bluuebunny/crossref_metadata_2025 huggingface dataset:
Land Cover Impacts on Land‐Atmosphere Coupling Strength in Climate Simulations With WRF Over Europe
Authors: Jach Lisa , Warrach‐Sagi Kirsten , Ingwersen Joachim , Kaas Eigil , Wulfmeyer Volker
Published: September 2020

Land use and land cover changes are important human forcings to the Earth's climate. This study examines the land‐atmosphere coupling strength and the relationship between surface fluxes and clouds and precipitation for three land cover scenarios in the European summer. The WRF model was used to simulate one scenario with extreme afforestation, one with extreme deforestation, and one with realistic land cover for the time period between 1986 and 2015. The simulations were forced with ERA‐Interim reanalysis data. The analysis followed a two‐step approach. First, the convective triggering potential–low‐level humidity index framework was applied to locate potential coupling hot spots, which were then analyzed with regard to their sensitivity toward land use and land cover changes. Second, actual feedbacks between evaporative fraction, cloud cover, and precipitation were analyzed statistically with focus on sign and location of the feedbacks. The results demonstrate that coupling hot spots, exhibiting predominantly positive feedbacks, were identified over parts of Eastern Europe and Scandinavia. In this strongly coupled region, afforestation and deforestation modified the atmospheric humidity and stability by changing the surface flux partitioning. Afforestation is associated with a net drying of the atmosphere due to a disproportionately strong increase in the sensible heat flux. In contrast, deforestation initiated a moistening of the atmosphere. The total precipitation changed only in limited areas significantly, which are mostly located in mountainous regions and the northeast of the domain. In summary, the results indicate a land surface influence on the atmospheric background conditions, and an impact on the potential strength of land surface‐precipitation feedbacks.
A Modeling Study of an Atmospheric Bore Associated With a Nocturnal Convective System Over China
Authors: Zhang Shushi , Parsons David B. , Xu Xin , Wang Yuan , Liu Jiufu , Abulikemu Abuduwaili , Shen Wenqiang , Zhang Xidi , Zhang Shengxi
Published: September 2020

Bores have been shown to play a role in the initiation and maintenance of mesoscale convective systems (MCSs), particularly during the night after the boundary layer stabilizes. To date, the generation, evolution, and structure of bores over China has received little attention. This study utilizes observations and simulations with the WRF‐ARW model to investigate the generation and evolution of an atmospheric bore observed over Yangtze‐Huai Plains of China. The bore was associated with a nocturnal MCS that first formed over elevated terrain. The bore was observed ahead of the MCS with a maximum lateral extension of ~100 km. The feature lasted for over 90 mins and propagated at a speed of ~13 m/s, slightly faster than the MCS. In the simulation, the bore evolved from the separating “head” of the convectively generated gravity current. The bore then continued to propagate ahead of the MCS, even after the dissipation of the feeder current, and took on the appearance of an undular bore. The bore lifted a layer of convectively unstable air above the nocturnal surface inversion, initiating new convection ahead of the MCS to help maintain the MCS. The Scorer parameter ahead of the bore revealed a low‐level wind profile with curvature of the vertical profile of horizontal wind, favoring the trapping of wave energy and the persistence of the bore. These results are generally consistent with the role of bores in the maintenance of nocturnal MCSs and emphasize the need for future studies into the relationship between bores and nocturnal MCSs over China.
Assessment of Upper Tropospheric Water Vapor Monthly Variation in Reanalyses With Near‐Global Homogenized 6.5‐μm Radiances From Geostationary Satellites
Authors: Xue Yunheng , Li Jun , Li Zhenglong , Lu Riyu , Gunshor Mathew M. , Moeller Szuchia L. , Di Di , Schmit Timothy J.
Published: September 2020

The monthly variation of upper tropospheric water vapor (UTWV) simulated by six reanalysis data sets is evaluated with homogenized water vapor radiance observations from international geostationary (GEO) weather satellites by using a profile‐to‐radiance approach over 45°N to 45°S regions for the period 2015–2017. Results show that reanalysis data sets have an overall good agreement with observations. However, a widespread wet bias is found in all reanalyses and is more dominant in large‐scale subsidence regions. JRA55 has the smallest wet bias while MERRA‐2 exhibits the most humid upper troposphere. The temporal variation of brightness temperatures in response to the warm phase of El Niño‐Southern Oscillation (ENSO) in 2015–2016 indicates that the UTWV field is regulated by both ascending and descending branches of the large‐scale circulation. All six reanalyses roughly capture the temporal variation of UTWV in the developing and decay year of this ENSO event. However, they tend to overestimate the eastward propagation of high UTWV in the developing year, especially MERRA‐2. The UTWV gradient over the tropical Pacific in the decay year is underestimated, with a dry bias over the convective western Pacific and a wet bias over the eastern Pacific in reanalysis data sets. These results may provide a useful tool for the climate modeling community for identifying and solving problems associated with UTWV simulation.
Regional Calibration With Isotope Tracers Using a Spatially Distributed Model: A Comparison of Methods
Authors: Holmes Tegan , Stadnyk Tricia A. , Kim Su Jin , Asadzadeh Masoud
Published: September 2020

