bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy
Authors: Richter M. L. , Deligiannis I. K. , Yin K. , Danese A. , Lleshi E. , Coupland P. , Vallejos C. A. , Matchett K. P. , Henderson N. C. , Colome-Tatche M. , Martinez-Jimenez C. P. 
Published: July 2021

AbstractSingle-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.
VCP maintains nuclear size by regulating the DNA damage-associated MDC1–p53–autophagy axis in Drosophila
Authors: Chang Ya-Chu , Peng Yu-Xiang , Yu Bo-Hua , Chang Henry C. , Liang Pei-Shin , Huang Ting-Yi , Shih Chao-Jie , Chu Li-An , Sang Tzu-Kang 
Published: July 2021

AbstractThe maintenance of constant karyoplasmic ratios suggests that nuclear size has physiological significance. Nuclear size anomalies have been linked to malignant transformation, although the mechanism remains unclear. By expressing dominant-negative TER94 mutants in Drosophila photoreceptors, here we show disruption of VCP (valosin-containing protein, human TER94 ortholog), a ubiquitin-dependent segregase, causes progressive nuclear size increase. Loss of VCP function leads to accumulations of MDC1 (mediator of DNA damage checkpoint protein 1), connecting DNA damage or associated responses to enlarged nuclei. TER94 can interact with MDC1 and decreases MDC1 levels, suggesting that MDC1 is a VCP substrate. Our evidence indicates that MDC1 accumulation stabilizes p53A, leading to TER94K2A-associated nuclear size increase. Together with a previous report that p53A disrupts autophagic flux, we propose that the stabilization of p53A in TER94K2A-expressing cells likely hinders the removal of nuclear content, resulting in aberrant nuclear size increase.
Transparent origami glass
Authors: Xu Yang , Li Ye , Zheng Ning , Zhao Qian , Xie Tao 
Published: July 2021

AbstractThe art of origami has emerged as an engineering tool with ever increasing potential, but the technique is typically limited to soft and deformable materials. Glass is indispensable in many applications, but its processing options are limited by its brittle nature and the requirement to achieve optical transparency. We report a strategy that allows making three dimensional transparent glass with origami techniques. Our process starts from a dynamic covalent polymer matrix with homogeneously dispersed silica nanoparticles. Particle cavitation and dynamic bond exchange offer two complementary plasticity mechanisms that allow the nanocomposite to be permanently folded into designable geometries. Further pyrolysis and sintering convert it into transparent three dimensional glass. Our method expands the scope of glass shaping and potentially opens up its utilities in unexplored territories.
The role of genetic polymorphisms in endolysosomal ion channels TPC2 and P2RX4 in cancer pathogenesis, prognosis, and diagnosis: a genetic association in the UK Biobank
Authors: Alharbi Abeer F. , Parrington John 
Published: July 2021

AbstractRecent studies have implicated important roles for endolysosomal ion channels in cancer biology. We used UK Biobank data to characterise the relationships between genetic variants in two genes coding for endolysosomal ion channels—i.e. TPCN2 and P2RX4—and cancer in terms of the definition of tumour types, susceptibility, and prognosis. We investigated these relationships at both global and local levels with regard to specific types of cancer, including malignant neoplasms of the brain, breast, bronchus, lung, colon, lymphoid and haematopoietic systems, skin, ovary, prostate, rectum, thyroid gland, lip, oral cavity, pharynx, and urinary tract. Apart from rs3829241 (p value < 0.05), all the genetic variants were in Hardy–Weinberg equilibrium. We included 468,436 subjects in the analysis and stratified them into two major cohorts: cancer-free controls (385,253) and cancer cases (83,183). For the first time, we report novel associations between genetic variants of TPCN2 and P2RX4 and cancer/cancer subtypes in the UK Biobank’s population. Genotype GG in TPCN2 rs3750965 was significantly associated with a decreased risk of cancer and an increased risk of lip, oral cavity, and pharynx cancer and cancer recurrence in patients with prostate cancer, and genotypes GA/GG were associated with a significantly lower risk of developing various malignant neoplasms (involving melanoma, prostate, mesothelial, and soft tissues). rs35264875:TA was associated with a high risk of cancer at the global level, with subtypes of cancer at the local level (including breast, colon, prostate, and stated or presumed primary cancer of lymphoid, haematopoietic, and related tissue), and with a significantly low risk of cancer metastasis. rs72932540:GA was associated with a higher incidence of cancer/cancer subtypes (including breast, melanoma, and rectal cancer), and genotypes GA/GG were associated with an increased risk of prostate cancer. The P2RX4 rs25644 allele GG was associated with a high risk of prostate cancer, whereas it was associated with a low risk of cancer recurrence in patients with prostate cancer. Genotypes GA/GG in rs28360472 were associated with an increased risk of breast, mesothelial, and soft tissue cancers but with a decreased risk of colon cancer. We also provide insights into the pathophysiological contributions made by these significant polymorphisms to cancer/cancer subtypes and their effects on expression or channel activity. Further investigations of these genetic variants could help identify novel cancer biomarkers and facilitate the development of new diagnostic and therapeutic strategies. This would constitute a further step towards personalised cancer care.
The 2021 update of the EPA’s adverse outcome pathway database
Authors: Mortensen Holly M. , Senn Jonathan , Levey Trevor , Langley Phillip , Williams Antony J. 
Published: July 2021

