bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review and narrative synthesis of data-driven studies in schizophrenia symptoms and cognitive deficits
Authors: Habtewold Tesfa Dejenie , Rodijk Lyan H. , Liemburg Edith J. , Sidorenkov Grigory , Boezen H. Marike , Bruggeman Richard , Alizadeh Behrooz Z.
Published: July 2020

To tackle the phenotypic heterogeneity of schizophrenia, data-driven methods are often applied to identify subtypes of its symptoms and cognitive deficits. However, a systematic review on this topic is lacking. The objective of this review was to summarize the evidence obtained from longitudinal and cross-sectional data-driven studies in positive and negative symptoms and cognitive deficits in patients with schizophrenia spectrum disorders, their unaffected siblings and healthy controls or individuals from general population. Additionally, we aimed to highlight methodological gaps across studies and point out future directions to optimize the translatability of evidence from data-driven studies. A systematic review was performed through searching PsycINFO, PubMed, PsycTESTS, PsycARTICLES, SCOPUS, EMBASE and Web of Science electronic databases. Both longitudinal and cross-sectional studies published from 2008 to 2019, which reported at least two statistically derived clusters or trajectories were included. Two reviewers independently screened and extracted the data. In this review, 53 studies (19 longitudinal and 34 cross-sectional) that conducted among 17,822 patients, 8729 unaffected siblings and 5520 controls or general population were included. Most longitudinal studies found four trajectories that characterized by stability, progressive deterioration, relapsing and progressive amelioration of symptoms and cognitive function. Cross-sectional studies commonly identified three clusters with low, intermediate (mixed) and high psychotic symptoms and cognitive profiles. Moreover, identified subgroups were predicted by numerous genetic, sociodemographic and clinical factors. Our findings indicate that schizophrenia symptoms and cognitive deficits are heterogeneous, although methodological limitations across studies are observed. Identified clusters and trajectories along with their predictors may be used to base the implementation of personalized treatment and develop a risk prediction model for high-risk individuals with prodromal symptoms.
Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin
Authors: Velletri Tania , Huang Yin , Wang Yu , Li Qing , Hu Mingyuan , Xie Ningxia , Yang Qian , Chen Xiaodong , Chen Qing , Shou Peishun , Gan Yurun , Candi Eleonora , Annicchiarico-Petruzzelli Margherita , Agostini Massimiliano , Yang Huilin , Melino Gerry , Shi Yufang , Wang Ying
Published: July 2020

p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/−, and p53−/− mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling.
Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
Authors: Chen Xingdong , Gole Jeffrey , Gore Athurva , He Qiye , Lu Ming , Min Jun , Yuan Ziyu , Yang Xiaorong , Jiang Yanfeng , Zhang Tiejun , Suo Chen , Li Xiaojie , Cheng Lei , Zhang Zhenhua , Niu Hongyu , Li Zhe , Xie Zhen , Shi Han , Zhang Xiang , Fan Min , Wang Xiaofeng , Yang Yajun , Dang Justin , McConnell Catie , Zhang Juan , Wang Jiucun , Yu Shunzhang , Ye Weimin , Gao Yuan , Zhang Kun , Liu Rui , Jin Li
Published: July 2020

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target
Authors: Yu Jiao-jiao , Zhou Dan-dan , Yang Xiao-xiao , Cui Bing , Tan Feng-wei , Wang Junjian , Li Ke , Shang Shuang , Zhang Cheng , Lv Xiao-xi , Zhang Xiao-wei , Liu Shan-shan , Yu Jin-mei , Wang Feng , Huang Bo , Hua Fang , Hu Zhuo-Wei
Published: July 2020

High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC.
Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth
Authors: Schiffmann L. M. , Werthenbach J. P. , Heintges-Kleinhofer F. , Seeger J. M. , Fritsch M. , Günther S. D. , Willenborg S. , Brodesser S. , Lucas C. , Jüngst C. , Albert M. C. , Schorn F. , Witt A. , Moraes C. T. , Bruns C. J. , Pasparakis M. , Krönke M. , Eming S. A. , Coutelle O. , Kashkar H.
Published: July 2020

The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.
Majority sensing in synthetic microbial consortia
Authors: Alnahhas Razan N. , Sadeghpour Mehdi , Chen Ye , Frey Alexis A. , Ott William , Josić Krešimir , Bennett Matthew R.
Published: July 2020

As synthetic biocircuits become more complex, distributing computations within multi-strain microbial consortia becomes increasingly beneficial. However, designing distributed circuits that respond predictably to variation in consortium composition remains a challenge. Here we develop a two-strain gene circuit that senses and responds to which strain is in the majority. This involves a co-repressive system in which each strain produces a signaling molecule that signals the other strain to down-regulate production of its own, orthogonal signaling molecule. This co-repressive consortium links gene expression to ratio of the strains rather than population size. Further, we control the cross-over point for majority via external induction. We elucidate the mechanisms driving these dynamics by developing a mathematical model that captures consortia response as strain fractions and external induction are varied. These results show that simple gene circuits can be used within multicellular synthetic systems to sense and respond to the state of the population.
Large positive magnetoresistance and Dzyaloshinskii–Moriya interaction in CrSi driven by Cr 3d localization
Authors: Banik Soma , Chattopadhyay M. K. , Tripathi Shilpa , Rawat R. , Jha S. N.
Published: July 2020

