bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
Authors: Buus Richard , Szijgyarto Zsolt , Schuster Eugene F. , Xiao Hui , Haynes Ben P. , Sestak Ivana , Cuzick Jack , Paré Laia , Seguí Elia , Chic Nuria , Prat Aleix , Dowsett Mitch , Cheang Maggie Chon U.
Published: February 2021

Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2− breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (rc(RS) = 0.96, 95% CI 0.93–0.97 with level of agreement (LoA) of −7.69 to 8.12; rc(EP) = 0.97, 95% CI 0.96–0.98 with LoA of −0.64 to 1.26 and rc(ROR) = 0.97 (95% CI 0.94–0.98) with LoA of −8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.
A randomized intervention involving family to improve communication in breast cancer care
Authors: Wolff Jennifer L. , Aufill Jennifer , Echavarria Diane , Blackford Amanda L. , Connolly Roisin M. , Fetting John H. , Jelovac Danijela , Papathakis Katie , Riley Carol , Stearns Vered , Zafman Nelli , Thorner Elissa , Levy Howard P. , Guo Amy , Dy Sydney M. , Wolff Antonio C.
Published: February 2021

We examined the effects of a communication intervention to engage family care partners on patient portal (MyChart) use, illness understanding, satisfaction with cancer care, and symptoms of anxiety in a single-blind randomized trial of patients in treatment for breast cancer. Patient-family dyads were recruited and randomly assigned a self-administered checklist to clarify the care partner role, establish a shared visit agenda, and facilitate MyChart access (n = 63) or usual care (n = 55). Interviews administered at baseline, 3, 9 (primary endpoint), and 12 months assessed anxiety (GAD-2), mean FAMCARE satisfaction, and complete illness understanding (4 of 4 items correct). Time-stamped electronic interactions measured MyChart use. By 9 months, more intervention than control care partners registered for MyChart (77.8 % vs 1.8%;p < 0.001) and logged into the patient’s account (61.2% vs 0% of those registered;p < 0.001), but few sent messages to clinicians (6.1% vs 0%;p = 0.247). More intervention than control patients viewed clinical notes (60.3% vs 32.7%;p = 0.003). No pre-post group differences in patient or care partner symptoms of anxiety, satisfaction, or complete illness understanding were found. Intervention patients whose care partners logged into MyChart were more likely to have complete illness understanding at 9 months (changed 70.0% to 80.0% vs 69.7% to 54.6%;p = 0.03); symptoms of anxiety were numerically lower (16.7% to 6.7% vs 15.2% to 15.2%;p = 0.24) and satisfaction numerically higher (15.8–16.2 vs 18.0–17.4;p = 0.25). A brief, scalable communication intervention led to greater care partner MyChart use and increased illness understanding among patients with more engaged care partners (NCT03283553).
Systematic evaluation of scoring methods for Ki67 as a surrogate for 21-gene recurrence score
Authors: Paik Soonmyung , Kwon Youngmee , Lee Moo Hyun , Kim Ji Ye , Lee Da Kyung , Cho Won Jeong , Lee Eun Young , Lee Eun Sook
Published: February 2021

Although Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath. We used OncotypeDx Recurrence Score (RS) as a benchmark to compare the potential clinical utility of each scoring methods. Both average and hotspot scores showed statistically significant but only modest correlation with OncotypeDx RS. Only hotspot score could meaningfully distinguish RS low-risk versus high-risk patients. However, hotspot score was less reproducible limiting its clinical utility. In summary, our data demonstrate that utility of the Ki67 labeling index is influenced by the choice of scoring method.
Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants
Authors: Lambertini Matteo , Ceppi Marcello , Hamy Anne-Sophie , Caron Olivier , Poorvu Philip D. , Carrasco Estela , Grinshpun Albert , Punie Kevin , Rousset-Jablonski Christine , Ferrari Alberta , Paluch-Shimon Shani , Toss Angela , Senechal Claire , Puglisi Fabio , Pogoda Katarzyna , Pérez-Fidalgo Jose Alejandro , De Marchis Laura , Ponzone Riccardo , Livraghi Luca , Estevez-Diz Maria Del Pilar , Villarreal-Garza Cynthia , Dieci Maria Vittoria , Clatot Florian , Duhoux Francois P. , Graffeo Rossella , Teixeira Luis , Córdoba Octavi , Sonnenblick Amir , Ferreira Arlindo R. , Partridge Ann H. , Di Meglio Antonio , Saule Claire , Peccatori Fedro A. , Bruzzone Marco , t’Kint de Roodenbeke Marie Daphne , Ameye Lieveke , Balmaña Judith , Del Mastro Lucia , Azim Hatem A.
Published: February 2021

