bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case–control study of paternal occupational exposures and childhood bone tumours and soft-tissue sarcomas in Great Britain, 1962–2010
Authors: Kendall Gerald M. , Bunch Kathryn J. , Stiller Charles A. , Vincent Timothy J. , Murphy Michael F. G. 
Published: February 2020

Abstract
Background
This nationwide study investigated associations between paternal occupational exposure and childhood bone tumours and soft- tissue sarcomas.

Methods
The UK National Registry of Childhood Tumours provided cases of childhood sarcomas born and diagnosed in Great Britain, 1962–2010. Control births, unaffected by childhood cancer, were matched on sex, birth period and birth registration sub-district. Fathers’ occupations were assigned to one or more of 33 exposure groups and coded for occupational social class.

Results
We analysed 5,369 childhood sarcoma cases and 5380 controls. Total bone tumours, total soft-tissue sarcomas and the subgroups osteosarcoma, rhabdomyosarcoma and Ewing Sarcoma Family of Tumours (ESFT) were considered separately. Significant positive associations were seen between rhabdomyosarcoma and paternal exposure to EMFs (odds ratio = 1.67, CI = 1.22–2.28) and also for ESFT and textile dust (1.93, 1.01–3.63). There were putative protective effects on total bone tumours of paternal dermal exposure to hydrocarbons, metal, metal working or oil mists.

Conclusions
Despite the large size and freedom from bias of this study, our results should be interpreted with caution. Many significance tests were undertaken, and chance findings are to be expected. Nevertheless, our finding of associations between ESFT and paternal exposure to textile dust may support related suggestions in the literature.
Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases
Authors: Masoodi Tariq , Siraj Sarah , Siraj Abdul K. , Azam Saud , Qadri Zeeshan , Parvathareddy Sandeep K. , Tulbah Asma , Al-Dayel Fouad , AlHusaini Hamed , AlOmar Osama , Al-Badawi Ismail A. , Alkuraya Fowzan S. , Al-Kuraya Khawla S. 
Published: February 2020

Abstract
Background
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian carcinoma, associated with poor clinical outcome and metastatic disease. Although metastatic processes are becoming more understandable, the genomic landscape and metastatic progression in HGSOC has not been elucidated.

Methods
Multi-region whole-exome sequencing was performed on HGSOC primary tumours and their metastases (n = 33 tumour regions) from six patients. The resulting somatic variants were analysed to delineate tumour evolution and metastatic dissemination, and to compare the repertoire of events between primary HGSOC and metastasis.

Results
All cases presented branching evolution patterns in primary HGSOC, with three cases further showing parallel evolution in which different mutations on separate branches of a phylogenetic tree converge on the same gene. Furthermore, linear metastatic progression was observed in 67% of cases with late dissemination, in which the metastatic tumour mostly acquires the same mutational process active in primary tumour, and parallel metastatic progression, with early dissemination in the remaining 33.3% of cases. Metastatic-specific SNVs were further confirmed as late dissemination events. We also found the involvement of metastatic-specific driver events in the Wnt/β-catenin pathway, and identified potential clinically actionable events in individual patients of the metastatic HGSOC cohort.

Conclusions
This study provides deeper insights into clonal evolution and mutational processes that can pave the way to new therapeutic targets.
The effect of posterior tethers on the biomechanics of proximal junctional kyphosis: The whole human finite element model analysis
Authors: Yagi Mitsuru , Nakahira Yuko , Watanabe Kota , Nakamura Masaya , Matsumoto Morio , Iwamoto Masami 
Published: February 2020

