bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling of retinal pigment epithelial cell differentiation for therapeutic use
Authors: Petrus-Reurer Sandra , Lederer Alex R. , Baqué-Vidal Laura , Douagi Iyadh , Pannagel Belinda , Aronsson Monica , Bartuma Hammurabi , Wagner Magdalena , André Helder , Sundström Erik , Bhaduri Aparna , Kriegstein Arnold , Kvanta Anders , Manno Gioele La , Lanner Fredrik 
Published: February 2021

ABSTRACTHuman embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) are a promising cell source to treat age-related macular degeneration (AMD). Despite several ongoing clinical studies, detailed single cell mapping of the transient cellular and molecular dynamics from the pluripotent state to mature RPE has not been performed. Here we conduct single-cell transcriptomic analyses of 25,718 cells during differentiation as well as in embryonic and adult retina references, revealing differentiation progression through an un-expected initial cell diversification recapitulating early embryonic development before converging towards an RPE lineage. We also identified NCAM1 to track and capture an intermediate retinal progenitor with the potential to give rise to multiple neuroepithelial lineages. Finally, we profiled hESC-RPE cells after subretinal transplantation into the rabbit eye, uncovering robustin vivomaturation towards an adult state. Our detailed evaluation of hESC-RPE differentiation supports the development of safe and efficient pluripotent stem cell-based therapies for AMD.
Cortical Processing of Arithmetic and Simple Sentences in an Auditory Attention Task
Authors: Kulasingham Joshua P. , Joshi Neha H. , Rezaeizadeh Mohsen , Simon Jonathan Z. 
Published: February 2021

AbstractCortical processing of arithmetic and of language rely on both shared and task-specific neural mechanisms, which should also be dissociable from the particular sensory modality used to probe them. Here, spoken arithmetical and non-mathematical statements were employed to investigate neural processing of arithmetic, compared to general language processing, in an attention-modulated cocktail party paradigm. Magnetoencephalography (MEG) data was recorded from 22 subjects listening to audio mixtures of spoken sentences and arithmetic equations while selectively attending to one of the two speech streams. Short sentences and simple equations were presented diotically at fixed and distinct word/symbol and sentence/equation rates. Critically, this allowed neural responses to acoustics, words, and symbols to be dissociated from responses to sentences and equations. Indeed, the simultaneous neural processing of the acoustics of words and symbols was observed in auditory cortex for both streams. Neural responses to sentences and equations, however, was predominantly to the attended stream, and originated primarily from left temporal, and parietal areas, respectively. Additionally, these neural responses were correlated with behavioral performance in a deviant detection task. Source-localized Temporal Response Functions revealed distinct cortical dynamics of responses to sentences in left temporal areas and equations in bilateral temporal, parietal and motor areas. Finally, the target of attention could be decoded from MEG responses, especially in left superior parietal areas. In short, the neural responses to arithmetic and language are especially well segregated during the cocktail party paradigm, and the correlation with behavior suggests that they may be linked to successful comprehension or calculation.Significance StatementNeural processing of arithmetic relies on dedicated, modality independent cortical networks that are distinct from those underlying language processing. Using a simultaneous cocktail party listening paradigm, we found that these separate networks segregate naturally when listeners selectively attend to one type over the other. Time-locked activity in the left temporal lobe was observed for responses to both spoken sentences and equations, but the latter additionally showed bilateral parietal activity consistent with arithmetic processing. Critically, these responses were modulated by selective attention and correlated with task behavior, consistent with reflecting high-level processing for speech comprehension or correct calculations. The response dynamics show task-related differences that were used to reliably decode the attentional target of sentences or equations.
Dendritic domain-specific sampling of long-range axons shapes feedforward and feedback connectivity of L5 neurons
Authors: Galloni Alessandro R. , Ye Zhiwen , Rancz Ede 
Published: February 2021

