bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nematode model to evaluate microdeletion phenotype expression
Authors: Antkowiak Katianna R. , Coskun Peren , Noronha Sharon T. , Tavella Davide , Massi Francesca , Ryder Sean P. 
Published: November 2022

ABSTRACTMicrodeletion syndromes are genetic diseases caused by chromosomal deletions too small to be detected by karyotyping. They are typified by complex pleiotropic developmental phenotypes that depend both on the extent of the deletion and variations in genetic background. Microdeletion alleles disrupt several genes simultaneously, often as the result of a single mutagenic event, causing a wide array of consequences across multiple systems involving multiple pathways. How simultaneous haploinsufficiency of numerous adjacent genes leads to complex and variable pleiotropic phenotypes is not well understood. CRISPR/Cas9 genome editing has been shown to induce microdeletion-like alleles at a meaningful rate. Here, we describe a microdeletion allele inCaenorhabditis elegansrecovered during a CRISPR/Cas9 genome editing experiment. We mapped the allele to chromosome V, balanced it with a reciprocal translocation crossover suppressor, and precisely defined the breakpoint junction. The allele simultaneously removes 32 protein-coding genes, yet animals homozygous for this mutation are viable as adults. Homozygous animals display a complex phenotype including maternal effect lethality, producing polynucleated embryos that grow into uterine tumors, vulva morphogenesis defects, body wall distensions, uncoordinated movement, and a shortened life span typified by death by bursting. Our work provides an opportunity to explore the complexity and penetrance of microdeletion phenotypes in a simple genetic model system.
Quantitative imaging of gene therapy delivery vehicles using CEST-NMR/MRI
Authors: Lam Bonnie , Velasquez Mark , Velasquez-Mao A.J. , Godines Kevin , AlGhuraibawi Wissam , Wendland Michael , Pelton Jeff , Vandsburger Moriel 
Published: November 2022

AbstractPurposeGene therapy employing AAV vector-mediated gene delivery has undergone substantial growth in recent years with promising results in both preclinical and clinical studies, as well as emerging regulatory approval. However, the lack of methods for quantifying the efficacy of gene therapy from cellular delivery of gene editing technology to specific functional outcomes remains an obstacle for the efficient development of gene therapy treatments. Building upon prior works that utilized a genetically encoded Lysine Rich Protein as a chemical exchange saturation transfer (CEST) reporter, we hypothesized that AAV viral capsids may generate endogenous CEST contrast from the large number of surface lysine residues.MethodsWater-suppressed NMR and NMR-CEST experiments were performed on isolated solutions of AAV serotypes 1-9 on a Bruker 800MHz vertical scanner. A series of in vitro experiments were performed for thorough testing of NMR-CEST contrast of AAV2 capsids under varying pH, density, biological transduction stage, and later across multiple serotypes and mixed biological media. Reverse transcriptase (RT)-polymerase chain reaction (PCR) was used to quantify virus concentration. Subsequent experiments determined the pH-dependent exchange rate and optimized CEST saturation schemes for AAV contrast detection at 7 T.ResultsNMR-CEST experiments revealed CEST contrast up to 52% for AAV2 viral capsids between 0.6-0.8 ppm. Evaluation of CEST contrast generated by AAV2 demonstrates high levels of CEST contrast across a variety of chemical environments, concentrations, and saturation schemes. AAV2 CEST contrast displayed significant positive correlations with capsid density (R2>0.99, P<0.001), pH (R2=0.97, P=0.01), and viral titer per cell count (R2=0.92, P<0.001). Transition to a preclinical field strength yielded up to 11.8% CEST contrast following optimization of saturation parameters.ConclusionAAV2 viral capsids exhibit strong capacity as an endogenous CEST contrast agent and can potentially be used for monitoring and evaluation of AAV vector-mediated gene therapy protocols.
Anin vitromicrofluidic culture device for peripheral neurotoxicity prediction at low concentration based on deep learning
Authors: Han Xiaobo , Matsuda Naoki , Matsuda Kazuki , Yamanaka Makoto , Suzuki Ikuro 
Published: November 2022

