bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spatial landscape of clonal somatic mutations in benign and malignant tissue
Authors: Lundeberg Joakim , Erickson Andrew , Berglund Emelie , He Mengxiao , Marklund Maja , Mirzazadeh Reza , Schultz Niklas , Kvastad Linda , Andersson Alma , Bergenstråhle Ludvig , Bergenstråhle Joseph , Larsson Ludvig , Shamikh Alia , Basmaci Elisa , de Ståhl Teresita Diaz , Rajakumar Timothy , Thrane Kim , Ji Andrew , Khavari Paul , Tarish Firaz , Tanoglidi Anna , Maaskola Jonas , Colling Richard , Mirtti Tuomas , Hamdy Freddie , Woodcock Dan , Helleday Thomas , Mills Ian , Lamb Alastair 
Published: July 2021

Abstract
Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to describe previously unidentified clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
New Oral Anticoagulants Versus Low Molecular Weight Heparins for the Treatment of Cancer-associated Thrombosis: a Cost-effectiveness Analysis
Authors: Wumaier Kaidireyahan , Li Wenqian , Chen Naifei , Cui Jiuwei 
Published: July 2021

Abstract
Background: Recently, new oral anticoagulants (NOACs) have been included in guidelines for the treatment of cancer-associated thrombosis (CAT) to be extended to suitable cancer patients. The purpose of this study was to compare the cost-effectiveness of using NOACs and low molecular weight heparins(LMWHs) for treating CAT from the perspective of the Chinese healthcare system. Methods: A Markov model was constructed to estimate the cost-effectiveness of the two strategies with a 6-month and 5-year time horizon. Input parameters were either sourced from the clinical trial, published literature. The primary outcome of the model was reported as incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to test model uncertainty. Results: The 6-month cost of NOACs was $ 654.65 with 0.40 QALYs while the 6-month cost of LMWHs was $ 1719.31 with 0.37 QALYs. Similarly, treatment with NOACs had a lower cost ($ 657.85 vs. $ 1716.56) and more health benefits (0.40 QALY vs. 0.37 QALY) than treatment with LMWHs in a subgroup of patients with gastrointestinal malignancy. We found treatment with NOACs would result in a large reduction in cost($ 1447.22 vs. $ 3374.70) but a small reduction in QALYs (3.07 QALY vs. 3.09 QALY) compared with LMWHs over a 5-year time frame, resulting in an ICER of $ 112895.50/QALY. Sensitivity analysis confirmed the robustness of the results. Conclusion: As compared to LMWHs, NOACs can be a cost-saving anticoagulant choice for the treatment of CAT in the general oncology population and gastrointestinal malignancy population.Classification codes: I.
A Peptide Encoding Gene MdCLE8 Regulates Lateral Root Development in Apple
Authors: Zhang Tian-en , Shi Yan , Li Xiu-ming , Zhao Qiang , You Chun-xiang 
Published: July 2021

Abstract
Nitrogen is not only an essential nutrient for plant, but also an important signal molecule to integrate and regulate gene expression, metabolism and growth. Plant peptides are considered as a new hormone, and play an important regulatory role in plant growth and development. However, there are few researches on the co-regulation network between nitrogen and peptide hormones in plant. Here we identified an apple MdCLE8 gene, which encodes a putative peptide, induced by nitrogen deficiency in apple. Ectopic expression of MdCLE8 inhibited lateral root formation in Arabidopsis under nitrogen deficiency. Similarly, overexpression of MdCLE8 inhibited lateral root development in apple adventitious roots, and this inhibition was amplified under nitrogen deficiency treatment. Further studies showed that MdCLE8 may inhibit the expression of several key genes during lateral root emergence stage in Arabidopsis, thereby inhibiting the emergence of lateral root from root cortex cells. Collectively, our study not only broadened the gene regulatory network under the influence of nitrogen in apple, but also expanded the function of CLE peptide hormones in apple.
Complete Nucleotide Sequence of an Endornavirus Isolated from Common Buckwheat (Fagopyrum Esculentum)
Authors: Okada Ryo , Moriyama Hiromitsu , Ogawara Takashi , Cizek Heather , Valverde Rodrigo A 
Published: July 2021

