bluuebunny/crossref_metadata_2025 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

Several 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

mRNA 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

The 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

Antibody 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

Previous 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

Neurofeedback 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

The 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

Bromodomain 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

To 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

Including 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

It 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

The 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

Ginkgo 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

Rapeseed, 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.
Eye irrigation as a first-line treatment and diagnostic method for emergency department patients who complain of ocular foreign bodies
Authors: Chou Hung-Da , Chen Kuan-Jen , Kang Eugene Yu-Chuan , Lin Jui-Yen , Yeh Po-Han , Chen Yen-Ting , Cheng Chi-Tung , Lai Chi-Chun , Wu Wei-Chi , Hwang Yih-Shiou , Hsiao Ching-Hsi
Published: December 2021

This prospective study aimed at determine whether eye irrigation removes ocular foreign bodies (FBs) and whether ocular pain predicts FBs. Emergency department patients complaining of ocular FBs were enrolled. In the irrigation group (n = 52), pain was evaluated with a visual analog scale before and after irrigation, and the presence of FBs was determined under a slit-lamp. In the nonirrigation group (n = 27), the evaluations were performed upon arrival. The corneal FB retention rate was found significantly lower in the irrigation (13/52, 25%) than in the nonirrigation groups (13/27, 48%; P = 0.04). After irrigation, those without FBs had more patients experiencing pain reduction (67%) compared to those with retained FBs (46%; P = 0.14) and had a greater magnitude of change in pain score (mean ± SD, − 2.6 ± 2.7 vs. − 0.7 ± 1.4; P = 0.02). An improvement in ocular pain score ≥ 5 points after irrigation predicted the absence of FBs with a negative predictive value of 100%. Eye irrigation significantly lowered corneal FB retention; if ocular pain decreased considerably, the probability of retained FBs was low, making irrigation-associated pain score reduction a feasible diagnostic method to exclude FB retention without needing specialized ophthalmic examinations.
Single-atom catalytic growth of crystals using graphene as a case study
Authors: Yang Xiaoqin , Liu Yu , Ta Huy Q. , Rezvani Ehsan , Zhang Yue , Zeng Mengqi , Fu Lei , Bachmatiuk Alicja , Luo Jinping , Liu Lijun , Rümmeli Mark H.
Published: December 2021

Anchored Single-atom catalysts have emerged as a cutting-edge research field holding tremendous appeal for applications in the fields of chemicals, energy and the environment. However, single-atom-catalysts for crystal growth is a nascent field. Of the few studies available, all of them are based on state-of-the-art in situ microscopy investigations and computational studies, and they all look at the growth of monolayer graphene from a single-atom catalyst. Despite the limited number of studies, they do, collectively, represent a new sub-field of single-atom catalysis, namely single-atom catalytic growth of crystalline solids. In this review, we examine them on substrate-supported and as freestanding graphene fabrication, as well as rolled-up graphene, viz., single-walled carbon nanotubes (SWCNT), grown from a single atom. We also briefly discuss the catalytic etching of graphene and SWCNT’s and conclude by outlining the future directions we envision this nascent field to take.
Wafer scale synthesis of organic semiconductor nanosheets for van der Waals heterojunction devices
Authors: Kalkan Sirri Batuhan , Najafidehaghani Emad , Gan Ziyang , Apfelbeck Fabian Alexander Christian , Hübner Uwe , George Antony , Turchanin Andrey , Nickel Bert
Published: December 2021

Organic semiconductors (OSC) are widely used for consumer electronic products owing to their attractive properties such as flexibility and low production cost. Atomically thin transition metal dichalcogenides (TMDs) are another class of emerging materials with superior electronic and optical properties. Integrating them into van der Waals (vdW) heterostructures provides an opportunity to harness the advantages of both material systems. However, building such heterojunctions by conventional physical vapor deposition (PVD) of OSCs is challenging, since the growth is disrupted due to limited diffusion of the molecules on the TMD surface. Here we report wafer-scale (3-inch) fabrication of transferable OSC nanosheets with thickness down to 15 nm, which enable the realization of heterojunction devices. By controlled dissolution of a poly(acrylic acid) film, on which the OSC films were grown by PVD, they can be released and transferred onto arbitrary substrates. OSC crystal quality and optical anisotropy are preserved during the transfer process. By transferring OSC nanosheets (p-type) onto prefabricated electrodes and TMD monolayers (n-type), we fabricate and characterize various electronic devices including unipolar, ambipolar and antiambipolar field-effect transistors. Such vdW p-n heterojunction devices open up a wide range of possible applications ranging from ultrafast photodetectors to conformal electronics.
Management of cardiovascular disease using an mHealth tool: a randomized clinical trial
Authors: Kang Si-Hyuck , Baek Hyunyoung , Cho Jihoon , Kim Seok , Hwang Hee , Lee Wonjae , Park Jin Joo , Yoon Yeonyee E. , Yoon Chang-Hwan , Cho Young-Seok , Youn Tae-Jin , Cho Goo-Yeong , Chae In-Ho , Choi Dong-Ju , Yoo Sooyoung , Suh Jung-Won
Published: December 2021