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.
Origin of perpendicular magnetic anisotropy in amorphous thin films
Authors: Lordan Daniel , Wei Guannan , McCloskey Paul , O’Mathuna Cian , Masood Ansar
Published: February 2021

The emergence of perpendicular magnetic anisotropy (PMA) in amorphous thin films, which eventually transforms the magnetic spins form an in-plane to the out-of-plane configuration, also known as a spin-reorientation transition (SRT), is a fundamental roadblock to attain the high flux concentration advantage of these functional materials for broadband applications. The present work is focused on unfolding the origin of PMA in amorphous thin films deposited by magnetron sputtering. The amorphous films were deposited under a broad range of sputtering pressure (1.6–6.2 mTorr), and its effect on the thin film growth mechanisms was correlated to the static global magnetic behaviours, magnetic domain structure, and dynamic magnetic performance. The films deposited under low-pressure revealed a dominant in-plane uniaxial anisotropy along with an emerging, however feeble, perpendicular component, which eventually evolved as a dominant PMA when deposited under high-pressure sputtering. This change in the nature of anisotropy redefined the orientation of spins from in-plane to out-of-plane. The SRT in amorphous films was attributed to the dramatic change in the growth mechanism of disorder atomic structure from a homogeneously dispersed to a porous columnar microstructure. We suggest the origin of PMA is associated with the columnar growth of the amorphous films, which can be eluded by a careful selection of a deposition pressure regime to avoid its detrimental effect on the soft magnetic performance. To the author’s best knowledge, no such report links the sputtering pressure as a governing mechanism of perpendicular magnetisation in technologically important amorphous thin films.
Use tumor suppressor genes as biomarkers for diagnosis of non-small cell lung cancer
Authors: Zhang Chuantao , Jiang Man , Zhou Na , Hou Helei , Li Tianjun , Yu Hongsheng , Tan Yuan-De , Zhang Xiaochun
Published: February 2021

Lung cancer is the leading cause of death worldwide. Especially, non-small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efficient biomarkers for detection, diagnosis and prognosis. To find high efficient biomarkers for clinical diagnosis of NSCLC patients, we used gene differential expression and gene ontology (GO) to define a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down-expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were significantly down-expressed in tumor samples of stage 1. We usedS-scores andN-scores defined in correlation networks to evaluate positive and negative influences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant effects and network effects globally impacting the other genes in expression and hence can be used as specific biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be differentially expressed and had very smallS-scores andN-scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer. Our findings are well consistent with functions of these TS genes. GSEA analysis found that these 26 TS genes as a gene set had high enrichment scores at stages 1, 2, 3 and all stages.
Fluoroquinolone treatment as a protective factor for 10-day mortality in Streptococcus pneumoniae bacteremia in cancer patients
Authors: Fontana Naihma Salum , Ibrahim Karim Yaqub , Bonazzi P. R. , Rossi F. , Almeida S. C. G. , Tengan F. M. , Brandileone M. C. C. , Abdala E.
Published: February 2021

To evaluate the prognostic factors in adult cancer patients with pneumococcal bacteremia, describe episode features and the phenotypic characteristics of the isolated strains. We evaluated the episodes in patients admitted to a cancer hospital between 2009 and 2015. The outcomes were defined as 48 h mortality and mortality within 10 days after the episode. The variables evaluated were: age, sex, ethnicity, ECOG, Karnofsky score, SOFA, cancer type, metastasis, chemotherapy, radiotherapy, neutropenia, previous antibiotic therapy, community or healthcare-acquired infection, comorbidities, smoking, pneumococcal vaccination, infection site, presence of fever, polymicrobial infection, antimicrobial susceptibility, serotype and treatment. 165 episodes were detected in 161 patients. The mean age was 61.3 years; solid tumors were the most prevalent (75%). 48 h and 10-day mortality were 21% (34/161) and 43% (70/161) respectively. The 48 h mortality- associated risk factors were SOFA and polymicrobial bacteremia; 10-day mortality-associated risk factors were fever, neutropenia, ECOG 3/4, SOFA and fluoroquinolones as a protective factor. Pneumococcal bacteremia presented high mortality in cancer patients, with prognosis related to intrinsic host factors and infection episodes features. Fluoroquinolone treatment, a protective factor in 10-day mortality, has potential use for IPDs and severe community-acquired pneumonia in cancer patients.
Reduced nest development of reared Bombus terrestris within apiary dense human-modified landscapes
Authors: Meeus Ivan , Parmentier Laurian , Pisman Matti , de Graaf Dirk C. , Smagghe Guy
Published: February 2021

