bluuebunny/crossref_metadata_2025_split huggingface dataset:
A histone demethylase links the loss of plasticity to nongenetic inheritance and morphological change
Authors: Levis Nicholas A. , Ragsdale Erik J. 
Published: December 2023

AbstractPlasticity is a widespread feature of development, enabling phenotypic change based on the environment. Although the evolutionary loss of plasticity has been linked both theoretically and empirically to increased rates of phenotypic diversification, molecular insights into how this process might unfold are generally lacking. Here, we show that a regulator of nongenetic inheritance links evolutionary loss of plasticity in nature to changes in plasticity and morphology as selected in the laboratory. Across nematodes of Diplogastridae, which ancestrally had a polyphenism, or discrete plasticity, in their feeding morphology, we use molecular evolutionary analyses to screen for change associated with independent losses of plasticity. Having inferred a set of ancestrally polyphenism-biased genes from phylogenetically informed gene-knockouts and gene-expression comparisons, selection signatures associated with plasticity’s loss identify the histone H3K4 di/monodemethylase gene spr-5/LSD1/KDM1A. Manipulations of this gene affect both sensitivity and variation in plastic morphologies, and artificial selection of manipulated lines drive multigenerational shifts in these phenotypes. Our findings thus give mechanistic insight into how traits are modified as they traverse the continuum of greater to lesser environmental sensitivity.
Multicenter evaluation of gut microbiome profiling by next-generation sequencing reveals major biases in partial-length metabarcoding approach
Authors: Roume Hugo , Mondot Stanislas , Saliou Adrien , Le Fresne-Languille Sophie , Doré Joël 
Published: December 2023

AbstractNext-generation sequencing workflows, using either metabarcoding or metagenomic approaches, have massively contributed to expanding knowledge of the human gut microbiota, but methodological bias compromises reproducibility across studies. Where these biases have been quantified within several comparative analyses on their own, none have measured inter-laboratory reproducibility using similar DNA material. Here, we designed a multicenter study involving seven participating laboratories dedicated to partial- (P1 to P5), full-length (P6) metabarcoding, or metagenomic profiling (MGP) using DNA from a mock microbial community or extracted from 10 fecal samples collected at two time points from five donors. Fecal material was collected, and the DNA was extracted according to the IHMS protocols. The mock and isolated DNA were then provided to the participating laboratories for sequencing. Following sequencing analysis according to the laboratories’ routine pipelines, relative taxonomic-count tables defined at the genus level were provided and analyzed. Large variations in alpha-diversity between laboratories, uncorrelated with sequencing depth, were detected among the profiles. Half of the genera identified by P1 were unique to this partner and two-thirds of the genera identified by MGP were not detected by P3. Analysis of beta-diversity revealed lower inter-individual variance than inter-laboratory variances. The taxonomic profiles of P5 and P6 were more similar to those of MGP than those obtained by P1, P2, P3, and P4. Reanalysis of the raw sequences obtained by partial-length metabarcoding profiling, using a single bioinformatic pipeline, harmonized the description of the bacterial profiles, which were more similar to each other, except for P3, and closer to the profiles obtained by MGP. This study highlights the major impact of the bioinformatics pipeline, and primarily the database used for taxonomic annotation. Laboratories need to benchmark and optimize their bioinformatic pipelines using standards to monitor their effectiveness in accurately detecting taxa present in gut microbiota.
Rapid seasonal changes in phenotypes in a wild Drosophila population
Authors: Ueno Takahisa , Takenoshita Akiko , Hamamichi Kaiya , Sato Mitsuhiko P. , Takahashi Yuma 
Published: December 2023

AbstractSeasonal environmental change is one of the most rapid and striking environmental variables. Although relatively rapid adaptation to environmental changes over several years or several decades has been described in many taxa, rapid responses to seasonal environments are delicate, and therefore, the detection of the evolutionary responses requires sensitive methods. In this study, we examined seasonal changes in phenotypes related to thermal tolerance and morphological traits of Drosophila lutescens collected at the spring and autumn periods from a single location. We first demonstrated that flies in the two seasonal periods were almost genetically identical using double-digest restriction site-associated DNA sequencing and analysis. Using an experimental design to eliminate the effect of possible confounding factors that influence phenotypes (i.e., maternal effects and the environmental conditions in which each phenotype was analyzed), we showed that the heat tolerance of D. lutescens was significantly higher in the autumn population than in the spring population. Furthermore, cold tolerance was slightly higher in the spring population than in the autumn one. Although wing length and thorax length did not change significantly between seasons, the ratio of wing length to thorax length changed significantly between them. These results suggest that seasonal environmental heterogeneity induces rapid phenotypic changes within a year. Finally, we discuss the possibility of rapid evolutionary responses to seasonal changes.
Effects of donor-specific microvascular anatomy on hemodynamic perfusion in human choriocapillaris
Authors: An Senyou , Yu Huidan , Islam MD Mahfuzul , Zhang Xiaoyu , Zhan Yuting , Olivieri Joseph J. , Ambati Jayakrishna , Yao Jun , Gelfand Bradley D. 
Published: December 2023

