bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex dimorphism in inflammatory response to obesity in childhood
Authors: Simoes Estefania , Correia-Lima Joanna , Sardas Leonardo , Storti Felipe , Otani Thais Zélia dos Santos , Vasques Daniel Augusto Correa , Otani Victor Henrique Oyamada , Bertolazzi Pamela , Kochi Cristiane , Seelaender Marilia , Uchida Ricardo Riyoiti 
Published: February 2021

Abstract
Background
Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient.

Design
Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = −0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey’s test, and Spearman’s correlation coefficient were employed, with a significance threshold set at p < 0.05.

Results
We identified increased levels of serum amyloid A (SAA), platelets, and leukocytes solely in male obese patients. We found a noteworthy sex-dependent pattern in regard to inflammatory response: obese boys showed higher TNFβ, IL15, and IL2 and lower IL10 and IL13, while obese girls showed increased TNFα, CCL3, CCL4, and IP10 content in the circulation. BMI Z-score was significantly linearly correlated with neutrophils, leukocytes, platelets, SAA, TNFα, CCL3, CCL4, IP10, and IL13 levels within the entire cohort (non-sex-dependent).

Conclusions
Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.
The P-factor and its genomic and neural equivalents: an integrated perspective
Authors: Sprooten Emma , Franke Barbara , Greven Corina U. 
Published: February 2021

AbstractDifferent psychiatric disorders and symptoms are highly correlated in the general population. A general psychopathology factor (or “P-factor”) has been proposed to efficiently describe this covariance of psychopathology. Recently, genetic and neuroimaging studies also derived general dimensions that reflect densely correlated genomic and neural effects on behaviour and psychopathology. While these three types of general dimensions show striking parallels, it is unknown how they are conceptually related. Here, we provide an overview of these three general dimensions, and suggest a unified interpretation of their nature and underlying mechanisms. We propose that the general dimensions reflect, in part, a combination of heritable ‘environmental’ factors, driven by a dense web of gene-environment correlations. This perspective calls for an update of the traditional endophenotype framework, and encourages methodological innovations to improve models of gene-brain-environment relationships in all their complexity. We propose concrete approaches, which by taking advantage of the richness of current large databases will help to better disentangle the complex nature of causal factors underlying psychopathology.
MAP2 is differentially phosphorylated in schizophrenia, altering its function
Authors: Grubisha M. J. , Sun X. , MacDonald M. L. , Garver M. , Sun Z. , Paris K. A. , Patel D. S. , DeGiosio R. A. , Lewis D. A. , Yates N. A. , Camacho C. , Homanics G. E. , Ding Y. , Sweet R. A. 
Published: February 2021

AbstractSchizophrenia (Sz) is a highly polygenic disorder, with common, rare, and structural variants each contributing only a small fraction of overall disease risk. Thus, there is a need to identify downstream points of convergence that can be targeted with therapeutics. Reduction of microtubule-associated protein 2 (MAP2) immunoreactivity (MAP2-IR) is present in individuals with Sz, despite no change in MAP2 protein levels. MAP2 is phosphorylated downstream of multiple receptors and kinases identified as Sz risk genes, altering its immunoreactivity and function. Using an unbiased phosphoproteomics approach, we quantified 18 MAP2 phosphopeptides, 9 of which were significantly altered in Sz subjects. Network analysis grouped MAP2 phosphopeptides into three modules, each with a distinct relationship to dendritic spine loss, synaptic protein levels, and clinical function in Sz subjects. We then investigated the most hyperphosphorylated site in Sz, phosphoserine1782 (pS1782). Computational modeling predicted phosphorylation of S1782 reduces binding of MAP2 to microtubules, which was confirmed experimentally. We generated a transgenic mouse containing a phosphomimetic mutation at S1782 (S1782E) and found reductions in basilar dendritic length and complexity along with reduced spine density. Because only a limited number of MAP2 interacting proteins have been previously identified, we combined co-immunoprecipitation with mass spectrometry to characterize the MAP2 interactome in mouse brain. The MAP2 interactome was enriched for proteins involved in protein translation. These associations were shown to be functional as overexpression of wild type and phosphomimetic MAP2 reduced protein synthesis in vitro. Finally, we found that Sz subjects with low MAP2-IR had reductions in the levels of synaptic proteins relative to nonpsychiatric control (NPC) subjects and to Sz subjects with normal and MAP2-IR, and this same pattern was recapitulated in S1782E mice. These findings suggest a new conceptual framework for Sz—that a large proportion of individuals have a “MAP2opathy”—in which MAP function is altered by phosphorylation, leading to impairments of neuronal structure, synaptic protein synthesis, and function.
Serotonin depletion amplifies distinct human social emotions as a function of individual differences in personality
Authors: Kanen Jonathan W. , Arntz Fréderique E. , Yellowlees Robyn , Cardinal Rudolf N. , Price Annabel , Christmas David M. , Apergis-Schoute Annemieke M. , Sahakian Barbara J. , Robbins Trevor W. 
Published: February 2021