Accurate representation of flow sources in process‐based hydrologic models remains challenging for remote, data‐scarce regions. This study applies stable isotope tracers (18O and 2H) in water as auxiliary data for the calibration of the isoWATFLOOD™ model. The most efficient method of those evaluated for introducing isotope data into model calibration was the PA‐DDS multiobjective search algorithm. The compromise solutions incorporating isotope data performed slightly inferior in terms of streamflow simulation compared to the calibrated solution using streamflow data only. However, the former solution outperformed the latter one in terms of isotope simulation. Approximation of the model parameter uncertainty into internal flow path partitioning was explored. Inclusion of isotope error facilitated a broader examination of the total parameter space, resulting in significant differences in internal storage and flow paths, most significantly for soil storage and evapotranspiration loss. Isotope‐optimized calibration reduced evaporation rates and increased soil moisture content within the model, impacting soil water velocity but not streamflow celerity. Flow‐only calibration resulted in artificially narrow model prediction bounds, significantly underestimating the propagation of parameter uncertainty, while isotope‐informed calibrations yielded more reliable and robust bound on model predictions. Our findings demonstrate that the accuracy of a complex, spatially distributed, and process‐based model cannot be judged from one summative flow‐based model performance evaluation metric alone.
Hippocampal volume in early psychosis: a 2-year longitudinal study
Authors: McHugo Maureen , Armstrong Kristan , Roeske Maxwell J. , Woodward Neil D. , Blackford Jennifer U. , Heckers Stephan
Published: September 2020

Cross-sectional studies suggest that hippocampal volume declines across stages of psychosis. In contrast, longitudinal studies indicate that hippocampal volume is stable in the critical period following illness onset. How can these seemingly disparate sets of findings be resolved? In the present study, we examine two previously unexplored reasons for this discrepancy. First, only specific subregions of the hippocampus may change during the early stage of psychosis. Second, there is diagnostic heterogeneity in the early stage of psychosis and cross-sectional analysis does not permit examination of illness trajectory. Some early stage individuals will have persistent illness leading to a diagnosis of schizophrenia, whereas in others, psychosis will remit. Hippocampal volume may be reduced only in individuals who will ultimately be diagnosed with schizophrenia. We acquired longitudinal structural MRI data from 63 early psychosis and 63 healthy control participants, with up to 4 time points per participant collected over 2 years. Subfield volumes were measured in the anterior and posterior hippocampus using automated segmentation specialized for longitudinal analysis. We observed a volume deficit in early psychosis participants compared to healthy controls that was most pronounced in the anterior hippocampus, but this deficit did not change over 2 years. Importantly, we found that anterior cornu ammonis volume is smaller at baseline in individuals who were diagnosed with schizophrenia at follow-up, but normal in those who maintained a diagnosis of schizophreniform disorder over 2 years. Smaller hippocampal volume is not diagnostic of psychosis, but is instead prognostic of clinical outcome.
Comparing measures of hematologic response after high-dose melphalan and stem cell transplantation in AL amyloidosis
Authors: Sarosiek Shayna , Zheng Luke , Sloan J. Mark , Quillen Karen , Brauneis Dina , Sanchorawala Vaishali
Published: September 2020

Hematologic complete response (hemCR) in AL amyloidosis requires absence of monoclonal protein by immunofixation electrophoreses (IFE) and normal serum free light chain ratio (FLCR). Recent literature suggests that an involved free light chain (iFLC) <20 mg/L or difference in free light chains (dFLC) <10 mg/L may more accurately predict outcomes after treatment. We evaluated overall survival in 340 patients treated with high-dose melphalan and stem cell transplantation (SCT). Of 305 patients evaluable 6 months after SCT, 90 (30%) achieved hemCR, 132 (43%) dFLC <10 mg/L, 118 (39%) iFLC <20 mg/L, and 176 (58%) normal FLCR. Of 215 patients without hemCR, 65 (30%) had dFLC <10 mg/L and 86 (40%) had normal FLCR. Overall survival (OS) in those achieving dFLC <10 mg/L or normal FLCR without hemCR was inferior to those achieving hemCR (p = 0.013 and p = 0.001). OS was not significantly different in patients achieving iFLC <20 mg/L without hemCR compared with hemCR (p = 0.243). Of those with hemCR, OS was not significantly improved if dFLC <10 mg/L was also achieved (p = 0.852), but OS was improved for those with hemCR who also attained iFLC <20 mg/L (p = 0.009). Multivariate analysis demonstrated absence of monoclonal protein in IFE and iFLC <20 mg/L as independent predictors of survival. Attainment of hemCR remains a treatment goal, although achieving iFLC <20 mg/L may also predict improved OS.
Pre-clinical animal models are poor predictors of human toxicities in phase 1 oncology clinical trials
Authors: Atkins Johnique T. , George Goldy C. , Hess Kenneth , Marcelo-Lewis Kathrina L. , Yuan Ying , Borthakur Gautam , Khozin Sean , LoRusso Patricia , Hong David S.
Published: September 2020

Background

Our objective was to determine the correlation between preclinical toxicity found in animal models (mouse, rat, dog and monkey) and clinical toxicity reported in patients participating in Phase 1 oncology clinical trials.

Methods

We obtained from two major early-Phase clinical trial centres, preclinical toxicities from investigational brochures and clinical toxicities from published Phase 1 trials for 108 drugs, including small molecules, biologics and conjugates. Toxicities were categorised according to Common Terminology Criteria for Adverse Events version 4.0. Human toxicities were also categorised based on their reported clinical grade (severity). Positive predictive values (PPV) and negative predictive values (NPV) were calculated to determine the probability that clinical studies would/would not show a particular toxicity category given that it was seen in preclinical toxicology analysis. Statistical analyses also included kappa statistics, and Matthews (MCC) and Spearman correlation coefficients.

Results

Overall, animal toxicity did not show strong correlation with human toxicity, with a median PPV of 0.65 and NPV of 0.50. Similar results were obtained based on kappa statistics and MCC.

