bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and interrogation of the gene regulatory network of CEBPA-double mutant acute myeloid leukemia
Authors: Adamo Assunta , Chin Paulynn , Keane Peter , Assi Salam A. , Potluri Sandeep , Kellaway Sophie G. , Coleman Daniel , Ames Luke , Ptasinska Anetta , Delwel H. Ruud , Cockerill Peter N. , Bonifer Constanze 
Published: November 2022

AbstractAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signaling genes. It is characterized by a disturbance of differentiation and abnormal proliferation of hematopoietic progenitors. We have previously shown that each AML subtype establishes its own core gene regulatory network (GRN), consisting of transcription factors binding to their target genes and imposing a specific gene expression pattern that is required for AML maintenance. In this study, we integrate gene expression, open chromatin and ChIP data with promoter-capture Hi-C data to define a refined core GRN common to all patients with CEBPA-double mutant (CEBPAN/C) AML. These mutations disrupt the structure of a major regulator of myelopoiesis. We identify the binding sites of mutated C/EBPα proteins in primary cells, we show that C/EBPα, AP-1 factors and RUNX1 colocalize and are required for AML maintenance, and we employ single cell experiments to link important network nodes to the specific differentiation trajectory from leukemic stem to blast cells. Taken together, our study provides an important resource which predicts the specific therapeutic vulnerabilities of this AML subtype in human cells.
Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein
Authors: Liu Xin Tracy , Chung Long Hoa , Liu Da , Chen Jinbiao , Huang Yu , Teo Jonathan D. , Han Xingxing Daisy , Zhao Yinan , Guan Fiona H. X. , Tran Collin , Lee Jun Yup , Couttas Timothy A. , Liu Ken , McCaughan Geoffery W. , Gorrell Mark D. , Don Anthony S. , Zhang Shubiao , Qi Yanfei 
Published: November 2022

AbstractHepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC.
Sensory nerves enhance triple-negative breast cancer invasion and metastasis via the axon guidance molecule PlexinB3
Authors: Le Thanh T. , Payne Samantha L. , Buckwald Maia N. , Hayes Lily A. , Parker Savannah R. , Burge Christopher B. , Oudin Madeleine J. 
Published: November 2022

AbstractIn breast cancer, nerve presence has been correlated with more invasive disease and worse prognosis, yet the mechanisms by which different types of peripheral nerves drive tumor progression remain poorly understood. In this study, we identified sensory nerves as more abundant in human triple-negative breast cancer (TNBC) tumors. Co-injection of sensory neurons isolated from the dorsal root ganglia (DRG) of adult female mice with human TNBC cells in immunocompromised mice increased the number of lung metastases. Direct in vitro co-culture of human TNBC cells with the dorsal root ganglia (DRG) of adult female mice revealed that TNBC cells adhere to sensory neuron fibers leading to an increase in migration speed. Species-specific RNA sequencing revealed that co-culture of TNBC cells with sensory nerves upregulates the expression of genes associated with cell migration and adhesion in cancer cells. We demonstrated that lack of the semaphorin receptor PlexinB3 in cancer cells attenuate their adhesion to and migration on sensory nerves. Together, our results identify a mechanism by which nerves contribute to breast cancer migration and metastasis by inducing a shift in TNBC cell gene expression and support the rationale for disrupting neuron-cancer cell interactions to target metastasis.
Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer
Authors: Vidula Neelima , Lipman Andrew , Kato Shumei , Weipert Caroline , Hesler Katherine , Azzi Georges , Elkhanany Ahmed , Juric Dejan , Rodriguez Estelamari , Faulkner Colleen , Makhlouf Paul , Price Kristin , O’Shaughnessy Joyce , Bardia Aditya 
Published: November 2022