Spin chiral systems with Dzyaloshinskii–Moriya (DM) interaction due to broken inversion symmetry are extensively studied for their technological applications in spintronics and thermoelectrics. Here, we report an experimental study on the magnetization, magnetoresistance (MR) and electronic structure of a non-centrosymmetric compound CrSi with B20 crystal structure. Both magnetization andMRshows competing ferromagnetic (FM) and antiferromagnetic (AFM) correlations with theFMcorrelations being comparatively weaker indicating the presence ofDMinteraction in CrSi. A large positiveMR$$\sim \,25\%$$∼25%obtained at 5 K and 5 T magnetic field arises due to the strongerAFMcorrelations. Resonant photoemission shows both localized and itinerant nature of Cr 3delectrons to be present in CrSi and this is supported by the temperature dependence of magnetic susceptibility. Drastic variation in the density of states along with valence band broadening at low temperature indicates the increase in hybridization between Cr 3dand Si 3s–3pstates which enhances the localization effects. Spin polarized itinerant Cr 3delectrons give rise toAFMspin density wave in CrSi. Magnetic interaction between the localized and itinerant Cr 3delectrons are found to be crucial for realizing DM interaction in this system. Spectral density of states derived from high resolution valence band measurements provides evidence of electronic topological transition in CrSi. Large density of polarized itinerant electrons which varies with temperature and the large positiveMRwithAFMcorrelations suggests CrSi as a potential candidate for both the thermoelectric and spintronics applications.
Rapid, precise, and reliable measurement of delay discounting using a Bayesian learning algorithm
Authors: Ahn Woo-Young , Gu Hairong , Shen Yitong , Haines Nathaniel , Hahn Hunter A. , Teater Julie E. , Myung Jay I. , Pitt Mark A.
Published: July 2020

Machine learning has the potential to facilitate the development of computational methods that improve the measurement of cognitive and mental functioning. In three populations (college students, patients with a substance use disorder, and Amazon Mechanical Turk workers), we evaluated one such method, Bayesian adaptive design optimization (ADO), in the area of delay discounting by comparing its test–retest reliability, precision, and efficiency with that of a conventional staircase method. In all three populations tested, the results showed that ADO led to 0.95 or higher test–retest reliability of the discounting rate within 10–20 trials (under 1–2 min of testing), captured approximately 10% more variance in test–retest reliability, was 3–5 times more precise, and was 3–8 times more efficient than the staircase method. The ADO methodology provides efficient and precise protocols for measuring individual differences in delay discounting.
Blueberry red ringspot virus genomes from Florida inferred through analysis of blueberry root transcriptomes
Authors: Saad N. , Alcalá-Briseño R. I. , Polston J. E. , Olmstead J. W. , Varsani A. , Harmon P. F.
Published: July 2020

A growing number of metagenomics-based approaches have been used for the discovery of viruses in insects, cultivated plants, and water in agricultural production systems. In this study, sixteen blueberry root transcriptomes from eight clonally propagated blueberry plants of cultivar ‘Emerald’ (interspecific hybrid of Vaccinium corymbosum and V. darrowi) generated as part of a separate study on varietal tolerance to soil salinity were analyzed for plant viral sequences. The objective was to determine if the asymptomatic plants harbored the latent blueberry red ringspot virus (BRRV) in their roots. The only currently known mechanism of transmission of BRRV is through vegetative propagation; however, the virus can remain latent for years with some plants of ‘Emerald’ never developing red ringspot symptoms. Bioinformatic analyses of ‘Emerald’ transcriptomes using de novo assembly and reference-based mapping approaches yielded eight complete viral genomes of BRRV (genus Soymovirus, family Caulimoviridae). Validation in vitro by PCR confirmed the presence of BRRV in 100% of the ‘Emerald’ root samples. Sequence and phylogenetic analyses showed 94% to 97% nucleotide identity between BRRV genomes from Florida and sequences from Czech Republic, Japan, Poland, Slovenia, and the United States. Taken together, this study documented the first detection of a complete BRRV genome from roots of asymptomatic blueberry plants and in Florida through in silico analysis of plant transcriptomes.
Relationship of preseismic, coseismic, and postseismic fault ruptures of two large interplate aftershocks of the 2011 Tohoku earthquake with slow-earthquake activity
Authors: Kubo Hisahiko , Nishikawa Tomoaki
Published: July 2020

