bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health
Authors: Barnes Jill N. , Pearson Andrew G. , Corkery Adam T. , Eisenmann Nicole A. , Miller Kathleen B. 
Published: May 2021

AbstractExercise is associated with higher cognitive function and is a promising intervention to reduce the risk of dementia. With advancing age, there are changes in the vasculature that have important clinical implications for brain health and cognition. Primary aging and vascular risk factors are associated with increases in arterial stiffness and pulse pressure, and reductions in peripheral vascular function.Objective:The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health.Methods:We performed a literature review and integrated with our published data.Results:Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear.Conclusion:Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.
Conversion of Forest to Agriculture Increases Colored Dissolved Organic Matter in a Subtropical Catchment and Adjacent Coastal Environment
Authors: Felgate Stacey L. , Barry Christopher D. G. , Mayor Daniel J. , Sanders Richard , Carrias Abel , Young Arlene , Fitch Alice , Mayorga‐Adame Claudia G. , Andrews Gilbert , Brittain Hannah , Cryer Sarah E. , Evans Chris D. , Goddard‐Dwyer Millie , Holt Jason T. , Hughes Bethany K. , Lapworth Dan J. , Pinder Adam , Price David M. , Rosado Samir , Evans Claire 
Published: May 2021

AbstractLand‐ocean dissolved organic matter (DOM) transport is a significant and changing term in global biogeochemical cycles which is increasing as a result of human perturbation, including land‐use change. Knowledge of the behavior and fate of transported DOM is lacking, particularly in the tropics and subtropics where land‐use change is occurring rapidly. We used Parallel Factor (PARAFAC) Analysis to investigate how land‐use influenced the composition of the DOM pool along a subtropical land‐use gradient (from near‐pristine broadleaf forest to agri‐urban settings) in Belize, Central America. Three humic‐like and two protein‐like components were identified, each of which was present across land uses and environments. Land‐use mapping identified a strong (R2 = 0.81) negative correlation between broadleaf forest and agri‐urban land. All PARAFAC components were positively associated with agri‐urban land‐use classes (cropland, grassland, and/or urban land), indicating that land‐use change from forested to agri‐urban exerts influence on the composition of the DOM pool. Humic‐like DOM exhibited linear accumulation with distance downstream and behaved conservatively in the coastal zone whilst protein‐like DOM exhibited nonlinear accumulation within the main river and nonconservative mixing in coastal waters, indicative of differences in reactivity. We used a hydrodynamic model to explore the potential of conservative humics to reach the region's environmentally and economically valuable coral reefs. We find that offshore corals experience short exposures (10 ± 11 days yr−1) to large (∼120%) terrigenous DOM increases, whilst nearshore corals experience prolonged exposure (113 ± 24 days yr−1) to relatively small (∼30%) terrigenous DOM increases.
Assimilation of Satellite Soil Moisture Products for River Flow Prediction: An Extensive Experiment in Over 700 Catchments Throughout Europe
Authors: De Santis D. , Biondi D. , Crow W. T. , Camici S. , Modanesi S. , Brocca L. , Massari C. 
Published: May 2021

AbstractIn this study, we perform a data assimilation (DA) experiment on a very large number (>700) of small‐ and medium‐scale (150–10,000 km2) European catchments to assess the impact of satellite soil moisture (SM) DA on streamflow simulations for different climatic and hydrologic conditions. In the experiment, Climate Change Initiative SM active, passive and combined products are assimilated over a time period 2003–2016 via an Ensemble Kalman Filter (EnKF). The results show that, on average, the assimilation of the three products provides relatively small improvements as compared to analogous open loop (OL) results (i.e., with an increase on median Kling‐Gupta Efficiency equal to 0.0048, 0.0033, and 0.0022 [−] for the active, the passive, and the combined products, respectively). OL performance itself is found to be a significant driver of the assimilation results: greater improvements are observed in catchments with poor OL streamflow predictions and inaccurate precipitation estimates. The remotely sensed product accuracy also emerges as relevant for assimilation efficiency, while factors affecting SM retrievals such as vegetation density, topographic complexity and basin area are found to have only a limited impact on the spatial pattern of performance. Small and detrimental effects of SM assimilation are observed over fully humid catchments and at high latitudes where pre‐storm soil moisture has reduced control on runoff generation as well as in basins where the hydrological model contains structural limitations.
Systematic misestimation of machine learning performance in neuroimaging studies of depression
Authors: Flint Claas , Cearns Micah , Opel Nils , Redlich Ronny , Mehler David M. A. , Emden Daniel , Winter Nils R. , Leenings Ramona , Eickhoff Simon B. , Kircher Tilo , Krug Axel , Nenadic Igor , Arolt Volker , Clark Scott , Baune Bernhard T. , Jiang Xiaoyi , Dannlowski Udo , Hahn Tim 
Published: May 2021

