bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac MRI Phasic Assessment of Strain in Right Ventricular Dysfunction
Authors: Janowski Alexandra M , Mueller Finley , Agarwal Shreya , Visovatti Scott , Vanderpool Rebecca R 
Published: August 2024

AbstractBackgroundRV strain associates with mortality in pulmonary hypertension (PH) but time-resolved strain is not typically assessed. The aim was to evaluate phasic changes in RV strain using cardiac magnetic resonance (CMR) images. We hypothesized that phasic changes in ejection and filling RV strain significantly associate with outcomes in PH.MethodsParticipants were identified from the Ohio State University CMR PH registry (n=96). RV endocardial areas were segmented from 4-chamber CMR Cine images. Time-resolved strains were calculated for RV global, free wall and septal strain. Ventricular dynamics were assessed during the ejection, early filling and late filling cardiac phases to quantify phasic changes in function. RV contractility, afterload and diastolic stiffness were quantified using the single-beat method. Outcomes were evaluated at one year.ResultsIn this retrospective, single-center study, 96 participants with and without pulmonary hypertension were included. Cohort was predominately female (n=53, 55%) with elevated mean pulmonary arterial pressure (38[26-48] mmHg) and reduced RV function (RVEF: 42[31-54] %, TAPSE of 19[15-23] cm). Filling strain patterns described changes in ventricular dynamics but did not associate with RV dilation or other measures characteristic of RV dysfunction. In comparison, decreased free wall strain and increased diastolic stiffness both associated with RV dysfunction but there were no significant differences in strain patterns. Participants with strain pattern 3, decreased free wall strain or increased Eed had increased one-year mortality. When investigated together, participants with decreased free wall strain, RVEF and increased Eed had greatly reduced one-year survival.ConclusionsAssessment of phasic changes in ventricular function does provide additional pathophysiological information but assessment of strain patterns alone are not sufficient for identifying reduced function. Deep phenotyping using a combination of RV strain and diastolic stiffness is highly selective of participants with increased one-year mortality.
Histone lactylation: a new epigenetic mark in the malaria parasitePlasmodium
Authors: Jabre Ibtissam , Andoh Nana Efua , Naldoni Juliana , Gregory William , Yoon Chae Eun , Cunnington Aubrey J. , Georgiadou Athina , Blagborough Andrew M. , Merrick Catherine J. 
Published: August 2024

ABSTRACTIn the malaria parasitePlasmodium falciparum,epigenetic modifications such as acetylation and methylation play important roles in parasite biology and virulence. Here, we characterised a new epigenetic mark, histone lactylation, recently discovered in humans and also present inPlasmodium. It was found in two human malaria parasites,P. falciparumand the zoonotic macaque parasiteP. knowlesi, and was also foundin vivoin two rodent malaria models. Histones were lactylated rapidly in response to elevated lactate levels, either exogenously added or endogenously generated by the parasite’s own metabolism, and they were rapidly delactylated when lactate levels fell. Thus, this epigenetic mark is well-placed to act as a metabolic sensor, since severe falciparum malaria characteristically leads to hyperlactataemia in infected patients. Mass spectrometry showed that lysines on several parasite histones could be lactylated, and that this was accompanied by lactylation of many non-histone chromatin proteins. Histone lactylation was less abundant and less inducible inP. knowlesithan inP. falciparum, suggesting thatP. falciparummay have evolved particular epigenetic responses to this characteristic feature of its pathology. Finally, in the rodent modelP. yoelii, hyperlactataemia correlated with parasite transcriptomic programmes that suggested metabolic ‘dormancy’.
Transcriptional and epigenetic response of rapeseed (Brassica napusL.) to PEG-triggered osmotic stress
Authors: Prasad Melvin , Shetty Prateek , Pal Avik Kumar , Rigó Gábor , Kant Kamal , Zsigmond Laura , Nagy István , Shivaprasad P. V. , Szabados László 
Published: August 2024

