bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high-fiber, low-fat diet improves the symptoms and metabolic profile of patients with Crohn’s disease
Authors: Abreu Maria T. , Quintero Maria A. , Garces Luis , Hazime Hajar , Killian Rose , Faust Katerina M. , Mendygral Payton , Pignac-Kobinger Judith , Mangarelli Cristiana , Santander Ana M. , Fernández Irina , Solis Norma , Ortega Mailenys , Damas Oriana M. , Proksell Siobhan , Kerman David H. , Deshpande Amar R. , Seminerio Jennifer , Hashash Jana A.L. , Harvey Philip , Barrera Ingrid , Crane Tracy 
Published: August 2024

ABSTRACTBackgroundCrohn’s disease (CD) is characterized by intestinal inflammation. Diet is a risk factor for inflammatory bowel diseases such as CD and represents a promising adjunctive treatment, yet there are few well-controlled dietary intervention studies in CD patients. Fiber may have beneficial effects; however, most CD patients are told to avoid high-fiber foods. We conducted a longitudinal patient-preference study to examine the effect of a catered low-fat, high- fiber diet (theMi-IBD diet) on CD symptoms, inflammation, and the microbiome.MethodsCD patients (n=73) received one-time diet counseling (Group 1, n=23), theMi-IBD diet (Group 2, n=26), or theMi-IBD diet along with a healthy household control (Group 3, n=24 patient- HHC dyads). TheMi-IBD diet was catered for 8 weeks, and CD symptoms were recorded. Serum samples were collected to measure inflammatory marker levels and evaluate systemic changes via proteomic analyses (SomaScan Discovery v4.1 assays). Stool samples were collected to perform metabolomic analyses.ResultsAt baseline, CD patients had a low-fiber, high-fat diet. One-time diet counseling did not result in dietary changes. In contrast, catering led to marked dietary changes in CD patients (increased fiber intake, decreased fat intake; all ps < 0.001) and high adherence rates (96%). Group 3 exhibited improvements in CD symptoms (PRO2 and sCDAI scores). Proteomic analysis revealed higher baseline serum levels of proinflammatory proteins (SAA and CRP) in CD patients than in HHCs; these levels decreased with the catered diet. The diet also improved fecal metabolites related to protein and energy metabolism as well as markers of oxidative stress and inflammation in CD patients.ConclusionA nonpharmacological approach involving a high-fiber, low-fat diet to manage CD was well tolerated, even by patients with fibrostenotic CD. These findings fill a gap in development of dietary recommendations for CD patients.Clinical trial registrationThis trial was registered atClinicalTrials.gov(ID:NCT04213729).
Isolating the genetic component of mania in bipolar disorder
Authors: Merola Giuseppe Pierpaolo , Zvrskovec Johan , Wang Rujia , Li Yuen Kaye , Castellini Giovanni , Ricca Valdo , Coleman Jonathan , Vassos Evangelos , Breen Gerome 
Published: August 2024

AbstractObjectiveBipolar disorder typically features episodes of mania and depression, frequently accompanied by psychosis. While progress has been made in understanding the genetics of depression and psychosis, mania remains underexplored.MethodsWe employed Genomic Structural Equation Modeling to subtract the genetic effects of schizophrenia and major depressive disorder (MDD) from bipolar disorder to identify a genetic trait specific to mania.ResultsThe SEM model revealed significant loadings for “mania” (0.67, p<0.001), “psychosis” (0.58, p<0.001), and “depression” (0.29, p<0.001) factors, with mania, MDD and schizophrenia explaining 45%, 8% and 34% of the variance in bipolar disorder, respectively. Seven significant genomic regions associated with mania were identified. Key regions include rs9834970 (3q12.1, previously associated with lithium response), rs6992333 (8q13.1, brain structure), and rs12206087 (6q14.3, intelligence and cortical surface). Additionally, mania exhibited distinct genetic correlations compared to bipolar disorder across psychiatric, substance abuse, somatic, social, and neurological traits, including significantly higher correlations with intelligence (rg=0.08 vs −0.07) and educational attainment (rg=0.17 vs 0.12), and an unexpected reduced correlation with risky sexual behavior (rg=0.14 vs 0.27).ConclusionsThese findings enhance understanding of bipolar disorder’s genetic architecture, potentially offering a more bipolar disorder-specific GWAS.
LSD600: the first corpus of biomedical abstracts annotated with lifestyle–disease relations
Authors: Nourani Esmaeil , Makri Evangelia-Mantelena , Mao Xiqing , Pyysalo Sampo , Brunak Søren , Nastou Katerina , Jensen Lars Juhl 
Published: August 2024