AbstractSerotonin is involved in a wide range of mental capacities essential for navigating the social world, including emotion and impulse control. Much recent work on serotonin and social functioning has focused on decision-making. Here we investigated the influence of serotonin on human emotional reactions to social conflict. We used a novel computerised task that required mentally simulating social situations involving unjust harm and found that depleting the serotonin precursor tryptophan—in a double-blind randomised placebo-controlled design—enhanced emotional responses to the scenarios in a large sample of healthy volunteers (n = 73), and interacted with individual differences in trait personality to produce distinctive human emotions. Whereas guilt was preferentially elevated in highly empathic participants, annoyance was potentiated in those high in trait psychopathy, with medium to large effect sizes. Our findings show how individual differences in personality, when combined with fluctuations of serotonin, may produce diverse emotional phenotypes. This has implications for understanding vulnerability to psychopathology, determining who may be more sensitive to serotonin-modulating treatments, and casts new light on the functions of serotonin in emotional processing.
Study of micro-trichome (mict) reveals novel connections between transcriptional regulation of multicellular trichome development and specific metabolism in cucumber
Authors: Pan Jian , Zhang Leyu , Chen Guanqun , Wen Haifan , Chen Yue , Du Hui , Zhao Junlong , He Huanle , Lian Hongli , Chen Huiming , Shi Jianxin , Cai Run , Wang Gang , Pan Junsong 
Published: February 2021

AbstractTrichomes that cover the epidermis of aerial plant organs play multiple roles in plant protection. Compared with a unicellular trichome in model plants, the development mechanism of the multicellular trichome is largely unclear. Notably, variations in trichome development are often accompanied by defects in the biosynthesis of cuticle and secondary metabolites; however, major questions about the interactions between developmental differences in trichomes and defects in metabolic pathways remain unanswered. Here, we characterized the glabrous mutantmict/csgl1/cstbhvia combined metabolomic and transcriptomic analyses to extend our limited knowledge regarding multicellular trichome development and metabolism in cucumber.Mictwas found to be explicitly expressed within trichome cells. Transcriptomic analysis indicated that genes involved in flavonoid and cuticle metabolism are significantly downregulated inmictmutants. Further metabolomic analysis confirmed that flavonoids, lipids, and cuticle compositions are dramatically altered inmictmutants. Additional studies revealed thatMictregulates flavonoid, lipid, and cuticle biosynthesis by likely directly binding to downstream functional genes, such asCsTT4,CsFLS1,CsCER26, andCsMYB36. These findings suggest that specific metabolic pathways (e.g., flavonoids and cuticle components) are co-regulated byMictand provide insights into transcriptional regulation mechanisms of multicellular trichome development and its specific metabolism in cucumber.
The apple 14-3-3 protein MdGRF11 interacts with the BTB protein MdBT2 to regulate nitrate deficiency-induced anthocyanin accumulation
Authors: Ren Yi-Ran , Zhao Qiang , Yang Yu-Ying , Zhang Tian-En , Wang Xiao-Fei , You Chun-Xiang , Hao Yu-Jin 
Published: February 2021