AbstractWe currently observe a disconcerting phenomenon in machine learning studies in psychiatry: While we would expect larger samples to yield better results due to the availability of more data, larger machine learning studies consistently show much weaker performance than the numerous small-scale studies. Here, we systematically investigated this effect focusing on one of the most heavily studied questions in the field, namely the classification of patients suffering from Major Depressive Disorder (MDD) and healthy controls based on neuroimaging data. Drawing upon structural MRI data from a balanced sample of N = 1868 MDD patients and healthy controls from our recent international Predictive Analytics Competition (PAC), we first trained and tested a classification model on the full dataset which yielded an accuracy of 61%. Next, we mimicked the process by which researchers would draw samples of various sizes (N = 4 to N = 150) from the population and showed a strong risk of misestimation. Specifically, for small sample sizes (N = 20), we observe accuracies of up to 95%. For medium sample sizes (N = 100) accuracies up to 75% were found. Importantly, further investigation showed that sufficiently large test sets effectively protect against performance misestimation whereas larger datasets per se do not. While these results question the validity of a substantial part of the current literature, we outline the relatively low-cost remedy of larger test sets, which is readily available in most cases.
Targeting non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex improves the efficacy of HEDGEHOG pathway inhibition in melanoma
Authors: Pietrobono Silvia , Gaudio Eugenio , Gagliardi Sinforosa , Zitani Mariapaola , Carrassa Laura , Migliorini Francesca , Petricci Elena , Manetti Fabrizio , Makukhin Nikolai , Bond Adam G. , Paradise Brooke D. , Ciulli Alessio , Fernandez-Zapico Martin E. , Bertoni Francesco , Stecca Barbara 
Published: May 2021

AbstractDespite the development of new targeted and immune therapies, the prognosis of metastatic melanoma remains bleak. Therefore, it is critical to better understand the mechanisms controlling advanced melanoma to develop more effective treatment regimens. Hedgehog/GLI (HH/GLI) signaling inhibitors targeting the central pathway transducer Smoothened (SMO) have shown to be clinical efficacious in skin cancer; however, several mechanisms of non-canonical HH/GLI pathway activation limit their efficacy. Here, we identify a novel SOX2-BRD4 transcriptional complex driving the expression ofGLI1, the final effector of the HH/GLI pathway, providing a novel mechanism of non-canonical SMO-independent activation of HH/GLI signaling in melanoma. Consistently, we find a positive correlation between the expression of GLI1 and SOX2 in human melanoma samples and cell lines. Further, we show that combined targeting of canonical HH/GLI pathway with the SMO inhibitor MRT-92 and of the SOX2-BRD4 complex using a potent Proteolysis Targeted Chimeras (PROTACs)-derived BRD4 degrader (MZ1), yields a synergistic anti-proliferative effect in melanoma cells independently of theirBRAF, NRAS, andNF1mutational status, with complete abrogation ofGLI1expression. Combination of MRT-92 and MZ1 strongly potentiates the antitumor effect of either drug as single agents in an orthotopic melanoma model. Together, our data provide evidence of a novel mechanism of non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex, and describe the efficacy of a new combinatorial treatment for a subset of melanomas with an active SOX2-BRD4-GLI1 axis.
Psychological responses among nurses caring for patients with COVID-19: a comparative study in China
Authors: Ren Honggang , Luo Xingguang , Wang Yincheng , Guo Xiaoyun , Hou Huiru , Zhang Yong , Yang Pengcheng , Zhu Fang , Hu Chao , Wang Runsheng , Sun Yu , Du Yingzhen , Yin Qin , Xu Guogang , Zuo Hui , Hu Qinyong , Wang Yahui 
Published: May 2021

