bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Ferredoxin Receptor FusA on the Virulence Mechanism of Pseudomonas plecoglossicida
Authors: He Rongchao , Wang Jiajia , Lin Miaozhen , Tian Jing , Wu Bi , Tan Xiaohan , Zhou Jianchuan , Zhang Jiachen , Yan Qingpi , Huang Lixing
Published: March 2022

Pseudomonas plecoglossicida is an aerobic Gram-negative bacterium, which is the pathogen of “Visceral white spot disease” in large yellow croaker. P. plecoglossicida is a temperature-dependent bacterial pathogen in fish, which not only reduces the yield of large yellow croaker but also causes continuous transmission of the disease, seriously endangering the healthy development of fisheries. In this study, a mutant strain of fusA was constructed using homologous recombination technology. The results showed that knockout of P. plecoglossicida fusA significantly affected the ability of growth, adhesion, and biofilm formation. Temperature, pH, H2O2, heavy metals, and the iron-chelating agent were used to treat the wild type of P. plecoglossicida; the results showed that the expression of fusA was significantly reduced at 4°C, 12°C, and 37°C. The expression of fusA was significantly increased at pH 4 and 5. Cu2+ has a significant inducing effect on the expression of fusA, but Pb2+ has no obvious effect; the expression of fusA was significantly upregulated under different concentrations of H2O2. The expression of the fusA gene was significantly upregulated in the 0.5~4-μmol/l iron-chelating agent. The expression level of the fusA gene was significantly upregulated after the logarithmic phase. It was suggested that fusA included in the TBDR family not only was involved in the transport of ferredoxin but also played important roles in the pathogenicity and environment adaptation of P. plecoglossicida.
Communicating Seismic Risk Information: The Effect of Risk Comparisons on Risk Perception Sensitivity
Authors: Savadori Lucia , Ronzani Piero , Sillari Giacomo , Di Bucci Daniela , Dolce Mauro
Published: March 2022

Communicating seismic risk to individuals can be difficult for an institution because it involves providing technical and scientific information, including the low probability of an adverse event, that is not always easy to understand. One way to facilitate understanding of low probabilities is to provide comparisons with the probability of occurrence of other more familiar events. In a randomized trials experiment, we investigated the effect of providing individuals with a set of risk comparisons on their sensitivity to different levels of seismic risk (1 in 100, 1 in 1,000, and 1 in 10,000). The findings show that providing risk comparisons increased individual risk sensitivity to information about the likelihood of experiencing a seismic event. Our findings are explained by the evaluability hypothesis, which states that a single probability value is better understood if the recipient is given some reference data to evaluate it. Our results have implications for disaster risk communication, providing ways to increase risk awareness and, consequently, disaster prevention.
The Association of Dietary Vitamin Intake Time Across a Day With Cardiovascular Disease and All-Cause Mortality
Authors: Gu Wenbo , Wu Huanyu , Hu Cong , Xu Jiaxu , Jiang Hongyan , Long Yujia , Han Tianshu , Yang Xue , Wei Wei , Jiang Wenbo
Published: March 2022

Background

Chrono-nutrition emphasized the importance of the intake time; however, less is known about the impact of dietary vitamin intake time on health. This study aimed to examine our hypothesis about which vitamin intake time could influence the natural course of cardiovascular disease (CVD).

Methods

A total of 27,455 adults enrolled in the National Health and Nutrition Examination Survey (NHANES) during 2003–2014 were recruited. The 12 dietary vitamin intakes in the morning, afternoon, and evening were categorized into tertiles or quartiles. Cox-proportional hazard regression models were developed to evaluate the association of vitamin intake time with CVD and all-cause mortalities.

Results

Compared with participants in the lowest quartile, participants in the highest quartile of dietary VB2 intake in the morning had significantly lowest mortality risk of CVD [hazard ratio (HR)VB2 = 0.75, 95% CI: 0.60–0.94, p = 0.017]; whereas, participants in the highest quartile of dietary-vitamin B6 (VB6), vitamin C (VC), vitamin E (VE), and folate-equivalent consumed in the evening showed the lowest risks of CVD (HRVB6 = 0.77, 95% CI: 0.60–0.99, p = 0.103; HRVC = 0.80, 95% CI: 0.65–0.98, p = 0.050; HRVE = 0.75, 95% CI: 0.56–0.99, p = 0.032; HRfolate–equivalent = 0.78, 95% CI: 0.63–0.97, p = 0.116) and all-cause mortalities (HRVB6 = 0.81, 95% CI: 0.71–0.93, p = 0.006; HRVC = 0.85, 95% CI: 0.76–0.95, p = 0.004; HRVE = 0.84, 95% CI: 0.72–0.97, p = 0.011; HRfolate–equivalent = 0.80, 95% CI: 0.71–0.90, p = 0.001). Moreover, equivalently replacing 10% intake of dietary VB6, VC, VE, and folate-equivalent in the morning with evening were associated with 4% (HRVB6 = 0.96, 95% CI: 0.92–0.99), 5% (HRVC = 0.95, 95% CI: 0.92–0.99), 4% (HRVE = 0.96, 95% CI: 0.91–0.99), and 5% (HRfolate–equivalent = 0.95, 95% CI: 0.92–0.99) lower risk of CVD mortality.

