bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Simulation of Water Tank Circulation and Water Age Under Different Working Conditions
Authors: Ma Rui , Yan Qi , Zhu Jian‐rong
Published: April 2022

With increasing real estate and apartment vacancy rates, the utilization rate of the water in water tanks is decreasing; this leads to an increase in the water age and deteriorates the water quality in water tanks. The general hydrostatic numerical model cannot simulate the flow field and water age of a water tank correctly because the horizontal scale of the water tank is equivalent to the vertical scale, and the vertical hydrostatic approximation assumption is no longer applicable. In this paper, the water age module is added to a three‐dimensional numerical model based on estuarine and coastal oceans, and a nonhydrostatic numerical model is developed to simulate and analyze the three‐dimensional flow field and the temporal and spatial variations in the water age of the water tank under different working conditions. The total water consumption and the effective volume of the water tank are the main factors affecting the water age, followed by the water level change range. The water age can be reduced to a lesser extent by setting the position of the inlet and outlet at a diagonal angle and adopting a larger inflow velocity. The distributions of the circulation and water age are mainly determined by the inlet in the influent process. There is no obvious dead water zone in the tank due to the strong disturbance, advection and diffusion in the secondary water supply process. The water age distribution in the water tank is mainly affected by advection, while diffusion plays a secondary role.
Automated Earthquake Detection and Local Travel Time Tomography in the South‐Central Andes (32–35°S): Implications for Regional Tectonics
Authors: Ammirati Jean‐Baptiste , Villaseñor Antonio , Chevrot Sébastien , Easton Gabriel , Lehujeur Maximilien , Ruiz Sergio , Flores María Constanza
Published: April 2022

In the South‐Central Andes, the crustal structures driving the tectonic evolution of the Andean Cordillera remain unresolved. So far, most seismological studies focused on the subduction interface, leaving crustal seismicity and its relationship with crustal deformation and Andean volcanism mostly unconstrained. However, because of their large number compared to higher magnitude events, the characterization of small‐magnitude crustal earthquakes is key to identify active structures and better constrain the tectonic models. In this work, we exploit 53 months of continuously recorded, three‐component waveforms from the permanent seismic network in central Chile using a deep‐learning approach to improve the detection of small‐magnitude earthquakes. To increase station coverage, we also use the seismic phases obtained from a previous temporary seismic deployment. We use the obtained seismicity catalog to refine tomographic models of that region, revealing a more detailed architecture of the Chilean forearc. Travel times calculated in the new 3‐D velocity model allowed us to locate ∼14,000 earthquakes. Refined double‐difference relocations of ∼4,900 events located beneath the West Andean Thrust suggest a large‐scale, west‐dipping structure which, together with the west‐verging tectonic front, likely contributed to the uplift and crustal deformation during the past ∼20 Myr.
Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review
Authors: He Qijin , Liu Limin , Wei Jingge , Jiang Jiaying , Rong Zheng , Chen Xin , Zhao Jingwen , Jiang Kui
Published: April 2022

Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.
Progress in the genetics of uveitis
Authors: Huang Xiu-Feng , Brown Matthew A.
Published: April 2022

Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet’s disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.
Lithium Niobate Piezoelectric Micromachined Ultrasonic Transducers for high data-rate intrabody communication
Authors: Pop Flavius , Herrera Bernard , Rinaldi Matteo
Published: April 2022

In recent years, there has been an increased interest in continuous monitoring of patients and their Implanted Medical Devices (IMDs) with different wireless technologies such as ultrasounds. This paper demonstrates a high data-rate intrabody communication link based on Lithium Niobate (LN) Piezoelectric Micromachined Ultrasonic Transducers (pMUTs). The properties of the LN allow to activate multiple flexural mode of vibration with only top electrodes. When operating in materials like the human tissue, these modes are merging and forming a large communication bandwidth. Such large bandwidth, up to 400 kHz, allows for a high-data rate communication link for IMDs. Here we demonstrate a full communication link in a tissue phantom with a fabricated LN pMUT array of 225 elements with an area of just 3 by 3 mm square, showing data-rates up to 800 kbits/s, starting from 3.5 cm and going up to 13.5 cm, which covers the vast majority of IMDs.
SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress
Authors: Zayed Abdallah , Baranowski Camille , Compagnion Anne-Claire , Vernochet Cécile , Karaki Samah , Cuttoli Romain Durand-de , Saint-Jour Estefani , Bhattacharya Soumee , Marti Fabio , Vanhoutte Peter , Yaniv Moshe , Faure Philippe , Barik Jacques , Amar Laurence , Tronche François , Parnaudeau Sébastien
Published: April 2022