AbstractNitrogen is an important factor that affects plant anthocyanin accumulation. In apple, the nitrate-responsive BTB/TAZ protein MdBT2 negatively regulates anthocyanin biosynthesis. In this study, we found that MdBT2 undergoes posttranslational modifications in response to nitrate deficiency. Yeast two-hybrid, protein pull-down, and bimolecular fluorescence complementation (BiFC) assays showed that MdBT2 interacts with MdGRF11, a 14-3-3 protein; 14-3-3 proteins compose a family of highly conserved phosphopeptide-binding proteins involved in multiple physiological and biological processes. The interaction of MdGRF11 negatively regulated the stability of the MdBT2 protein via a 26S proteasome-dependent pathway, which increased the abundance of MdMYB1 proteins to activate the expression of anthocyanin biosynthesis-related genes. Taken together, the results demonstrate the critical role of 14-3-3 proteins in the regulation of nitrate deficiency-induced anthocyanin accumulation. Our results provide a novel avenue to elucidate the mechanism underlying the induction of anthocyanin biosynthesis in response to nitrate deficiency.
Genetic characterization of an almond germplasm collection and volatilome profiling of raw and roasted kernels
Authors: Di Guardo M. , Farneti B. , Khomenko I. , Modica G. , Mosca A. , Distefano G. , Bianco L. , Troggio M. , Sottile F. , La Malfa S. , Biasioli F. , Gentile A. 
Published: February 2021

AbstractAlmond is appreciated for its nutraceutical value and for the aromatic profile of the kernels. In this work, an almond collection composed of 96 Sicilian accessions complemented with 10 widely cultivated cultivars was phenotyped for the production of volatile organic compounds using a proton-transfer time-of-flight mass spectrometer and genotyped using the Illumina Infinium®18 K Peach SNP array. The profiling of the aroma was carried out on fresh and roasted kernels enabling the detection of 150 mass peaks. Sixty eight, for the most related with sulfur compounds, furan containing compounds, and aldehydes formed by Strecker degradation, significantly increased during roasting, while the concentration of fifty-four mass peaks, for the most belonging to alcohols and terpenes, significantly decreased. Four hundred and seventy-one robust SNPs were selected and employed for population genetic studies. Structure analysis detected three subpopulations with the Sicilian accessions characterized by a different genetic stratification compared to those collected in Apulia (South Italy) and the International cultivars. The linkage-disequilibrium (LD) decay across the genome was equal tor2 = 0.083. Furthermore, a high level of collinearity (r2 = 0.96) between almond and peach was registered confirming the high synteny between the two genomes. A preliminary application of a genome-wide association analysis allowed the detection of significant marker-trait associations for 31 fresh and 33 roasted almond mass peaks respectively. An accurate genetic and phenotypic characterization of novel germplasm can represent a valuable tool for the set-up of marker-assisted selection of novel cultivars with an enhanced aromatic profile.
Breath can discriminate tuberculosis from other lower respiratory illness in children
Authors: Bobak Carly A. , Kang Lili , Workman Lesley , Bateman Lindy , Khan Mohammad S. , Prins Margaretha , May Lloyd , Franchina Flavio A. , Baard Cynthia , Nicol Mark P. , Zar Heather J. , Hill Jane E. 
Published: February 2021

AbstractPediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose symptoms improved while treated for TB. While more work is necessary to validate the utility of using patient breath to diagnose pediatric TB, it shows promise as a triage instrument or paired as part of an aggregate diagnostic scheme.
Cyclophosphamide exposure assessed with the biomarker phosphoramide mustard-hemoglobin in breast cancer patients: The TailorDose I study
Authors: Gernaat S. A. M. , von Stedingk H. , Hassan M. , Nilsson H. P. , Rodriguez-Wallberg K. A. , Hedayati E. , Rydberg P. 
Published: February 2021

