bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exaggerated postural sway improves orthostatic cardiovascular and cerebrovascular control
Authors: Williams Erin L. , Hockin Brooke C. D. , Heeney Natalie D. , Elabd Karam , Chong Helen , Blaber Andrew P. , Robinovitch Stephen N. , Parsons Iain T. , Claydon Victoria E. 
Published: February 2023

IntroductionHealthy individuals with poor cardiovascular control, but who do not experience syncope (fainting), adopt an innate strategy of increased leg movement in the form of postural sway that is thought to counter orthostatic (gravitational) stress on the cardiovascular system. However, the direct effect of sway on cardiovascular hemodynamics and cerebral perfusion is unknown. If sway produces meaningful cardiovascular responses, it could be exploited clinically to prevent an imminent faint.MethodsTwenty healthy adults were instrumented with cardiovascular (finger plethysmography, echocardiography, electrocardiogram) and cerebrovascular (transcranial Doppler) monitoring. Following supine rest, participants performed a baseline stand (BL) on a force platform, followed by three trials of exaggerated sway (anterior-posterior, AP; mediolateral, ML; square, SQ) in a randomized order.ResultsAll exaggerated postural sway conditions improved systolic arterial pressure (SAP, p = 0.001) responses, while blunting orthostatic reductions in stroke volume (SV, p &lt; 0.01) and cerebral blood flow (CBFv, p &lt; 0.05) compared to BL. Markers of sympathetic activation (power of low-frequency oscillations in SAP, p &lt; 0.001) and maximum transvalvular flow velocity (p &lt; 0.001) were reduced during exaggerated sway conditions. Responses were dose-dependent, with improvements in SAP (p &lt; 0.001), SV (p &lt; 0.001) and CBFv (p = 0.009) all positively correlated with total sway path length. Coherence between postural movements and SAP (p &lt; 0.001), SV (p &lt; 0.001) and CBFv (p = 0.003) also improved during exaggerated sway.DiscussionExaggerated sway improves cardiovascular and cerebrovascular control and may supplement cardiovascular reflex responses to orthostatic stress. This movement provides a simple means to boost orthostatic cardiovascular control for individuals with syncope, or those with occupations that require prolonged motionless standing.
Effects of lifestyle intervention on adults with metabolic associated fatty liver disease: A systematic review and meta-analysis
Authors: Chai Xiao-Ni , Zhou Bing-Qian , Ning Ni , Pan Ting , Xu Fan , He Si-Han , Chen Ni-Ni , Sun Mei 
Published: February 2023

IntroductionThis systematic review and meta-analysis evaluates the overall effects of lifestyle interventions upon hepatic fat content and metabolism-related indicators among adults with metabolic associated fatty liver disease.MethodsIt was registered under PROSPERO (CRD42021251527). We searched PubMed, EMBASE, MEDLINE, Cochrane, CINAHL, Scopus, CNKI, Wan-fang, VIP, and CBM from the inception of each database to May 2021 for RCT studies of lifestyle interventions on hepatic fat content and metabolism-related indicators. We used Review Manager 5.3 for meta-analysis and used text and detailed tabular summaries when heterogeneity existed.ResultsThirty-four RCT studies with 2652 participants were included. All participants were obesity, 8% of whom also had diabetes, and none was lean or normal weight. Through subgroup analysis, we found low carbohydrate diet, aerobic training and resistance training significantly improved the level of HFC, TG, HDL, HbA1c, and HOMA-IR. Moreover, low carbohydrate diet is more effective in improving HFC than low fat diet and resistance training is better than aerobic training in reduction in HFC and TG (SMD, -0.25, 95% CI, -0.45 to -0.06; SMD, 0.24, 95% CI, 0.03 to 0.44, respectively).DiscussionOverall, this is the first review that systematically synthesizes studies focused on the effects of various lifestyle on adults with MAFLD. The data generated in this systematic review were more applicable to obesity MAFLD rather than lean or normal weight MAFLD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42021251527).
Inadequate detection of the FSHR complicates future research on extragonadal FSHR localization
Authors: Tedjawirja Victoria N. , Hooijer Gerrit K. J. , Savci-Heijink C. Dilara , Kovac Kristina , Balm Ron , de Waard Vivian 
Published: February 2023