Conclusions

There is an urgent need to assess more novel approaches to the type and conduct of preclinical toxicity studies in an effort to provide better predictive value for human investigation.
Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI)
Authors: Hanna Glenn J. , Ruiz Emily S. , LeBoeuf Nicole R. , Thakuria Manisha , Schmults Chrysalyne D. , Decaprio James A. , Silk Ann W.
Published: September 2020

Background

Immunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma (cSCC). It is important to understand both safety and efficacy in a real-world and trial-ineligible cSCC population. We aimed to evaluate safety, efficacy and molecular insights among a broader cSCC population, including immunosuppressed patients, treated with immune checkpoint inhibitors (CPI).

Methods

We present a cohort of advanced cSCC patients (n = 61) treated from 2015 to 2020 evaluating the best overall response (BOR) (RECISTv1.1) to CPI therapy, immune-related adverse events (irAEs) and tumour mutational burden (TMB) to correlate with outcomes. A validated geriatric scoring index (CIRS-G) was utilised to assess comorbidities among patients ≥75. These data were compared with published clinical trial results among the broader cSCC population.

Results

BOR to CPI was lower among the entire cohort when compared with trial data (31.5 vs. 48%, P < 0.01), with higher rates of progression (59 vs. 16.5%, P < 0.01), regardless of immunosuppression history or age. Grade 3+ irAEs were more common among responders (P = 0.02), while pre-treatment lymphocyte count and TMB predicted response (P = 0.02).

Conclusions

We demonstrate comparatively lower response rates to CPI among real-world cSCC patients not explained by older age or immunosuppression history alone. Immune-related toxicity, absolute lymphocyte count and TMB predicted CPI response.
Myo-inositol mediates reactive oxygen species-induced programmed cell death via salicylic acid-dependent and ethylene-dependent pathways in apple
Authors: Hu Lingyu , Zhou Kun , Ren Guijin , Yang Shulin , Liu Yuan , Zhang Zhijun , Li Yangtiansu , Gong Xiaoqing , Ma Fengwang
Published: September 2020

As a versatile compound, myo-inositol plays vital roles in plant biochemistry and physiology. We previously showed that exogenous application of myo-inositol had a positive role in salinity tolerance in Malus hupehensis Rehd. In this study, we used MdMIPS (the rate-limiting gene of myo-inositol biosynthesis) transgenic apple lines to gain new insights into the physiological role of myo-inositol in apple. Decreasing myo-inositol biosynthesis in apple lines by RNA silencing of MdMIPS1/2 led to extensive programmed cell death, which manifested as necrosis of both the leaves and roots and, ultimately, plant death. Necrosis was directly caused by the excessive accumulation of reactive oxygen species, which may be closely associated with the cell wall polysaccharide-mediated increase in salicylic acid and a compromised antioxidant system, and this process was enhanced by an increase in ethylene production. In addition, a high accumulation of sorbitol promoted necrosis. This synergetic interplay between salicylic acid and ethylene was further supported by the fact that increased myo-inositol accumulation significantly delayed leaf senescence in MdMIPS1-overexpressing apple lines. Taken together, our results indicated that apple myo-inositol regulates reactive oxygen species-induced programmed cell death through salicylic acid-dependent and ethylene-dependent pathways.
The IAA- and ABA-responsive transcription factor CgMYB58 upregulates lignin biosynthesis and triggers juice sac granulation in pummelo
Authors: Shi Meiyan , Liu Xiao , Zhang Haipeng , He Zhenyu , Yang Hongbin , Chen Jiajing , Feng Jia , Yang Wenhui , Jiang Youwu , Yao Jia-Long , Deng Cecilia Hong , Xu Juan
Published: September 2020

In citrus, lignin overaccumulation in the juice sac results in granulation and an unpleasant fruit texture and taste. By integrating metabolic phenotyping and transcriptomic analyses, we found 702 differentially expressed genes (DEGs), including 24 transcription factors (TFs), to be significantly correlated with lignin content. CgMYB58 was further identified as a critical R2R3 MYB TF involved in lignin overaccumulation owing to its high transcript levels in Huanong Red-fleshed pummelo (HR, Citrus grandis) fruits. Transient expression of CgMYB58 led to an increase in the lignin content in the pummelo fruit mesocarp, whereas its stable overexpression significantly promoted lignin accumulation and upregulated 19 lignin biosynthetic genes. Among these genes, CgPAL1, CgPAL2, Cg4CL1, and CgC3H were directly modulated by CgMYB58 through interaction with their promoter regions. Moreover, we showed that juice sac granulation in pummelo fruits could be affected by indole-3-acetic acid (IAA) and abscisic acid (ABA) treatments. In HR pummelo, ABA significantly accelerated this granulation, whereas IAA effectively inhibited this process. Taken together, these results provide novel insight into the lignin accumulation mechanism in citrus fruits. We also revealed the theoretical basis via exogenous IAA application, which repressed the expression of CgMYB58 and its target genes, thus alleviating juice sac granulation in orchards.
Rapid dehydration of grape berries dampens the post-ripening transcriptomic program and the metabolite profile evolution
Authors: Zenoni Sara , Amato Alessandra , D’Incà Erica , Guzzo Flavia , Tornielli Giovanni Battista
Published: September 2020