AbstractEvidence from histopathology and clinical imaging suggest that choroidal anatomy and hemodynamic perfusion are among the earliest changes in retinal diseases such as age-related macular degeneration (AMD). However, how inner choroidal anatomy affects hemodynamic perfusion is not well understood. Therefore, we sought to understand the influences of choroidal microvascular architecture on the spatial distribution of hemodynamic parameters in choriocapillaris from human donor eyes using image-based computational hemodynamic (ICH) simulations. We subjected image-based inner choroid reconstructions from eight human donor eyes to ICH simulation using a kinetic-based volumetric lattice Boltzmann method to compute hemodynamic distributions of velocity, pressure, and endothelial shear stress. Here, we demonstrate that anatomic parameters, including arteriolar and venular arrangements and intercapillary pillar density and distribution exert profound influences on inner choroidal hemodynamic characteristics. Reductions in capillary, arteriolar, and venular density not only reduce the overall blood velocity within choriocapillaris, but also substantially increase its spatial heterogeneity. These first-ever findings improve understanding of how choroidal anatomy affects hemodynamics and may contribute to pathogenesis of retinal diseases such as AMD.
Self-supervised MRI denoising: leveraging Stein’s unbiased risk estimator and spatially resolved noise maps
Authors: Pfaff Laura , Hossbach Julian , Preuhs Elisabeth , Wagner Fabian , Arroyo Camejo Silvia , Kannengiesser Stephan , Nickel Dominik , Wuerfl Tobias , Maier Andreas 
Published: December 2023

AbstractThermal noise caused by the imaged object is an intrinsic limitation in magnetic resonance imaging (MRI), resulting in an impaired clinical value of the acquisitions. Recently, deep learning (DL)-based denoising methods achieved promising results by extracting complex feature representations from large data sets. Most approaches are trained in a supervised manner by directly mapping noisy to noise-free ground-truth data and, therefore, require extensive paired data sets, which can be expensive or infeasible to obtain for medical imaging applications. In this work, a DL-based denoising approach is investigated which operates on complex-valued reconstructed magnetic resonance (MR) images without noise-free target data. An extension of Stein’s unbiased risk estimator (SURE) and spatially resolved noise maps quantifying the noise level with pixel accuracy were employed during the training process. Competitive denoising performance was achieved compared to supervised training with mean squared error (MSE) despite optimizing the model without noise-free target images. The proposed DL-based method can be applied for MR image enhancement without requiring noise-free target data for training. Integrating the noise maps as an additional input channel further enables the regulation of the desired level of denoising to adjust to the preference of the radiologist.
Online real-time learning of dynamical systems from noisy streaming data
Authors: Sinha S. , Nandanoori S. P. , Barajas-Solano D. A. 
Published: December 2023

AbstractRecent advancements in sensing and communication facilitate obtaining high-frequency real-time data from various physical systems like power networks, climate systems, biological networks, etc. However, since the data are recorded by physical sensors, it is natural that the obtained data is corrupted by measurement noise. In this paper, we present a novel algorithm for online real-time learning of dynamical systems from noisy time-series data, which employs the Robust Koopman operator framework to mitigate the effect of measurement noise. The proposed algorithm has three main advantages: (a) it allows for online real-time monitoring of a dynamical system; (b) it obtains a linear representation of the underlying dynamical system, thus enabling the user to use linear systems theory for analysis and control of the system; (c) it is computationally fast and less intensive than the popular extended dynamic mode decomposition (EDMD) algorithm. We illustrate the efficiency of the proposed algorithm by applying it to identify the Van der Pol oscillator, the chaotic attractor of the Henon map, the IEEE 68 bus system, and a ring network of Van der Pol oscillators.
Developing a model to predict the early risk of hypertriglyceridemia based on inhibiting lipoprotein lipase (LPL): a translational study
Authors: Hernandez-Baixauli Julia , Chomiciute Gertruda , Alcaide-Hidalgo Juan María , Crescenti Anna , Baselga-Escudero Laura , Palacios-Jordan Hector , Foguet-Romero Elisabet , Pedret Anna , Valls Rosa M. , Solà Rosa , Mulero Miquel , Del Bas Josep M. 
Published: December 2023

AbstractHypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). One of the multiple origins of HTG alteration is impaired lipoprotein lipase (LPL) activity, which is an emerging target for HTG treatment. We hypothesised that early, even mild, alterations in LPL activity might result in an identifiable metabolomic signature. The aim of the present study was to assess whether a metabolic signature of altered LPL activity in a preclinical model can be identified in humans. A preclinical LPL-dependent model of HTG was developed using a single intraperitoneal injection of poloxamer 407 (P407) in male Wistar rats. A rat metabolomics signature was identified, which led to a predictive model developed using machine learning techniques. The predictive model was applied to 140 humans classified according to clinical guidelines as (1) normal, less than 1.7 mmol/L; (2) risk of HTG, above 1.7 mmol/L. Injection of P407 in rats induced HTG by effectively inhibiting plasma LPL activity. Significantly responsive metabolites (i.e. specific triacylglycerols, diacylglycerols, phosphatidylcholines, cholesterol esters and lysophospholipids) were used to generate a predictive model. Healthy human volunteers with the impaired predictive LPL signature had statistically higher levels of TG, TC, LDL and APOB than those without the impaired LPL signature. The application of predictive metabolomic models based on mechanistic preclinical research may be considered as a strategy to stratify subjects with HTG of different origins. This approach may be of interest for precision medicine and nutritional approaches.
Sequential deregulation of histone marks, chromatin accessibility and gene expression in response to PROTAC-induced degradation of ASH2L
Authors: Barsoum Mirna , Sayadi-Boroujeni Roksaneh , Stenzel Alexander T. , Bussmann Philip , Lüscher-Firzlaff Juliane , Lüscher Bernhard 
Published: December 2023

AbstractThe trithorax protein ASH2L is essential for organismal and tissue development. As a subunit of COMPASS/KMT2 complexes, ASH2L is necessary for methylation of histone H3 lysine 4 (H3K4). Mono- and tri-methylation at this site mark active enhancers and promoters, respectively, although the functional relevance of H3K4 methylation is only partially understood. ASH2L has a long half-life, which results in a slow decrease upon knockout. This has made it difficult to define direct consequences. To overcome this limitation, we employed a PROTAC system to rapidly degrade ASH2L and address direct effects. ASH2L loss resulted in inhibition of proliferation of mouse embryo fibroblasts. Shortly after ASH2L degradation H3K4me3 decreased with its half-life varying between promoters. Subsequently, H3K4me1 increased at promoters and decreased at some enhancers. H3K27ac and H3K27me3, histone marks closely linked to H3K4 methylation, were affected with considerable delay. In parallel, chromatin compaction increased at promoters. Of note, nascent gene transcription was not affected early but overall RNA expression was deregulated late after ASH2L loss. Together, these findings suggest that downstream effects are ordered but relatively slow, despite the rapid loss of ASH2L and inactivation of KMT2 complexes. It appears that the systems that control gene transcription are well buffered and strong effects are only beginning to unfold after considerable delay.
Dementia risk analysis using temporal event modeling on a large real-world dataset
Authors: Taylor R. Andrew , Gilson Aidan , Chi Ling , Haimovich Adrian D. , Crawford Anna , Brandt Cynthia , Magidson Phillip , Lai James M. , Levin Scott , Mecca Adam P. , Hwang Ula 
Published: December 2023