To improve our understanding of the interactions between regular and slow earthquakes along the Japan Trench, we investigated the spatial relationship of slow-earthquake activity with the preseismic, coseismic, and postseismic fault ruptures of interplate earthquakes off the Iwate and Ibaraki coasts, Japan, including two large interplate aftershocks of the 2011 Tohoku earthquake: the 2011 off Iwate earthquake (MJMA 7.4) and the 2011 off Ibaraki earthquake (MJMA 7.6). We found that the coseismic ruptures of these earthquakes did not overlap with the active areas of slow earthquakes, while their foreshocks and aftershocks occurred in slow-earthquake-prone areas. Moreover, the 2011 off Iwate earthquake and the previous M7-class events shared common fault rupture characteristics: coseismic rupture occurred in a common asperity area, and afterslip with many aftershocks was triggered in the active area of slow earthquakes. Off the Ibaraki coast, tremor activity on a subducting seamount located updip of the coseismic rupture of the 2011 off Ibaraki earthquake implies that the seamount acted as a soft barrier to the coseismic rupture of the 2011 off Ibaraki earthquake. This study demonstrates that large earthquakes off the Iwate and Ibaraki coasts feature similar rupture behaviors, spatially complementary distributions of coseismic ruptures with slow-earthquake activity and foreshock and aftershock activities within and around slow-earthquake-prone areas. This information is useful in considering future large earthquakes along the Japan Trench.
The food contaminant deoxynivalenol provokes metabolic impairments resulting in non-alcoholic fatty liver (NAFL) in mice
Authors: Barbouche Rym , Gaigé Stéphanie , Airault Coraline , Poirot Kevin , Dallaporta Michel , Troadec Jean-Denis , Abysique Anne
Published: July 2020

The ribotoxin deoxynivalenol (DON) is a trichothecene found on cereals responsible for mycotoxicosis in both humans and farm animals. DON toxicity is characterized by reduced food intake, diminished nutritional efficiency and immunologic effects. The present study was designed to further characterize the alterations in energy metabolism induced by DON intoxication. We demonstrated that acute DON intoxication triggered liver steatosis associated with an altered expression of genes related to lipids oxidation, lipogenesis and lipolysis. This steatosis was concomitant to anorexia, hypoglycemia and a paradoxical transient insulin release. DON treatment resulted also in stimulation of central autonomic network regulating sympathetic outflow and adrenaline and glucocorticoids secretion. Furthermore, an increased expression of genes linked to inflammation and reticulum endoplasmic stress was observed in the liver of DON-treated mice. Finally, we propose that lipids mobilization from adipose tissues (AT) induced by DON intoxication drives hepatic steatosis since (1) genes encoding lipolytic enzymes were up-regulated in AT and (2) plasma concentration of triglycerides (TGs) and non-esterified fatty acids were increased during DON intoxication. Altogether, these data demonstrate that DON induced hormonal and metabolic dysregulations associated with a spectrum of hepatic abnormalities, evocative of a non-alcoholic fatty liver disease.
Rich essential properties of Si-doped graphene
Authors: Nguyen Duy Khanh , Tran Ngoc Thanh Thuy , Chiu Yu-Huang , Gumbs Godfrey , Lin Ming-Fa
Published: July 2020

The diverse structural and electronic properties of the Si-adsorbed and -substituted monolayer graphene systems are studied by a complete theoretical framework under the first-principles calculations, including the adatom-diversified geometric structures, the Si- and C-dominated energy bands, the spatial charge densities, variations in the spatial charge densities and the atom- and orbital-projected density of states (DOSs). These critical physical quantities are unified together to display a distinct physical and chemical picture in the studying systems. Under the Si-adsorption and Si-substitution effects, the planar geometric structures are still remained mainly owing to the very strong C–C and Si–C bonds on the honeycomb lattices, respectively. The Si-adsorption cases can create free carriers, while the finite- or zero-gap semiconducting behaviors are revealed in various Si-substitution configurations. The developed theoretical framework can be fully generalized to other emergent layered materials. The Si-doped graphene systems might be a highly promising anode material in the lithium-ion battery owing to its rich potential properties.
Effects of vegetation restoration and environmental factors on understory vascular plants in a typical karst ecosystem in southern China
Authors: Ou Zhiyang , Pang Shilong , He Qinfei , Peng Yuhua , Huang Xiaorong , Shen Wenhui
Published: July 2020