IntroductionRecently, follicle stimulating hormone (FSH) through interaction with its receptor (FSHR) has been proposed to play a role in postmenopausal osteoporosis and cardiovascular disease, rather than the loss of estrogen. To explore this hypothesis, unravelling which cells express extragonadal FSHR on protein level is key.MethodsWe used two commercial anti-FSHR antibodies and validated them by performing immunohistochemistry on positive (ovary, testis) and negative controls (skin).ResultsThe monoclonal anti-FSHR antibody could not identify the FSHR in ovary or testis. The polyclonal anti-FSHR antibody stained the granulosa cells (ovary) and Sertoli cells (testis), yet there was equally intense staining of other cells/extracellular matrix. Furthermore, the polyclonal anti-FSHR antibody also stained skin tissue extensively, suggesting that the antibody stains more than just FSHR.DiscussionThe findings in this study may add accuracy to literature on extragonadal FSHR localization and warrants attention to the use of inadequate anti-FSHR antibodies to value the potential role of FSH/FSHR in postmenopausal disease.
The nonlinear correlation between the cardiometabolic index and the risk of diabetes: A retrospective Japanese cohort study
Authors: Zha Fubing , Cao Changchun , Hong Mengru , Hou Huili , Zhang Qionghua , Tang Bin , Hu Haofei , Han Yong , Zan Yibing , Wang Yulong , Xu Jianwen 
Published: February 2023

BackgroundThe cardiometabolic index (CMI) has been proposed as a novel indicator of cardiometabolic status. However, evidence on the relationship between CMI and diabetes mellitus (DM) risk was limited. Our study aimed to explore the relationship between CMI and DM risk among a large cohort of Japanese adults.MethodsThis retrospective cohort study recruited 15453 Japanese adults without diabetes at baseline who underwent physical examinations at the Murakami Memorial Hospital between 2004 and 2015. Cox proportional-hazards regression was applied to evaluate the independent relationship between CMI and diabetes. Our study performed a generalized smooth curve fitting (penalized spline technique) and an additive model (GAM) to determine the non-linear relationship between CMI and DM risk. In addition, a set of sensitivity analyses and subgroup analyses were employed to evaluate the relationship between CMI and incident DM.ResultsAfter adjusting for confounding covariates, CMI was positively related to the DM risk in Japanese adults (HR: 1.65, 95%CI: 1.43-1.90, P&lt;0.0001). A series of sensitivity analyses were also employed in this study to guarantee the reliability of the findings. In addition, our study discovered a non-linear association between CMI and diabetes risk. CMI’s inflection point was 1.01. A strong positive association between CMI and diabetes incidence was also discovered to the left of the inflection point (HR: 2.96, 95%CI: 1.96-4.46, P&lt;&lt;0.0001). However, their association was not significant when CMI was higher than 1.01 (HR: 1.27, 95%CI: 0.98-1.64, P=0.0702). Interaction analysis showed that gender, BMI, habit of exercise, and smoking status interacted with CMI.ConclusionIncreased CMI level at baseline is associated with incident DM. The association between CMI and incident DM is also non-linear. A high CMI level is associated with an increased risk for DM when CMI is below 1.01.
Algal removal from raw water by electro-flotation
Authors: Jiang Shuangcheng , Wang Fuli , Lin Feng , Du Hong 
Published: February 2023

In order to reduce the influence of algae on the conventional treatment process of the water plant, the electro-flotation process was used to test the raw water of a lake-type reservoir. After raw water with cyanobacteria as the dominant algae is treated by the best electro-flotation process, the average removal rate of algal density can reach 99.1%. The effects of current density, residence time, and electrode spacing on the algal removal efficiency of the electro-floating process were investigated by orthogonal experiments. The order of influence was current density &gt; residence time &gt; electrode spacing. Considering economics, the optimal process conditions were as follows: the current density was 5 mA/cm2, the dwell time was 6 min, and electrode spacing was 10 mm.
Targeting tumor-associated macrophages with STING agonism improves the antitumor efficacy of osimertinib in a mouse model of EGFR-mutant lung cancer
Authors: Lin Ziying , Wang Qiwei , Jiang Tao , Wang Weihua , Zhao Jean J. 
Published: February 2023

IntroductionDespite the impressive clinical response rate of osimertinib, a third-generation EGFR-TKI, as a frontline treatment for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) or as a salvage therapy for patients with T790M mutation, resistance to osimertinib is common in the clinic. The mechanisms underlying osimertinib resistance are heterogenous. While genetic mutations within EGFR or other cancer driver pathways mediated mechanisms are well-documented, the role of tumor cell and tumor immune microenvironment in mediating the response to osimertinib remains elusive.Methods and resultsHere, using a syngeneic mouse model of EGFR-mutant lung cancer, we show that tumor regression elicited by osimertinib requires activation of CD8+ T cells. However, tumor-associated macrophages (TAMs) accumulated in advanced tumors inhibit CD8+ T cell activation and diminish the response to osimertinib. These results are corroborated by analyses of clinical data. Notably, reprogramming TAMs with a systemic STING agonist MSA-2 reinvigorates antitumor immunity and leads to durable tumor regression in mice when combined with osimertinib.DiscussionOur results reveal a new mechanism of EGFR-TKI resistance and suggest a new therapeutic strategy for the treatment of EGFR-mutant tumors.
Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies
Authors: Besbassi Hajar , Garcia-Fogeda Irene , Quinlivan Mark , Breuer Judy , Abrams Steven , Hens Niel , Ogunjimi Benson , Beutels Philippe 
Published: February 2023

