bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-Cerebrum distortion-free three-dimensional pseudo-Continuous Arterial Spin Labeling at 7T
Authors: Zhao Chenyang , Shao Xingfeng , Shou Qinyang , Ma Samantha J. , Gokyar Sayim , Graf Christina , Stollberger Rudolf , Wang Danny JJ 
Published: April 2023

AbstractFulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave=0.4mT/m, Gratio=14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R=2×2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2×2×4 mm3resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.
Metabolite Signature of Life’s Essential 8 and Risk of Coronary Heart Disease among Low-Income Black and White Americans
Authors: Deng Kui , Gupta Deepak K. , Shu Xiao-Ou , Lipworth Loren , Zheng Wei , Thomas Victoria E. , Cai Hui , Cai Qiuyin , Wang Thomas J. , Yu Danxia 
Published: April 2023

AbstractBackground and AimsLife’s Essential 8 (LE8) is a comprehensive construct of cardiovascular health. Yet, little is known about LE8 score, its metabolic correlates, and their predictive implications among Black Americans and low-income individuals.MethodsIn a nested case-control study of coronary heart disease (CHD) among 598 Black and 596 White low-income Americans, we estimated LE8 score, conducted untargeted plasma metabolites profiling, and used elastic net with leave-one-out cross-validation to identify metabolite signature (MetaSig) of LE8. Associations of LE8 score and MetaSig with incident CHD were examined using conditional logistic regression. Mediation effect of MetaSig on the LE8-CHD association was also examined. The external validity of MetaSig was evaluated in another nested CHD case-control study among 598 Chinese adults.ResultsHigher LE8 score was associated with lower CHD risk [standardized OR (95% CI)=0.61 (0.53-0.69)]. The identified MetaSig, consisting of 133 metabolites, showed strong correlation with LE8 score (r=0.61) and inverse association with CHD risk [OR (95% CI)=0.57 (0.49-0.65)], robust to adjustment for LE8 score and across participants with different sociodemographic and health status (ORs: 0.42-0.69; allP<0.05). MetaSig mediated a large portion of the LE8-CHD association: 53% (32%-80%) (P<0.001). Significant associations of MetaSig with LE8 score and CHD risk were found in validation cohort [r=0.49; OR (95% CI)=0.57 (0.46-0.69)].ConclusionsHigher LE8 score and its MetaSig were associated with lower CHD risk among low-income Black and White Americans. Metabolomics may offer an objective and comprehensive measure of LE8 score and its metabolic phenotype relevant to CHD prevention among diverse populations.
Genome-wide Association Study of Postpartum Depression Identifies a Novel Susceptibility Locus at 18q12.1
Authors: Cordova-Palomera Aldo , Diogo Dorothée , Szalma Sándor 
Published: April 2023

AbstractPostpartum depression (PPD) is among the most frequent and incapacitating conditions following childbirth, with significant consequences for mothers, newborns and families. Genetic factors have been proposed to influence disease risk and symptom heterogeneity, and can potentially inform drug target discovery and treatment strategies.Here, we conducted a genetic association study to further our understanding of the genetic architecture of PPD. We identified PPD cases and controls in the UK Biobank using multiple sources of medical history and self-reported information. We performed genome-wide association studies of common and rare variants in in a harmonized set of up to 11,782 PPD cases and 167,480 controls among European-ancestry females.Genetic association results displayed a significantly associated locus at chromosome 18q12.1 led by the common rs10502503 marker (minor allele frequency: 29.9%, effect allele: C, odds ratio: 0.92,p=6.4×10−9), within silicofunctional mapping suggesting Cadherin 2 (CDH2) as a candidate causal gene. This signal, if confirmed in independent replication cohorts with PPD diagnosis confirmed through psychometry, may contribute novel insights into the genetic basis of PPD.The results illustrate the use of minimal phenotyping in large-scale general population cohorts to investigate the genetic etiology and heterogeneity of PPD, and to generate therapeutic hypotheses.
Development and application of an algorithm for statin-induced myopathy based on electronic health record-derived structured elements
Authors: Oni-Orisan Akinyemi , Lu Meng , Peng Jonathan A. , Krauss Ronald M. , Iribarren Carlos , Medina Marisa W. 
Published: April 2023

