bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of direct involvement of a diazepam long-term treatment in the occurrence of irreversible cognitive impairment: a pre-clinical approach
Authors: Carton Louise , Niot Candice , Kyheng Maéva , Petrault Maud , Laloux Charlotte , Potey Camille , Lenski Marie , Bordet Régis , Deguil Julie 
Published: December 2021

AbstractSeveral observational studies have found a link between the long-term use of benzodiazepines and dementia, which remains controversial. Our study was designed to assess (i) whether the long-term use of benzodiazepines, at two different doses, has an irreversible effect on cognition, (ii) and whether there is an age-dependent effect. One hundred and five C57Bl/6 male mice were randomly assigned to the 15 mg/kg/day, the 30 mg/kg/day diazepam-supplemented pellets, or the control group. Each group comprised mice aged 6 or 12 months at the beginning of the experiments and treated for 16 weeks. Two sessions of behavioral assessment were conducted: after 8 weeks of treatment and after treatment completion following a 1-week wash-out period. The mid-treatment test battery included the elevated plus maze test, the Y maze spontaneous alternation test, and the open field test. The post-treatment battery was upgraded with three additional tests: the novel object recognition task, the Barnes maze test, and the touchscreen-based paired-associated learning task. At mid-treatment, working memory was impaired in the 15 mg/kg diazepam group compared to the control group (p = 0.005). No age effect was evidenced. The post-treatment assessment of cognitive functions (working memory, visual recognition memory, spatial reference learning and memory, and visuospatial memory) did not significantly differ between groups. Despite a cognitive impact during treatment, the lack of cognitive impairment after long-term treatment discontinuation suggests that benzodiazepines alone do not cause irreversible deleterious effects on cognitive functions and supports the interest of discontinuation in chronically treated patients.
Inhibition of cytoplasmic EZH2 induces antitumor activity through stabilization of the DLC1 tumor suppressor protein
Authors: Tripathi Brajendra K. , Anderman Meghan F. , Bhargava Disha , Boccuzzi Luciarita , Qian Xiaolan , Wang Dunrui , Durkin Marian E. , Papageorge Alex G. , de Miguel Fernando J. , Politi Katerina , Walters Kylie J. , Doroshow James H. , Lowy Douglas R. 
Published: December 2021

AbstractmRNA expression of the DLC1 tumor suppressor gene is downregulated in many lung cancers and their derived cell lines, with DLC1 protein levels being low or absent. Although the role of increased EZH2 methyltransferase in cancer is usually attributed to its histone methylation, we unexpectedly observed that post-translational destabilization of DLC1 protein is common and attributable to its methylation by cytoplasmic EZH2, leading to CUL-4A ubiquitin-dependent proteasomal degradation of DLC1. Furthermore, siRNA knockdown of KRAS in several lines increases DLC1 protein, associated with a drastic reduction in cytoplasmic EZH2. Pharmacologic inhibition of EZH2, CUL-4A, or the proteasome can increase the steady-state level of DLC1 protein, whose tumor suppressor activity is further increased by AKT and/or SRC kinase inhibitors, which reverse the direct phosphorylation of DLC1 by these kinases. These rational drug combinations induce potent tumor growth inhibition, with markers of apoptosis and senescence, that is highly dependent on DLC1 protein.
Resonant tunneling driven metal-insulator transition in double quantum-well structures of strongly correlated oxide
Authors: Yukawa R. , Kobayashi M. , Kanda T. , Shiga D. , Yoshimatsu K. , Ishibashi S. , Minohara M. , Kitamura M. , Horiba K. , Santander-Syro A. F. , Kumigashira H. 
Published: December 2021

AbstractThe metal-insulator transition (MIT), a fascinating phenomenon occurring in some strongly correlated materials, is of central interest in modern condensed-matter physics. Controlling the MIT by external stimuli is a key technological goal for applications in future electronic devices. However, the standard control by means of the field effect, which works extremely well for semiconductor transistors, faces severe difficulties when applied to the MIT. Hence, a radically different approach is needed. Here, we report an MIT induced by resonant tunneling (RT) in double quantum well (QW) structures of strongly correlated oxides. In our structures, two layers of the strongly correlated conductive oxide SrVO3 (SVO) sandwich a barrier layer of the band insulator SrTiO3. The top QW is a marginal Mott-insulating SVO layer, while the bottom QW is a metallic SVO layer. Angle-resolved photoemission spectroscopy experiments reveal that the top QW layer becomes metallized when the thickness of the tunneling barrier layer is reduced. An analysis based on band structure calculations indicates that RT between the quantized states of the double QW induces the MIT. Our work opens avenues for realizing the Mott-transistor based on the wave-function engineering of strongly correlated electrons.
Directed evolution of and structural insights into antibody-mediated disruption of a stable receptor-ligand complex
Authors: Pennington Luke F. , Gasser Pascal , Kleinboelting Silke , Zhang Chensong , Skiniotis Georgios , Eggel Alexander , Jardetzky Theodore S. 
Published: December 2021