AbstractWe evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360®, 74 gene next-generation sequencing (NGS) with MBC are identified. We conduct a retrospective review. The median number of alterations and a median maximum mutant allelic fraction (MAF) in MSI-H and non-MSI-H cohorts are compared with Mann–Whitney U-test. Of 6718 patients with breast cancer with ≥1 plasma NGS alteration, 42 (0.63%) have MSI-H. A median number of genomic alterations per sample is 11 in MSI-H vs. 3 in non-MSI-H (Mann–Whitney U-test p < 0.0001) and the median maximum MAF is 16.8% in MSI-H vs. 2.6% in non-MSI-H (Mann–Whitney U-test p < 0.0001). The co-existing genomic landscape is heterogeneous. The median response duration for seven patients receiving immunotherapy is 92 days (range 29–273 days). CfDNA can identify MSI-H in MBC. Research is needed to validate immunotherapy usage in cfDNA-detected MSI-H MBC.
A multicenter study of genetic testing for Parkinson’s disease in the clinical setting
Authors: Kovanda Anja , Rački Valentino , Bergant Gaber , Georgiev Dejan , Flisar Dušan , Papić Eliša , Brankovic Marija , Jankovic Milena , Svetel Marina , Teran Nataša , Maver Aleš , Kostic Vladimir S. , Novakovic Ivana , Pirtošek Zvezdan , Rakuša Martin , Vuletić Vladimira , Peterlin Borut 
Published: November 2022

AbstractParkinson’s disease (PD) guidelines lack clear criteria for genetic evaluation. We assessed the yield and rationale of genetic testing for PD in a routine clinical setting on a multicenter cohort of 149 early-onset and familial patients by exome sequencing and semi-quantitative multiplex ligation-dependent probe amplification of evidence-based PD-associated gene panel. We show that genetic testing for PD should be considered for both early-onset and familial patients alike, and a clinical yield of about 10% in the Caucasian population can be expected.
Coherent control of electron spin qubits in silicon using a global field
Authors: Vahapoglu E. , Slack-Smith J. P. , Leon R. C. C. , Lim W. H. , Hudson F. E. , Day T. , Cifuentes J. D. , Tanttu T. , Yang C. H. , Saraiva A. , Abrosimov N. V. , Pohl H.-J. , Thewalt M. L. W. , Laucht A. , Dzurak A. S. , Pla J. J. 
Published: November 2022

AbstractSilicon spin qubits promise to leverage the extraordinary progress in silicon nanoelectronic device fabrication over the past half century to deliver large-scale quantum processors. Despite the scalability advantage of using silicon technology, realising a quantum computer with the millions of qubits required to run some of the most demanding quantum algorithms poses several outstanding challenges, including how to control many qubits simultaneously. Recently, compact 3D microwave dielectric resonators were proposed as a way to deliver the magnetic fields for spin qubit control across an entire quantum chip using only a single microwave source. Although spin resonance of individual electrons in the globally applied microwave field was demonstrated, the spins were controlled incoherently. Here we report coherent Rabi oscillations of single electron spin qubits in a planar SiMOS quantum dot device using a global magnetic field generated off-chip. The observation of coherent qubit control driven by a dielectric resonator establishes a credible pathway to achieving large-scale control in a spin-based quantum computer.
Optimisation of electron spin qubits in electrically driven multi-donor quantum dots
Authors: Sarkar Abhikbrata , Hochstetter Joel , Kha Allen , Hu Xuedong , Simmons Michelle Y. , Rahman Rajib , Culcer Dimitrie 
Published: November 2022

AbstractMulti-donor quantum dots have been at the forefront of recent progress in Si-based quantum computation. Among them, 2P: 1P spin qubits have a built-in dipole moment, making them ideal for electron dipole spin resonance (EDSR) using the donor hyperfine interaction, and thus all-electrical spin operation. We report fast EDSR, with Tπ ~ 10 − 50 ns and a Rabi ratio (T1/Tπ) ~ 106. The fastest EDSR time Tπ occurs when the 2P: 1P axis is ∥ [111], while the best Rabi ratio occurs when it is ∥ [100]. Sensitivity to random telegraph noise due to nearby charge defects depends strongly on the location of the nearby defects. The qubit is robust against 1/f noise provided it is operated away from the charge anti-crossing. Entanglement via exchange is several orders of magnitude faster than dipole-dipole coupling. These findings pave the way towards fast, low-power, coherent and scalable donor dot-based quantum computing.
Phenotypic trait variation in a long-term multisite common garden experiment of Scots pine in Scotland
Authors: Beaton Joan , Perry Annika , Cottrell Joan , Iason Glenn , Stockan Jenni , Cavers Stephen 
Published: November 2022