ABSTRACTObjectiveConsidering the non-specific nature of muscle symptoms, studies of statin-induced myopathy (SIM) in electronic health records require accurate algortihms that can reliably identify true statinrelated cases. However, prior algorithms have been constructed in study populations that preclude broad applicability. Here we developed and validated an algorithm that accurately defines SIM from electronic health records using structured data elements and conducted a study of determinants of SIM after applying the algorithm.Materials and MethodsWe used electronic records from an integrated health care delivery system (including comprehensive pharmacy dispensing records) and defined SIM as elevated creatine kinase (CK) ≥4 x upper limit of normal. A diverse cohort of participants receiving a variety of statin regimens met the criteria for study inclusion.ResultsWe identified multiple conditions strongly associated with elevated CK independent of statin use. A 2-step algorithm was developed using these all-cause conditions as secondary causes (step 1) along with evidence of a statin regimen change (step 2). We identified 1,262 algorithm-derived statininduced elevated CK cases. Gold standard SIM cases determined from manual chart reviews on a random subset of the all-cause elevated CK cases were used to validate the algorithm, which had a 76% sensitivity and 77% specificity for detecting the most certain cases. Pravastatin use was associated with a 2.18 odds (95% confidence interval 1.39-3.40, P=0.0007) for statin-induced CK elevation compared to lovastatin use after adjusting for dose and other factors.ConclusionsWe have produced an efficient, easy-to-apply methodological tool that can improve the quality of future research on statin-induced myopathy.
Stratigraphic distribution of ammonoids and other macrofossils from the upper Albian–lower Cenomanian interval in Putumayo, Colombia, northern South America: new data for mid-Cretaceous basin correlation
Authors: Luque Javier , Bustos Jonatan , Beltrán-Triviño Alejandro , Rodriguez Angie , Delgado Alexandra , Sanchez Johan M. , Caraballo Julián , Paez-Reyes Manuel , López-Horgue Mikel A. 
Published: April 2023

ABSTRACTDespite the rich paleontological heritage of Colombia, in the equatorial Neotropics, one of the least explored regions in terms of its fossil record is the Putumayo region near Ecuador, largely due to its considerable ground cover, thick vegetation, rock weathering, geographic remoteness, and overall inaccessibility to well-exposed outcrops. This precludes detailed comparisons with neighboring basins, and thus the generation of more comprehensive biostratigraphic correlations for western northern South America and other paleobiogeographic regions, e.g., Mediterranean Tethys, northern Africa, Western Interior Basin. Here, we report 67 occurrences of mid- Cretaceous ammonoids and other macrofossils (e.g., bivalves, decapod crustaceans, fish remains, plant remains), from the middle Albian of the uppermost Caballos Formation and the upper Albian–lower Cenomanian of the lower Villeta Formation, collected in-situ from a stratigraphic section cropping out on the Mocoa–San Francisco road in the Department of Putumayo, Colombia. Among the ammonoid taxa recovered are several morphotypes assignable to ?Schloenbachiasp., cf.Engonocerassp.,Oxytropidoceras(Venezoliceras) sp.,Oxytropidoceras(Laraiceras) sp., cf.Oxytropidocerassp.,Mortoniceras(Mortoniceras) cf.vespertinum,Mortoniceras(Mortoniceras) sp.,Algericerassp.,Hysterocerassp. 1,Hysterocerassp. 2, cf,Hysterocerassp., cf.Forbesicerassp.,Graysonitessp.,Hamitessp., and two isolated aptychi. The occurrence of the ammonoid generaOxytropidoceras,Mortoniceras, andSchloenbachia, suggest interconnection of the Putumayo Basin during the mid-Cretaceous with the Upper Magdalena Valley in Colombia and the Oriente Basin in Ecuador, which, together with the rest of the ammonoid assemblage, provide biostratigraphic data to define the upper Albian–lower Cenomanian in the basin and thus in northwestern South America.
Evaluating the efficiency and accuracy of a commercial test for estimating genetic risk of bovine congestive heart failure
Authors: Carlson Jaden M. , Heaton Michael P. , Allison Nathan , Hangman Alyssa , Petrik Dustin , Piscatelli Heather , Vander Ley Brian L. 
Published: April 2023

