bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Treatment, ATM, BRCA1/2, and CHEK2*1100delC Pathogenic Variants and Risk of Contralateral Breast Cancer
Authors: Reiner Anne S , Robson Mark E , Mellemkjær Lene , Tischkowitz Marc , John Esther M , Lynch Charles F , Brooks Jennifer D , Boice John D , Knight Julia A , Teraoka Sharon N , Liang Xiaolin , Woods Meghan , Shen Ronglai , Shore Roy E , Stram Daniel O , Thomas Duncan C , Malone Kathleen E , Bernstein Leslie , Riaz Nadeem , Woodward Wendy , Powell Simon , Goldgar David , Concannon Patrick ,   The WECARE Study Collaborative Group, Bernstein Jonine L 
Published: February 2020

Abstract
Whether radiation therapy (RT) affects contralateral breast cancer (CBC) risk in women with pathogenic germline variants in moderate- to high-penetrance breast cancer–associated genes is unknown. In a population-based case-control study, we examined the association between RT; variants in ATM, BRCA1/2, or CHEK2*1100delC; and CBC risk. We analyzed 708 cases of women with CBC and 1399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2000 and aged younger than 55 years at diagnosis and screened for variants in breast cancer–associated genes. Rate ratios (RR) and 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (eg, BRCA1/2 pathogenic variant carriers without RT: RR = 3.52, 95% CI = 1.76 to 7.01; BRCA1/2 pathogenic variant carriers with RT: RR = 4.46, 95% CI = 2.96 to 6.71), suggesting that modifying RT plans for young women with breast cancer is unwarranted. Rare ATM missense variants, not currently identified as pathogenic, were associated with increased risk of RT-associated CBC (carriers of ATM rare missense variants of uncertain significance without RT: RR = 0.38, 95% CI = 0.09 to 1.55; carriers of ATM rare missense variants of uncertain significance with RT: RR = 2.98, 95% CI = 1.31 to 6.80). Further mechanistic studies will aid clinical decision-making related to RT.
Low-mass planet migration in three-dimensional wind-driven inviscid discs: a negative corotation torque
Authors: McNally Colin P , Nelson Richard P , Paardekooper Sijme-Jan , Benítez-Llambay Pablo , Gressel Oliver 
Published: February 2020

ABSTRACT
We present simulations of low-mass planet–disc interactions in inviscid three-dimensional discs. We show that a wind-driven laminar accretion flow through the surface layers of the disc does not significantly modify the migration torque experienced by embedded planets. More importantly, we find that 3D effects lead to a dramatic change in the behaviour of the dynamical corotation torque compared to earlier 2D theory and simulations. Although it was previously shown that the dynamical corotation torque could act to slow and essentially stall the inward migration of a low-mass planet, our results in 3D show that the dynamical corotation torque has the complete opposite effect and speeds up inward migration. Our numerical experiments implicate buoyancy resonances as the cause. These have two effects: (i) they exert a direct torque on the planet, whose magnitude relative to the Lindblad torque is measured in our simulations to be small; (ii) they torque the gas librating on horseshoe orbits in the corotation region and drive evolution of its vortensity, leading to the negative dynamical corotation torque. This indicates that at low turbulent viscosity, the detailed vertical thermal structure of the protoplanetary disc plays an important role in determining the migration behaviour of embedded planets. If this result holds up under a more refined treatment of disc thermal evolution, then it has important implications for understanding the formation and early evolution of planetary systems.
TimeMeter assesses temporal gene expression similarity and identifies differentially progressing genes
Authors: Jiang Peng , Chamberlain Connie S , Vanderby Ray , Thomson James A , Stewart Ron 
Published: February 2020

AbstractComparative time series transcriptome analysis is a powerful tool to study development, evolution, aging, disease progression and cancer prognosis. We develop TimeMeter, a statistical method and tool to assess temporal gene expression similarity, and identify differentially progressing genes where one pattern is more temporally advanced than the other. We apply TimeMeter to several datasets, and show that TimeMeter is capable of characterizing complicated temporal gene expression associations. Interestingly, we find: (i) the measurement of differential progression provides a novel feature in addition to pattern similarity that can characterize early developmental divergence between two species; (ii) genes exhibiting similar temporal patterns between human and mouse during neural differentiation are under strong negative (purifying) selection during evolution; (iii) analysis of genes with similar temporal patterns in mouse digit regeneration and axolotl blastema differentiation reveals common gene groups for appendage regeneration with potential implications in regenerative medicine.
APPLICABILITY OF PURE PROPANE GAS FOR MICRODOSIMETRY AT BRACHYTHERAPY ENERGIES: A FLUKA STUDY
Authors: Chattaraj Arghya , Selvam T Palani 
Published: February 2020