Understory vegetation is an important component in most forest ecosystems. It is very important for soil and water conservation in karst region, study on understory will provide valuable information for understanding the interaction mechanism between understory flora and karst environment. Thirty-two plots were sampled in three vegetation types along with a restoration gradient (shrubland, forest–shrub transition, and mixed-species broadleaf forest) in typical karst mountains in Southwest Guangxi, China. Overstory trees, understory vascular plants, soil nutrients, and topographic factors were recorded in each 400-m2 plot. Multivariate statistics were used, including the multi-response permutation procedure (MRPP), indicator species analysis, and canonical correlation analysis (CCA). MRPP showed understory species composition significantly differed among the three vegetation types, with the greatest difference between the shrubland and the mixed forest. Twenty-one understory species were identified as significant indicator species, with 13 species being identified as indicators of the shrubland, two of forest–shrub transition, and six of the mixed forest. Light-demanding herbaceous seed plants were common in shrubland, while shade-tolerant calcicole assembled under the mixed forest. Forward selection of CCA ordination revealed that understory plant distribution was most strongly influenced by elevation, followed by soil pH, the concentration of total potassium and exchangeable calcium, slope aspect, slope degree, and the concentration of available potassium. The result reveals that vegetation types affect understory species composition by modifying understory environments. Elevation affects the spatial distribution of vegetation and soil factors, and then the understory plants. Meanwhile, soil Ca content also plays a key role in the understory species distribution. Understory diversity increased with increasing canopy structure complexity from shrubland to mixed-species forest. Thus, it is necessary to take measures to promote natural vegetation restoration and to protect the mixed forests in degraded karst areas.
Cortical network responses map onto data-driven features that capture visual semantics of movie fragments
Authors: Berezutskaya Julia , Freudenburg Zachary V. , Ambrogioni Luca , Güçlü Umut , van Gerven Marcel A. J. , Ramsey Nick F.
Published: July 2020

Research on how the human brain extracts meaning from sensory input relies in principle on methodological reductionism. In the present study, we adopt a more holistic approach by modeling the cortical responses to semantic information that was extracted from the visual stream of a feature film, employing artificial neural network models. Advances in both computer vision and natural language processing were utilized to extract the semantic representations from the film by combining perceptual and linguistic information. We tested whether these representations were useful in studying the human brain data. To this end, we collected electrocorticography responses to a short movie from 37 subjects and fitted their cortical patterns across multiple regions using the semantic components extracted from film frames. We found that individual semantic components reflected fundamental semantic distinctions in the visual input, such as presence or absence of people, human movement, landscape scenes, human faces, etc. Moreover, each semantic component mapped onto a distinct functional cortical network involving high-level cognitive regions in occipitotemporal, frontal and parietal cortices. The present work demonstrates the potential of the data-driven methods from information processing fields to explain patterns of cortical responses, and contributes to the overall discussion about the encoding of high-level perceptual information in the human brain.
Genetic architecture of complex traits and disease risk predictors
Authors: Yong Soke Yuen , Raben Timothy G. , Lello Louis , Hsu Stephen D. H.
Published: July 2020

Genomic prediction of complex human traits (e.g., height, cognitive ability, bone density) and disease risks (e.g., breast cancer, diabetes, heart disease, atrial fibrillation) has advanced considerably in recent years. Using data from the UK Biobank, predictors have been constructed using penalized algorithms that favor sparsity: i.e., which use as few genetic variants as possible. We analyze the specific genetic variants (SNPs) utilized in these predictors, which can vary from dozens to as many as thirty thousand. We find that the fraction of SNPs in or near genic regions varies widely by phenotype. For the majority of disease conditions studied, a large amount of the variance is accounted for by SNPs outside of coding regions. The state of these SNPs cannot be determined from exome-sequencing data. This suggests that exome data alone will miss much of the heritability for these traits—i.e., existing PRS cannot be computed from exome data alone. We also study the fraction of SNPs and of variance that is in common between pairs of predictors. The DNA regions used in disease risk predictors so far constructed seem to be largely disjoint (with a few interesting exceptions), suggesting that individual genetic disease risks are largely uncorrelated. It seems possible in theory for an individual to be a low-risk outlier in all conditions simultaneously.
Medication adherence and its determinants in patients after myocardial infarction
Authors: Pietrzykowski Łukasz , Michalski Piotr , Kosobucka Agata , Kasprzak Michał , Fabiszak Tomasz , Stolarek Wioleta , Siller-Matula Jolanta M. , Kubica Aldona
Published: July 2020

Non-adherence to prescribed medication is a serious limitation of long-term treatment in patients after myocardial infarction (MI), which can be associated with medical, social and economical consequences. Improvement of medication adherence has been shown to be a challenge for healthcare providers. The aim of this study was to evaluate changes in medication adherence and variability of adherence determinants during follow-up in patients after MI. A single-center, cohort observational study was conducted in 225 post-MI patients treated with primary coronary intervention (PCI) (27% women and 73% men) aged 30–91 years. Adherence was defined as availability of evaluated drugs within 1-year after discharge from hospital, based on completed prescriptions data obtained from the National Health Fund. The analysis of therapeutic plan realization (adherence to medication prescribed at discharge from hospital) embraced only reimbursed drugs: ACEIs (ramipril, perindopril), P2Y12 receptor inhibitors (clopidogrel) and statins (atorvastatin, simvastatin, rosuvastatin). Sufficient adherence was defined as ≥ 80%. During 1-year follow-up, adherence for all three drug classes was 64 ± 25%, with 67 ± 32% for ACEIs, 62 ± 34% for P2Y12 receptor inhibitor and 64 ± 32% for statins. A gradual decline in adherence was observed from 65% ± 26% in the first quarter of follow-up to 51% ± 34% in the last quarter of follow-up (p < 0.00001). Sufficient adherence for all drugs classes was found only in 29% of patients throughout the whole follow-up period (44% for ACEI, 36% for P2Y12 receptor inhibitor and 41% for statins). According to a multivariate analysis, age, prior CABG, level of education, place of residence, economic status and marital status were independent predictors of drug adherence. Whereas patients > 65 years and having a history of prior CABG more often had an insufficient adherence to drugs, married and hypertensive patients, city inhabitants and patients with higher education tended to have a sufficient drug adherence. Adherence to pharmacotherapy after myocardial infarction decreases over time in a similar manner for all pivotal groups of drugs prescribed after MI. A number of socioeconomic and clinical factors have been identified to affect medication adherence over time.
Transcriptome analysis of feather follicles reveals candidate genes and pathways associated with pheomelanin pigmentation in chickens
Authors: Zheng Xiaotong , Zhang Bo , Zhang Yawen , Zhong Haian , Nie Ruixue , Li Junying , Zhang Hao , Wu Changxin
Published: July 2020

