bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Analysis of In-Hospital Outcomes and Care Cost Between Surgical and Transcatheter Valve Replacement for Aortic Stenosis: Insights From the U.S Nationwide Inpatient Sample Database
Authors: Uwumiro Fidelis E. , Bojerenu Michael , Ogbodo Charles T. , Okpujie Victory O. , Nwabueze Cherechi O. , Otabor Emmanuel O. , Shielu Muhammed L. , Nwume Chuka G. , Oshodi Omolade J. , Alemenzohu Hillary , Abesin Olawale O. 
Published: August 2023

ABSTRACTBackground/objectivesTranscatheter aortic valve replacement (TAVR) has emerged as a preferred alternative to surgical aortic valve replacement (SAVR) for symptomatic aortic stenosis. This study aimed to compare the clinical outcomes and care costs of TAVR and SAVR to medical management using five years of inpatient data.MethodsAdult hospitalizations with a principal diagnosis of aortic stenosis were analyzed from the Nationwide Inpatient Sample database (2016-2020). Diagnosis and procedure variables, as well as confounders and comorbidities, were identified using the International Classification of Diseases (ICD-10) codes. Multivariable regression models were utilized to assess mortality odds, length of stay (LOS), periprocedural complications, and care costs.ResultsAmong the 364,515 admissions for aortic stenosis analyzed, the mean age was 76 ± 0.5 years, with a majority of male patients (57.8%) and White Americans comprising 85.5% of the population. SAVR was performed in 29.3% of cases, and TAVR in 50.8%. TAVR demonstrated significantly lower in-hospital mortality compared to SAVR (aOR: 0.463; 95% CI: 0.366-0.587; P < 0.001), whereas SAVR did not show a significant difference (aOR: 0.786; 95% CI: 0.601-1.029; P = 0.079). TAVR also resulted in a significantly shorter mean LOS compared to SAVR (adjusted mean LOS: 2.37; 95% CI: 2.12-2.63; P < 0.001 vs. 6.25; 95% CI: 6.00-6.50; P < 0.001). While TAVR patients had a lower likelihood of complications, they incurred higher hospital costs.ConclusionTAVR demonstrated significantly lower odds of in-hospital mortality and shorter length of stay compared to medical management or SAVR. However, TAVR patients incurred higher hospital costs despite a lower likelihood of complications.
Decoding EEG for optimizing naturalistic memory
Authors: Rudoler J.H. , Bruska J.P. , Chang W. , Dougherty M.R. , Katerman B.S. , Halpern D.J. , Diamond N.B. , Kahana M.J. 
Published: August 2023

AbstractBackgroundSpectral features of human electroencephalographic (EEG) recordings during learning predict subsequent recall variability.New methodCapitalizing on these fluctuating neural features, we develop a non-invasive closed-loop (NICL) system for real-time optimization of human learning. Participants play a virtual navigation and memory game; recording multi-session data across days allowed us to build participant-specific classification models of recall success. In subsequent closed-loop sessions, our platform manipulated the timing of memory encoding, selectively presenting items during periods of predicted good or poor memory function based on EEG features decoded in real time.ResultsWe observed greater memory modulation (difference between recall rates when presenting items during predicted good vs. poor learning periods) for participants with higher out-of-sample classification accuracy.Comparison with Existing MethodsThis study demonstrates greater-than-chance memory decoding from EEG recordings in a naturalistic virtual navigation task with greater real-world validity than basic word-list recall paradigms. Here we modulate memory by timing stimulus presentation based on noninvasive scalp EEG recordings, whereas prior closed-loop studies for memory improvement involved intracranial recordings and direct electrical stimulation. Other noninvasive studies have investigated the use of neurofeedback or remedial study for memory improvement.ConclusionsThese findings present a proof-of-concept for using non-invasive closed-loop technology to optimize human learning and memory through principled stimulus timing, but only in those participants for whom classifiers reliably predict out-of-sample memory function.
Decreased accuracy of forensic DNA mixture analysis for groups with lower genetic diversity
Authors: Flores Maria , Ly Cara , Ho Evan , Ceberio Niquo , Felix Kamillah , Thorner Hannah Mariko , Guardado Miguel , Paunovich Matt , Godek Chris , Kalaydjian Carina , Rohlfs Rori 
Published: August 2023