Enduring behavioral changes upon stress exposure involve changes in gene expression sustained by epigenetic modifications in brain circuits, including the mesocorticolimbic pathway. Brahma (BRM) and Brahma Related Gene 1 (BRG1) are ATPase subunits of the SWI/SNF complexes involved in chromatin remodeling, a process essential to enduring plastic changes in gene expression. Here, we show that in mice, social defeat induces changes in BRG1 nuclear distribution. The inactivation of the Brg1/Smarca4 gene within dopamine-innervated regions or the constitutive inactivation of the Brm/Smarca2 gene leads to resilience to repeated social defeat and decreases the behavioral responses to cocaine without impacting midbrain dopamine neurons activity. Within striatal medium spiny neurons, Brg1 gene inactivation reduces the expression of stress- and cocaine-induced immediate early genes, increases levels of heterochromatin and at a global scale decreases chromatin accessibility. Altogether these data demonstrate the pivotal function of SWI/SNF complexes in behavioral and transcriptional adaptations to salient environmental challenges.
MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers
Authors: Alhalabi Omar , Chen Jianfeng , Zhang Yuxue , Lu Yang , Wang Qi , Ramachandran Sumankalai , Tidwell Rebecca Slack , Han Guangchun , Yan Xinmiao , Meng Jieru , Wang Ruiping , Hoang Anh G. , Wang Wei-Lien , Song Jian , Lopez Lidia , Andreev-Drakhlin Alex , Siefker-Radtke Arlene , Zhang Xinqiao , Benedict William F. , Shah Amishi Y. , Wang Jennifer , Msaouel Pavlos , Zhang Miao , Guo Charles C. , Czerniak Bogdan , Behrens Carmen , Soto Luisa , Papadimitrakopoulou Vassiliki , Lewis Jeff , Rinsurongkawong Waree , Rinsurongkawong Vadeerat , Lee Jack , Roth Jack , Swisher Stephen , Wistuba Ignacio , Heymach John , Wang Jing , Campbell Matthew T. , Efstathiou Eleni , Titus Mark , Logothetis Christopher J. , Ho Thai H. , Zhang Jianjun , Wang Linghua , Gao Jianjun
Published: April 2022

Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAPdef) in tumors with 9p21 loss and hypothetically renders tumors susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAPdef urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAPdef patients show response to pemetrexed (ORR 43%). Furthermore, a historic cohort shows 4 of 4 MTAPdef patients respond to pemetrexed as compared to 1 of 10 MTAP-proficient patients. In vitro and in vivo preclinical data using UC cell lines demonstrate increased sensitivity to pemetrexed by inducing DNA damage, and distorting nucleotide pools. In addition, MTAP-knockdown increases sensitivity to pemetrexed. Furthermore, in a lung adenocarcinoma retrospective cohort (N = 72) from the published BATTLE2 clinical trial (NCT01248247), MTAPdef associates with an improved response rate to pemetrexed. Our data demonstrate a synthetic lethal interaction between MTAPdef and de novo purine inhibition, which represents a promising therapeutic strategy for larger prospective trials.
Photo-induced trifunctionalization of bromostyrenes via remote radical migration reactions of tetracoordinate boron species
Authors: Li Chaokun , Liao Shangteng , Chen Shanglin , Chen Nan , Zhang Feng , Yang Kai , Song Qiuling
Published: April 2022

Tetracoordinate boron species have emerged as radical precursors via deboronation by photo-induced single electron transfer (SET) pathway. These reactions usually produce an alkyl radical and boron-bound species, and the valuable boron species are always discarded as a by-product. Given the importance of boron species, it will be very attractive if the two parts could be incorporated into the eventual products. Herein we report a photo-catalyzed strategy in which in situ generated tetracoordinated boron species decomposed into both alkyl radicals and boron species under visible light irradiation, due to the pre-installation of a vinyl group on the aromatic ring, the newly generated alkyl radical attacks the vinyl group while leaving the boron species on ipso-position, then both radical part and boron moiety are safely incorporated into the final product. Tertiary borons, secondary borons, gem-diborons as well as 1,2-diborons, and versatile electrophiles are all well tolerated under this transformation, of note, ortho-, meta- and para-bromostyrenes all demonstrated good capabilities. The reaction portraits high atom economy, broad substrate scope, and diversified valuable products with tertiary or quaternary carbon center generated, with diborons as substrates, Csp2-B and Csp3-B are established simultaneously, which are precious synthetic building blocks in chemical synthesis.
Structure and reactivity of germylene-bridged digold complexes
Authors: Wang Liliang , Zhen Guorong , Li Yinhuan , Kira Mitsuo , Yan Liping , Chang Xiao-Yong , Huang Lu , Li Zhifang
Published: April 2022

The bonding between gold and main-group metallic elements (M) featuring Auδ−−Mδ+ polarity, has been studied recently. The gold in the bonds is expected to have the oxidation number of −1, and hence, nucleophilic. However, the knowledge of the reactivity of the gold-metal bonds remains limited. Here, we report digold-substituted germanes of the form of R’2Ge(AuPR3)(AuGeR’2) (3a; R = Me, 3b; R = Et), featuring two Au-Ge(IV) and one Au-Ge(II) bonds. DFT calculations of 3a revealed the existence of high-lying σ(Ge-Au) type HOMO and low-lying LUMO with germylene pπ nature. A pendular motion of AuPR3 group between Ge(IV) and Ge(II) of 3 occurs in the NMR time scale, suggesting that the Ge(II) center has an enhanced electrophilicity to be attacked by the nucleophilic gold (−I) atom. 3a reacts with nucleophilic Cl− and electrophilic MeOTf reagents at Ge(II) and Ge(IV) centers, respectively.
Corrosion of aluminum alloy 7075 induced by marine Aspergillus terreus with continued organic carbon starvation
Authors: Zhang Yuxuan , He Jiaqi , Zheng Li , Jin Zhengyu , Liu Haixian , Liu Lan , Gao Zhizeng , Meng Guozhe , Liu Hongfang , Liu Hongwei
Published: April 2022

