bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cell characterization of lung cancer brain metastases in the cerebrospinal fluid through single‐cell transcriptome analysis
Authors: Ruan Haoyu , Zhou Yihang , Shen Jie , Zhai Yue , Xu Ying , Pi Linyu , Huang Ruofan , Chen Kun , Li Xiangyu , Ma Weizhe , Wu Zhiyuan , Deng Xuan , Wang Xu , Zhang Chao , Guan Ming 
Published: December 2020

AbstractBackgroundBrain metastases explain the majority of mortality associated with lung cancer, which is the leading cause of cancer death. Cytology analysis of the cerebrospinal fluid (CSF) remains the diagnostic gold standard, however, the circulating tumor cells (CTCs) in CSF (CSF‐CTCs) are not well defined at the molecular and transcriptome levels.MethodsWe established an effective CSF‐CTCs collection procedure and isolated individual CSF cells from five lung adenocarcinoma leptomeningeal metastases (LUAD‐LM) patients and three controls. Three thousand seven hundred ninety‐two single‐cell transcriptomes were sequenced, and single‐cell RNA sequencing (scRNA‐seq) gene expression analysis was used to perform a comprehensive characterization of CSF cells.ResultsThrough clustering and expression analysis, we defined CSF‐CTCs at the transcriptome level based on epithelial markers, proliferation markers, and genes with lung origin. The metastatic‐CTC signature genes are enriched for metabolic pathway and cell adhesion molecule categories, which are crucial for the survival and metastases of tumor cells. We discovered substantial heterogeneity in patient CSF‐CTCs. We quantified the degree of heterogeneity and found significantly greater among‐patient heterogeneity compared to among‐cell heterogeneity within a patient. This observation could be explained by spatial heterogeneity of metastatic sites, cell‐cycle gene, and cancer‐testis antigen (CTA) expression profiles as well as the proportion of CTCs displaying mesenchymal and cancer stem cell properties. In addition, our CSF‐CTCs transcriptome profiling allowed us to determine the biomarkers during the progression of an LM patient with cancer of unknown primary site (CUP).ConclusionsOur results will provide candidate genes for an RNA‐based digital detection of CSF‐CTCs from LUAD‐LM and CUP‐LM cases, and shed light on the therapy and mechanism of LUAD‐LM.
Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies
Authors: Zhang Cheng , Chen Zuhua , Chong Xiaoyi , Chen Yang , Wang Zhenghang , Yu Ruoying , Sun Tingting , Chen Xiaoxi , Shao Yang , Zhang Xiaotian , Gao Jing , Shen Lin 
Published: December 2020

AbstractBackgroundGastric cancer (GC) is confronted with limited options for precision medicine. Human epidermal growth factor receptor 2 (HER2) is the principal druggable target of GC, yet proper biomarkers for response/resistance prediction remain unveiled.MethodsFrom 40 GC patients received HER2‐targeted therapy, a total of 327 peripheral blood plasma specimens was collected including baseline and treatment time points. Circulating tumor DNA (ctDNA) was extracted and sequenced with a target panel of 425 genes. Experimental validation of resistant mutations was carried out in NIH‐3T3 cell line.ResultsGenomic features, includingERBB2copy number variation (CNV), total copy number load, and tumor mutation burdens (TMBs), dynamically changed along with the treatment process and correlated with disease progression. Plasma ctDNA‐based diagnosis was more sensitive than conventional computed tomography scanning in 40% of investigated patients, gaining additional time for clinical management. Compared to baseline, new gene alterations were emerged in 12 patients who developed drug resistance during treatment.ERBB2mutations potentially related to Pyrotinib resistance were identified in plasma ctDNA of one patient and functional analysis of their downstream signaling pathways was carried out in NIH‐3T3 cell line. TMB exhibited more power thanERBB2CNV in predicting treatment responses and prognosis for HER2‐targeted therapy in GC patients. Interestingly, survival analysis indicated that patients harboring both HER2 (ERBB2) positivity and high TMB might gain more therapeutic benefits from immune checkpoint inhibitors instead of HER2‐targeted regimens that required further studies and validationsConclusionsOur work showed that the dynamic surveillance of plasma ctDNA genomic features provided instructive information for the precision medication of GC patients.
Phylogeny and biogeography of the Japanese rhinoceros beetle, Trypoxylus dichotomus (Coleoptera: Scarabaeidae) based on SNP markers
Authors: Yang Huan , You Chong Juan , Tsui Clement K. M. , Tembrock Luke R. , Wu Zhi Qiang , Yang De Po 
Published: December 2020