AbstractLittle is known about the effects of posterior tethers on the development of proximal junctional kyphosis (PJK). We evaluated the ability of posterior tethers to the proximal motion segment stiffness in long instrumented spinal instrumentation and fusion using a whole body human FE model. A series of finite element (FE) analysis of long segmental spinal fusion (SF) from the upper thoracic vertebra (T1) or lower thoracic vertebra (T9) to the sacrum with pedicle screws and rods were performed using an entire human body FE model (includes 234,910 elements), and compressive stresses (CS) on the anterior column, and tensile stresses (TS) on the posterior ligamentous complex (PLC) in the upper-instrumented vertebra (UIV) and the vertebra adjacent to the UIV (UIV + 1) were evaluated with posterior tethers or without posterior tethers. The models were tested at three T1 tilts (0, 20, 40 deg.), with 20% muscle contraction. Deformable material models were assigned to all body parts. Muscle-tendon complexes were modeled by truss elements with a Hill-type muscle material model. The CS of anterior column decreased with increasing T1 slope with tethers in both models, while the CS remained relatively large in T9 model compared with T1 model (T1 UIV; 0.96 to 1.56 MPa, T9 UIV; 4.79 to 5.61 MPa). The TS of the supraspinous ligament was markedly reduced in both T1 and T9 models with posterior tethers (11–35%). High vertebral CS on UIV and UIV + 1 were seen in the T9 UIV model, and the TS on the PLC were increased in both UIV models. Posterior tethers may decrease PJK development after SF with a proximal thoracic UIV, while both posterior tethers and vertebral augmentation may be necessary to reduce PJK development with a lower thoracic UIV.
Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Authors: Hu Ying , Ranganathan Mohini , Shu Chang , Liang Xiaoyu , Ganesh Suhas , Osafo-Addo Awo , Yan Chunhua , Zhang Xinyu , Aouizerat Bradley E. , Krystal John H. , D’Souza Deepak C. , Xu Ke 
Published: February 2020

AbstractDelta-9-tetrahydrocannabinol (THC) is known to modulate immune response in peripheral blood cells. The mechanisms of THC’s effects on gene expression in human immune cells remains poorly understood. Combining a within-subject design with single cell transcriptome mapping, we report that THC acutely alters gene expression in 15,973 blood cells. We identified 294 transcriptome-wide significant genes among eight cell types including 69 common genes and 225 cell-type-specific genes affected by THC administration, including those genes involving in immune response, cytokine production, cell proliferation and apoptosis. We revealed distinct transcriptomic sub-clusters affected by THC in major immune cell types where THC perturbed cell-type-specific intracellular gene expression correlations. Gene set enrichment analysis further supports the findings of THC’s common and cell-type-specific effects on immune response and cell toxicity. This comprehensive single-cell transcriptomic profiling provides important insights into THC’s acute effects on immune function that may have important medical implications.
Immunosuppressive effect and global dysregulation of blood transcriptome in response to psychosocial stress in vervet monkeys (Chlorocebus sabaeus)
Authors: Jasinska Anna J. , Pandrea Ivona , He Tianyu , Benjamin Cassandra , Newton Maurice , Lee Jen Chieh , Freimer Nelson B. , Coppola Giovanni , Jentsch James D. 
Published: February 2020

AbstractPsychosocial stressors - life events that challenge social support and relationships - represent powerful risk factors for human disease; included amongst these events are relocation, isolation and displacement. To evaluate the impact of a controlled psychosocial stressor on physiology and underlying molecular pathways, we longitudinally studied the influence of a 28-day period of quarantine on biomarkers of immune signalling, microbial translocation, glycaemic health and blood transcriptome in the wild-born vervet monkey. This event caused a coordinated, mostly transient, reduction of circulating levels of nine immune signalling molecules. These were paralleled by a massive dysregulation of blood transcriptome, including genes implicated in chronic pathologies and immune functions. Immune and inflammatory functions were enriched among the genes downregulated in response to stress. An upregulation of genes involved in blood coagulation, platelet activation was characteristic of the rapid response to stress induction. Stress also decreased neutrophils and increased CD4 + T cell proportions in blood. This model of psychosocial stress, characterised by an immune dysregulation at the transcriptomic, molecular and cellular levels, creates opportunities to uncover the underlying mechanisms of stress-related diseases with an immune component, including cardiovascular diseases and susceptibility to infections.
UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma
Authors: Farooq Muhammad Umar , Mumtaz Muhammad Waseem , Mukhtar Hamid , Rashid Umer , Akhtar Muhammad Tayyab , Raza Syed Ali , Nadeem Muhammad 
Published: February 2020