SUMMARYForensic investigation of DNA samples from multiple contributors has become commonplace. These complex analyses use statistical frameworks accounting for multiple levels of uncertainty in allelic contributions from different individuals, particularly for samples containing few molecules of DNA. These methods have been thoroughly tested along some axes of variation, but less attention has been paid to accuracy across human genetic variation. Here, we quantify the accuracy of DNA mixture analysis over 244 human groups. We find higher false inclusion rates for mixtures with more contributors, and for groups with lower genetic diversity. Even for two-contributor mixtures where one contributor is known and the reference group is correctly specified, false inclusion rates are 1e-5 or higher for 56 out of 244 groups. This means that, depending on multiple testing, some false inclusions may be expected. These false positives could be lessened with more selective and conservative use of DNA mixture analysis.HIGHLIGHTSGroups with lower genetic diversity have higher mixture analysis false positive rates.Analyses with mis-specified references have somewhat higher false positive rates.Mixture analysis accuracy decreases with more mixture contributors.GRAPHICAL ABSTRACT
Uncovering the molecular signatures of russet skin formation in Niagara grapevine (Vitis vinifera x Vitis labrusca)
Authors: Niederauer Guilherme Francio , de Oliveira Geovani Luciano , Aono Alexandre Hild , Graciano Diego da Silva , Carmello-Guerreiro Sandra Maria , Moura Mara Fernandes , de Souza Anete Pereira 
Published: August 2023

ABSTRACTGrape breeding programs are mostly focused on developing new varieties with high production volume, sugar contents, and phenolic compound diversity combined with resistance and tolerance to the main pathogens under culture and adverse environmental conditions. The ‘Niagara’ variety (Vitis labruscaxVitis vinifera) is one of the most widely produced and commercialized table grapes in Brazil. In this work, we selected three Niagara somatic variants with contrasting berry phenotypes and performed morphological and transcriptomic analyses of their berries. Histological sections of the berries were also performed to understand anatomical and chemical composition differences of the berry skin between the genotypes. An RNA-Seq pipeline was implemented, followed by global coexpression network modeling. ‘Niagara Steck’, an intensified russet mutant with the most extreme phenotype, showed the largest difference in expression and showed selection of coexpressed network modules involved in the development of its russet-like characteristics. Enrichment analysis of differently expressed genes and hub network modules revealed differences in transcription regulation, auxin signaling and cell wall and plasmatic membrane biogenesis. Cutin- and suberin-related genes were also differently expressed, supporting the anatomical differences observed with microscopy.
Using a multiscale lidar approach to determine variation in canopy structure from African forest elephant trails
Authors: Keany Jenna M. , Burns Patrick , Abraham Andrew J. , Jantz Patrick , Makaga Loic , Saatchi Sassan , Maisels Fiona , Abernethy Katharine , Doughty Christopher 
Published: August 2023

ABSTRACTRecently classified as a unique species by the IUCN, African forest elephants (Loxodonta cyclotis) are critically endangered due to severe poaching. With limited knowledge about their ecological role due to the dense tropical forests they inhabit in central Africa, it is unclear how the Afrotropics would change if forest elephants were to go extinct. Although their role as seed dispersers is well known, they may also drive large-scale processes that determine forest structure, through the creation of elephant trails and browsing the understory and allowing larger, carbon-dense trees to succeed. Multiple scales of lidar were collected by NASA in Lopé National Park, Gabon from 2015-2022. Utilizing two airborne lidar datasets and one spaceborne lidar in an African forest elephant stronghold, detailed canopy structural information was used in conjunction with elephant trail data to determine how forest structure varies on and off trails. Forest above elephant trails displayed different structural characteristics than forested areas off trails, with lower canopy height, canopy cover, and different vertical distribution of plant mass. Less plant area density was found on trails at 1 m in height, while more vegetation was found at 12 m, compared to off trail locations. Trails with previous logging history had lower plant area in the top of the canopy.
Tryptophan wasting and disease activity as a systems phenomenon in inflammation – an analysis across 13 chronic inflammatory diseases
Authors: Harris Danielle MM , Szymczak Silke , Schuchardt Sven , Labrenz Johannes , Tran Florian , Welz Lina , Graßhoff Hanna , Zirpel Henner , Sümbül Melike , Oumari Mhmd , Engelbogen Nils , Junker Ralf , Conrad Claudio , Thaçi Diamant , Frey Norbert , Franke Andre , Weidinger Stephan , Rosenstiel Philip , Hoyer Bimba , Waschina Silvio , Schreiber Stefan , Aden Konrad 
Published: August 2023

