bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships Between Food Groups and Eating Time Slots According to Diabetes Status in Adults From the UK National Diet and Nutrition Survey (2008–2017)
Authors: Wang Chaochen , Almoosawi Suzana , Palla Luigi
Published: September 2021

Time of eating is associated with diabetes and obesity but little is known about less healthy foods and specific time of their intake over the 24 h of the day. In this study, we aimed to identify potential relationships between foods and their eating time and to see whether these associations may vary by diabetes status. The National Diet and Nutrition Survey (NDNS) including 6,802 adults (age ≥ 19 years old) collected 749,026 food recordings by a 4-day-diary. The contingency table cross-classifying 60 food groups with 7 pre-defined eating time slots (6–9 a.m., 9 a.m.–12 p.m., 12–2 p.m., 2–5 p.m., 8–10 p.m., 10 p.m.–6 a.m.) was analyzed by Correspondence Analysis (CA). CA biplots were generated for all adults and separately by diabetes status (self-reported, pre-diabetes, undiagnosed-diabetes, and non-diabetics) to visually explore the associations between food groups and time of eating across diabetes strata. For selected food groups, odds ratios (OR, 99% CI) were derived of consuming unhealthy foods at evening/night (8 p.m.–6 a.m.) vs. earlier time in the day, by logistic regression models with generalized estimating equations. The biplots suggested positive associations between evening/night and consumption of puddings, regular soft drinks, sugar confectioneries, chocolates, beers, ice cream, biscuits, and crisps for all adults in the UK. The OR (99% CIs) of consuming these foods at evening/night were, respectively, 1.43 (1.06, 1.94), 1.72 (1.44, 2.05), 1.84 (1.31, 2.59), 3.08 (2.62, 3.62), 7.26 (5.91, 8.92), 2.45 (1.84, 3.25), 1.90 (1.68, 2.16), and 1.49 (1.22, 1.82) vs. earlier time in the day adjusted for age, sex, body mass index (BMI), and social-economic levels. Stratified biplots found that sweetened beverages, sugar-confectioneries appeared more strongly associated with evening/night among undiagnosed diabetics. Foods consumed in the evening/night time tend to be highly processed, easily accessible, and rich in added sugar or saturated fat. Individuals with undiagnosed diabetes are more likely to consume unhealthy foods at night. Further longitudinal studies are required to ascertain the causal direction of the association between late-eating and diabetes status.
Correlation Between Serum Concentrations of Menaquinone-4 and Developmental Quotients in Children With Autism Spectrum Disorder
Authors: Dong Hanyu , Wang Bing , Feng Junyan , Yue Xiaojing , Jia Feiyong
Published: September 2021

Objective: The vitamin K family has a wide range of effects in the body, including the central nervous system. Menaquinone-4 (MK-4), a form of vitamin K2, is converted from phylloquinone (PK), which is the main source of dietary vitamin K and is the main form of vitamin K in the brain. We conducted this study to investigate the serum concentration of MK-4 and the correlations between MK-4 and developmental quotients in children with autism spectrum disorder (ASD).

Methods: We selected 731 children with ASD who were diagnosed for the first time. During the same period, 332 neurotypical children who underwent regular physical examinations in our outpatient department were selected as the TD group. We investigated the general situation of children, including gender and age. Children in ASD group were assessed for autistic symptoms and development quotients, including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), ADOS-2, and Griffiths Development Scales-Chinese Language Edition (GDS-C). Both groups of children were tested for serum menaquinone-4. We compared serum menaquinone-4 levels of ASD group and TD group. We then conducted a correlation analysis between the level of menaquinone-4 and the developmental quotient of children with ASD.

Results: The results of this study indicate that the serum concentration of MK-4 in children with ASD is lower than that in children with typical development (t = −2.702, P = 0.007). The serum concentration of MK-4 is related to the developmental quotients of several subscales in ASD children, and this correlation is more obvious in males.