AbstractDrought hinders growth, development, and productivity of higher plants. While physiological and molecular background of plant responses to drought has extensively studied, the role of epigenetic modifications in response to dehydration remains largely elusive. In this study, we deciphered genome-wide transcriptomic and epigenetic responses of rapeseed (Brassica napusL.) to dehydration. High-throughput transcript profiling (RNA-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) of PEG-treated rapeseed plants revealed genome-scale changes in transcription and histone methylation patterns, focusing on histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 tri-methylated lysine 27 (H3K27me3). We have identified large gene sets with altered transcript profiles and changed histone methylation marks in response to osmotic stress, revealed a close correlation between gain or loss of histone methylation and activation or repression of gene expression. Significant epigenetic regulation of Delta 1-Pyrroline-5-Carboxylate Synthetase (P5CS) genes, which control the key step in proline synthesis, was discovered as several PEG-inducedBnP5CSAgenes displayed enhanced H3K4me3 and/or H3K36me3 marks. Targeted bisulphite sequencing revealed that oneBnP5CSAgene has stress-dependent gene body DNA methylation also. By integrating physiological, transcriptional and epigenetic data, our study facilitates better understanding drought response control in higher plants.
Detection of novelPlasmodium falciparumhaplotypes under treatment pressure in pediatric severe malaria
Authors: Fogang Balotin , Guillochon Emilie , Kamaliddin Claire , Agbota Gino , Ezinmegnon Sem , Alao Maroufou Jules , Deloron Philippe , Bertin Gwladys , Claessens Antoine 
Published: August 2024

AbstractBackgroundIn Africa, the clearance time forP. falciparumsevere malaria varies significantly, likely due to the complexity ofP. falciparuminfections and the sequestration phenomenon exhibited by this parasite. This study aims to evaluate different methods to study intra-host dynamics of polygenomic infections during parasite clearance under antimalarial treatment. Additionally, it seeks to determine the association between parasite clearance rate following artesunate or quinine treatment and the genetic complexity ofP. falciparumin Beninese children with severe malaria.MethodsSixty-fiveP. falciparumsevere malaria individuals diagnosed by microscopy and treated with artesunate or quinine were sampled every 8 hours for 24 hours. Using whole genome sequencing (WGS) data, we estimated the multiplicity of infection (MOI) with three algorithms (Fws, THE REAL McCOIL, and RoH). We then characterized theP. falciparumgenetic complexity in WGS-identified polyclonal infections using amplicon sequencing (AmpSeq) on DNA extracted from plasma and from the red blood cells pellet.ResultsAmpSeq demonstrated greater sensitivity in detecting multiple genomes within isolates compared to WGS methods. The MOI from AmpSeq was significantly higher in RBC pellets compared to plasma (2.4 vs 1.8 distinct microhaplotypes per isolate). However, at parasitaemia over 1000 parasites/uL, the same MOI was detected in both plasma and pellet samples in 85.4% of the isolates. We observed a high variability in parasite clearance rate among participants, but it was not associated with parasite MOI at diagnostic. Interestingly, in 60.9% of participants, previously undetected microhaplotypes appeared in circulation 16 hours after treatment initiation.ConclusionThese findings demonstrate that combining different haplotyping techniques effectively determines parasite genetic complexity. Additionally, plasma can be effectively used for parasite genotyping at sufficient parasitaemia levels. The parasite clearance rate of severe malaria is independent of parasite MOI. However, genotyping a single blood sample upon hospital admission does not capture the full spectrum of parasite genotypes present in the infection.
Sex Disparities in Chlamydia and Gonorrhea Treatment in US Adult Emergency Departments: A Systematic Review and Meta-analysis
Authors: Solnick Rachel E , Patel Rahi , Chang Ethan , Vargas-Torres Carmen , Munawar Maaz , Pendell Carlin , Smith Judith E. , Cowan Ethan , Kocher Keith E , Merchant Roland C 
Published: August 2024