AbstractIn this study, a microfluidic culture device was developed including related evaluation methods using deep learning for the purpose of constructing a rapid assessment platform for peripheral neuropathy caused by compounds. Primary rodent dorsal root ganglion was cultured in the microfluidic culture device that could separate the cell body and neurites, and the neurites’ morphological changes were analyzed by immunofluorescence images. Separated neurites successful culture in the microfluidic device for more than 1 month indicated that a series of test processes from culture to drug stimulation and fluorescence observation is possible. Additionally, cultured samples were treated with several anticancer drugs known to cause peripheral neurotoxicity (i.e., vincristine, oxaliplatin, and paclitaxel) and analyzed the neurites’ morphological changes by deep learning for image analysis. After training, artificial intelligence (AI) could identify neurite morphological changes caused by each compound and precisely predicted the toxicity positivity, even at low concentrations. For testing compounds, AI could also precisely detect toxicity negative and positive based on neurite images, even at low concentrations. Therefore, this microfluidic culture system is supposed to be useful forin vitrotoxicity assessment.
Identification of a unique transcriptomic signature associated with islet amyloidosis
Authors: Barovic Marko , Steinmeyer Klaus , Kipke Nicole , Schöniger Eyke , Friedland Daniela , Marzetta Flavia , Forberger Almuth , Baretton Gustavo , Weitz Jürgen , Aust Daniela , Ibberson Mark , Distler Marius , Schulte Anke M , Solimena Michele 
Published: November 2022

AbstractAimsThis cross-sectional study aims to identify potential transcriptomic changes conveyed by presence of amyloid deposits in islets from pancreatic tissue obtained from metabolically profiled living donors.MethodsAfter establishing Thioflavin S as the most sensitive approach to detect islet amyloid plaques, we utilized RNA sequencing data obtained from laser capture microdissected islets to define transcriptomic effects of this pathological entity. The RNA sequencing data was used to identify differentially expressed genes by linear modeling. Further analyses included functional enrichment analysis of KEGG and Hallmark gene sets as well as a weighted gene correlation network analysis.ResultsEleven differentially expressed genes were identified in islets affected by amyloidosis. Enrichment analyses pointed to signatures related to protein aggregation diseases, energy metabolism and inflammatory response. A gene co-expression module was identified that correlated to islet amyloidosis.ConclusionAlthough the influence of underlying Type 2 diabetes could not be entirely excluded, this study presents a valuable insight into the biology of islet amyloidosis, particularly providing hints into the potential relationship between islet amyloid deposition and structural and functional proteins involved in insulin secretion.Research in contextWhat is already known about this subject?Islet amyloidosis is the only histological marker of Type 2 diabetes in the pancreasIndividuals not suffering from Type 2 diabetes can also be affected by islet amyloidosisThe clinicopathological significance of this phenomenon is still unclearWhat is the key question?Does the islet transcriptome of individuals with islet amyloidosis provide explanations for the onset of this phenomenon and its pathophysiological value?What are the new findings?Islet transcriptomes of affected subjects exhibit only limited transcriptomic differences compared to unaffected ones.Structural and functional proteins involved in insulin secretion machinery may be involved in the pathophysiological sequence of amyloid formation
Conceptual structure and current trends in Artificial Intelligence, Machine Learning, and Deep Learning research in sports: A bibliometric review
Authors: Dindorf Carlo , Bartaguiz Eva , Gassmann Freya , Fröhlich Michael 
Published: November 2022

AbstractArtificial intelligence and its subcategories of machine learning and deep learning are gaining increasing importance and attention in the context of sports research. This has also meant that the number of corresponding publications has become complex and unmanageably large in human terms. In the current state of the research field, there is a lack of bibliometric analysis, which would prove useful for obtaining insights into the large amounts of available literature. Therefore, the present work aims to identify important research issues, elucidate the conceptual structure of the research field, and unpack the evolutionary trends and the direction of hot topics regarding key themes in the research field of artificial intelligence in sports. Using the Scopus database, 1215 documents (reviews and articles) were selected. Bibliometric analysis was performed using VOSviewer and bibliometrix R package. The main findings are as follows: (a) the literature and research interest concerning AI and its subcategories is growing exponentially; (b) the top 20 most cited works comprise 32.52% of the total citations; (c) the top 10 journals are responsible for 28.64% of all published documents; (d) strong collaborative relationships are present, as along with small, isolated collaboration networks of individual institutions; (e) the three most productive countries are China, the USA, and Germany; (f) different research themes can be characterized using author keywords with current trend topics, e.g., in the fields of biomechanics, injury prevention or prediction, new algorithms, and learning approaches. AI research activities in the fields of sports pedagogy, sports sociology, and sports economics seem to have played a subordinate role thus far. Overall, the findings of this study expand knowledge on the research situation as well as the development of research topics regarding the use of artificial intelligence in sports, and may guide researchers to identify currently relevant topics and gaps in the research.
Genebank genomics allows greatly improved taxonomic correction forCapsicum spp. accessions using a novel automated classification method
Authors: Rabanus-Wallace M. Timothy , Stein Nils 
Published: November 2022

