bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin and regulatory differentiation between bundle sheath and mesophyll cells in maize
Authors: Dai Xiuru , Tu Xiaoyu , Du Baijuan , Dong Pengfei , Sun Shilei , Wang Xianglan , Sun Jing , Li Gang , Lu Tiegang , Zhong Silin , Li Pinghua 
Published: November 2021

SUMMARYC4 plants partition photosynthesis enzymes between the bundle sheath (BS) and the mesophyll (M) cells for the better delivery of CO2 to RuBisCO and to reduce photorespiration. To better understand how C4 photosynthesis is regulated at the transcriptional level, we performed RNA‐seq, ATAC‐seq, ChIP‐seq and Bisulfite‐seq (BS‐seq) on BS and M cells isolated from maize leaves. By integrating differentially expressed genes with chromatin features, we found that chromatin accessibility coordinates with epigenetic features, especially H3K27me3 modification and CHH methylation, to regulate cell type‐preferentially enriched gene expression. Not only the chromatin‐accessible regions (ACRs) proximal to the genes (pACRs) but also the distal ACRs (dACRs) are determinants of cell type‐preferentially enriched expression. We further identified cell type‐preferentially enriched motifs, e.g. AAAG for BS cells and TGACC/T for M cells, and determined their corresponding transcription factors: DOFs and WRKYs. The complex interaction between cis and trans factors in the preferential expression of C4 genes was also observed. Interestingly, cell type‐preferentially enriched gene expression can be fine‐tuned by the coordination of multiple chromatin features. Such coordination may be critical in ensuring the cell type‐specific function of key C4 genes. Based on the observed cell type‐preferentially enriched expression pattern and coordinated chromatin features, we predicted a set of functionally unknown genes, e.g. Zm00001d042050 and Zm00001d040659, to be potential key C4 genes. Our findings provide deep insight into the architectures associated with C4 gene expression and could serve as a valuable resource to further identify the regulatory mechanisms present in C4 species.
Enhancing the dark side: asymmetric gain of cone photoreceptors underpins their discrimination of visual scenes based on skewness
Authors: Yedutenko Matthew , Howlett Marcus H. C. , Kamermans Maarten 
Published: November 2021

AbstractPsychophysical data indicate that humans can discriminate visual scenes based on their skewness, i.e. the ratio of dark and bright patches within a visual scene. It has also been shown that at a phenomenological level this skew discrimination is described by the so‐called blackshot mechanism, which accentuates strong negative contrasts within a scene. Here, we present a set of observations suggesting that the underlying computation might start as early as the cone phototransduction cascade, whose gain is higher for strong negative contrasts than for strong positive contrasts. We recorded from goldfish cone photoreceptors and found that the asymmetry in the phototransduction gain leads to responses with larger amplitudes when using negatively rather than positively skewed light stimuli. This asymmetry in amplitude was present in the cone photocurrent, voltage response and synaptic output. Given that the properties of the phototransduction cascade are universal across vertebrates, it is possible that the mechanism shown here gives rise to a general ability to discriminate between scenes based only on their skewness, which psychophysical studies have shown humans can do. Thus, our data suggest the importance of non‐linearity of the early photoreceptor for perception. Additionally, we found that stimulus skewness leads to a subtle change in photoreceptor kinetics. For negatively skewed stimuli, the impulse response functions of the cone peak later than for positively skewed stimuli. However, stimulus skewness does not affect the overall integration time of the cone.Key points
Humans can discriminate visual scenes based on skewness, i.e. the relative prevalence of bright and dark patches within a scene.
Here, we show that negatively skewed time‐series stimuli induce larger responses in goldfish cone photoreceptors than comparable positively skewed stimuli.
This response asymmetry originates from within the phototransduction cascade, where gain is higher for strong negative contrasts (dark patches) than for strong positive contrasts (bright patches).
Unlike the implicit assumption often contained within models of downstream visual neurons, our data show that cone photoreceptors do not simply relay linearly filtered versions of visual stimuli to downstream circuitry, but that they also emphasize specific stimulus features.
Given that the phototransduction cascade properties among vertebrate retinas are mostly universal, our data imply that the skew discrimination by human subjects reported in psychophysical studies might stem from the asymmetric gain function of the phototransduction cascade.
Simultaneous Validation of Count-to-Activity Thresholds for Five Commonly Used Activity Monitors in Adolescent Research: A Step Toward Data Harmonization
Authors: Hayes Gráinne , Dowd Kieran , MacDonncha Ciaran , Donnely Alan 
Published: November 2021