Conclusion

This study found that the optimal intake time of dietary VB2 was in the morning, and the optimal intake times of dietary VB6, VC, VE, and folate-equivalent were in the evening.
Pacing Characteristics of His Bundle Pacing vs. Left Bundle Branch Pacing: A Systematic Review and Meta-Analysis
Authors: Zhuo Wen , Zhong Xiaojie , Liu Hualong , Yu Jianhua , Chen Qi , Hu Jinzhu , Xiong Qinmei , Hong Kui
Published: March 2022

Background

His bundle pacing (HBP) is a physiological pacing strategy, which aims to capture the His bundle-Purkinje system and synchronously activate the ventricles. Left bundle branch pacing (LBBP) is a newly discovered physiological pacing technique similar to HBP. We conducted this meta-analysis to compare the pacing parameters and clinical results between HBP and LBBP.

Methods

We systematically retrieved studies using the PubMed, Embase database, and Cochrane Library. Mean difference (MD) and relative risk (RR) with their 95% confidence intervals [CIs] were used to measure the outcomes. A random-effect model was used when studies were of high heterogeneity.

Results

A total of seven studies containing 867 individuals were included. Compared with HBP, LBBP was associated with higher implant success rates (RR: 1.12, 95% CI: 1.05–1.18; I2 = 60%, P = 0.0003), lower capture threshold at implantation (V/0.5 ms) (MD: 0.63, 95% CI: 0.35–0.90, I2 = 89%, P < 0.0001) and capture threshold at follow-up (V/0.5 ms) (MD: 0.76, 95% CI: 0.34–1.18, I2 = 93%, P = 0.0004), and larger sensed R wave amplitude (mV) at implantation (MD: 7.23, 95% CI: 5.29–9.16, P < 0.0001) and sensed R wave amplitude (mV) at follow-up (MD: 7.53, 95% CI: 6.85–8.22, P < 0.0001). In LBBP recipients, greater QRS wave complex reduction was found in the paced QRS duration at follow-up compared with HBP recipients at follow-up (MD: 6.12, 95% CI: 1.23–11.01, I2 = 0%, P = 0.01). No statistical differences were found in procedure duration, fluoroscopy time, native left ventricular ejection fractions (LVEF), LVEF improvement, native QRS duration, and QRS reduction from the native QRS duration vs. paced QRS duration at implantation.

Conclusion

Current evidence suggests that pacing characteristics are better in LBBP compared with HBP. Further prospective studies are needed to validate the clinical advantages of LBBP.
Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art
Authors: Al-abcha Abdullah , Radwan Yasser , Blais Danielle , Mazzaferri Ernest L. , Boudoulas Konstantinos Dean , Essa Essa M. , Gumina Richard J.
Published: March 2022

The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of “antiplatelet” therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.
Using Eruption Source Parameters and High-Resolution Grain-Size Distributions of the 7.7 ka Cleetwood Eruption of Mount Mazama (Oregon, United States) to Reveal Primary and Secondary Eruptive Processes
Authors: Wiejaczka Joshua , Giachetti Thomas
Published: March 2022

Numerical simulations of real-time volcanic ash dispersal forecasts and ensuing tephra hazard assessments rely on field-derived Eruption Source Parameters (ESPs) such as plume height, erupted volume, mass eruption rate and the Total Grain-Size Distribution (TGSD) of particles ejected from a volcano into the atmosphere. Here we calculate ESPs for the ∼7.7 ka Cleetwood eruption of Mount Mazama (Crater Lake/giiwas, Oregon, United States) that immediately preceded the caldera-forming eruption. We also introduce a novel approach to produce high-resolution grain-size distributions (GSDs) of individual samples over a wide range of particle sizes (0.00035–35 mm) by combining laser diffraction with dynamic image analysis. Detailed field analysis allows us to divide the Cleetwood eruptive sequence into a series of two distinct and consecutive VEI four eruptions: the lower (∼0.98 km3) and upper (∼0.20 km3) Cleetwood units. The lower Cleetwood was the most intense with a plume height of ∼19 km and an average mass discharge rate of ∼3.1×107 kg s−1. Its Total Grain-Size Distribution yields a fractal dimension D∼3.1, like other similar eruptions. All twelve high-resolution GSDs produced in this study exhibit two systematic breaks in slope from a power-law relationship at ∼0.125 mm and ∼0.510 mm. These breaks in slope create three segments: S1 (<0.125 mm), S2 (0.125–0.510 mm), and S3 (>0.510 mm) that can be fit by power-law relationships with fractal dimensions of D1=2.5 ± 0.2, D2=0.5 ± 0.1, and D3=3.6 ± 1.1, respectively. Together with ESPs and detailed componentry, D values at various locations give insight into magma fragmentation and tephra transport. We find that D1 values are positively correlated with the median grain-size and are similar to values found in rapid decompression magma fragmentation experiments. We infer that D1 values reflect the size distribution of the primary products of magma fragmentation and could thus be used to infer the potential energy at fragmentation. We interpret the relatively low values of D2 to an increase in dense components due to particle rafting. Our work shows that comparing high-resolution grain-size distributions at several locations on the dispersal axis can further constrain primary and secondary eruptive processes which prove crucial to improving tephra hazard assessments and dispersal forecasting.
Pin Bolt State Identification Using Cascaded Object Detection Networks
Authors: Li Yaocheng , Li Zhe , Liu Yadong , Sheng Gehao , Jiang Xiuchen
Published: March 2022