ABSTRACTImportanceIn US emergency departments (EDs), empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common due to the unavailability of immediate test results. Evidence suggests sex-based disparities in treatment practices, with females potentially receiving less empiric treatment than males.ObjectiveTo investigate sex differences in empiric antibiotic treatment for GC and CT in EDs, comparing practices to subsequent laboratory-confirmed results.Design, Setting, and ParticipantsThis systematic review and meta-analysis included studies from US EDs reporting GC/CT testing and empiric antibiotic treatment from January 2010 to February 2021. A total of 1,644 articles were screened, with 17 studies (n = 31,062 patients) meeting inclusion criteria.Main Outcomes and MeasuresThe primary outcomes were GC/CT test positivity, empiric antibiotic treatment rates, and discordance between treatment and test results, stratified by sex. Data were analyzed using a random-effects model.ResultsOverall GC/CT positivity was 14% (95% CI, 11%-16%): 11% (95% CI, 8%-14%) in females and 25% (95% CI, 23%-26%) in males. Empiric antibiotic treatment was administered in 46% (95% CI, 38%-55%) of cases: 31% (95% CI, 24%-37%) in females and 73% (95% CI, 65%-80%) in males. Among patients without a laboratory-confirmed infection, 38% (95% CI, 30%-47%) received treatment: 27% (95% CI, 20%-34%) of females and 64% (95% CI, 55%-73%) of males. Conversely, 39% (95% CI, 31%-48%) of patients with laboratory-confirmed infections were not treated: 52% (95% CI, 46%-57%) of females and 15% (95% CI, 12%-17%) of males.Conclusions and RelevanceThere is significant discordance between ED empiric antibiotic treatment and laboratory-confirmed results, with notable sex-based disparities. Females were 3.5 times more likely than males to miss treatment despite confirmed infection. These findings highlight the need for improved strategies to reduce sex-based disparities and enhance empiric treatment accuracy for GC/CT in ED settings.Key PointsQuestionAre there sex-based differences in empiric antibiotic treatment for gonorrhea and chlamydia in US emergency departments (EDs), and how do these practices compare to laboratory-confirmed results?FindingsIn this systematic review and meta-analysis of 17 studies with 31,062 patients, females were significantly less likely than males to receive empiric antibiotic treatment for gonorrhea and chlamydia. Additionally, 39% of patients with a laboratory-confirmed infection were not empirically treated, with females 3.5 times more likely to miss treatment than males.MeaningThe findings indicate significant sex disparities in ED empiric antibiotic treatment for sexually transmitted infections, underscoring the need for improved strategies to ensure equitable and accurate treatment across sexes.
Interrelationship of Substrate Crystallinity, Enzyme Binding Strength, and Cellulase Activity
Authors: Avelar Molina Gustavo , Schaller Kay , Kari Jeppe , Schiano-di-Cola Corinna , Peters Günther H. J. , Borch Kim , Westh Peter 
Published: August 2024

AbstractStructural polysaccharides are difficult to degrade due to their crystalline structure. Hence, industrial conversion of biomass has focused on both substrate pretreatment and enzyme engineering to improve the biochemical conversion of biomass into fuels and chemicals. However, few studies have explored the interrelationship between substrate crystallinity and cellulase activity. Here, we systematically investigated the kinetics of structurally diverse cellulases on five cellulosic substrates with varying crystallinity. Regardless of enzyme structure and catalytic mechanism, we observed a linear scaling of the kinetic parameters (KMandkcat) in a log-log plot, indicating a linear free energy relationship (LFER) between binding and activation energy. LFERs were observed for all investigated substrates, but their slopes varied distinctly and appeared linked to the substrate crystallinity. Substrates with low crystallinity exhibited LFERs with a slope near 1, while highly crystalline substrates had a slope of approximately 0.25, providing insights into the transition state (TS) for the rate-limiting step. We propose that maximal turnover was limited by slow dissociation, with the TS structurally close to the enzyme-ligand complex on crystalline substrate, while on amorphous substrate, the TS structure was closer to the dissociated system. We suggest that these observations reflect competing interactions of the ligand with respectively the enzyme binding cleft and the substrate matrix. This study emphasizes the interconnected nature of substrate pretreatment and enzyme engineering, urging a holistic approach to propel the biochemical conversion of lignocellulosic biomass, crucial for advancing sustainable production of fuels and chemicals.
Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety
Authors: Le Borgne T. , Nguyen C. , Vicq E. , Jehl J. , Solié C. , Guyon N. , Daussy L. , Gulmez A. , Reynolds L.M. , Mondoloni S. , Tolu S. , Pons S. , Maskos U. , Valjent E. , Mourot A. , Faure P. , Marti F. 
Published: August 2024