Background: Multiple activity monitors are utilized for the estimation of moderate- to vigorous-intensity physical activity in youth. Due to differing methodological approaches, results are not comparable when developing thresholds for the determination of moderate- to vigorous-intensity physical activity. This study aimed to develop and validate count-to-activity thresholds for 1.5, 3, and 6 metabolic equivalents of task in five of the most commonly used activity monitors in adolescent research. Methods: Fifty-two participants (mean age = 16.1 [0.78] years) selected and performed activities of daily living while wearing a COSMED K4b2 and five activity monitors; ActiGraph GT1M, ActiGraph wGT3X-BT, activPAL3 micro, activPAL, and GENEActiv. Receiver-operating-characteristic analysis was used to examine the area under the curve and to define count-to-activity thresholds for the vertical axis (all monitors) and the sum of the vector magnitude (ActiGraph wGT3X-BT and activPAL3 micro) for 15 s (all monitors) and 60 s (ActiGraph monitors) epochs. Results: All developed count-to-activity thresholds demonstrated high levels of sensitivity and specificity. When cross-validated in an independent group (N = 20), high levels of sensitivity and specificity generally remained (≥73.1%, intensity and monitor dependent). Conclusions: This study provides researchers with the opportunity to analyze and cross-compare data from different studies that have not employed the same motion sensors.
Visual Strategies Underpinning the Spatiotemporal Demands During Visuomotor Tasks in Predicting Ball Direction
Authors: Piras Alessandro , Timmis Matthew A. , Trofè Aurelio , Raffi Milena 
Published: November 2021

We investigated gaze behavior of expert goalkeepers during the prediction of penalty kicks in different spatiotemporal constraints: penalties taken from 11 and 6 m. From 11 m, goalkeepers were more successful in predicting ball direction, with longer movement time initiation and a visual strategy with more fixations and greater saccade rates than penalties from 6 m, where they exhibited fewer fixations with higher microsaccade rates. As long as the opponent’s distance is large and time pressure low, gaze can be frequently shifted between the kicker’s body and the ball, due to the low cost of saccades. Conversely, when the objects are close, there is increased reliance on foveal and parafoveal information. In conclusion, when the spatiotemporal constraint is less severe, goalkeepers adopt a visual strategy with more fixations and small saccades. When the spatiotemporal constraint is more severe, they rely on peripheral vision to monitor kickers’ movements through the use of microsaccades.
Treponema pallidum PCR testing for diagnosis of mucocutaneous ulcers suspicious for syphilis
Authors: Junejo Muhammad Hyder , Collery Mark , Whitlock Gary , McOwan Alan , Tittle Victoria , Nugent Diarmuid 
Published: November 2021

BackgroundPrimary syphilis is characterised by the appearance of an ulcerated lesion (chancre) on the anogenital or oral mucosa from which Treponema pallidum DNA may be detectable by PCR. Serological tests for syphilis may be non-reactive in early infection, even after the appearance of a chancre. We reviewed the use of a multiplex-PCR (M-PCR) test to determine the added value of T. pallidum DNA detection in the management of individuals presenting with mucocutaneous ulceration at a sexual health service in central London.MethodsWe performed a cross-sectional analysis of all individuals with detectable T. pallidum DNA from September 2019 to April 2020. Electronic patient records were reviewed and concomitant results for treponemal serology and/or rapid plasma reagin (RPR) extracted, along with demographic data, history of syphilis and indices of sexual behaviour including number of sexual partners contacted. Any subsequent treponemal serology and RPR results were also reviewed.ResultsM-PCR swab specimens were performed in 450 individuals, of whom 63 (14%) had detectable T. pallidum DNA; 60 of 63 (95%) were gay or bisexual men and 11 of 63 (17%) were living with HIV. A history of treated syphilis was present in 17 of 63 (27%). Same-day treponemal serology/RPR testing was performed in 58 of 63 (92%) patients. Of the 58 who had same-day syphilis serology/RPR, 9 (16%) had their syphilis infection confirmed by treponemal DNA PCR alone. A total of 165 partners were traced as contacts of infection, of whom 25 (15%) were contacts of individuals diagnosed by M-PCR testing alone.ConclusionIn individuals with T. pallidum PCR-positive lesions, around one in six in our cohort were negative on standard diagnostic serological tests for syphilis. Treponemal DNA testing is an important addition to serological assays in individuals with mucocutaneous ulceration who are at risk of recent syphilis infection and facilitates early diagnosis and contact tracing.
Evaluation of unprotected and rumen-protected L-carnitine in vitro and in vivo
Authors: Zheng Lin , Han Rui , Jiang Wei , Chen Long , Yu Wei , Zhong Wei-guang , Wei Bing-dong 
Published: November 2021