AbstractThe Japanese rhinoceros beetle Trypoxylus dichotomus is one of the largest beetle species in the world and is commonly used in traditional Chinese medicine. Ten subspecies of T. dichotomus and a related Trypoxylus species (T. kanamorii) have been described throughout Asia, but their taxonomic delimitations remain problematic. To clarify issues such as taxonomy, and the degree of genetic differentiation of Trypoxylus populations, we investigated the genetic structure, genetic variability, and phylogeography of 53 specimens of Trypoxylus species from 44 locations in five Asian countries (China, Japan, Korea, Thailand, and Myanmar). Using specific‐locus amplified fragment sequencing (SLAF‐seq) techniques, we developed 330,799 SLAFs over 114.16M reads, in turn yielding 46,939 high‐resolution single nucleotide polymorphisms (SNPs) for genotyping. Phylogenetic analysis of SNPs indicated the presence of three distinct genetic groups, suggesting that the various subspecies could be treated as three groups of populations. PCA and ADMIXTURE analysis also identified three genetic clusters (North, South, West), which corresponded to their locations, suggesting that geographic factors were important in maintaining within population homogeneity and between population divergence. Analyses of SNP data confirmed the monophyly of certain subspecies on islands, while other subspecies (e.g., T. d. septentrionalis) were found to be polyphyletic and nested in more than one lineage. AMOVA demonstrated high level of differentiation among populations/groups. Also, pairwise FST values revealed high differentiation, particularly between South and West, as well as between North and South. Despite the differentiation, measurable gene flow was inferred between genetic clusters but at varying rates and directions. Our study demonstrated that SLAF‐seq derived markers outperformed 16S and COII sequences and provided improved resolution of the genetic differentiation of rhinoceros beetle populations from a large part of the species’ range.
The influence of nutrient enrichment on riverine food web function and stability
Authors: Canning Adam D. , Death Russell G. 
Published: December 2020

AbstractNutrient enrichment of rivers and lakes has been increasing rapidly over the past few decades, primarily because of agricultural intensification. Although nutrient enrichment is known to drive excessive algal and microbial growth, which can directly and indirectly change the ecological community composition, the resulting changes in food web emergent properties are poorly understood. We used ecological network analysis (ENA) to examine the emergent properties of 12 riverine food webs across a nutrient enrichment gradient in the Manawatu, New Zealand. We also derive Keystone Sensitivity Indices to explore whether nutrients change the trophic importance of species in a way that alters the resilience of the communities to further nutrient enrichment or floods. Nutrient enrichment resulted in communities composed of energy inefficient species with high community (excluding microbes) respiration. Community respiration was several times greater in enriched communities, and this may drive hypoxic conditions even without concomitant changes in microbial respiration. Enriched communities exhibited weaker trophic cascades, which may yield greater robustness to energy flow loss. Interestingly, enriched communities were also more structurally and functionally affected by species sensitive to flow disturbance making these communities more vulnerable to floods.
Impact of body mass index on surgical coronary revascularization for ischaemic heart failure: insights from STICHES
Authors: Hendren Nicholas S. , Zhong Lin , Neeland Ian J. , Michelis Katherine C. , Drazner Mark H. , Tang W.H. Wilson , Pandey Ambarish , Grodin Justin L. 
Published: December 2020