Abstract
A double-stranded RNA (dsRNA) of approximately 16 kbp was isolated from symptomless common buckwheat (Fagopyrum esculentum) plants. The size of the dsRNA suggested that it was the replicative form of an endornavirus. The dsRNA was sequenced, and it consisted of 15,677 nt containing a single open reading frame that potentially encoded a polyprotein of 5,190 aa. The polyprotein contained conserved domains for a viral methyltransferase, viral RNA helicase 1, MSCRAMM family adhesion SdrC, UDP-glycosyltransferase, and viral RNA dependent RNA polymerase 2. A site-specific nick in the plus strand was detected near the 5' end of the dsRNA. BLASTP analysis showed that the polyprotein shared the highest identity with the polyprotein of winged bean endornavirus 1. Results of phylogenetic analysis supported placing the novel virus from common buckwheat, which was provisionally named Fagopyrum esculentum endornavirus 1, in the genus Alphaendornavirus of the family Endornaviridae.
X-type Soliton, Resonance Y-type Soliton and Hybrid Solutions of a (2+1)-dimensional Hirota-Satsuma-Ito System for the Shallow Water Waves
Authors: Shen Yuan , Tian Bo , Zhou Tian-Yu , Gao Xiao-Tian 
Published: July 2021

Abstract
Water waves are observed in the rivers, lakes, oceans, etc. Under investigation in this paper is a (2+1)-dimensional Hirota-Satsuma-Ito system arising in the shallow water waves. Via the Hirota method and symbolic computation, we derive some X-type and resonance Y-type soliton solutions. We also work out some hybrid solutions consisting of the resonance Y-type solitons, solitons, breathers and lumps. Graphics we present reveal that the hybrid solutions consisting of the resonance Y-type solitons and solitons/breathers/lumps describe the interactions between the resonance Y-type solitons and solitons/breathers/lumps, respectively. The obtained results rely on the water-wave coefficient in that system.
Predicting Outcomes for Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation With CT-Based Radiomics
Authors: Wang Fuqiang , Tan Boon Fei , Poh Sharon Shuxian , Siow Tian Rui , Lim Faye Lynette Wei Tching , Yip Connie Siew Poh , Wang Michael Lian Chek , Nei Wenlong , Tan Hong Qi 
Published: July 2021

Abstract
A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR>16 and NAR<8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR>16 and NAR<8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model.
Energy Recovery Linac Based Fully Coherent Light Source
Authors: Zhao Z. T. , Wang Z. , Feng C. , Chen S. , Cao L. 
Published: July 2021

Abstract
Energy recovery linac (ERL) holds great promise for generating high repetition-rate and high brightness electron beams. The application of ERL to drive a free-electron laser is currently limited by its low peak current. In this paper, we consider the combination of ERL with the recently proposed angler-dispersion induced microbunching technique to generate fully coherent radiation pulses with high average brightness and tunable pulse length. Start-to-end simulations have been performed based on a low energy ERL (600 MeV) for generating coherent EUV radiation pulses. The results indicate an average brightness over 1025 phs/s/mm2/mrad2/0.1%BW and average power of about 100 W at 13.5 nm or 20 W with the spectral resolution of about 0.5 meV with the proposed technique. Further extension of the proposed scheme to shorter wavelength based on an ERL complex is also discussed.
Cytokine’s Imbalance, the Hallmark of Immune Dysfunction in HIV/AIDS Patients in Rwanda
Authors: Ngangali Jean Pierre , Mutesa Leon , NSANZIMANA Sabin , Munyemana Jean Bosco , INJERA Emonyi Wilfred , KIRTIKA Patel , GATARE Swaibu , Rutayisire Robert , NDISHIMYE Isabelle Valois , NTAGWABIRA Edouard , Nkinda Lilian , CHEMTAI Alex k. 
Published: July 2021