AbstractThe objective of the study is to identify healthcare events leading to a diagnosis of dementia from a large real-world dataset. This study uses a data-driven approach to identify temporally ordered pairs and trajectories of healthcare codes in the electronic health record (EHR). This allows for discovery of novel temporal risk factors leading to an outcome of interest that may otherwise be unobvious. We identified several known (Down syndrome RR = 116.1, thiamine deficiency RR = 76.1, and Parkinson's disease RR = 41.1) and unknown (Brief psychotic disorder RR = 68.6, Toxic effect of metals RR = 40.4, and Schizoaffective disorders RR = 40.0) factors for a specific dementia diagnosis. The associations with the greatest risk for any dementia diagnosis were found to be primarily related to mental health (Brief psychotic disorder RR = 266.5, Dissociative and conversion disorders RR = 169.8), or neurologic conditions or procedures (Dystonia RR = 121.9, Lumbar Puncture RR = 119.0). Trajectory and clustering analysis identified factors related to cerebrovascular disorders, as well as diagnoses which increase the risk of toxic imbalances. The results of this study have the ability to provide valuable insights into potential patient progression towards dementia and improve recognition of patients at risk for developing dementia.
Production and purification of 43Sc and 47Sc from enriched [46Ti]TiO2 and [50Ti]TiO2 targets
Authors: Cingoranelli Shelbie J. , Bartels Jennifer L. , Kankanamalage Pavithra H. A. , Loveless C. Shaun , Rotsch David A. , Lapi Suzanne E. 
Published: December 2023

AbstractThe radioscandium isotopes, 43Sc and 47Sc, compose a promising elementally matched theranostic pair that can be used for the development of imaging and therapeutic radiopharmaceuticals with identical structures. This study aimed to investigate the production of high radionuclidic purity 43Sc from enriched [46Ti]TiO2 targets and 47Sc from enriched [50Ti]TiO2 targets and establish a target recycling technique. Enriched [46Ti]TiO2 targets were irradiated with 18 MeV protons, and enriched [50Ti]TiO2 targets were bombarded with 24 MeV protons. 43Sc and 47Sc were purified using ion chromatography attaining recovery yields of 91.7 ± 7.4% and 89.9 ± 3.9%, respectively. The average radionuclidic purity for 43Sc was 98.8 ± 0.3% and for 47Sc 91.5 ± 0.6%, while the average recovery of enriched titanium target material was 96 ± 4.0%. The highest apparent molar activity for [43Sc]Sc-DOTA was 23.2 GBq/µmol and 3.39 GBq/µmol for [47Sc]Sc-DOTA. This work demonstrates the feasibility of using enriched recycled [46Ti]TiO2 and [50Ti]TiO2 targets to produce high purity 43Sc and 47Sc as an elementally matched theranostic isotope pair.
A priori prediction of breast cancer response to neoadjuvant chemotherapy using quantitative ultrasound, texture derivative and molecular subtype
Authors: Sannachi Lakshmanan , Osapoetra Laurentius O. , DiCenzo Daniel , Halstead Schontal , Wright Frances , Look-Hong Nicole , Slodkowska Elzbieta , Gandhi Sonal , Curpen Belinda , Kolios Michael C. , Oelze Michael , Czarnota Gregory J. 
Published: December 2023

AbstractThe purpose of this study was to investigate the performances of the tumor response prediction prior to neoadjuvant chemotherapy based on quantitative ultrasound, tumour core-margin, texture derivative analyses, and molecular parameters in a large cohort of patients (n = 208) with locally advanced and earlier-stage breast cancer and combined them to best determine tumour responses with machine learning approach. Two multi-features response prediction algorithms using a k-nearest neighbour and support vector machine were developed with leave-one-out and hold-out cross-validation methods to evaluate the performance of the response prediction models. In a leave-one-out approach, the quantitative ultrasound-texture analysis based model attained good classification performance with 80% of accuracy and AUC of 0.83. Including molecular subtype in the model improved the performance to 83% of accuracy and 0.87 of AUC. Due to limited number of samples in the training process, a model developed with a hold-out approach exhibited a slightly higher bias error in classification performance. The most relevant features selected in predicting the response groups are core-to-margin, texture-derivative, and molecular subtype. These results imply that that baseline tumour-margin, texture derivative analysis methods combined with molecular subtype can potentially be used for the prediction of ultimate treatment response in patients prior to neoadjuvant chemotherapy.
The use of photosynthetic pigments and SPAD can help in the selection of bean genotypes under fertilization organic and mineral
Authors: Carreño Siqueira José Andres , Marques Douglas José , Silva Maria Clara Gabriel , Silva Cristian Araújo 
Published: December 2023

