the accessions harbored phyllosphere microbiomes with distinct community compositions. Six bacterial and 82 fungal amplicon sequence variants (ASVs) differed in relative abundance between MITC-333 and MITC-331, including bacterial putative biocontrol agents and a high proportion of fungal pathogens, and nine fungal ASVs were correlated with increased lesion development. The roles of contrasting light availability and host mineral nutrition, particularly potassium, are also discussed. Results of this preliminary study can be used to guide research into microbiome-informed integrated pest management strategies effective against
Phytophthora
spp. in cacao.

IMPORTANCE

Up to 40% of the world’s cacao is lost each year to diseases, the most devastating of which is black pod rot, caused by
Phytophthora palmivora
. Though disease resistance is often attributed to cacao genotypes (i.e., disease-resistant rootstocks), this study highlights the role of the microbiome in contributing to differences in resistance even among accessions of the same cacao cultivar. Future studies of plant-pathogen interactions may need to account for variation in the host microbiome, and optimizing the cacao phyllosphere microbiome could be a promising new direction for
P. palmivora
resistance research.
Catalase produced by
Candida albicans
protects
Streptococcus mutans
from H
2
O
2
stress—one more piece in the cross-kingdom synergism puzzle
Authors: Katrak Callahan , Garcia Bruna A. , Dornelas-Figueira Louise M. , Nguyen Mary , Williams Robert B. , Lorenz Michael C. , Abranches Jacqueline
Published: August 2023

Co-infection with
Streptococcus mutans
and
Candida albicans
is associated with dental caries, and their co-cultivation results in enhanced biofilm matrix production that contributes to increased virulence and caries risk. Moreover, the catalase-negative
S. mutans
demonstrates increased oxidative stress tolerance when co-cultivated in biofilms with
C. albicans,
a catalase-producing yeast. Here, we sought to obtain mechanistic insights into the increased H
2
O
2
tolerance of
S. mutans
when co-cultivated with clinical isolates of
Candida glabrata
,
Candida tropicalis,
and
C. albicans
. Additionally, the
C. albicans
SC5314 laboratory strain, its catalase mutant (SC5314
Δcat1
), and
S. mutans
UA159 and its glucosyltransferase B/C mutant (UA159
ΔgtfB/C
) were grown as single- and dual-species biofilms. Time-kill assays revealed that upon acute H
2
O
2
challenge, the survival rates of
S. mutans
in dual-species biofilms with the clinical isolates and
C. albicans
SC5314 were greater than when paired with SC5314
Δcat1
or as a single-species biofilm. Importantly, this protection was independent of glucan production through
S. mutans
GtfB/C. Transwell assays and treatment with H
2
O
2
-pre-stimulated
C. albicans
SC5314 supernatant revealed that this protection is contact-dependent. Biofilm stability assays with sublethal H
2
O
2
or peroxigenic
Streptococcus
A12 challenge resulted in biomass reduction of single-species
S. mutans
UA159 and dual-species with SC5314
Δcat1
biofilms compared to UA159 biofilms co-cultured with
C. albicans
SC5314.
S. mutans
oxidative stress genes were upregulated in single-species biofilms when exposed to H
2
O
2,
but not when
S. mutans
was co-cultivated with
C. albicans
SC5314. Here, we uncovered a novel, contact-dependent, synergistic interaction in which the catalase of
C. albicans
protects
S. mutans
against H
2
O
2
.

IMPORTANCE

It is well established that co-infection with the gram-positive caries-associated bacterium
Streptococcus mutans
and the yeast pathobiont
Candida albicans
results in aggressive forms of caries in humans and animal models. Together, these microorganisms form robust biofilms through enhanced production of extracellular polysaccharide matrix. Further, co-habitation in a biofilm community appears to enhance these microbes’ tolerance to environmental stressors. Here, we show that catalase produced by
C. albicans
protects
S. mutans
from H
2
O
2
stress in a biofilm matrix-independent manner. Our findings uncovered a novel synergistic trait between these two microorganisms that could be further exploited for dental caries prevention and control.
Tezacaftor/Ivacaftor therapy has negligible effects on the cystic fibrosis gut microbiome
Authors: Marsh Ryan , Dos Santos Claudio , Hanson Liam , Ng Christabella , Major Giles , Smyth Alan R. , Rivett Damian , van der Gast Christopher
Published: August 2023