AbstractTo maximise the benefit of exploiting genebank resources, accurate and complete taxonomic assignments are imperative. The rise of genebank genomics allows genetic methods to be used for this task, but these need to be largely automated since the number of samples dealt with is too great for efficient manual recategorisation, but no clearly optimal method has yet arisen. A recent landmark genebank genomic study sequenced over 10,000 accessions of peppers (Capsicum spp.), for which the exploitation of genebank material is of huge commercial, cultural, and scientific importance. This study resulted in precisely the type of dataset that will, in coming decades, be likely be produced for hundreds of plant taxa. The long-appreciated difficulties of pepper taxonomy are evident from the many obvious misclassifications noted in this and other studies, providing a perfect opportunity to simultaneously advance methods development in the area, to correct many genebank taxonomic assignments of pepper accessions, and to provide insights into pepper taxonomy in general. This paper aims to achieve these goals using an approach that combines several ideas from standard classification algorithms to create a highly flexible and customisable classifier that performs favourably when compared with key alternative methods. The various characteristics of different methods are discussed, and possible sensible alterations to pepper taxonomy based on the results are proposed for discussion by the community.
Using Haplotype and QTL Analysis to Fix Favorable Alleles in Diploid Potato Breeding
Authors: Song Lin , Endelman Jeffrey B. 
Published: November 2022

AbstractAt present, the potato of international commerce is autotetraploid, and the complexity of this genetic system creates limitations for breeding. Diploid potato breeding has long been used for population improvement, and thanks to improved understanding of the genetics of gametophytic self-incompatibility, there is now sustained interest in the development of uniform F1hybrid varieties based on inbred parents. We report here on the use of haplotype and QTL analysis in a modified backcrossing (BC) scheme, using primary dihaploids ofS.tuberosumas the recurrent parental background. In Cycle 1 we selected XD3-36, a self-fertile F2clone homozygous for the self-compatibility geneSli. Signatures of gametic and zygotic selection were observed at multiple loci in the F2generation, includingSli. In the BC1cycle, an F1population derived from XD3-36 showed a bimodal response for vine maturity, which led to the identification of late vs. early alleles in XD3-36 for the geneStCDF1(Cycling DOF Factor 1). Greenhouse phenotypes and haplotype analysis were used to select a vigorous and self-fertile F2individual with 43% homozygosity, including forSliand the early-maturing alleleStCDF1.3. Partially inbred lines from the BC1and BC2cycles have been used to initiate new cycles of selection, with the goal of reaching higher homozygosity while maintaining plant vigor, fertility, and yield.Core IdeasPartially inbred, diploid potato lines were developed for transitioning to an inbred-hybrid breeding system.Multi-generational linkage analysis was used to track and fix favorable alleles without haplotype-specific markers.Signatures of gametic and zygotic selection were detected by maximum likelihood.
Survivin is a mechanosensitive cell cycle regulator in vascular smooth muscle cells
Authors: Biber John C. , Sullivan Andra , Brazzo Joseph A. , Krajnik Amanda , Heo Yuna , Poppenberg Kerry E. , Tutino Vincent M. , Heo Su-Jin , Kolega John , Lee Kwonmoo , Bae Yongho 
Published: November 2022