Unmanned aerial vehicle-based transmission line inspections produce a large number of photos; significant manpower and time are required to inspect the abnormalities and faults in such photos. As such, there has been increasing interest in the use of computer vision algorithms to automate the detection of defects in these photos. One of the most challenging problems in this field is the identification of defects in small pin bolts. In this paper, we propose a pin state identification framework cascaded by two object detectors. First, the bolts are located in the transmission line photos by an initial object detector. These bolts are expanded in the original picture and cropped. These processed bolts are then passed to a second object detector that identifies three states of the pins: normal, pin missing, and pin falling off. The proposed framework can attain 54.3 mAP and 63.4 mAR in our test dataset.
Mechanical Feasibility Analysis of the Surface Microstructure to Be Used in the Nuclear Reactor
Authors: Huang Shan , Yue Ti , Yuan Pan , Zhu Fawen , Wang Haoyu , Liu Menglong , Huang Chunlan , Li Hua , Li Yun
Published: March 2022

With the continuous improvement of nuclear reactor power, the use of surface microstructures to enhance the heat exchange between the coolant and the solid surface has become the research focus of many researchers. However, the extreme environment inside the core, especially the continuous impact of the high-velocity liquid on the solid surface, poses a severe challenge to the reliable service of the microstructure. To this end, this paper establishes a numerical calculation method for the droplet scouring the solid wall to analyze and evaluate the mechanical feasibility and reliability of the surface microstructure under the impact of high-speed droplets. First of all, the physical process of the liquid droplet scouring the solid surface was described and analyzed, then the mathematical equations which describe the physical process were built by coupling the key physical parameters of the interface such as displacement and stress. Finally, the internal stress distribution and its change trend with and without the microstructure were obtained. The calculation results show that during the process of a droplet hitting the solid surface, due to the superposition of shock waves inside the droplet, there will be a stress field distribution on the solid side that cannot be ignored. The introduction of the surface microstructure will significantly change the stress field distribution on the solid side. The liquid film formed on the surface of the microstructure has a significant buffering effect on the impact of the droplets, which greatly reduces the stress level in the solid. The maximum stress level in the solid with microstructure is only about 50% of that in the solid without the microstructure. Therefore, it can be judged that the surface microstructure can meet the mechanical performance requirements under the condition of droplet scouring.
Extreme Hot Weather Has Stronger Impacts on Avian Reproduction in Forests Than in Cities
Authors: Pipoly Ivett , Preiszner Bálint , Sándor Krisztina , Sinkovics Csenge , Seress Gábor , Vincze Ernő , Bókony Veronika , Liker András
Published: March 2022

Climate change and urbanisation are among the most salient human-induced changes affecting Earth’s biota. Extreme weather events can have high biological impacts and are becoming more frequent recently. In cities, the urban heat island can amplify the intensity and frequency of hot weather events. However, the joint effects of heat events and urban microclimate on wildlife are unclear, as urban populations may either suffer more from increased heat stress or may adapt to tolerate warmer temperatures. Here, we test whether the effects of hot weather on reproductive success of great tits (Parus major) are exacerbated or dampened in urban environments compared to forest habitats. By studying 760 broods from two urban and two forest populations over 6 years, we show that 14–16 days-old nestlings have smaller body mass and tarsus length, and suffer increased mortality when they experience a higher number of hot days during the nestling period. The negative effects of hot weather on body mass and survival are significantly stronger in forests than in urban areas, where these effects are dampened or even reversed. These results suggest that urban nestlings are less vulnerable to extreme hot weather conditions than their non-urban conspecifics. This difference might be the result of adaptations that facilitate heat dissipation, including smaller body size, altered plumage and reduced brood size. Alternatively or additionally, parental provisioning and food availability may be less affected by heat in urban areas. Our findings suggest that adaptation to heat stress may help birds cope with the joint challenges of climate change and urbanisation.
Whole-Genome Sequencing of Vero E6 (VERO C1008) and Comparative Analysis of Four Vero Cell Sublines
Authors: Konishi Kazuhiro , Yamaji Toshiyuki , Sakuma Chisato , Kasai Fumio , Endo Toshinori , Kohara Arihiro , Hanada Kentaro , Osada Naoki
Published: March 2022

The Vero cell line is an immortalized cell line established from kidney epithelial cells of the African green monkey. A variety of Vero sublines have been developed and can be classified into four major cell lineages. In this study, we determined the whole-genome sequence of Vero E6 (VERO C1008), which is one of the most widely used cell lines for the proliferation and isolation of severe acute respiratory syndrome coronaviruses (SARS-CoVs), and performed comparative analysis among Vero JCRB0111, Vero CCL-81, Vero 76, and Vero E6. Analysis of the copy number changes and loss of heterozygosity revealed that these four sublines share a large deletion and loss of heterozygosity on chromosome 12, which harbors type I interferon and CDKN2 gene clusters. We identified a substantial number of genetic differences among the sublines including single nucleotide variants, indels, and copy number variations. The spectrum of single nucleotide variants indicated a close genetic relationship between Vero JCRB0111 and Vero CCL-81, and between Vero 76 and Vero E6, and a considerable genetic gap between the former two and the latter two lines. In contrast, we confirmed the pattern of genomic integration sites of simian endogenous retroviral sequences, which was consistent among the sublines. We identified subline-specific/enriched loss of function and missense variants, which potentially contribute to the differences in response to viral infection among the Vero sublines. In particular, we identified four genes (IL1RAP, TRIM25, RB1CC1, and ATG2A) that contained missense variants specific or enriched in Vero E6. In addition, we found that V739I variants of ACE2, which functions as the receptor for SARS-CoVs, were heterozygous in Vero JCRB0111, Vero CCL-81, and Vero 76; however, Vero E6 harbored only the allele with isoleucine, resulting from the loss of one of the X chromosomes.
Eukaryotic mRNA Decapping Activation
Authors: Vidya Elva , Duchaine Thomas F.
Published: March 2022