People with cystic fibrosis (pwCF) experience a range of persistent gastrointestinal symptoms throughout life. There is evidence indicating interaction between the microbiota and gut pathophysiology in CF. However, there is a paucity of knowledge on the potential effects of CF transmembrane conductance regulator (CFTR) modulator therapies on the gut microbiome. In a pilot study, we investigated the impact of Tezacaftor/Ivacaftor dual combination CFTR modulator therapy on the gut microbiota and metabolomic functioning in pwCF. Fecal samples from 12 pwCF taken at baseline and following placebo or Tezacaftor/Ivacaftor administration were subjected to microbiota sequencing and to targeted metabolomics to assess the short-chain fatty acid (SCFA) composition. Ten healthy matched controls were included as a comparison. Inflammatory calprotectin levels and patient symptoms were also investigated. No significant differences were observed in overall gut microbiota characteristics between any of the study stages, extended also across intestinal inflammation, gut symptoms, and SCFA-targeted metabolomics. However, microbiota and SCFA metabolomic compositions, in pwCF, were significantly different from controls in all study treatment stages. CFTR modulator therapy with Tezacaftor/Ivacaftor had negligible effects on both the gut microbiota and SCFA composition across the course of the study and did not alter toward compositions observed in healthy controls. Future longitudinal CFTR modulator studies will investigate more effective CFTR modulators and should use prolonged sampling periods, to determine whether longer-term changes occur in the CF gut microbiome.

IMPORTANCE

People with cystic fibrosis (pwCF) experience persistent gastrointestinal (GI) symptoms throughout life. The research question “how can we relieve gastrointestinal symptoms, such as stomach pain, bloating, and nausea?” remains a top priority for clinical research in CF. While CF transmembrane conductance regulator (CFTR) modulator therapies are understood to correct underlying issues of CF disease and increasing the numbers of pwCF are now receiving some form of CFTR modulator treatment. It is not known how these therapies affect the gut microbiome or GI system. In this pilot study, we investigated, for the first time, effects of the dual combination CFTR modulator medicine, Tezacaftor/Ivacaftor. We found it had negligible effects on patient GI symptoms, intestinal inflammation, or gut microbiome composition and functioning. Our findings are important as they fill important knowledge gaps on the relative effectiveness of these widely used treatments. We are now investigating triple combination CFTR modulators with prolonged sampling periods.
Genomic diversity and biogeographic distributions of a novel lineage of bacteriophages that infect marine OM43 bacteria
Authors: Yang Mingyu , Du Sen , Zhang Zefeng , Xia Qian , Liu He , Qin Fang , Wu Zuqing , Ying Hanqi , Wu Yin , Shao Jiabing , Zhao Yanlin
Published: August 2023

The marine methylotrophic OM43 clade is considered an important bacterial group in coastal microbial communities. OM43 bacteria, which are closely related to phytoplankton blooms, have small cell sizes and streamlined genomes. Bacteriophages profoundly shape the evolutionary trajectories, population dynamics, and physiology of microbes. The prevalence and diversity of several phages that infect OM43 bacteria have been reported. In this study, we isolated and sequenced two novel OM43 phages, MEP401 and MEP402. These phages share 90% of their open reading frames (ORFs) and are distinct from other known phage isolates. Furthermore, a total of 99 metagenomic viral genomes (MVGs) closely related to MEP401 and MEP402 were identified. Phylogenomic analyses suggest that MEP401, MEP402, and these identified MVGs belong to a novel subfamily in the family
Zobellviridae
and that they can be separated into two groups. Group I MVGs show conserved whole-genome synteny with MEP401, while group II MVGs possess the MEP401-type DNA replication module and a distinct type of morphogenesis and packaging module, suggesting that genomic recombination occurred between phages. Most members in these two groups were predicted to infect OM43 bacteria. Metagenomic read-mapping analysis revealed that the phages in these two groups are globally ubiquitous and display distinct biogeographic distributions, with some phages being predominant in cold regions, some exclusively detected in estuarine stations, and others displaying wider distributions. This study expands our knowledge of the diversity and ecology of a novel phage lineage that infects OM43 bacteria by describing their genomic diversity and global distribution patterns.