AbstractMultisite common garden experiments, exposing common pools of genetic diversity to a range of environments, allow quantification of plastic and genetic components of trait variation. For tree species, such studies must be long term as they typically only express mature traits after many years. As well as evaluating standing genetic diversity, these experiments provide an ongoing test of genetic variation against changing environmental conditions and form a vital resource for understanding how species respond to abiotic and biotic variation. Finally, quantitative assessments of phenotypic variation are essential to pair with rapidly accumulating genomic data to advance understanding of the genetic basis of trait variation, and its interaction with climatic change. We describe a multisite, population-progeny, common garden experiment of the economically and ecologically important tree species, Scots pine, collected from across its native range in Scotland and grown in three contrasting environments. Phenotypic traits, including height, stem diameter and budburst were measured over 14 growing seasons from nursery to field site. The datasets presented have a wide range of applications.
Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing
Authors: Fujimoto Kana , Nakajima Akira , Hori Shohei , Tanaka Yumiko , Shirasaki Yoshitaka , Uemura Sotaro , Irie Naoki 
Published: November 2022

AbstractEven though the mother and the fetus of placental mammals are immunologically non-self with respect to one other, mutual exchange of small numbers of cells between them is known to occur. Maternal cells entering the fetus, called maternal microchimeric cells (MMc cells), are thought to be involved in different physiological phenomena, such as establishing immune tolerance, tissue repair, and the pathogenesis or deterioration of some inflammatory diseases and congenital malformations. While specific MMc cell types have been reported as associated with these phenomena, the contribution of MMc cells to these different outcomes remains unknown. As one possibility, we hypothesized that different embryos have differing repertoires of MMc cell types, leading to or biasing embryos toward different fates. To date, no studies have succeeded in identifying the MMc cell type repertoire of a single embryo. Accordingly, here, we isolated MMc cells from whole mouse embryos, determined their types, and analyzed their MMc cell type variability. By combining our previously established, whole-embryonic MMc isolation method with single-cell RNA sequencing, we successfully estimated the cell type repertoires of MMc cells isolated from 26 mouse embryos. The majority of MMc cells were immune-related cells, such as myeloid cells and granulocytes. We also detected stem cell-like MMc cells expressing proliferation marker genes and terminally differentiated cells. As hypothesized, we noted statistically significant inter-individual variation in the proportion of immune-related cells in the different embryos. We here successfully estimated MMc cell types in individual whole mouse embryos. The proportion of immune-related cells significantly differed among the individual embryos, suggesting that the variations are one of the potential mechanisms underlying the differing MMc-related physiological phenomena in offspring. These findings provide insight into cell-level epigenetics by maternal cells.
Grafting of short elastin-like peptides using an electric field
Authors: Pramounmat Nuttanit , Asaei Sogol , Hostert Jacob D. , Young Kathleen , von Recum Horst A. , Renner Julie N. 
Published: November 2022

AbstractSurface-grafted elastin has found a wide range of uses such as sensing, tissue engineering and capture/release applications because of its ability to undergo stimuli-responsive phase transition. While various methods exist to control surface grafting in general, it is still difficult to control orientation as attachment occurs. This study investigates using an electric field as a new approach to control the surface-grafting of short elastin-like polypeptide (ELP). Characterization of ELP grafting to gold via quartz crystal microbalance with dissipation, atomic force microscopy and temperature ramping experiments revealed that the charge/hydrophobicity of the peptides, rearrangement kinetics and an applied electric field impacted the grafted morphology of ELP. Specifically, an ELP with a negative charge on the opposite end of the surface-binding moiety assembled in a more upright orientation, and a sufficient electric field pushed the charge away from the surface compared to when the same peptide was assembled in no electric field. In addition, this study demonstrated that assembling charged ELP in an applied electric field impacts transition behavior. Overall, this study reveals new strategies for achieving desirable and predictable surface properties of surface-bound ELP.
The use of biological amniotic membranes in the treatment of recurrent macular holes
Authors: Qiao Gang , Xie Lijun , Zou Qiangxing , He Chunmei , Zhang Xiaojuan , Tang Ziyan , Zou Shuai , Cao Kui 
Published: November 2022

