Abstract In many legumes, roots that are exposed to blue light do not form nodules, and blue light induces the biosynthesis of hydrogen peroxide (H2O2). The mechanism of blue light restraining nodulation is poorly understood. Whether H2O2 induced by blue light inhibits nodulation needs to be further studied. In this work, blue light could promote the production of H2O2, activate the expression of LjRbohD and LjRbohE, while inhibit the expression of LjRbohB. After applying exogenous H2O2 and diphenyleneiodonium chloride (DPI), the results show H2O2 induced by blue light represses the nodulation of MG20. The accumulated H2O2 may be generated by LjRbohD, which supported by Q-PCR. Cryptochrome 1A, a blue light photoreceptor, is high expression under blue light. However, there seems to be no direct relationship between LjRbohD and LjCry1A. On the contrary, LjRbohB, a positive governor in the regulation of nitrogen fixation activity in L. japonicus, may be negatively regulated by LjCry1A according to the hairy roots transformation results. Therefore, the mechanisms of regulating the nodulation in L. japonicus by LjRbohB and LjRbohD are quite different under blue light. Keywords: Louts japonicus, accumulated H2O2, blue light, nodulation, LjRbohs.

Sparse (fast) representations of deterministic signals have been well studied. Among other types there exists one called adaptive Fourier decomposition (AFD) for functions in analytic Hardy spaces. Through the Hardy space decomposition of the $L^2$ space the AFD algorithm also gives rise to sparse representations of signals of finite energy. To deal with multivariate signals the general Hilbert space context comes into play. The multivariate counterpart of AFD in general Hilbert spaces with a dictionary has been named pre-orthogonal AFD (POAFD). In the present study we generalize AFD and POAFD to random analytic signals through formulating stochastic analytic Hardy spaces and stochastic Hilbert spaces. To analyze random analytic signals we work on two models, both being called stochastic AFD, or SAFD in brief. The two models are respectively made for (i) those expressible as the sum of a deterministic signal and an error term (SAFDI); and for (ii) those from different sources obeying certain distributive law (SAFDII). In the later part of the paper we drop off the analyticity assumption and generalize the SAFDI and SAFDII to what we call stochastic Hilbert spaces with a dictionary. The generalized methods are named as stochastic pre-orthogonal adaptive Fourier decompositions, SPOAFDI and SPOAFDII. Like AFDs and POAFDs for deterministic signals, the developed stochastic POAFD algorithms offer powerful tools to approximate and thus to analyze random signals.

A 56-year-old female with definite FH was reported based on clinical algorithms. Whole exome sequencing identified a heterozygous LDLR mutation (c.1599G>A), which is pathogenic according to ACMG guidelines. Sanger sequencing was performed in family members, and the mutation site was co-segregated with the disease in the family.

Chronic paracoccidioidomycosis is an endemic fungal infection in Latin America and, although uncommon, the opening of the clinical condition can be an obstructive abdominal syndrome that can simulate a pancreatic head neoplasm. There are few cases like this reported in the literature.

One could be excused for assuming that deep learning had or will soon usurp all credible work in reasoning, artificial intelligence and statistics, but like most ‘meme’ class broad generalizations the concept does not hold up to scrutiny. Memes don’t generally matter since the experts will always know better but in the case of Bayesian software like Stan and PyMC3 even its developers and advocates bemoan the apparent dominance of deep learning as manifested in popular culture, breathtaking performance and most problematically from funding agency peer review that impacts our ability to further advance the field. The facts however do not support the assumed dominance of deep learning in science upon closer examination. This letter simply makes the argument by the crudest of possible metrics, citation count, that once Computer Science is subtracted, Bayesian software accounts for nearly a third of research citations. Stan and PyMC3 dominate some fields, PyTorch, Keras and TensorFlow dominate others with lots of variation in between. Bayesian and deep learning approaches are related but very different technologies in goals, implementation and applicability with little actual overlap so this is not a surprise. While deep learning is backed by industry behemoths (Google, Facebook) the Bayesian efforts are not and it would behoove funders to recognize the impact of Bayesian software given its centrality to science.

Genome sequencing(GS) has been applied in the diagnosis of global developmental delay(GDD)/intellectual disability(ID). However, the performance in those with inconclusive results from chromosomal microarray analysis(CMA) and exome sequencing(ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test prior to enrollment. Reanalysis of CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 23%. Seven families could have been solved with reanalysis of ES data. 13 families were missed by previous CMA/ES due to improper method. Three remained unsolved after ES reanalysis due to allele dropout, complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this cohort of undiagnosed GDD/ID patients, detecting a wide range of variant types of different sizes in a single workflow.