AbstractCyclophosphamide (CPA) dosing by body surface area (BSA, m2) has been questioned as a predictor for individual drug exposure. This study investigated phosphoramide mustard-hemoglobin (PAM-Hb, pmol g−1Hb) as a biomarker of CPA exposure in 135 female breast cancer patients receiving CPA during three courses based on BSA: 500 mg/m2(C500 group, n = 67) or 600 mg/m2(C600 group, n = 68). The inter-individual difference was calculated for both groups by dividing the highest through the lowest PAM-Hb value of each course. The inter-occasion difference was calculated in percentage for each individual by dividing their PAM-Hb value through the group mean per course, and subsequently dividing this ratio of the latter through the previous course. A multivariable linear regression (MLR) was performed to identify factors that explained the variation of PAM-Hb. During the three courses, the inter-individual difference changed from 3.5 to 2.1 and the inter-occasion difference ranged between 13.3% and 11.9% in the C500 group. In the C600 group, the inter-individual difference changed from 2.7 to 2.9 and the inter-occasion difference ranged between 14.1% and 11.7%. The MLR including BSA, age, GFR, and albumin explained 17.1% of the variation of PAM-Hb and was significantly better then the model including only BSA. These factors should be considered when calculating the first dose of CPA for breast cancer patients.
A multilevel assessment of the social determinants associated with the late stage diagnosis of breast cancer
Authors: de Oliveira Nayara Priscila Dantas , de Camargo Cancela Marianna , Martins Luís Felipe Leite , de Souza Dyego Leandro Bezerra 
Published: February 2021

AbstractThe advanced-stage diagnosis of breast cancer reveals the inequalities associated with socioeconomic conditions and the offer of health services. This study analyzes the prevalence of advanced breast cancer and its relationship with individual and contextual socioeconomic indicators and offer of health service. A cross-sectional study is presented herein, on the assessment of malignant breast neoplasms in women diagnosed between 2006 and 2015 (n = 195,201). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A multilevel Poisson Regression was carried out with random intercept. The prevalence of advanced breast cancer diagnosis was 40.0%. Advanced staging was associated with younger age groups (PR 1.41), race/nonwhite (PR 1.13), lower education levels (PR 1.38), and public access to health services (PR 1.25). There was also an association with a low density of mammographic equipment (PR 1.08), and with low indices of local social inequality (PR 1.33) and human development (PR 0.80). This study maps and highlights the causes related to inequalities in the diagnosis of advanced breast cancer in Brazil, and presents essential data to reorient public policies and health-related actions to strengthen the control of breast cancer in Brazil.
Value of Patlak Ki images from 18F-FDG-PET/CT for evaluation of the relationships between disease activity and clinical events in cardiac sarcoidosis
Authors: Nakajo Masatoyo , Ojima Satoko , Kawakami Hirofumi , Tani Atsushi , Hirayama Akira , Jinguji Megumi , Kubozono Takuro , Ohishi Mitsuru , Yoshiura Takashi 
Published: February 2021

AbstractThe association between 18F-fluorodeoxyglucose (18F-FDG) myocardial uptake and clinical presentations in cardiac sarcoidosis (CS) has not yet been clarified. The Patlak slope, Ki, which represents the rate of 18F-FDG uptake is a quantitative index of 18F-FDG metabolism. This study aims to investigate the usefulness of standardized uptake value (SUV) and Patlak Ki images (Ki images) extracted from dynamic 18F-FDG-PET/CT for evaluating the risk of clinical events (CEs) in CS. The SUV and Ki myocardial images were generated from 30 dynamic 18F-FDG-PET/CT scans of 21 CS patients. The SUV and Ki images both were rated as positive in 19 scans and negative in 11 scans with the same incidence of CEs which were significantly higher in positive than negative scans [cardiac dysfunction: 78.9% (15/19) vs. 27.2% (3/11); arrhythmic events: 65.5% (10/19) vs. 0% (0/11)]. In 19 positive scans, the three Ki parameters (Ki max, Ki mean and Ki volume) were significantly higher in scans for patients with arrhythmic events than in those without. Logistic regression analysis showed that the Ki volume alone was significantly associated with the risk of arrhythmic events. Our study suggests that Ki images may add value to SUV images for evaluating the risk of CEs in CS patients.
Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans
Authors: Diez Veronica , Traikov Sofia , Schmeisser Kathrin , Adhikari Akshay Kumar Das , Kurzchalia Teymuras Vakhtang 
Published: February 2021