AbstractFrontline healthcare nurses devoted themselves to deal with the outbreak of COVID-19, saving many lives. However, they are under incredible unknown psychological pressures with a considerable risk of infection. In this study, a self-administered questionnaire was used to survey 593 frontline nurses in Wuhan City and non-Hubei provinces for psychological responses from March 1 to March 10, 2020. Compared with nurses outside Hubei Province, those working in Wuhan were more likely to feel physically and mentally exhausted. Their probable depression and anxiety were significantly higher than those of nurses outside Hubei province (31.2%, 18.3% vs. 13.8%, 5.9%). Correspondingly, the depressive symptoms were more often reported in the Wuhan group (70.8% vs. 41.4%). Although Wuhan received wishes, concerns, and abundant psychological and material resources from all of the world, the survey-based study found that frontline nurses in Wuhan still had higher depression and anxiety with less social support compared with nurses from non-Hubei provinces. Unexpectedly, only 4.0% of nurses have sought psychological assistance. These findings suggested that the short-term psychological impact of frontline nurses in Wuhan during the COVID-19 outbreak was extremely high compared with nurses outside Hubei Province. This research enlightened the efficient integration of psychological resources, the optimization of the nurse emergency psychological assistance system, and the mental health care of medical staff during the outbreak of epidemics.
Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group
Authors: Rossetti Maria Gloria , Mackey Scott , Patalay Praveetha , Allen Nicholas B. , Batalla Albert , Bellani Marcella , Chye Yann , Conrod Patricia , Cousijn Janna , Garavan Hugh , Goudriaan Anna E. , Hester Robert , Martin-Santos Rocio , Solowij Nadia , Suo Chao , Thompson Paul M. , Yücel Murat , Brambilla Paolo , Lorenzetti Valentina 
Published: May 2021

AbstractMales and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.
Pure bulk orbital and spin photocurrent in two-dimensional ferroelectric materials
Authors: Mu Xingchi , Pan Yiming , Zhou Jian 
Published: May 2021

AbstractWe elucidate a bias-free light-induced orbital and spin current through nonlinear response theory, which generalizes the well-known bulk photovoltaic effect in centrosymmetric broken materials from charge to the spin and orbital degrees of freedom. We use two-dimensional nonmagnetic ferroelectric materials (such as GeS and its analogs) to illustrate this bulk orbital/spin photovoltaic effect, through first-principles calculations. These materials possess a vertical mirror symmetry and time-reversal symmetry but lack of inversion symmetry. We reveal that in addition to the conventional photocurrent that propagates parallel to the mirror plane (under linearly polarized light), the symmetric forbidden photocurrent perpendicular to the mirror actually contains electrons flow, which carries angular momentum information and move oppositely. This generates a pure orbital moment current with zero electric charge current. Such hidden photo-induced pure orbital current could lead to a pure spin current via spin–orbit coupling interactions. Therefore, a four-terminal device can be designed to detect and measure photo-induced charge, orbital, and spin currents simultaneously. All these currents couple with electric polarization P, hence their amplitude and direction can be manipulated through ferroelectric phase transition. Our work provides a route to generalizing nanoscale devices from their photo-induced electronics to orbitronics and spintronics.
Metabolic modelling reveals broad changes in gut microbial metabolism in inflammatory bowel disease patients with dysbiosis
Authors: Heinken Almut , Hertel Johannes , Thiele Ines 
Published: May 2021

AbstractInflammatory bowel diseases, such as Crohn’s Disease, are characterised by an altered blood and faecal metabolome, and changes in gut microbiome composition. Here, we present an efficient, scalable, tractable systems biology framework to mechanistically link microbial strains and faecal metabolites. We retrieve strain-level relative abundances from metagenomics data from a cohort of paediatric Crohn’s Disease patients with and without dysbiosis and healthy control children and construct and interrogate a personalised microbiome model for each sample. Predicted faecal secretion profiles and strain-level contributions to each metabolite vary broadly between healthy, dysbiotic, and non-dysbiotic microbiomes. The reduced microbial diversity in IBD results in reduced numbers of secreted metabolites, especially in sulfur metabolism. We demonstrate that increased potential to synthesise amino acids is linked to Proteobacteria contributions, in agreement with experimental observations. The established modelling framework yields testable hypotheses that may result in novel therapeutic and dietary interventions targeting the host-gut microbiome-diet axis.
Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema
Authors: Rhee Sang Youl , Jung Eun Sung , Suh Dong Ho , Jeong Su Jin , Kim Kiyoung , Chon Suk , Yu Seung-Young , Woo Jeong-Taek , Lee Choong Hwan 
Published: May 2021