AbstractButea monospermais one of the extensively used plants in traditional system of medicines for many therapeutic purposes. In this study, the antioxidant activity,α-glucosidase andα-amylase inhibition properties of freeze drying assisted ultrasonicated leaf extracts (hydro-ethanolic) ofB. monospermahave been investigated. The findings revealed that 60% ethanolic fraction exhibited high phenolic contents, total flavonoid contents, highest antioxidant activity, and promisingα-glucosidase andα-amylase inhibitions. The UHPLC-QTOF-MS/MS analysis indicated the presence of notable metabolites of significant medicinal potential including apigenin, apigeninC-hexosideC-pentoside, apigeninC-hexosideC-hexoside, apigenin-6,8-di-C-pentoside and genistin etc., inB. monospermaleave extract. Docking studies were carried out to determine the possible role of each phytochemical present in leaf extract. Binding affinity data and interaction pattern of all the possible phytochemicals in leaf extract ofB. monospermarevealed that they can inhibitα-amylase andα-glucosidase synergistically to prevent hyperglycemia.
Prognostic value of the delta neutrophil index in pediatric cardiac arrest
Authors: Yoon Seo Hee , Lee Eun Ju , Lee Jinae , Kim Moon Kyu , Ahn Jong Gyun 
Published: February 2020

AbstractThe delta neutrophil index (DNI), which reflects the ratio of circulating immature neutrophils, has been reported to be highly predictive of mortality in systemic inflammation. We investigated the prognostic significance of DNI value for early mortality and neurologic outcomes after pediatric cardiac arrest (CA). We retrospectively analyzed the data of eligible patients (<19 years in age). Among 85 patients, 55 subjects (64.7%) survived and 36 (42.4%) showed good outcomes at 30 days after CA. Cox regression analysis revealed that the DNI values immediately after the return of spontaneous circulation, at 24 hours and 48 hours after CA, were related to an increased risk for death within 30 days after CA (P < 0.001). A DNI value of higher than 3.3% at 24 hours could significantly predict both 30-day mortality (hazard ratio: 11.8; P < 0.001) and neurologic outcomes (odds ratio: 8.04; P = 0.003). The C statistic for multivariable prediction models for 30-day mortality (incorporating DNI at 24 hours, compression time, and serum sodium level) was 0.799, and the area under the receiver operating characteristic curve of DNI at 24 hours for poor neurologic outcome was 0.871. Higher DNI was independently associated with 30-day mortality and poor neurologic outcomes after pediatric CA.
A2B adenosine receptor inhibition by the dihydropyridine calcium channel blocker nifedipine involves colonic fluid secretion
Authors: Asano Teita , Noda Yuto , Tanaka Ken-Ichiro , Yamakawa Naoki , Wada Mitsuhito , Mashimo Tadaaki , Fukunishi Yoshifumi , Mizushima Tohru , Takenaga Mitsuko 
Published: February 2020

AbstractThe adenosine A2B receptor is a critical protein in intestinal water secretion. In the present study, we screened compound libraries to identify inhibitors of the A2B receptor and evaluated their effect on adenosine-induced intestinal fluid secretion. The screening identified the dihydropyridine calcium antagonists nifedipine and nisoldipine. Their respective affinities for the A2B receptor (Ki value) were 886 and 1,399 nM. Nifedipine and nisoldipine, but not amlodipine or nitrendipine, inhibited both calcium mobilization and adenosine-induced cAMP accumulation in cell lines. Moreover, adenosine injection into the lumen significantly increased fluid volume in the colonic loop of wild-type mice but not A2B receptor-deficient mice. PSB-1115, a selective A2B receptor antagonist, and nifedipine prevented elevated adenosine-stimulated fluid secretion in mice. Our results may provide useful insights into the structure–activity relationship of dihydropyridines for A2B receptor. As colonic fluid secretion by adenosine seems to rely predominantly on the A2B receptor, nifedipine could be a therapeutic candidate for diarrhoea-related diseases.
A system-level mechanistic explanation for asymmetric stem cell fates: Arabidopsis thaliana root niche as a study system
Authors: García-Gómez Mónica L. , Ornelas-Ayala Diego , Garay-Arroyo Adriana , García-Ponce Berenice , Sánchez María de la Paz , Álvarez-Buylla Elena R. 
Published: February 2020