Abstract
Background: Cytokines network drive Human Immunodeficiency Virus (HIV) inflammation and pathogenesis. Highly Active Antiretroviral Therapy (HAART) maintains low HIV viral load (VL) but chronic inflammation remains high in HIV subjects compared to HIV naïve population. To date, there is no surrogate biomarker that gives the hallmark picture of immune activation, chronic inflammation in HIV programs. This study aimed at determining the plasma cytokine levels and their association with HIV VL at initiation and after six months on HAART in Rwanda. Methods: We used a matching groups approach based on sex and systematic sampling within the groups were used to enrol fifty (50) patients in each group. Fifteen (15) HIV naive people were included in the study as control group. BD Flow cytometry was used to determine cytokine levels while revised WHO questionnaire was used to collect socio-demographic and clinical data. Independent sample T tests (T) and Wilcoxon rank (W) were used to compare cytokine mean levels while Pearson's Product Moment Coefficient (PPMC) r was used for correlation of parameters at HAART initiation and after six months of treatment. The statistically significant differences and the correlation between assessed parameters were determined at p ≤0.05. Results: At the initiation of HAART, Interleukin (IL)-10, IL-6 plasma levels were higher while IFN-γ and TNF-α were lower compared to its levels after six months of HAART. The present study found a positive association between IL-10, IL-6 and HIV VL. Conclusion: Proinflammatory and antinflammatory cytokines levels change differently following HAART and correlate with the HIV VL. The IL-10, IL-6 plasma levels are an alternative biomarker for assessment of hallmark of immune activation and inflammation in HIV infection.
Vitiligo-Specific Soluble Biomarkers as Early Indicators of Response to Immune Checkpoint Inhibitors in Metastatic Melanoma Patients
Authors: Carbone Maria Luigia , Madonna Gabriele , Bove Marianna , Mastroeni Simona , Levati Lauretta , Capone Mariaelena , Ascierto Paolo , De Galitiis Federica , D'Atri Stefania , Fortes Cristina , Failla Cristina Maria 
Published: July 2021

Abstract
Background: Immunotherapy with checkpoint inhibitors strongly improved the outcome of metastatic melanoma patients. However, not all the patients respond to treatment and identification of prognostic biomarkers able to select patients who would respond to this therapy is of outmost importance. Considering that development of vitiligo-like depigmentation in melanoma patients represents both an adverse event of immunotherapy and a favorable prognostic factor for overall survival, we analyzed known soluble biomarkers of vitiligo to validate them as early indicators of response to checkpoint inhibitors in metastatic melanoma.Methods: Fifty-seven patients with metastatic melanoma receiving anti-PD-1 checkpoint inhibitor immunotherapy were enrolled. Patient sera and plasma were evaluated for vitiligo biomarkers at pre-treatment and after 1 and 3 months of therapy. Patients were divided and analyzed according to the best overall response to treatment. Characteristic vitiligo proteins were analyzed by ELISA, while expression of circulating microRNAs, distinctive of vitiligo, was determined using real-time RT-PCR.Results: Basal serum CD25 levels were higher in stable and responder melanoma patients and remained higher during the first 3 months of anti-PD-1 therapy compared to non-responder patients. The chemokine CXCL9 was absent in non-responder patients before therapy beginning. Moreover, an increase of CXCL9 levels was observed at 1 and 3 months of therapy for all patients, although higher CXCL9 amounts were present in stable and responder compared to non-responder patients. Finally, higher levels of miR-19b, miR-25 and miR-16 were observed after 1 month of therapy in plasma of stable and responder compared to non-responder patients.Conclusions: Serum levels of CD25 and CXCL9 before and during the first months of treatment could represent biomarkers of response to anti-PD-1 immunotherapy in metastatic melanoma patients. Plasmatic miR-19b, miR-25 and miR-16 could also represent possible early biomarkers of response to anti-PD-1 treatment, but they must be validated in a higher number of patients.
Temporal Activity Patterns of Sympatric Bornean Carnivore Species: Implications for Niche Partitioning and Conservation
Authors: Nakabayashi Miyabi , Kanamori Tomoko , Matsukawa Aoi , Tangah Joseph , Tuuga Augustine , Malim Titol Peter , Bernard Henry , Ahmad Abdul Hamid , Matsuda Ikki , Hanya Goro 
Published: July 2021