The 5′-terminal cap is a fundamental determinant of eukaryotic gene expression which facilitates cap-dependent translation and protects mRNAs from exonucleolytic degradation. Enzyme-directed hydrolysis of the cap (decapping) decisively affects mRNA expression and turnover, and is a heavily regulated event. Following the identification of the decapping holoenzyme (Dcp1/2) over two decades ago, numerous studies revealed the complexity of decapping regulation across species and cell types. A conserved set of Dcp1/2-associated proteins, implicated in decapping activation and molecular scaffolding, were identified through genetic and molecular interaction studies, and yet their exact mechanisms of action are only emerging. In this review, we discuss the prevailing models on the roles and assembly of decapping co-factors, with considerations of conservation across species and comparison across physiological contexts. We next discuss the functional convergences of decapping machineries with other RNA-protein complexes in cytoplasmic P bodies and compare current views on their impact on mRNA stability and translation. Lastly, we review the current models of decapping activation and highlight important gaps in our current understanding.
Genetic Parameter Estimation and Whole Sequencing Analysis of the Genetic Architecture of Chicken Keel Bending
Authors: Zhang Zhihao , Yang Weifang , Zhu Tao , Wang Liang , Zhao Xiaoyu , Zhao Guoqiang , Qu Lujiang , Jia Yaxiong
Published: March 2022

Bone health is particularly important for high-yielding commercial layer chickens. The keel of poultry is an extension of the abdomen side of the sternum along the sagittal plane and is one of the most important bones. In this study, the keel phenotype of White Leghorns laying hen flocks showed significant individual differences. To clarify its genetic mechanism, we first estimated the heritability of keel bend (KB) in White Leghorn, recorded the production performance of the chicken flock, examined the blood biochemical indexes and bone quality in KB and keel normal (KN) chickens, and performed whole-genome pooled sequencing in KB and KN chickens. We then performed selection elimination analysis to determine the genomic regions that may affect the keel phenotypes. The results show that KB is a medium heritability trait. We found that cage height had a significant effect on the KB (p < 0.01). At 48 weeks, there were significant differences in the number of eggs, the number of normal eggs, and eggshell strength (p < 0.05). The content of parathyroid hormone was lower (p < 0.01) and that of calcitonin was higher (p < 0.01) in KB chickens than in KN chickens. The differences in bone mineral density, bone strength, and bone cortical thickness of the humerus and femur were extremely significant (p < 0.01), with all being lower in KB chickens than in KN chickens. In addition, the bones of KB chickens contained more fat organization. A total of 128 genes were identified in selective sweep regions. We identified 10 important candidate genes: ACP5, WNT1, NFIX, CNN1, CALR, FKBP11, TRAPPC5, MAP2K7, RELA, and ENSGALG00000047166. Among the significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways found, we identifed two bone-related pathways, one involving “osteoclast differentiation” and the other the “MAPK signaling pathway.” These results may help us better understand the molecular mechanism of bone traits in chickens and other birds and provide new insights for the genetic breeding of chickens.
Whole-Genome Analyses Reveal Genomic Characteristics and Selection Signatures of Lincang Humped Cattle at the China–Myanmar Border
Authors: Sun Luyang , Qu Kaixing , Ma Xiaohui , Hanif Quratulain , Zhang Jicai , Liu Jianyong , Chen Ningbo , Suolang Quji , Lei Chuzhao , Huang Bizhi
Published: March 2022

The location on the Yunnan border with Myanmar and its unique cultural landscape has shaped Lincang humped cattle over time. In the current study, we investigated the genetic characteristics of 22 Lincang humped cattle using whole-genome resequencing data. We found that Lincang humped cattle derived from both Indian indicine and Chinese indicine cattle depicted higher levels of genomic diversity. Based on genome-wide scans, candidate genomic regions were identified that were potentially involved in local thermal and humid environmental adaptions, including genes associated with the body size (TCF12, SENP2, KIF1C, and PFN1), immunity (LIPH, IRAK3, GZMM, and ELANE), and heat tolerance (MED16, DNAJC8, HSPA4, FILIP1L, HELB, BCL2L1, and TPX2). Missense mutations were detected in candidate genes IRAK3, HSPA4, and HELB. Interestingly, eight missense mutations observed in the HELB gene were specific to the indicine cattle pedigree. These mutations may reveal differences between indicine and taurine cattle adapted to variable climatic conditions. Our research provides new insights into the genetic characteristics of Lincang humped cattle representing Lincang and Pu’er areas as an important channel for the migration of Indian indicine from domestication centers toward southwestern China.
Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis
Authors: Kundu Suman , Shetty Advait , Gomes-Solecki Maria
Published: March 2022

Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbreaks were reported in California and New York, respectively. In this study we evaluated the role that cell death processes play in the inflammatory response to Leptospira. Groups of male C3H/HeJ mice were infected with pathogenic L. interrogans and non-pathogenic L. biflexa for 24 and 72 hours; inflammatory processes were characterized for apoptosis and necroptosis by flowcytometry of spleen cells and were further assessed for expression of biomarkers of necroptosis by western blot. We found that pathogenic L. interrogans promotes apoptosis in myeloid neutrophils and monocytes at 24h and 72h post-infection, whereas L. biflexa promotes apoptosis of myeloid monocytes only at 24h post-infection. It is interesting that the immune cells undergoing the common programmed cell death pathway (apoptosis) are the cell types which were not increased in frequency in spleen of mice infected with L. interrogans (neutrophils) and L. biflexa (monocytes) in our previous study. The same trend was observed with pathogenic L. interrogans inducing necroptosis of myeloid neutrophils in addition to monocytes and macrophages at 24h and/or 72h post-infection, whereas L. biflexa promoted this pro-inflammatory cell death process in monocytes and macrophages only at 24h post-infection. Thus, early apoptosis and necroptosis of these cell types may explain its absence in frequency in spleen. Furthermore, at 24h and 72h, expression of the necroptosis molecular biomarkers p-MLKL, p-RIP1 and p-RIP3 was increased post infection with pathogenic L. interrogans. These data suggest that the underlying cell death processes involved in immune responses to pathogenic Leptospira contribute directly to persistent inflammation during the early stages of leptospirosis.
Development and Validation of an Immune-Based Prognostic Risk Score for Patients With Resected Non-Small Cell Lung Cancer
Authors: He Lan , Huang Yanqi , Chen Xin , Huang Xiaomei , Wang Huihui , Zhang Yuan , Liang Changhong , Li Zhenhui , Yan Lixu , Liu Zaiyi
Published: March 2022

Background

Despite the well-known role of immunoscore, as a prognostic tool, that appeared to be superior to tumor–node–metastasis (TNM) staging system, no prognostic scoring system based on immunohistochemistry (IHC) staining digital image analysis has been established in non-small cell lung cancer (NSCLC). Hence, we aimed to develop and validate an immune-based prognostic risk score (IMPRS) that could markedly improve individualized prediction of postsurgical survival in patients with resected NSCLC.

Methods

In this retrospective study, complete resection of NSCLC (stage I–IIIA) was performed for two independent patient cohorts (discovery cohort, n=168; validation cohort, n=115). Initially, paraffin-embedded resected specimens were stained by immunohistochemistry (IHC) of three immune cell types (CD3+, CD4+, and CD8+ T cells), and a total of 5,580 IHC-immune features were extracted from IHC digital images for each patient by using fully automated pipeline. Then, an IHC-immune signature was constructed with selected features using the LASSO Cox analysis, and the association of signature with patients’ overall survival (OS) was analyzed by Kaplan–Meier method. Finally, IMPRS was established by incorporating IHC-immune signature and independent clinicopathological variables in multivariable Cox regression analysis. Furthermore, an external validation cohort was included to validate this prognostic risk score.

Results

Eight key IHC-immune features were selected for the construction of IHC-immune signature, which showed significant associations with OS in all cohorts [discovery: hazard ratio (HR)=11.518, 95%CI, 5.444–24.368; validation: HR=2.664, 95%CI, 1.029–6.896]. Multivariate analyses revealed IHC-immune signature as an independent prognostic factor, and age, T stage, and N stage were also identified and entered into IMPRS (all p<0.001). IMPRS had good discrimination ability for predicting OS (C-index, 0.869; 95%CI, 0.861–0.877), confirmed using external validation cohort (0.731, 0.717–0.745). Interestingly, IMPRS had better prognostic value than clinicopathological-based model and TNM staging system termed as C-index (clinicopathological-based model: 0.674; TNM staging: 0.646, all p<0.05). More importantly, decision curve analysis showed that IMPRS had adequate performance for predicting OS in resected NSCLC patients.

Conclusions

Our findings indicate that the IMPRS that we constructed can provide more accurate prognosis for individual prediction of OS for patients with resected NSCLC, which can help in guiding personalized therapy and improving outcomes for patients.
Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not
Authors: Zheng Rui-zhe , Lee Kuin-yu , Qi Zeng-xin , Wang Zhe , Xu Ze-yu , Wu Xue-hai , Mao Ying
Published: March 2022

Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework.
Genomic Analyses of Halioticoli Clade Species in Vibrionaceae Reveal Genome Expansion With More Carbohydrate Metabolism Genes During Symbiotic to Planktonic Lifestyle Transition
Authors: Jiang Chunqi , Mino Sayaka , Sawabe Tomoo
Published: March 2022