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death and morbidity worldwide. This randomized controlled, single-center, open-label trial tested the impact of a mobile health (mHealth) service tool optimized for ASCVD patient care. Patients with clinical ASCVD were enrolled and randomly assigned to the intervention or control group. Participants in the intervention group were provided with a smartphone application named HEART4U, while a dedicated interface integrated into the electronic healthcare record system was provided to the treating physicians. A total of 666 patients with ASCVD were enrolled, with 333 patients in each group. The estimated baseline 10-year risk of cardiovascular disease was 9.5% and 10.8% in the intervention and control groups, respectively, as assessed by the pooled cohort risk equations. The primary study endpoint was the change in the estimated risk at six months. The estimated risk increased by 1.3% and 1.1%, respectively, which did not differ significantly (P = 0.821). None of the secondary study endpoints showed significant differences between the groups. A post-hoc subgroup analysis showed the benefit was greater if a participant in the intervention group accessed the application more frequently. The present study demonstrated no significant benefits associated with the use of the mHealth tool in terms of the predefined study endpoints in stable patients with ASCVD. However, it also suggested that motivating patients to use the mHealth tool more frequently may lead to greater clinical benefit. Better design with a positive user experience needs to be considered for developing future mHealth tools for ASCVD patient care.

Trial Registration:ClinicalTrials.gov NCT03392259
Crystal structure of human METTL6, the m3C methyltransferase
Authors: Chen Ran , Zhou Jie , Liu Ling , Mao Xue-Ling , Zhou Xiaolong , Xie Wei
Published: December 2021

In tRNA, the epigenetic m3C modification at position 32 in the anticodon loop is highly conserved in eukaryotes, which maintains the folding and basepairing functions of the anticodon. However, the responsible enzymes METTL2 and METTL6 were identified only in recent years. The loss of human METTL6 (hMETTL6) affects the translational process and proteostasis in cells, while in mESCs cells, it leads to defective pluripotency potential. Despite its important functions, the catalytic mechanism of the C32 methylation by this enzyme is poorly understood. Here we present the 1.9 Å high-resolution crystal structure of hMETTL6 bound by SAH. The key residues interacting with the ligand were identified and their roles were confirmed by ITC. We generated a docking model for the hMETTL6-SAH-CMP ternary complex. Interestingly, the CMP molecule binds into a cavity in a positive patch with the base ring pointing to the inside, suggesting a flipped-base mechanism for methylation. We further generated a model for the quaternary complex with tRNASer as a component, which reasonably explained the biochemical behaviors of hMETTL6. Taken together, our crystallographic and biochemical studies provide important insight into the molecular recognition mechanism by METTL6 and may aid in the METTL-based rational drug design in the future.
Hadal aragonite records venting of stagnant paleoseawater in the hydrated forearc mantle
Authors: Oyanagi Ryosuke , Okamoto Atsushi , Satish-Kumar Madhusoodhan , Minami Masayo , Harigane Yumiko , Michibayashi Katsuyoshi
Published: December 2021