AbstractFeedforward and feedback pathways interact in specific dendritic domains to enable cognitive functions such as predictive processing and learning. Based on axonal projections, hierarchically lower areas are thought to form synapses primarily on dendrites in middle cortical layers, while higher-order areas are posited to target dendrites in layer 1 and in deep layers. However, the extent to which functional synapses form in regions of axo-dendritic overlap has not been extensively studied. Here, we use viral tracing in the secondary visual cortex of mice to map brain-wide inputs to thick-tufted layer 5 pyramidal neurons. Furthermore, we provide a comprehensive map of input locations through subcellular optogenetic circuit mapping. We show that input pathways target distinct dendritic domains with far greater specificity than appears from their axonal branching, often deviating substantially from the canonical patterns. Common assumptions regarding the dendrite-level interaction of feedforward and feedback inputs may thus need revisiting.
Processes Underlying Interfirm Cooperation
Authors: Lahiri Somnath , Kundu Sumit , Munjal Surender 
Published: February 2021

AbstractThis special issue intended to bring together scholarly insights on the processes that underlie the formation, growth, management and termination of interfirm cooperation (IFC). In this introductory paper, we highlight what we know about IFC and why fresh perspectives are warranted on this phenomenon from a conceptual and practical standpoint. We also highlight the contribution of each paper published in this special issue. The seven selected papers differ in their theoretical perspective, context, research methodology and findings, but collectively they enhance our understanding of various IFC processes. We end this paper by highlighting fertile avenues of future research.
The effects of function‐based communication intervention for a student with emotional disturbance in a general education setting
Authors: Perihan Celal , Bicer Ali 
Published: February 2021

AbstractResearch has shown that most children with emotional disturbance (ED) are struggling to use communication skills and they may tend to use inappropriate behaviours as a form of communication to disclose their needs. A function‐based communication intervention might be an effective approach to decrease inappropriate behaviours of children with ED. The purpose of this single‐case multiple baseline reversal design (ABAB) study was to examine the effectiveness of the function‐based communication intervention for on‐task and disruptive behaviours of an 8‐year‐old student with ED. Functional behavioural assessment (FBA) was conducted and based on the findings of FBA, a colour‐coded communication system, was implemented during reading and math classes. The findings indicated that function‐based communication intervention was effective in increasing on‐task as well as decreasing disruptive behaviours. Furthermore, the function‐based communication intervention improved communication between the teacher and the student that resulted in decreasing disruptive behaviours in a general classroom setting. The generalisability of the findings due to the limited number of participants was an important limitation for this study. Future directions, as well as implications for practices, are discussed.
Determination of antibiotics in meat samples using analytical methodologies: A review
Authors: Moga Ancuta , Vergara‐Barberán María , Lerma‐García María Jesús , Carrasco‐Correa Enrique Javier , Herrero‐Martínez José Manuel , Simó‐Alfonso Ernesto Francisco 
Published: February 2021

AbstractAntibiotics are widely used to prevent or treat some diseases in human and veterinary medicine and also as animal growth promoters. The presence of these compounds in foods derived from food‐producing animals can be a risk for human health. Consequently, regulatory agencies have set maximum residue limits for antibiotics in food samples. Therefore, the development of novel methodologies for its determination in food samples is required. Specifically, the analysis and quantification of these substances in meat tissues is a challenge for the analytical chemistry research community. This is due to the complexity of the matrix and the low detection limits required by the regulatory agencies. In this sense, a comprehensive review on the development of new sample preparation treatments involving extraction, cleanup, and enrichment steps of antibiotics in meat samples in combination with sensitive and sophisticated determination techniques that have been carry out in the last years is necessary. Therefore, the aim of this work is to summarize the published methodologies for the determination of antibiotics from 2016 until the beginning of the second semester of 2020. The first part of this review includes an introduction about antibiotic families, followed by sample preparation and determination techniques applied to the different families. Finally, a detailed discussion of the current trends and the future possible perspectives in this field are also included.
Effect of growth and parturition on hair cortisol in Holstein cattle
Authors: Hayashi Hideaki , Arai Chigusa , Ikeuchi Yurie , Yamanaka Maho , Hirayama Takuji 
Published: February 2021