Wild bees are in decline on a local to global scale. The presence of managed honey bees can lead to competition for resources with wild bee species, which has not been investigated so far for human-modified landscapes. In this study we assess if managed honey bee hive density influence nest development (biomass) of bumble bees, an important trait affecting fitness. We hypothesize that domesticated honey bees can negatively affect Bombus terrestris nest development in human-modified landscapes. In Flanders, Belgium, where such landscapes are dominantly present, we selected 11 locations with landscape metrics ranging from urban to agricultural. The bee hive locations were mapped and each location contained one apiary dense (AD) and one apiary sparse (AS) study site (mean density of 7.6 ± 5.7 managed honey bee hives per km2 in AD sites). We assessed the effect of apiary density on the reproduction of reared B. terrestris nests. Reared B. terrestris nests had more biomass increase over 8 weeks in apiary sparse (AS) sites compared to nests located in apiary dense (AD) sites. This effect was mainly visible in urban locations, where nest in AS sites have 99.25 ± 60.99 g more biomass increase compared to nest in urban AD sites. Additionally, we found that managed bumble bee nests had higher biomass increase in urban locations. We conclude that the density of bee hives is a factor to consider in regard to interspecific competition between domesticated honey bees and bumble bees.
Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells
Authors: Kim Donguk , Park Na Yeon , Kang Keunsoo , Calderwood Stuart K. , Cho Dong-Hyung , Bae Ill Ju , Bunch Heeyoun
Published: February 2021

Arsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.
Understanding and recognition of the right ventricular function and dysfunction via a numerical study
Authors: Comunale Giulia , Peruzzo Paolo , Castaldi Biagio , Razzolini Renato , Di Salvo Giovanni , Padalino Massimo A. , Susin Francesca M.
Published: February 2021

The role played by the right ventricular (RV) dysfunction has long been underestimated in clinical practice. Recent findings are progressively confirming that when the RV efficiency deteriorates both the right and the left circulation is (significantly) affected, but studies dedicated to a detailed description of RV hemodynamic role still lack. In response to such a gap in knowledge, this work proposes a numerical model that for the first time evaluates the effect of isolated RV dysfunction on the whole circulation. Lumped parameter modelling was applied to represent the physio-pathological hemodynamics. Different grades of impairment were simulated for three dysfunctions i.e., systolic, diastolic, and combined systolic and diastolic. Hemodynamic alterations (i.e., of blood pressure, flow, global hemodynamic parameters), arising from the dysfunctions, are calculated and analysed. Results well accord with clinical observations, showing that RV dysfunction significantly affects both the pulmonary and systemic hemodynamics. Successful verification against in vivo data proved the clinical potentiality of the model i.e., the capability of identifying the degree of RV impairment for given hemodynamic conditions. This study aims at contributing to the improvement of RV dysfunction recognition and treatment, and to the development of tools for the clinical management of pathologies involving the right heart.
Predictors of stunting among children age 6–59 months in Ethiopia using Bayesian multi-level analysis
Authors: Muche Amare , Gezie Lemma Derseh , Baraki Adhanom Gebre-egzabher , Amsalu Erkihun Tadesse
Published: February 2021