The hadal zone at trenches is a unique region where forearc mantle rocks are directly exposed at the ocean floor owing to tectonic erosion. Circulation of seawater in the mantle rock induces carbonate precipitation within the deep-sea forearc mantle, but the timescale and rates of the circulation are unclear. Here we investigated a peculiar occurrence of calcium carbonate (aragonite) in forearc mantle rocks recovered from ~6400 m water depth in the Izu–Ogasawara Trench. On the basis of microtextures, strontium–carbon–oxygen isotope geochemistry, and radiocarbon analysis, we found that the aragonite is sourced from seawater that accumulated for more than 42,000 years. Aragonite precipitation is triggered by episodic rupture events that expel the accumulated fluids at 10−2–10−1 m s−1and which continue for a few decades at most. We suggest that the recycling of subducted seawater from the shallowest forearc mantle influences carbon transport from the surface to Earth’s interior.
A novel near-infrared theranostic probe for accurate cancer chemotherapy in vivo by a dual activation strategy
Authors: Wang Wen-Xin , Jiang Wen-Li , Mao Guo-Jiang , Tan Zhi-Ke , Tan Min , Li Chun-Yan
Published: December 2021

A novel theranostic probe called CX-B-DF is constructed for chemotherapy guided by near-infrared (NIR) fluorescence imaging. Moreover, the accuracy of drug release is improved under dual activation (H2O2 and TP).
Low field control of spin switching and continuous magnetic transition in an ErFeO3 single crystal
Authors: Ma Xiaoxuan , Fan Wencheng , Zhao Gang , Chen Haiyang , Wang Chuankun , Kang Baojuan , Feng Zhenjie , Ge Jun-Yi , Ren Wei , Cao Shixun
Published: December 2021

The magnetic behavior of a rare-earth orthoferrite ErFeO3 single crystal can be controlled by low magnetic fields from a few to hundreds of Oe.
Flavonoid constituents ofAmomum tsao-koCrevost et Lemarie and their antioxidant and antidiabetic effects in diabetic rats –in vitroandin vivostudies
Authors: Zhang Xiao-Feng , Tang Yu-Jun , Guan Xiao-Xian , Lu Xin , Li Jiao , Chen Xiao-Li , Deng Jin-Lan , Fan Jian-Ming
Published: December 2021

Amomum tsao-koCrevost et Lemarie (A. tsao-ko) is a well-known dietary spice and traditional Chinese medicine.
Fermented egg-milk beverage alleviates dextran sulfate sodium-induced colitis in mice through the modulation of intestinal flora and short-chain fatty acids
Authors: Lyu Siwen , Pan Fengguang , Ge Huifang , Yang Qi , Duan Xuehui , Feng Mengmeng , Liu Xuanting , Zhang Ting , Liu Jingbo
Published: December 2021

Fermented egg-milk beverage (FEMB) alleviate the symptoms of colitis by regulating intestinal flora and short-chain fatty acids.
Overview of renewable polysaccharide-based composites for biodegradable food packaging applications
Authors: Deng Jia , Zhu En-Qing , Xu Gao-Feng , Naik Nithesh , Murugadoss Vignesh , Ma Ming-Guo , Guo Zhanhu , Shi Zheng-Jun
Published: December 2021

Renewable environmentally friendly polysaccharides and their composites have been critically reviewed for biodegradable food packaging applications.
Size and isotopic ratio measurements of individual nanoparticles by a continuous ion-monitoring method using Faraday detectors equipped on a multi-collector-ICP-mass spectrometer
Authors: Yamashita Shuji , Yamamoto Kota , Takahashi Hiroaki , Hirata Takafumi
Published: December 2021

We investigated the capability of high-gain Faraday detectors equipped on a multi-collector-ICP-mass spectrometer (MFC-ICP-MS) in performing both particle size and Ag isotopic ratio determination for individual silver nanoparticles (Ag NPs).
Mixed-dimensional organic–inorganic metal halide perovskite (OIMHP) based gas sensors with superior stability for NO2 detection
Authors: Duong The , John Alishba T. , Chen Hongjun , Pham Huyen , Murugappan Krishnan , Tran-Phu Thanh , Tricoli Antonio , Catchpole Kylie
Published: December 2021

Mixed-dimensional 2D/3D perovskite-based NO2 gas sensors were developed with swift response, great sensitivity and good selectivity. The 2D/3D devices have significantly better moisture stability than the 3D devices.
Investigation of cattle plasma proteome in response to pain and inflammation using next generation proteomics technique, SWATH-MS
Authors: Ghodasara Priya , Satake Nana , Sadowski Pawel , Kopp Steven , Mills Paul C.
Published: December 2021

SWATH-MS provides comprehensive protein profile of cattle plasma in response to tissue injury induced pain and inflammation.
Improving sensing of formaldehyde using ZnO nanostructures with surface-adsorbed oxygen
Authors: Tawfik‡ Sherif Abdulkader , Tran Hang , Spencer Michelle J. S.
Published: December 2021