AbstractThe effect of growth and parturition on hair cortisol concentrations of cattle was investigated. Plasma, saliva, and hair (black and white from the shoulders and hip) samples were collected from calves at 6 and 24 weeks old and from dairy cattle at the dry (1 and 2 months prepartum) and lactation (10, 50, 150, and 250 days postpartum) periods. Plasma and saliva cortisol concentrations were lower in 24‐week‐old calves than those of 6‐week‐old calves, and hair cortisol concentrations decreased regardless of color and position. In 6‐week‐old calves, hair cortisol concentrations differed between sampling positions, but this difference was not observed in 24‐week‐old calves. Plasma and saliva cortisol concentrations increased before parturition until 10 days postpartum then decreased until 50 days postpartum. The same trend was observed in the cortisol concentrations of white hair. Contrarily, cortisol concentrations in black hair remained unchanged and was lower than that in white hair. Hair cortisol concentration can vary greatly depending on the location on the body, hair color, cattle age, or parturition. When this method is used, all of the above factors must be considered.
Tumour microenvironment‐based molecular profiling reveals ideal candidates for high‐grade serous ovarian cancer immunotherapy
Authors: Lu Xiaofan , Ji Caoyu , Jiang Liyun , Zhu Yue , Zhou Yujie , Meng Jialin , Gao Jun , Lu Tao , Ye Junmei , Yan Fangrong 
Published: February 2021

AbstractObjectiveDue to limited immunological profiles of high‐grade serous ovarian cancer (HGSOC), we aimed to characterize its molecular features to determine whether a specific subset that can respond to immunotherapy exists.Materials and MethodsA training cohort of 418 HGSOC samples from TCGA was analysed by consensus non‐negative matrix factorization. We correlated the expression patterns with the presence of immune cell infiltrates, immune regulatory molecules and other genomic or epigenetic features. Two independent cohorts containing 482 HGSOCs and in vitro experiments were used for validation.ResultsWe identified immune and non‐immune groups where the former was enriched in signatures that reflect immune cells, infiltration and PD‐1 signalling (all, P < 0.001), and presented with a lower chromosomal aberrations but increased neoantigens, tumour mutation burden, and microsatellite instability (all, P < 0.05); this group was further refined into two microenvironment‐based subtypes characterized by either immunoactivation or carcinoma‐associated fibroblasts (CAFs) and distinct prognosis. CAFs‐immune subtype was enriched for factors that mediate immunosuppression and promote tumour progression, including highly expressed stromal signature, TGF‐β signalling, epithelial‐mesenchymal transition and tumour‐associated M2‐polarized macrophages (all, P < 0.001). Robustness of these immune‐specific subtypes was verified in validation cohorts, and in vitro experiments indicated that activated‐immune subtype may benefit from anti‐PD1 antibody therapy (P < 0.05).ConclusionOur findings revealed two immune subtypes with different responses to immunotherapy and indicated that some HGSOCs may be susceptible to immunotherapies or combination therapies.
Transient characteristics of universal cells on human‐induced pluripotent stem cells and their differentiated cells derived from foetal stem cells with mixed donor sources
Authors: Sung Tzu‐Cheng , Jiang Yi‐Peng , Hsu Jhe‐Yu , Ling Qing‐Dong , Chen Hao , Kumar Suresh S. , Chang Yung , Hsu Shih‐Tien , Ye Qingsong , Higuchi Akon 
Published: February 2021

AbstractIntroductionIt is important to prepare ‘hypoimmunogenic’ or ‘universal’ human pluripotent stem cells (hPSCs) with gene‐editing technology by knocking out or in immune‐related genes, because only a few hypoimmunogenic or universal hPSC lines would be sufficient to store for their off‐the‐shelf use. However, these hypoimmunogenic or universal hPSCs prepared previously were all genetically edited, which makes laborious processes to check and evaluate no abnormal gene editing of hPSCs.MethodsUniversal human‐induced pluripotent stem cells (hiPSCs) were generated without gene editing, which were reprogrammed from foetal stem cells (human amniotic fluid stem cells) with mixing 2‐5 allogenic donors but not with single donor. We evaluated human leucocyte antigen (HLA)‐expressing class Ia and class II of our hiPSCs and their differentiated cells into embryoid bodies, cardiomyocytes and mesenchymal stem cells. We further evaluated immunogenic response of transient universal hiPSCs with allogenic mononuclear cells from survival rate and cytokine production, which were generated by the cells due to immunogenic reactions.ResultsOur universal hiPSCs during passages 10‐25 did not have immunogenic reaction from allogenic mononuclear cells even after differentiation into cardiomyocytes, embryoid bodies and mesenchymal stem cells. Furthermore, the cells including the differentiated cells did not express HLA class Ia and class II. Cardiomyocytes differentiated from transient universal hiPSCs at passage 21‐22 survived and continued beating even after treatment with allogenic mononuclear cells.
Oral function and its association with nutrition and quality of life in nursing home residents with and without dementia: A cross‐sectional study
Authors: van de Rijt Liza J. M. , Feast Alexandra R. , Vickerstaff Victoria , Sampson Elizabeth L. , Lobbezoo Frank 
Published: February 2021