This study aimed to evaluate the effectiveness of unprotected and rumen-protected L-carnitine through in vitro tests, rumen degradation tests, and in vivo tests. Twelve rumen-fistulated crossbred rams with similar body weights of 55 ± 3.6 kg and ages of 3 ± 0.2 yr old were divided into three treatment groups in a 3 × 3 Latin square design, G1 (basal diet with no additives), G2 (unprotected L-carnitine), or G3 (rumen-protected L-carnitine). Ruminal fluid and blood samples were collected before morning feeding on the last day of each experimental period (21 d). The percentage of L-carnitine remaining in the simulated rumen and abomasum and rumen increased with the increase in the wall material ratio (P < 0.05). L-carnitine supplementation decreased the plasma urea nitrogen concentration in the sheep (P < 0.05). G3 resulted in higher glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities as well as higher total antioxidant capacity (T-AOC) and lower malondialdehyde (MDA) concentrations in plasma than G1, and the difference was significant among the groups (P < 0.01). Thus, L-carnitine in the rumen could be protected by encapsulation for a certain time. Unprotected and rumen-protected L-carnitine supplementation effectively enhanced the antioxidant capacity of sheep, and the antioxidant capacity of sheep supplemented with rumen-protected L-carnitine was higher than that of sheep supplemented with unprotected L-carnitine.
Direction-Aware User Recommendation Based on Asymmetric Network Embedding
Authors: Zhou Sheng , Wang Xin , Ester Martin , Li Bolang , Ye Chen , Zhang Zhen , Wang Can , Bu Jiajun 
Published: November 2021

User recommendation aims at recommending users with potential interests in the social network. Previous works have mainly focused on the undirected social networks with symmetric relationship such as friendship, whereas recent advances have been made on the asymmetric relationship such as the following and followed by relationship. Among the few existing direction-aware user recommendation methods, the random walk strategy has been widely adopted to extract the asymmetric proximity between users. However, according to our analysis on real-world directed social networks, we argue that the asymmetric proximity captured by existing random walk based methods are insufficient due to the inbalance in-degree and out-degree of nodes.
To tackle this challenge, we propose InfoWalk, a novel informative walk strategy to efficiently capture the asymmetric proximity solely based on random walks. By transferring the direction information into the weights of each step, InfoWalk is able to overcome the limitation of edges while simultaneously maintain both the direction and proximity. Based on the asymmetric proximity captured by InfoWalk, we further propose the qualitative (DNE-L) and quantitative (DNE-T) directed network embedding methods, capable of preserving the two properties in the embedding space. Extensive experiments conducted on six real-world benchmark datasets demonstrate the superiority of the proposed DNE model over several state-of-the-art approaches in various tasks.
Comparison of Fecal Sample Collection Methods for Microbial Analysis Embedded within Colorectal Cancer Screening Programs
Authors: Zouiouich Semi , Mariadassou Mahendra , Rué Olivier , Vogtmann Emily , Huybrechts Inge , Severi Gianluca , Boutron-Ruault Marie-Christine , Senore Carlo , Naccarati Alessio , Mengozzi Giulio , Kozlakidis Zisis , Jenab Mazda , Sinha Rashmi , Gunter Marc J. , Leclerc Marion 
Published: November 2021

Abstract

Background:
Colorectal cancer screening programs with fecal sample collection may provide a platform for population-based gut microbiome disease research. We investigated sample collection and storage method impact on the accuracy and stability of the V3-V4 region of the 16S rRNA genes and bacterial quantity across seven different collection methods [i.e., no solution, two specimen collection cards, and four types of fecal immunochemical test (FIT) used in four countries] among 19 healthy volunteers.

Methods:
Intraclass correlation coefficients (ICC) were calculated for the relative abundance of the top three phyla, the most abundant genera, alpha diversity metrics, and the first principal coordinates of the beta diversity matrices to estimate the stability of microbial profiles after storage for 7 days at room temperature, 4°C or 30°C, and after screening for the presence of occult blood in the stool. In addition, accuracy was estimated for samples frozen immediately compared to samples with no solution (i.e., the putative gold standard).

Results:
When compared with the putative gold standard, we observed significant variation for all collection methods. However, interindividual variability was much higher than the variability introduced by the collection method. Stability ICCs were high (≥0.75) for FIT tubes that underwent colorectal cancer screening procedures. The relative abundance of Actinobacteria (0.65) was an exception and was lower for different FIT tubes stored at 30°C (range, 0.41–0.90) and room temperature (range, 0.06–0.94).