The effect of surface adsorbed oxygen on the gas–sensor reaction mechanism of formaldehyde on ZnO nanowires has been determined.
A peptidomimetic-based thixotropic organogel showing syneresis-induced anti-adhesion against water and ice
Authors: Gumtya Milan , Mondal Sahabaj , Kumar Santosh , Ibukun Olamilekan Joseph , Haldar Debasish
Published: December 2021

A peptidomimetic containing 2,6-dimethylpyridine-3,5-dicarboxylic acid and phenylalanine formed a thixotropic gel which shows syneresis under appropriate conditions and anti-adhesion against water and ice.
Irradiation stability and induced ferromagnetism in a nanocrystalline CoCrCuFeNi highly-concentrated alloy
Authors: Tunes Matheus A. , Greaves Graeme , Rack Philip D. , Boldman Walker L. , Schön Cláudio G. , Pogatscher Stefan , Maloy Stuart A. , Zhang Yanwen , El-Atwani Osman
Published: December 2021

Thermodynamic instabilities driven by temperature and irradiation in a nanocrystalline highly-concentrated alloy promote the nucleation and growth of FeCo-rich “nanomagnets”.
Mechanochemical synthesis of air-stable hexagonal Li4SnS4-based solid electrolytes containing LiI and Li3PS4
Authors: Otoyama Misae , Kuratani Kentaro , Kobayashi Hironori
Published: December 2021

Addition of LiI and Li3PS4 to hexagonal Li4SnS4 enhances ionic conductivity without decreasing the air stability of Li4SnS4.
Oxygen-vacancy-rich BiOCl materials with ultrahigh photocatalytic efficiency by etching bismuth glass
Authors: Dong Wenjing , Xie Tianyi , Wu Zhilun , Peng Haiyi , Ren Haishen , Meng Fancheng , Lin Huixing
Published: December 2021

(a) EPR spectra of (a) the as-prepared BiOCl samples under dark, (b) BBZSN and Intermediate Bi2O(OH)2SO4 under dark, (c) BiOCl–NaCl under dark and ultraviolet light and (d) the as-prepared BiOCl samples under ultraviolet light.
Synthesis of 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: a way forward for targeting hypoxia and drug resistance of cancer cells
Authors: Buravchenko Galina I. , Scherbakov Alexander M. , Dezhenkova Lyubov G. , Monzote Lianet , Shchekotikhin Andrey E.
Published: December 2021

New water-soluble hypoxia activated 7-aminoquinoxaline 1,4-dioxides, prepared by the regioselective Beirut reaction, acted as HIF-1α suppressors and induced apoptosis in hypoxic and MDR cancer cells.
The role of crosslinking density in surface stress and surface energy of soft solids
Authors: Zhao Weiwei , Zhou Jianhui , Hu Haitao , Xu Chang , Xu Qin
Published: December 2021

Surface stress and surface energy are two fundamental parameters that determine the surface properties of any material. We show experimentally that the two material parameters vary with crosslinking density in different ways for soft polymeric gels.
Solar-driven interfacial evaporation toward clean water production: burgeoning materials, concepts and technologies
Authors: He Fang , Wu Xiaochun , Gao Jie , Wang Zhenxing
Published: December 2021

Burgeoning materials, concepts and technologies for solar-driven interfacial evaporation have been reviewed.
Construction of a stereocomplex between poly(d-lactide) grafted hydroxyapatite and poly(l-lactide): toward a bioactive composite scaffold with enhanced interfacial bonding
Authors: Shuai Cijun , Yu Li , Feng Pei , Peng Shuping , Pan Hao , Bai Xinna
Published: December 2021

Hydroxyapatite (HAP) grafted with poly( d-lactide) (PDLA) was incorporated into poly(l-lactide) (PLLA) to construct a stereocomplex, thus improving the interfacial bonding between PLLA and HAP like a zip-lock structure in a scaffold.
Design of bridge blasting demolition
Authors: Jangl Stefan , Kavicky Vladimir , Pilat Michal
Published: December 2021