In developing countries including Ethiopia stunting remained a major public health burden. It is associated with adverse health consequences, thus, investigating predictors of childhood stunting is crucial to design appropriate strategies to intervene the problem stunting. The study uses data from the Ethiopian Demographic and Health Survey (EDHS) conducted from January 18 to June 27, 2016 in Ethiopia. A total of 8117 children aged 6–59 months were included in the study with a stratified two stage cluster sampling technique. A Bayesian multilevel logistic regression was fitted using Win BUGS version 1.4.3 software to identify predictors of stunting among children age 6–59 months. Adjusted odds ratio (AOR) with 95% credible intervals was used to ascertain the strength and direction of association. In this study, increasing child’s age (AOR = 1.022; 95% CrI 1.018–1.026), being a male child (AOR = 1.16; 95%CrI 1.05–1.29), a twin (AOR = 2.55; 95% CrI 1.78–3.56), having fever (AOR = 1.23; 95%CrI 1.02–1.46), having no formal education (AOR = 1.99; 95%CrI 1.28–2.96) and primary education (AOR = 83; 95%CrI 1.19–2.73), birth interval less than 24 months (AOR = 1.40; 95% CrI 1.20–1.61), increasing maternal BMI (AOR = 0.95; 95% CrI 0.93–0.97), and poorest household wealth status (AOR = 1.78; 95% CrI 1.35–2.30) were predictors of childhood stunting at individual level. Similarly, region and type of toilet facility were predictors of childhood stunting at community level. The current study revealed that both individual and community level factors were predictors of childhood stunting in Ethiopia. Thus, more emphasize should be given by the concerned bodies to intervene the problem stunting by improving maternal education, promotion of girl education, improving the economic status of households, promotion of context-specific child feeding practices, improving maternal nutrition education and counseling, and improving sanitation and hygiene practices.
A transcriptomic view to wounding response in young Scots pine stems
Authors: Lim Kean-Jin , Paasela Tanja , Harju Anni , Venäläinen Martti , Paulin Lars , Auvinen Petri , Kärkkäinen Katri , Teeri Teemu H.
Published: February 2021

We studied the stress response of five-year-old Scots pine xylem to mechanical wounding using RNA sequencing. In general, we observed a bimodal response in pine xylem after wounding. Transcripts associated with water deficit stress, defence, and cell wall modification were induced at the earliest time point of three hours; at the same time, growth-related processes were down-regulated. A second temporal wave was triggered either at the middle and/or at the late time points (one and four days). Secondary metabolism, such as stilbene and lignan biosynthesis started one day after wounding. Scots pine synthesises the stilbenes pinosylvin and its monomethyl ether both as constitutive and induced defence compounds. Stilbene biosynthesis is induced by wounding, pathogens and UV stress, but is also developmentally regulated when heartwood is formed. Comparison of wounding responses to heartwood formation shows that many induced processes (in addition to stilbene biosynthesis) are similar and relate to defence or desiccation stress, but often specific transcripts are up-regulated in the developmental and wounding induced contexts. Pine resin biosynthesis was not induced in response to wounding, at least not during the first four days.
Retraction Note: Accelerated oral wound healing using a pre-vascularized mucosal cell sheet
Authors: Lee Jaewang , Kim Eun Hye , Shin Daiha , Roh Jong-Lyel
Published: February 2021

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-82919-5.
Genetic and endosymbiotic diversity of Greek populations of Philaenus spumarius, Philaenus signatus and Neophilaenus campestris, vectors of Xylella fastidiosa
Authors: Kapantaidaki Despoina Ev. , Antonatos Spyridon , Evangelou Vasiliki , Papachristos Dimitrios P. , Milonas Panagiotis
Published: February 2021

The plant-pathogenic bacteriumXylella fastidiosawhich causes significant diseases to various plant species worldwide, is exclusively transmitted by xylem sap-feeding insects. Given the fact thatX. fastidiosaposes a serious potential threat for olive cultivation in Greece, the main aim of this study was to investigate the genetic variation of Greek populations of three spittlebug species (Philaenus spumarius,P. signatusandNeophilaenus campestris), by examining the molecular markers Cytochrome Oxidase I, cytochrome b and Internal Transcribed Spacer. Moreover, the infection status of the secondary endosymbiontsWolbachia,Arsenophonus,Hamiltonella,CardiniumandRickettsia, among these populations, was determined. According to the results, theITS2region was the less polymorphic, while the analyzed fragments ofCOIandcytbgenes, displayed high genetic diversity. The phylogenetic analysis placed the Greek populations ofP. spumariusinto the previously obtained Southwest clade in Europe. The analysis of the bacterial diversity revealed a diverse infection status.Rickettsiawas the most predominant endosymbiont whileCardiniumwas totally absent from all examined populations.Philaenus spumariusharboredRickettsia,Arsenophonus,HamiltonellaandWolbachia,N. campestriscarriedRickettsia,HamiltonellaandWolbachiawhileP. signatuswas infected only byRickettsia. The results of this study will provide an important knowledge resource for understanding the population dynamics of vectors ofX. fastidiosawith a view to formulate effective management strategies towards the bacterium.
Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial
Authors: Hoang Ngan T. D. , Orellana Liliana , Gibson Rosalind S. , Le Tuyen D. , Worsley Anthony , Sinclair Andrew J. , Hoang Nghien T. T. , Szymlek-Gay Ewa A.
Published: February 2021