Yellow plumage is common in chickens, especially in breeds such as the Huiyang Bearded chicken, which is indigenous to China. We evaluated plumage colour distribution in F1, F2, and F3 populations of an Huiyang Bearded chicken × White Leghorn chicken cross, the heredity of the yellow plumage trait was distinguished from that of the gold plumage and other known plumage colours. Microscopic analysis of the feather follicles indicated that pheomelanin particles were formed in yellow but not in white feathers. To screen genes related to formation of the pheomelanin particles, we generated transcriptome data from yellow and white feather follicles from 7- and 11-week-old F3 chickens using RNA-seq. We identified 27 differentially expressed genes (DEGs) when comparing the yellow and white feather follicles. These DEGs were enriched in the Gene Ontology classes ‘melanosome’ and ‘melanosome organization’ related to the pigmentation process. Down-regulation of TYRP1, DCT, PMEL, MLANA, and HPGDS, verified using quantitative reverse transcription PCR, may lead to reduced eumelanin and increased pheomelanin synthesis in yellow plumage. Owing to the presence of the Dominant white locus, both white and yellow plumage lack eumelanin, and white feathers showed no pigments. Our results provide an understanding of yellow plumage formation in chickens.
Characterization of Gromphadorhina coquereliana hemolymph under cold stress
Authors: Lubawy Jan , Słocińska Małgorzata
Published: July 2020

Low temperatures in nature occur together with desiccation conditions, causing changes in metabolic pathways and cellular dehydration, affecting hemolymph volume, water content and ion homeostasis. Although some research has been conducted on the effect of low temperature onGromphadorhina coquereliana, showing that it can survive exposures to cold or even freezing, no one has studied the effect of cold on the hemolymph volume and the immune response of this cockroach. Here, we investigated the effect of low temperature (4 °C) on the abovementioned parameters, hemocyte morphology and total number. Cold stress affected hemocytes and the immune response, but not hemolymph volume. After stress, the number of circulating hemocytes decreased by 44.7%, but the ratio of apoptotic cells did not differ significantly between stressed and control individuals: 8.06% and 7.18%, respectively. The number of phagocyting hemocytes decreased by 16.66%, the hemocyte morphology drastically changed, and the F-actin cytoskeleton differed substantially in cold-stressed insects compared to control insects. Moreover, the surface area of the cells increased from 393.69 µm2in the control to 458.38 µm2in cold-treated animals. Together, our results show the links between cold stress and the cellular immune response, which probably results in the survival capability of this species.
The closed eye harbours a unique microbiome in dry eye disease
Authors: Willis Kent A. , Postnikoff Cameron K. , Freeman Amelia , Rezonzew Gabriel , Nichols Kelly , Gaggar Amit , Lal Charitharth V.
Published: July 2020

Dry eye affects millions of individuals. In experimental models, dry eye disease is associated with T helper cell 17-mediated inflammation of the ocular surface that may cause persistent damage to the corneal epithelium. However, the initiating and perpetuating factors associated with chronic inflammation of the ocular surface remain unclear. The ocular microbiota alters ocular surface inflammation and may influence dry eye disease development and progression. Here, we collected serial samples of tears on awakening from sleep, closed eye tears, during a randomized clinical trial of a non-pharmaceutical dry eye therapy and used 16S rRNA metabarcoding to characterize the microbiome. We show the closed dry eye microbiome is distinct from the healthy closed eye microbiome, and that the microbiome remains distinct despite daily saline eye wash upon awakening. The ocular microbiome was described only recently, and this report implicates a distinct microbiome in ocular disease development. Our findings suggest an interplay between microbial commensals and inflammation on the ocular surface. This information may inform future studies of the pathophysiological mechanisms of dry eye disease.
Design of thienopyranone-based BET inhibitors that bind multiple synthetic lethality targets
Authors: Vann Kendra R. , Pal Dhananjaya , Morales Guillermo A. , Burgoyne Adam M. , Durden Donald L. , Kutateladze Tatiana G.
Published: July 2020