AbstractBackgroundBovine congestive heart failure (BCHF) is a significant cause of death in feedlot cattle in the Western Great Plains of North America. Single nucleotide polymorphisms (SNPs) in theARRDC3andNFIAgenes have been previously associated with BCHF and genetic tests can classify animals by their risk for disease. Here, our aims were to evaluate the efficiency (genotypes obtained / samples tested) of a rapid DNA extraction kit and the accuracy of a 2-SNP assay for BCHF risk.MethodsSkin biopsies from 100 cattle were randomized and extracted with a proprietary rapid DNA extraction kit. A custom duplex, combined sequence amplification and nucleotide detection (C-SAND) assay was developed and run once on a commercial thermocycling machine to determine the genotypes. Both the rapidly extracted DNA and highly purified reference DNA from the same individuals were genotyped with the 2-SNP assay by operators blinded to the sample identity. The C-SAND genotypes were compared to known genotypes derived from a bead array assay.A prioristandards for missing and incorrect genotypes were set at less than 3% and 1%, respectively.ResultsWhen using reference DNA samples, there were no missing and no incorrect C-SAND-derived genotypes, meeting thea prioristandards. When DNA samples from the rapid extraction kit were used, genotypes were not determined for 5% of the samples. Of the 95 samples successfully extracted, there were 0% and 3% incorrect genotypes for the respectiveARRDC3andNFIASNPs.ConclusionsThis duplex C-SAND assay and thermocycling machine combination were efficient and accurate when reference DNA was used, meetinga prioristandards. Although the reduced efficiency of the rapid extraction kit can be overcome by repeated testing, increased genotype errors present an important issue. Despite these challenges, this rapid extraction kit and assay can be a reasonable tool for producers to select animals with reduced BCHF risk.
Females exhibit smaller volumes of brain activation and lower inter-subject variability during motor tasks
Authors: Andrushko Justin W. , Rinat Shie , Kirby Eric D. , Dahlby Julia , Ekstrand Chelsea , Boyd Lara A. 
Published: April 2023

AbstractPast work has shown that brain structure and function differ between females and males. Males have larger cortical and sub-cortical volume and surface area (both total and subregional), while females have greater cortical thickness in most brain regions. Functional differences are also reported in the literature, yet to date little work has systematically considered whether patterns of brain activity indexed with functional magnetic resonance imaging (fMRI) differ between females and males. Recently, an attempt to modernize and improve our understanding of the homunculus, a somatotopic representation of the human body within the brain, was made. Still, in the decades since it was introduced, no research has considered sex differences in the somatotopic representation. The current study sought to remediate this issue by employing brain somatotopic motor mapping from a previously published and openly available dataset. We tested differences in patterns of functional brain activity associated with 12 voluntary movement patterns in females versus males. Results suggest that females exhibited smaller volumes of brain activation across all 12 movement tasks, and lower patterns of variability in 10 of the 12 movements. We also observed that females had greater cortical thickness, which is in alignment with previous analyses of structural differences. Overall, these findings provide a basis for considering biological sex in future fMRI research and provide a foundation of understanding differences in how neurological pathologies present in females vs males.
Capture-recapture for -omics data meta-analysis
Authors: Juodakis Julius 
Published: April 2023

AbstractOne of the major goals of modern -omics studies, in particular genome-wide association studies (GWASs), is to understand the polygenicity of various traits, i.e. the number of genetic factors causally determining them. Analogous measures could also be used to estimate the number of trait markers from non-genetic studies, such as proteomics or transcriptomics.Here, we describe how capture-recapture (C-R) models, originating in animal ecology, can be applied to this task. Our approach works by comparing the lists of trait-associated genes (or other markers) from several studies. In contrast to existing methods, C-R is specifically designed to make use of heterogeneous input studies, differing in analysis methods, populations or other factors: it extrapolates from their variability to estimate how many causal genes still remain undetected.We present a brief tutorial on C-R models, and demonstrate our proposed usage of it with code examples and simulations. We then apply it to GWASs and proteomic studies of preterm birth, a major clinical problem with largely unknown causes. The C-R estimates a relatively low number of causal genes for this trait, but many still undetected protein markers, suggesting that diverse environmentally-initiated pathways can lead to this clinical outcome.
Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress
Authors: Jain Greeshma , Trombetta-Lima Marina , Matlahov Irina , Taborda Ribas Hennrique , Chen Tingting , Parlato Raffaella , Portale Giuseppe , Dolga Amalia M. , van der Wel Patrick C.A. 
Published: April 2023