AbstractChronic inflammatory diseases (CID) are systems disorders affecting various organs including the intestine, joint and skin. The essential amino acid tryptophan (Trp) is not only used for protein synthesis but can also be catabolized to various bioactive derivatives that are important for cellular energy metabolism and immune regulation. Increased Trp catabolism via the kynurenine pathway is seen across individual CID entities1–5. Here, we assessed the levels of Trp and tryptophan derivatives across 13 CID to investigate the extent and nature of Trp wasting as a systems phenomenon in CID. We found reduced serum Trp levels across the majority of CID and a prevailing negative relationship between Trp and systemic inflammatory marker C-reactive protein (CRP). Increases in the kynurenine-to-Trp ratio (Kyn:Trp) indicate that the kynurenine pathway is a major route for CID-related Trp wasting. However, the extent of Trp depletion and its relationship with disease activity varies by disease, indicating potential differences in Trp metabolism. In addition, we find that amino acid catabolism in chronic inflammation is specific to tryptophan wasting, whereas other proteinogenic amino acids are not affected. Hence, our results suggest that increased Trp catabolism is a common metabolic occurrence in CID that may directly affect systemic immunity.Grant supportThis work was supported by the DFG Cluster of Excellence 1261 “Precision medicine in chronic inflammation” (KA, SSchr, PR, BH, SWa), the BMBF (e:Med Juniorverbund “Try-IBD” 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), DFG RU5042 (PR, KA), and Innovative Medicines Initiative 2 Joint Undertakings (“Taxonomy, Treatments, Targets and Remission”, No. 831434, “ImmUniverse”, grant agreement No. 853995, “BIOMAP”, grant agreement No. 821511).
Glymphatic Inhibition Exacerbates Tau Propagation in an Alzheimer’s Disease Model
Authors: Lopes Douglas M , Wells Jack A , Ma Da , Wallis Lauren , Park Daniel , Llewellyn Sophie K , Ahmed Zeshan , Lythgoe Mark F , Harrison Ian F 
Published: August 2023

AbstractBackgroundThe aggregation and spread of misfolded amyloid structured proteins, such as tau and α-synuclein, are key pathological features associated with neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. These proteins possess a prion-like property, enabling their transmission from cell to cell leading to propagation throughout the central and peripheral nervous systems. While the mechanisms underlying their intracellular spread are still being elucidated, targeting the extracellular space has emerged as a potential therapeutic approach. The glymphatic system, a brain-wide pathway responsible for clearing extracellular metabolic waste from the central nervous system, has gained attention as a promising target for removing these toxic proteins.MethodsIn this study, we investigated the impact of long-term modulation of glymphatic function on tau aggregation and spread by chronically treating a mouse model of tau propagation with a pharmacological inhibitor of AQP4, TGN-020. Thy1-hTau.P301S mice were intracerebrally inoculated with tau into the hippocampus and overlying cortex, and subsequently treated with TGN-020 (3 doses/week, 50mg/kg TGN-020, i.p.) for 10-weeks. During this time, animal memory was studied using cognitive behavioural tasks, and structural MR images were acquired of the brainin vivoprior to brain extraction for immunohistochemical characterisation.ResultsOur findings demonstrate increased tau aggregation in the brain and transhemispheric propagation in the hippocampus and cortex following the inhibition of glymphatic clearance. Moreover, disruption of the glymphatic system aggravated recognition memory in tau inoculated mice and exacerbated regional changes in brain volume detected in the model. When initiation of drug treatment was delayed for several weeks post-inoculation, the aforementioned alterations were attenuated.ConclusionsThese results indicate that by modulating AQP4 function and, consequently, glymphatic clearance, it is possible to modify the propagation and pathological impact of tau in the brain, particularly during the initial stages of the disease. These findings highlight the critical role of the glymphatic system in preserving healthy brain homeostasis and offer valuable insights into the therapeutic implications of targeting this system for managing neurodegenerative diseases characterized by protein aggregation and spread.
Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion
Authors: Kudo Rei , Safonov Anton , Silva Edaise da , Li Qing , Shao Hong , Will Marie , Fushimi Atsushi , Nakshatri Harikrishna , Reis-Filho Jorge S. , Goel Shom , Koff Andrew , Weigelt Britta , Khan Qamar J. , Razavi Pedram , Chandarlapaty Sarat 
Published: August 2023

AbstractInhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a clinically-annotated cohort of patients with metastatic HR+ breast cancer, we identifiedTP53loss (28.8%) andMDM2amplification (6.7%) to be associated with lack of long-term disease control. Human breast cancer models revealed that p53 loss did not affect CDK4/6 activity or G1-blockade, but instead promoted drug-insensitive p130 phosphorylation by CDK2. Persistence of phospho-p130 prevented DREAM complex assembly, enabling cell cycle reentry and tumor progression. Inhibitors of CDK2 could overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically-diverse HR+ breast cancers.
Stromal signals dominate gene expression signature scores that aim to describe cancer-intrinsic stemness or mesenchymality characteristics
Authors: Kreis Julian , Aybey Bogac , Geist Felix , Brors Benedikt , Staub Eike 
Published: August 2023

AbstractPurposeEpithelial-to-mesenchymal transition (EMT) in cancer cells confers migratory ability, a crucial aspect of tumor metastasis that frequently leads to death. In multiple studies, authors proposed gene expression signatures for EMT, stemness, and mesenchymality (EMT-related) characteristics of tumors based on bulk tumor expression profiling. However, recent studies have suggested that non-cancerous cells in the tumor micro- or macroenvironment heavily influence individual signature profiles.Experimental DesignWe analyzed scores of 11 published and frequently referenced gene expression signatures in bulk, single cell, and pseudo bulk expression data across multiple cancer types.ResultsOur study strengthens and extends the influence of non-cancerous cells on signatures that were proposed to describe EMT-related (EMT, mesenchymal, or stemness) characteristics in various cancer types. The cell type composition, especially the amount of tumor cells, of a tumor sample frequently dominates EMT-related signature scores. Additionally, our analyses revealed that stromal cells, most often fibroblasts, are the main drivers of the EMT-related signature scores.ConclusionsWe call attention to the risk of false conclusions about tumor properties when interpreting EMT-related signatures, especially in a clinical setting: high patient scores of EMT-related signatures or calls of “stemness subtypes” often result from low tumor cell content in tumor biopsies rather than cancer cell-specific stemness or mesenchymality/EMT characteristics.
A low-cost and open-source imaging platform reveals spatiotemporal insight intoArabidopsisleaf elongation and movement
Authors: Oskam Lisa , Snoek Basten L. , Pantazopoulou Chrysoula K. , van Veen Hans , Matton Sanne E. A. , Dijkhuizen Rens , Pierik Ronald 
Published: August 2023

AbstractPlant organs move throughout the diurnal cycle, changing leaf and petiole positions to balance light capture, leaf temperature and water loss under dynamic environmental conditions. Upward movement of the petiole, called hyponasty, is one of several traits of the shade avoidance syndrome (SAS). SAS traits are elicited upon perception of vegetation shade signals such as far-red light (FR) and improve light capture in dense vegetation. Monitoring plant movement at a high temporal resolution allows studying functionality, as well as molecular regulation of hyponasty. However, high temporal resolution imaging solutions are often very expensive, making this unavailable to many researchers. Here, we present a modular and low-cost imaging set-up, based on small Raspberry Pi computers, that can track leaf movements and elongation growth with high temporal resolution. We also developed an open-source, semi-automated image analysis pipeline. Using this setup we followed responses to FR enrichment, light intensity and their interactions. Tracking both elongation and angle of petiole, lamina and entire leaf revealed insight into R:FR sensitivities of leaf growth and movement dynamics, and its interactions with background light intensity. We also identified spatial separation in hyponastic response regulation for the petiole and the lamina of the leaf, depending on the light conditions.
Constructing networks for comparison of collagen types
Authors: Wesp Valentin , Scholz Lukas , Ziermann-Canabarro Janine M. , Schuster Stefan , Stark Heiko 
Published: August 2023