Development of small molecule compounds that target several cancer drivers has shown great therapeutic potential. Here, we developed a new generation of highly potent thienopyranone (TP)-based inhibitors for the BET bromodomains (BDs) of the transcriptional regulator BRD4 that have the ability to simultaneously bind to phosphatidylinositol-3 kinase (PI3K) and/or cyclin-dependent kinases 4/6 (CDK4/6). Analysis of the crystal structures of the complexes, NMR titration experiments and IC50 measurements reveal the molecular basis underlying the inhibitory effects and selectivity of these compounds toward BDs of BRD4. The inhibitors show robust cytotoxic effects in multiple cancer cell lines and induce cell-cycle arrest and apoptosis. We further demonstrate that concurrent disruption of the acetyllysine binding function of BRD4 and the kinase activities of PI3K and CDK4/6 by the TP inhibitor improves efficacy in several cancer models. Together, these findings provide further compelling evidence that these multi-action inhibitors are efficacious and more potent than single inhibitory chemotypes.
The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses
Authors: Montes-Fernández Mª Angeles , Pérez-Villegas Eva Mª , Garcia-Gonzalo Francesc R. , Pedrazza Leonardo , Rosa Jose Luis , de Toledo Guillermo Alvarez , Armengol José A.
Published: July 2020

HERC1 is a ubiquitin ligase protein, which, when mutated, induces several malformations and intellectual disability in humans. The animal model of HERC1 mutation is the mouse tambaleante characterized by: (1) overproduction of the protein; (2) cerebellar Purkinje cells death by autophagy; (3) dysregulation of autophagy in spinal cord motor neurons, and CA3 and neocortical pyramidal neurons; (4) impairment of associative learning, linked to altered spinogenesis and absence of LTP in the lateral amygdala; and, (5) motor impairment due to delayed action potential transmission, decrease synaptic transmission efficiency and altered myelination in the peripheral nervous system. To investigate the putative role of HERC1 in the presynaptic dynamics we have performed a series of experiments in cultured tambaleante hippocampal neurons by using transmission electron microscopy, FM1-43 destaining and immunocytochemistry. Our results show: (1) a decrease in the number of synaptic vesicles; (2) reduced active zones; (3) less clathrin immunoreactivity and less presynaptic endings over the hippocampal main dendritic trees; which contrast with (4) a greater number of endosomes and autophagosomes in the presynaptic endings of the tambaleante neurons relative to control ones. Altogether these results show an important role of HERC1 in the regulation of presynaptic membrane dynamics.
Robust performance of deep learning for distinguishing glioblastoma from single brain metastasis using radiomic features: model development and validation
Authors: Bae Sohi , An Chansik , Ahn Sung Soo , Kim Hwiyoung , Han Kyunghwa , Kim Sang Wook , Park Ji Eun , Kim Ho Sung , Lee Seung-Koo
Published: July 2020

We evaluated the diagnostic performance and generalizability of traditional machine learning and deep learning models for distinguishing glioblastoma from single brain metastasis using radiomics. The training and external validation cohorts comprised 166 (109 glioblastomas and 57 metastases) and 82 (50 glioblastomas and 32 metastases) patients, respectively. Two-hundred-and-sixty-five radiomic features were extracted from semiautomatically segmented regions on contrast-enhancing and peritumoral T2 hyperintense masks and used as input data. For each of a deep neural network (DNN) and seven traditional machine learning classifiers combined with one of five feature selection methods, hyperparameters were optimized through tenfold cross-validation in the training cohort. The diagnostic performance of the optimized models and two neuroradiologists was tested in the validation cohort for distinguishing glioblastoma from metastasis. In the external validation, DNN showed the highest diagnostic performance, with an area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.956 (95% confidence interval [CI], 0.918–0.990), 90.6% (95% CI, 80.5–100), 88.0% (95% CI, 79.0–97.0), and 89.0% (95% CI, 82.3–95.8), respectively, compared to the best-performing traditional machine learning model (adaptive boosting combined with tree-based feature selection; AUC, 0.890 (95% CI, 0.823–0.947)) and human readers (AUC, 0.774 [95% CI, 0.685–0.852] and 0.904 [95% CI, 0.852–0.951]). The results demonstrated deep learning using radiomic features can be useful for distinguishing glioblastoma from metastasis with good generalizability.
Prognostic value of systemic inflammatory markers for oral cancer patients based on the 8th edition of AJCC staging system
Authors: Lee Sanghoon , Kim Dong Wook , Kwon Sunmo , Kim Hyung Jun , Cha In-Ho , Nam Woong
Published: July 2020