IMPORTANCE

OM43 phages that infect marine OM43 bacteria are important for host mortality, community structure, and physiological functions. In this study, two OM43 phages were isolated and characterized. Metagenomic viral genome (MVG) retrieval using these two OM43 phages as baits led to the identification of two phage groups of a new subfamily in the family
Zobellviridae
. We found that group I MVGs share similar genomic content and arrangement with MEP401 and MEP402, whereas group II MVGs only possess the MEP401-type DNA replication module. Metagenomic mapping analysis suggests that members in these two groups are globally ubiquitous with distinct distribution patterns. This study provides important insights into the genomic diversity and biogeography of the OM43 phages in the global ocean.
Interseismic creep of carbonate-hosted seismogenic normal faults: Insights from central Italy
Authors: Del Sole Leonardo , Mazzoli Stefano , Carafa Michele M.C. , Toffol Giovanni , Pennacchioni Giorgio , Giuli Gabriele , Invernizzi Chiara , Tondi Emanuele
Published: August 2023

Understanding fault behavior in carbonates is critical because they represent loci of earthquake nucleation. Models of fault-slip mode generally assume: (1) seismic sliding and aseismic sliding occur in different fault patches, (2) creep is restricted to lithology-controlled weak domains, and (3) rate-weakening patches are interseismically locked. We studied three carbonate-hosted seismogenic normal faults in central Italy by combining (micro)structural and geochemical analyses of fault rocks integrated with new seismic coupling estimates. The (upper bound) seismic coupling was estimated to be ∼0.75, which indicates that at least 25% of the long-term deformation in the study area is released aseismically in the upper crust. Microscopy and electron-backscatter diffraction analyses revealed that whereas the localized principal slip zone records seismic slip (as ultracataclastic material, calcite crystallographic preferred orientation (CPO), and truncated clasts), the bulk fault rock below behaves differently. Cataclasites in massive limestones deform by cataclastic flow, pressure solution, and crystal plasticity, along with CPO development. Foliated tectonites in micritic limestones deform by pressure solution and frictional sliding, with CPO development. We suggest these mechanisms accommodate on-fault interseismic creep. This is consistent with experimental results reporting velocity-strengthening behavior at low slip rates. We present multiscale evidence of coexisting seismic and aseismic slip along the same fault in limestones during the seismic cycle. Our results imply that on-fault aseismic motion must be added to seismic slip to reconcile the long-term deformation rates and that creep is not exclusive to phyllosilicate-bearing units. Our work constitutes a step forward in understanding fault behavior and the seismic cycle in carbonates, and it may profoundly impact future studies on seismogenic potential and earthquake hazard assessment.
He Isotopic Composition of Alkaline Intrusions of the Hovsgol Area, Northwestern Mongolia
Authors: Vrublevskii V. V. , Petlina A. A. , Gudkov A. V. , Sidorov M. Yu. , Semiryuakov A. S. , Shelepaev R. A. , Vishnevskii A. V. , Gertner I. F. , Fomina E. N. , Kozlov E. N. , Udoratina O. V.
Published: August 2023

The He isotopic composition of fluid inclusions in magnetite of alkaline and subalkaline intrusion of the Hovsgol region, Northwestern Mongolia, is studied. The measured 4He content varies from 6.6 × 10–7 to 114 × 10–7 cm3/g. The 3He/4He isotope ratio of most samples is 0.23–0.59 Ra indicating the presence of He from different sources in magmatic fluid. The maximum of mantle He (2.51 Ra) is observed in magnetite of subalkali gabbro. The mantle He component was ~40–60% during the generation of parental magma with possible involvement of subcontinental lithospheric mantle material or a plume-like reservoir less enriched in 3He. The mantle He component did not exceed 10–15% during the evolution of the foidoitic and alkali-syenitic melts because of mixing with crustal radiogenic He. We suggest the interaction of intrusions with fragments of the Precambrian accretionary–collision complexes of the Tuva–Mongolian Terrane. This mixing of He isotopes in melts and fluids can serve as indirect evidence of the development of mantle magmatism at the active continental margin.
Possibility of Using Zoning of Fallow Vegetation by Vegetation Indices to Assess Organic Matter Accumulation in Postagrogenic Soils
Authors: Giniyatullin K. G. , Sahabiev I. A. , Ryazanov S. S. , Smirnova E. V. , Tishin D. V. , Latypova L. I.
Published: August 2023