The postharvest dehydration of grape berries allows the concentration of sugars and other solutes and promotes the synthesis of metabolites and aroma compounds unique to high-quality raisin wines such as the passito wines made in Italy. These dynamic changes are dependent on environmental parameters such as temperature and relative humidity, as well as endogenous factors such as berry morphology and genotype, but the contribution of each variable is not well understood. Here, we compared berries subjected to natural or accelerated dehydration, the latter driven by forced air flow. We followed the evolution of transcript and metabolite profiles and found that accelerated dehydration clearly dampened the natural transcriptomic and metabolomic programs of postharvest berries. We found that slow dehydration over a prolonged duration is necessary to induce gene expression and metabolite accumulation associated with the final quality traits of dehydrated berries. The accumulation of key metabolites (particularly stilbenoids) during postharvest dehydration is inhibited by rapid dehydration conditions that shorten the berry life time.
Rhizosphere microbial communities associated to rose replant disease: links to plant growth and root metabolites
Authors: Yim B. , Baumann A. , Grunewaldt-Stöcker G. , Liu B. , Beerhues L. , Zühlke S. , Sapp M. , Nesme J. , Sørensen S. J. , Smalla K. , Winkelmann T.
Published: September 2020

Growth depression ofRosaplants at sites previously used to cultivate the same or closely related species is a typical symptom of rose replant disease (RRD). Currently, limited information is available on the causes and the etiology of RRD compared to apple replant disease (ARD). Thus, this study aimed at analyzing growth characteristics, root morphology, and root metabolites, as well as microbial communities in the rhizosphere of the susceptible rootstockRosacorymbifera‘Laxa’ grown in RRD-affected soil from two sites (Heidgraben and Sangerhausen), either untreated or disinfected by γ-irradiation. In a greenhouse bioassay, plants developed significantly more biomass in the γ-irradiated than in the untreated soils of both sites. Several plant metabolites detected inR. corymbifera‘Laxa’ roots were site- and treatment-dependent. Although aloesin was recorded in significantly higher concentrations in untreated than in γ-irradiated soils from Heidgraben, the concentrations of phenylalanine were significantly lower in roots from untreated soil of both sites. Rhizosphere microbial communities of 8-week-old plants were studied by sequencing of 16S rRNA, ITS, and cox gene fragments amplified from total community DNA. Supported by microscopic observations, sequences affiliated to the bacterial genusStreptomycesand the fungal genusNectriawere identified as potential causal agents of RRD in the soils investigated. The relative abundance of oomycetes belonging to the genusPythiogetonshowed a negative correlation to the growth of the plants. Overall, the RRD symptoms, the effects of soil treatments on the composition of the rhizosphere microbial community revealed striking similarities to findings related to ARD.
Natural variation and evolutionary dynamics of transposable elements in Brassica oleracea based on next-generation sequencing data
Authors: Liu Zhen , Fan Miao , Yue Er-Kui , Li Yu , Tao Ruo-Fu , Xu Hai-Ming , Duan Ming-Hua , Xu Jian-Hong
Published: September 2020

Brassica oleraceacomprises various economically important vegetables and presents extremely diverse morphological variations. They provide a rich source of nutrition for human health and have been used as a model system for studying polyploidization. Transposable elements (TEs) account for nearly 40% of theB. oleraceagenome and contribute greatly to genetic diversity and genome evolution. Although the proliferation of TEs has led to a large expansion of theB. oleraceagenome, little is known about the population dynamics and evolutionary activity of TEs. A comprehensive mobilome profile of 45,737 TE loci was obtained from resequencing data from 121 diverse accessions across nineB. oleraceamorphotypes. Approximately 70% (32,195) of the loci showed insertion polymorphisms between or within morphotypes. In particular, up to 1221 loci were differentially fixed among morphotypes. Further analysis revealed that the distribution of the population frequency of TE loci was highly variable across different TE superfamilies and families, implying a diverse expansion history during host genome evolution. These findings provide better insight into the evolutionary dynamics and genetic diversity ofB. oleraceagenomes and will potentially serve as a valuable resource for molecular markers and association studies between TE-based genomic variations and morphotype-specific phenotypic differentiation.
Validity assessment of the single-point insulin sensitivity estimator (spise) for diagnosis of cardiometabolic risk in post-pubertal hispanic adolescents
Authors: Correa-Burrows Paulina , Blanco Estela , Gahagan Sheila , Burrows Raquel
Published: September 2020

Insulin measurements are not advised for cardiometabolic risk screening in large groups. Here we assessed the accuracy of the single-point insulin sensitivity estimator (SPISE) to diagnose cardiometabolic risk in Chilean adolescents. In 678 post-pubertal adolescents (52% males, M(SD) age = 16.8 (0.2) years), height, weight, waist circumference, blood lipids, glucose, insulin, and blood pressure were measured. BMI, HOMA-IR, and SPISE were estimated; HOMA-IR values ≥ 2.6 were considered insulin resistance (IR). Metabolic syndrome (MetS) was defined with the joint IDF/AHA/NHBLI standard. Using receiver operating characteristic curves, we obtained optimal SPISE cutpoints for IR and MetS diagnosis. The prevalence of MetS and IR was 8.2% and 17.1%, respectively. In males, the optimal cutoff for MetS diagnosis was 5.0 (sensitivity: 97%; specificity: 82%), and the optimal cutoff for IR diagnosis was 5.9 (sensitivity: 71%; specificity: 83%). In females, a SPISE of 6.0 had the highest sensitivity (90%) and specificity (74%) for MetS diagnosis. A SPISE of 6.4 was the optimal cutoff for IR diagnosis; however, sensitivity and specificity were 61% and 75%. In males and female post-pubertal adolescents, SPISE had a very good and good diagnostic performance, respectively, in predicting MetS. It was an accurate diagnostic tool for IR prediction in males, but not necessarily in females.
Aggravation of symptom severity in adult attention-deficit/hyperactivity disorder by latent Toxoplasma gondii infection: a case–control study
Authors: Lam Alexandra P. , de Sordi Dominik , Müller Helge H. O. , Lam Martin C. , Carl Angelika , Kohse Klaus P. , Philipsen Alexandra
Published: September 2020

