bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormally high exertional breathlessness predicts mortality in people referred for incremental cycle exercise testing
Authors: Elmberg Viktor , Zhou Xingwu , Lindow Thomas , Hedman Kristofer , Malinovschi Andrei , Lewthwaite Hayley , Jensen Dennis , Brudin Lars , Ekström Magnus 
Published: April 2024

ABSTRACTBackgroundExertional breathlessness is a key symptom in cardiorespiratory disease and can be quantified using incremental exercise testing (IET), but its prognostic significance is unknown.Research questionWe evaluated the ability of abnormally high breathlessness intensity during IET to predict all-cause, respiratory, and cardiac mortality.Study Design and MethodsLongitudinal cohort study of adults referred for cycle IET followed prospectively for mortality assessed using the Swedish National Causes of Death Registry. Abnormally high exertional breathlessness was defined as a breathlessness intensity response (Borg 0-10 scale) > the upper limit of normal (ULN) using published reference equations. Mortality was analyzed using multivariable Cox regression, unadjusted and adjusted for age, sex, and body mass index.ResultsOf the 13,506 people included (46% female, age 59±15 years), 2,867 (21%) had abnormally high breathlessness during IET. Over a median follow up of 8.0 years, 1,687 (12%) people died. No participant was lost to follow-up. Compared to those within normal predicted ranges, people with abnormally high exertional breathlessness had higher mortality from all causes (adjusted hazard ratio [aHR] 2.3, [95% confidence interval] 2.1-2.6), respiratory causes (aHR 5.2 [3.4-8.0]) and cardiac causes (aHR 3.0 [2.5-3.6]). Even among people with normal exercise capacity (defined as peak Watt ≥75% of predicted exercise capacity, n=10,284) those with abnormally high exertional breathlessness were at greater risk of all-cause mortality than people with exertional breathlessness within the normal predicted range (aHR 1.5 [1.2-1.8]).InterpretationAmong people referred for cycle IET, abnormally high exertional breathlessness, quantified using healthy reference values, independently predicted all-cause, respiratory and cardiac mortality.
Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation during zebrafish maternal-to-zygotic transition
Authors: Serradimigni Rosemaria , Rojas Alfredo , Leong Connor , Pal Uttam , Bryan Madeline , Sharma Sunil , Dasgupta Subham 
Published: April 2024

ABSTRACT3,3’,5.5’-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40μM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 μM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 μM. Embryos exposed to sublethal TBBPA concentrations from 0.75-6 hpf and raised in clean water to 120 hpf showed altered larval photomotor response (LPR), suggesting a compromised developmental health. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 μM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we immunostained embryos with an H3K27Ac antibody and demonstrated reduced acetylation in TBBPA-exposed embryos. Leveraging in silico molecular docking studies and in vitro assays, we also showed that TBBPA potentially binds to P300- a protein that catalyzes acetylation- and inhibits P300 activity. Finally, we co-exposed embryos to 20 μM TBBPA and 50 μM n-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTPB co or pre-exposures significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.
Mosquitoes asses interspecific competition by larvae-released semiochemicals during oviposition habitat selection
Authors: Shteindel Nimrod , Gerchman Yoram , Silberbush Alon 
Published: April 2024

AbstractNumerous species of animals alter their behavior in response to increasing competition. To do so, they must possess the ability to detect the presence and density of interspecific competitors. We studied the role of semiochemicals released by increasing densities of larvalCuliseta longiareolataMacquart on female oviposition habitat selection in two sets of field mesocosms. Similarly toC. longiareolatalarvae, subordinateCulex laticinctusEdwards are periphyton grazers who dwell in rain-filled pools in the Mediterranean region. We show thatC. laticinctusfemales oviposited significantly less in mesocosm pools that were treated with crowding signals originating fromC. longiareolatalarvae. In a second field experiment, we placed a similar number of larvae directly inside the 50 L mesocosms. These low-density mesocosms did not affectC. laticinctusoviposition but were attractive to conspecific oviposition. These results increase our understanding of the female’s ability to detect species-specific signals indicating increased larval competition.Abstract Figure
Older Age and Vaccination Protect Against Transaminase Elevation in Pediatric SARS-CoV2
Authors: Ovale Antonia Fernandez , Charles Cassandra , Rosenbaum Janet , Villalba-Davila Priscila , Mora Mauricio , Sharma Shagun , Lemus Vivian Vega , Khandakar Saema , Wallach Thomas 
Published: April 2024

