bluuebunny/crossref_metadata_2025 huggingface dataset:
United States local health department engagement in activities that support active transportation considerations in land use and transportation policies: Results of a national survey
Authors: Sreedhara Meera , Goins Karin Valentine , Frisard Christine , Lemon Stephenie C.
Published: October 2022

Active transportation by walking or biking can improve health and quality of life. Public health official participation in transportation and land use policy-related decision-making is recommended to improve opportunities for active transportation. However, United States local health department (LHD) engagement in activities that support this decision-making is not well understood. The purpose of this study was to describe engagement in activities that support inclusion of active transportation in transportation and land use decision-making among small and midsize LHDs, identify LHD characteristics associated with engagement, and describe interest in training activities to increase engagement. Data are from a 2017 national probability cross-sectional survey of United States LHDs serving fewer than 500,000 residents that assessed departmental engagement in eleven activities related to ten cross-cutting capabilities that support engagement in transportation and land use decision-making (30.2% response rate). Negative binomial regression of 183 LHDs with complete data determined the relationship between LHD characteristics and engagement in activities. Survey weights were applied to generate nationally representative statistics. LHDs reported their engagement in eleven activities that support active transportation in land use and transportation decision-making as a major responsibility, secondary responsibility, or neither. Responses were summed to generate a score. LHDs reporting major responsibility varied by activity and ranged from 8.6% for data and assessment to 32.7% for public outreach to community. The distribution of engagement scores was skewed (mean = 6.2, variance = 34.7). Larger population size served, any staff working on active transportation issues, and contracting with an individual/organization on active transportation were significantly associated with greater engagement in activities related to land use and transportation decision-making that support active transportation. High interest in training or technical assistance for activities ranged from 12.2% for dedicated staffing to 42.8% for public outreach to community. These data demonstrate room for improvement in activities and capabilities supportive of active transportation in land use and transportation decision-making and modest but promising interest in assistance for greater engagement among LHDs.
Recycling channel selection and financing strategy for capital-constrained retailers in a two-period, closed-loop supply chain
Authors: Zhang Weisi , Zhang Tao
Published: October 2022

This article studies a two-period, closed-loop supply chain (CLSC) with manufacturer or retailer recycling. It establishes a model analysis framework to analyze pricing optimization strategies and the channel-mode selection of electric vehicle batteries and considers manufacturer recycling and retailer recycling scenarios. When a retailer recycles, it needs to invest capital to build its recycling channel and so suffers from capital constraints. For this reason, retailers consider bank loans or trade-credit financing from manufacturers. This work explores a two-stage, CLSC pricing strategy that considers consumers’ preferences for remanufactured products and recycling rates, and it investigates financing channels for capital-constrained retailers. It analyzes optimal equilibrium strategies in three modes and compares the recycling and financing modes. Through numerical examples, it analyzes the effects of value preference rates and recycling rates of remanufactured products on supply chain profits, product demand, and model selection. The results show that the recycling rate can effectively incentivize the demand for new products in the first period. For any remanufactured product recycling cost, the manufacturer’s profit is most significant in the retailer-recycling bank financing model, and the retailer’s profit is largest in the manufacturer recycling model. As the consumer preference rate for remanufactured products increases, the demand for new products in the second stage decreases and the demand for remanufactured products increases. The retailer recycling trade-credit financing from the manufacturer model gives the largest profit to the retailer when the preference rate is significant or when the preference rate is low with a moderate recycling rate.
IκBNS expression in B cells is dispensable for IgG responses to T cell-dependent antigens
Authors: Khoenkhoen Sharesta , Ádori Monika , Solís-Sayago Darío , Soulier Juliette , Russell Jamie , Beutler Bruce , Pedersen Gabriel K. , Karlsson Hedestam Gunilla B.
Published: October 2022

Mice lacking the atypical inhibitory kappa B (IκB) protein, IκBNS, a regulator of the NF-κB pathway encoded by the nfkbid gene, display impaired antibody responses to both T cell-independent (TI) and T cell-dependent (TD) antigens. To better understand the basis of these defects, we crossed mice carrying floxed nfkbid alleles with mice expressing Cre under the transcriptional control of the Cd79a gene to create mice that lacked IκBNS expression only in B cells. Analyses of these conditional knock-out mice revealed intact CD4+ and CD8+ T cell populations, including preserved frequencies of FoxP3+ regulatory T cells, which are known to be reduced in IκBNS knock-out mice. Like IκBNS knock-out mice, mice with conditional IκBNS ablation in B cells displayed defective IgM responses to TI antigens and a severe reduction in peritoneal B-1a cells. However, in contrast to mice lacking IκBNS altogether, the conditional IκBNS knock-out mice responded well to TD antigens compared to the control mice, with potent IgG responses following immunization with the viral antigen, rSFV-βGal or the widely used hapten-protein model antigen, NP-CGG. Furthermore, B cell intrinsic IκBNS expression was dispensable for germinal center (GC) formation and T follicular helper cell responses to NP-CGG immunization. The results presented here suggest that the defect in antibody responses to TD antigens observed in IκBNS knock-out mice results from a B cell extrinsic defect.
Humoral immunity and transcriptome differences of COVID-19 inactivated vacciane and protein subunit vaccine as third booster dose in human
Authors: Zhang Yuwei , Yao Mingxiao , Guo Xingyu , Han Shanshan , Zhang Shu , Zhang Jinzhong , Jiang Xiangkun , Wang Jianxing , Fang Ming , Wang Shuang , Pang Bo , Liu Xiaolin , Kou Zengqiang , Jiang Xiaolin
Published: October 2022