Toxoplasma gondii (T. gondii) has a high worldwide prevalence and an underestimated impact on neuropsychiatric disorders. Previous studies related T. gondii to disorders associated with the dysfunctional dopaminergic system. However, an association between T. gondii infection and adult attention-deficit/hyperactivity disorder (ADHD) has not yet been studied. In a sex- and age-matched case–control study, we investigated the seropositivity, serointensity, and avidity of latent T. gondii infection in adult ADHD patients and examined the influence of those variables on the symptomatology of ADHD. Of 140 participants, 20.0% were seropositive for anti-T. gondii IgG and 0% for anti-T. gondii IgM. T. gondii seropositivity was associated with 2.8-fold increase in the odds of ADHD in a confounder-adjusted multivariable analysis. Age and consumption of raw/undercooked meat were confirmed as significant predictors of T. gondii seropositivity. Multiple linear regression analysis of self-rated ADHD-related symptom severity in all participants revealed a significant association with T. gondii seropositivity, elevated IgG titers (serointensity), and stronger anti-T. gondii IgG avidity. Overall symptom severity was increased in seropositive ADHD patients compared to seronegative subjects with ADHD. In particular, hyperactivity was significantly associated with serointensity. We conclude that there is a high rate of T. gondii seropositivity in adults with ADHD. Additionally, our results suggest a clinical impact of latent T. gondii infection on ADHD-related symptoms in a serointensity- and avidity-dependent manner.
Differential contribution of bone marrow-derived infiltrating monocytes and resident macrophages to persistent lung inflammation in chronic air pollution exposure
Authors: Gangwar Roopesh Singh , Vinayachandran Vinesh , Rengasamy Palanivel , Chan Ricky , Park Bongsoo , Diamond-Zaluski Rachel , Cara Elaine Ann , Cha Anthony , Das Lopa , Asase Courteney , Maiseyeu Andrei , Deiuliis Jeffrey , Zhong Jixin , Mitzner Wayne , Biswal Shyam , Rajagopalan Sanjay
Published: September 2020

Chronic exposure to particulate matter < 2.5µ (PM2.5) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (AΦ) are long-lived, self-renew and critical to the health impact of inhalational insults. There is an inadequate understanding of the impact of PM2.5 exposure on the nature/time course of transcriptional responses, self-renewal of AΦ, and the contribution from bone marrow (BM) to this population. Accordingly, we exposed chimeric (CD45.2/CD45.1) mice to concentrated PM2.5 or filtered air (FA) to evaluate the impact on these end-points. PM2.5 exposure for 4-weeks induced an influx of BM-derived monocytes into the lungs with no contribution to the overall TR-AΦ pool. Chronic (32-weeks) PM2.5 exposure on the other hand while associated with increased recruitment of BM-derived monocytes and their incorporation into the AΦ population, resulted in enhanced apoptosis and decreased proliferation of TR-AΦ. RNA-seq analysis of isolated TR-AΦ and BM-AΦ from 4- and 32-weeks exposed mice revealed a unique time-dependent pattern of differentially expressed genes. PM2.5 exposure resulted in altered histological changes in the lungs, a reduced alveolar fraction which corresponded to protracted lung inflammation. Our findings suggest a time-dependent entrainment of BM-derived monocytes into the AΦ population of PM2.5 exposed mice, that together with enhanced apoptosis of TR-AΦ and reorganization of transcriptional responses, could collectively contribute to the perpetuation of chronic inflammation.
Effectiveness of dismantling strategies on moderated vs. unmoderated online social platforms
Authors: Artime Oriol , d’Andrea Valeria , Gallotti Riccardo , Sacco Pier Luigi , De Domenico Manlio
Published: September 2020

Online social networks are the perfect test bed to better understand large-scale human behavior in interacting contexts. Although they are broadly used and studied, little is known about how their terms of service and posting rules affect the way users interact and information spreads. Acknowledging the relation between network connectivity and functionality, we compare the robustness of two different online social platforms, Twitter and Gab, with respect to banning, or dismantling, strategies based on the recursive censor of users characterized by social prominence (degree) or intensity of inflammatory content (sentiment). We find that the moderated (Twitter) vs. unmoderated (Gab) character of the network is not a discriminating factor for intervention effectiveness. We find, however, that more complex strategies based upon the combination of topological and content features may be effective for network dismantling. Our results provide useful indications to design better strategies for countervailing the production and dissemination of anti-social content in online social platforms.
Myocardial proteomic profile in pulmonary arterial hypertension
Authors: Hołda Mateusz K. , Stachowicz Aneta , Suski Maciej , Wojtysiak Dorota , Sowińska Natalia , Arent Zbigniew , Palka Natalia , Podolec Piotr , Kopeć Grzegorz
Published: September 2020