We aimed to determine the efficacy of multiple micronutrient supplementation on the biomarkers of iron, zinc, and vitamin A status across anthropometric status categories in Vietnamese school children. In this 22-week randomised controlled trial, 347 undernourished, normal weight, or overweight/obese children aged 6–9 years were allocated to receive every school day a multiple micronutrient supplement (10 mg iron, 10 mg zinc, 400 µg vitamin A) or a placebo. Haematological indices; circulating ferritin, zinc, and retinol (corrected for inflammation); and C-reactive protein were measured at baseline and 22 weeks. At week 22, linear mixed models showed that mean corpuscular volume increased by 0.3 fL, serum ferritin by 9.1 µg/L, plasma zinc by 0.9 µmol/L, and plasma retinol by 15%, and the prevalence of zinc deficiency decreased by 17.3% points in the intervention group compared to placebo. No intervention effects were found for other haematological indices, or the prevalence of anaemia. Multiple micronutrient supplementation for 22 weeks improved the biomarkers of zinc and vitamin A status and some biomarkers of iron status, and reduced the prevalence of zinc deficiency in Vietnamese school children.

Trial registration: This trial was registered on 06/09/2016 atwww.anzctr.org.auas ACTRN12616001245482.
Faceted-rough surface with disassembling of macrosteps in nucleation-limited crystal growth
Authors: Akutsu Noriko
Published: February 2021

To clarify whether a surface can be rough with faceted macrosteps that maintain their shape on the surface, crystal surface roughness is studied by a Monte Carlo method for a nucleation-limited crystal-growth process. As a surface model, the restricted solid-on-solid (RSOS) model with point-contact-type step–step attraction (p-RSOS model) is adopted. At equilibrium and at sufficiently low temperatures, the vicinal surface of the p-RSOS model consists of faceted macrosteps with (111) side surfaces and smooth terraces with (001) surfaces (the step-faceting zone). We found that a surface with faceted macrosteps has an approximately self-affine-rough structure on a ‘faceted-rough surface’; the surface width is strongly divergent at the step-disassembling point, which is a characteristic driving force for crystal growth. A ‘faceted-rough surface’ is realized in the region between the step-disassembling point and a crossover point where the single nucleation growth changes to poly-nucleation growth.
The identification of the Rosa S-locus and implications on the evolution of the Rosaceae gametophytic self-incompatibility systems
Authors: Vieira J. , Pimenta J. , Gomes A. , Laia J. , Rocha S. , Heitzler P. , Vieira C. P.
Published: February 2021

In Rosaceae species, two gametophytic self-incompatibility (GSI) mechanisms are described, the Prunus self-recognition system and the Maleae (Malus/Pyrus/Sorbus) non-self- recognition system. In both systems the pistil component is a S-RNase gene, but from two distinct phylogenetic lineages. The pollen component, always a F-box gene(s), in the case of Prunus is a single gene, and in Maleae there are multiple genes. Previously, the Rosa S-locus was mapped on chromosome 3, and three putative S-RNase genes were identified in the R. chinensis ‘Old Blush’ genome. Here, we show that these genes do not belong to the S-locus region. Using R. chinensis and R. multiflora genomes and a phylogenetic approach, we identified the S-RNase gene, that belongs to the Prunus S-lineage. Expression patterns support this gene as being the S-pistil. This gene is here also identified in R. moschata, R. arvensis, and R. minutifolia low coverage genomes, allowing the identification of positively selected amino acid sites, and thus, further supporting this gene as the S-RNase. Furthermore, genotype–phenotype association experiments also support this gene as the S-RNase. For the S-pollen GSI component we find evidence for multiple F-box genes, that show the expected expression pattern, and evidence for diversifying selection at the F-box genes within an S-haplotype. Thus, Rosa has a non-self-recognition system, like in Maleae species, despite the S-pistil gene belonging to the Prunus S-RNase lineage. These findings are discussed in the context of the Rosaceae GSI evolution. Knowledge on the Rosa S-locus has practical implications since genes controlling floral and other ornamental traits are in linkage disequilibrium with the S-locus.
Global exposure to flooding from the new CMIP6 climate model projections
Authors: Hirabayashi Yukiko , Tanoue Masahiro , Sasaki Orie , Zhou Xudong , Yamazaki Dai
Published: February 2021