IntroductionStudying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research.MethodsWe adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients.ResultsStarting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population’s characteristics.ConclusionThe results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines.
Beclin-1 dependent autophagy improves renal outcomes following Unilateral Ureteral Obstruction (UUO) injury
Authors: Lopez-Soler Reynold I. , Nikouee Azadeh , Kim Matthew , Khan Saman , Sivaraman Lakshmi , Ding Xiangzhong , Zang Qun Sophia 
Published: February 2023

BackgroundInterstitial Fibrosis and Tubular Atrophy (IFTA) is the most common cause of long-term graft failure following renal transplant. One of the hallmarks of IFTA is the development of interstitial fibrosis and loss of normal renal architecture. In this study, we evaluated the role of autophagy initiation factor Beclin-1 in protecting against post-renal injury fibrosis.MethodsAdult male wild type (WT) C57BL/6 mice were subjected to Unilateral Ureteral Obstruction (UUO), and kidney tissue samples were harvested at 72-hour, 1- and 3-week post-injury. The UUO-injured and uninjured kidney samples were examined histologically for fibrosis, autophagy flux, inflammation as well activation of the Integrated Stress Response (ISR). We compared WT mice with mice carrying a forced expression of constitutively active mutant form of Beclin-1, Becn1F121A/F121A.ResultsIn all experiments, UUO injury induces a progressive development of fibrosis and inflammation. These pathological signs were diminished in Becn1F121A/F121A mice. In WT animals, UUO caused a strong blockage of autophagy flux, indicated by continuously increases in LC3II accompanied by an over 3-fold accumulation of p62 1-week post injury. However, increases in LC3II and unaffected p62 level by UUO were observed in Becn1F121A/F121A mice, suggesting an alleviation of disrupted autophagy. Beclin-1 F121A mutation causes a significant decrease in phosphorylation of inflammatory STING signal and limited production of IL6 and IFNγ, but had little effect on TNF-α, in response to UUO. Furthermore, activation of ISR signal cascade was detected in UUO-injured in kidneys, namely the phosphorylation signals of elF2S1 and PERK in addition to the stimulated expression of ISR effector ATF4. However, Becn1F121A/F121A mice did not reveal signs of elF2S1 and PERK activation under the same condition and had a dramatically reduced ATF level at 3-week post injury.ConclusionsThe results suggest that UUO causes a insufficient, maladaptive renal autophagy, which triggered downstream activation of inflammatory STING pathway, production of cytokines, and pathological activation of ISR, eventually leading to the development of fibrosis. Enhancing autophagy via Beclin-1 improved renal outcomes with diminished fibrosis, via underlying mechanisms of differential regulation of inflammatory mediators and control of maladaptive ISR.
The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections
Authors: Föhse Konstantin , Taks Esther J.M. , Moorlag Simone J. C. F. M. , Bonten Marc J. M. , van Crevel Reinout , ten Oever Jaap , van Werkhoven Cornelis H. , Netea Mihai G. , van de Maat Josephine S. , Hoogerwerf Jacobien J. 
Published: February 2023

Background and objectiveA recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs).MethodsThis is a post-hoc analysis of the BCG-CORONA-ELDERLY (NCT04417335) multicenter, placebo-controlled trial, in which participants aged 60 years and older were randomly assigned to vaccination with BCG or placebo, and followed for 12 months. The primary endpoint was the cumulative incidence of SARS-CoV-2 infection. To assess the impact of circadian rhythm on the BCG effects, participants were divided into four groups: vaccinated with either BCG or placebo in the morning (between 9:00h and 11:30h) or in the afternoon (between 14:30h and 18:00h).ResultsThe subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods.ConclusionAlthough there was a difference in effect between morning and afternoon BCG vaccination, the vaccine did not protect against SARS-COV-2 infections and clinically relevant RTI’s at either timepoint.
Insights into the ecological generalist lifestyle of Clonostachys fungi through analysis of their predicted secretomes
Authors: Piombo Edoardo , Guaschino Micol , Jensen Dan Funck , Karlsson Magnus , Dubey Mukesh 
Published: February 2023