AbstractAimsPatients with obesity and ischaemic heart failure may counter‐intuitively have better outcomes compared with patients with normal body weight due to an ‘obesity paradox’. This study sought to determine if body mass index (BMI) impacts the treatment effects or safety outcomes of the treatment of ischaemic heart failure with coronary artery bypass grafting (CABG).Methods and resultsWe obtained and reviewed the Surgical Treatment of Ischaemic Heart Failure (STICHES) data for 1212 patients. We categorized obesity by the World Health Organization (WHO) classes to define baseline characteristics and test for treatment interactions for the primary and secondary STICHES outcomes by treatment groups. While CABG decreased the risk of death, there was no evidence of treatment interaction by BMI per 5 kg/m2 (P = 0.83) or WHO obesity class. For the overall cohort, there was no interaction by WHO obesity class for the cumulative incidence of death in either the medical therapy or CABG plus medical therapy (P‐interaction = 0.90). There was a non‐significant trend for higher BMI and a lower risk of death [hazard ratio 0.92, 95% confidence interval (CI) 0.85–1.00, P = 0.051]. Increasing body size (per 5 kg/m2) was associated with return to the operating room (odds ratio 2.48, 95% CI 1.45–4.26, P < 0.001) and infectious mediastinitis (odds ratio 2.09, 95% CI 1.10–3.97, P = 0.024) at 30 days but not other 30 day safety outcomes.ConclusionsThe benefit of CABG vs. medical therapy for ischaemic heart failure was consistent regardless of BMI or WHO obesity class for death or secondary clinical outcomes. However, higher BMI was associated with some short‐term post‐CABG complications.
Preserved ejection fraction and structural heart disease in 446 848 patients investigated with echocardiography
Authors: Playford David , Strange Geoffrey , Stewart Simon ,   NEDA Investigators
Published: December 2020

AbstractBackgroundSex‐specific differences in left ventricular ejection fraction (LVEF) and responses to neurohormonal modulating therapies are relevant to clinical trials of treatment for heart failure with preserved ejection fraction (HFpEF).AimsThis study aimed to identify the proportion and characteristics of patients presenting with possible or confirmed HFpEF within the National Echo Database of Australia.ResultsA total of 237 046 women (48.1%) and 256 019 men (aged 61.0 ± 18.3 vs. 60.6 ± 17.1 years, respectively) had sex‐specific distributions of LVEF: 94.3% of women had LVEF ≥ 45% (mean LVEF 66.0 ± 8.6%), compared with 87.2% of men (mean LVEF 63.4 ± 8.7%). The presence of structural heart disease (SHD) according to the PARAGON‐HF criteria could be calculated in 93.8% of women and 93.4% of men with an LVEF ≥ 45%. Of these, 64 502 (30.8%) women and 104 344 (50.0%) of men had left ventricular hypertrophy, and 78 948 (35.3%) and 95 846 (42.9%), respectively, had left atrial enlargement. As a result, the proportion of women vs. men fulfilling echocardiographic criteria for HFpEF was very different: 111 497 (53.2%) vs. 146 359 (70.1%). SHD markedly increased with age, associated with a greater increase in women than men. The same signal was observed in those referred for suspected or previously confirmed HFpEF.ConclusionsDouble the number of men than women had LVEF < 45%, and the distribution of SHD had was highly sex specific. Left ventricular hypertrophy and left atrial enlargement were more common in men and becoming more frequent in women with advancing age. The echocardiographic SHD distribution was similar in those referred with suspected or confirmed HFpEF. The findings are relevant to sex‐specific recruitment criteria for future clinical trials.
Epstein Barr virus infection and immune defense related to HLA‐DR15: consequences for multiple sclerosis
Authors: Olsson Tomas 
Published: December 2020

AbstractMS is a multifactorial disease in which a series of genetic and non‐genetic, environmental factors plays a role in its etiology. In particular, HLA class II alleles, mainly HLADRB1*15:01 (HLA‐DR15), increase the risk for this disease. Out of several environmental factors, and with regard to infections, EBV remains to be a strong candidate, and may synergize with HLA‐DR15 thus increasing the risk for MS. In this issue of the European Journal of Immunology, Zdimerova et al. present highly interesting experimental data using EBV infection in immune‐deficient mice engrafted with human immune cells, either HLA‐DR15+ or HLA‐DRB1*04:01 (HLA DR4), here after denoted as HLA‐DR15−. As a result of EBV infection, the viral load and CD8+ cell expansion were conspicuously higher in mice engrafted with HLA‐DR15+ compared to HLA‐DR15− mice; and myelin basic protein specific T cells emerged in mice engrafted with HLA‐DR15 bearing cells. This study sheds light on how EBV and the class II DR15 haplotype may jointly predispose and synergize in the etiology of MS.
PIFA‐Mediated Cross‐Dehydrogenative Coupling of N‐Heteroarenes with Cyclic Ethers: Ethanol as an Efficient Promoter
Authors: Li Xiang , Liu Chaoyang , Guo Shixun , Wang Wei , Zhang Yongqiang 
Published: December 2020