The corrosion of aluminum alloys (AA) caused by fungi has been considered as the typical reason causing the failure of aviation materials, but its corrosion mechanism is still unclear. In this work, AA 7075 corrosion induced by Fungus Aspergillus terreus with continued organic carbon starvation was investigated in artificial seawater. Results indicate that A. terreus can survive with organic carbon starvation and form a biofilm on AA surface, then accelerate AA corrosion. The pitting corrosion is more severe in biotic environments, and it is closely related to the initial spore concentration. The higher initial spore concentration, the more A. terreus survivors, leading to the more severe pitting corrosion. Acid corrosion caused by organic acids of A. terreus has no contribution to the corrosion acceleration of aluminum alloys. A. terreus can help to destroy the passive film of aluminum alloys, leading to more corrosion pits compared with the control.
Relationships between cognitive performance, clinical insight and regional brain volumes in schizophrenia
Authors: Alkan Erkan , L. H. Evans Simon
Published: April 2022

Impairments in cognitive performance are common in schizophrenia, and these contribute to poor awareness of symptoms and treatment (‘clinical insight’), which is an important predictor of functional outcome. Although relationships between cognitive impairment and reductions in regional brain volumes in patients are relatively well characterised, less is known about the brain structural correlates of clinical insight. To address this gap, we aimed to explore brain structural correlates of cognitive performance and clinical insight in the same sample. 108 patients with schizophrenia (SZH) and 94 age and gender-matched controls (CON) (from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) database) were included. SZH had smaller grey matter volume across most fronto-temporal regions and significantly poorer performance on all cognitive domains. Multiple regression showed that higher positive symptoms and poorer attention were significant predictors of insight in SZH; however, no significant correlations were seen between clinical insight and regional brain volumes. In contrast, symptomology did not contribute to cognitive performance, but robust positive relationships were found between regional grey matter volumes in fronto-temporal regions and cognitive performance (particularly executive function). Many of these appeared to be unique to SZH as they were not observed in CON. Findings suggest that while there exists a tight link between cognitive functioning and neuropathological processes affecting gross brain anatomy in SZH, this is not the case for clinical insight. Instead, clinical insight levels seem to be influenced by symptomology, attentional performance and other subject-specific variables.
A combination screening to identify enhancers of para-aminosalicylic acid against Mycobacterium tuberculosis
Authors: Heo Jinyeong , Koh Dahae , Woo Minjeong , Kwon Doyoon , de Almeida Falcão Virgínia Carla , Wood Connor , Lee Honggun , Kim Kideok , Choi Inhee , Jang Jichan , Brodin Priscille , Shum David , Delorme Vincent
Published: April 2022

Para-aminosalicylic acid (PAS) is an antibiotic that was largely used for the multi-therapy of tuberculosis in the twentieth century. To try to overcome the inconvenience of its low efficacy and poor tolerance, we searched for novel chemical entities able to synergize with PAS using a combination screening against growing axenic Mycobacterium tuberculosis. The screening was performed at a sub-inhibitory concentration of PAS on a library of about 100,000 small molecules. Selected hit compounds were analyzed by dose–response and further probed with an intracellular macrophage assay. Scaffolds with potential additive effect with PAS are reported, opening interesting prospects for mechanism of action studies. We also report here evidence of a yet unknown bio-activation mechanism, involving activation of pyrido[1,2-a]pyrimidin-4-one (PP) derivatives through the Rv3087 protein.
Proposal of a population wide genome-based testing for Covid-19
Authors: Lehrach Hans , Curtis Jon , Lange Bodo , Ogilvie Lesley A. , Gauss Richard , Steininger Christoph , Scholz Erhard , Kreck Matthias
Published: April 2022

Our lives (and deaths) have by now been dominated for two years by COVID-19, a pandemic that has caused hundreds of millions of disease cases, millions of deaths, trillions in economic costs, and major restrictions on our freedom. Here we suggest a novel tool for controlling the COVID-19 pandemic. The key element is a method for a population-scale PCR-based testing, applied on a systematic and repeated basis. For this we have developed a low cost, highly sensitive virus-genome-based test. Using Germany as an example, we demonstrate by using a mathematical model, how useful this strategy could have been in controlling the pandemic. We show using real-world examples how this might be implemented on a mass scale and discuss the feasibility of this approach.
The human milk microbiome aligns with lactation stage and not birth mode
Authors: Lyons Katriona E. , Shea Carol-Anne O.’ , Grimaud Ghjuvan , Ryan C. Anthony , Dempsey Eugene , Kelly Alan L. , Ross R. Paul , Stanton Catherine
Published: April 2022