Light gray forest soils (Eutric Retisols (Loamic, Cutanic, Ochric)) were studied under a 20–25-yr-old fallow at the stage of overgrowing by meadow vegetation, pine, and birch. The studied area plot was confined to one element of topography, without morphological evidences of erosion processes, and with relatively homogenous soil texture. To assess the influence of fallow vegetation on the formation of soil organic matter (SOM), the plant cover was zoned according to vegetation indices calculated on the basis of remote sensing data. The k-means algorithms and the Random Forest method were used for this purpose. It was shown that there were statistically significant differences between the types of land cover in terms of the SOM stocks in the upper layer of the old-arable horizon with the specification of three and four clusters. The specification of three classes of vegetation on the fallow—coniferous woody vegetation, deciduous woody vegetation, and herbaceous vegetation—proved to be the most expedient; the correctness of their allocation was confirmed by the geobotanical survey of the territory. The results of a pairwise comparison of sites occupied by different types of fallow vegetation indicated that they significantly differ in the SOM stocks only in the uppermost 5-cm-thick layer of the old-arable horizon and only for the pair of coniferous woody and herbaceous vegetation. Differences in the accumulated humus stocks in the layer of 0–10 cm were statistically significant for the soils under deciduous and coniferous woody vegetation and under herbaceous and coniferous woody vegetation. There was no significant difference in this indicator between the soils under deciduous woody vegetation and herbaceous vegetation.
Implementation of the HepClinktest-and-treat community strategy targeting Pakistani migrants with hepatitis C living in Catalonia (Spain) compared with the current practice of the Catalan health system: budget impact analysis
Authors: Reyes-Urueña Juliana , Costell-González Francisco , Egea-Cortés Laia , Ouaarab Hakima , Saludes Veronica , Buti Maria , Majó Xavier , Colom Joan , Gómez i Prat Jordi , Casabona Jordi , Martró Elisa
Published: August 2023

Objectives

To perform a budget impact analysis of the HepClinktest-and-treat strategy in which community health agents offer hepatitis C virus (HCV) testing, diagnosis and treatment to the Pakistani population living in Catalonia compared with the current practice of the Catalan health system (without targeted screening programmes).

Methods

We estimated the population of adult Pakistani migrants registered at the primary care centres in Catalonia by means of the Information System for the Development of Research in Primary Care (n=37 972 in 2019, Barcelona health area). This cohort was followed for a time period of 10 years after HCV diagnosis (2019–2028). The statistical significance of the differences observed in the anti-HCV positivity rate between screened and non-screened was confirmed (α=0.05). The budget impact was calculated from the perspective of the Catalan Department of Health. Sensitivity analyses included different levels of participation in HepClink: pessimistic, optimistic and maximum.

Results

The HepClinkscenario screened a higher percentage of individuals (69.8%) compared with the current scenario of HCV care (39.7%). Viraemia was lower in the HepClinkscenario compared with the current scenario (1.7% vs 2.5%, respectively). The budget impact of the HepClinkscenario was €884 244.42 in 10 years.

Conclusions

Scaling up the HepClinkstrategy to the whole Catalan territory infers a high budget impact for the Department of Health and allows increasing the detection of viraemia (+17.8%) among Pakistani migrants ≥18 years. To achieve a sustainable elimination of HCV by improving screening and treatment rates, there is room for improvement at two levels. First, taking advantage of the fact that 68.08% of the Pakistani population had visited their primary care physicians to reinforce targeted screening in primary care. Second, to use HepClinkat the community level to reach individuals with reluctance to use healthcare services.
Can a nation-wide e-cohort of ADHD and ASD in childhood be established using Welsh routinely available datasets?
Authors: Langley Kate , Del Pozo-Banos Marcos , Daalsgard Søren , Paranjothy Shantini , Riglin Lucy , John Ann , Thapar Anita
Published: August 2023

Objectives

We investigated the feasibility and validity of establishing a nationwide e-cohort of individuals with a diagnosis of attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) for future longitudinal research.