The paper presents the design of bridge blasting demolition scheme. The blasting methods has become the preferred method for bridge demolition not only in war period but also where bridge service life is exceeded. Compared with the other demolition method, blasting evince more advantages as higher demolishing progress, lower cost and easier construction safety control. The design of bridge blasting demolition scheme contents blasting position, blasting parameters and safety protections.
Behaviour of steel beam subjected to the fire
Authors: Figuli Lucia , Leitner Bohus , Magdolénová Paulína
Published: December 2021

Fire as one of the extraordinary load is essential to study in all its aspects. It evolve to study the fire development as well as the structural analysis of elements subjected to the fire. The present paper deals with steel beam fire resistance determination by these two approaches (analytical and numerical) and compares the results.
Material model Johnson-Holmquist and its application in numerical analysis
Authors: Ondrušková Lucia , Brodniansky Ján
Published: December 2021

Model Johnson-Holmquist is commonly used for simulation of brittle materials under impacts and blast loading. In this paper is described its application to a model of a bolted connection in glass, when constant force is applied, and effect of two mesh sizings is compared.
Development of analytical fragility curves for structural glass frames by using Cloud Analysis
Authors: Mattei Silvana , Bedon Chiara
Published: December 2021

The design of glass structures under dynamic loads still presents a high degree of uncertainty. Among others, one of the methods to study the vulnerability of structural systems is based on the use of fragility curves. This study includes a seismic evaluation of structural glass frame as a function of fragility curves in earthquake engineering. In particular, the Cloud method is used to perform non-linear dynamic analysis which provide a set of data pairs implemented in a linear-regression-based probabilistic model.
Les noms de l’eau
Authors: Cecchi Philippe
Published: December 2021

Les appellations de 152 pièces d’eau d’un bassin-versant du centre du Burkina Faso ont été répertoriées par l’autorité en charge de la mise en œuvre de la gestion intégrée des ressources en eau, dans l’objectif d’établir les bases d’une nomenclature du réseau hydrographique. 125 de ces pièces d’eau portent un nom en langue vernaculaire (en mòoré), dont le sens est indiqué en français dans le rapport technique qui synthétise les résultats de l’enquête. L’échantillon offre la possibilité de comparer le sens des noms attribués aux éléments naturels (les « cours d’eau ») et aux éléments artificiels (les « étendues d’eau » ou « petits barrages » comme on les dénomme localement). Les deux catégories ne partagent pas totalement les mêmes dénominations : les noms de l’eau varient, comme varient les perceptions et représentations qu’en ont leurs riverains. Des intuitions en lien avec l’appropriation plus ou moins revendiquée des réservoirs artificiels et les modalités de leurs mises en valeur peuvent être avancées.
Extraktion erkrankter Unterkieferinzisivi beim Meerschweinchen (Cavia porcellus) via ventraler Mandibulatrepanation
Authors: Witt Sandra , Köstlinger Saskia , Fehr Michael
Published: December 2021

Gegenstand und Ziel Diese retrospektive Studie beschreibt die Methode der ventralen Mandibulatrepanation zur Extraktion erkrankter Unterkieferinzisivi beim Meerschweinchen und evaluiert das klinische Outcome.

Material und Methoden Bei 40 Meerschweinchen mit veränderter Futteraufnahme wurde mindestens ein Unterkieferschneidezahn via ventraler Mandibulatrepanation extrahiert, nachdem Befunde der klinischen Allgemeinuntersuchung sowie der intraoralen und radiologischen Untersuchung in Allgemeinanästhesie die Diagnose einer primären mandibulären Inzisivuserkrankung ergeben hatten. Nach dem Eingriff wurden Röntgenaufnahmen angefertigt und die Patienten bis zur Entlassung stationär überwacht und versorgt. Zur Beurteilung und Behandlung der Wunden erfolgten regelmäßige Kontrollen.

Ergebnisse Bei den insgesamt 42 extrahierten Unterkieferinzisivi stellten Makrodonten (25/42) den häufigsten Extraktionsgrund dar, gefolgt von periapikalen und alveolären Veränderungen (8/42). Extrahiert wurden ferner Zahnresiduen unklarer Genese (4/42) sowie nach fehlgeschlagenem konventionellem Extraktionsversuch mittels Luxatoren (3/42) und traumatisch bedingt gelockerte Inzisivi (2/42). Bei jeweils 40 % (16/42) der Meerschweinchen lagen zahnassoziierte Kieferabszesse bzw. eine therapiebedürftige sekundäre Elongation der Backenzähne vor. Allen Patienten konnten die veränderten Inzisivi bzw. Residuen vollständig entfernt werden. Durchschnittlich 2 Tagen nach dem Eingriff nahmen die Tiere eigenständig Futter auf und konnten entlassen werden. Die Ausheilung der Wunde war nach durchschnittlich 39 Tagen (Minimum 9 Tage, Maximum 98 Tage) festzustellen. Die 22 Tiere, die 6 Monate nach dem Eingriff nachuntersucht werden konnten, wiesen keine erneuten zahnassoziierten Erkrankungen auf.