AbstractLifestyle factors (LSFs) are increasingly recognized as instrumental in both the development and control of diseases. Despite their importance, there is a lack of methods to extract relations between LSFs and diseases from the literature, a step necessary to consolidate the currently available knowledge into a structured form. As simple co-occurrence-based relation extraction (RE) approaches are unable to distinguish between the different types of LSF-disease relations, context-aware transformer-based models are required to extract and classify these relations into specific relation types. No comprehensive LSF–disease RE system existed, primarily due to the lack of a suitable corpus for developing it. We present LSD600, the first corpus specifically designed for LSF-disease RE, comprising 600 abstracts with 1900 relations of eight distinct types between 5,027 diseases and 6,930 LSF entities. We evaluated LSD600’s quality by training a RoBERTa model on the corpus, achieving an F-score of 68.5% for the multi-label RE task on the held-out test set. We further validated LSD600 by using the trained model on the two Nutrition-Disease and FoodDisease datasets, where it achieved F-scores of 70.7% and 80.7%, respectively. Building on these performance results, LSD600 and the RE system trained on it can be valuable resources to fill the existing gap in this area and pave the way for downstream applications.
Aortic root anatomy and impact on new-onset conduction abnormalities after transcatheter aortic valve implantation
Authors: Layoun Habib , Kassab Joseph , Chedid El Helou Michel , El Dahdah Joseph , Iskandar Odette , Ali Majeed Saidan Maryam Muhammad , Abushouk Abdelrahman , Isogai Toshiaki , Reed Grant , Puri Rishi , Wazni Oussama M. , Krishnaswamy Amar , Harb Serge , Kapadia Samir 
Published: August 2024

AbstractBackgroundAngulation of virtual basal ring (VBR), also known as aortic annulus, in relation to sino-tubular joint (STJ) may lead to greater exposure of implanted stent to the conduction system, consequently increasing the risk of LBBB.ObjectiveTo measure VBR-STJ angle and explore its impact on the development of LBBB post TAVR.MethodsPatients undergoing TAVR using the Sapiens 3 valve between 2016 and 2021, without pre-TAVR conduction anomalies were included. The angle between the VBR and the ascending aorta was measured as the angle between the VBR plane and the plane of the STJ on cardiac CT, along with the annulus dimensions. TAVR implantation depth was measured on intra-procedural fluoroscopy images.Results1204 patients were included, with 145 having new-onset LBBB. The VBR-STJ angle was significantly greater in the new-onset LBBB group (7.3 ± 4.7 vs 5.9 ± 4.6, p=0.002), and the difference in implantation depth between the levels of right and none coronary cusp (RCC and NCC) was significantly correlated with the VBR-STJ angle (r=0.1, p=0.03). This angle was further associated with new-onset LBBB after adjustment to patient and procedural characteristics (OR 1.08 CI: [1.04, 1.13], p<0.001).ConclusionPatients developing LBBB have larger VBR-STJ angle which was associated with greater depth of implantation of the TAVR valve below the RCC compared to the NCC. Precise understanding of the aortic root anatomy can help to predict onset of LBBB which in turn can inform decision making regarding optimal way of treating aortic stenosis and may improve procedure planning.Condensed abstractThis study explores the impact of the virtual basal ring (VBR) to the sino-tubular junction (STJ) angle on the development of new-onset left bundle branch block (LBBB) post TAVR. The angle was measured in 1204 patients who underwent TAVR, with 145 developing LBBB post TAVR. The measured angle was significantly higher in patient with new-onset LBBB and was independently correlated with new-onset LBBB. These findings emphasize the importance of understanding the aortic root anatomy to improve TAVR planning and reduce the incidence of LBBB.
Is it me or the train moving? Humans resolve sensory conflicts with a nonlinear feedback mechanism in balance control
Authors: Assländer Lorenz , Albrecht Matthias , Gruber Markus , Peterka Robert J. 
Published: August 2024