Pulmonary arterial hypertension (PAH) is a rare, fatal, and incurable disorder. Although advances in the understanding of the PAH pathobiology have been seen in recent years, molecular processes underlying heart remodelling over the course of PAH are still insufficiently understood. Therefore, the aim of this study was to investigate myocardial proteomic profile of rats at different stages of monocrotaline-induced PAH. Samples of left and right ventricle (LV and RV) free wall collected from 32 Wistar rats were subjected to proteomic analysis using an isobaric tag for relative quantitation method. Hemodynamic parameters indicated development of mild elevation of pulmonary artery pressure in the early PAH group (27.00 ± 4.93 mmHg) and severe elevation in the end-stage PAH group (50.50 ± 11.56 mmHg). In early PAH LV myocardium proteins that may be linked to an increase in inflammatory response, apoptosis, glycolytic process and decrease in myocardial structural proteins were differentially expressed compared to controls. During end-stage PAH an increase in proteins associated with apoptosis, fibrosis and cardiomyocyte Ca2+ currents as well as decrease in myocardial structural proteins were observed in LV. In RV during early PAH, especially proteins associated with myocardial structural components and fatty acid beta-oxidation pathway were upregulated. During end-stage PAH significant changes in RV proteins abundance related to the increased myocardial structural components, intensified fibrosis and glycolytic processes as well as decreased proteins related to cardiomyocyte Ca2+ currents were observed. At both PAH stages changes in RV proteins linked to apoptosis inhibition were observed. In conclusion, we identified changes of the levels of several proteins and thus of the metabolic pathways linked to the early and late remodelling of the left and right ventricle over the course of monocrotaline-induced PAH to delineate potential therapeutic targets for the treatment of this severe disease.
Five years’ trajectories of functionality and pain in patients after hip or knee replacement and association with long-term patient survival
Authors: Repky Stefan , Büchele Gisela , Günther Klaus-Peter , Huch Klaus , Brenner Hermann , Stürmer Til , Beyersmann Jan , Brenner Rolf E. , Rothenbacher Dietrich
Published: September 2020

To describe the 5 years’ trajectories in functionality and pain of patients with hip or knee osteoarthritis and arthroplasty and analyze the association of these with long-term patients survival. Patients with OA receiving total hip or knee arthroplasty were recruited and completed two sets of standardized questionnaires for functionality and pain 6, 12, and 60 months postoperatively. Multivariate mixed models were conducted to assess trajectories over time and the resulting improvement per month during the last time period was included in a landmark-model to estimate adjusted hazard ratios for mortality. In total 809 patients with joint replacement were included (mean age 65.0 years, 62.2% female), 407 patients died (median follow-up 18.4 years). Both instruments of functionality and pain showed extensive improvement during the first 6 months. Baseline and change in functionality (both p < 0.001) and pain (p = 0.02) during the first 6 months were associated with mortality. Better values in functionality corresponded with improved survival whereas the association with the pain scores was inverse. In patients with hip and knee OA, an explicit improvement in function is seen within the first 6 months after arthroplasty. In addition, especially the functionality scores at baseline as well as their improvement showed an association with long-term patient survival.
JNK signaling regulates oviposition in the malaria vector Anopheles gambiae
Authors: Peirce Matthew J. , Mitchell Sara N. , Kakani Evdoxia G. , Scarpelli Paolo , South Adam , Shaw W. Robert , Werling Kristine L. , Gabrieli Paolo , Marcenac Perrine , Bordoni Martina , Talesa Vincenzo , Catteruccia Flaminia
Published: September 2020

The reproductive fitness of theAnopheles gambiaemosquito represents a promising target to prevent malaria transmission. The ecdysteroid hormone 20-hydroxyecdysone (20E), transferred from male to female during copulation, is key toAn. gambiaereproductive success as it licenses females to oviposit eggs developed after blood feeding. Here we show that 20E-triggered oviposition in these mosquitoes is regulated by the stress- and immune-responsive c-Jun N-terminal kinase (JNK). The heads of mated females exhibit a transcriptional signature reminiscent of a JNK-dependent wounding response, while mating—or injection of virgins with exogenous 20E—selectively activates JNK in the same tissue. RNAi-mediated depletion of JNK pathway components inhibits oviposition in mated females, whereas JNK activation by silencing the JNK phosphatasepuckeredinduces egg laying in virgins. Together, these data identify JNK as a potential conduit linking stress responses and reproductive success in the most important vector of malaria.
Ultrasound measurements of superficial and deep masticatory muscles in various postures: reliability and influencers
Authors: Chang Pei-Hsuan , Chen Yunn-Jy , Chang Ke-Vin , Wu Wei-Ting , Özçakar Levent
Published: September 2020

Masticatory muscle thickness provides objective measurements of the oral motor function, which may change in patients with oral myofascial pain. In this study, we aimed to establish a reliable ultrasound (US) protocol for imaging the superficial and deep masticatory muscles and to identify the potential influencers of the measurements. Forty-eight healthy participants without orofacial pain were enrolled. The intra-and inter-rater reliabilities of US measurements for masseter, temporalis, and lateral pterygoid muscles were assessed. Intraclass correlation coefficients for all muscles were greater than 0.6. The generalised estimating equation was used to analyse the impact of age, gender, laterality, and body mass index on the measurements, whereby age and body mass index were likely to be associated with an increase in masticatory muscle thickness. The thickness tended to be lesser in females. Laterality seemed to exert minimal influence on masticatory muscle thickness. Our study shows acceptable reliability of US in the evaluation of superficial and deep masticatory muscle thickness. Future studies are warranted to validate the usefulness of US imaging in patients with oral myofascial pain syndrome.
TICAM2-related pathway mediates neutrophil exhaustion
Authors: Lin RuiCi , Zhang Yao , Pradhan Kisha , Li Liwu
Published: September 2020