Schlussfolgerung und klinische Relevanz Die ventrale Mandibulatrepanation ermöglicht es, erkrankte Unterkieferinzisivi beim Meerschweinchen in toto in einer Operation zu entfernen und stellt somit einen kurativen Eingriff dar. Im Gegensatz zur klassischen Extraktion mit Luxatoren birgt sie nicht das Risiko von Zahnfrakturen mit der Folge verbleibender Zahnfragmente in der Alveole.
Stellenwert der elektromagnetischen Navigationsbronchoskopie bei der Abklärung pulmonaler Rundherde
Authors: Schwick Björn , Sodi Luna José Miguel , Tonder Beate
Published: December 2021

Die elekromagnetische Navigationsbronchoskopie ist eine sehr hilfreiche Untersuchung zur Abklärung pulmonaler Rundherde. Vorteile sind die niedrige Komplikationsrate 3
10, die Möglichkeit von Punktionen an mehreren Bereichen der Lunge während einer Untersuchung in Vollnarkose und die fehlende Strahlenbelastung. Im Falle einer Bestätigung von Malignität sind RH häufig Krebserkrankungen im Frühstadium und kurativ behandelbar, im Falle von Benignität nicht selten infektiologische therapiebedürftige Erkrankungen bei Patienten mit strukturellen Lungenveränderungen. Das ENB-Verfahren kann bei vorhandener Erfahrung und routinemäßigem Einsatz zur erfolgreichen Diagnose von peripheren Läsionen (mindestens ab 1,5 cm Größe) in etwa 75 % der Fälle beitragen. Wegen Zunahme von CT-Thoraxuntersuchungen und der älter werdenden Bevölkerung nimmt die Abklärung von Patienten mit Lungenrundherden einen wachsenden Stellenwert in Lungenkliniken ein. Die ENB sollte sich deswegen neben der heute unverzichtbaren endobronchialen Ultraschalluntersuchung (EBUS) zu einem routinemäßig durchgeführten Untersuchungsverfahren in der interventionellen Pneumologie entwickeln. Bedauerlicherweise ist die ENB noch nicht im DRG-System kostenrelevant abgebildet.
HLA-B27 assoziierte anteriore Uveitis: Herausforderung für
eine interdisziplinäre Zusammenarbeit
Authors: Pohlmann Dominika , Rademacher Judith , Pleyer Uwe
Published: December 2021

Die akute anteriore Uveitis (AAU) ist die häufigste Form intraokularer
Entzündungen, die v. a. Personen im erwerbsfähigen Alter
betrifft und mit erheblichen sozioökonomischen Auswirkungen verbunden
ist. Etwa die Hälfte der AAU-Patienten sind HLA-B27 positiv und teilen
ein hohes Risiko zu HLA-B27-assoziierten Erkrankungen, insbesondere zur
Spondyloarthritis (SpA). Sowohl die SpA als auch die AAU sind komplexe
entzündliche Erkrankungen, deren genaue Pathogenese unbekannt ist. Da
bei bis zu 40% der AAU-Patienten eine nicht diagnostizierte SpA
vorliegt, bietet die AAU die Möglichkeit einer frühzeitigen
Erkennung der zugrundeliegenden rheumatologischen Erkrankung. Die klinische
Präsentation der AAU bei SpA weist eine Reihe typischer Augenbefunde
auf, die diagnostisch wegweisend sind und auf eine systemische Grunderkrankung
hindeuten können. Daher ist eine abgestimmte
Überweisungsstrategie zur zügigen Diagnostik und Behandlung
notwendig. Dieser Beitrag fokussiert daher auf die interdisziplinäre
Zusammenarbeit und bietet gleichzeitig Hinweise für die
differentialdiagnostische Abklärung.