AbstractObjectivesSARS-CoV2 infection is reported to induce transaminase elevations. There are case reports of severe liver injury in adult SARS-CoV2 patients and some have theorized that acute SARS-CoV2 infection may be a driver of severe liver injury in children. While pediatric hepatic injury has previously been described, clear shifts in immunogenic response secondary to prior immune exposure and vaccination since initial reports from 2020 warrant further evaluation. We sought to identify the impact of variant shifts and vaccination on this phenomenon in children.MethodsA retrospective, cross-sectional study of pediatric SARS-CoV2 patients seen at two hospital facilities in an urban neighborhood in New York City between March 2020 and March 2022 was conducted via chart review. Data was extracted relating to patient’s demographics, clinical presentation, including the level of care and the laboratory results of comprehensive metabolic panels (CMP).Results133 pediatric cases were identified as having positive SARS-CoV2 and CMP obtained in the same visit. Patients were predominantly Black (79.2%) and non-Hispanic (87%) with a mean age of 9.2 years. Risk of transaminase elevation was increased in younger patients and patients with higher level of care. BMI was not a risk factor noted for transaminase elevation. Vaccination decreased degree, not incidence, of transaminase elevation but given low rates of vaccination unable to determine significance of protective efficacy.ConclusionsOur study has identified a profound increased risk of transaminase elevation in younger patients, the absence of BMI as a correlating factor in our primarily Black patient population, a shift towards non-specific AST elevation with variant windows and a strong signal of vaccine protection.What is KnownSARS-CoV2 can cause Transaminemia, and in rare cases, possible fulminant hepatic injuryPediatric SARS-CoV2 infections are statistically milder than adult.SARS-Cov2 case severity and complications like multisystem inflammatory syndrome in children have declined over timeWhat is NewWith population immunity and variant shifts transaminase elevations increasingly may not be of hepatic originRisk of transaminase elevation is substantially higher in younger patients, and decreases with ageVaccines are protective against degree of transaminase elevation, and likely against incidence of transaminase elevation, although further study is needed.Article SummaryCross sectional study of an urban pediatric population demonstrates SARS-CoV2 transaminase elevation linked with younger age, unvaccinated status, and higher level of care.
Paper 3: - Towards a Knowledge Sharing Maturity Model for medical imaging departments
Authors: Almashmoum Maryam , Cunningham James , Ainsworth John 
Published: April 2024

AbstractBackgroundKnowledge sharing in medical imaging departments is being driven by the need to improve healthcare services, develop healthcare professionals’ skills, and reduce repetitive mistakes. It is considered an important step in the implementation of knowledge management solutions. By following a maturity model of knowledge sharing, knowledge sharing practices can be improved. The aim of this study was to develop a maturity model knowledge sharing in medical imaging department for helping managers to assess the level of maturity for knowledge sharing practices.ObjectivesIn the modern healthcare institutions, improvements in healthcare professionals’ skills and healthcare services are often driven through practicing knowledge sharing behaviours. To understand the level of maturity of knowledge sharing, mangers can follow the indicators of maturity model knowledge sharing and its measurements in order to identify the current level and move to the next level.MethodsThis study was conducted in three stages: An ‘overview stage’ which highlighted the factors that affect knowledge sharing practices in medical imaging departments; an ‘Analysis factor stage’ which was designed to assess the factors that affect knowledge sharing by using a concurrent mixed method approach’s (questionnaires, and semi-structured interviews) in two medical imaging departments; and ‘Structuring maturity model knowledge sharing stage’, where a maturity model of knowledge sharing was developed based on the findings of the other stages.ResultsThe model presented in this study includes 17 indicators divided into 11 components. Those components derived from the findings of the questionnaires and semi-structured interviews that were applied in the medical imaging departments. It consists of five maturity levels: initial, aware, define, managed, and optimised. In each level were included measurements in order to help managers to assess the current level by answering to the measurement’s questions.ConclusionThis maturity model of knowledge sharing in medical imaging departments allows managers and policy makers to measure the maturity level of knowledge sharing in those departments. Although the model has been applied to the medical imaging departments, it might easily be modified to apply it to other institutions.
Long-lasting cigarette smoking alterations in immune function occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life
Authors: Lehrer Steven , Rheinstein Peter H. 
Published: April 2024