AbstractEthanol is typically used in organic synthesis as an environmentally benign solvent. Herein, we report a mild and efficient cross‐dehydrogenative coupling (CDC) reaction of N‐heteroarenes with cyclic ethers by uncovering the new reactivity of ethanol as an efficient promoter in PIFA‐mediated radical process. The reaction proceeds smoothly under the irradiation of visible light and features excellent functional group compatibility, which allows the expedite synthesis of a variety of medicinally valuable Cα‐heteroarylated cyclic ethers in moderate to high yields.
Synthesis of Porphyrins Di‐ and Tetra‐Functionalized with Nucleobases
Authors: Tufenkjian Elsa , Kahlfuss Christophe , Kyritsakas Nathalie , Hosseini Mir Wais , Bulach Véronique 
Published: December 2020

AbstractA library composed of ten porphyrins bearing nucleobases is prepared, following two strategies: substitution or Sonogashira cross‐coupling reactions. The former strategy led to the synthesis of four porphyrins (T2−Po1, A2−Po1, C2−Po1 and P2−Po1) bearing nucleobases (NBs) at two trans meso‐positions. These 4 porphyrins were obtained by reacting 5,15‐di(4‐(bromomethyl)phenyl)‐10,20‐dimesitylporphyrin (Po1) with thymine (T), adenine (A), cytosine (C) and 2‐amino‐6‐chloropurine (P), a precursor of guanine (G), respectively in the presence of a suitable base. A fifth porphyrin, 5,15‐di(N9‐methylphenylguanine)‐10,20‐dimesitylporphyrin (G2−Po1) was obtained by hydrolysis of P2−Po1. A thymine tetra‐functionalized porphyrin was also synthesized following the same strategy starting from T and 5,10,15,20‐tetrakis[4‐(bromomethyl)phenyl]porphyrin (Po2). The second strategy based on Sonogashira cross‐coupling reactions between 5,15‐dibromo‐10,20‐dipentylporphyrin (Po3) and ethynyl‐substituted nucleobases resulted in four rigid porphyrins (U2−Po3, C2−ZnPo3, A2−ZnPo3, and G2−ZnPo3).
A novel two‐step process to produce high‐quality basil flavoured chicken powder: Effect of ultrasonication followed by microwave vacuum and hot air drying
Authors: Xu Kejing , Zhang Min , Mujumdar Arun S. , Liu Yaping 
Published: December 2020

AbstractThe objective of this experimental investigation was to develop a novel two‐step process for production of high‐quality chicken powder infused with basil. The first step consists of ultrasonication of an aqueous chicken pieces mixed with chopped basil leaves to enhance extraction of basil flavour and also pretreat the chicken microstructure to intensify the drying kinetics in the second step. The drying was carried out using microwave vacuum followed by hot air. The results showed that the drying time of chicken was the shortest (110 minutes) after US 40 minutes. In terms of product quality, the best rehydration (136.18%), the lowest hygroscopicity (3.84%) and the best colour of basil chicken powder were obtained after US 40 minutes. In the aspect of flavour addition, the content of linalool, estragole and eucalyptol in the chicken powder treated by US 40 minutes was the highest, and these three compounds were the main flavour substances of basil. At the same time, the content of some substances with bad smell, such as benzaldehyde, was greatly reduced after adding basil flavour. The overall quality of chicken powder produced by this novel process was found to be superior to that of commercially available spray‐dried chicken powder.
Effectiveness of a Decentralized Hub and Spoke Model for the Treatment of Hepatitis C Virus in a Federally Qualified Health Center
Authors: Rojas Sarah A. , Godino Job G. , Northrup Adam , Khasira Maureen , Tam Aaron , Asmus Lisa , Frenette Catherine , Ramers Christian B. 
Published: December 2020