Groundwater recharge in highly-fractured volcanic aquifers remains poorly understood in the humid tropics, whereby rapid demographic growth and unregulated land use change are resulting in extensive surface water pollution and a large dependency on groundwater extraction. Here we present a multi-tracer approach including δ18O-δ2H, 3H/3He, and noble gases within the most prominent multi-aquifer system of central Costa Rica, with the objective to assess dominant groundwater recharge characteristics and age distributions. We sampled wells and large springs across an elevation gradient from 868 to 2,421 m asl. Our results suggest relatively young apparent ages ranging from 0.0±3.2 up to 76.6±9.9 years. Helium isotopes R/RA (0.99 to 5.4) indicate a dominant signal from the upper mantle across the aquifer. Potential recharge elevations ranged from ~1,400 to 2,650 m asl, with recharge temperatures varying from ~11°C to 19°C with a mean value of 14.5±1.9°C. Recharge estimates ranged from 129±78 to 1,605±196 mm/yr with a mean value of 642±117 mm/yr, representing 20.1±4.0% of the total mean annual rainfall as effective recharge. The shallow unconfined aquifer is characterised by young and rapidly infiltrating waters, whereas the deeper aquifer units have relatively older waters. These results are intended to guide the delineation and mapping of critical recharge areas in mountain headwaters to enhance water security and sustainability in the most important headwater dependent systems of Costa Rica.

Organometallic sandwich complexes have been attracting tremendous interest for their potential applications in electronics and spintronics. Here, we systematically studied the structures, electronic and magnetic properties of one dimensional (1D) transition metal (TM)-anthracene (Ant) sandwich molecular wires (SMWs), [TM2Ant]∞ and [TM3Ant]∞ (TM=Ti, V, Cr, Mn), based on density functional theory calculations. Our results showed that all the 1D SMWs display normal sandwich configurations with their binding energies closely related to the choice of TM atoms. Excepting 1D [Mn2Ant]∞ and [Fe3Ant]∞ favoring antiferromagnetic ordering, most 1D [TM2Ant]∞ and [TM3Ant]∞ SMWs display robust ferromagnetic feathers. Particularly, 1D [Cr3Ant]∞ SMW is revealed to be ferromagnetic half-metal with large magnetic moment of 28.0µB per unit cell. Further spintransport calculations double proved that 1D [Cr3Ant]∞ SMW are good spintransport molecular devices. Our findings shed light on the properties of 1D Ant based SMWs and propose a new way to design potential electronic and spintronic devices.

Global economic development and population increase public concerns about the sustainable use of water resources. As one of the main drivers of landscape change, human disturbance is altering rivers’ hydrochemical indices and trophic states. Studying the relationship between human disturbances and river’ status is of significance for regional water conservation and ecosystem safety. In this study, we created a quantitative model to explore the correlation between human disturbance and rivers’ status using remote sensing data, measured hydrochemical indices, and the concept of hemeroby index (HI). The results indicated that the river’s status including hydrochemical indices and trophic states both had a significant negative correlation with HI (p<0.05). The river’s status in regions was relatively sensitive to the changes of completely disturbed land-use types, such as urban and industrial land. This paper provides additional spatial information and evidence for the relationship between anthropogenic activities and the river environment. The findings may be helpful for policymakers to make strategic decisions of water resources management and land-use planning in an arid area of China.

A document by Peter Shaw. Click on the document to view its contents.

Background: We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. Methods: In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. Results: In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per interquartile range (IQR) increase observed for sleep quality (odds ratio [OR] =1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00–1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). Conclusion: The most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children’s sleep quality and preventing obesity comorbidities such as SDB.

Bipolar disorder is a chronic and recurring psychiatric illness. Emphasis on enhancing key protective factors like social support systems and promoting this to minimize risk factors like non-compliance is one of the key strategies tied to enhance overall health for symptoms remission and relapse prevention even during the COVID-19 Pandemic.

All species must balance their allocation to growth, survival and recruitment. Among trees, evolution has resulted in different strategies of partitioning resources to these key demographic processes, i.e. demographic trade-offs. It is unclear whether the same demographic trade-offs structure tropical forests worldwide. Here, we used data from 13 large-scale and long-term tropical forest plots to estimate the principal trade-offs in growth, survival, recruitment, and tree stature at each site. For ten sites, two trade-offs appeared repeatedly. One trade-off showed a negative relationship between growth and survival, i.e. the well-known fast−slow continuum. The second trade-off distinguished between tall-statured species and species with high recruitment rates, i.e. a stature−recruitment trade-off. Thus, the fast-slow continuum and tree stature are two independent dimensions structuring most tropical tree communities. Our discovery of the consistency of demographic trade-offs and strategies across forest types in three continents substantially improves our ability to predict tropical forest dynamics worldwide.