We analysed the human milk microbiome in a cohort of 80 lactating women and followed the dynamics in taxa over the course of lactation from birth to 6 months. Two hundred and thirty one milk samples were collected from full-term lactating women at 1, 4, 8 and 24 weeks following birth and analysed for microbiota composition using 16S rRNA sequencing. A significant decrease in milk microbiota diversity was observed throughout the first 6 months of lactation, with the greatest difference seen between week 8 and week 24. Nine genera predominated in milk over lactation from week 1 to week 24, comprising ofStaphylococcus,Streptococcus,Pseudomonas,Acinetobacter, Bifidobacterium, Mesorhizobium, Brevundimonas, Flavobacterium,andRhodococcus; however, fluctuations in these core genera were apparent over time. There was a significant effect of stage of lactation on the microbiome, while no effect of birth mode, infant sex and maternal BMI was observed throughout lactation.Streptococcushad the highest mean relative abundance at week 1 and 24 (17.3% and 24% respectively), whereasPseudomonaspredominated at week 4 (22%) and week 8 (19%).BifidobacteriumandLactobacillushad the highest mean relative abundance at week 4 (5% and 1.4% respectively), and occurred at a relative abundance of ≤ 1% at all other time points. A decrease in milk microbiota diversity throughout lactation was also observed. This study concluded that lactation stage was the primary driving factor in milk microbiota compositional changes over lactation from birth to 6 months, while mode of delivery was not a factor driving compositional changes throughout human lactation.
A targetable ‘rogue’ neutrophil-subset, [CD11b+DEspR+] immunotype, is associated with severity and mortality in acute respiratory distress syndrome (ARDS) and COVID-19-ARDS
Authors: Herrera Victoria L. M. , Walkey Allan J. , Nguyen Mai Q. , Gromisch Christopher M. , Mosaddhegi Julie Z. , Gromisch Matthew S. , Jundi Bakr , Lukassen Soeren , Carstensen Saskia , Denis Ridiane , Belkina Anna C. , Baron Rebecca M. , Pinilla-Vera Mayra , Mueller Meike , Kimberly W. Taylor , Goldstein Joshua N. , Lehmann Irina , Shih Angela R. , Eils Roland , Levy Bruce D. , Ruiz-Opazo Nelson
Published: April 2022

Neutrophil-mediated secondary tissue injury underlies acute respiratory distress syndrome (ARDS) and progression to multi-organ-failure (MOF) and death, processes linked to COVID-19-ARDS. This secondary tissue injury arises from dysregulated neutrophils and neutrophil extracellular traps (NETs) intended to kill pathogens, but instead cause cell-injury. Insufficiency of pleiotropic therapeutic approaches delineate the need for inhibitors of dysregulated neutrophil-subset(s) that induce subset-specific apoptosis critical for neutrophil function-shutdown. We hypothesized that neutrophils expressing the pro-survival dual endothelin-1/VEGF-signal peptide receptor, DEspR, are apoptosis-resistant like DEspR+ cancer-cells, hence comprise a consequential pathogenic neutrophil-subset in ARDS and COVID-19-ARDS. Here, we report the significant association of increased peripheral DEspR+CD11b+ neutrophil-counts with severity and mortality in ARDS and COVID-19-ARDS, and intravascular NET-formation, in contrast to DEspR[-] neutrophils. We detect DEspR+ neutrophils and monocytes in lung tissue patients in ARDS and COVID-19-ARDS, and increased neutrophil RNA-levels of DEspR ligands and modulators in COVID-19-ARDS scRNA-seq data-files. Unlike DEspR[-] neutrophils, DEspR+CD11b+ neutrophils exhibit delayed apoptosis, which is blocked by humanized anti-DEspR-IgG4S228P antibody, hu6g8, in ex vivo assays. Ex vivo live-cell imaging of Rhesus-derived DEspR+CD11b+ neutrophils showed hu6g8 target-engagement, internalization, and induction of apoptosis. Altogether, data identify DEspR+CD11b+ neutrophils as a targetable ‘rogue’ neutrophil-subset associated with severity and mortality in ARDS and COVID-19-ARDS.
Oligocene moisture variations as evidenced by an aeolian dust sequence in Inner Mongolia, China
Authors: Wasiljeff Joonas , Salminen Johanna M. , Stenman Jarkko , Zhang Zhaoqun , Kaakinen Anu
Published: April 2022

The aridification of Central Asia since the Eocene has widespread evidence, but climate-controlled environmental reorganizations during the Oligocene remain ambiguous. We employed environmental magnetic, mineralogical and geochemical methods on a latest Eocene to late Oligocene terrestrial sequence in Inner Mongolia, China, to examine how global climatic trends and regional factors influenced the evolution of moisture and weathering in the region. Highlighting the climatic influence, our weathering and rainfall proxy data document the drawdown of atmospheric CO2and global cooling during the early Oligocene semi-arid phase, which culminated in the Early Oligocene Aridification Event at 31 Ma. Moreover, for the first time in the terrestrial eastern Central Asian setting, we provide geochemical and geophysical evidence for a second major Oligocene aridification event nearly synchronous to the mid-Oligocene Glacial Maximum at around 28 Ma. These aridification events were interrupted by periods of increased rainfall and weathering and can be associated with the terminations of glacial events seen in marine oxygen isotope records.
Programmable photonic neural networks combining WDM with coherent linear optics
Authors: Totovic Angelina , Giamougiannis George , Tsakyridis Apostolos , Lazovsky David , Pleros Nikos
Published: April 2022

Neuromorphic photonics has relied so far either solely on coherent or Wavelength-Division-Multiplexing (WDM) designs for enabling dot-product or vector-by-matrix multiplication, which has led to an impressive variety of architectures. Here, we go a step further and employ WDM for enriching the layout with parallelization capabilities across fan-in and/or weighting stages instead of serving the computational purpose and present, for the first time, a neuron architecture that combines coherent optics with WDM towards a multifunctional programmable neural network platform. Our reconfigurable platform accommodates four different operational modes over the same photonic hardware, supporting multi-layer, convolutional, fully-connected and power-saving layers. We validate mathematically the successful performance along all four operational modes, taking into account crosstalk, channel spacing and spectral dependence of the critical optical elements, concluding to a reliable operation with MAC relative error $$< 2\%$$