Conclusions:
Paper-based collection cards and different types of FIT are acceptable tools for microbiome measurements.

Impact:
Our findings inform on the utility of commonly used fecal sample collection methods for developing microbiome-focused cohorts nested within screening programs.
Excess Body Fatness during Early to Mid-Adulthood and Survival from Colorectal and Breast Cancer: A Pooled Analysis of Five International Cohort Studies
Authors: Charvat Hadrien , Freisling Heinz , Noh Hwayoung , Gaudet Mia M. , Gunter Marc J. , Cross Amanda J. , Tsilidis Konstantinos K. , Tjønneland Anne , Katzke Verena , Bergmann Manuela , Agnoli Claudia , Rylander Charlotta , Skeie Guri , Jakszyn Paula , Rosendahl Ann H. , Sund Malin , Severi Gianluca , Tsugane Shoichiro , Sawada Norie , Brenner Hermann , Adami Hans-Olov , Weiderpass Elisabete , Soerjomataram Isabelle , Arnold Melina 
Published: November 2021

Abstract

Background:
Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries.

Methods:
Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis.

Results:
We found a significant dose–response relationship (P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07–1.60) and the time to death shortened by 16% for average BMI above 25 kg/m2 compared with average BMI less than or equal to 22.5 kg/m2, respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer.

Conclusions:
Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer.

Impact:
Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes.
Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy
Authors: Nguyen Cong Trung , Caruso Stefano , Maille Pascale , Beaufrère Aurélie , Augustin Jérémy , Favre Loetitia , Pujals Anaïs , Boulagnon-Rombi Camille , Rhaiem Rami , Amaddeo Giuliana , di Tommaso Luca , Luciani Alain , Regnault Hélène , Brustia Raffaele , Scatton Olivier , Charlotte Frédéric , Brochériou Isabelle , Sommacale Daniele , Soussan Patrick , Leroy Vincent , Laurent Alexis , Le Van Ky , Ta Van To , Trinh Hong Son , Tran Thi Lan , Gentien David , Rapinat Audrey , Nault Jean Charles , Allaire Manon , Mulé Sebastien , Zucman-Rossi Jessica , Pawlotsky Jean-Michel , Tournigand Christophe , Lafdil Fouad , Paradis Valérie , Calderaro Julien 
Published: November 2021

AbstractPurpose:Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome.Experimental Design:We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing.Results:Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an “immune-high” (IH) subtype (57% of the cases) and an “immune-low” (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P &lt; 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival.Conclusions:We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.
Mapa de confiabilidade: um método quantitativo para análise do grau de confiança nas reconstruções digitais de patrimônios históricos demolidos ou fortemente modificados
Authors: Gomes Emerson Bruno de Oliveira , Araujo Talita Simão Luiz , Ferraz Abner Simões Portilho , Aflalo Anna-Beatriz Bassalo 
Published: November 2021

O presente trabalho objetiva propor um “mapa de confiabilidade”: método quantitativo que visa informar o grau de confiança da reconstrução virtual de um cenário do passado, cuja reconstituição tenha partido, principalmente, de fotografias e mapas de épocas anteriores. O método proposto é dividido em duas partes: a primeira refere-se ao fluxo de produção do cenário 3D, que inclui a coleta de dados iconográficos e o cruzamento de mapas e fotos antigas, com vistas à modelagem tridimensional do ambiente, e a segunda parte, que diz respeito à utilização de um algoritmo (produzido no software @Rhino/plugin Grasshopper) que, através das informações das fotografias, realiza cálculos, cujo resultado é um mapa de calor que informa quais são as áreas que possuem maior ou menor grau de confiabilidade em relação às hipóteses do pesquisador sobre o aspecto arquitetônico e urbanístico do local reconstruído. Por fim, como forma de demonstrar a metodologia quantitativa, aplicou-se o algoritmo em duas reconstruções virtuais que retratam épocas diferentes de um mesmo lugar. Escolheu-se como estudo de caso o Largo de Nazaré, localizado na cidade de Belém. A comparação dos resultados entre ambas as épocas mostrou que, apesar de se tratar da mesma área e das mesmas técnicas de reconstituição virtual, os mapas ajudaram a esclarecer onde cada maquete digital necessitou de maior ou menor grau de dedução, portanto, mostrou-se útil para auxiliar os leitores sobre quais partes são mais ou menos confiáveis em relação aos registros do passado.