Flower-visiting insects have co-evolved with flowering-plants. While it has been shown that floral traits and environmental factors influence insects visitations during the day, it is yet unclear how these factors influence insects visitations at night. We sampled a montane meadow located near Jilin in northeastern China in July and August in 2019, 4 nights each month, and two time periods each night. We sampled 94 flower-visiting insect species in total and documented the floral traits and ambient factors. First, focusing on the insects functions, we allocated all insects into three functional groups (pollination, predation, and feeding). We found that most nocturnal insects exhibited predation behavior, and they had the highest species turnover rate. Second, focusing on the environmental factors, we found that ambient temperature and relative humidity strongly influence the diversity of flower-visiting insects. Variation partitioning analysis further suggested that ambient temperature has a stronger effect on the flowering-visiting insects at early night, while the relative humidity has a stronger effect on the flowering-visiting insects at late night. Third, focusing on floral traits, we found that most insects have a preference for flowers with moderately-sized corolla diameters (20 to 30 mm). Furthermore, display size had a strong linear correlation with flowering-visiting insect species richness and frequency of presence. In sum, our findings suggest that ambient temperature, relative humidity, and floral display size strongly regulate nocturnal flower-visiting insects.

Acidification-induced changes in cognitive function and behavior have recently been documented in tropical marine fishes, raising concerns about related shifts in species interactions. Here, we investigate whether similar patterns of broad neurological impacts are observed in a temperate Pacific fish that experiences regular and often large shifts in environmental pH due to upwelling events and other natural phenomena. In two manipulative laboratory experiments, we tested the effect of acidification, as well as pH variability, on gene expression in the brain tissue of a common temperate kelp forest/estuarine fish, Embiotoca jacksoni. We found that patterns of global gene expression in brain tissue differed significantly across pH level treatments. Additionally, differential gene expression analysis and gene set enrichment analysis identified significant differential expression of specific genes and gene sets both in comparisons of static pH level treatments as well as in static vs. variable pH treatment comparisons where mean pH was consistent. Enriched gene sets included those related to ion transport, signaling pathways, mRNA processing and splicing, and epigenetic regulation of gene expression, among others. Importantly, we found that pH variability decreased the number of differentially expressed genes detected between high and low pH treatments, and that the inter-individual variability in gene expression was significantly greater in variable pH treatments than static treatments of the same mean pH. By demonstrating a broad shift in brain gene expression, these results provide important confirmation of neurological impacts of acidification in a temperate fish species, which are likely to translate to shifts in behavior. This study also provides critical insight into the potential of natural environmental variability to mediate the impacts of ocean acidification.

Aims: To investigate pharmacokinetics (PK) and exposure-response of the 400 mg once daily venetoclax dose regimen in combination with obinutuzumab in the phase 3 CLL14 study approved for the treatment of first-line (1L) chronic lymphocytic leukaemia (CLL). Methods: Parameter estimates and uncertainty estimated by a previously developed population PK (popPK) model were used as informative priors for this analysis. They were re-estimated, then used to evaluate additional covariate effects, describe venetoclax PK when administered with obinutuzumab, and provide empirical Bayes estimates of PK parameters and exposure. Exposure-progression-free survival (PFS) and exposure-safety relationships were assessed using CLL14 data, with steady-state exposure at the nominal target dose (CmeanSS,nominal) as the predictor variable. Exposure-safety analyses were conducted using logistic regression for selected treatment-emergent grade ≥3 adverse events (AEs) and serious AEs (SAEs). Dose intensities were summarized by tertiles of CmeanSS,nominal. Results: PK data from 274 patients (CLL14, n=194; phase 1b dose-finding study GP28331, n=80) were included. The final model provided good fit of observed data. Obinutuzumab co administration, history of prior treatments, and disease severity at baseline had no appreciable influence on venetoclax steady-state exposure. No significant correlations were observed between venetoclax exposure and PFS, or between venetoclax exposure and the probability of treatment-emergent grade ≥3 neutropenia, grade ≥3 thrombocytopenia, grade ≥3 infections and SAEs. Median dose intensities for venetoclax and obinutuzumab remained similar across venetoclax exposure tertiles. Conclusion: PopPK and exposure efficacy, -safety and -tolerability analyses support the 400 mg once-daily venetoclax dose plus obinutuzumab in patients with 1L CLL.