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Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers
Authors: Holz Olaf , Müller Meike , Carstensen Saskia , Olin Anna-Carin , Hohlfeld Jens M.
Published: April 2022

Particles in exhaled air (PEx) are generated when collapsed small airways reopen during breathing. PEx can be noninvasively collected by particle impaction, allowing the analysis of undiluted epithelial lining fluid (ELF). We used the endotoxin (LPS) challenge model to proof the concept that PEx can be used to monitor inflammatory changes in the lung. In this pilot study PEx were collected from ten healthy nonsmoking subjects using the PExA® instrument twice before and twice after a segmental LPS challenge (5, 21 h). Following a 4-week washout period, PEx were collected during the week before and 5 h after a whole lung LPS inhalation challenge. PEx biomarkers were compared to blood, bronchoalveolar lavage (BAL) following segmental challenge and induced sputum (ISP) following inhalation challenge. A clear LPS-induced inflammatory response was detectable in BAL fluid, ISP and blood. Albumin and surfactant–protein D were detectable in all PEx samples. While most baseline cytokines were close to or below the detection limit, the median (IQR) IL-6 and IL-8 concentrations in PEx increased significantly after segmental (0.04 (0.03; 0.06) fg/ng PEx; 0.10 (0.08; 0.17) fg/ng PEx) and inhalation LPS challenge (0.19 (0.15; 0.23) fg/ng PEx; 0.32 (0.23; 0.42) fg/ng PEx). Using a highly sensitive analysis platform, we were able to detect a cytokine response in PEx during the early phase of LPS-induced inflammation. This will broaden the spectrum of applications for this noninvasive method to monitor inflammatory processes in the lung, including its use in clinical trials for respiratory drug development.

Trial registration: The study has been registered on 07.02.2017 at Clinicaltrials.gov (NCT03044327).
Associations of pulmonary and extrapulmonary computed tomographic manifestations with impaired physical activity in symptomatic patients with chronic obstructive pulmonary disease
Authors: Hamakawa Yoko , Tanabe Naoya , Shima Hiroshi , Terada Kunihiko , Shiraishi Yusuke , Maetani Tomoki , Kubo Takeshi , Kozawa Satoshi , Koizumi Koji , Kanezaki Masashi , Shimizu Kaoruko , Oguma Tsuyoshi , Sato Atsuyasu , Sato Susumu , Hirai Toyohiro
Published: April 2022

In patients with chronic obstructive pulmonary disease (COPD), emphysema, airway disease, and extrapulmonary comorbidities may cause various symptoms and impair physical activity. To investigate the relative associations of pulmonary and extrapulmonary manifestations with physical activity in symptomatic patients, this study enrolled 193 patients with COPD who underwent chest inspiratory/expiratory CT and completed COPD assessment test (CAT) and the Life-Space Assessment (LSA) questionnaires to evaluate symptom and physical activity. In symptomatic patients (CAT ≥ 10, n = 100), emphysema on inspiratory CT and air-trapping on expiratory CT were more severe and height-adjusted cross-sectional areas of pectoralis muscles (PM index) and adjacent subcutaneous adipose tissue (SAT index) on inspiratory CT were smaller in those with impaired physical activity (LSA < 60) than those without. In contrast, these findings were not observed in less symptomatic patients (CAT < 10). In multivariable analyses of the symptomatic patients, severe air-trapping and lower PM index and SAT index, but not CT-measured thoracic vertebrae bone density and coronary artery calcification, were associated with impaired physical activity. These suggest that increased air-trapping and decreased skeletal muscle and subcutaneous adipose tissue quantity are independently associated with impaired physical activity in symptomatic patients with COPD.
Ferric perchlorate hydrate as a new catalyst for highly efficient esterification of cellulose at room temperature
Authors: Ragab Safaa , Eleryan Ahmed , El Nemr Ahmed
Published: April 2022

Ferric perchlorate was tested for the first time as a new catalyst to accelerate the esterification of microcrystalline cellulose (MCC) at room temperature in a less amount of acetic anhydride compared to the amount used in the conventional methods. It was possible to manufacture cellulose acetate (CA) with a high yield of up to 94%. The influence of changes in reaction time, catalyst amounts, and acetic anhydride on the characterization of cellulose acetate produced was investigated. The optimum condition for esterification of 2.0 g (12.34 mmol) MCC was found to be: 10 mL (105.98 mmol) AC2O, 200 mg (0.564 mmol, anhydrous basis) of Fe(ClO4)3·xH2O and 1 h reaction time at room temperature. The substitution degree of CA was investigated by FTIR and 1H-NMR spectroscopy. Thermal stability of CA was studied using TGA, DTA and DSC analyses. The degree of polymerization and the polydispersity index (PDI) were obtained using Gel permeation chromatography (GPC). This study verified the direct and efficient synthesis of di- and tri-cellulose acetate in one–pot reaction using Fe(ClO4)3·xH2O as a catalyst without using solvent.
Effect of relative GGBS/fly contents and alkaline solution concentration on compressive strength development of geopolymer mortars subjected to sulfuric acid
Authors: Mohamed Osama A. , Al Khattab Rania , Al Hawat Waddah
Published: April 2022