It has been recognized that systemic inflammatory markers (SIMs) are associated with patient survival in various types of cancer. This study aimed to determine the optimal cut-off values, and to evaluate the prognostic performance of SIMs for oral squamous cell carcinoma (OSCC) within the framework of the American Joint Committee of Cancer (AJCC) cancer staging manual, 8th edition. Records were collected for a total 291 patients who had had a peripheral blood test within 1 week prior to surgery and had undergone the surgical resection of OSCC in a single institution between 2005 and 2018. The cut-off values of SIMs were obtained, and the survival analyses for overall survival (OS) and disease-free survival (DFS) were performed. Multivariate analyses incorporating other clinicopathologic factors were performed to verify the independent risk factors for survival. The cut-off values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were 2.23, 135.14 for OS and 2.16, 131.07 for DFS, respectively, demonstrating a significant association for OS and DFS in OSCC. AJCC pathologic regional lymph node category (pN) (P < 0.001), perineural invasion (PNI) (P < 0.001) and NLR (P < 0.001) were independent predictors for OS. Meanwhile, for DFS, AJCC pN (P = 0.018) and NLR (P = 0.015) were shown to be independent predictors. Before the curative surgery, NLR and PLR could be auxiliary parameters for OS and DFS in OSCC. And based on the 8th edition of AJCC staging system, elevated NLR will be a potential indicator of the worse OS or DFS along with pN or PNI in OSCC.
Effects of add-on transcranial direct current stimulation on pain in Korean patients with fibromyalgia
Authors: Kang Ji-Hyoun , Choi Sung-Eun , Park Dong-Jin , Xu Haimuzi , Lee Jung-Kil , Lee Shin-Seok
Published: July 2020

Despite promising preliminary results of transcranial direct current stimulation (tDCS) treatment in patients with fibromyalgia (FM), several issues need to be addressed, including its limited efficacy, low response rate, and poor tolerability. We investigated the efficacy and safety of tDCS as an add-on treatment for chronic pain in Korean patients with FM. This study enrolled 46 patients who were refractory to pain medications from May 2016 to February 2017. A conventional tDCS device was used to supply 2 mA of current for 20 min on five consecutive days. The primary end-point was a change in visual analogue scale (VAS) pain score at the end of treatment; secondary end-points included changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Medical Outcomes Study Sleep Scale (MOS-SS) scores. After tDCS, 46 patients showed clinical improvements in VAS pain scores on days 6, 13, and 36 compared with day 0 (p < 0.001). Improvement in FIQ was seen on day 13. The BDI decreased significantly on days 6 and 36, and BFI improved significantly on days 6 and 13. There were no significant improvements in STAI-I, STAI-II, and MOS-SS scores after tDCS. No serious adverse events were observed. Our results suggest that tDCS can result in significant pain relief in FM patients and may be an effective add-on treatment.
Publisher Correction: Differences in the intrinsic chondrogenic potential of equine umbilical cord matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration
Authors: Rakic Rodolphe , Bourdon Bastien , Demoor Magali , Maddens Stéphane , Saulnier Nathalie , Galéra Philippe
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Integration of metabolome and transcriptome reveals flavonoid accumulation in the intergeneric hybrid between Brassica rapa and Raphanus sativus
Authors: Zhang Libin , Ma Chuang , Chao Hongbo , Long Yan , Wu Jiangsheng , Li Zaiyun , Ge Xianhong , Xia Heng , Yin Yongtai , Batley Jacqueline , Li Maoteng
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Identifying threshold responses of Australian dryland rivers to future hydroclimatic change
Authors: Larkin Z. T. , Ralph T. J. , Tooth S. , Fryirs K. A. , Carthey A. J. R.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Unrevealed genetic diversity of GII Norovirus in the swine population of North East Italy
Authors: Cavicchio L. , Tassoni L. , Laconi A. , Cunial G. , Gagliazzo L. , Milani A. , Campalto M. , Di Martino G. , Forzan M. , Monne I. , Beato M. S.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood
Authors: Kaur Sarabjit , Sarma Saurav J. , Marshall Brittney L. , Liu Yang , Kinkade Jessica A. , Bellamy Madison M. , Mao Jiude , Helferich William G. , Schenk A. Katrin , Bivens Nathan J. , Lei Zhentian , Sumner Lloyd W. , Bowden John A. , Koelmel Jeremy P. , Joshi Trupti , Rosenfeld Cheryl S.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Interaction of N-acetylcysteine with DPPC liposomes at different pH: a physicochemical study
Authors: Arias Juan Marcelo , Cobos Picot Rafael A. , Tuttolomondo María Eugenia , Ben Altabef Aida , Díaz Sonia Beatriz
Published: July 2020

The N-acetylcysteine (NAC) is a commonly used mucolytic and antioxidant agent.
Laser-induced acoustic desorption coupled with electrospray ionization mass spectrometry for rapid qualitative and quantitative analysis of glucocorticoids illegally added in creams
Authors: Lin Rongkun , Lu Qiao , Lin Zheng , Hang Wei , Huang Benli
Published: July 2020