AbstractUpon exposure to excessive reactive oxygen species (ROS), organismal survival depends on the strength of the endogenous antioxidant defense barriers that prevent mitochondrial and cellular deterioration. Previously, we showed that glycolic acid can restore the mitochondrial membrane potential of C. elegans treated with paraquat, an oxidant that produces superoxide and other ROS species, including hydrogen peroxide. Here, we demonstrate that glycolate fully suppresses the deleterious effects of peroxide on mitochondrial activity and growth in worms. This endogenous compound acts by entering serine/glycine metabolism. In this way, conversion of glycolate into glycine and serine ameliorates the drastically decreased NADPH/NADP+ and GSH/GSSG ratios induced by H2O2 treatment. Our results reveal the central role of serine/glycine metabolism as a major provider of reducing equivalents to maintain cellular antioxidant systems and the fundamental function of glycolate as a natural antioxidant that improves cell fitness and survival.
Vapor selenization produced Bi2Se3 nanoparticles in carbon fiber 3D network as binder-free anode for flexible lithium-ion batteries
Authors: Qu Hong-Qing , Yin Hong , Wang Ya-Long , Fan Cheng , Hui Kwun Nam , Li Chong , Zhu Ming-Qiang 
Published: February 2021

Bi2Se3 nanoparticles embedded carbon fibers network prepared by electrospinning and selenization in vacuum delivered a large capacity of 443 mA h g-1 after 260 cycles at 100 mA g-1 and a high rate performance as a binder-free flexible anode for LIBs.
Merging radical-polar crossover/cycloisomerization processes: access to polyfunctional furans enabled by metallaphotoredox catalysis
Authors: Liu Yongjun , Luo Wenping , Xia Tingting , Fang Yewen , Du Chan , Jin Xiaoping , Li Yan , Zhang Li , Lei Wan , Wu Hao 
Published: February 2021

Metallaphotoredox catalysis for furan synthesis: The cyclisation of yne-enones proceeds smoothly via consecutive reductive radical-polar crossover and cycloisomerization processes enabled by cooperative photoredox-neutral and copper catalysis.
Untergrenzen = Obergrenzen?
Authors: Bechtel Peter 
Published: February 2021

ZusammenfassungPünktlich zu Beginn des neuen Jahres werden uns für vier weitere Bereiche der Personaluntergrenzen beschert. Sinnvoll oder eine schöne Bescherung? Mehr dazu im Kommentar von Peter Bechtel, dem Vorsitzenden im Bundesverband Pflegemanagement.
Competition, Productive Capabilities and Structural Transformation in South Africa
Authors: Mondliwa Pamela , Goga Sumayya , Roberts Simon 
Published: February 2021

AbstractCompetition law has been promoted across developing countries as part of a market liberalisation package which is premised on a neo-classical model of competition, privileging static allocative efficiency and largely ignoring production. This article critiques this approach through an assessment of its application in South Africa where substantial weight was given to competition law. Building on the critical assessment, the article proposes an alternative framework based on the conception of ‘optimal competition’ of Amsden and Singh (The optimal degree of competition and dynamic efficiency in Japan and Korea. Eur Econ Rev 38:940–951, 1994). It does this through assessing the relationship between competitive rivalry, productive investment and the development of capabilities in two key industry groupings in South Africa, metals and machinery, and plastics and chemicals. We argue that the failure to develop diversified production capabilities in South Africa reflects the entrenched incumbent firm advantages and the lack of a coordinated policy agenda which proceeds from a recognition of economic power and the need to reshape markets to alter competitive rivalry. An optimal competition framework allows analysis of dynamic rivalry and capabilities development.