SUMMARYNicotine activates ventral tegmental area (VTA) dopaminergic (DA) neurons projecting to the nucleus accumbens (NAc) to drive its reinforcing effects. Simultaneously, it inhibits those projecting to the amygdala (Amg) to mediate anxiety through a process that remains unknown. Here we show that NAc- and Amg-projecting DA neurons respond with similar polarities to ethanol and nicotine, suggesting a shared network-based mechanism underlying the inhibitory effect of these otherwise pharmacologically-distinct drugs. Selective activation of NAc-projecting DA neurons, using genetic or optogenetic strategies, produced inhibition of Amg-projecting DA neurons, through a GABAergic feedback loop. Furthermore, optogenetically silencing this feedback loop prevented nicotine from inducing both inhibition of DA neurons and anxiety-like behavior. Therefore, nicotine-induced inhibition of the VTA-Amg DA pathway results from a VTA-NAc inhibitory feedback loop, mediating anxiety.
Epigenetic control of tetrapyrrole biosynthesis bym4C DNA methylation in a cyanobacterium
Authors: Schmidt Nils , Stappert Nils , Nimura-Matsune Kaori , Watanabe Satoru , Sobotka Roman , Hagemann Martin , Hess Wolfgang R. 
Published: August 2024

AbstractEpigenetic DNA modifications are pivotal in eukaryotic gene expression, but their regulatory significance in bacteria is less understood. InSynechocystis6803, the DNA methyltransferase M.Ssp6803II modifies the first cytosine in the GGCC motif, forming N4-methylcytosine (GGm4CC). Deleting thesll0729gene (Δsll0729) caused a bluish phenotype due to reduced chlorophyll levels, which was reversed by suppressor mutations. Re-sequencing of seven suppressor clones revealed a common GGCC to GGTC mutation in theslr1790promoter’s discriminator sequence, encoding protoporphyrinogen IX oxidase, HemJ, crucial for tetrapyrrole biosynthesis. Transcriptomic and qPCR analyses indicated aberrantslr1790expression in Δsll0729mutants. This aberration led to the accumulation of coproporphyrin III and protoporphyrin IX, indicative of impaired HemJ activity. To confirm the importance of DNA methylation inhemJexpression, native and mutatedhemJpromoter variants were introduced into the wild type, followed bysll0729deletion. Thesll0729deletion segregated in strains with the GGTC motif in thehemJpromoter, resulting in wild-type-like pigmentation, whereas freshly prepared Δsll0729mutants with the nativehemJpromoter exhibited the bluish phenotype. These findings demonstrate thathemJis tightly regulated inSynechocystisand that N4-methylcytosine is essential for properhemJexpression.
Identification of phenotypic and transcriptomic signatures underpinning maize crown root systems
Authors: Callwood Jodi B. , Townsend Ella G. , Malik Shikha , Draves Melissa A. , Khor Jasper , Marshall Jackson P. , Sweers Heather , Cowling Craig L. , Walley Justin W. , Kelley Dior R. 
Published: August 2024