We present a strategy for the coupling of laser-induced acoustic desorption (LIAD) with electrospray ionization (ESI) mass spectrometry.
ZIF-8-modified Au–Ag/Si nanoporous pillar array for active capture and ultrasensitive SERS-based detection of pentachlorophenol
Authors: Yan Lingling , Yang Peng , Cai Hongxin , Chen Liang , Wang Yongqiang , Li Ming
Published: July 2020

A novel SERS substrate based on a zeolitic imidazolate framework-8 (ZIF-8) film-modified Au–Ag/Si nanoporous pillar array (ZIF-8/Au–Ag/Si-NPA) was successfully fabricated for pentachlorophenol (PCP) detection.
Boosting the abscopal effect of radiotherapy: a smart antigen-capturing radiosensitizer to eradicate metastatic breast tumors
Authors: Chen Yuanyuan , Pan Wei , Gao Peng , Shi Mingwan , Wu Tong , Li Na , Tang Bo
Published: July 2020

A smart antigen-capturing radiosensitizer based on hollow mesoporous titanium dioxide (HTiO2) has been developed for metastatic breast tumor treatment.
Proteins as diverse, efficient, and evolvable scaffolds for artificial metalloenzymes
Authors: Jeong Woo Jae , Yu Jaeseung , Song Woon Ju
Published: July 2020

We have extracted and categorized the desirable properties of proteins that are adapted as the scaffolds for artificial metalloenzymes.
A sulfur-containing hetero-octulene: synthesis, host–guest properties, and transistor applications
Authors: Yang Longfei , Zhang Ning , Han Yi , Zou Ya , Qiao Yanjun , Chang Dongdong , Zhao Yan , Lu Xuefeng , Wu Jishan , Liu Yunqi
Published: July 2020

A heterocycloarene derivative (S-Octulene) possessing two sulfur atoms was conveniently synthesized through Bi(OTf)3-catalyzed cyclization from a macrocyclic tetramethoxyethenylated precursor.
Efficient construction of a stable linear gene based on a TNA loop modified primer pair for gene delivery
Authors: Lu Xuehe , Wu Xiaohui , Wu Tiantian , Han Lin , Liu Jianbing , Ding Baoquan
Published: July 2020

A TNA loop modified primer pair was designed to construct a stable terminal-closed linear gene, which can be used as an efficient gene expression system in eukaryotic cells.
The combination of halogen and hydrogen bonding: a versatile tool in coordination chemistry
Authors: González Lucia , Graus Sara , Tejedor Rosa M. , Chanthapally Anjana , Serrano José Luis , Uriel Santiago
Published: July 2020

4-Iodo-N-(4-pyridyl)benzamide (INPBA) and four derived coordination complexes were synthesized in order to explore the combination of halogen and hydrogen bonding interactions in coordination chemistry.
Different structural transitions of rapidly supercooled tantalum melt under pressure
Authors: Mo Yunfei , Tian Zean , Lang Lin , Zhou Lili , Liang Yongchao , Zhang Haitao , Liu Rangsu , Peng Ping , Wen Dadong
Published: July 2020

Molecular dynamic simulation revealed that the β-, α-, and hcp-Ta can be achieved in order by rapid cooling at a cooling rate 2.0 K/ps when the static pressure increases from zero to 100 GPa.
Ground state of the Fe(ii)-porphyrin model system corresponds to quintet: a DFT and DMRG-based tailored CC study
Authors: Antalík Andrej , Nachtigallová Dana , Lo Rabindranath , Matoušek Mikuláš , Lang Jakub , Legeza Örs , Pittner Jiří , Hobza Pavel , Veis Libor
Published: July 2020

Fe(ii)-porphyrins play an important role in many reactions, due to their closely lying spin states. We present a thorough study of a Fe(ii)-porphyrin model system, in which we examine how the geometrical parameters influence its spin state ordering.
Strategies for development of nanoporous materials with 2D building units
Authors: Zhang Liping , Jaroniec Mietek
Published: July 2020

Development of nanoporous structures with two-dimensional (2D) building units is important because of their great potential in energy conversion and storage, gas storage, chemical sensing, and many other applications closely related to human life.
Investigation into antiproliferative activity and apoptosis mechanism of new arene Ru(ii) carbazole-based hydrazone complexes
Authors: Sathiya Kamatchi Thangavel , Mohamed Subarkhan Mohamed Kasim , Ramesh Rengan , Wang Hangxiang , Małecki Jan Grzegorz
Published: July 2020

In vitro antiproliferative and apoptosis inducing properties of new arene Ru(ii) carbazolone benzhydrazone complexes are described.
Synergistic effect of mixed ligands on the anisotropy axis of two dinuclear dysprosium complexes
Authors: Ke Hongshan , Yang Yongsheng , Wei Wen , Jiang Youdong , Zhang Yi-Quan , Xie Gang , Chen Sanping
Published: July 2020

We present the synergistic effect of mixed ligands on the anisotropy axis of two dinuclear dysprosium complexes.