Pathogenic inflammation and immune suppression are the cardinal features that underlie the pathogenesis of severe systemic inflammatory syndrome and sepsis. Neutrophil exhaustion may play a key role during the establishment of pathogenic inflammation and immune suppression through elevated expression of inflammatory adhesion molecules such as ICAM1 and CD11b as well as immune-suppressors such as PD-L1. However, the mechanism of neutrophil exhaustion is not well understood. We demonstrated that murine primary neutrophils cultured in vitro with the prolonged lipopolysaccharides (LPS) stimulation can effectively develop an exhaustive phenotype resembling human septic neutrophils with elevated expression of ICAM1, CD11b, PD-L1 as well as enhanced swarming and aggregation. Mechanistically, we observed that TICAM2 is involved in the generation of neutrophil exhaustion, as TICAM2 deficient neutrophils have the decreased expression of ICAM1, CD11b, PD-L1, and the reduced aggregation following the prolonged LPS challenge as compared to wild type (WT) neutrophils. LPS drives neutrophil exhaustion through TICAM2 mediated activation of Src family kinases (SFK) and STAT1, as the application of SFK inhibitor Dasatinib blocks neutrophil exhaustion triggered by the prolonged LPS challenge. Functionally, TICAM2 deficient mice were protected from developing severe systemic inflammation and multi-organ injury following the chemical-induced mucosal damage. Together, our data defined a key role of TICAM2 in facilitating neutrophil exhaustion and that targeting TICAM2 may be a potential approach to treating the severe systemic inflammation.
Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration
Authors: Kim Min Seok , Ryoo Na-Kyung , Park Kyu Hyung
Published: September 2020

This study aims to report the 12 months results of efficacy and safety of laser photocoagulation and anti-vascular endothelial growth factor (VEGF) injections for drusenoid pigment epithelial detachment (dPED). In this prospective study, patients with treatment naïve bilateral intermediate age-related macular degeneration, featuring dPED, with visual acuity ≤ 83 letters were enrolled. The study group received PASCAL laser (532 nm) along the periphery of the dPED, and the fellow eye served as a control group. To prevent complications of choroidal neovascularization, intravitreal anti-VEGF injections to laser treated eye were performed on a 3-month interval up to 1 year. Primary outcomes—drusen area, PED height—and secondary outcomes—best-corrected visual acuity (BCVA), contrast sensitivity, degree of metamorphopsia, NEI-VFQ 25, and fundus autofluorescence—were analyzed. Among 21 patients, a total of 20 patients satisfied the 12 months follow-up. Drusen area and PED height decreased significantly in the laser group, while no significant change appeared in the control group (74.1% vs. − 3.5%, P < 0.001; 76.6% vs. 0.1%, P < 0.001). Mean BCVA improved 4.6 letters in the laser group (vs. 1.1 letters in the control group, P = 0.019). As for safety, one study eye developed retinal pigment epithelial tear, and one control eye developed retinal angiomatous proliferation. Low energy laser photocoagulation and anti-VEGF injection in eyes with dPED showed some improvement in visual acuity. dPED regressed without developing center involving GA in the study eye, but a longer term follow-up is necessary to reveal the efficacy and safety of these treatments. The 2-year results of this study will be followed to reveal long term efficacy and safety of the treatment for dPED.
Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
Authors: Duffy Ciara , Sorolla Anabel , Wang Edina , Golden Emily , Woodward Eleanor , Davern Kathleen , Ho Diwei , Johnstone Elizabeth , Pfleger Kevin , Redfern Andrew , Iyer K. Swaminathan , Baer Boris , Blancafort Pilar
Published: September 2020

Despite decades of study, the molecular mechanisms and selectivity of the biomolecular components of honeybee (Apis mellifera) venom as anticancer agents remain largely unknown. Here, we demonstrate that honeybee venom and its major component melittin potently induce cell death, particularly in the aggressive triple-negative and HER2-enriched breast cancer subtypes. Honeybee venom and melittin suppress the activation of EGFR and HER2 by interfering with the phosphorylation of these receptors in the plasma membrane of breast carcinoma cells. Mutational studies reveal that a positively charged C-terminal melittin sequence mediates plasma membrane interaction and anticancer activity. Engineering of an RGD motif further enhances targeting of melittin to malignant cells with minimal toxicity to normal cells. Lastly, administration of melittin enhances the effect of docetaxel in suppressing breast tumor growth in an allograft model. Our work unveils a molecular mechanism underpinning the anticancer selectivity of melittin, and outlines treatment strategies to target aggressive breast cancers.
Aptamer-based strategies for recognizing adenine, adenosine, ATP and related compounds
Authors: Li Yuqing , Liu Juewen
Published: September 2020

Adenine, adenosine, ATP and related compounds are highly important in biology. A variety of DNA and RNA aptamers have been found to selectively bind them. This article reviews important aptamers for them and their representative applications.
A two-chip acoustofluidic particle manipulation platform with a detachable and reusable surface acoustic wave device
Authors: Qian Jingui , Ren Jifeng , Liu Yi , Lam Raymond H. W. , Lee Joshua E.-Y.
Published: September 2020

A two-chip acoustofluidic particle manipulation platform with a detachable and reusable surface acoustic wave device enables manipulation of microparticles in 2D on a replaceable silicon superstrate.
Substrate stiffness induced mechanotransduction regulates temporal evolution of human fetal neural progenitor cell phenotype, differentiation, and biomechanics
Authors: Kothapalli Chandrasekhar , Mahajan Gautam , Farrell Kurt
Published: September 2020

We here report on the substrate stiffness dependent spatiotemporal evolution of mechanical properties of neural stem cells and their progenies.
Excimer emission and magnetoluminescence of radical-based zinc(ii) complexes doped in host crystals
Authors: Kimura Shun , Kimura Shojiro , Nishihara Hiroshi , Kusamoto Tetsuro
Published: September 2020