Under the background of the severe human health and world economic burden caused by COVID-19, the attenuation of vaccine protection efficacy, and the prevalence and immune escape of emerging variants of concern (VOCs), the third dose of booster immunization has been put on the agenda. Systems biology approaches can help us gain new perspectives on the characterization of immune responses and the identification of factors underlying vaccine-induced immune efficacy. We analyzed the antibody signature and transcriptional responses of participants vaccinated with COVID-19 inactivated vaccine and protein subunit vaccine as a third booster dose. The results from the antibody indicated that the third booster dose was effective, and that heterologous vaccination with the protein subunit vaccine as a booster dose induced stronger humoral immune responses than the homologous vaccination with inactivated vaccine, and might be more effective against VOCs. In transcriptomic analysis, protein subunit vaccine induced more differentially expressed genes that were significantly associated with many important innate immune pathways. Both the homologous and heterologous boosters could increase the effectiveness against COVID-19, and compared with the inactivated vaccine, the protein subunit vaccine, mediated a stronger humoral immune response and had a more significant correlation with the innate immune function module, which provided certain data support for the third booster immunization strategy.
Humoral and cellular immune responses to CoronaVac up to one year after vaccination
Authors: Costa Priscilla Ramos , Correia Carolina Argondizo , Marmorato Mariana Prado , Dias Juliana Zanatta de Carvalho , Thomazella Mateus Vailant , Cabral da Silva Amanda , de Oliveira Ana Carolina Soares , Gusmão Arianne Fagotti , Ferrari Lilian , Freitas Angela Carvalho , Patiño Elizabeth González , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Scharf Rami , Kallás Esper Georges , Silveira Cássia Gisele Terrassani
Published: October 2022

Coronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4+ T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4+ T cells were predominantly of central and effector memory T cell phenotypes and were sustained for at least 6 months. We also detected a balanced Th1-, Th2- and Th17/Th22-type cytokine production that was associated with response over time, together with particular cytokine profile linked to poor responses in older vaccinees. SARS-CoV-2-specific IgG levels peaked 14 days after the second dose and were mostly stable over one year. CoronaVac was able to induce a potent and durable antiviral antigen-specific cellular response and the cytokine profiles related to the response over time and impacted by the senescence were defined.
Spatial-digital joint self-interference cancellation method for in-band full-duplex underwater acoustic communication
Authors: Lu Yinheng , Qing Xin , Yang Chenlu , Zhao Yunjiang , Wu Songwen , Qiao Gang
Published: October 2022

The in-band full-duplex underwater acoustic communication (IBFD-UWAC) mode has twice the information throughput of the traditional half-duplex communication mode, significantly increasing the communication efficiency. Extracting the weak desired signal from the high-power self-interference signal without distortion remains a challenging problem in implementing IBFD-UWAC systems. This paper proposes a spatial-digital joint self-interference cancellation (SDSIC) method for IBFD-UWAC. We first perform spatial self-interference cancellation (SSIC) and propose an improved wideband constant-beamwidth beamformer to overcome the problem of direction- and array-dependent interference in IBFD-UWAC systems. Convex optimization is used to maintain a constant beam response in the main flap and cancel the self-interference signal from a fixed direction, thus increasing the signal-to-interference ratio of the desired signal. Subsequently, we perform digital self-interference cancellation (DSIC) on the residual self-interference signal, and propose a variable-step-size least-mean-squares algorithm based on the spatial noise threshold. This algorithm modifies the least-mean-squares step-size adjustment criterion according to the noise level after SSIC and the desired signal, resulting in better DSIC. A series of simulations are implemented in a hardware-in-the-loop platform to verify the practicality and real-time performance of the proposed SDSIC method. The results show that the self-interference signal power can be reduced by 41.5 dB using the proposed method, an improvement of 13.5 dB over the conventional SIC method.
A novel active deep-sea low-damage pressure-retaining organisms sampler
Authors: Liu Guangping , Jin Yongping , Peng Youduo , Liu Deshun , Wan Buyan
Published: October 2022