Abstract
To propose proper conservation measures and to elucidate coexistence mechanisms of sympatric carnivore species, we assessed their temporal activity patterns using 37,379 photos collected for more than three years at three study sites in Borneo. We categorized activity patterns of nine carnivore species (one bear, three civets, two felids, one skunk, one mustelid, one linsang) by calculating the photo-capturing proportions at each period (day, night, twilight). We then evaluated temporal activity overlaps by calculating the overlap coefficients. We identified six nocturnal (three civets, one felid, one skunk, one linsang), two diurnal (one felids, one mustelid), and one cathemeral (bear) species. Temporal activity overlaps were high among the nocturnal species. The two felid species possessing morphological and ecological similarities exhibited clear temporal niche segregation, but the three civet species did not. Broad dietary breadth may compensate for the high temporal niche overlaps among the nocturnal species. Despite the high species richness of Bornean carnivores, almost half are threatened with extinction. By comparing individual radio-tracking and our data, we propose that a long-term study of at least three years is necessary to understand animals’ temporal activity patterns by camera-trapping and to avoid diverting conservationists away from effective protection measures.
Alpha and Theta Transcranial Alternating Current Stimulation Over the Right Dorsolateral Prefrontal Cortex Modulates Vigilance Performance, but Only When Arousal Levels Are Non-optimal
Authors: Martínez-Pérez Víctor , Tortajada Miriam , Palmero Lucía B. , Campoy Guillermo , Fuentes Luis J. 
Published: July 2021

Abstract
BackgroundCurrent theoretical accounts on the oscillatory nature of sustained attention predict that entrainment via transcranial alternating current stimulation (tACS) at alpha and theta frequencies on the frontoparietal network could prevent the drops in vigilance across time-on-task. Nonetheless, most previous studies have neglected both the fact that vigilance comprises two dissociable components (i.e. arousal and executive vigilance) and the potential role of differences in arousal baseline. MethodWe examined the effects of theta- and alpha-tACS over the right dorsolateral prefrontal cortex on both components of vigilance and on participants that differed in arousal baseline according to their chronotype and the time of testing. Intermediate-types performed the vigilance tasks when their arousal baseline was at the optimal level, whereas evening-types performed the vigilance tasks when their arousal baseline was at non-optimal levels. ResultsBoth theta- and alpha-tACS improved arousal vigilance, whereas alpha-tACS, but not theta-tACS, improved accuracy and attenuated the typical vigilance decrement in the executive vigilance task. Importantly, these stimulation effects were only found when arousal baseline was low (i.e., with evening-types performing the tasks at their non-optimal time of day).ConclusionThe results support the multicomponent view of vigilance, the relevance of heeding individual differences in arousal baseline, and the role of alpha oscillations as a long-range cortical scale synchronization mechanism that compensates the decrements in performance as a function of time-on-task by exerting and maintaining cognitive control attributed to activation of the frontoparietal network.
Giants Among Dwarfs: The Arrival Of A New Clade Of Southern Dinosaurs In The Latest Cretaceous Of Europe
Authors: Vila Bernat , Selles Albert , Moreno-Azanza Miguel , Razzolini Novella , Gil-Delgado Alejandro , Canudo José , Galobart Àngel 
Published: July 2021