Estimates of future flood risk rely on projections from climate models. The relatively few climate models used to analyze future flood risk cannot easily quantify of their associated uncertainties. In this study, we demonstrated that the projected fluvial flood changes estimated by a new generation of climate models, the collectively known as Coupled Model Intercomparison Project Phase 6 (CMIP6), are similar to those estimated by CMIP5. The spatial patterns of the multi-model median signs of change (+ or −) were also very consistent, implying greater confidence in the projections. The model spread changed little over the course of model development, suggesting irreducibility of the model spread due to internal climate variability, and the consistent projections of models from the same institute suggest the potential to reduce uncertainties caused by model differences. Potential global exposure to flooding is projected to be proportional to the degree of warming, and a greater threat is anticipated as populations increase, demonstrating the need for immediate decisions.
COVID-19 patients with hypertension are at potential risk of worsened organ injury
Authors: Xia Fei , Zhang Mingwei , Cui Bo , An Wei , Chen Min , Yang Ping , Qin Tao , Zhou Xiaoyang , Liao Yaling , Xu Xin , Liu Shiguo , Li Kuangyu , Zhou Qin , Wang Keke , Hu Guangxu , Du Ming , Chen Songrui , Zhang Yafang , Wei Wei , Xiang Ming , Zhang Jianjun
Published: February 2021

In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3–25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.
Impressive response to dabrafenib, trametinib, and osimertinib in a metastatic EGFR-mutant/BRAF V600E lung adenocarcinoma patient
Authors: Ribeiro Maurício Fernando Silva Almeida , Knebel Franciele Hinterholz , Bettoni Fabiana , Saddi Rodrigo , Sacardo Karina Perez , Canedo Felipe Sales Nogueira Amorim , Alessi João Victor Machado , Shimada Andrea Kazumi , Marin José Flávio Gomes , Camargo Anamaria Aranha , Katz Artur
Published: February 2021

The survival outcomes of the FLAURA trial support osimertinib as the new standard of care for untreated patients harboring activating mutations in the epidermal growth factor receptor (EGFR). Despite the initial response, disease progression invariably occurs. Although uncommon, BRAF V600E mutation arises as a unique mechanism of resistance, and thus far, no prospective studies are available to support concurrent EGFR/BRAF blockade. We report a case of impressive radiological and ctDNA response under dabrafenib, trametinib, and osimertinib in an advanced EGFR-mutant lung adenocarcinoma patient who developed BRAF V600E as one of the acquired resistance mechanisms to second-line osimertinib. Moreover, the patient experienced remarkable clinical improvement and good tolerance to combination therapy. The present case suggests the importance of prospective studies evaluating both efficacy and safety of the combination in later line settings and points towards the potential of ctDNA to monitor resistance mechanisms and treatment benefit in clinical practice.
Quantitative linear dichroism imaging of molecular processes in living cells made simple by open software tools
Authors: Bondar Alexey , Rybakova Olga , Melcr Josef , Dohnálek Jan , Khoroshyy Petro , Ticháček Ondřej , Timr Štěpán , Miclea Paul , Sakhi Alina , Marková Vendula , Lazar Josef
Published: February 2021

Fluorescence-detected linear dichroism microscopy allows observing various molecular processes in living cells, as well as obtaining quantitative information on orientation of fluorescent molecules associated with cellular features. Such information can provide insights into protein structure, aid in development of genetically encoded probes, and allow determinations of lipid membrane properties. However, quantitating and interpreting linear dichroism in biological systems has been laborious and unreliable. Here we present a set of open source ImageJ-based software tools that allow fast and easy linear dichroism visualization and quantitation, as well as extraction of quantitative information on molecular orientations, even in living systems. The tools were tested on model synthetic lipid vesicles and applied to a variety of biological systems, including observations of conformational changes during G-protein signaling in living cells, using fluorescent proteins. Our results show that our tools and model systems are applicable to a wide range of molecules and polarization-resolved microscopy techniques, and represent a significant step towards making polarization microscopy a mainstream tool of biological imaging.
Efficient manipulation of gene dosage in human iPSCs using CRISPR/Cas9 nickases
Authors: Ye Tao , Duan Yangyang , Tsang Hayley W. S. , Xu He , Chen Yuewen , Cao Han , Chen Yu , Fu Amy K. Y. , Ip Nancy Y.
Published: February 2021