Design

Individuals with a childhood diagnosis of ADHD/ASD as recorded on routinely available healthcare datasets were compared with matched controls and a sample of directly assessed individuals with ADHD.

Setting

This study used data from the Welsh Secure Anonymised Information Linkage Databank in Wales, UK. Routinely collected data from primary care, emergency department and hospital admissions were linked at person level.

Participants

All individuals in Wales, UK born between 1 January 1991 and 31 December 2000. Individuals with a recorded diagnosis of ADHD and/or ASD by age 18 years were identified using International Classification of Diseases, 10th Revision and National Health Service (NHS) READ codes and matched to 3 controls each and 154 individuals with ADHD recruited from an established research study.

Outcome measures

Recorded service use for anxiety and depression, alcohol and drug use and self-harm including emergency department use in young adulthood (age 16–25 years).

Results

7726 individuals had a recorded diagnosis of ADHD (80% male) and 5001 of ASD (79% male); 1.4% and 0.9% of the population, respectively. Cox’s regression analyses showed ADHD was associated with increased risks of anxiety/depression (HR: 2.36, 95% CI: 2.20 to 2.53), self-harm (HR: 5.70, 95% CI: 5.07 to 6.40), alcohol (HR: 3.95, 95% CI: 3.42 to 4.56), drug use (HR: 5.88, 95% CI: 5.08 to 6.80) and emergency department service use (HR: 1.36, 95% CI: 1.31 to 1.41). Those with ASD were at increased risk of anxiety/depression (HR: 2.11, 95% CI: 1.91 to 2.34), self-harm (HR: 2.93, 95% CI: 2.45 to 3.50) and drug use (HR: 2.21, 95% CI: 1.66 to 2.95) but not alcohol use. The ADHD e-cohort were similar to the directly assessed cohort.

Conclusions

Our identification strategy demonstrated the feasibility of establishing a large e-cohort of those with ADHD/ASD with expected patterns of poorer early adult outcomes, demonstrating a valid method of identifying large samples for future longitudinal studies without selective attrition.
Carbon footprint of industry-sponsored late-stage clinical trials
Authors: Mackillop Neil , Shah Jayesh , Collins Michael , Costelloe Thomas , Öhman Daniel
Published: August 2023

Objectives

To quantify the carbon footprint from a sample of pharma industry sponsored phase III trials. To develop an approach that can readily be applied to future trials by AstraZeneca and other trial sponsors.

Design

Life cycle assessment including all the sources of carbon emissions associated with a completed, an ongoing and a planned clinical trial. The methodology followed the guidance on appraising the sustainability of Care Pathways, developed by the UK National Health Service in collaboration with parties across the healthcare system.

Setting

Three multicentre late phase trials. One completed heart failure trial, one ongoing oncology trial and one asthma trial with the addition of devices to be representative of current practice.

Participants

The three trials had a total number of 7412 participants.

Main outcome measures

Total carbon emissions from each trial, the drivers of those emissions and the emissions per patient.

Results

The total carbon footprint for the cardiovascular trial was calculated as 2498 tonnes carbon dioxide equivalents (CO2e), the first 3 years of the oncology trial resulted in 1632 tonnes CO2e and the respiratory trial 1437 tonnes CO2e.

Conclusions

We have shown that it is feasible to perform a retrospective life cycle assessment to appraise the carbon footprint of large clinical trials and confirmed that phase III trials result in significant emissions. Having identified all the drivers of emissions and their magnitude, we are well placed to develop a plan for achieving net-zero carbon clinical trials. Now it is possible to expand the use of life cycle assessment to planned studies so that scientific aims can be achieved with a minimum of carbon emissions. We encourage other trialists to apply the same methodology as a necessary first step in reducing the carbon footprint of clinical trials.
Effect of aqueous olanexidine versus alcohol-based chlorhexidine for surgical skin antisepsis on incidence of surgical site infections in gastrointestinal surgery: multicentre randomised controlled clinical trial (OEDO trial) protocol
Authors: Takeuchi Masashi , Obara Hideaki , Furube Tasuku , Kawakubo Hirofumi , Kitago Minoru , Okabayashi Koji , Aoyama Junya , Amemiya Ryusuke , Fujisaki Hiroto , Sano Junichi , Goto Rei , Sato Yasunori , Kitagawa Yuko
Published: August 2023

Introduction

Surgical site infections (SSIs) are among the most common nosocomial infections in surgery patients. Two types of preparations, povidone-iodine and chlorhexidine-alcohol, are commonly used in preoperative antiseptic procedures worldwide. However, there are inconsistencies among international guideline recommendations concerning skin antiseptics. This trial aimed to evaluate the superiority of olanexidine, which reduced SSI rates more than povidone-iodine in our previous randomised trial, over chlorhexidine-alcohol in clean-contaminated surgery.