AbstractCollagens are structural proteins that are predominantly found in the extracellular matrix of multicellular animals, where they are mainly responsible for the stability and structural integrity of various tissues. All collagens contain polypeptide strands (ɑ-chains). There are several types of collagens, some of which differ significantly in form, function, and tissue specificity. Because of their importance in clinical research, they are grouped into subdivisions, the so-called collagen families, and their sequences are often analysed. However, problems arise with highly homologous sequence segments. To increase the accuracy of collagen classification and prediction of their functions, the structure of these collagens and their expression in different tissues could result in a better focus on sequence segments of interest. Here, we analyse collagen families with different levels of conservation. As a result, clusters with high interconnectivity can be found, such as the fibrillar collagens, the COL4 network-forming collagens, and the COL9 FACITs. Furthermore, a large cluster between network-forming, FACIT, and COL28a1 ɑ-chains is formed with COL6a3 as a major hub node. The formation of clusters also signifies, why it is important to always analyse the ɑ-chains and why structural changes can have a wide range of effects on the body.
Integration of graph neural networks and genome-scale metabolic models for predicting gene essentiality
Authors: Hasibi Ramin , Michoel Tom , Oyarzún Diego A. 
Published: August 2023

AbstractGenome-scale metabolic models are powerful tools for understanding cellular physiology. Flux balance analysis (FBA), in particular, is a popular optimization approach for predicting metabolic phenotypes under genetic and environmental perturbations. In model microbes such asEscherichia coli, FBA has been successful at predicting essential genes, i.e. those genes that impair survival when deleted. A central assumption in this approach, however, is that both wild type and deletion strains optimize the same fitness objective. While the optimality assumption may hold for the wild type metabolic network, deletion strains are not subject to the same evolutionary pressures and knock-out mutants may steer their metabolism to meet other objectives for survival. Here, we present FlowGAT, a hybrid FBA-machine learning strategy for predicting essentiality directly from wild type metabolic phenotypes. The approach is based on graph-structured representation of metabolic fluxes predicted by FBA, where nodes correspond to enzymatic reactions and edges quantify the propagation of metabolite mass flow between a reaction and its neighbours. We integrate this information into a graph neural network that can be trained on knock-out fitness assay data. Comparisons across different model architectures reveal that FlowGAT predictions forE. coliare close to those of FBA for several growth conditions. This suggests that gene essentiality can be accurately predicted by exploiting the network structure of metabolism, without additional assumptions beyond optimality of the wild type. Our approach demonstrates the benefits of combining the mechanistic insights afforded by genome-scale models with the ability of deep learning models to extract patterns from complex data.
Infection with the chytrid fungus (Batrachochytrium dendrobatidis) may distort sex ratio via sex reversal but not sex-dependent mortality in a common Eurasian amphibian
Authors: Ujszegi János , Ujhegyi Nikolett , Balogh Emese , Mikó Zsanett , Kásler Andrea , Hettyey Attila , Bókony Veronika 
Published: August 2023

AbstractOne of the major factors driving the currently ongoing biodiversity crisis is the anthropogenic spread of infectious diseases. Diseases can have conspicuous consequences, such as mass mortality events, but may also exert covert but similarly severe effects, such as sex ratio distortion via sex-biased mortality or sex reversal. Chytridiomycosis, caused by the fungal pathogenBatrachochytrium dendrobatidis(Bd) is among the most important threats to amphibian biodiversity. Yet, whether Bd infection can skew sex ratios in amphibians is currently unknown, although such a hidden effect may cause the already dwindling amphibian populations to collapse. To investigate this possibility, we collected common toad (Bufo bufo) tadpoles from a natural habitat in Hungary, and continuously treated them until metamorphosis with sterile Bd culture medium (control), or a liquid culture of a Hungarian or a Spanish Bd isolate. Three months after metamorphosis we dissected the individuals and diagnosed their phenotypic and genetic sex. Bd prevalence was high in animals that died during the experiment but was almost zero at sexing. Survival was generally low in the control group, but it was further lowered by the Bd treatments. We did not observe sex-dependent mortality in either treatment. However, treatment with the Spanish Bd isolate significantly increased the frequency of sex reversal: 3 out of 9 genetic females developed into phenotypic males. Based on our results, Bd infection may have the potential to affect sex ratio in common toads through female-to-male sex reversal, but future research is needed to ascertain the generality of these findings.