Abstract Background: Location of cancer care (LOC: pediatric versus adult center) impacts outcomes in adolescents and young adults (AYA) with some cancer types. Data on impact of LOC on survival in AYA with osteogenic sarcoma (OGS) and Ewing sarcoma (EWS) are limited. Objectives: To compare differences in demographics, disease/treatment characteristics, and survival in a population-based cohort of AYA with OGS or EWS treated at pediatric versus adult centers Methods: The IMPACT Cohort captured demographic, disease, and treatment data for all AYA (15-21 years old) diagnosed with OGS and EWS in Ontario, Canada between 1992-2012. Patients were linked to provincial administrative healthcare databases. Outcomes were compared between patients treated in pediatric versus adult centers using appropriate statistical methods. Results: 137 AYA were diagnosed with OGS (LOC: 47 pediatric, 90 adult) and 84 with EWS (LOC: 38 pediatric, 46 adult). AYA treated at pediatric centers were more likely to be enrolled in a clinical trial (OGS 55% vs 1%, [p<0.001]; EWS 53% vs 2%, [p<0.001]) and received higher cumulative chemotherapy doses. Five-year event-free survival (EFS ± Standard Error) in OGS and EWS were 47% ± 4 and 43% ± 5, respectively. In multivariable analysis, the impact of LOC (pediatric vs adult center) on EFS in OGS (adjusted hazard ratio [HR] 1.15, 95% CI 0.58-2.27, P=0.69) and EWS (adjusted HR 1.82, 95% CI 0.97-3.43, P=0.06) were not statistically significant. Conclusion: Outcomes did not differ by LOC suggesting that AYA with bone tumors can be treated at either pediatric or adult centers.

Title: The Practical Matters of Including Patient Reported Outcomes in Pediatric Oncology Clinical CareEmily L Mueller, MD MSc1,2Center for Pediatric and Adolescent Comparative Effectiveness Research, Indiana University, Indianapolis, IN 46202Section of Pediatric Hematology Oncology, Department of Pediatrics, Indiana University, Indianapolis, IN 46202Correspondence:Emily L Mueller, MD, MSc705 Riley Hospital Dr, ROC 4340Indianapolis, IN 46202Cell: 312-399-0245 Fax: 317-944-3107elmuelle@iu.eduAbstract word count: 0Main text word count: 6654Number of tables: 0Number of figures: 0Short Title: Practicalities of PRO in Clinical CareAbbreviations:

The Impella 5.5 with SmartAssist (Abiomed; Danvers, MA) is a life-saving treatment option in acute heart failure which utilizes a continuous heparin purge solution to prevent thrombosis. In patients with contraindications to heparin, alternative anticoagulation strategies are required. We describe the stepwise management of anticoagulation in a coagulopathic patient with persistent cardiogenic shock following a coronary artery bypass procedure who underwent Impella 5.5 placement. A direct thrombin inhibitor-based purge solution was utilized while evaluating for heparin-induced thrombocytopenia. Use of a novel bicarbonate-based purge solution (BBPS) was successfully used due to severe coagulopathy. There were no episodes of pump thrombosis or episodes of severe bleeding on the BBPS and systemic effects of alkalosis and hypernatremia were minimal.