AbstractAntibody drugs exert therapeutic effects via a range of mechanisms, including competitive inhibition, allosteric modulation, and immune effector mechanisms. Facilitated dissociation is an additional mechanism where antibody-mediated “disruption” of stable high-affinity macromolecular complexes can potentially enhance therapeutic efficacy. However, this mechanism is not well understood or utilized therapeutically. Here, we investigate and engineer the weak disruptive activity of an existing therapeutic antibody, omalizumab, which targets IgE antibodies to block the allergic response. We develop a yeast display approach to select for and engineer antibody disruptive efficiency and generate potent omalizumab variants that dissociate receptor-bound IgE. We determine a low resolution cryo-EM structure of a transient disruption intermediate containing the IgE-Fc, its partially dissociated receptor and an antibody inhibitor. Our results provide a conceptual framework for engineering disruptive inhibitors for other targets, insights into the failure in clinical trials of the previous high affinity omalizumab HAE variant and anti-IgE antibodies that safely and rapidly disarm allergic effector cells.
Nurturing the reading brain: home literacy practices are associated with children’s neural response to printed words through vocabulary skills
Authors: Girard Cléa , Bastelica Thomas , Léone Jessica , Epinat-Duclos Justine , Longo Léa , Prado Jérôme 
Published: December 2021

AbstractPrevious studies indicate that children are exposed to different literacy experiences at home. Although these disparities have been shown to affect children’s literacy skills, it remains unclear whether and how home literacy practices influence brain activity underlying word-level reading. In the present study, we asked parents of French children from various socioeconomic backgrounds (n = 66; 8.46 ± 0.36 years, range 7.52–9.22; 20 girls) to report the frequency of home literacy practices. Neural adaptation to the repetition of printed words was then measured using functional magnetic resonance imaging (fMRI) in a subset of these children (n = 44; 8.49 ± 0.33 years, range 8.02–9.14; 13 girls), thereby assessing how sensitive was the brain to the repeated presentation of these words. We found that more frequent home literacy practices were associated with enhanced word adaptation in the left posterior inferior frontal sulcus (r = 0.32). We also found that the frequency of home literacy practices was associated with children’s vocabulary skill (r = 0.25), which itself influenced the relation between home literacy practices and neural adaptation to words. Finally, none of these effects were observed in a digit adaptation task, highlighting their specificity to word recognition. These findings are consistent with a model positing that home literacy experiences may improve children’s vocabulary skill, which in turn may influence the neural mechanisms supporting word-level reading.
Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks
Authors: Krylova Marina , Skouras Stavros , Razi Adeel , Nicholson Andrew A. , Karner Alexander , Steyrl David , Boukrina Olga , Rees Geraint , Scharnowski Frank , Koush Yury 
Published: December 2021

AbstractNeurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.
Thomson and collisional regimes of in-phase coherent microwave scattering off gaseous microplasmas
Authors: Patel Adam R. , Ranjan Apoorv , Wang Xingxing , Slipchenko Mikhail N. , Shneider Mikhail N. , Shashurin Alexey 
Published: December 2021

AbstractThe total number of electrons in a classical microplasma can be non-intrusively measured through elastic in-phase coherent microwave scattering (CMS). Here, we establish a theoretical basis for the CMS diagnostic technique with an emphasis on Thomson and collisional scattering in short, thin unmagnetized plasma media. Experimental validation of the diagnostic is subsequently performed via linearly polarized, variable frequency (10.5–12 GHz) microwave scattering off laser induced 1–760 Torr air-based microplasmas (287.5 nm O2 resonant photoionization by ~ 5 ns, < 3 mJ pulses) with diverse ionization and collisional features. Namely, conducted studies include a verification of short-dipole-like radiation behavior, plasma volume imaging via ICCD photography, and measurements of relative phases, total scattering cross-sections, and total number of electrons $$N_{e}$$

N
e

in the generated plasma filaments following absolute calibration using a dielectric scattering sample. Findings of the paper suggest an ideality of CMS in the Thomson “free-electron” regime—where a detailed knowledge of plasma and collisional properties (which are often difficult to accurately characterize due to the potential influence of inhomogeneities, local temperatures and densities, present species, and so on) is unnecessary to extract $$N_{e}$$