AbstractBackgroundOral health problems increase with age, and are common in nursing home residents, especially in those with dementia. These problems can lead to tooth loss, diminished oral function and malnutrition.ObjectivesTo compare oral function, nutritional status and quality of life (QoL) between residents with and without dementia, and to examine associations between these variables.MethodsCross‐sectional study conducted in four UK nursing homes. Residents aged 65 + with and without dementia were included. Information was collected on demographics, dental status, quality of swallowing and chewing, xerostomia and orofacial pain. During oral examination, information was collected on number of teeth and occlusal units (OU), and functional categories (eg, OU combined with dentures). Multiple linear regression was used for statistical analysis.ResultsOf 84 residents with and 27 without dementia participated. Residents with dementia had significantly fewer teeth (Dementia median (IQR) = 14 (6‐21), vs No dementia 22 (12.75‐24.25); P = .021), fewer OU (Dementia median (IQR) = 0 (0‐3), vs No dementia 4 (0‐7); P = .001) and poorer functional categories (Z = −3.283; P = .001), and nutritional status was significantly poorer than those without (Dementia Mean (SD) = 8.3 (2.7), vs No dementia 10.4 (2.0); P = .002). In the regression model, quality of chewing (Coef (95% CI) = −1.27 (−2.22, −0.31); P = .010) was significantly correlated with nutritional status.ConclusionOral function and nutritional status of residents with dementia was poorer than those without. Almost half of all residents had insufficient oral function, which was negatively associated with QoL and nutritional status.
High‐speed rail and city tourism: Evidence from Tencent migration big data on two Chinese golden weeks
Authors: Gao Yanyan , Nan Yongqing , Song Shunfeng 
Published: February 2021

AbstractThis paper estimates the effect of high‐speed rail (HSR) on city tourism. To identify the causal effect, we measure tourism outcomes with population flow data from Tencent migration big data and construct daily panel data of two national holidays from April 2015 to May 2019. Empirical results reveal that HSR connection increases the intercity tourist flows, which holds under a number of robustness checks. Such effect is greater in the Labor Day holiday than in the National Day holiday, and the impact on tourist outflow in the first‐half holiday is greater than that on tourist inflow. We also find that HSR connection increases the intensity that tourists travel by train. Our findings provide solid evidence on the contribution of transportation improvement to city tourism economy.
Current challenges for men and women with mild‐to‐moderate haemophilia
Authors: Rajpurkar Madhvi , Forsyth Angela , Manco‐Johnson Marilyn 
Published: February 2021

AbstractCurrent treatments in the field of haemophilia are changing the phenotype of many patients with severe haemophilia to that of mild haemophilia. Despite this improvement, those with mild‐to‐moderate haemophilia A and haemophilia B continue to experience unmet needs. Whereas some patients with mild‐to‐moderate haemophilia experience similar complications to those of patients with severe haemophilia, they possess several unique attributes. These include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, haemophilia is an under‐recognized condition in women even though many women with mild‐to‐moderate haemophilia experience the same symptoms and complications as men with haemophilia. These women also have their own unique challenges with this disease. This supplement highlights many of the unmet needs in men and women with mild‐to‐moderate haemophilia. The conclusions of each of these papers reinforce the need for additional research and resources for this patient population.
Blood glucose levels and bodyweight change after dapagliflozin administration
Authors: Kim Hyunah , Lee Seung‐Hwan , Lee Hyunyong , Yim Hyeon Woo , Cho Jae‐Hyoung , Yoon Kun‐Ho , Kim Hun‐Sung 
Published: February 2021