Abstract
Applicability of pure propane gas for microdosimetric measurements at photon energies relevant in brachytherapy is studied using the Monte Carlo-based FLUKA code. Monoenergetic photons in the energy range of 20–1250 keV and brachytherapy sources such as 103Pd, 125I, 169Yb, 192Ir, 137Cs and 60Co are considered in the study. Using the calculated values of energy deposited in the sensitive region of LET-1/2 tissue-equivalent proportional counter filled with pure propane gas and tissue-equivalent propane gas, values of density scaling factor for the site sizes of 1 and 8 μm are obtained. The study shows that density of propane gas should be lowered by a factor of about 0.93 for 169Yb, 192Ir, 137Cs and 60Co sources for the site sizes of 1–8 μm. For 125I source, the density of propane gas requires a scaling of 0.93 for 1 μm site size, whereas for site sizes 2–8 μm, density need not be altered. 103Pd source does not require density scaling for site sizes 1–8 μm.
Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease
Authors: Yan Peng-Guang , Li Jing-Nan 
Published: February 2020

Abstract
The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.
Ki67 in Gleason Pattern 3 as a Marker of the Presence of Higher-Grade Prostate Cancer
Authors: Caputo Alessandro , D’Antonio Antonio , Memoli Domenico , Sabbatino Francesco , Altieri Vincenzo , Zeppa Pio 
Published: February 2020

Purpose:
Prostate biopsies may undergrade up to half of all prostate cancers (PCs), delaying definitive treatment by up to 3 years. One cause of undergrading is the partial sampling inherent in the technique. Because of this, a prostate biopsy that appears to be Gleason 3+3=6 may come either from a true 3+3=6 tumor or from a higher-grade tumor that has been sampled only partially. The main goal of the present study is to identify a way to distinguish these 2 kinds of “Gleason 3+3=6” biopsies.
Mounting evidence hints at the possibility that Gleason pattern 3 associated with higher-grade PC (aG3) is biologically distinct from pure Gleason pattern 3 (pG3).

Materials and Methods:
In this study, we used immunohistochemistry and computer-aided image analysis to compare the expression of Ki67, cyclin D1, MYC, and p53 between foci of aG3 and pG3, to search for a marker that could distinguish them.

Results:
The expression of Ki67 differed significantly between pG3 and aG3. The average Ki67 labeling index was 1.63% for pG3 and 7.62% for aG3 (P<0.01); the average number of Ki67+ cells per high-power field was 17 for pG3 and 60 for aG3 (P<0.01). The other markers did not differ significantly between pG3 and aG3.

Conclusions:
When a biopsy only shows Gleason pattern 3 PC, Ki67 immunohistochemistry could be used to distinguish the nodules of true Gleason score 3+3=6 from those that only appear to be 3+3=6 because of a sampling error. This would dramatically improve the diagnostic performance of prostate biopsies and the management of early PC.
Atomoxetine Induced Skin Picking: A Case Report
Authors: Kasar Nurdan , Yurteri Nihal 
Published: February 2020

Abstract
“Skin picking disorder,” also known as “dermatillomania” or “psychogenic excoriation,” is classified in the “Obsessive Compulsive and Related Disorders” category in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and characterized by repetitive skin picking behaviors resulting in skin lesions. Atomoxetine (ATX) is a selective norepinephrine (noradrenaline) reuptake inhibitor commonly used in the management of attention-deficit/hyperactivity disorder. Atomoxetine is considered to increase levels of noradrenaline and dopamine by inhibiting norepinephrine transporters. In this case report, we present an 8-year-old male attention-deficit/hyperactivity disorder patient with skin picking behavior due to ATX treatment. We discussed possible explanations of skin picking behavior with ATX in the light of the current literature. To our knowledge, this is the first report of skin picking due to ATX in literature, and further studies are needed to investigate the frequency and mechanisms of skin picking with ATX.
The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing
Authors: Liao Minfeng , Liu Yang , Yuan Jin , Wen Yanling , Xu Gang , Zhao Juanjuan , Chen Lin , Li Jinxiu , Wang Xin , Wang Fuxiang , Liu Lei , Zhang Shuye , Zhang Zheng 
Published: February 2020