Abstract
The authors have requested that this preprint be removed from Research Square.
The Impact of Mindfulness Training on the Attention to Facial Expressions
Authors: Bi Taiyong , Kou Hui , Li Xue , He Yuxia , Chen Siqi , Xie Qinhong 
Published: July 2021

Abstract
The improvements of attention by mindfulness training had been proved. But the effects of mindfulness training on attention to emotional stimuli were mixed. We employed a randomized, controlled design to investigate the effects of mindfulness training on the attention to emotional expressions, and investigated whether baseline levels of dispositional mindfulness and emotional intelligence would moderate the intervention effects. Forty participants received 8-week mindfulness training and another forty participants attended two lectures about mindfulness. All participants completed the visual search task, the Five Facet Mindfulness Questionnaire, and the Emotional Intelligence Scale at both pre-training and post-training. The improvements of search efficiencies were larger in the mindfulness group than those in the control group for sad and angry faces, but not for happy faces (F(2, 156)=4.04, p=0.019, η2=0.05). In addition, baseline emotional intelligence (βsadness=-4.49, t=-2.08, p=0.041, 95%CI [-8.78, -0.19]; βanger=-7.39, t=-4.08, p<0.001, 95%CI [-10.99, -3.78]) but not dispositional mindfulness (βsadness=3.17, t=1.56, p=0.124, 95%CI [-0.89, 7.22]; βanger=-1.89, t=-1.02, p=0.313, 95%CI [-5.61, 1.82]) played a significantly moderating role in the relationship between mindfulness training and emotional attention to sadness and anger. The search efficiencies of negative emotions (i.e., anger and sadness) but not positive emotions (i.e., happiness) were significantly improved by mindfulness training. Individuals with high level of baseline emotional intelligence showed significant improvement on the search efficiencies relative to those with low level of emotional intelligence.
Zinc Titanate Nanopowders. Synthesis and Characterization
Authors: Gabal M , Angari Y.M. Al 
Published: July 2021

Abstract
Zinc titanates nanopowders viz.; Zn2TiO4, ZnTi3O8 and ZnTiO3 were synthesized through the thermal decomposition course of ZnC2O4.2H2O-TiO2 precursor (1:1 mole ratio), prepared via a new co-precipitation method up to 900oC. Thermogravimetric measurement (TG) was utilized to characterize the precursor decomposition while X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) were used to characterize the decomposition products as well as the phase transitions at different temperatures. XRD revealed the starting of titanates formation at 700oC via detecting Zn2TiO4 along with ZnO and TiO2 (anatase) diffraction peaks. By increasing the calcination temperature to 800oC, the ZnO content vanished with the appearing of Zn2Ti3O8 besides ZnTi2O4 and impurities of TiO2 (anatase). Finally at 900oC, the Zn2Ti3O8 content was decomposed into ZnTiO3. Nitrogen adsorption-desorption isotherm of the calcined precursor at 900oC indicated low specific surface area of 7.1 m2 g-1 in accordance with the agglomeration nature estimated via transmission electron microscopy (TEM) study. The conductivity measurements showed semiconducting behavior of the prepared titanates with ferroelectric transition in the range 200-308oC.The obtained low dielectric value suggests the uses of present titanates as a co-fired ceramic or resonator ceramics.
Acute Myeloid Leukemia Treatment Outcomes: First Report from Single Center Retrospective Study in Kazakhstan
Authors: Saparbay Jamilya , Kulkayeva Gulnara , Kemaykin Vadim , Kuttymuratov Aset , Burlaka Zhanna , Zhakhina Gulnur , Adusheva Aisha , Dosayeva Saltanat 
Published: July 2021

Abstract
Acute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan-Meier method, and hazard ratios were defined with Cox regression. Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p=0.7), and 12 months in the poor prognosis group (p=0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with previous reports.