The effect of submerging geopolymer mortar samples in highly acidic solution for 7-, 28-, and 90-days on stability of mass and the development of compressive strength development was assessed experimentally. The mortar binder consisted of GGBS or blends of GGBS and fly ash activated using combinations of NaOH and Na2SiO3 solutions, and samples were cured in room temperature. It was found that maintaining mortar samples continuously under sulfuric acid doesn’t cause reduction compressive strength or mass from one age to the other, up to 90 days. While decalcification, delaumination, and formation of calcium salts due to sulfate attack may have affected mass and strength, submerging samples under water supported formation of geopolymerization products C-A-S-H and N-A-S-H, and consequently increased the mass and compressive strength of cubic mortar samples with fly ash + GGBS blended binder. The resistance of mortar to sulfuric acid remained consistent when mortars were prepared using GGBS:fly ash ratio of 3:1, equal amounts of GGBS and fly ash, and GGBS as sole binder. When geopolymer mortar samples made with each of the three binders was left exposed to air after casting, compressive strength increased from 7- to 28-days after casting, but at 90-days, all mortar samples experienced decrease in compressive strength relative to the 28-day values. The relatively high content of GGBS (≥ 50%) and absence of curing water in relatively dry conditions caused shrinkage cracking and decrease in compressive strength.
Developing a shared sepsis data infrastructure: a systematic review and concept map to FHIR
Authors: Brant Emily B. , Kennedy Jason N. , King Andrew J. , Gerstley Lawrence D. , Mishra Pranita , Schlessinger David , Shalaby James , Escobar Gabriel J. , Angus Derek C. , Seymour Christopher W. , Liu Vincent X.
Published: April 2022

The development of a shared data infrastructure across health systems could improve research, clinical care, and health policy across a spectrum of diseases, including sepsis. Awareness of the potential value of such infrastructure has been heightened by COVID-19, as the lack of a real-time, interoperable data network impaired disease identification, mitigation, and eradication. TheSepsis on FHIRcollaboration establishes a dynamic, federated, and interoperable system of sepsis data from 55 hospitals using 2 distinct inpatient electronic health record systems. Here we report on phase 1, a systematic review to identify clinical variables required to define sepsis and its subtypes to produce a concept mapping of elements onto Fast Healthcare Interoperability Resources (FHIR). Relevant papers described consensus sepsis definitions, provided criteria for sepsis, severe sepsis, septic shock, or detailed sepsis subtypes. Studies not written in English, published prior to 1970, or “grey” literature were prospectively excluded. We analyzed 55 manuscripts yielding 151 unique clinical variables. We then mapped variables to their corresponding US Core FHIR resources and specific code values. This work establishes the framework to develop a flexible infrastructure for sharing sepsis data, highlighting how FHIR could enable the extension of this approach to other important conditions relevant to public health.
Sand flies: Basic information on the vectors of leishmaniasis and their interactions with Leishmania parasites
Authors: Cecílio Pedro , Cordeiro-da-Silva Anabela , Oliveira Fabiano
Published: April 2022

Blood-sucking arthropods transmit a variety of human pathogens acting as disseminators of the so-called vector-borne diseases. Leishmaniasis is a spectrum of diseases caused by different Leishmania species, transmitted quasi worldwide by sand flies. However, whereas many laboratories focus on the disease(s) and etiological agents, considerably less study the respective vectors. In fact, information on sand flies is neither abundant nor easy to find; aspects including basic biology, ecology, and sand-fly-Leishmania interactions are usually reported separately. Here, we compile elemental information on sand flies, in the context of leishmaniasis. We discuss the biology, distribution, and life cycle, the blood-feeding process, and the Leishmania-sand fly interactions that govern parasite transmission. Additionally, we highlight some outstanding questions that need to be answered for the complete understanding of parasite–vector–host interactions in leishmaniasis.
A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1
Authors: Yang Yifeng , Lu Wenwen , Ning Mei , Zhou Xianhao , Wan Xinyao , Mi Qianglong , Yang Xiaoyan , Zhang Di , Zhang Yuanyuan , Jiang Biao , He Lin , Liu Jia , Zou Yan
Published: April 2022

The aberrant expression or genomic mutations of microRNA are associated with several human diseases. This study analyzes the relationship between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 subjects. All these ten SNPs were on or near mature microRNAs. We identified the association between bipolar disorder and the T/C polymorphism at rs895819. To illustrate the function of miR-27a, we constructed several miR-27a knockout (KO) cell lines, determined candidates of miR-27a, and then verifiedNCAM1as a target gene of miR-27a. Further studies revealed that the T/C polymorphism on miR-27a led to the differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Furthermore, the C mutation on pre-miR-27a suppresses cell migration and dopamine expression levels. Our study highlights the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.
Intermittent non-axial dipolar-field dominance of twin Laschamp excursions
Authors: Hyodo Masayuki , Nakagawa Takeshi , Matsushita Hayato , Kitaba Ikuko , Yamada Keitaro , Tanabe Shota , Bradák Balázs , Miki Masako , McLean Danielle , Staff Richard A. , Smith Victoria C. , Albert Paul G. , Bronk Ramsey Christopher , Yamasaki Akiteru , Kitagawa Junko ,   Suigetsu 2014 Project, Schlolaut Gordon , Gotanda Katsuya , Tsumura Kosuke , Inagawa Kaito , Kumazawa Koyo , Abe Haruka , Sugo Saki , Takahashi Koki , Kitamura Atsumi
Published: April 2022