AbstractThe novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+macrophages, whereas notFABP4+alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.HighlightsImmune microenvironment of SARS-CoV-2-infected lungs revealed by scRNA/TCR seqIncreased inflammatory FCN1+ macrophages are replacing FABP4+ macrophages in the BALF from severe COVID-19 patientsHighly expanded and functional competent tissue resident clonal CD8+ T cells in mild COVID-19 patients
microRNA signatures of perioperative myocardial injury after elective non-cardiac surgery: prospective observational cohort study
Authors: May Shaun M. , Abbott Tom E.F. , Del Arroyo Ana Gutierrez , Reyes Anna , Martir Gladys , Stephens Robert C.M. , Brealey David , Cuthbertson Brian H. , Wijeysundera Duminda N. , Pearse Rupert M. , Ackland Gareth L. 
Published: February 2020

BackgroundElevated plasma/serum troponin, indicating perioperative myocardial injury (PMI), is common after non-cardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident.MethodsNested case-control study of samples obtained before and after non-cardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with/without PMI, matched for age, gender and comorbidity. Real-time polymerase chain reaction quantified relative microRNA expression (cycle quantification threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO).ResultsMicroRNA were detectable in all 59 patients (median age:67yrs (61-75); 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, PMI was not associated with increased serum microRNA expression levels after surgery (hsa-miR-1-3p mean fold-change (FC):3.99 (95%CI:1.95-8.19); hsa-miR-133-3p FC:5.67(95%CI:2.94-10.91); p<0.001). hsa-miR-208b-3p was more commonly detected after PMI (odd ratio (OR):10.0 (95%CI:1.9-52.6); p<0.01). Bioinformatic analysis of differentially expressed microRNAs from cohorts one and two identified pathways associated with adrenergic stress involving calcium dysregulation, rather than ischaemia.ConclusionsCirculating microRNAs synonymous with cardiac ischaemia were universally elevated in patients after surgery, independent of developing myocardial injury.
Spread and control of COVID-19 in China and their associations with population movement, public health emergency measures, and medical resources
Authors: Ying Songmin , Li Fei , Geng Xinwei , Li Zhouyang , Du Xufei , Chen Haixia , Chen Sisi , Zhang Min , Shao Zhehua , Wu Yinfang , Syeda Madiha Zahra , Yan Fugui , Che Luanqing , Zhang Bin , Lou Jian , Wang Shaobin , Chen Zhengming , Li Wen , Shen Ye , Chen Zhihua , Shen Huahao 
Published: February 2020

ABSTRACTBACKGROUNDThe COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year has significantly influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its control of population movement from Wuhan, local emergency response, and medical resources in China.METHODSSpearman’s correlation analysis was performed between official data of confirmed COVID-19 cases from Jan 20th to Feb 19th, 2020 and real-time travel data and health resources data.RESULTSThere were 74,675 confirmed COVID-19 cases in China by Feb 19th, 2020. The overall fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p<0.001; City r=0.6311, p<0.001) and primary cases (Provincial r=0.8702, p<0.001; City r=0.6358, p<0.001). The local health emergency measures (eg, city lockdown and traffic control) were associated with reduced infections nationwide. Moreover, the number of public health employees per capita was inversely correlated with total cases (r=−0.6295, p <0.001) and infection rates (r =−0.4912, p <0.01). Similarly, cities with less medical resources had higher fatality (r =−0.4791, p<0.01) and lower cure rates (r = 0.5286, p<0.01) among the confirmed cases.CONCLUSIONSThe spread of the COVID-19 in China in its early phase was attributed primarily to population movement from Hubei, and effective governmental health emergency measures and adequate medical resources played important roles in subsequent control of epidemic and improved prognosis of affected individuals.
Age-dependent risks of Incidence and Mortality of COVID-19 in Hubei Province and Other Parts of China
Authors: Li Hongdou , Wang Shuang , Zhong Fan , Bao Wuyin , Li Yipeng , Liu Lei , Wang Hongyan , He Yungang 
Published: February 2020

AbstractNew coronavirus SARS-CoV-2 poses a big challenge for global public health in early 2020. Coronavirus Disease 2019 (COVID-19) caused by the virus rapidly spreads all over the world and takes thousands of lives in just two months. It is critical to refine the incidence and mortality risks of COVID-19 for the effective management of the general public and patients in the outbreak. In this report, we investigate the incidence and mortality risks of the infection by analyzing the age composition of 5319 infected patients, 76 fatal cases, and 1,144,648 individuals of the general public in China. Our result shows a relatively low incidence risk for young people but a very high mortality risk for seniors. Notably, mortality risk could be as high as 0.48 for people older than 80 years. Furthermore, our study suggests that a good medical service can effectively reduce the mortality rate of the viral infection to 1% or less.
Anticipatory energization revealed by pupil and brain activity guides human effort-based decision making
Authors: Kurniawan Irma T. , Grueschow Marcus , Ruff Christian C. 
Published: February 2020