Vibrionaceaeis one of the most diverse bacterial families and is currently classified into over 50 clades, some members of which play an important role in the symbiotic relationships with humans and animals. Halioticoli clade, which currently consists of 10 species: 8 species associated with the gut of abalone (symbiotic), 1 species (V. breoganii) from bivalves, and 1 species (V. ishigakensis) from subtropical seawater (planktonic). To accelerate studies in the evolution, ecogenomics, and biotechnology of Halioticoli clade species, the genomic backbones and pangenome analyses based on complete genome sequences are needed. Genome sizes of Halioticoli clade species ranged from 3.5 Mb to 4.8 Mb, withV. ishigakensisthe biggest. The evolutionary relationships using multilocus sequence analysis based on eight housekeeping genes and 125 single-copy core genes revealed a division of five sub-clades in this clade; 1)V. breoganii,V. comitans,V. inusitatusandV. superstes, 2)V. ezurae,V. neonatus, andV. halioticoli, 3)V. rarus, 4)V. gallicus, and 5)V. ishigakensis. The pan-genomic analysis combined with function and metabolism estimations showed that the planktonic group (sub-clade 5) contained the greatest number of specific genes, and more genes responsible for carbohydrate metabolisms, especially the genes encoding D-galactonate degradation. These results demonstrated that the genome expanded by acquiring more abilities for utilizing various carbohydrates during the evolution from symbiotic to a planktonic lifestyle. Moreover, according to Carbohydrate-Active enZYmes (CAZy) profiling, genes encoding alginate degrading enzymes (aly), classified into PL6, PL7, PL15, and PL17 were common in the ten genomes, but sub-clade 1 had the most. Meanwhile, sub-clade 1and 5 also possessed abundant genes related to macroalgae substrates degradation (GHs), which are also responsible for the genome expansion of sub-clade 1 and 5.
Effects of Frailty on Outcomes Following Surgery Among Patients With Hip Fractures: A Systematic Review and Meta-Analysis
Authors: Ma Yan , Wang Ansu , Lou Yijiao , Peng Daojuan , Jiang Zhongyan , Xia Tongxia
Published: March 2022

Background

Frailty is a syndrome of multisystem dysfunction in the elderly. The association between preoperative frailty and postoperative outcomes in patients with hip fractures is unclear. To address this issue, we performed a meta-analysis to determine the association of frailty with postoperative mortality, complications, and readmission in patients with hip fractures.

Methods

We searched PubMed, Web of Science, Embase, and The Cochrane Library for cohort studies of frailty associated with postoperative adverse events in patients with hip fractures from inception to November 6, 2021. The Newcastle-Ottawa Scale was used to evaluate the quality of the included literature. Statistical analysis of meta-analysis was performed using Review Manager 5.3.

Results

Twelve retrospective cohort studies and seven prospective cohort studies involving a total of 62,132 patients met the inclusion criteria for this meta-analysis. Compared with non-frail patients, the pooled results showed that frailty was associated with patient in-hospital mortality (relative risk [RR] = 2.93; 95% confidence intervals [CI]: 2.56–3.34), 30-day mortality (RR = 2.85, 95%CI: 1.67–4.85) and total complications (RR = 1.79, 95%CI: 1.50–2.15). Subgroup analysis showed that the type of study design and frailty assessment tool had no significant effect on the results. Sensitivity analysis showed that the polled results of frailty predicted one-year mortality and 30-day readmission was unstable.

Conclusions

In this meta-analysis, we found that preoperative frailty may be associated with postoperative adverse events in patients with hip fractures, including in-hospital mortality, 30-day mortality, and postoperative complications.

Systematic Review Registration: PROSPERO, identifier: CRD42021287739.
Efficacy and Safety of Dupilumab in Chinese Patients With Atopic Dermatitis: A Real-World Study
Authors: Zhou Bingjing , Peng Cong , Li Liqiao , Liu Runqiu , Zhu Lei , Chen Xiang , Li Jie
Published: March 2022

Background

Atopic dermatitis (AD) is a common skin disease, but treatment of this disease has been challenging. Dupilumab is a new biological agent for AD that has been proven to be safe and effective in clinical trials. Although dupilumab was approved for listing in China in June 2020, real-world data about the application of dupilumab in China are lacking. This study aimed to collect and analyze real-world data on dupilumab among Chinese AD patients.

Methods

Demographic and clinical data for 116 AD patients receiving dupilumab treatment were reviewed. The Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) of patients were evaluated every 2 weeks from baseline to 16 weeks of treatment. Any adverse events during treatment were recorded.

Results

Among the 116 patients in this study, baseline levels of IgE, eosinophils, and LDH were elevated in 62.79% (n = 86), 45.30% (n = 86), and 54.20% of patients (n = 48), respectively. The SCORAD index and POEM, DLQI, and NRS scores were significantly improved in all patients at 2 weeks (p < 0.0001), 4 weeks (p < 0.01), and 16 weeks (p < 0.001). EASI scores also improved significantly in all patients at 2 weeks (p < 0.01), 4 weeks (> 0.05), and 16 weeks (p < 0.01). However, 11 patients (9.48%) had no response. IgE and LDH levels (p > 0.05), Eosinophil counts (p < 0.01) in blood increased temporarily in the first 4 weeks and then decreased and stabilized during dupilumab treatment. Conjunctivitis was the most common adverse event (2.59%) among the patients. We found that the curative efficacy of dupilumab at 4th weeks was related to the patient’s age and course of disease. Nevertheless, there is no relationship between levels of eosinophils, IgE, LDH and the therapeutic efficacy of dupilumab.