Capturing less damaged organisms samples is the basis for research on the biological communities, living environments, biological life compositions, and biological tissue structures of organisms livinin the deep seabed. The hadal snailfish is pressure-tolerant, cold-tolerant, and easily damaged. This research used a hydraulic suction macro-biological pressure-retaining sampler (HSMPS) to capture less damaged hadal snailfish samples via pumping. As the hadal snailfish is sucked into the macro-organism pressure-maintaining sampler, it inevitably collides with the suction pipe in the diversion area (SPDA) and the inner wall of the pressure-maintaining cylinder in the pressure-maintaining area (PCPA). Therefore, a finite element analysis model of a hadal snailfish with a real geometric shape was constructed by obtaining the material mechanical properties of different parts of the fish on the seabed through static compression tests, and the dynamic modeling and response analysis of the hadal snailfish during the capture process was carried out. Moreover, the dynamic response changes of the stress, strain and acceleration of various tissues and organs of the hadal snailfish during the capture process were determined, thereby providing technical support for the research and development of marine biological sampling equipment.
Molecular dynamics simulation of nanocrack closure mechanism and interface behaviors of polycrystalline austenitic steel
Authors: Chen Huiqin , He Sizhe , Chen Juan , Chen Fei , Zhang Sairu , Zhang Yingfan
Published: October 2022

Void-type defects in heavy forgings deteriorate their mechanical properties and service life. In this work, the evolutions of a pre-crack closure and the healing and mechanical properties of FeCrNi polycrystalline samples are assessed under different loading conditions using molecular dynamics simulation. The stress–strain curves show that the sample with interface exhibits higher Young’s modulus and yield strength than those with cracks, despite the loading conditions. These results imply that samples under compression loading have a higher ability to resist plasticity, while the shear stress facilitates plastic flow. Crack closure and healing occur under compression stress by dislocation-dominant plastic deformation, while the crack length shrinks and the crack tips expand along grain boundaries (GBs) and the interface because of its higher stress under shear loading. Dislocation activities, including dislocation emission, slip, and interactions with cracks, grain boundaries, and dislocations, contribute to the plasticity of the specimen under compressive loading. In addition to dislocation activities, grain boundary slip, grain rotation, and twinning are potential plastic-deformation mechanisms under shear loading.
Design of broadband high efficiency absorption antenna based on metamaterial nano-ring array
Authors: Li Na , Tian Yanwei , Bao Jianqiang , Wang Yan , Zhao Chi
Published: October 2022

Compared with the traditional solar cells, the nano-optical antenna breaks through the band-gap limitation of semiconductor materials, and provides a new scheme for solar energy collection. In order to solve the problems of complex structure, low efficiency and narrow bandwidth of nano-optical antenna, a novel nano-ring-cylinder based on metamaterials is proposed in this paper. The antenna has an average absorption efficiency of 96.93% in the wide-band absorption range of visible and near-infrared light. First of all, the basic design theory of the antenna was given based on the surface plasma theory. Then, the antenna structure design scheme was determined, the overall structure consists of two layers of metal and an insulating layer formed by Al2O3. Finally, on the basis of the established antenna model, the absorption characteristics were analyzed by simulation. The analysis result shows that the super-absorption ability of the antenna is independent of the polarization of the incident light, and the average absorption ability can be maintained at about 91% when the incident angle is ±60°. The absorption capability of the antenna is mainly due to the synergistic effect of Fabry-Perot resonance and localized surface plasmon resonance enhancement. The conclusion can provide a theoretical guidance for the structural design of nano-optical antenna.
Influence of fault forms on the evolution of concrete damage patterns in tunnels
Authors: Chen Yuting , Wu Jie , Zhang Shuai , Teng Shuai
Published: October 2022

Quickly and accurately estimating the seismic weak surface of a fault tunnel is one of the most severe challenges in tunnel seismic design. Therefore, the strong nonlinear response of the Jinping II Hydropower Station under the dislocations of positive, reverse, and slip faults was investigated through the finite element method using a static elastoplastic model. The results reveal the damage and failure mechanism of tunnels under different faults. By using the IDA damage rating index, the damage initiation, evolution, and development process of tunnels under different types of faults are analyzed. The results showed that the affected area of fault dislocation is concentrated and intense, which is mainly distributed along the two sides of the fault surface. The damage of the positive and reverse faults to the tunnel extends from the arch waist to the vault and the invert of the arch, while the influence of the slip fault on the tunnel is the greatest at the vault and invert of the arch and then extends to the arch waist. In terms of the impact range, the reverse fault is the biggest, followed by the slip fault, while the positive fault is the lowest. This study contributes to the design and construction of tunnels through the faults.
Variational Approach to Damage Induced by Drainage in Partially Saturated Granular Geomaterials
Authors: Ommi Siddhartha H. , Sciarra Giulio , Kotronis Panagiotis
Published: October 2022

Within the context of immiscible biphasic flow in porous media, when the nonwetting fluid invades the pore spaces which are a priori saturated with the wetting fluid, capillary forces dominate if the pore network is formed by fine-grained soils. Owing to the cohesion-less frictional behavior of such soils, a capillary force–driven fracturing phenomenon has been put forward by some researchers. Unlike the purely mechanistic tensile force–driven mode-I fracturing that typically has been attributed to the formation of desiccation cracks in soils, attempts to model this alternate capillarity-driven mechanism have not yet been realized at a continuum scale. However, the macro-scale counterpart of the capillary energy associated with the various pore-scale menisci is well-established as the interfacial energy characterized by the soil-water retention curve. An investigation of the possible contribution of this interfacial energy in supplying the dissipation related to fracture initiation is the essence of this work, inspired by the vast literature on gradient damage modeling.
Marital status as an independent prognostic factor for patients of malignant pleural mesothelioma
Authors: Pan Shu , Yan Na , Zhao Yuanyuan , Li Zhiwen
Published: October 2022

Objectives

The prognostic impact of marital status on malignant pleural mesothelioma (MPM) is not investigated. This paper probes into the relationship between the prognosis of MPM and marital status.