Geomagnetic excursions represent the dynamic nature of the geodynamo. Accumulated palaeomagnetic records indicate that such excursions are dominated by dipolar-fields, but exhibit different structures. Here we report a palaeomagnetic record from the varved sediments of Lake Suigetsu, central Japan, which reveals fine structures in the Laschamp Excursion and a new post-Laschamp excursion that coincides with the Δ14C maxima. The record’s high-resolution chronology provides IntCal20 mid-ages and varve-counted durations. Both excursions comprise multiple subcentennial directional-swings. Simulations of filtering effects on sediment-magnetisations demonstrate that this high-resolution record replicates most of the features in existing, lower-resolution Laschamp excursion records, including the apparent clockwise open-loop of the virtual geomagnetic pole pass. The virtual geomagnetic poles during the ‘swing’ phases make four clusters centred in hemispherically-symmetric regions, three of which encompass the virtual geomagnetic poles associated with the Laschamp Excursion recorded in lavas at various locations. The stationary dipolar-field sources under each cluster should have intermittently dominated one after another during the excursions.
Auditory deep sleep stimulation in older adults at home: a randomized crossover trial
Authors: Lustenberger Caroline , Ferster M. Laura , Huwiler Stephanie , Brogli Luzius , Werth Esther , Huber Reto , Karlen Walter
Published: April 2022

Background

Auditory stimulation has emerged as a promising tool to enhance non-invasively sleep slow waves, deep sleep brain oscillations that are tightly linked to sleep restoration and are diminished with age. While auditory stimulation showed a beneficial effect in lab-based studies, it remains unclear whether this stimulation approach could translate to real-life settings.

Methods

We present a fully remote, randomized, cross-over trial in healthy adults aged 62–78 years (clinicaltrials.gov: NCT03420677). We assessed slow wave activity as the primary outcome and sleep architecture and daily functions, e.g., vigilance and mood as secondary outcomes, after a two-week mobile auditory slow wave stimulation period and a two-week Sham period, interleaved with a two-week washout period. Participants were randomized in terms of which intervention condition will take place first using a blocked design to guarantee balance. Participants and experimenters performing the assessments were blinded to the condition.

Results

Out of 33 enrolled and screened participants, we report data of 16 participants that received identical intervention. We demonstrate a robust and significant enhancement of slow wave activity on the group-level based on two different auditory stimulation approaches with minor effects on sleep architecture and daily functions. We further highlight the existence of pronounced inter- and intra-individual differences in the slow wave response to auditory stimulation and establish predictions thereof.

Conclusions

While slow wave enhancement in healthy older adults is possible in fully remote settings, pronounced inter-individual differences in the response to auditory stimulation exist. Novel personalization solutions are needed to address these differences and our findings will guide future designs to effectively deliver auditory sleep stimulations using wearable technology.
DLSSAffinity: protein–ligand binding affinity prediction via a deep learning model
Authors: Wang Huiwen , Liu Haoquan , Ning Shangbo , Zeng Chengwei , Zhao Yunjie
Published: April 2022

We propose a novel deep learning-based approach, DLSSAffinity, to accurately predict protein–ligand binding affinity. We show that combining global sequence and local structure information as the input features of a deep learning model can improve the prediction accuracy.
Organic photosensitizers for antimicrobial phototherapy
Authors: Nguyen Van-Nghia , Zhao Zheng , Tang Ben Zhong , Yoon Juyoung
Published: April 2022

This tutorial review highlights the concept and significance of antibacterial phototherapy. Recent developments, advantages, and challenges of organic photosensitizers in this area are also discussed.
Ultra-efficient highly-selective MFC-7 cancer cell therapy enabled by combined electric-pulse carbon 1D-nanomaterials platforms
Authors: Chan Sophia S. Y. , Go Shao Xiang , Meivita Maria Prisca , Lee Denise , Bajalovic Natasa , Loke Desmond K.
Published: April 2022

A combined alternating current pulse carbon nanotube platform that can enhance cancer cell-specific thermal ablation via Joule heating.
In silico design of RORγ inverse agonists based on 3D-QSAR and molecular docking
Authors: Deng Renjin , He Wenjing , Guo Hongwei , Su Zhiheng , Wu Weijun , Wu Zheng
Published: April 2022

Computationally designing novel RORγ inverse agonists with higher activity using a systematic modeling study.
One-pot synthesis and versatile applications of recyclable aminal-linked dynamic framework
Authors: Liu Sha , Dong Hao , Zhang Renjie , Zhang Wei , Sun Xinwei , Geng Shuchen , Wang Kai , Ma Lina , Huang Yudong
Published: April 2022

A recyclable polyhemiaminal dynamic network (PHDN) and its composites were prepared via in situ polymerization. The obtained versatile materials is promising for high-performance functional thermosetting materials and electrochemical active materials.
Nanotechnology-based combinatorial phototherapy for enhanced cancer treatment
Authors: Chen Han , Timashev Peter , Zhang Yuanyuan , Xue Xiangdong , Liang Xing-Jie
Published: April 2022

In this review, we summarize the recently ingenious design of nanotechnology-based phototherapy combined with different therapeutic modalities, like chemotherapy, immunotherapy, radiotherapy, etc., as well as its anti-cancer therapeutic benefits.
Phenylene as an efficient mediator for intermetallic electronic coupling
Authors: Miller-Clark Lyndsy A. , Raghavan Adharsh , Clendening Reese A. , Ren Tong
Published: April 2022