Conclusion

The real-world data in China showed that dupilumab can effectively treat AD and is well tolerated with a low incidence of adverse events.
Combining Biocontrol Agent With Plant Nutrients for Integrated Control of Tomato Early Blight Through the Modulation of Physio-Chemical Attributes and Key Antioxidants
Authors: Awan Zoia Arshad , Shoaib Amna , Iftikhar Muhammad Sarmad , Jan Basit Latief , Ahmad Parvaiz
Published: March 2022

Early blight (EB) is one of the major fungal diseases caused by Alternaria solani that is responsible for destructive tomato production around the globe. Biocontrol agent/s can be adequately implemented in an integrated management framework by using it in combination with vital plant nutrients, e.g., nitrogen, phosphorus, and potassium (NPK) and zinc (Zn). The current study was aimed to assess the integrated effect of a biocontrol agent Bacillus subtilis (BS-01) and the selective plant nutrients (NPK and Zn) on EB disease management and tomato crop performance. A field experiment was conducted for the off-season tomato production (under walk-in tunnels) in Punjab, Pakistan. The trial was set in a randomized complete block design (RCBD) and comprised nine treatments of a biocontrol agent (BS-01) either alone or in combination with the plant nutrients, viz., NPK (64:46:50 kg acre–1) and Zn (10 kg acre–1) as sustainable disease managing approach against EB. In addition, the biocontrol efficacy of B. subtilis (BS-01) on a fungal load of A. solani was estimated by quantitative PCR assays, where the foliar application of BS-01 on tomato plants either alone or in combination with the plant nutrients was done as a preventive measure. Our results revealed that the interactive effect of BS-01 with plant nutrients conferred significantly a varying degree of resilience in the infected tomato plants against EB by effectively modifying the content of total chlorophyll, carotenoids, and total phenolics along with the activities of antioxidant enzymes (SOD, CAT, POX, PPO, and PAL). In addition, the integrative effect of BS-01 and plant nutrients proved significantly effective in reducing pathogen load on inoculated tomato foliage, displaying the desired level of protection against A. solani infection. Besides, the complementary interaction of BS-01 + Zn + NPK worked synergistically to improve crop productivity by providing the highest marketable yield (21.61 tons acre–1) and net profit (361,363 Pakistani rupees acre–1). This integrated approach is put forward as a way to reduce the fungicide doses to control EB that would act as a sustainable plant protection strategy to generate profitable tomato production.
Effects of Antimony on Rice Growth and Its Existing Forms in Rice Under Arbuscular Mycorrhizal Fungi Environment
Authors: Zhou Min , Li Xinru , Liu Xuesong , Mi Yidong , Fu Zhiyou , Zhang Ruiqing , Su Hailei , Wei Yuan , Liu Huifang , Wang Fanfan
Published: March 2022

Arbuscular mycorrhizal fungi (AMF) can form symbiotic relationships with most terrestrial plants and regulate the uptake and distribution of antimony (Sb) in rice. The effect of AMF on the uptake and transport of Sb in rice was observed using pot experiments in the greenhouse. The results showed that AMF inoculation increased the contact area between roots and metals by forming mycelium, and changed the pH and Eh of the root soil, leading to more Sb entering various parts of the rice, especially at an Sb concentration of 1,200 mg/kg. The increase in metal toxicity further led to a decrease in the rice chlorophyll content, which directly resulted in a 22.7% decrease in aboveground biomass, 21.7% in underground biomass, and 11.3% in grain biomass. In addition, the antioxidant enzyme results showed that inoculation of AMF decreased 22.3% in superoxide dismutase, 9.9% in catalase, and 20.7% in peroxidase compared to the non-inoculation groups, further verifying the negative synergistic effect of AMF inoculation on the uptake of Sb in rice. The present study demonstrated the effect of AMF on the uptake and transport of Sb in the soil–rice system, facilitating future research on the related mechanism in the soil–rice system under Sb stress.
Flammulinavelutipes Polysaccharides Modulate Gut Microbiota and Alleviate Carbon Tetrachloride-Induced Hepatic Oxidative Injury in Mice
Authors: Xu Yingyin , Zhang Zhiyuan , Wang Bo , He Xiaolan , Tang Jie , Peng Weihong , Zhou Jie , Wang Yong
Published: March 2022

A carbon tetrachloride-induced acute liver injury mouse model is used to study the regulation of gut microbiota and hepatoprotective effect of polysaccharides from Flammulina velutipes (FVPs). The hepatoprotective effect of the FVPs leads to reduced levels of serum aspartate transaminase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), total bile acid (TBA) content, and change in liver histopathology. Their anti-oxidant activity is exhibited by decreased levels of hepatic malonaldehyde (MDA) and protein carbonyl (PC) content and increased catalase (CAT) and superoxide dismutase (SOD) content. The anti-inflammatory ability of the FVPs is reflected in a decrease in pro-inflammatory cytokines (including IL-6, IL-1β, and TNF-α). 16S rRNA sequencing shows that the FVPs change the composition of the gut microbiota. A subsequent metabolomics analysis of the gut bacteria (UHPLC–MS/MS-based) revealed that fatty acid biosynthesis, tryptophan metabolism, and metabolism of xenobiotics by cytochrome P450 play important roles in the hepatoprotective effect. This study provides a potential way to modulate gut microbiota and manage liver diseases using natural products.
New Insight in the Occurrence of Early Blight Disease on Potato Reveals High Distribution of Alternaria solani and Alternaria protenta in Serbia
Authors: Ivanović Žarko , Blagojević Jovana , Jovanović Gordana , Ivanović Borko , Žeželj Danica
Published: March 2022