N
e

from the scattered signal. The Thomson scattering regime of microwaves is further experimentally verified via measurements of the relative phase between the incident electric field and electron displacement.
The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
Authors: Jermakowicz Anna M. , Rybin Matthew J. , Suter Robert K. , Sarkaria Jann N. , Zeier Zane , Feng Yangbo , Ayad Nagi G. 
Published: December 2021

AbstractBromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNA-sequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM.
Meibomian gland dysfunction is highly prevalent among first-time visitors at a Norwegian dry eye specialist clinic
Authors: Badian Reza A. , Utheim Tor Paaske , Chen Xiangjun , Utheim Øygunn Aass , Ræder Sten , Ystenæs Ann Elisabeth , Aakre Bente Monica , Sundling Vibeke 
Published: December 2021

AbstractTo investigate the prevalence of meibomian gland dysfunction (MGD) in patients presenting with subjective dry eye-related symptoms at their first-time consultation in a Norwegian specialized ocular surface clinic. Additionally, to explore the accuracy of the ocular surface disease index score (OSDI) as an extensively applied tool to assess the severity of dry eye symptoms and MGD diagnosis. Patients with subjective dry eye-related complaints (n = 900) attending the clinic for the first time, from 2012 to 2016, were included in the study. At the baseline, patients completed the OSDI questionnaire. Subsequently, objective clinical tests, including fluorescein break-up time (FBUT), Schirmer-I test, ocular surface staining (OSS), and meibomian gland function assessment using gland expressibility and meibum quality were performed. The association between MGD and its severity in relation to symptom severity defined by OSDI-score was examined. MGD was found in 93.8% of the study group. MGD prevalence was not significantly different between groups based on age (p = 0.302) or sex (p = 0.079). There was a significant association between severity of MGD and dry eye-related symptoms (p = 0.014). OSS was significantly higher in patients with severe symptoms (p = 0.031). Sensitivity and specificity of positive symptom-score (OSDI ≥ 13) for disclosing MGD were 85.5% and 30.4%, respectively. MGD was highly prevalent, not associated with age and sex. OSDI ≥ 13 had high sensitivity and high positive predictive value (PPV), but low specificity and negative predictive value (NPV) for disclosing MGD. This underscores the importance of meibomian gland assessment in patients with dry eye-related symptoms.
Relationship between indirect genetic effects for growth, environmental enrichment, coping style and sex with the serum metabolome profile of pigs
Authors: Dervishi Elda , Reimert Inonge , van der Zande Lisette E. , Mathur Pramod , Knol Egbert F. , Plastow Graham S. 
Published: December 2021

AbstractIncluding Indirect Genetic Effects (IGE) in breeding programs to reduce aggression in group housed animals has been proposed. However, the effect of selection for IGE for growth on animal metabolism and physiology is unknown. The purpose of this study was twofold: (1) To investigate the effects of this new breeding method along with two housing (barren and straw), coping style (high and low resisters) and sex (female and castrated males) options on the metabolome profile of pigs. (2) To identify and map biological processes associated with a regrouping test at 9 weeks of age. We used Nuclear Magnetic Resonance to quantify 49 serum metabolites at week 8, 9 and 22. Also, we quantified 3 catecholamines (tyramine, epinephrine, phenylethylamine) and serotonin and three water soluble vitamins (B2, B5 and B7). Overall, no significant differences were observed between negative and positive IGE animals. The magnitude of change (delta) of many metabolites as a response to the regrouping test was significantly affected by IGE, especially that of the amino acids (P < 0.05), being greater in positive IGE pigs. The regrouping test was associated with alteration in glycine, serine and threonine metabolism. In conclusion positive and negative IGE animals respond differently to the regrouping test.
A cohort study investigating the occurrence of differences in care provided to men and women in an intensive care unit
Authors: Zettersten Erik , Jäderling Gabriella , Bell Max , Larsson Emma 
Published: December 2021

AbstractIt has been reported that there are differences in the care given within the intensive care unit (ICU) between men and women. The aim of this study is to investigate if any differences still exist between men and women regarding the level of intensive care provided, using prespecified intensive care items. This is a retrospective cohort study of 9017 ICU patients admitted to a university hospital between 2006 and 2016. Differences in use of mechanical ventilation, invasive monitoring, vasoactive treatment, inotropic treatment, echocardiography, renal replacement therapy and central venous catheters based on the sex of the patient were analysed using univariate and multivariable logistic regressions. Subgroup analyses were performed on patients diagnosed with sepsis, cardiac arrest and respiratory disease. Approximately one third of the patients were women. Overall, men received more mechanical ventilation, more dialysis and more vasoactive treatment. Among patients admitted with a respiratory disease, men were more likely to receive mechanical ventilation. Furthermore, men were more likely to receive levosimendan if admitted with cardiac arrest. We conclude that differences in the level of intensive care provided to men and women still exist.
Risk factors for Bell’s palsy based on the Korean National Health Insurance Service National Sample Cohort data
Authors: Jeong Junhui , Yoon So Ra , Lim Hyunsun , Oh Jangwon , Choi Hyun Seung 
Published: December 2021