IntroductionThe fungal secretome comprise diverse proteins that are involved in various aspects of fungal lifestyles, including adaptation to ecological niches and environmental interactions. The aim of this study was to investigate the composition and activity of fungal secretomes in mycoparasitic and beneficial fungal-plant interactions.MethodsWe used six Clonostachys spp. that exhibit saprotrophic, mycotrophic and plant endophytic lifestyles. Genome-wide analyses was performed to investigate the composition, diversity, evolution and gene expression of Clonostachys secretomes in relation to their potential role in mycoparasitic and endophytic lifestyles.Results and discussionOur analyses showed that the predicted secretomes of the analyzed species comprised between 7 and 8% of the respective proteomes. Mining of transcriptome data collected during previous studies showed that 18% of the genes encoding predicted secreted proteins were upregulated during the interactions with the mycohosts Fusarium graminearum and Helminthosporium solani. Functional annotation of the predicted secretomes revealed that the most represented protease family was subclass S8A (11–14% of the total), which include members that are shown to be involved in the response to nematodes and mycohosts. Conversely, the most numerous lipases and carbohydrate-active enzyme (CAZyme) groups appeared to be potentially involved in eliciting defense responses in the plants. For example, analysis of gene family evolution identified nine CAZyme orthogroups evolving for gene gains (p ≤ 0.05), predicted to be involved in hemicellulose degradation, potentially producing plant defense-inducing oligomers. Moreover, 8–10% of the secretomes was composed of cysteine-enriched proteins, including hydrophobins, important for root colonization. Effectors were more numerous, comprising 35–37% of the secretomes, where certain members belonged to seven orthogroups evolving for gene gains and were induced during the C. rosea response to F. graminearum or H. solani. Furthermore, the considered Clonostachys spp. possessed high numbers of proteins containing Common in Fungal Extracellular Membranes (CFEM) modules, known for their role in fungal virulence. Overall, this study improves our understanding of Clonostachys spp. adaptation to diverse ecological niches and establishes a basis for future investigation aiming at sustainable biocontrol of plant diseases.
Accurate module induced brain network construction for mild cognitive impairment identification with functional MRI
Authors: Du Yue , Wang Guangyu , Wang Chengcheng , Zhang Yangyang , Xi Xiaoming , Zhang Limei , Liu Mingxia 
Published: February 2023

IntroductionFunctional brain networks (FBNs) estimated from functional magnetic resonance imaging (fMRI) data has become a potentially useful way for computer-aided diagnosis of neurological disorders, such as mild cognitive impairment (MCI), a prodromal stage of Alzheimer's Disease (AD). Currently, Pearson's correlation (PC) is the most widely-used method for constructing FBNs. Despite its popularity and simplicity, the conventional PC-based method usually results in dense networks where regions-of-interest (ROIs) are densely connected. This is not accordance with the biological prior that ROIs may be sparsely connected in the brain. To address this issue, previous studies proposed to employ a threshold or l_1-regularizer to construct sparse FBNs. However, these methods usually ignore rich topology structures, such as modularity that has been proven to be an important property for improving the information processing ability of the brain.MethodsTo this end, in this paper, we propose an accurate module induced PC (AM-PC) model to estimate FBNs with a clear modular structure, by including sparse and low-rank constraints on the Laplacian matrix of the network. Based on the property that zero eigenvalues of graph Laplacian matrix indicate the connected components, the proposed method can reduce the rank of the Laplacian matrix to a pre-defined number and obtain FBNs with an accurate number of modules.ResultsTo validate the effectiveness of the proposed method, we use the estimated FBNs to classify subjects with MCI from healthy controls. Experimental results on 143 subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) with resting-state functional MRIs show that the proposed method achieves better classification performance than previous methods.
Profiling the low-beta characteristics of the subthalamic nucleus in early- and late-onset Parkinson’s disease
Authors: Wu Delong , Zhao Baotian , Xie Hutao , Xu Yichen , Yin Zixiao , Bai Yutong , Fan Houyou , Zhang Quan , Liu Defeng , Hu Tianqi , Jiang Yin , An Qi , Zhang Xin , Yang Anchao , Zhang Jianguo 
Published: February 2023

ObjectivesLow-beta oscillation (13–20 Hz) has rarely been studied in patients with early-onset Parkinson’s disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson’s disease (LOPD).MethodsWe enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group.ResultsWe found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500–650 ms, p = 0.008), while LOPD had higher proportion of short burst (200–350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300–460 Hz) amplitude (p = 0.019).ConclusionWe found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.