Conclusion: we conclude that MK-4 is present in lower concentrations in children with ASD, which may affect cognition and developmental quotients. The role of MK-4 in ASD needs to be further explored.
Antimicrobial Peptides in Gut Health: A Review
Authors: Gong Tao , Fu Jie , Shi Lexuan , Chen Xin , Zong Xin
Published: September 2021

Animal antimicrobial peptides (AMPs), known as broad-spectrum and high-efficiency antibacterial activity, are important effector molecules in innate immune system. AMPs not only have antimicrobial, antiviral and antitumor effects but also exhibit important effects in vivo, such as anti-inflammatory response, recruiting immune cells, promoting epithelial damage repair, and promoting phagocytosis of bacteria. However, research on the application of AMPs is incomplete and controversial. This review mainly introduces the classification of AMPs, biological functions, as well as the mechanisms of action, expression rules, and nutrition regulation from three perspectives, aiming to provide important information for the application of AMPs.
Patterns of Tyrosine Kinase Inhibitor Utilization in Newly Treated Patients With Chronic Myeloid Leukemia: An Exhaustive Population-Based Study in France
Authors: Pajiep Marie , Conte Cécile , Huguet Françoise , Gauthier Martin , Despas Fabien , Lapeyre-Mestre Maryse
Published: September 2021

We analyzed demographic characteristics, comorbidities and patterns of treatment with tyrosine kinase inhibitors (TKIs) in a cohort of 3,633 incident cases of chronic myeloid leukemia (CML) identified across France from 1 January 2011 to 31 December 2014. Patients were identified through a specific algorithm in the French Healthcare Data System and were followed up 12 months after inclusion in the cohort. The estimated incidence rate of CML for this period in France was 1.37 per 100,000 person-years (95% Confidence Interval 1.36-1.38) and was higher in men, with a peak at age 75-79 years. At baseline, the median age of the cohort was 60 years (Inter Quartile Range 47-71), the Male/Female ratio was 1.2, and 25% presented with another comorbidity. Imatinib was the first-line TKI for 77.6% of the patients, followed by nilotinib (18.3%) and dasatinib (4.1%). Twelve months after initiation, 86% of the patients remained on the same TKI, 13% switched to another TKI and 1% received subsequently three different TKIs. During the follow-up, 23% discontinued and 52% suspended the TKI. Patients received a mean of 16.7 (Standard Deviation (SD) 9.6) medications over the first year of follow-up, and a mean of 2.7 (SD 2.3) concomitant medications on the day of first TKI prescription: 24.4% of the patients received allopurinol, 6.4% proton pump inhibitors (PPI) and 6.5% antihypertensive agents. When treatment with TKI was initiated, incident CML patients presented with comorbidities and polypharmacy, which merits attention because of the persistent use of these concomitant drugs and the potential increased risk of drug-drug interactions.
The Balance Between the Effectiveness and Safety for Chemotherapy-Induced Nausea and Vomiting of Different Doses of Olanzapine (10 mg Versus 5 mg): A Systematic Review and Meta-Analysis
Authors: Wang Dong-Yang , Chen Yi , Zhang You , Shen Ying-Qiang
Published: September 2021

Introduction

The aim of this study is to rigorously review the efficacy and safety of olanzapine in chemotherapy-induced nausea and vomiting (CINV) settings including (1) at 5- and 10-mg doses, and (2) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

Methods

Embase, Pubmed, and Cochrane Library were searched from the establishment of the database through April 18, 2021. The primary efficacy endpoints were the rate of complete response (CR; no emesis and no rescue), in the acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy), and overall (0–120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of complete control (CC, no nausea, and no emesis), for each phase. Safety endpoints were the rate of somnolence, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel–Haenszel, random, or fixed-effect analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO.