AbstractAsymmetric divisions maintain long-term stem cell populations while producing new cells that proliferate and then differentiate. Recent reports in animal systems show that divisions of stem cells can be uncoupled from their progeny differentiation, and the outcome of a division could be influenced by microenvironmental signals. But the underlying system-level mechanisms, and whether this dynamics also occur in plant stem cell niches (SCN), remain elusive. This article presents a cell fate regulatory network model that contributes to understanding such mechanism and identify critical cues for cell fate transitions in the root SCN. Novel computational and experimental results show that the transcriptional regulator SHR is critical for the most frequent asymmetric division previously described for quiescent centre stem cells. A multi-scale model of the root tip that simulated each cell’s intracellular regulatory network, and the dynamics of SHR intercellular transport as a cell-cell coupling mechanism, was developed. It revealed that quiescent centre cell divisions produce two identical cells, that may acquire different fates depending on the feedback between SHR’s availability and the state of the regulatory network. Novel experimental data presented here validates our model, which in turn, constitutes the first proposed systemic mechanism for uncoupled SCN cell division and differentiation.
Investigation of finishing of leather for inside parts of the shoes with a natural biocide
Authors: Bielak Elżbieta , Marcinkowska Ewa , Syguła-Cholewińska Justyna 
Published: February 2020

AbstractThe prevention of decrease of quality caused by microbial activity in footwear materials entails the use of biocides. However, these substances may pose a hazard to humans and to the natural environment. The paper presents the results of antimicrobial effect investigation for cowhide leather treated with oregano oil. In these studies oil was applied by spraying onto the finished leather surface and examined to determine its antimicrobial activity by using the Agar Diffusion Plate Test. These results were compared with those where a cowhide leather was treated with oil at the stage of fatliquoring. In addition, the oregano oil toxicity level was assessed and compared with biocides used in the tanning industry. Introducing oregano oil into the leather at the stage of fatliquoring provides a better antimicrobial effect than by spraying, however hygienic finishing of leather can be obtained by introducing oil into the raw material by these both methods. The oregano oil is characterised by the lowest number of hazards and toxicity as compared with commercial biocides. The use of essential oils as natural biocides in the tanning industry seems to be especially important and suitable solution considering the harmful effects of synthetic biocides to humans and the environment.
Preparing Multipartite Entangled Spin Qubits via Pauli Spin Blockade
Authors: Bugu Sinan , Ozaydin Fatih , Ferrus Thierry , Kodera Tetsuo 
Published: February 2020

AbstractPreparing large-scale multi-partite entangled states of quantum bits in each physical form such as photons, atoms or electrons for each specific application area is a fundamental issue in quantum science and technologies. Here, we propose a setup based on Pauli spin blockade (PSB) for the preparation of large-scale W states of electrons in a double quantum dot (DQD). Within the proposed scheme, two W states of n and m electrons respectively can be fused by allowing each W state to transfer a single electron to each quantum dot. The presence or absence of PSB then determines whether the two states have fused or not, leading to the creation of a W state of n + m − 2 electrons in the successful case. Contrary to previous works based on quantum dots or nitrogen-vacancy centers in diamond, our proposal does not require any photon assistance. Therefore the ‘complex’ integration and tuning of an optical cavity is not a necessary prerequisite. We also show how to improve the success rate in our setup. Because requirements are based on currently available technology and well-known sensing techniques, our scheme can directly contribute to the advances in quantum technologies and, in particular in solid state systems.
Metabolomics and the pig model reveal aberrant cardiac energy metabolism in metabolic syndrome
Authors: Karimi Maryam , Petkova Victoria , Asara John M. , Griffin Michael J. , Sellke Frank W. , Bishop Alan R. , Alexandrov Boian S. , Usheva Anny 
Published: February 2020