AbstractHuntington’s disease (HD) is a neurodegenerative disorder in which mutated fragments of the huntingtin protein (Htt) undergo misfolding and aggregation. Since misfolded and aggregated proteins can cause cellular stress and cytotoxicity, there is an interest in the development of small molecule aggregation inhibitors as potential modulators of HD pathogenesis. Here, we study how a polyphenol modulates the aggregation mechanism of huntingtin exon 1 (HttEx1) even at sub-stoichiometric ratios. Sub-stoichiometric amounts of curcumin impacted the primary and/or secondary nucleation events, extending the pre-aggregation lag phase. Remarkably, the disrupted aggregation process changed both the aggregate structure and its cell metabolic properties. When administered to neuronal cells, the ‘break-through’ protein aggregates induced a significantly reduced cellular stress compared to aggregates formed in absence of inhibitors. Structural analysis by electron microscopy, small angle X-ray scattering (SAXS), and solid-state NMR spectroscopy identified changes in the fibril structures, probing both the flanking domains that form the fuzzy coat, as well as the fibril core. The biggest changes affected the latter, which we propose to relate to the presence or absence of polyglutamine (polyQ) β-hairpin structures. Our findings highlight multifaceted consequences of small molecule inhibitors that modulate the protein misfolding landscape, with potential implications for treatment strategies in HD and other amyloid disorders.
Dynamics of the epigenetic landscape during development and in response to drought stress in sorghum
Authors: Hu Yongfeng , He Chao , Shen Yuning , Zeng Gongjian , Bi Siteng , Huang Quanjun , Qin Xiner , Deng Zhuying , He Zhengquan , Shen Xiangling 
Published: April 2023

AbstractSorghum bicoloris a C4 plant with the characteristics of high stress tolerance, which may be conferred partly by the underlying epigenetic mechanism unique to sorghum. In this study, we revealed some epigenomic features in sorghum that have never been reported before. The long H3K27me3 regions clustered in four areas, which we defined as H3K27me3 islands, were identified in sorghum. H3K36me3 plays some role in inhibiting the deposition of both H3K27me3 and H2A.Z, which may serve as partial motivation for the removal of H3K27me3 and H2A.Z in leaf and root. All the 7 histone marks are involved in the regulation of tissue-specific genes, especially the specific expression of C4 genes in leaf and peroxidase (POD) encoding genes in root, which are involved in the photosynthesis in leaf and lignin synthesis in root, respectively. These marks except H3K36me3 and H3K27me3 also engage in the regulation of stress genes in response to PEG treatment. However, we found that differential enrichment of histone marks on many tissue-specific genes was observed only between leaf and root but hardly in response to PEG treatment, although expression of these genes changed after PEG treatment.
Integration of microbial and chemical synthesis for the efficient production of plitidepsin, a promising anticancer and antiviral agent
Authors: Zhang Haili , Hui Zhen , Cai Mingwei , Huang Shipeng , Shi Wenguang , Liang Mengdi , Lin Yang , Shen Jie , Sui Minghao , Li Xuyang , Lai Qiliang , Dou Jie , Ge Yun , Zheng Min , Shao Zongze , Luo Xiaozhou , Tang Xiaoyu 
Published: April 2023

AbstractPlitidepsin, a marine-derived anticancer medicine, is being tested in phase III clinical trials for treating COVID-19. However, the current supply of plitidepsin relies on laborious chemical synthesis processes. Here, we present a new approach that combines microbial and chemical synthesis to produce plitidepsin. We screened a Tistrella strain library to identify a high-yield didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in the highest yield of didemnin B reported in the literature. Next, we developed two straightforward chemical strategies to convert didemnin B to plitidepsin, one of which involved a one-step synthetic route giving over 90% overall yield. We also synthesized two new didemnin analogues and assessed their anticancer and antiviral activities. Our findings offer a practical and sustainable solution for producing plitidepsin and its derivatives, potentially expediting didemnin drug development.
Transcriptional immune suppression and upregulation of double stranded DNA damage and repair repertoires in ecDNA-containing tumors
Authors: Lin Miin S. , Jo Se-Young , Luebeck Jens , Chang Howard Y. , Wu Sihan , Mischel Paul S. , Bafna Vineet 
Published: April 2023

AbstractExtrachromosomal DNA is a common cause of oncogene amplification in cancer. The non-chromosomal inheritance of ecDNA enables tumors to rapidly evolve, contributing to treatment resistance and poor outcome for patients. The transcriptional context in which ecDNAs arise and progress, including chromosomally-driven transcription, is incompletely understood. We examined gene expression patterns of 870 tumors of varied histological types, to identify transcriptional correlates of ecDNA. Here we show that ecDNA containing tumors impact four major biological processes. Specifically, ecDNA containing tumors upregulate DNA damage and repair, cell cycle control, and mitotic processes, but downregulate global immune regulation pathways. Taken together, these results suggest profound alterations in gene regulation in ecDNA containing tumors, shedding light on molecular processes that give rise to their development and progression.