Result

Nine studies reported the use of 10 mg olanzapine to prevent CINV; three studies reported the use of 5 mg olanzapine to prevent CINV. When olanzapine was administered at 10 mg for HEC patients, the six endpoints were statistically and clinically better than the control group. For MEC patients, four out of six endpoints were better than the control group. When olanzapine is administered at 5 mg for MEC patients, four endpoints have statistical and clinical advantages. The sedative effects of 10 and 5 mg olanzapine were statistically more significant than those of the control group. The sedative effect of the 10-mg olanzapine group was more significant than that of the 5-mg olanzapine group, both statistically and clinically.

Conclusion

5 mg olanzapine may be as effective as 10 mg olanzapine for patients with HEC and MEC, and its sedative effect is lower than 10 mg olanzapine. Fewer studies on 5 mg olanzapine have led to uncertain data. In the future, more randomized controlled trials of 5 mg olanzapine are needed to study the balance between the effectiveness and safety of olanzapine.
Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer
Authors: Burke Michael , Rashdan Sawsan
Published: September 2021

With proven efficacy of the use of immunotherapy in almost all stages of NSCLC, immunotherapy toxicity has become a very important topic that requires immediate recognition and management. The diagnosis of toxicities associated with immunotherapy in lung cancer can be very challenging and often requires multidisciplinary effort. This mini review gives an overview of the diagnosis and management of immune-related adverse events that arise from using immunotherapy in NSCLC, as well as the potential biomarkers for its early identification and future directions.
Periodontal Pathogens Promote Oral Squamous Cell Carcinoma by Regulating ATR and NLRP3 Inflammasome
Authors: Yao Yufei , Shen Xin , Zhou Maolin , Tang Boyu
Published: September 2021

Periodontitis is closely related to oral cancer, but the molecular mechanism of periodontal pathogens involved in the occurrence and development of oral cancer is still inconclusive. Here, we demonstrate that, in vitro, the cell proliferation ability and S phase cells of the periodontitis group (colonized by Porphyromonas gingivalis and Fusobacterium nucleatum, P+) significantly increased, but the G1 cells were obviously reduced. The animal models with an in situ oral squamous cell carcinoma (OSCC) and periodontitis-associated bacteria treatment were constructed, and micro-CT showed that the alveolar bone resorption of mice in the P+ group (75.3 ± 4.0 μm) increased by about 53% compared with that in the control group (48.8 ± 1.3 μm). The tumor mass and tumor growth rate in the P+ group were all higher than those in the blank control group. Hematoxylin–eosin (H&E) staining of isolated tumor tissues showed that large-scale flaky necrosis was found in the tumor tissue of the P+ group, with lots of damaged vascular profile and cell debris. Immunohistochemistry (IHC) of isolated tumor tissues showed that the expression of Ki67 and the positive rate of cyclin D1 were significantly higher in tumor tissues of the P+ group. The qRT-PCR results of the expression of inflammatory cytokines in oral cancer showed that periodontitis-associated bacteria significantly upregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-18, apoptosis-associated speck-like protein containing a CARD (ASC) (up to six times), and caspase-1 (up to four times), but it downregulated nuclear factor (NF)-κB, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and IL-1β (less than 0.5 times). In addition, the volume of spleen tissue and the number of CD4+ T cells, CD8+ T cells, and CD206+ macrophages in the P+ group increased significantly. IHC and Western blotting in tumor tissues showed that expression levels of γ-H2AX, p-ATR, RPA32, CHK1, and RAD51 were upregulated, and the phosphorylation level of CHK1 (p-chk1) was downregulated. Together, we identify that the periodontitis-related bacteria could promote tumor growth and proliferation, initiate the overexpressed NLRP3, and activate upstream signal molecules of ATR-CHK1. It is expected to develop a new molecular mechanism between periodontitis-related bacteria and OSCC.
68Ga-Labeled GX1 Dimer: A Novel Probe for PET/Cerenkov Imaging Targeting Gastric Cancer
Authors: Yin Jipeng , Xin Bo , Zhang Mingru , Hui Xiaoli , Chai Na , Hu Hao , Xu Bing , Wang Jing , Nie Yongzhan , Zhou Guangqing , Wang Guanliang , Lu Hongbing , Yao Liping , Chen Liusheng , Wu Kaichun
Published: September 2021