The dysregulation of gene dosage due to duplication or haploinsufficiency is a major cause of autosomal dominant diseases such as Alzheimer’s disease. However, there is currently no rapid and efficient method for manipulating gene dosage in a human model system such as human induced pluripotent stem cells (iPSCs). Here, we demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. We first generate a Cas9 nickase variant with broader protospacer-adjacent motif specificity to expand the targetability of double-nicking–mediated genome editing. As a proof-of-concept study, we examine the gene dosage effects on an Alzheimer’s disease patient-derived iPSC line that carries three copies of APP (amyloid precursor protein). This method enables the rapid and simultaneous generation of iPSC lines with monoallelic, biallelic, or triallelic knockout of APP. The cortical neurons generated from isogenically corrected iPSCs exhibit gene dosage-dependent correction of disease-associated phenotypes of amyloid-beta secretion and Tau hyperphosphorylation. Thus, the rapid generation of iPSCs with different gene dosages using our method described herein can be a useful model system for investigating disease mechanisms and therapeutic development.
Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia
Authors: Börsch Anastasiya , Ham Daniel J. , Mittal Nitish , Tintignac Lionel A. , Migliavacca Eugenia , Feige Jérôme N. , Rüegg Markus A. , Zavolan Mihaela
Published: February 2021

Sarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.
Bridgehead effect and multiple introductions shape the global invasion history of a termite
Authors: Blumenfeld Alexander J. , Eyer Pierre-André , Husseneder Claudia , Mo Jianchu , Johnson Laura N. L. , Wang Changlu , Kenneth Grace J. , Chouvenc Thomas , Wang Shichen , Vargo Edward L.
Published: February 2021

Native to eastern Asia, the Formosan subterranean termiteCoptotermes formosanus(Shiraki) is recognized as one of the 100 worst invasive pests in the world, with established populations in Japan, Hawaii and the southeastern United States. Despite its importance, the native source(s) ofC. formosanusintroductions and their invasive pathway out of Asia remain elusive. Using ~22,000 SNPs, we retraced the invasion history of this species through approximate Bayesian computation and assessed the consequences of the invasion on its genetic patterns and demography. We show a complex invasion history, where an initial introduction to Hawaii resulted from two distinct introduction events from eastern Asia and the Hong Kong region. The admixed Hawaiian population subsequently served as the source, through a bridgehead, for one introduction to the southeastern US. A separate introduction event from southcentral China subsequently occurred in Florida showing admixture with the first introduction. Overall, these findings further reinforce the pivotal role of bridgeheads in shaping species distributions in the Anthropocene and illustrate that the global distribution ofC. formosanushas been shaped by multiple introductions out of China, which may have prevented and possibly reversed the loss of genetic diversity within its invasive range.
Direct observation of knock-on reaction with umbrella inversion arising from zero-impact-parameter collision at a surface
Authors: Timm Matthew J. , Leung Lydie , Anggara Kelvin , Polanyi John C.
Published: February 2021

In Surface-Aligned-Reactions (SAR), the degrees of freedom of chemical reactions are restricted and therefore the reaction outcome is selected. Using the inherent corrugation of a Cu(110) substrate the adsorbate molecules can be positioned and aligned and the impact parameter, the collision miss-distance, can be chosen. Here, substitution reaction for a zero impact parameter collision gives an outcome which resembles the classic Newton’s cradle in which an incident mass ‘knocks-on’ the same mass in the collision partner, here F + CF3 → (CF3)′ + (F)′ at a copper surface. The mechanism of knock-on was shown by Scanning Tunnelling Microscopy to involve reversal of the CF3 umbrella as in Walden inversion, with ejection of (F)′ product along the continuation of the F-reagent direction of motion, in collinear reaction.
Phase transitions and stability of dynamical processes on hypergraphs
Authors: Ferraz de Arruda Guilherme , Tizzani Michele , Moreno Yamir
Published: February 2021

Hypergraphs naturally represent higher-order interactions, which persistently appear in social interactions, neural networks, and other natural systems. Although their importance is well recognized, a theoretical framework to describe general dynamical processes on hypergraphs is not available yet. In this paper, we derive expressions for the stability of dynamical systems defined on an arbitrary hypergraph. The framework allows us to reveal that, near the fixed point, the relevant structure is a weighted graph-projection of the hypergraph and that it is possible to identify the role of each structural order for a given process. We analytically solve two dynamics of general interest, namely, social contagion and diffusion processes, and show that the stability conditions can be decoupled in structural and dynamical components. Our results show that in social contagion process, only pairwise interactions play a role in the stability of the absorbing state, while for the diffusion dynamics, the order of the interactions plays a differential role. Our work provides a general framework for further exploration of dynamical processes on hypergraphs.
Exploring the interactions betweenLactobacillus rhamnosusGG and whey protein isolate for preservation of the viability of bacteria through spray drying
Authors: Lu Wenjie , Fu Nan , Woo Meng Wai , Chen Xiao Dong
Published: February 2021