AbstractMaize is pivotal in supporting global agriculture and addressing food security challenges. Crop root systems are critical for water uptake and nutrient acquisition, which impacts yield. Quantitative trait phenotyping is essential to understand better the genetic factors underpinning maize root growth and development. Root systems are challenging to phenotype given their below-ground, soil-bound nature. In addition, manual trait annotations of root images are tedious and can lead to inaccuracies and inconsistencies between individuals, resulting in data discrepancies. To address these issues, we have developed an automated phenotyping pipeline for field-grown maize crown roots by leveraging open-source software. Phenotypic variation of 20 maize genotypes from the Wisconsin Diversity panel was significant for numerous root traits, suggesting a genetic basis for the observed developmental deviations. In addition, juvenile root traits from controlled environment conditions exhibited inconsistent correlation with field-grown adult root traits, underscoring the developmental plasticity prevalent during maize root morphogenesis. Transcripts involved in hormone signaling and stress responses were among differentially expressed genes in roots from 20 maize genotypes, suggesting many molecular processes may underlie the observed phenotypic variance. This study furthers our understanding of genotype-phenotype relationships, which is relevant for informing agricultural strategies to improve maize root physiology.
CLEAR-IT: Contrastive Learning to Capture the Immune Composition of Tumor Microenvironments
Authors: Spengler Daniel , Korovin Serafim , Prakash Kirti , Bankhead Peter , Debets Reno , Smith Carlas , Balcioglu Hayri E. 
Published: August 2024

AbstractAccurate phenotyping of cells in the tumor microenvironment is crucial for understanding cancer biology and developing effective therapies. However, current methods require precise cell segmentations and struggle to generalize across different imaging modalities, limiting their utility in digital pathology. Here, we show that Contrastive Learning Enabled Accurate Registration of Immune and Tumor Cells (CLEAR-IT) overcomes these limitations, providing a robust and versatile tool for cell phenotyping. CLEAR-IT accurately phenotypes cells comparable to state-of-the-art methods, generalizes across multiplex imaging modalities, maintains high performance even with limited number of labels, and enables the extraction of prognostic markers. Additionally, CLEAR-IT can be combined with existing methods to boost their performance, whereas its lack of need for precise cell segmentations significantly reduces training efforts. This method enhances the robustness and efficiency of digital pathology workflows, making it a valuable tool for cancer research and diagnostics.
Pollen foraging mediates exposure to dichotomous stressor syndromes in honey bees
Authors: Wizenberg Sydney B. , French Sarah K. , Newburn Laura R. , Pepinelli Mateus , Conflitti Ida M. , Moubony Mashaba , Ritchie Caroline , Jamieson Aidan , Richardson Rodney T. , Travas Anthea , Imrit Mohammed Arshad , Chihata Matthew , Higo Heather , Common Julia , Walsh Elizabeth M. , Bixby Miriam , Guarna M. Marta , Pernal Stephen F. , Hoover Shelley E. , Currie Robert W. , Giovenazzo Pierre , Guzman-Novoa Ernesto , Borges Daniel , Foster Leonard J. , Zayed Amro 
Published: August 2024

AbstractRecent declines in the health of honey bee colonies used for crop pollination pose a considerable threat to global food security. Foraging by honey bee workers represents the primary route of exposure to a plethora of toxins and pathogens known to affect bee health, but it remains unclear how foraging preferences impact colony-level patterns of stressor exposure. Resolving this knowledge gap is crucial for enhancing the health of honey bees and the agricultural systems that rely on them for pollination. To address this, we carried out a national-scale experiment encompassing 456 Canadian honey bee colonies to first characterize pollen foraging preferences in relation to major crops, then explore how foraging behaviour influences patterns of stressor exposure. We used a metagenetic approach to quantify honey bee dietary breadth and found that bees display distinct foraging preferences that vary substantially relative to crop type and proximity, and the breadth of foraging interactions can be used to predict the abundance and diversity of stressors a colony is exposed to. Foraging on diverse plant communities was associated with increased exposure to pathogens, while the opposite was associated with increased exposure to xenobiotics. Our work provides the first large-scale empirical evidence that pollen foraging behaviour plays an influential role in determining exposure to dichotomous stressor syndromes in honey bees.Significance StatementInsect-mediated pollination is an important ecological process that is crucial for food production. Managed honey bee colonies are one of the most important insect pollinators, but their health has been under threat from a variety of stressors. Bee workers are primarily exposed to stressors while foraging and understanding how bee foraging preferences are related to exposure risk could provide pivotal information to improve management efforts. Here, we studied honey bee foraging preferences in relation to prominent Canadian crops and across a gradient of modified environments. We found that honey bees show distinct, measurable foraging preferences and that dietary diversity is a strong predictor of the stressors that colonies are exposed to.