AbstractThe common bean is cultivated in all regions of the country, representing a product of great economic and social importance. In order to ensure food security in the world, it is necessary to create alternatives to reduce the dependence on fertilizers and seeds, and in this context, organic agriculture is a sustainable alternative to ensure it. Therefore, it becomes necessary to adapt rapid methods to monitor plant nutrition in real-time. The reflectance index determined by SPAD and pigment determination can be a sustainable alternative to identify genotypes in different fertilizations (organic × mineral fertilizer). The research hypothesis is to monitor nutritional management through pigment levels and reflectance index in common bean cultivars and their adaptation into different types of fertilization (organic × mineral fertilizer). Therefore, the objective of the research was to evaluate the common bean genotypes of the type carioca, in different fertilizations (organic × mineral fertilizer), and their effects on photosynthetic pigments, and the relationship between SPAD reflectance index and productivity. The experimental design used was a 2 × 7 factorial in randomized blocks with four replications: The first factor was the fertilization (organic × mineral fertilizer)and the second were the 7 genotypes (UFU-1; UFU-2; UFU-3; UFU-4; UFU-5; UFU-6 UFU-7), with UFU-1 being a hybrid obtained between genotypes UFU-4 and UFU-7; UFU-2 and UFU-3 were commercial genotypes; and UFU-4, UFU-5, UFU-6 and UFU-7 were genotypes from the UFU germplasm bank, located in the city of Monte Carmelo, Brazil. Evaluations were carried out for the agronomic characteristics of the plants, which were: height, number of branches, length and volume of roots, dry matter, leaf area index, number of flowers, number of pods, number of seeds per pod, 100 seed weight, and productivity of the genotypes. The results were compared with chlorophyll content and SPAD reflectance index, and the genotypes showed distinct behavior for each fertilization (organic × mineral fertilizer). The genotypes recommended for the organic fertilizer were UFU-2, UFU-6, and UFU-7, which showed higher productivity. For themineral fertilizer, the best-adapted genotype was UFU-4, with a higher productive yield. In conclusion, we can affirm that the highest chlorophyll and SPAD indices can help select common bean genotypes with higher productivity and adaptation within the organic fertilizer being this the main focus of this research. However, the other variables carried out during this research also demonstrated to have significant effects, so they could be analyzed individually and could offer valuable information in the selection of the best-adapted genotypes.
Examining acute psychopharmacological effects of nicotine vaping versus heated tobacco products in a randomised crossover study of product naïve adult smokers
Authors: Kale Dimitra , Tattan-Birch Harry , Brown Jamie , Cox Sharon , Dawkins Lynne , Goniewicz Maciej L. , Morris Kierra , Shahab Lion 
Published: December 2023

AbstractNicotine vaping products (NVPs) and heated tobacco products (HTPs) are designed to replicate the sensory and behavioural aspects of smoking cigarettes while avoiding combustion. The success of these products as harm reduction tools will partially depend on their ability to satisfy smokers and alleviate nicotine-related withdrawal symptoms. This study aims to compare short-term effects of NVPs (Juul and Aspire PockeX) versus HTPs (IQOS) on smoking-related withdrawal relief, product satisfaction, intention to switch to NVP/HTP, perceptions and attitudes in UK adult cigarette smokers naïve to these products. In a randomized cross-over study, 45 participants visited the lab twice, at each visit trying one of the two products (NVP/HTP) and completing a questionnaire. Responses were normalized on a 0–100% scale and mean differences (MD) between NVP and HTP scores computed, with positive and negative MD values indicating greater endorsement for NVP and HTP, respectively. Cigarette cravings were reduced similarly (~ 20.0%) by both products (MD = 4.5%, 95%Confidence Interval (CI) − 4.8, 13.8). Direct positive effects (MD = − 3.5%, 95%CI − 7.2, 0.2) and adverse side effects (MD = 1.8%, 95%CI − 0.3, 3.8) were comparable after each product use, though marginally favouring HTPs. HTPs were perceived as more satisfying overall (MD = − 13.2%, 95%CI − 20.3 − 6.1) than NVPs but both were perceived as similarly addictive (MD = 3.6%, 95%CI − 4.6, 11.8), relative to cigarettes. Intention to switch to either product was comparable (MD = 4.0%, 95%CI − 5.7, 13.8). Comparison of acute use of NVP versus HTP in a sample of UK smokers naïve to these products suggests that HTPs are perceived as more satisfying than NVPs, though still less satisfying than cigarettes.Registration: The analysis plan was pre-registered, and it is available athttps://osf.io/6ymdu