ABSTRACTHumans use multiple sensory systems to estimate body orientation in space. A predominant concept for the underlying multisensory integration (MSI) is the linear summation of weighted inputs from individual sensory systems. The sensory contributions change depending on context and environmental conditions. These changes are typically attributed to ‘reweighting’ by some higher order mechanism. We provide evidence for a conceptually different mechanism that 1) performs a multisensory correction if the reference of a sensory input moves in space and is therefore unreliable and 2) combines the corrected sensory inputs with fixed weights. The correction is based on a sensory reconstruction of the sensory reference frame motion (RFM) and allows humans to automatically counteract erroneous inputs, e.g., when looking at a moving train. The proposed RFM estimator contains a nonlinear deadzone that blocks corrections at slow velocities. We first demonstrate that this mechanism accounts for the apparent changes in sensory contributions. Secondly, we hypothesized that such a nonlinearity would distort balance responses to perturbations in a very specific way. We predicted such distortions in body sway using a balance control model. Experiments using visual scene movements confirmed the predictions. The findings indicate that the central nervous system resolves sensory conflicts by an internal reconstruction of the cause of the conflict. Thus, the mechanism links the concept of causal inference to shifts in sensory contributions, providing a cohesive picture of MSI for the estimation of body orientation in space.
Spatiotemporal Single-Cell Roadmap of Human Skin Wound Healing
Authors: Liu Zhuang , Li Dongqing , Bian Xiaowei , Luo Lihua , Björklund Åsa K. , Li Li , Zhang Letian , Chen Yongjian , Guo Lei , Gao Juan , Cao Chunyan , Wang Jiating , He Wenjun , Xiao Yunting , Zhu Liping , Annusver Karl , Gopee Huda , Bennett Clare L. , Kasper Maria , Haniffa Muzlifah , Sommar Pehr , Xu Landén Ning 
Published: August 2024

SummaryWound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell and spatial transcriptomics analyses on human skin and acute wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.HighlightsA spatiotemporal atlas to explore humanin vivogene expression across wound healingWound margin architecture unveils a model for human re-epithelializationDistinct healing challenges in venous ulcers and diabetic foot ulcersUnique human healing traits emerge in cellular heterogeneity and gene expression
Fluralaner treatment of chickens kills the southern house mosquito,Culex quinquefasciatus
Authors: Knape Koyle , Tian Yuexun , Durden Cassandra , Adams Dayvion R. , Garza Macie , Carey John B. , Hamer Sarah A. , Hamer Gabriel L. 
Published: August 2024

AbstractThe control of zoonotic and vector-borne pathogens is challenging due to the limited availability of intervention tools. West Nile virus (WNV) is an example of globally distributed zoonotic arbovirus that circulates betweenCulexspecies mosquitoes and avian hosts, with spillover transmission to humans, resulting in disease cases. Interventions delivering systemic insecticides to vertebrate hosts used by vector species, known as xenointoxication, are potential tools for managing vector populations by creating toxic bloodmeals. In this study, we evaluated the impact of three systemic insecticides on the mortality ofCx. quinquefasciatus: fenbendazole (Safe-Guard® Aquasol), ivermectin (Ivomec® Pour-On), and fluralaner (Bravecto®). We found no significant difference in the feeding rates of mosquitoes that fed on treated chickens compared to those fed on untreated chickens, suggesting that the treatment did not repel mosquitoes. The mortality ofCx. quinquefasciatusmosquitoes feeding on fluralaner-treated chickens was significantly higher (p < 0.01) than those fed on control chickens at 3 and 7 days post-treatment, but this effect was not observed in mosquitoes fed on chickens treated with fenbendazole or ivermectin. No differences in mortality were observed among the groups at 14, 26, or 56 days post-treatment. These data support fluralaner as a xenointoxication tool to controlCx. quinquefasciatuspopulations and decrease the risk of human exposure to their associated pathogens.
High-throughput unsupervised quantification of patterns in the natural behavior of marmosets
Authors: Menegas William , Corbett Erin , Beliard Kimberly , Xu Haoran , Parmar Shivangi , Desimone Robert , Feng Guoping 
Published: August 2024