Materials and methods

The Surveillance, Epidemiology, and End Results (SEER) database of American had been applied to choose eligible patients over the 2004–2015 periods. Moreover, cancer-specific survival (CSS) and overall survival (OS) of unmarried and married groups were compared.

Results

A total of 3,997 patients in total had been identified, including 2,735 (68.43%) married patients. In comparison to unmarried patients, married ones tended to be younger, male, white, and received active treatment (surgery, chemotherapy, or radiotherapy). In addition, the 1, 3, and 5-year CSS rates were 44.40, 12.09, and 6.88% in married patients, while 35.75, 12.12, and 6.37% in unmarried group (p = 0.0014). At the same time, the 1, 3, and 5-year OS rates were 41.84, 10.56, and 5.91% in married patients, while 33.67, 10.44, and 4.93%, respectively, in the unmarried group (p < 0.0001). As revealed by the multivariate analysis results, the marital status was an independent favorable prognostic factor, in which the married groups showed better CSS [hazard ratio (HR): 0.870; 95% confidence interval (CI): 0.808–0.938; p < 0.001] as well as OS (HR: 0.871; 95% CI: 0.810–0.936; p < 0.001). According to the results of subgroup analysis, the CSS and OS survival of married groups were better than the unmarried groups in almost all the subgroups.

Conclusion

Marital status is an independent favorable prognostic indicator of MPM. Poor prognosis in unmarried patients is likely to be related to insufficient treatments and socioeconomic and psychosocial factors.
Intrinsic capacity rather than intervention exposure influences reversal to robustness among prefrail community-dwelling older adults: A non-randomized controlled study of a multidomain exercise and nutrition intervention
Authors: Tay Laura , Tay Ee-Ling , Mah Shi Min , Latib Aisyah , Ng Yee-Sien
Published: October 2022

Background

The differential risk profiles associated with prefrailty may be attributable to underlying intrinsic capacity (IC).

Objectives

We examine (i) effect of a multi-domain physical exercise and nutrition intervention on pre-frailty reversal in community-dwelling older adults at 1-year, and (ii) whether IC contributes to pre-frailty reversal.

Methods

Prefrail participants in this non-randomized study were invited to attend a 4-month exercise and nutritional intervention following a frailty screen in the community. Prefrailty was operationalized as (i) FRAIL score 1–2 or (ii) 0 positive response on FRAIL but with weak grip strength or slow gait speed based on the Asian Working Group for Sarcopenia cut-offs. Participants who fulfilled operational criteria for prefrailty but declined enrolment in the intervention programme served as the control group. All participants completed baseline IC assessment: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Reversal of prefrailty was defined as achieving a FRAIL score of 0, with unimpaired grip strength and gait speed at 1-year follow-up.

Results

Of 81 participants (70.0 ± 6.6 years, 79.0% female), 52 participants (64.2%) were enrolled in the multi-domain intervention, and 29 participants (35.8%) who declined intervention constituted the control group. There was no difference in age, gender and baseline composite IC between groups. Reversal to robustness at 1-year was similar between intervention and control groups (30.8% vs. 44.8% respectively, p = 0.206). Reduced prevalence of depression was observed among participants in the intervention group at 1-year relative to baseline (7.8% vs. 23.1%, p = 0.022). In multiple logistic regression, intervention had no effect on prefrailty reversal, while higher composite IC exhibited reduced likelihood of remaining prefrail at 1-year (OR = 0.67, 95% CI 0.45–1.00, p = 0.049).

Conclusion

Focusing only on the locomotion and vitality domains through a combined exercise and nutritional intervention may not adequately address component domain losses to optimize prefrailty reversal. Future studies should examine whether an IC-guided approach to target identified domain declines may be more effective in preventing frailty progression.
Sourcing cells for in vitro models of human vascular barriers of inflammation
Authors: McCloskey Molly C. , Zhang Victor Z. , Ahmad S. Danial , Walker Samuel , Romanick Samantha S. , Awad Hani A. , McGrath James L.
Published: October 2022