AbstractAlthough metabolic syndrome (MS) is a significant risk of cardiovascular disease (CVD), the cardiac response (MR) to MS remains unclear due to traditional MS models’ narrow scope around a limited number of cell-cycle regulation biomarkers and drawbacks of limited human tissue samples. To date, we developed the most comprehensive platform studying MR to MS in a pig model tightly related to human MS criteria. By incorporating comparative metabolomic, transcriptomic, functional analyses, and unsupervised machine learning (UML), we can discover unknown metabolic pathways connections and links on numerous biomarkers across the MS-associated issues in the heart. For the first time, we show severely diminished availability of glycolytic and citric acid cycle (CAC) pathways metabolites, altered expression, GlcNAcylation, and activity of involved enzymes. A notable exception, however, is the excessive succinate accumulation despite reduced succinate dehydrogenase complex iron-sulfur subunit b (SDHB) expression and decreased content of precursor metabolites. Finally, the expression of metabolites and enzymes from the GABA-glutamate, GABA-putrescine, and the glyoxylate pathways significantly increase, suggesting an alternative cardiac means to replenish succinate and malate in MS. Our platform discovers potential therapeutic targets for MS-associated CVD within pathways that were previously unknown to corelate with the disease.
A persistent memory advantage is specific to grapheme-colour synaesthesia
Authors: Lunke Katrin , Meier Beat 
Published: February 2020

AbstractFor people with synaesthesia ordinary stimuli such as digits or letters induce concurrent experiences such as colours. Synaesthesia is associated with a memory advantage and the aim of this study was to investigate whether this advantage persists across time. We tested recognition memory of four different types of synaesthesia with different inducer-concurrent pairings across two sessions with a one-year retention interval. In the study phase, participants learned three kinds of stimuli (i.e., related to their inducer, related to their concurrent, or synaesthesia-unrelated): music, words and colours. Recognition memory was tested after one hour and after one year. After one hour, grapheme-colour and grapheme-colour-and-sound-colour synaesthetes showed synaesthesia-specific advantages. After one year, only grapheme-colour synaesthetes still showed an advantage. The results imply that a benefit through enhanced colour-processing is particularly strong and that synaesthesia can lead to a long-lasting memory benefit.
Functional connections between and within brain subnetworks under resting-state
Authors: Parente Fabrizio , Colosimo Alfredo 
Published: February 2020

AbstractThe focus of this paper is on the functional role of brain regions focusing on their modular architecture and individual variability. Our main assumption is that the more variable anti-correlation patterns reflect random connections, while the more conserved ones play a functional role. Within this framework, we expanded on previous results using a different database and a different methodological approach. Aiming to identify the role of specific functional connections within a global network organization which includes subnetworks, we found that the fronto-parietal module acts as the main source of anti-correlations. In addition, the pre-frontal regions (namely: frontal middle, frontal middle orbital, frontal inferior triangular) and the parietal inferior region are highly conserved and, at the same time, act as highly connected nodes, thus confirming their importance in functional modulation.
Combining DNMT and HDAC6 inhibitors increases anti-tumor immune signaling and decreases tumor burden in ovarian cancer
Authors: Moufarrij Sara , Srivastava Aneil , Gomez Stephanie , Hadley Melissa , Palmer Erica , Austin Paul Tran , Chisholm Sarah , Diab Noor , Roche Kyle , Yu Angela , Li Jing , Zhu Wenge , Lopez-Acevedo Micael , Villagra Alejandro , Chiappinelli Katherine B. 
Published: February 2020

AbstractNovel therapies are urgently needed for ovarian cancer, the deadliest gynecologic malignancy. Ovarian cancer has thus far been refractory to immunotherapies that stimulate the host immune system to recognize and kill cancer cells. This may be because of a suppressive tumor immune microenvironment and lack of recruitment and activation of immune cells that kill cancer cells. Our previous work showed that epigenetic drugs including DNA methyltransferase inhibitors and histone deacetylase 6 inhibitors (DNMTis and HDAC6is) individually increase immune signaling in cancer cells. We find that combining DNMTi and HDAC6i results in an amplified type I interferon response, leading to increased cytokine and chemokine expression and higher expression of the MHC I antigen presentation complex in human and mouse ovarian cancer cell lines. Treating mice bearing ID8 Trp53−/− ovarian cancer with HDAC6i/DNMTi led to an increase in tumor-killing cells such as IFNg+ CD8, NK, and NKT cells and a reversal of the immunosuppressive tumor microenvironment with a decrease in MDSCs and PD-1hi CD4 T cells, corresponding with an increase in survival. Thus combining the epigenetic modulators DNMTi and HDAC6i increases anti-tumor immune signaling from cancer cells and has beneficial effects on the ovarian tumor immune microenvironment.