Methods and analysis

This multicentre randomised controlled clinical trial will compare two antiseptics (1.5% olanexidine and 1.0% chlorhexidine-alcohol) to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. On providing consent, patients aged <18 years will be included. The primary outcome will be the postoperative 30-day overall SSI rate, while the secondary outcomes will be the postoperative 30-day superficial incisional SSI rate, deep incisional SSI rate, organ/space SSI rate, positive bacterial wound culture rate, cultured bacterial strains, rates of intervention-related toxicity and allergic events (eg, erythema, pruritus, dermatitis and other symptoms of allergy around the region disinfected by the antiseptic during surgery), rate of reoperations due to SSI, medical economic effect indicators (based on health insurance claims) and hospital duration. The Mantel-Haenszel method will be used to estimate the adjusted risk ratio and its 95% CI for the primary analysis, which will compare the treatment effects.

Ethics and dissemination

The protocol was approved by the Institutional Review Board of Keio University School of Medicine and subsequently by the board of each participating site. Participant recruitment began in January 2023. The final results will be published in medical journals after international peer review.

Trial registration number

UMIN000049712.
TP53gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma
Authors: Shi Yewen , Ren Xiaoyong , Cao Shaolong , Chen Xi , Yuan Bo , Brasil da Costa Fabio Henrique , Rodriguez Rosario Alanis E , Corona Arnoldo , Michikawa Chieko , Veeramachaneni Ratna , Osman Abdullah A , Xie Tongxin , Wang Wenyi , Sikora Andrew G , Myers Jeffrey N , Rangel Roberto
Published: August 2023

Background

TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. SomaticTP53mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role ofTP53gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.

Methods

Short hairpin RNA knockdown of mutantp53R172Hin syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutantp53R172H. Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutantp53R172Hin the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level.

Results

Mutantp53R172Hcontributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8+T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover,p53R172Halso regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly,p53R172H-mutated tumors are infiltrated with CD8+and CD4+T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and theTP53R175Hmutation, which paralleled the findings from our syngeneic mouse tumor model.

Conclusions

These findings demonstrate that syngeneic tumors bearing theTP53R172Hgain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.
Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy
Authors: Schina Aimilia , Sztupinszki Zsofia , Marie Svane Inge , Szallasi Zoltan , Jönsson Göran , Donia Marco
Published: August 2023

Background

Effective cooperation between B-cells and T-cells within the tumor microenvironment may lead to the regression of established tumors. B-cells and T-cells can recognize tumor antigens with exquisite specificity via their receptor complexes. Nevertheless, whether a diverse intratumoral B-cells and T-cell receptor (BCR, TCR) repertoire affects the tumor immune microenvironment (TIME) and clinical outcomes in patients treated with immunotherapy is unclear.

Methods

We extracted information on BCR and TCR repertoire diversity from large clinical datasets and measured the association between immune receptor diversity features, the TIME, and clinical outcomes of patients treated with anti-PD-1/PD-L1 immunotherapy.

Results

In multiple tumor types, an increasingly diverse TCR repertoire was strongly associated with a highly activated TIME, while BCR diversity was more associated with antibody responses but not with the overall B-cell infiltration nor with measures related to intratumoral CD8+T cell activity. Neither TCR nor BCR diversity was independent prognostic biomarkers of survival across multiple cancer types. However, both TCR and BCR diversity improved the performance of predictive models combined with established biomarkers of response to immunotherapy.

Conclusion

Overall, these data indicate a currently unexplored immunological role of intratumoral B-cells associated with BCR diversity and antibody responses but independent of classical anticancer T-cells intratumoral activities.