The vascular system plays a critical role in the progression and resolution of inflammation. The contributions of the vascular endothelium to these processes, however, vary with tissue and disease state. Recently, tissue chip models have emerged as promising tools to understand human disease and for the development of personalized medicine approaches. Inclusion of a vascular component within these platforms is critical for properly evaluating most diseases, but many models to date use “generic” endothelial cells, which can preclude the identification of biomedically meaningful pathways and mechanisms. As the knowledge of vascular heterogeneity and immune cell trafficking throughout the body advances, tissue chip models should also advance to incorporate tissue-specific cells where possible. Here, we discuss the known heterogeneity of leukocyte trafficking in vascular beds of some commonly modeled tissues. We comment on the availability of different tissue-specific cell sources for endothelial cells and pericytes, with a focus on stem cell sources for the full realization of personalized medicine. We discuss sources available for the immune cells needed to model inflammatory processes and the findings of tissue chip models that have used the cells to studying transmigration.
Soil pqqC-harboring bacterial community response to increasing aridity in semi-arid grassland ecosystems: Diversity, co-occurrence network, and assembly process
Authors: Zhang Mei , Zhang Ruixi , Song Riquan , An Xilong , Chu Guixin , Jia Hongtao
Published: October 2022

Aridity is increasing in several regions because of global climate change, which strongly affects the soil microbial community. The soil pqqC-harboring bacterial community plays a vital role in soil P cycling and P availability. However, the effect of shifts in aridity on the pqqC community is largely unknown. Here, based on high-throughput sequencing technology, we investigated the response patterns of the diversity, co-occurrence networks, and assembly mechanisms of the soil pqqC communities along a natural aridity gradient in adjacent pairs of natural and disturbed grasslands in Inner Mongolia, China. The results showed that the α-diversity of the pqqC community first increased and then decreased with increasing aridity in the natural grassland, while it linearly increased as aridity increased in the disturbed grassland. The pqqC community dissimilarity significantly increased with increased aridity, exhibiting a steeper change rate in the disturbed grassland than in the natural grassland. Increased aridity altered the pqqC community composition, leading to increases in the relative abundance of Actinobacteria but decreases in Proteobacteria. The composition and structure of the pqqC community showed significant differences between natural and disturbed grasslands. In addition, the network analysis revealed that aridity improved the interactions among pqqC taxa and promoted the interspecific competition of pqqC microorganisms. The pqqC community assembly was primarily governed by stochastic processes, and the relative contribution of stochastic processes increased with increasing aridity. Furthermore, disturbances could affect pqqC-harboring bacterial interactions and assembly processes. Overall, our findings fill an important knowledge gap in our understanding of the influence of aridity on the diversity and assembly mechanism of the soil pqqC community in grassland ecosystems, and this work is thus conducive to predicting the pqqC community and its ecological services in response to future climate change.
Viroscope: Plant viral diagnosis from high-throughput sequencing data using biologically-informed genome assembly coverage
Authors: Valenzuela Sandro L. , Norambuena Tomás , Morgante Verónica , García Francisca , Jiménez Juan C. , Núñez Carlos , Fuentes Ignacia , Pollak Bernardo
Published: October 2022

High-throughput sequencing (HTS) methods are transforming our capacity to detect pathogens and perform disease diagnosis. Although sequencing advances have enabled accessible and point-of-care HTS, data analysis pipelines have yet to provide robust tools for precise and certain diagnosis, particularly in cases of low sequencing coverage. Lack of standardized metrics and harmonized detection thresholds confound the problem further, impeding the adoption and implementation of these solutions in real-world applications. In this work, we tackle these issues and propose biologically-informed viral genome assembly coverage as a method to improve diagnostic certainty. We use the identification of viral replicases, an essential function of viral life cycles, to define genome coverage thresholds in which biological functions can be described. We validate the analysis pipeline, Viroscope, using field samples, synthetic and published datasets, and demonstrate that it provides sensitive and specific viral detection. Furthermore, we developed Viroscope.io a web-service to provide on-demand HTS data viral diagnosis to facilitate adoption and implementation by phytosanitary agencies to enable precise viral diagnosis.
Detection of an IMI-2 carbapenemase-producing Enterobacter asburiae at a Swedish feed mill
Authors: Börjesson Stefan , Brouwer Michael S. M. , Östlund Emma , Eriksson Jenny , Elving Josefine , Karlsson Lindsjö Oskar , Engblom Linda I.
Published: October 2022