AbstractRecent advances in genetic engineering have accelerated the production of nonhuman primate models for neuropsychiatric disorders. To use these models for preclinical drug testing, behavioral screening methods will be necessary to determine how the model animals deviate from controls, and whether treatments can restore typical patterns of behavior. In this study, we collected a multimodal dataset from a large cohort of marmoset monkeys and described typical patterns in their natural behavior. We found that these behavioral measurements varied substantially across days, and that behavioral state usage was highly correlated to the behavior of cagemates and to the vocalization rate of other animals in the colony. To elicit acute behavioral responses, we presented animals with a panel of stimuli including novel, appetitive, neutral, aversive, and social stimuli. By comparing these behavioral conditions, we demonstrate that outlier detection can be used to identify atypical responses to a range of stimuli. This data will help guide the study of marmosets as models for neuropsychiatric disorders.
A wheat tandem kinase sensor activates an NLR helper to trigger immunity
Authors: Chen Renjie , Chen Jian , Outram Megan A. , Powell Oliver R. , Arndell Taj , Gajendiran Karthick , Wang Yan L. , Ayliffe Michael A. , Blundell Cheryl , Figueroa Melania , Sperschneider Jana , Vanhercke Thomas , Tang Dingzhong , Xu Yang , Zhong Guitao , Gardener Catherine , Yu Guotai , Gourdoupis Spyridon , Jaremko Łukasz , Matny Oadi , Steffenson Brian J. , Boshoff Willem H. P. , Meyer Wilku B. , Arold Stefan T. , Dodds Peter N. , Wulff Brande B. H. 
Published: August 2024

AbstractMost plant resistance genes encode membrane-anchored receptor-like proteins or intracellular nucleotide-binding and leucine-rich repeat (NLR) receptors. In wheat and barley, tandem kinases (TKs) have emerged as a new class of resistance determinants. To understand the modus operandi of the wheat stem rust resistance protein Sr62TK, we identified two genetic interactors— a host gene required for Sr62TKfunction and the corresponding fungal AvrSr62 effector. We discovered that theSR62locus consists of a digenic module encoding Sr62TKand an NLR (Sr62NLR). AvrSr62 binds to the N-terminal kinase of Sr62TK. This triggers displacement of the C-terminal kinase allowing it to recruit Sr62NLRfor activation of immune responses. Understanding the mechanism of this two-component resistance complex will help engineering and breeding for durable resistance.
Multimodal Spatial Proteomic Profiling in Acute Myeloid Leukemia
Authors: Ly Christopher P. , Veletic Ivo , Pacheco Christopher D. , Dasdemir Enes , Jelloul Fatima Z. , Ferri-Borgongo Sammy , Basi Akshay V. , Gomez Javier A. , Root Jessica L. , Reville Patrick K. , Sharma Padmanee , Basu Sreyashi , Quesada Andres E. , Bueso-Ramos Carlos , Manshouri Taghi , Garcia Miriam , Burks Jared K. , Abbas Hussein A. 
Published: August 2024

AbstractAcute myeloid leukemia (AML) resides in an immune rich microenvironment, yet, immune-based therapies have faltered in eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized a high-throughput tissue-microarray based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on a single slide, capturing immune, tumor, and structural components. Using unbiased clustering on the spatial K function, we unveiled the presence of tertiary lymphoid-like aggregates in bone marrow which we validated using spatial transcriptomics and an independent proteomics approach. We then found validated TLS signatures predictive of outcomes in AML using an integrated public 480 patient transcriptomic dataset. By harnessing high-plex spatial proteomics, we open the possibility of discovering of novel structures and interactions that underpin leukemic immune response. Further, our study’s methodologies and resources can be adapted for other bone marrow diseases where decalcification and autofluorescence present challenges.
Rapid synthesis and screening of natively paired antibodies against influenza hemagglutinin stem via oPool+display
Authors: Ouyang Wenhao O. , Lv Huibin , Liu Wenkan , Mou Zongjun , Lei Ruipeng , Pholcharee Tossapol , Wang Yiquan , Dailey Katrine E. , Gopal Akshita B. , Choi Danbi , Ardagh Madison R. , Talmage Logan , Rodriguez Lucia A. , Dai Xinghong , Wu Nicholas C. 
Published: August 2024