WPI-treated LGG showed enhanced thermotolerance, with reduced survival and activity after spray drying.  WPI treatment might trigger cellular response, causing a decline in metabolic activity and further reducing the stability of cell surface charge.
Antenna-coupled field-effect transistors as detectors for terahertz near-field microscopy
Authors: Wiecha Matthias M. , Kapoor Rohit , Chernyadiev Alexander V. , Ikamas Kęstutis , Lisauskas Alvydas , Roskos Hartmut G.
Published: February 2021

We report the successful implementation of antenna-coupled terahertz field-effect transistors (TeraFETs) as homodyne detectors in a scattering-type scanning near-field optical microscope (s-SNOM) operating with radiation at 246.5 GHz.
Induced pluripotent stem cell-derived vascular networks to screen nano–bio interactions
Authors: Estronca Luís , Francisco Vitor , Pitrez Patrícia , Honório Inês , Carvalho Lara , Vazão Helena , Blersch Josephine , Rai Akhilesh , Nissan Xavier , Simon Ulrich , Grãos Mário , Saúde Leonor , Ferreira Lino
Published: February 2021

The vascular bioactivity/safety of nanomaterials is typically evaluated by animal testing, which is of low throughput and does not account for biological differences between animals and humans such as ageing, metabolism and disease profiles.
Localization of light induced in ordered colloidal suspensions: powerful sensing tools
Authors: Ermakov Viktor A. , Martins Weliton S. , Wetter Niklaus U. , Marques Francisco C. , Jiménez-Villar Ernesto
Published: February 2021

Strongly enhanced light-matter coupling is reported in an ordered colloidal-photonic structure. Localization of light in this three-dimensional system (true Anderson localization) is demonstrated unambiguously providing compelling explanations for this striking phenomenon.
Promoting dry reforming of methane via bifunctional NiO/dolomite catalysts for production of hydrogen-rich syngas
Authors: Shamsuddin Mohd Razali , Asikin-Mijan Nurul , Marliza Tengku Sharifah , Miyamoto Manabu , Uemiya Shigeyuki , Yarmo Mohd Ambar , Taufiq-Yap Yun Hin
Published: February 2021

Catalytic conversion of methane dry reforming via NiO/Dolomite catalysts.
Chlorophyll excitation energies and structural stability of the CP47 antenna of photosystem II: a case study in the first-principles simulation of light-harvesting complexes
Authors: Sirohiwal Abhishek , Neese Frank , Pantazis Dimitrios A.
Published: February 2021

Advanced QM/MM simulations explore the excited states of a photosynthetic light-harvesting antenna in its physiologically complexed state and model the consequences of extraction on conformational and electronic properties.
Tuning the hydrogen evolution performance of 2D tungsten disulfide by interfacial engineering
Authors: Shi Meiqin , Jiang Zhuangzhuang , Mei Bingbao , Li Yingying , Sun Fanfei , Yu Haisheng , Xu Yinghua
Published: February 2021

Each nanolayer was composed of WC|WS2 interfaces by forming WS2 layers firstly and then inducing carbon as the interstitial atoms to partially replace the S atoms.
Ultrasound-visualized, site-specific vascular embolization using magnetic protein microcapsules
Authors: Chen Lanxi , Zhou Jianhua , Deng Qiurong , Feng Jialin , Qiu Qiong , Huang Wenwei , Chen Yin , Li Yan
Published: February 2021

A novel embolization strategy combining ultrasound visualization and magnetic targeting functions was developed using the fabricated magnetic protein microcapsules (MPMs) and holds great potential in the treatment of hepatocellular carcinoma (HCC).
Quercetin regulates skeletal muscle fiber type switching via adiponectin signaling
Authors: Chen Xiaoling , Liang Dahui , Huang Zhiqing , Jia Gang , Zhao Hua , Liu Guangmang
Published: February 2021

The role and underlying molecular mechanism of quercetin on skeletal muscle fiber type switching.
A remark on memory effects in constrained fluid systems
Authors: Perrin Charlotte
Published: February 2021

The goal of this note is to put into perspective the recent results obtained on memory effects in partially congested fluid systems of Euler or Navier-Stokes type with former studies on free boundary obstacle problems and Hele-Shaw equations. In particular, we relate the notion of adhesion potential initially introduced in the context of dense suspension flows with the one of Baiocchi variable used in the analysis of free boundary problems.