A ZnIIcomplex with luminescent organic radical ligands doped into host molecular crystals showed an excimer emission and its luminescent behavior was significantly modulated by an external magnetic field.
Cu2O@Fe–Ni3S2 nanoflower in situ grown on copper foam at room temperature as an excellent oxygen evolution electrocatalyst
Authors: Wu Li Li , Yang Yu Xian , Chen Xiao Hui , Luo Juan , Fu Hong Chuan , Shen Li , Luo Hong Qun , Li Nian Bing
Published: September 2020

A 3D/2D core–shell Cu2O@Fe–Ni3S2 nanoflower is prepared at room temperature through an etching precipitation strategy for enhanced electrochemical water oxidation.
Boosting the sensitivity ofin vitroβ-lactam allergy diagnostic tests
Authors: Peña-Mendizabal Edurne , Morais Sergi , Maquieira Ángel
Published: September 2020

The synthesis of structurally new haptens and the development of suitable antigens are essential for boosting the sensitivity of drug allergy diagnostic testing.
Spatially resolved electrochemistry enabled by thin-film optical interference
Authors: Wang Yafeng , Yang Qian , Su Bin
Published: September 2020

Electrochemical reactions occurring on the local surface can be spatially resolved by successive interferometric imaging of the nanochannel membrane coated electrode.
Advances and challenges for experiment and theory for multi-electron multi-proton transfer at electrified solid–liquid interfaces
Authors: Sakaushi Ken , Kumeda Tomoaki , Hammes-Schiffer Sharon , Melander Marko M. , Sugino Osamu
Published: September 2020

Understanding microscopic mechanism of multi-electron multi-proton transfer reactions at complexed systems is important for advancing electrochemistry-oriented science in the 21st century.
Triangulenium dyes: the comprehensive photo-absorption and emission story of a versatile family of chromophores
Authors: Barsuk Irina , Lainé Philippe P. , Maurel François , Brémond Éric
Published: September 2020

The triangulenium dyes constitute a family of versatile chromophores whose impressive vibrationally-resolved photo-absorption and emission properties are faithfully modeled at TDDFT level.
Theoretical insights into single-atom catalysts
Authors: Li Lulu , Chang Xin , Lin Xiaoyun , Zhao Zhi-Jian , Gong Jinlong
Published: September 2020

Schematic diagram of theoretical models and applications of single atom catalysts. A review on the theoretical models, intrinsic properties, and the related application of SACs.
Ionic liquid-stabilized vanadium oxo-clusters catalyzing alkane oxidation by regulating oligovanadates
Authors: Zhou Qingqing , Zhang Ran , Li Difan , Ding Bingjie , Zheng Anna , Yao Yefeng , Gong Xueqing , Hou Zhenshan
Published: September 2020

The specific ionic liquid [TBA][Pic]-stabilized vanadium oxo-clusters exist in the form of a trimer and a dimer and are highly active for catalyzing C–H bond oxidation with H2O2 as an oxidant.
Significant power enhancement of magneto-mechano-electric generators by magnetic flux concentration
Authors: Song Hyunseok , Patil Deepak Rajaram , Yoon Woon-Ha , Kim Kwang-Ho , Choi Cheol , Kim Jong-Hyun , Hwang Geon-Tae , Jeong Dae-Yong , Ryu Jungho
Published: September 2020

A magneto-mechano-electric (MME) generator comprising a magnetoelectric (ME) composite and magnetic flux concentrator (MFC) can effectively harvest the tiny magnetic noise to power the autonomous internet of things (IoT) sensor networks.
Amyloid hybrid membranes for removal of clinical and nuclear radioactive wastewater
Authors: Bolisetty Sreenath , Coray Nastasia M. , Palika Archana , Prenosil George A. , Mezzenga Raffaele
Published: September 2020

Highly efficient hybrid amyloid membrane to remove clinical and nuclear radioactive wastewater.
Exogenous natural EPA-enriched phosphatidylcholine and phosphatidylethanolamine ameliorate lipid accumulation and insulin resistance via activation of PPARα/γ in mice
Authors: Tian Yingying , Liu Yanjun , Xue Changhu , Wang Jingfeng , Wang Yuming , Xu Jie , Li Zhaojie
Published: September 2020

Dietary eicosapentaenoic acid in the form of phosphatidylcholine and phosphatidylethanolamine improves lipid accumulation and insulin resistance via activation of PPARα/γ.
Interplay between local distortion at lattice sites with optical and electrical properties of Eu3+-doped MNbO3 (M = Na and K) compounds
Authors: Pathak Nimai , Mukherjee Sumanta , Mandal Balaji Prasad , Yadav A. K. , Jha S. N. , Bhattacharyya D.
Published: September 2020

An effort was made to understand the correlation between local distortion at the lattice site with optical and electrical properties of Eu3+-doped MNbO3 (M = Na and K) compounds for their potential application in piezophotonic devices.
Machine learning approaches for elucidating the biological effects of natural products
Authors: Zhang Ruihan , Li Xiaoli , Zhang Xingjie , Qin Huayan , Xiao Weilie
Published: September 2020

This review presents the basic principles, protocols and examples of using the machine learning approaches to investigate the bioactivity of natural products.
Novel excited-state nanothermometry combining the red-shift of charge-transfer bands and a thermal coupling effect
Authors: Jia Mochen , Lin Fang , Sun Zhen , Fu Zuoling
Published: September 2020

Unprecedented excited-state nanothermometry with high sensitivity and low temperature uncertainty is proposed by combining the red-shift of V–O charge-transfer bands and a thermal coupling effect.