ABSTRACTAntibody discovery is crucial for developing therapeutics and vaccines as well as understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we presented oPool+display, which combines oligo pool synthesis and mRNA display to construct and characterize many natively paired antibodies in parallel. As a proof-of-concept, we applied oPool+display to rapidly screen the binding activity of >300 natively paired influenza hemagglutinin (HA) antibodies against the conserved HA stem domain. Structural analysis of 16.ND.92, one of the identified HA stem antibodies, revealed a unique binding mode distinct from other known broadly neutralizing HA stem antibodies with convergent sequence features. Yet, despite such differences, 16.ND.92 remained broadly reactive and conferredin vivoprotection. Overall, this study not only established an experimental platform that can be applied in both research and therapeutics to accelerate antibody discovery, but also provides molecular insights into antibody responses to the influenza HA stem, which is a major target for universal influenza vaccine development.
Predicting the irrelevant: Neural effects of distractor predictability depend on load
Authors: Lui Troby Ka-Yan , Obleser Jonas , Wöstmann Malte 
Published: August 2024

AbstractDistraction is ubiquitous in human environments. Distracting input is often predictable, but we do not understand when or how humans can exploit this predictability. Here we ask whether predictable distractors are able to reduce uncertainty in updating the internal predictive model. We show that utilising a predictable distractor identity is not fully automatic but in part depends on available resources. In an auditory spatial n-back task, listeners (n= 33) attended to spoken numbers presented to one ear and detected repeating items. Distracting numbers presented to the other ear either followed a predictable (i.e., repetitive) sequence or were unpredictable. We used electroencephalography (EEG) to uncover neural responses to predictable versus unpredictable auditory distractors, as well as their dependence on perceptual and cognitive load. Neurally, pairs of targets and unpredictable distractors induced a sign-reversed lateralization of pre-stimulus alpha oscillations (∼10 Hz) and larger amplitude of the stimulus-evoked P2 event-related potential component. Under low versus high memory load, distractor predictability increased the magnitude of the frontal negativity component. Behaviourally, predictable distractors under low task demands (i.e., good signal-to-noise ratio and low memory load) made participants adopt a less biased response strategy. We conclude that predictable distractors decrease uncertainty and reduce the need for updating the internal predictive model. In turn, unpredictable distractors might mislead proactive spatial attention orientation, elicit larger neural responses, and put higher demand on memory.
Dual and spatially resolved drought responses in the Arabidopsis leaf mesophyll revealed by single-cell transcriptomics
Authors: Berrío Rubén Tenorio , Verhelst Eline , Eekhout Thomas , Grones Carolin , De Veylder Lieven , De Rybel Bert , Dubois Marieke 
Published: August 2024

ABSTRACTDrought stress imposes severe challenges on agriculture by impacting crop performance. Understanding drought responses in plants at a cellular level is a crucial first step towards engineering improved drought resilience. However, the molecular responses to drought are complex as they depend on multiple factors including the severity of drought, the profiled organ, its developmental stage or even the cell types therein. Thus, deciphering the transcriptional responses to drought is specially challenging. Here, we investigated tissue-specific responses to mild drought in youngArabidopsis thaliana(Arabidopsis) leaves using single-cell RNA sequencing (scRNA-seq). To preserve transcriptional integrity during cell isolation, we inhibited RNA synthesis using the transcription inhibitor actinomycin D, demonstrating the benefits of transcriptome fixation for studying mild stress responses at single-cell level. We present a curated and validated single-cell atlas comprising 50,797 high-quality cells from almost all known cell types present in the leaf. We show that the mesophyll contains two spatially separated cell populations with distinct responses to drought: one enriched in canonical abscisic acid-related drought-responsive genes, and another one depicting iron starvation responses. Our study thus reveals a dual adaptive mechanism of the leaf mesophyll in response to mild drought and provides a valuable resource for future research on stress responses.