AbstractTo evaluate the clinical therapeutic effects of a technique in which biological amniotic membranes (bAMs) are used in the treatment of patients with recurrent macular holes. In this prospective nonrandomized case series study, 23 eyes of 23 patients with recurrent macular holes who had already undergone surgery with pars plana vitrectomy with internal limiting membrane peeling were evaluated. In the surgery, a bAM was used to cover the macular area, and C3F8 tamponade was performed on these patients. Phacoemulsification combined with intraocular lens implantation was performed simultaneously in patients who had cataracts. Patients were followed up for at least half a year. The main outcomes were whether the macular hole closed, the morphological changes in the macular graft, the best-corrected visual acuity, intraocular pressure (IOP) and other indicators. In all eyes, the recurrent macular holes were closed. Two cases (8.69%, 2/23) had bAM shifting half a month after surgery, and these patients underwent a second surgery to adjust the position of the bAM and perform C3F8 tamponade. In the 6-month follow-up, 21 patients (91.30%, 21/23) had improved visual acuity (VA), and 2 patients (8.69%, 2/23) had no change in VA. The mean VA increased from 1.73 ± 0.32 before surgery to 1.12 ± 0.42 after surgery (t = 10.63, P = 0.00 < 0.01), and the mean IOP decreased from 22.13 ± 5.56 before surgery to 17.23 ± 1.71 after surgery (t = 5.14, P = 0.00 < 0.01). No serious complications occurred in any of the cases. The technique of using a biological amniotic membrane can be an effective treatment for patients with recurrent macular holes.
Deciphering sex-specific miRNAs as heat-recorders in zebrafish
Authors: van Gelderen Tosca A. , Montfort Jérôme , Álvarez-Dios José Antonio , Thermes Violette , Piferrer Francesc , Bobe Julien , Ribas Laia 
Published: November 2022

AbstractIn the last decade, a plethora of microRNAs (miRNAs) has been reported in a wide variety of physiological processes, including reproduction, in many aquatic organisms. However, miRNAome alterations occurred by environmental cues due to water temperature increment have not yet been elucidated. With the aim to identify epigenetic regulations mediated by miRNAs in the gonads in a climate change scenario, the animal model zebrafish (Danio rerio) were subjected to high temperatures during sex differentiation, a treatment that results in male-skewed sex ratios in the adulthood. Once the fish reached adulthood, gonads were sequenced by high-throughput technologies and a total of 23 and 1 differentially expressed miRNAs in ovaries and testes, respectively, were identified two months after the heat treatment. Most of these heat-recorder miRNAs were involved in human sex-related cancer and about 400 predicted-target genes were obtained, some with reproduction-related functions. Their synteny in the zebrafish genome was, for more than half of the predicted target genes, in the chromosomes 7, 2, 4, 3 and 11 in the ovaries, chromosome 4 being the place where the sex-associated-region (sar) is localized in wild zebrafish. Further, spatial localization in the gonads of two selected heat-recorder miRNAs (miR-122-5p and miR-146-5p) showed exclusive expression in the ovarian germ cells. The present study expands the catalog of sex-specific miRNAs and deciphers, for the first time, thermosensitive miRNAs in the zebrafish gonads that might be used as potential epimarkers to predict environmental past events.
Implication of EEG theta/alpha and theta/beta ratio in Alzheimer’s and Lewy body disease
Authors: Baik Kyoungwon , Jung Jin Ho , Jeong Seong Ho , Chung Seok Jong , Yoo Han Soo , Lee Phil Hyu , Sohn Young H. , Kang Seung Wan , Ye Byoung Seok 
Published: November 2022