Occurrence of multidrug resistant Enterobacteriaceae in livestock is of concern as they can spread to humans. A potential introduction route for these bacteria to livestock could be animal feed. We therefore wanted to identify if Escherichia spp., Enterobacter spp., Klebsiella spp., or Raoutella spp. with transferable resistance to extended spectrum cephalosporins, carbapenems or colistin could be detected in the environment at feed mills in Sweden. A second aim was to compare detected isolates to previous described isolates from humans and animals in Sweden to establish relatedness which could indicate a potential transmission between sectors and feed mills as a source for antibiotic resistant bacteria. However, no isolates with transferable resistance to extended-cephalosporins or colistin could be identified, but one isolate belonging to the Enterobacter cloacae complex was shown to be carbapenem-resistant and showing carbapenemase-activity. Based on sequencing by both short-read Illumina and long-read Oxford Nanopore MinIon technologies it was shown that this isolate was an E. asburiae carrying a blaIMI-2 gene on a 216 Kbp plasmid, designated pSB89A/IMI-2, and contained the plasmid replicons IncFII, IncFIB, and a third replicon showing highest similarity to the IncFII(Yp). In addition, the plasmid contained genes for various functions such as plasmid segregation and stability, plasmid transfer and arsenical transport, but no additional antibiotic resistance genes. This isolate and the pSB89A/IMI-2 was compared to three human clinical isolates positive for blaIMI-2 available from the Swedish antibiotic monitoring program Swedres. It was shown that one of the human isolates carried a plasmid similar with regards to gene content to the pSB89A/IMI-2 except for the plasmid transfer system, but that the order of genes was different. The pSB89A/IMI-2 did however share the same transfer system as the blaIMI-2 carrying plasmids from the other two human isolates. The pSB89A/IMI-2 was also compared to previously published plasmids carrying blaIMI-2, but no identical plasmids could be identified. However, most shared part of the plasmid transfer system and DNA replication genes, and the blaIMI-2 gene was located next the transcription regulator imiR. The IS3-family insertion element downstream of imiR in the pSB89A was also related to the IS elements in other blaIMI-carrying plasmids.
Reduced platelet mitochondrial respiration and oxidative phosphorylation in patients with post COVID-19 syndrome are regenerated after spa rehabilitation and targeted ubiquinol therapy
Authors: Sumbalová Zuzana , Kucharská Jarmila , Rausová Zuzana , Palacka Patrik , Kovalčíková Eleonóra , Takácsová Timea , Mojto Viliam , Navas Plácido , Lopéz-Lluch Guillermo , Gvozdjáková Anna
Published: October 2022

European Association of Spa Rehabilitation recommend spa rehabilitation for patients with post COVID-19 syndrome (post C-19). We studied effects of special mountain spa rehabilitation program and its combination with ubiquinol (reduced form of coenzyme Q10—CoQ10) supplementation on pulmonary function, clinical symptoms, endogenous CoQ10 levels, and platelet mitochondrial bioenergetics of patients with post C-19. 36 patients with post C-19 enrolled for rehabilitation in mountain spa resort and 15 healthy volunteers representing the control group were included in this study. 14 patients with post C-19 (MR group) were on mountain spa rehabilitation lasting 16–18 days, 22 patients (MRQ group) were supplemented with ubiquinol (2 × 100 mg/day) during the rehabilitation and additional 12–14 days at home. Clinical symptoms and functional capacity of the lungs were determined in the patients before and after the spa rehabilitation program. Platelet bioenergetics by high-resolution respirometry, plasma TBARS concentration, and CoQ10 concentration in blood, plasma and platelets were evaluated before and after the spa rehabilitation program, and in 8 patients of MRQ group also after additional 12–14 days of CoQ10 supplementation. Pulmonary function and clinical symptoms improved after the rehabilitation program in both groups, 51.8% of symptoms disappeared in the MR group and 62.8% in the MRQ group. Platelet mitochondrial Complex I (CI)-linked oxidative phosphorylation (OXPHOS) and electron transfer (ET) capacity were markedly reduced in both groups of patients. After the rehabilitation program the improvement of these parameters was significant in the MRQ group and moderate in the MR group. CI-linked OXPHOS and ET capacity increased further after additional 12–14 days of CoQ10 supplementation. CoQ10 concentration in platelets, blood and plasma markedly raised after the spa rehabilitation with ubiquinol supplementation, not in non-supplemented group. In the MRQ group all parameters of platelet mitochondrial respiration correlated with CoQ10 concentration in platelets, and the increase in CI-linked OXPHOS and ET capacity correlated with the increase of CoQ10 concentration in platelets. Our data show a significant role of supplemented ubiquinol in accelerating the recovery of mitochondrial health in patients with post C-19. Mountain spa rehabilitation with coenzyme Q10 supplementation could be recommended to patients with post C-19. This study was registered as a clinical trial: ClinicalTrials.gov ID: NCT05178225.
Novel pathogenic variant (c.2947C > T) of the carbamoyl phosphate synthetase 1 gene in neonatal-onset deficiency
Authors: Bai Ruimiao , He ALing , Guo Jinzhen , Li Zhankui , Yu Xiping , Zeng JunAn , Mi Yang , Wang Lin , Zhang Jingjing , Yang Dong
Published: October 2022

Background

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder characterized by hyperammonaemia. The biochemical measurement of the intermediate metabolites is helpful for CPS1D diagnosis; it however cannot distinguish CPS1D from N-acetylglutamate synthetase deficiency. Therefore, next-generation sequencing (NGS) is often essential for the accurate diagnosis of CPS1D.

Methods

NGS was performed to identify candidate gene variants of CPS1D in a Asian neonatal patient presented with poor feeding, reduced activity, tachypnea, lethargy, and convulsions. The potential pathogenicity of the identified variants was predicted by various types of bioinformatical analyses, including evolution conservation, domain and 3D structure simulations.