Fast hole delocalization across 1,4-phenylene between Ru2 termini was demonstrated using Vis-NIR and IR spectroelectrochemistry.
High turnover photocatalytic hydrogen formation with an Fe(iii) N-heterocyclic carbene photosensitiser
Authors: Schwarz Jesper , Ilic Aleksandra , Johnson Catherine , Lomoth Reiner , Wärnmark Kenneth
Published: April 2022

The first high turnover photocatalytic hydrogen formation reaction using an earth-abundant iron photosensitiser is presented.
Oxidative coupling of silylated nonagermanide clusters
Authors: Wallach Christoph , Klein Wilhelm , Fässler Thomas F.
Published: April 2022

The oxidative coupling of silylated [Ge9] clusters mediated by the borane Cy2BCl as oxide-scavenger is reported.
Combined crystallographic and computational investigation of the solvent disorder present in a new tipiracil hydrochloride methanol solvate–hydrate
Authors: Barbas Rafael , Font-Bardia Mercè , de Sande Dafne , Frontera Antonio , Prohens Rafel
Published: April 2022

We report a computational and crystallographic analysis of tipiracil hydrochloride (methanol solvate–hydrate). It shows a complex network of H-bonds with static discrete disorder in two out of the three symmetry-independent solvent molecules.
Dichlorine-containing chlorobismuthate(iii) supramolecular hybrid: structure and experimental studies of stability
Authors: Korobeynikov Nikita A. , Usoltsev Andrey N. , Kolesov Boris A. , Abramov Pavel A. , Plyusnin Pavel E. , Sokolov Maxim N. , Adonin Sergey A.
Published: April 2022

The chlorine-rich complex (Me4N)3{[Bi2Cl9](Cl2)} (1) features dichlorine units incorporated into a chlorometalate matrix via halogen bonding.
Pressure-induced phase transitions, amorphization and alloying in Sb2S3
Authors: Hu Cheng , Xu Yixuan , Gong Yu , Yang Dongliang , Li Xiaodong , Li Yanchun
Published: April 2022

Schematic views of the structural evolutions of Sb2S3 during compression and recompression.
Implications of sample treatment on characterization of riverine dissolved organic matter
Authors: Nelson Amelia R. , Toyoda Jason , Chu Rosalie K. , Tolić Nikola , Garayburu-Caruso Vanessa A. , Saup Casey M. , Renteria Lupita , Wells Jacqueline R. , Stegen James C. , Wilkins Michael J. , Danczak Robert E.
Published: April 2022

We compared how FTICR-MS characterization of riverine dissolved organic matter varied across four sample pre-treatment and instrument ionization methods to provide guidelines for future researchers utilizing FTICR-MS in environmental analyses.
Stainless steel-initiated chloro sulfoximidations of allenes under solvent-free conditions in a ball mill
Authors: Kong Deshen , Amer Mostafa M. , Bolm Carsten
Published: April 2022

Under solvent-free conditions in a mixer mill, sulfoximidoyl chlorides react with allenes by stainless steel-initiated radical addition reactions.
Covalent cannabinoid receptor ligands – structural insight and selectivity challenges
Authors: Liddle Ian , Glass Michelle , Tyndall Joel D. A. , Vernall Andrea J.
Published: April 2022

X-ray crystallography and cryogenic electronic microscopy have provided significant advancement in the knowledge of GPCR structure and have allowed the rational design of covalent GPCR ligands.
Lvsiyujins A–G, new sesquiterpenoids, fromCurcuma phaeocaulisValeton root tuber and their preliminary pharmacological property assessment based on ADME evaluation, molecular docking andin vitroexperiments
Authors: Dong Ying , Zhao Chongjun , Wang Xiuhuan , Xie Meng , Zhong Xiangjian , Song Ruolan , Yu Axiang , Wei Jing , Yao Jianling , Shan Dongjie , Lv Fang , She Gaimei
Published: April 2022

Seven new sesquiterpenoids were isolated from the root tuber ofC. phaeocaulis. A combination of calculations and experiments was used in structural analysis and biological activity exploration.
Surface morphology evolution of cobalt nanoparticles induced by hydrogen adsorption: a theoretical study
Authors: Geng Xiaobin , Liu Jinjia , Yang Hui , Guo Wenping , Bai Jie , Wen Xiao-Dong
Published: April 2022

Determining the surface structure and morphology under working conditions is essential to obtain facet-dependent catalytic performance.
Acetic acid formation from methane and carbon dioxidevianon-thermal plasma reactions towards an effective carbon fixation
Authors: Nishimura Naoyuki , Akaogi Takayuki , Onishi Kazuhiro , Tojo Masahiro
Published: April 2022

A non-thermal plasma reaction with CO2and isotopic CH4revealed that the primly produced CH3COOH could comprise both CH4-derived carbons, indicating the importance of a particular CO2activation control for an effective carbon fixation.
Degradation of upconverting nanoparticles in simulated fluids evaluated by ratiometric luminescence
Authors: Zhou Mingzhu , Zou Xi , Liu Yachong , Wang Haifang , Su Qianqian
Published: April 2022

The effect of artificially simulated fluids on the optical properties of upconversion nanoparticles and the degradation mechanism was systematically studied.