SUMMARYStiffened arteries are a pathology of atherosclerosis, hypertension, and coronary artery disease and a key risk factor for cardiovascular disease events. The increased stiffness of arteries triggers the hypermigration and hyperproliferation of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia and accelerated neointima formation, but the mechanism of this trigger is not known. Our analyses of whole-transcriptome microarray data sets from mouse VSMCs cultured on stiff hydrogels simulating arterial pathology and from injured mouse femoral arteries revealed 80 genes that were differentially regulated (74 upregulated and 6 downregulated) relative to expression in control VSMCs cultured on soft hydrogels and in uninjured femoral arteries. A functional enrichment analysis revealed that these stiffness-sensitive genes are linked to cell cycle progression and proliferation. Furthermore, we found that survivin, a member of the inhibitor of apoptosis protein family, mediates stiffness-sensitive cell cycling and proliferationin vivoandin vitroas determined by gene network and pathway analyses, RT-qPCR, and immunoblotting. The stiffness signal is mechanotransduced via FAK and Rac signaling to regulate survivin expression, establishing a regulatory pathway for how the stiffness of the cellular microenvironment affects VSMC behaviors. Our findings indicate that survivin is necessary for VSMC cycling and proliferation and regulates stiffness-responsive phenotypes.
FOCUS: fast Monte Carlo approach to coherence of undulator sources
Authors: Siano M. , Geloni G. , Paroli B. , Butti D. , Lefèvre T. , Mazzoni S. , Trad G. , Iriso U. , Nosych A. A. , Torino L. , Potenza M. A. C. 
Published: November 2022

FOCUS (Fast Monte CarlO approach to Coherence of Undulator Sources) is a new GPU-based simulation code to compute the transverse coherence of undulator radiation from ultra-relativistic electrons. The core structure of the code, which is written in the language C++ accelerated with CUDA, combines an analytical description of the emitted electric fields and massively parallel computations on GPUs. The combination is rigorously justified by a statistical description of synchrotron radiation based on a Fourier optics approach. FOCUS is validated by direct comparison with multi-electron Synchrotron Radiation Workshop (SRW) simulations, evidencing a reduction in computation times by up to five orders of magnitude on a consumer laptop. FOCUS is then applied to systematically study the transverse coherence in typical third- and fourth-generation facilities, highlighting peculiar features of undulator sources close to the diffraction limit. FOCUS is aimed at fast evaluation of the transverse coherence of undulator radiation as a function of the electron beam parameters, to support and help prepare more advanced and detailed numerical simulations with traditional codes like SRW.
Do expressions of sadness, anxiety and fear have different impacts on attracting donations? Evidence from a Chinese online charitable crowdfunding platform
Authors: Ge Ruichen , Zhang Sha , Zhao Hong 
Published: November 2022

PurposeExtant research shows mixed results on the impact of expressed negative emotions on donations in online charitable crowdfunding. This study solves the puzzle by examining how different types of negative emotions (i.e. sadness, anxiety and fear) expressed in crowdfunding project descriptions affect donations.Design/methodology/approachData on 15,653 projects across four categories (medical assistance, education assistance, disaster assistance and poverty assistance) from September 2013 to May 2019 come from a leading online crowdfunding platform in China. Text analysis and regression models serve to test the hypotheses.FindingsIn the medical assistance category, the expression of sadness has an inverted U-shaped effect on donations, while the expression of anxiety has a negative effect. An appropriate number of sadness words is helpful but should not exceed five times. In the education assistance and disaster assistance categories, the expression of sadness has a positive effect on donations, but disclosure of anxiety and fear has no influence on donations. Expressions of sadness, anxiety and fear have no impact on donations in the poverty assistance category.Research limitations/implicationsThis work has important implications for fundraisers on how to regulate the fundraisers' expressions of negative emotions in a project's description to attract donations. These insights are also relevant for online crowdfunding platforms.Originality/valueOnline crowdfunding research often studies negative emotions as a whole and does not differentiate project types. The current work contributes by empirically testing the impact of three types of negative emotions on donations across four major online crowdfunding categories.
Increased touch‐evoked itch (punctate hyperknesis) in postherpetic itch: Implications of reduced intraepidermal nerve fibers representing small fiber neuropathy
Authors: Hashimoto Takashi , Okuzawa Manami , Yamamoto Mihiro , Okuno Satoshi , Satoh Takahiro 
Published: November 2022