AbstractThe EPA developed the Adverse Outcome Pathway Database (AOP-DB) to better characterize adverse outcomes of toxicological interest that are relevant to human health and the environment. Here we present the most recent version of the EPA Adverse Outcome Pathway Database (AOP-DB), version 2. AOP-DB v.2 introduces several substantial updates, which include automated data pulls from the AOP-Wiki 2.0, the integration of tissue-gene network data, and human AOP-gene data by population, semantic mapping and SPARQL endpoint creation, in addition to the presentation of the first publicly available AOP-DB web user interface. Potential users of the data may investigate specific molecular targets of an AOP, the relation of those gene/protein targets to other AOPs, cross-species, pathway, or disease-AOP relationships, or frequencies of AOP-related functional variants in particular populations, for example. Version updates described herein help inform new testable hypotheses about the etiology and mechanisms underlying adverse outcomes of environmental and toxicological concern.
Global soil moisture data derived through machine learning trained with in-situ measurements
Authors: O. Sungmin , Orth Rene 
Published: July 2021

AbstractWhile soil moisture information is essential for a wide range of hydrologic and climate applications, spatially-continuous soil moisture data is only available from satellite observations or model simulations. Here we present a global, long-term dataset of soil moisture derived through machine learning trained with in-situ measurements, SoMo.ml. We train a Long Short-Term Memory (LSTM) model to extrapolate daily soil moisture dynamics in space and in time, based on in-situ data collected from more than 1,000 stations across the globe. SoMo.ml provides multi-layer soil moisture data (0–10 cm, 10–30 cm, and 30–50 cm) at 0.25° spatial and daily temporal resolution over the period 2000–2019. The performance of the resulting dataset is evaluated through cross validation and inter-comparison with existing soil moisture datasets. SoMo.ml performs especially well in terms of temporal dynamics, making it particularly useful for applications requiring time-varying soil moisture, such as anomaly detection and memory analyses. SoMo.ml complements the existing suite of modelled and satellite-based datasets given its distinct derivation, to support large-scale hydrological, meteorological, and ecological analyses.
Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro
Authors: Cagno Valeria , Medaglia Chiara , Cerny Andreas , Cerny Thomas , Zwygart Arnaud Charles-Antoine , Cerny Erich , Tapparel Caroline 
Published: July 2021

AbstractMethylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.
Transcriptome profiling by combined machine learning and statistical R analysis identifies TMEM236 as a potential novel diagnostic biomarker for colorectal cancer
Authors: Maurya Neha Shree , Kushwaha Sandeep , Chawade Aakash , Mani Ashutosh 
Published: July 2021

AbstractColorectal cancer (CRC) is a common cause of cancer-related deaths worldwide. The CRC mRNA gene expression dataset containing 644 CRC tumor and 51 normal samples from the cancer genome atlas (TCGA) was pre-processed to identify the significant differentially expressed genes (DEGs). Feature selection techniques Least absolute shrinkage and selection operator (LASSO) and Relief were used along with class balancing for obtaining features (genes) of high importance. The classification of the CRC dataset was done by ML algorithms namely, random forest (RF), K-nearest neighbour (KNN), and artificial neural networks (ANN). The significant DEGs were 2933, having 1832 upregulated and 1101 downregulated genes. The CRC gene expression dataset had 23,186 features. LASSO had performed better than Relief for classifying tumor and normal samples through ML algorithms namely RF, KNN, and ANN with an accuracy of 100%, while Relief had given 79.5%, 85.05%, and 100% respectively. Common features between LASSO and DEGs were 38, from them only 5 common genes namely, VSTM2A, NR5A2, TMEM236, GDLN, and ETFDH had shown statistically significant survival analysis. Functional review and analysis of the selected genes helped in downsizing the 5 genes to 2, which are VSTM2A and TMEM236. Differential expression of TMEM236 was statistically significant and was markedly reduced in the dataset which solicits appreciation for assessment as a novel biomarker for CRC diagnosis.
Movement patterns and activity levels are shaped by the neonatal environment in Antarctic fur seal pups
Authors: Nagel Rebecca , Mews Sina , Adam Timo , Stainfield Claire , Fox-Clarke Cameron , Toscani Camille , Langrock Roland , Forcada Jaume , Hoffman Joseph I. 
Published: July 2021