AbstractWe evaluated the patterns of quantitative electroencephalography (EEG) in patients with Alzheimer’s disease (AD), Lewy body disease (LBD), and mixed disease. Sixteen patients with AD, 38 with LBD, 20 with mixed disease, and 17 control participants were recruited and underwent EEG. The theta/alpha ratio and theta/beta ratio were measured. The relationship of the log-transformed theta/alpha ratio (TAR) and theta/beta ratio (TBR) with the disease group, the presence of AD and LBD, and clinical symptoms were evaluated. Participants in the LBD and mixed disease groups had higher TBR in all lobes except for occipital lobe than those in the control group. The presence of LBD was independently associated with higher TBR in all lobes and higher central and parietal TAR, while the presence of AD was not. Among cognitively impaired patients, higher TAR was associated with the language, memory, and visuospatial dysfunction, while higher TBR was associated with the memory and frontal/executive dysfunction. Increased TBR in all lobar regions and temporal TAR were associated with the hallucinations, while cognitive fluctuations and the severity of Parkinsonism were not. Increased TBR could be a biomarker for LBD, independent of AD, while the presence of mixed disease could be reflected as increased TAR.
Learning complex dependency structure of gene regulatory networks from high dimensional microarray data with Gaussian Bayesian networks
Authors: Graafland Catharina E. , Gutiérrez José M. 
Published: November 2022

AbstractReconstruction of Gene Regulatory Networks (GRNs) of gene expression data with Probabilistic Network Models (PNMs) is an open problem. Gene expression datasets consist of thousand of genes with relatively small sample sizes (i.e. are large-p-small-n). Moreover, dependencies of various orders coexist in the datasets. On the one hand transcription factor encoding genes act like hubs and regulate target genes, on the other hand target genes show local dependencies. In the field of Undirected Network Models (UNMs)—a subclass of PNMs—the Glasso algorithm has been proposed to deal with high dimensional microarray datasets forcing sparsity. To overcome the problem of the complex structure of interactions, modifications of the default Glasso algorithm have been developed that integrate the expected dependency structure in the UNMs beforehand. In this work we advocate the use of a simple score-based Hill Climbing algorithm (HC) that learns Gaussian Bayesian networks leaning on directed acyclic graphs. We compare HC with Glasso and variants in the UNM framework based on their capability to reconstruct GRNs from microarray data from the benchmarking synthetic dataset from the DREAM5 challenge and from real-world data from theEscherichia coligenome. We conclude that dependencies in complex data are learned best by the HC algorithm, presenting them most accurately and efficiently, simultaneously modelling strong local and weaker but significant global connections coexisting in the gene expression dataset. The HC algorithm adapts intrinsically to the complex dependency structure of the dataset, without forcing a specific structure in advance.
Environmental pathways affecting gene expression (E.PAGE) as an R package to predict gene–environment associations
Authors: Muralidharan Sachin , Ali Sarah , Yang Lilin , Badshah Joshua , Zahir Syeda Farah , Ali Rubbiya A. , Chandra Janin , Frazer Ian H. , Thomas Ranjeny , Mehdi Ahmed M. 
Published: November 2022

AbstractThe purpose of this study is to manually and semi-automatically curate a database and develop an R package that will act as a comprehensive resource to understand how biological processes are dysregulated due to interactions with environmental factors. The initial database search run on the Gene Expression Omnibus and the Molecular Signature Database retrieved a total of 90,018 articles. After title and abstract screening against pre-set criteria, a total of 237 datasets were selected and 522 gene modules were manually annotated. We then curated a database containing four environmental factors, cigarette smoking, diet, infections and toxic chemicals, along with a total of 25,789 genes that had an association with one or more of gene modules. The database and statistical analysis package was then tested with the differentially expressed genes obtained from the published literature related to type 1 diabetes, rheumatoid arthritis, small cell lung cancer, COVID-19, cobalt exposure and smoking. On testing, we uncovered statistically enriched biological processes, which revealed pathways associated with environmental factors and the genes. The curated database and enrichment tool are available as R packages at https://github.com/AhmedMehdiLab/E.PATH and https://github.com/AhmedMehdiLab/E.PAGE respectively.