AbstractChronic itch conditions are often accompanied by neural itch sensitization, known as hyperknesis (excessive itch induced by stimuli that would normally induce only mild itching or pain) and alloknesis (considerable itch evoked by light tactile stimuli). Herpes zoster (shingles) can cause neuropathic itch (postherpetic itch), although it is unknown whether hyperknesis accompanies postherpetic itch. The authors report five patients with postherpetic itch who showed increased touch‐evoked itch (punctate hyperknesis) in the affected skin areas compared with the contralateral site. Collected skin biopsy specimens from two patients showed histopathologically detected reduced intraepidermal nerve fibers in the affected skin areas, reflective of small C/Aδ fiber neuropathy. In one case, improvement in itching and comparable levels of touch‐evoked itch on the affected and contralateral sites were noted after 6 months without any medication, accompanied by restored intraepidermal nerve fibers proven through rebiopsy of the affected site. Reduced intraepidermal nerve fibers could be one of the precipitating factors for postherpetic itch and its associated punctate hyperknesis.
Changes in odorants and flavor profile of heat‐processed beef flavor during storage
Authors: Zhang Zeyu , Blank Imre , Wang Bei , Cao Yanping 
Published: November 2022

AbstractFlavor quality changes of heat‐processed beef flavor (HPBF) upon storage are greatly affected by storage conditions. Flavor characterization of HPBF stored for 168 days resulted in 17 key odor‐active compounds having flavor dilution factors log3FD ≥ 3 and odor activity values > 1. Based on the concentration changes of these key odorants, a total of 13 HPBF samples were divided into four groups by hierarchical cluster analysis. Combined with flavor profile analysis, the overall flavor of HPBF gradually changed from a characteristic beef aroma to burnt and fermented soybean paste‐like notes. Some of the 17 key odorants, such as 2‐methyl‐3‐furanthiol, 2‐furfurylthiol, methyl furfuryl disulfide, and difurfuryl disulfide, contributed to the characteristic beef aroma of the freshly prepared product and in the early stage of storage. On the other hand, the odor‐active compounds 2‐methylbutanal, dimethyl disulfide, dimethyl trisulfide, and 2‐ethyl‐3,5‐dimethylpyrazine were associated with the later stage of storage showing a positive correlation with the intensity of burnt and fermented soybean paste‐like notes. A molecular understanding of flavor profile changes of HPBF during storage will provide the basis for developing characteristic beef aroma notes and maintaining the keeping quality of beef products upon storage.Practical ApplicationThe relationship between sensory quality and changes in odorant concentration of heat‐processed beef flavor during storage will provide the molecular basis for developing high‐quality thermal reaction meat flavorings.
Co‐production of biofuel, bioplastics and biochemicals during extended fermentation of Halomonas bluephagenesis
Authors: Park Helen , Toogood Helen S. , Chen Guo‐Qiang , Scrutton Nigel S. 
Published: November 2022

AbstractHalomonas bluephagenesis TD1.0 was engineered to produce the biofuel propane, bioplastic poly‐3‐hydroxybutyrate (PHB), and biochemicals mandelate and hydroxymandelate in a single, semi‐continuous batch fermentation under non‐sterile conditions. Multi‐product separation was achieved by segregation of the headspace gas (propane), fermentation broth ([hydroxy]mandelate) and cellular biomass (PHB). Engineering was performed by incorporating the genes encoding fatty acid photodecarboxylase (CvFAP) and hydroxymandelic acid synthase (SyHMAS) into a H. bluephagenesis hmgCAB cassette knockout to channel flux towards (hydroxy)mandelate. Design of Experiment strategies were coupled with fermentation trials to simultaneously optimize each product. Propane and mandelate titres were the highest reported for H. bluephagenesis (62 g/gDCW and 71 ± 10 mg/L respectively) with PHB titres (69% g/gDCW) comparable to other published studies. This proof‐of‐concept achievement of four easily separated products within one fermentation is a novel achievement probing the versatility of biotechnology, further elevating H. bluephagenesis as a Next Generation Industrial Biotechnology (NGIB) chassis by producing highly valued products at a reduced cost.