AbstractTracking studies of juveniles are rare compared to those of adults, and consequently little is known about the influence of intrinsic and extrinsic factors on activity during this critical life stage. We used hourly GPS data, collected from 66 Antarctic fur seal pups from birth until moulting, to investigate the explanatory power of multiple individual-based and environmental variables on activity levels. Pups were sampled from two nearby breeding colonies of contrasting density during two subsequent years, and a two-state hidden Markov model was used to identify modalities in their movement behaviour, specifically ‘active’ and ‘inactive’ states. We found that movement was typified by central place exploration, with active movement away from and subsequent return to a location of inactivity. The probability of such directed exploration was unaffected by several factors known to influence marine mammal movement including sex, body condition, and temperature. Compared to pups born at the high-density colony, pups at low-density were more active, increased their activity with age, and transitioned earlier into the tussock grass, which offers protection from predators and extreme weather. Our study illustrates the importance of extrinsic factors, such as colony of birth, to early-life activity patterns and highlights the adaptive potential of movement.
Effects of long-term norepinephrine treatment on normal immortalized ovarian and fallopian tube cells
Authors: Dash Sweta , Yoder Sean , Mesa Tania , Smith Andrew , Cen Ling , Eschrich Steven , Armaiz-Pena Guillermo N. , Monteiro Alvaro N. A. 
Published: July 2021

AbstractSustained adrenergic stimulation by norepinephrine (NE) contributes to ovarian carcinoma metastasis and impairment of chemotherapy response. Although the effect of sustained NE stimulation in cancer progression is well established, less is known about its role in cancer initiation. To determine the extent to which stress hormones influence ovarian cancer initiation, we conducted a long-term (> 3 months; > 40 population doublings) experiment in which normal immortalized fallopian tube secretory (iFTSEC283) and ovarian surface epithelial (iOSE11) cell lines and their isogenic pairs containing a p53 mutation (iFTSEC283p53R175H; iOSE11p53R175H), were continuously exposed to NE (100 nM, 1 μM, 10 μM). Fallopian tube cells displayed a p53-independent increase in proliferation and colony-forming ability in response to NE, while ovarian surface epithelial cells displayed a p53-independent decrease in both assays. Fallopian tube cells with mutant p53 showed a mild loss of chromosomes and TP53 status was also a defining factor in transcriptional response of fallopian tube cells to long-term NE treatment.
COUnty aggRegation mixup AuGmEntation (COURAGE) COVID-19 prediction
Authors: Er Siawpeng , Yang Shihao , Zhao Tuo 
Published: July 2021

AbstractThe global spread of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, has casted a significant threat to mankind. As the COVID-19 situation continues to evolve, predicting localized disease severity is crucial for advanced resource allocation. This paper proposes a method named COURAGE (COUnty aggRegation mixup AuGmEntation) to generate a short-term prediction of 2-week-ahead COVID-19 related deaths for each county in the United States, leveraging modern deep learning techniques. Specifically, our method adopts a self-attention model from Natural Language Processing, known as the transformer model, to capture both short-term and long-term dependencies within the time series while enjoying computational efficiency. Our model solely utilizes publicly available information for COVID-19 related confirmed cases, deaths, community mobility trends and demographic information, and can produce state-level predictions as an aggregation of the corresponding county-level predictions. Our numerical experiments demonstrate that our model achieves the state-of-the-art performance among the publicly available benchmark models.
Gene body DNA methylation in seagrasses: inter- and intraspecific differences and interaction with transcriptome plasticity under heat stress
Authors: Entrambasaguas Laura , Ruocco Miriam , Verhoeven Koen J. F. , Procaccini Gabriele , Marín-Guirao Lazaro 
Published: July 2021