AbstractBackgroundActive cigarette smoking leads to increased CXCL5 production. CXCL5 mediates the immune response by attracting immune cells to areas of inflammation. Elevated CXCL5 levels are associated with various inflammatory diseases and tumorigenesis. In addition, smoking is linked to an increase in the level of the cytokine CEACAM6 in the bloodstream of smokers. CEACAM6 is increased in pancreatic adenocarcinoma, breast cancer, non⍰small cell lung cancer, gastric cancer, colon cancer and other cancers and promotes tumor progression, invasion, and metastasis. Although cytokine secretion in the innate immune response returns to nonsmoker levels after quitting smoking, the effects on the adaptive response appear to persist for years or decades due to epigenetic memory. As a result, epigenetic changes induced by smoking may contribute to long-lasting alterations in immune function, including elevated CXCL5 and CEACAM6. The effects of cannabis smoking might be similar.MethodsIn the current study we used UK Biobank (UKB) data to assess the relationship of CXCL5, CEACAM6, and pulmonary function to cigarette and cannabis smoking. Our UK Biobank application was approved as UKB project 57245 (S.L., P.H.R.). Our analysis included all subjects with smoking and/or marijuana use data in the UK Biobank database. Circulating levels of CXCL5 and CEACAM6 were from UKB Olink data. Individual CXCL5 and CEACAM6 levels are NPX, Normalized Protein expression, Olink arbitrary unit in Log2 scale (Olink Proteomics AB, Uppsala, Sweden;http://www.olink.com).ResultsCurrent smokers and past smokers had elevated circulating levels of CXCL5 and CECAM6. In multivariate analysis, current, past, or no smoking history was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex. Frequency of cannabis use had a similar effect. In multivariate analysis, frequency of cannabis use was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex, and years between last cannabis use and enrollment in study.Conclusionwe can confirm a previous report of epigenetic changes induced by cigarette smoking that may contribute to long-lasting alterations in immune function related to CXCL5 and CEACAM6. In addition, we have found that these same long-lasting smoking alterations in immune function related to CXCL5 and CEACAM6 occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life.
GLYCEMIC CONTROL AND PERIPHERAL ARTERIAL DISEASE IN DIABETIC FOOT PATIENTS
Authors: Carreño María Patricia Aragón , Figueroa Alfredo Aldama , de Jesús Fermín Rafael Martínez , Cvetkovic-Vega Aleksandar , Maguiña Quispe Jorge L. 
Published: April 2024

ABSTRACTIntroductionDiabetic foot is a severe complication of diabetes mellitus that can cause many amputations.ObjectivesTo evaluate the association between glycemic control and peripheral arterial disease in patients with diabetic foot.Materials and MethodsAn analytical cross-sectional study was performed on patients diagnosed with diabetic foot with more than ten years of evolution of diabetes mellitus who were attended in the diabetic foot outpatient clinic of the Guillermo Almenara National Hospital between June 2015 and February 2017. Glycosylated hemoglobin (HbA1C) and ankle brachial index (ABI) were used to diagnose glycemic control and peripheral arterial disease, respectively. Generalized poisson log linear regression model was used to calculate the crude (cPR) and adjusted (aPR) prevalence ratios, with 95% confidence intervals, and a significance level of p < 0.05.Results226 patients were included in the study, finding 23% (n=52) with good glycemic control, and 44.7% (n=101) with peripheral arterial disease. The adjusted model found statistically significant associations for glycemic control, age, and sedentary lifestyle with peripheral arterial disease. Compared with patients with good glycemic control, those with poor glycemic control had a 34% higher probability to present peripheral arterial disease (aPR: 1.34, 95%CI: 1.01-1.79, p=0.045).ConclusionsThe prevalence of good glycemic control in the population with diabetic foot is low. Poor glycemic control was found to be independently associated with the presence of peripheral arterial disease.
Somatic epimutations enable single-cell lineage tracing in native hematopoiesis across the murine and human lifespan
Authors: Scherer Michael , Singh Indranil , Braun Martina , Szu-Tu Chelsea , Kardorff Michael , Rühle Julia , Frömel Robert , Beneyto-Calabuig Sergi , Raffel Simon , Rodriguez-Fraticelli Alejo , Velten Lars 
Published: April 2024

SummaryCurrent approaches to lineage tracing of stem cell clones require genetic engineering or rely on sparse somatic DNA variants, which are difficult to capture at single-cell resolution. Here, we show that targeted single-cell measurements of DNA methylation at single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a droplet-based method for transgene-free lineage tracing, and apply it to study hematopoiesis, capturing hundreds of clonal trajectories across almost 100,000 single-cells. Using ground-truth genetic barcodes, we demonstrate that EPI-clone accurately identifies clonal lineages throughout hematopoietic differentiation. Applied to unperturbed hematopoiesis, we describe an overall decline of clonal complexity during murine ageing and the expansion of rare low-output stem cell clones. In aged human donors, we identified expanded hematopoietic clones with and without genetic lesions, and various degrees of clonal complexity. Taken together, EPI-clone enables accurate and transgene-free single-cell lineage tracing at scale.
Genes in Humans and Mice: Insights from Deep learning of 777K Bulk Transcriptomes
Authors: Su Zheng , Fang Mingyan , Smolnikov Andrei , Vafaee Fatemeh , Dinger Marcel E. , Oates Emily C. 
Published: April 2024