Results

Compound heterozygosity of CPS1D were identified. One was in exon 24 with a novel heterozygous missense variant c.2947C > T (p.P983S), and another was previously reported in exon 20 with c.2548C > T (p.R850C). Both variants were predicted to be deleterious. Conservation analysis and structural modeling showed that the two substituted amino acids were highly evolutionarily conserved, resulting in potential decreases of the binding pocket stability and the partial loss of enzyme activity.

Conclusion

In this study, two pathogenic missense variants were identified with NGS, expanding the variants pectrum of theCPS1gene. The variants and related structural knowledge of CPS enzyme demonstrate the applicability for the accurate diagnosis of CPS1D.
Sex separation unveils the functional plasticity of the vomeronasal organ in rabbits
Authors: Villamayor Paula R. , Gullón Julián , Quintela Luis , Sánchez-Quinteiro Pablo , Martínez Paulino , Robledo Diego
Published: October 2022

Chemosensory cues are vital for social and sexual behaviours and are primarily detected and processed by the vomeronasal system (VNS), whose plastic capacity has been investigated in mice. However, studying chemosensory plasticity outside of laboratory conditions may give a more realistic picture of how the VNS adapts to a changing environment. Rabbits are a well-described model of chemocommunication since the discovery of the rabbit mammary pheromone and their vomeronasal organ (VNO) transcriptome was recently characterised, a first step to further study plasticity-mediated transcriptional changes. In this study, we assessed the plastic capacity of the rabbit male and female VNO under sex-separation vs. sex-combined scenarios, including adults and juveniles, to determine whether the rabbit VNO is plastic and, if so, whether such plasticity is already established at early stages of life. First, we characterised the number of differentially expressed genes (DEGs) between the VNO of rabbit male and female under sex-separation and compared it to sex-combined individuals, both in adults and juveniles, finding that differences between male and female were larger in a sex-separated scenario. Secondly, we analysed the number of DEGs between sex-separated and sex-combined scenarios, both in males and females. In adults, both sexes showed a high number of DEGs while in juveniles only females showed differences. Additionally, the vomeronasal receptor genes were strikingly downregulated in sex-separated adult females, whereas in juveniles upregulation was shown for the same condition, suggesting a role of VRs in puberty onset. Finally, we described the environment-modulated plastic capacity of genes involved in reproduction, immunity and VNO functional activity, including G-protein coupled receptors. Our results show that sex-separation induces sex- and stage-specific gene expression differences in the VNO of male and female rabbit, both in adults and juveniles. These results bring out for the first time the plastic capacity of the rabbit VNO, supporting its functional adaptation to specifically respond to a continuous changing environment. Finally, species-specific differences and individual variability should always be considered in VNO studies and overall chemocommunication research.
The impact of a self-selected time restricted eating intervention on eating patterns, sleep, and late-night eating in individuals with obesity
Authors: Simon Stacey L. , Blankenship Jennifer , Manoogian Emily N. C. , Panda Satchidananda , Mashek Douglas G. , Chow Lisa S.
Published: October 2022

Background

Time restricted eating (TRE), limiting eating to a specific daily window, is a novel dietary intervention, but the mechanisms by which TRE results in weight loss remain unclear. The goal of the current study was to examine changes in eating patterns, sleep, and late-night eating, and associations with health outcomes in a secondary analysis of a 12-week self-selected TRE intervention.

Methods

Twenty participants 18–65 years with BMI ≥25 kg/m2 completed the 12-week trial. Participants randomized to TRE (n = 11) were instructed to eat during a self-selected 8-h window, while the non-TRE group (n = 9) followed their typical eating habits. All participants logged oral intake using the myCircadian Clock mobile application throughout the entire intervention. Anthropometrics, HbA1c, an oral glucose tolerance test, and 2 weeks of actigraphy monitoring were completed at pre-intervention and end-intervention. Independent samples t-tests compared differences between groups. Data are presented as mean ± standard deviation.

Results

At preintervention, late night eating was significantly associated with higher fasting glucose (r = 0.59, p = 0.006) and higher HbA1c (r = 0.46, p = 0.016). The TRE group significantly delayed the timing of the first eating occasion by 2.72 ± 1.48 h relative to wake time (p < 0.001) and advanced the timing of the last eating occasion by 1.25 ± 0.8 h relative to bedtime (p < 0.001). The non-TRE group, on average, maintained their eating pattern. Sleep measures did not change from pre- to end-intervention, however greater restriction of the eating window was associated with longer sleep duration at end-intervention (β = −0.46 [95% CI −9.2, −0.4], p = 0.03). The TRE group significantly reduced the prevalence of late night eating (eating within 2 h of bedtime) by 14 ± 6% (p = 0.028) with 63% of participants completely eliminating late night eating at end-intervention.

Conclusion

A self-selected TRE intervention significantly shifted meal timing, reduced late-night eating while prolonging sleep duration.