AbstractAn organism’s fitness is determined by how it chooses to adapt effort in response to challenges. Actual effort exertion correlates with activity in dorsomedial prefrontal cortex (dmPFC) and noradrenergic pupil dilation, but little is known about how these neurophysiological processes guide decisions about future efforts: They may either provide anticipatory energization helping to accept the challenge, or a cost representation weighted against expected rewards. Here we provide evidence for the former, by measuring pupil and fMRI brain responses while humans chose whether to exert efforts to obtain rewards. Pupil-dilation rate and dMPFC fMRI activity related to anticipated effort level, with stronger correlations when participants chose to accept the challenge. These choice-dependent effort representations were stronger in participants whose behavioral choices were more sensitive to effort. Our results identify a process involving the peripheral and central human nervous system that guides decisions to exert effort by simulating the required energization.
Codon usage bias in radioresistant bacteria
Authors: Dilucca Maddalena , Pavlopoulou Athanasia , Georgakilas Alexandros G. , Giansanti Andrea 
Published: February 2020

AbstractThe relationship between patterns of codon usage bias (CUB), the preferential usage of synonimous nucleotide triplets encoding the same amino acid, and radioresistance was investigated int he genomes of 16 taxonomically distinct radioresistant prokaryotic organisms and in a control set of 11 non-radioresistant bacteria. The radioresistant species were found to be strongly biased towards G and C in the third synonimous codon position. ENC and neutrality plots also sugest that CUB in radioresistant bacteria is mainly affected by mutational bias. Furthermore, the availability of tRNA gene copy number was analyzed and it was found that nine radioresistant species have the sam number of tRNA gene copies for each codon. This suggests that tRNA gene copies and codon bias co-evolved in a specific way in radioresistant species.
LRRK2 mutation alters behavioral, synaptic and non-synaptic adaptations to acute social stress
Authors: Guevara Christopher A. , Matikainen-Ankney Bridget A. , Kezunovic Nebojsa , LeClair Katherine , Conway Alexander P. , Menard Caroline , Flanigan Meghan E. , Pfau Madeline , Russo Scott J. , Benson Deanna L. , Huntley George W. 
Published: February 2020

AbstractParkinson’s disease (PD) risk is increased by stress and certain gene mutations, including the most prevalent PD-linked mutationLRRK2-G2019S. Both PD and stress increase risk for psychiatric symptoms, yet it is unclear how PD-risk genes alter neural circuitry in response to stress that may promote psychopathology. Here we show significant differences between adult G2019S knockin and wildtype (wt) mice in stress-induced behaviors, with an unexpected uncoupling of depression-like and hedonic-like responses in G2019S mice. Moreover, mutant spiny projection neurons in nucleus accumbens (NAc) lack an adaptive, stress-induced change in excitability displayed by wt neurons, and instead show stress-induced changes in synaptic properties that wt neurons lack. Some synaptic alterations in NAc are already evident early in postnatal life. Thus, G2019S alters the magnitude and direction of behavioral responses to stress that may reflect unique modifications of adaptive plasticity in cells and circuits implicated in psychopathology in humans.
Feasibility of axon density metrics for brain asymmetry evaluation in the UK Biobank subsample
Authors: Maximov Ivan I. , Westlye Lars T. 
Published: February 2020

AbstractStandard diffusion MRI model with intra- and extra-axonal water pools offers a set of microstructural parameters describing brain white matter architecture. However, a non-linearity of the general model and diffusion data contamination by noise and imaging artefacts make estimation of diffusion metrics challenging. In order to develop reproducible and reliable diffusion approaches and to avoid computational model degeneracy, one needs to devise additional theoretical assumptions allowing a stable numerical implementation. As a result, it is possible to estimate intra-axonal water fraction (AWF) representing one of the important structural parameters. AWF can be treated as an indirect measure of axon density and has a strong potential as useful clinical biomarker. A few diffusion approaches such as white matter tract integrity, neurite orientation dispersion and density imaging, and spherical mean technique, allow one to evaluate AWF in the frame of their theoretical assumptions. In the present study, we considered the compatibility of axon density metrics obtained from different diffusion models and the influence of the diffusion metric on a brain asymmetry estimation in UK Biobank sample consisting of 182 subjects. We found AWF derived from a spherical mean technique is the most statistically representative measure. As a result, we revealed that brain asymmetry indecies derived from intra-axonal water fraction weakly decrease along the lifespan, reducing the left-right hemisphere difference within increased age.