AbstractThe role of DNA methylation and its interaction with gene expression and transcriptome plasticity is poorly understood, and current insight comes mainly from studies in very few model plant species. Here, we study gene body DNA methylation (gbM) and gene expression patterns in ecotypes from contrasting thermal environments of two marine plants with contrasting life history strategies in order to explore the potential role epigenetic mechanisms could play in gene plasticity and responsiveness to heat stress. In silico transcriptome analysis of CpGO/E ratios suggested that the bulk of Posidonia oceanica and Cymodocea nodosa genes possess high levels of intragenic methylation. We also observed a correlation between gbM and gene expression flexibility: genes with low DNA methylation tend to show flexible gene expression and plasticity under changing conditions. Furthermore, the empirical determination of global DNA methylation (5-mC) showed patterns of intra and inter-specific divergence that suggests a link between methylation level and the plants’ latitude of origin and life history. Although we cannot discern whether gbM regulates gene expression or vice versa, or if other molecular mechanisms play a role in facilitating transcriptome responsiveness, our findings point to the existence of a relationship between gene responsiveness and gbM patterns in marine plants.
Motion blur invariant for estimating motion parameters of medical ultrasound images
Authors: Honarvar Shakibaei Asli Barmak , Zhao Yifan , Erkoyuncu John Ahmet 
Published: July 2021

AbstractHigh-quality medical ultrasound imaging is definitely concerning motion blur, while medical image analysis requires motionless and accurate data acquired by sonographers. The main idea of this paper is to establish some motion blur invariant in both frequency and moment domain to estimate the motion parameters of ultrasound images. We propose a discrete model of point spread function of motion blur convolution based on the Dirac delta function to simplify the analysis of motion invariant in frequency and moment domain. This model paves the way for estimating the motion angle and length in terms of the proposed invariant features. In this research, the performance of the proposed schemes is compared with other state-of-the-art existing methods of image deblurring. The experimental study performs using fetal phantom images and clinical fetal ultrasound images as well as breast scans. Moreover, to validate the accuracy of the proposed experimental framework, we apply two image quality assessment methods as no-reference and full-reference to show the robustness of the proposed algorithms compared to the well-known approaches.
Incidence and outcomes of refractory immune thrombocytopenic purpura in children: a retrospective study in a single institution
Authors: Ito Masataka , Yagasaki Hiroshi , Kanezawa Koji , Shimozawa Katsuyoshi , Hirai Maiko , Morioka Ichiro 
Published: July 2021

AbstractTreatment of children with refractory immune thrombocytopenic purpura (ITP) is challenging and poorly established. We retrospectively reviewed the clinical data of 87 patients under the age of 16 years who were diagnosed with ITP from April 1998 to March 2017 in our institution. Refractory ITP was defined as a platelet count of < 50 × 109/L at 14 days after receiving intravenous immunoglobulin (IVIG) and prednisolone. We presumed that there was a pathophysiological overlap between refractory ITP and refractory thrombocytopenia (RT): a subtype of refractory cytopenia of childhood (RCC). Immunosuppressive therapies including anti-thymocyte globulin and cyclosporine (CsA) have been adopted for children with RCC in Japan. Thus, from 2009 onwards, we changed the diagnosis from refractory ITP to RT and introduced CsA for refractory ITP/RT. Nine of 42 patients developed refractory ITP in the 1998–2008 group, who received conventional treatments such as IVIG and steroid therapy. Eight of 45 patients developed refractory ITP in the 2009–2017 group, who received CsA with or without IVIG therapy. The response rate at three years after diagnosis was significantly higher in the 2009–2017 group (98%) than in the 1998–2008 group (83%) (p = 0.019). In conclusion, our strategy of introducing CsA for refractory ITP/RT contributed to better outcomes.
Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
Authors: Pecori Giraldi Francesca , Sesta Antonella , Tapella Laura , Cassarino Maria Francesca , Castelli Luigi 
Published: July 2021

AbstractRetinoids play a pivotal role in adrenal development and differentiation. Recent clinical trials revealed therapeutic potential of both all-trans and 9-cis retinoic acid in patients with cortisol excess due to a pituitary ACTH-secreting adenoma and indicated that retinoids might act also on the adrenal. Aim of the present study was to evaluate the effect of 9-cis retinoic acid on adrenals from patients with ACTH-dependent Cushing’s syndrome. Adrenal specimens from six patients with Cushing’s disease were incubated with 10 nM–1 µM 9-cis retinoic acid with and without 10 nM ACTH. Cortisol secretion was measured by immunoassay and expression of genes involved in steroidogenesis as well as retinoic acid action were evaluated by real-time RT-PCR. Incubation with 10–100 nM 9-cis retinoic acid increased spontaneous cortisol secretion and expression of STAR and CYP17A. On the other hand, in wells treated with ACTH, 9-cis retinoic acid markedly diminished ACTH receptor upregulation and no stimulatory effect on cortisol secretion or steroidogenic enzyme synthesis was observed. ACTH itself increased ligand-induced retinoic acid receptor expression, possibly enhancing sensitivity to retinoic acid. Our findings indicate that the effect of 9-cis retinoic acid in presence of ACTH is distinct from unchallenged wells and support the hypothesis of a direct adrenal action in patients with Cushing’s disease.