AbstractTo investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.
Diversification, selective sweep, and body size in the invasive Palearctic alfalfa weevil infected with Wolbachia
Authors: Tuda Midori , Iwase Shun-ichiro , Kébé Khadim , Haran Julien , Skuhrovec Jiri , Sanaei Ehsan , Tsuji Naomichi , Podlussány Attila , Merkl Ottó , El-Heneidy Ahmed H. , Morimoto Katsura 
Published: May 2021

AbstractThe alfalfa weevil Hypera postica, native to the Western Palearctic, is an invasive legume pest with two divergent mitochondrial clades in its invading regions, the Western clade and the Eastern/Egyptian clade. However, knowledge regarding the native populations is limited. The Western clade is infected with the endosymbiotic bacteria Wolbachia that cause cytoplasmic incompatibility in host weevils. Our aim was to elucidate the spatial genetic structure of this insect and the effect of Wolbachia on its population diversity. We analyzed two mitochondrial and two nuclear genes of the weevil from its native ranges. The Western clade was distributed in western/central Europe, whereas the Eastern/Egyptian clade was distributed from the Mediterranean basin to central Asia. Intermediate mitotypes were found from the Balkans to central Asia. Most Western clade individuals in western Europe were infected with an identical Wolbachia strain. Mitochondrial genetic diversity of the infected individuals was minimal. The infected clades demonstrated a higher nonsynonymous/synonymous substitution rate ratio than the uninfected clades, suggesting a higher fixation of nonsynonymous mutations due to a selective sweep by Wolbachia. Trans-Mediterranean and within-European dispersal routes were supported. We suggest that the ancestral populations diversified by geographic isolation due to glaciations and that the diversity was reduced in the west by a recent Wolbachia-driven sweep(s). The intermediate clade exhibited a body size and host plant that differed from the other clades. Pros and cons of the possible use of infected-clade males to control uninfected populations are discussed.
Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
Authors: Tyler J. J. , Smaczynska-de Rooij I. I. , Abugharsa L. , Palmer J. S. , Hancock L. P. , Allwood E. G. , Ayscough K. R. 
Published: May 2021

AbstractActin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. WH2 domains are short sequence motifs found in many different actin binding proteins including WASP family proteins which regulate the actin nucleating complex Arp2/3. In this study we reveal a phosphorylation site, Serine 554, within the WH2 domain of the yeast WASP homologue Las17. Both phosphorylation and a phospho-mimetic mutation reduce actin monomer binding affinity while an alanine mutation, generated to mimic the non-phosphorylated state, increases actin binding affinity. The effect of these mutations on the Las17-dependent process of endocytosis in vivo was analysed and leads us to propose that switching of Las17 phosphorylation states may allow progression through distinct phases of endocytosis from site assembly through to the final scission stage. While the study is focused on Las17, the sole WASP family protein in yeast, our results have broad implications for our understanding of how a key residue in this conserved motif can underpin the many different actin regulatory roles with which WH2 domains have been associated.
ATHB2 is a negative regulator of germination in Arabidopsis thaliana seeds
Authors: Tognacca Rocío Soledad , Carabelli Monica , Morelli Giorgio , Ruberti Ida , Botto Javier Francisco 
Published: May 2021

AbstractThe germination timing of seeds is of the utmost adaptive importance for plant populations. Light is one of the best characterized factors promoting seed germination in several species. The germination is also finely regulated by changes in hormones levels, mainly those of gibberellin (GA) and abscisic acid (ABA). Here, we performed physiological, pharmacological, and molecular analyses to uncover the role of ATHB2, an HD-ZIP II transcription factor, in germination of Arabidopsis seeds. Our study demonstrated that ATHB2 is a negative regulator and sustains the expression of transcription factors to block germination promoted by light. Besides, we found that ATHB2 increases ABA sensitivity. Moreover, ABA and auxin content in athb2-2 mutant is higher than wild-type in dry seeds, but the differences disappeared during the imbibition in darkness and the first hours of exposition to light, respectively. Some ABA and light transcription factors are up-regulated by ATHB2, such as ABI5, ABI3, XERICO, SOMNUS and PIL5/PIF1. In opposition, PIN7, an auxin transport, is down-regulated. The role of ATHB2 as a repressor of germination induced by light affecting the gemination timing, could have differential effects on the establishment of seedlings altering the competitiveness between crops and weeds in the field.