AbstractMice are widely used as animal models in biomedical research, favored for their small size, ease of breeding, and anatomical and physiological similarities to humans1,2. However, discrepancies between mouse gene experimental results and the actual behavior of human genes are not uncommon, despite their shared DNA sequence similarity3–8. This suggests that DNA sequence similarity does not always reliably predict functional similarity. On the other hand, RNA-level gene expression could offer additional information about gene function9,10. In this study, we undertook characterization and inter-species comparison of human and mouse genes by applying innovative deep learning methodologies to a large dataset of 410K human and 366K mouse bulk RNA-seq samples. This was achieved by using gene representations from our Transformer-based GeneRAIN model11,12. These gene representations aggregate information from large gene expression datasets, and provide insights beyond DNA sequence similarity. We identified 2,407 human-mouse homologous genes with high DNA similarity but distinct RNA characteristics, and showed that these genes are more likely to have differing disease/phenotype associations between the two species. Additionally, we found 3,070 homologous genes with low similarity at both the DNA and RNA levels, suggesting the highest risk of discrepancies in study results between the two species. We propose that this approach will support future decision making around whether the mouse will be an appropriate model for studying specific human genes, and whether the results of specific mouse gene studies are likely to be recapitulated in humans. Our methodological innovations offer valuable lessons for future deep learning applications in cross-species omics data. The interspecies gene relationship findings from our study also contribute valuable insights into the gene biology and evolution of the two species.
The histone demethylase JMJ27 acts during the UV-induced modulation of H3K9me2 landscape and facilitates photodamage repair
Authors: Johann to Berens Philippe , Peter Jackson , Koechler Sandrine , Bruggeman Mathieu , Staerck Sébastien , Molinier Jean 
Published: April 2024

ABSTRACTPlants have evolved sophisticated DNA repair mechanisms to cope with the deleterious effects of UV-induced DNA damage. Indeed, DNA repair pathways cooperate with epigenetic-related processes to efficiently maintain genome integrity. However, it remains to be deciphered how photodamages are recognized within different chromatin landscapes, especially in compacted genomic regions such as constitutive heterochromatin. We combined cytogenetics and epigenomics to identify that UV-C irradiation induces modulation of the main epigenetic mark found in constitutive heterochromatin, H3K9me2. We demonstrated that the histone demethylase, Jumonji27 (JMJ27), is responsible for the UV-induced reduction of H3K9me2 content at chromocenters. In addition, we identified that JMJ27 forms a complex with the photodamage recognition factor, DNA Damage Binding protein 2 (DDB2), and that the fine tuning of H3K9me2 contents orchestrates DDB2 dynamics on chromatin in response to UV-C exposure. Hence, this study uncovers the existence of an interplay between photodamage repair and H3K9me2 homeostasis.
Enhancing altruism by electrically augmenting frontoparietal gamma-band phase coupling
Authors: Hu Jie , Moisa Marius , Ruff Christian C. 
Published: April 2024

SummaryCooperation, productivity, and cohesion in human societies depend on altruism, the tendency to share resources with others even though this is costly. While altruism is a widely shared social norm, people vary strongly in their inclination to behave altruistically, in particular across situations with different types of inequality in resource distribution. What neurobiological factors underlie this variability? And can these be targeted by interventions to enhance altruistic behavior? Here, we build on recent EEG findings that altruistic choices during disadvantageous inequality correlate with oscillatory gamma-band coherence between frontal regions (representing other’s interest) and parietal regions (representing neural evidence accumulation). We apply a transcranial alternating current stimulation (tACS) protocol designed to exogenously enhance this fronto-parietal coherence and find that this leads to increased altruism, specifically during disadvantageous inequality as hypothesized based on the EGG findings. Computational modeling reveals that this transcranial entrainment does not just add noise to the decision process but specifically increases the weight individuals assign to other-regarding concerns during choices. Our findings show that altruism can be enhanced by neurostimulation designed to enhance oscillatory synchronization between frontal and parietal areas. This establishes a neural basis for altruism and identifies a neural target for interventions aimed at improving prosocial behavior.