Trial registry

ClinicalTrials.gov, identifier: 03129581.
The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study
Authors: Sánchez-Pérez Sònia , Comas-Basté Oriol , Duelo Adriana , Veciana-Nogués M. Teresa , Berlanga Mercedes , Vidal-Carou M. Carmen , Latorre-Moratalla M. Luz
Published: October 2022

Restrictive diets for the treatment of different gastrointestinal disorders are reported to change the composition of intestinal microbiota. Recently, it has been proposed that individuals with histamine intolerance suffer from intestinal dysbiosis, having an overabundance of histamine-secreting bacteria, but how it is still unknown this state is affected by the usual dietary treatment of histamine intolerance [i.e., low-histamine diet and the supplementation with diamine oxidase (DAO) enzyme]. Thus, a preliminary study was carried out aiming to evaluate the potential changes on the composition of the intestinal microbiota in a group of five women diagnosed with histamine intolerance undergoing 9 months of the dietary treatment of histamine intolerance. After sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database, we observed a reduction in certain histamine-secreting bacteria, including the genera Proteus and Raoultella and the specie Proteus mirabilis. Moreover, it was also observed an increase in Roseburia spp., a bacterial group frequently related to gut health. These changes could help to explain the clinical improvement experienced by histamine intolerant women underwent a dietary treatment.
In vitro inhibition of acetylcholinesterase activity by yellow field pea (Pisum sativum) protein-derived peptides as revealed by kinetics and molecular docking
Authors: Asen Nancy D. , Okagu Ogadimma D. , Udenigwe Chibuike C. , Aluko Rotimi E.
Published: October 2022

Compounds with structural similarities to the neurotransmitter (acetylcholine) are mostly used to inhibit the activity of acetylcholinesterase (AChE) in Alzheimer’s disease (AD) therapy. However, the existing drugs only alleviate symptoms of moderate to mild conditions and come with side effects; hence, the search is still on for potent and safer options. In this study, High performance liquid chromatography (HPLC) fractionations of AChE-inhibitory pea protein hydrolysates obtained from alcalase, flavourzyme and pepsin digestions were carried out followed by sequence identification of the most active fractions using mass spectrometry. Subsequently, 20 novel peptide sequences identified from the active fractions were synthesized and five peptides, QSQS, LQHNA, SQSRS, ETRSQ, PQDER (IC50 = 1.53 – 1.61 μg/mL) were selected and analyzed for ability to change AChE protein conformation (fluorescence emission and circular dichroism), kinetics of enzyme inhibition, and enzyme-ligand binding configurations using molecular docking. The kinetics studies revealed different inhibition modes by the peptides with relatively low (<0.02 mM and <0.1 mM) inhibition constant and Michaelis constant, respectively, while maximum velocity was reduced. Conformational changes were confirmed by losses in fluorescence intensity and reduced α-helix content of AChE after interactions with different peptides. Molecular docking revealed binding of the peptides to both the catalytic anionic site and the peripheral anionic site. The five analyzed peptides all contained glutamine (Q) but sequences with Q in the penultimate N-terminal position (LQHNA, SQSRS, and PQDER) had stronger binding affinity. Results from the different analysis in this study confirm that the peptides obtained from enzymatic digestion of pea protein possess the potential to be used as novel AChE-inhibitory agents in AD management.
Folate (vitamin B9) content analysis in bread wheat (Triticum aestivum L.)
Authors: Zheng Jun , Wang Xingsu , Wu Bangbang , Qiao Ling , Zhao Jiajia , Pourkheirandish Mohammad , Wang Juanling , Zheng Xingwei
Published: October 2022

Vitamin B9, particularly folic acid, is an essential molecule for human health. Wheat flour is one of the major sources of calorie intake by humans. The selection of folate-rich genotypes in wheat breeding can enhance the natural folate value in the daily diet. This study used a precise, high-performance liquid chromatography (HPLC) assay to analyze folate content in a 262-accession Chinese wheat mini-core collection (MCC) grown under three environments. Four folate derivatives in grains including tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-CH3-THF), 5-formyltetrahydrofolate (5-CHO-THF), and 5,10-methenyltetrahydrofolate (5,10-CH+THF) were considered. An association analysis of water regimes, accession types, released years, geographical origin, and agronomic traits with folate content was conducted for the first time. There was a large amount of variation in folate content in the analyzed accessions, with genotype identified as the main influencing factor. Total folate content was significantly correlated with the content of the four MCC derivatives under the three environments. 5-CH3-THF and 5-CHO-THF were the most abundant among the four folate derivatives and were positively correlated with high folate content. The 12 accessions with the highest folate content showed an average of more than 80 μg/100 g. The analysis demonstrated that this Chinese wheat had not undergone extensive selection for folate content during breeding, which is unrelated to the geographical origin, accession types, winter/spring types, and grain colors of wheat. The content of THF, 5-CH3-THF, and 5,10-CH+THF was significantly negatively correlated with grain width, grain thickness, and thousand kernel weight. A relatively weak negative relationship manifested between folate contents and flowering date, whereas no significant correlation with tiller number, grain number per spike, maturity date, height, and spike length was detected. The investigation benefits wheat breeders for folate enhancement.