Hepatitis C virus (HCV) is a major cause of cirrhosis, liver cancer, and mortality in the United States. We assessed the effectiveness of decentralized HCV treatment delivered by nurse practitioners (NPs), primary care physicians (PMDs), or an infectious disease physician (ID MD) using direct‐acting antivirals in a Federally Qualified Health Center (FQHC) in urban San Diego, CA. We conducted a cross‐sectional analysis of 1,261 patients who received treatment from six NPs, 10 PMDs, and one ID MD practicing in 10 clinics between January 2014 and January 2020. Care was delivered based on the Extension for Community Healthcare Outcomes (Project ECHO) model with one hub and nine spokes. HCV was deemed cured if a patient had a sustained virologic response (SVR) after 12 weeks of treatment (SVR12). We evaluated differences in the prevalence of cure between provider types and hub or spoke status using Poisson regression. Patients were 34% Latino, 16% black, 63% were aged >50 years, and 59% were homeless; 53% had advanced fibrosis, 69% had genotype 1, and 5% were coinfected with human immunodeficiency virus. A total of 943 patients achieved SVR12 (96% per protocol and 73% intention to treat). Even after adjustment for demographics, resources, and disease characteristics, the prevalence of cure did not differ between the ID MD and PMDs (prevalence ratio [PR], 1.00; 95% confidence interval [CI], 0.95‐1.04) or NPs (PR, 1.01; 95% CI, 0.96‐1.05). Similarly, there were no differences between the hub and spokes (PR, 1.01; 95% CI, 0.98‐1.04). Conclusion: Among a low‐income and majority homeless cohort of patients at urban FQHC clinics, HCV treatment administered by nonspecialist providers was not inferior to that provided by a specialist.
The study of changing characteristics of the winter temperature and extreme cold events in China over the past six decades
Authors: Fu Dongxue , Ding Yihui 
Published: December 2020

AbstractBy using winter (December–February) daily temperature at 1629 meteorological stations over China during 1960/61‐2017/18, spatial–temporal changes and probability distribution characteristics of winter temperature and extreme cold events in China were analysed, with a special emphasis on the warming hiatus in China. The results are as follows: (1) the winter temperature in China showed an overall upward trend during the past six decades. However, since the winter of 2006 (so‐called the warming hiatus period), the winter temperature in China has remained stable and even decreased slightly. (2) There is an obvious difference in winter temperature between South China and North China. North China witnessed a more obvious temperature rise during the warm period (1986–2005) than South China did. However, since 2006, winter temperature in most parts of North China has dropped slightly, with a marked increase in extreme cold events. In contrast, South China did not undergo an obvious temperature drop during the hiatus period. (3) The range of temperature change in North China is larger than that in South China. The range of minimum temperature is also wider than that of maximum temperature, with a noticeable increase in extreme low temperature events since 2006. In such situation, North China is more likely to encounter extreme low temperature events, such as cold wave and low temperature weather. (4) China has experienced an increase in extreme cold events during the hiatus period. There is an obvious upward trend in regional long‐lasting extreme cold events (3–5 and 11–20 days duration). Consequently, this study has revealed that winter temperature and frequency of extreme cold events in China was not only influenced by global warming, with a persistent warming, but also showed an obvious inter‐decadal variation which is associated with the natural forcing. It indicates that the natural forcing factor is also a main factor influencing and modulating the winter temperature change at the inter‐decadal scale at the regional scale as China even in the era of the global warming caused by anthropogenic forcing.
Brief communication: CMIP6 does not suggest any atmospheric blocking increase in summer over Greenland by 2100
Authors: Delhasse Alison , Hanna Edward , Kittel Christoph , Fettweis Xavier 
Published: December 2020

AbstractThe Greenland blocking index (GBI), an indicator of the synoptic‐scale circulation over Greenland, has been anomalously positive during most summers since the late 1990s. Such changes in atmospheric circulation, favouring anticyclonic conditions, have led to an increase in Greenland summer temperatures, a decrease in cloud cover and larger surface melt. The GBI is therefore a key indicator of melting and surface mass balance variability over the Greenland ice sheet. However, the models of fifth phase of the Coupled Model Intercomparison Project (CMIP5) do not represent the increase in GBI that is suggested by recent observations, and do not project any significant increase in GBI until 2100. In this study, the new generation of CMIP6 Earth‐system models is evaluated in order to analyse the evolution of the future GBI. All CMIP5 and CMIP6 projections reveal the same trend towards a decrease of the GBI until 2100 and no model reproduces the strong increase in the persistence of summer blocking events observed over the last few decades. Significant melting events related to a highly positive GBI, as observed in summer 2019, are still not considered by CMIP6 models and therefore the projected surface melt increase of the ice sheet could be underestimated if such summer circulation changes persist in the next decades.