AbstractAims/IntroductionIncreased blood glucose or increased weight is often observed in patients who are prescribed sodium–glucose cotransporter 2 inhibitors (SGLT2i). The aim of this study was to determine in advance which patients, among those prescribed a SGLT2i, would be likely to have improved or worsened blood glucose levels and gain or loss of weight through the use of real‐world data‐based prescriptions.Materials and MethodsAfter 3 months of dapagliflozin prescription, patients were divided into four groups: H(+)W(+) for improved glucose and weight loss; H(+)W(−) for improved blood glucose and weight gain; H(−)W(+) for worsened glucose and weight loss; and H(−)W(−) for worsened glucose and weight gain.ResultsThe proportion of patients in the H(+)W(+) group was 53.5% (325/608 patients), H(+)W(−) was 19.7% (120/608), H(−)W(+) was 26.8% (114/608) and H(−)W(−) was 8.1% (49/608). The odds of proceeding to H(+)W(−) compared with H(+)W(+), which served as the reference, were 144% in baseline hemoglobin A1c (HbA1c) 7.0–8.0%, 233% in baseline HbA1c 8.0–9.0% and 359% in baseline HbA1c ≥ 9.0% (odds ratio 3.59, P < 0.05) compared with the reference. The odds of proceeding to H(−)W(+) were 29, 13 and 8%, respectively (all P < 0.05), and to H(−)W(−) were 17, 15 and 8%, respectively (all P < 0.05), compared with the reference. The results were expected to vary individually, because changes in blood glucose and bodyweight are more affected by diet and exercise than by drugs.ConclusionsWhen first prescribing dapagliflozin, a physician should be aware of the weight gain rather than glucose change if the baseline HbA1c is high, and might concentrate on weight‐related lifestyle training, such as diet and exercise.
Association between plasma irisin in pregnancy and postpartum glucose levels among Chinese women: A cohort study
Authors: Tang Nu , Chen Yajun , Wu Weijia , Pan Wenting , Wang Dongyu , Zhang Jingshu , Tan Kaiyun , Jing Jin , Cai Li 
Published: February 2021

AbstractAims/IntroductionThe association between plasma irisin and glucose levels in the general population is controversial, and few studies have longitudinally detected this correlation. We aimed to examine whether irisin in pregnancy was associated with postpartum glucose levels among Chinese women and explore the modifiable factors.Materials and MethodsWe carried out a prospective cohort study in Guangzhou, China, during 2017 and 2018, and 453 pregnant women (20–28 weeks) were enrolled. Plasma irisin levels in pregnancy were tested. At 6–8 weeks after delivery, 93 women with gestational diabetes mellitus (GDM) underwent a 75‐g oral glucose tolerance test, and the other 360 women had a fasting blood glucose (FBG) test. Multivariable linear, quantile and logistic regressions were carried out.ResultsThe mean plasma irisin in mid‐pregnancy was 13.73 ng/mL. We observed a significantly negative association between mid‐pregnancy irisin and postpartum FBG (β: −0.056 ± 0.024). However, quantile regression showed the association was only significant in high percentiles of FBG levels (P50 to P95), and the magnitude showed an increasing trend. Higher baseline irisin was also associated with a lower risk of postpartum impaired fasting glucose (relative risk 0.563, 95% confidence interval 0.384–0.825). Furthermore, we found significant interactions between irisin and predominant breast‐feeding on FBG and impaired fasting glucose (both Pinteraction < 0.05). In women with GDM, baseline irisin was non‐significantly associated with postpartum postprandial 2‐h glucose levels (β: −0.305 ± 0.160, P = 0.061).ConclusionsPlasma irisin levels in mid‐pregnancy were negatively associated with FBG levels and impaired fasting glucose at 6–8 weeks postpartum among Chinese women, and stronger associations were observed in women with higher FBG values. Furthermore, breast‐feeding might modify this relationship.