Early blight is an economically important disease of potato worldwide. Understanding which fungal pathogens are the causal agents of early blight and their distribution on the same host is essential to finding the best strategy for the control of this disease. Previous studies have shown that Alternaria solani is the main early blight pathogen parasitizing potato. Here, we analyzed genetic and phenotypic diversity in isolates of Alternaria spp. covering all potato production areas in Serbia. We showed that the four species of Alternaria were found in areas with different distributions of the species. The occurrence of Alternaria spp. was studied by analyzing isolates from symptomatic potato leaves during multiyear sampling. In addition to Alternaria solani, we detected three more large-spored species identified as A. linariae (syn. A. tomatophila), A. protenta, and A. grandis that were involved in early blight disease on naturally infected potato leaves in Serbia. Differentiation of species was supported by phylogeny obtained from the DNA sequences of the GAPDH, calmodulin and Rpb2 genes. Our findings present a new perspective into the population structure of large-spored Alternaria species associated with early blight disease. Within the groups of large-spored Alternaria present in Serbia, evidence of A. protenta at high frequency reveals new insight into the contribution of Alternaria species in early blight disease. This work opens new perspectives for early blight management, while the distribution of different species on the same host suggests that the etiology of disease could depend on crop organization and the presence of other Alternaria hosts in close proximity to potato plants.
Investigating the Impact of Environment and Data Aggregation by Walking Bout Duration on Parkinson’s Disease Classification Using Machine Learning
Authors: Rehman Rana Zia Ur , Guan Yu , Shi Jian Qing , Alcock Lisa , Yarnall Alison J. , Rochester Lynn , Del Din Silvia
Published: March 2022

Parkinson’s disease (PD) is a common neurodegenerative disease. PD misdiagnosis can occur in early stages. Gait impairment in PD is typical and is linked with an increased fall risk and poorer quality of life. Applying machine learning (ML) models to real-world gait has the potential to be more sensitive to classify PD compared to laboratory data. Real-world gait yields multiple walking bouts (WBs), and selecting the optimal method to aggregate the data (e.g., different WB durations) is essential as this may influence classification performance. The objective of this study was to investigate the impact of environment (laboratory vs. real world) and data aggregation on ML performance for optimizing sensitivity of PD classification. Gait assessment was performed on 47 people with PD (age: 68 ± 9 years) and 52 controls [Healthy controls (HCs), age: 70 ± 7 years]. In the laboratory, participants walked at their normal pace for 2 min, while in the real world, participants were assessed over 7 days. In both environments, 14 gait characteristics were evaluated from one tri-axial accelerometer attached to the lower back. The ability of individual gait characteristics to differentiate PD from HC was evaluated using the Area Under the Curve (AUC). ML models (i.e., support vector machine, random forest, and ensemble models) applied to real-world gait showed better classification performance compared to laboratory data. Real-world gait characteristics aggregated over longer WBs (WB 30–60 s, WB > 60 s, WB > 120 s) resulted in superior discriminative performance (PD vs. HC) compared to laboratory gait characteristics (0.51 ≤ AUC ≤ 0.77). Real-world gait speed showed the highest AUC of 0.77. Overall, random forest trained on 14 gait characteristics aggregated over WBs > 60 s gave better performance (F1 score = 77.20 ± 5.51%) as compared to laboratory results (F1 Score = 68.75 ± 12.80%). Findings from this study suggest that the choice of environment and data aggregation are important to achieve maximum discrimination performance and have direct impact on ML performance for PD classification. This study highlights the importance of a harmonized approach to data analysis in order to drive future implementation and clinical use.

Clinical Trial Registration

[09/H0906/82].
Non-linear Character of Plasma Amyloid Beta Over the Course of Cognitive Decline in Alzheimer’s Continuum
Authors: Pan Feng-Feng , Huang Qi , Wang Ying , Wang Yi-Fan , Guan Yi-Hui , Xie Fang , Guo Qi-Hao
Published: March 2022

Plasma amyloid-β (Aβ) was associated with brain Aβ deposition and Alzheimer’s disease (AD) development. However, changes of plasma Aβ over the course of cognitive decline in the Alzheimer’s continuum remained uncertain. We recruited 449 participants to this study, including normal controls (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and non-AD dementia. All the participants underwent plasma Aβ42, Aβ40, and t-tau measurements with single-molecule array (Simoa) immunoassay and PET scan with 18F-florbetapir amyloid tracer. In the subgroup of Aβ-PET positive, plasma Aβ42 and Aβ42/Aβ40 ratio was significantly lower in AD than NC, SCD and MCI, yet SCD had significantly higher levels of plasma Aβ42 than both NC and MCI. In the diagnostic groups of MCI and dementia, participants with Aβ-PET positive had lower plasma Aβ42 and Aβ42/40 ratio than participants with Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ42/40 ratio indicated lower risks of Aβ-PET positive. However, in the participants with SCD, plasma Aβ42 and Aβ40 were higher in the subgroup of Aβ-PET positive than Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ40 indicated higher risks of Aβ-PET positive. No significant association was observed between plasma Aβ and Aβ-PET status in normal controls. These findings showed that, in the continuum of AD, plasma Aβ42 had a significantly increasing trend from NC to SCD before decreasing in MCI and AD. Furthermore, the predictive values of plasma Aβ for brain amyloid deposition were inconsistent over the course of cognitive decline.