AbstractThe associations between hypertension, diabetes, and dyslipidemia with Bell’s palsy have been controversial and only a few studies have assessed risk factors for Bell’s palsy based on population-based data. The aim of the present study was to evaluate whether sociodemographic factors such as sex, age, residence, household income, and metabolic diseases such as hypertension, diabetes, and dyslipidemia were risk factors for Bell’s palsy using the National Health Insurance Service National Sample Cohort data of Korea. Patients who visited an outpatient clinic twice or more or had one or more admission and received steroid medication under the International Classification of Diseases diagnostic codes for Bell’s palsy from 2006 to 2015 were defined as patients with Bell’s palsy in this study. The associations between sociodemographic factors and metabolic diseases to Bell’s palsy were analyzed with univariate and multivariate Cox proportional hazard regression models. There were 2708 patients with Bell’s palsy recorded from 2006 to 2015. Male sex, advanced age, residence in a location other than the capital and metropolitan cities, hypertension, and diabetes were significant risk factors for Bell’s palsy. This study is significant for patients and providers because we analyzed the relationships using a population-based database over a long-term follow-up period.
Genome-wide characterization of bZIP gene family identifies potential members involved in flavonoids biosynthesis in Ginkgo biloba L.
Authors: Han Huan , Xu Feng , Li Yuting , Yu Li , Fu Mingyue , Liao Yongling , Yang Xiaoyan , Zhang Weiwei , Ye Jiabao 
Published: December 2021

AbstractGinkgo biloba L. is an ancient relict plant with rich pharmacological activity and nutritional value, and its main physiologically active components are flavonoids and terpene lactones. The bZIP gene family is one of the largest gene families in plants and regulates many processes including pathogen defense, secondary metabolism, stress response, seed maturation, and flower development. In this study, genome-wide distribution of the bZIP transcription factors was screened from G. biloba database in silico analysis. A total of 40 bZIP genes were identified in G. biloba and were divided into 10 subclasses. GbbZIP members in the same group share a similar gene structure, number of introns and exons, and motif distribution. Analysis of tissue expression pattern based on transcriptome indicated that GbbZIP08 and GbbZIP15 were most highly expressed in mature leaf. And the expression level of GbbZIP13 was high in all eight tissues. Correlation analysis and phylogenetic tree analysis suggested that GbbZIP08 and GbbZIP15 might be involved in the flavonoid biosynthesis. The transcriptional levels of 20 GbbZIP genes after SA, MeJA, and low temperature treatment were analyzed by qRT-PCR. The expression level of GbbZIP08 was significantly upregulated under 4°C. Protein–protein interaction network analysis indicated that GbbZIP09 might participate in seed germination by interacting with GbbZIP32. Based on transcriptome and degradome data, we found that 32 out of 117 miRNAs were annotated to 17 miRNA families. The results of this study may provide a theoretical foundation for the functional validation of GbbZIP genes in the future.
QTL mapping for low temperature germination in rapeseed
Authors: Zhu Jifeng , Wang Weirong , Jiang Meiyan , Yang Liyong , Zhou Xirong 
Published: December 2021

AbstractRapeseed, a major oil crop in the world, is easily affected by low-temperature stress. A low temperature delays seed germination and increases seedling mortality, adversely affecting rapeseed growth and production. In the present study, a tolerant cultivar (Huyou21) was crossed with a susceptible genotype (3429) to develop a mapping population consisting of 574 F2 progenies and elucidate the genetic mechanisms of seed germination under low temperatures. Two quantitative trait loci (QTL) for low-temperature germination (LTG) were detected, one on chromosome A09 (named qLTGA9-1) and the other on chromosome C01 (named qLTGC1-1), using the QTL-seq approach and confirmed via linkage analysis in the mapping population. Further, qLTGA9-1 was mapped to a 341.86 kb interval between the SSR markers Nys9A212 and Nys9A215. In this region, 69 genes including six specific genes with moderate or high effect function variants were identified based on the Ningyou7 genome sequence. Meanwhile, qLTGC1-1 was mapped onto a 1.31 Mb interval between SSR markers Nys1C96 and Nys1C117. In this region, 133 genes including five specific genes with moderate effect function variants were identified. These specific genes within the two QTL could be used for further studies on cold tolerance and as targets in rapeseed breeding programs.