Changes in sensitization rates in patients with asthma and/or rhinitis in China between 2008 and 2018: a national cross-sectional studyWanjun Wang1*, Jianhong Wang2*, Guihua Song3*, Hua Xie4*, Xiaoping Lin4*, Ruonan Chai4*, Rongfei Zhu5*, Yong He6*, Jun Tang7*, Junge Wang8*, Jinghua Yang9*, Lili Zhi10*, Lin Wu11*, Yan Jiang12*, Xiaoqin Zhou13*, Dongming Huang14*, Ning Wang15*, Rui Xu16*, Yuan Gao17*, Zhimin Chen18*, Jinling Liu18*, Xiaoli Han19*, Guolin Tan20*, Jinzhun Wu21*, Deyu Zhao22*, Jianjun Chen23*, Xiwei Zhang24*, Mengrong Li24*, Yuemei Sun25*, Yi Jiang26*, Weitian Zhang27*, Qianhui Qiu28*, Chuanhe Liu29*, Jie Yin30*, Guodong Hao31*, Huabin Li32*, Yongsheng Xu33*, Shaohua Chen34*, Hua Zhang35, Shi Chen36, Juan Meng37, Dan Zeng38, Wei Tang39, Chuangli Hao40, Jing Li1†, Nanshan Zhong1†, for the China Alliance of Research on Respiratory Allergic Disease*Contributed equally†Joint corresponding authors1 National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University;2 The First People’s Hospital of Yibin, Sichuan;3 The First Affiliated Hospital of Henan University of Traditional Chinese Medicine;4 General Hospital of Northern Theater Command;5 Tongji Hospital, Tongji Medical College, Huazhong University of Science&Technology;6 The Affiliated Hospital of Medical School, Ningbo University;7 Foshan First people’s hospital;8 Beijing Hospital of Traditional Chinese Medicine;9 GuangDong Provincial Hospital of Chinese Medicine;10 The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases;11 Hangzhou Hospital of Traditional Chinese;12 The Affiliated Hospital of Qingdao University;13 Hubei Province Maternal and Child Health Hospital;14 Boai Hospital of Zhongshan City;15 Xi’an Children’s Hospital;16 The First Affiliated Hospital of Sun-Yat University;17 The First Affiliated Hospital of Zhengzhou University;18 Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health;19 Hebei General Hospital;20 Third Xiangya Hospital of Central South University;21 The Women and Children’s Hospital affiliated to Xiamen University;22 Children’s Hospital of Nanjing Medical University;23 Union hospital of Tongji medical college;24 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University;25 Yu Huang Ding Hospital;26 The First Hospital of Shanxi Medical University;27 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital;28 Zhujiang Hospital of Southern Medical University;29 Children’s Hospital Capital Institute of Pediatrics;30 Chengdu First People’s Hospital;31 Tangshan Gongren Hospital;32 ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University;33 Children’s Hospital of Tianjin University;34 Guangdong Provincial People’s Hospital;35 The First Affiliated Hospital of Xinjiang Medical University;36 Hainan provincial people’s Hospital;37 West China Hospital of Sichuan University;38 Chongqing General Hospital, University of Chinese Academy of Sciences;39 Ruijin Hospital of Shanghai Jiaotong University;40 Children’s Hospital of Soochow University.

The work reported in this investigation involves the determination of the hydrodynamic properties of the Trickle Bed Reactor which has been loaded in various ways to mark the effect of the loading methodologies employed to pack the catalyst pellets. The bed structure of a packed three-phase reactor is critical to study as it provides the essential contact between the phases and provides the catalytic sites where the reaction takes place. Depending on the structural properties of the bed such as local void structure, liquid distribution, two-phase pressure drop, and holdup of fluids gets affected. The study aims to envelop the catalyst bed characteristics such as the local void structure, the length of the catalyst bed, flow characteristics such as liquid and gas flow rate, and liquid distributor at the top of the catalyst bed to gauge and quantify their effect on the hydrodynamics of a trickle bed reactor.

The definite solutions of the differential equations from a three-component triangle reaction network have been obtained by utilizing the concept of virtual component concentration and some mathematical techniques. The kinetic model forming from the above definite solutions reveals that the overall reaction rate will be affected by the distribution entropy of the rate coefficients. The improved eigenvector method including a basic equation, algorithm, and criterion has been proposed for calculating the rate coefficients from experimental concentration curves.

Coarse-grained methods have been widely used in simulations of gas-solid fluidization. However, as a key parameter, the coarse-graining ratio, and its relevant scaling law is still far from reaching a consensus. In this work, a scaling law is developed based on a similarity analysis, and then it is used to scale the multi-phase particle-in-cell (MP-PIC) method, and validated in the simulation of two bubbling fluidized beds. The simulation result shows this scaled MP-PIC can reduce the errors of solids volume fraction and velocity distributions over a wide range of coarse-graining ratios. In future, we expect that a scaling law with consideration of the heterogeneity inside a parcel or numerical particle will further improve the performance of coarse-grained modeling in simulation of fluidized beds.

Yttrium-doped barium cerate (BaCe0.8Y0.2O3-δ, BCY) is the most widely studied proton conducting material and is frequently fabricated as dense membranes for hydrogen separation. However, the difficulty to prepare dense BCY membranes is the extremely high sintering temperature, normally higher than 1500 oC. Herein, the BCY 7-channel hollow fiber membrane was prepared by one-step thermal processing (OSTP). It proved that adding Co2O3 as sintering aid is beneficial to the densification and 1wt% Co2O3 was the optimum addition to form a homogeneous phase structure. The dense sintering temperature was greatly reduced from over 1500 to 1350 oC. The hydrogen permeation flux of the BCY hollow fiber membrane reached up to 0.34 ml min-1cm-2 at 900 oC. The long-term stability test last for 300 h. The properties of OSTP samples were demonstrated to be essentially higher than samples made by conventional ceramic hollow fiber fabrication methods.