Purpose

To synthesize the dimer of GX1 and identify whether its affinity and targeting are better than those of GX1. To prepare 68Ga-DOTA-KEK-(GX1)2 and to apply it to PET and Cerenkov imaging of gastric cancer.

Methods

68Ga-DOTA-KEK-(GX1)2 was prepared, and the labeling yield and stability were determined. Its specificity and affinity were verified using an in vitro cell binding assay and competitive inhibition test, cell immunofluorescence, and cell uptake and efflux study. Its tumor-targeting ability was determined by nano PET/CT and Cerenkov imaging, standardized uptake value (SUV), signal-to-background ratio (SBR) quantification, and a biodistribution study in tumor-bearing nude mice.

Results

68Ga-DOTA-KEK-(GX1)2 was successfully prepared, and the labeling yield was more than 97%. It existed stably for 90 min in serum. The binding of 68Ga-DOTA-KEK-(GX1)2 to cocultured HUVECs (Co-HUVECs) was higher than that to human umbilical vein endothelial cells (HUVECs), BGC823 cells, and GES cells. It was also higher than that of 68Ga-DOTA-GX1, indicating that the dimer did improve the specificity and affinity of GX1. The binding of KEK-(GX1)2 to Co-HUVECs was significantly higher than that of GX1. Additionally, the uptake of 68Ga-DOTA-KEK-(GX1)2 by Co-HUVECs was higher than that of 68Ga-DOTA-GX1 and reached a maximum at 60 min. Nano PET/CT and Cerenkov imaging showed that the tumor imaging of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 was clear, and the SUV and SBR value of the tumor sites were significantly higher than those of the nude mice injected with 68Ga-DOTA-GX1, indicating that the probe had better targeting in vivo. Finally, the biodistribution showed quantitatively that when organs such as the kidney and liver metabolized rapidly, the radioactivity of the tumor site of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 decreased relatively slowly. At the same time, the percentage of injected dose per gram (%ID/g) of the tumor site was higher than that of other normal organs except the liver and kidney at 60 min, which indicated that the tumor had good absorption of the probe.

Conclusion

GX1 was modified successfully, and the in vivo and in vitro properties of the GX1 dimer were significantly better than those of GX1. The imaging probe, 68Ga-DOTA-KEK-(GX1)2, was successfully prepared, which provides a candidate probe for PET and Cerenkov diagnosis of gastric cancer.
Identification of Therapeutic Targets and Prognostic Biomarkers Among Integrin Subunits in the Skin Cutaneous Melanoma Microenvironment
Authors: Nurzat Yeltai , Su Weijie , Min Peiru , Li Ke , Xu Heng , Zhang Yixin
Published: September 2021

The roles of different integrin alpha/beta (ITGA/ITGB) subunits in skin cutaneous melanoma (SKCM) and their underlying mechanisms of action remain unclear. Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, and Webgestalt analysis tools were used. The expression levels of ITGA3, ITGA4, ITGA6, ITGA10, ITGB1, ITGB2, ITGB3, ITGB4, and ITGB7 were significantly increased in SKCM tissues. The expression levels of ITGA1, ITGA4, ITGA5, ITGA8, ITGA9, ITGA10, ITGB1, ITGB2, ITGB3, ITGB5, ITGB6 and ITGB7 were closely associated with SKCM metastasis. The expression levels of ITGA1, ITGA4, ITGB1, ITGB2, ITGB6, and ITGB7 were closely associated with the pathological stage of SKCM. The expression levels of ITGA6 and ITGB7 were closely associated with disease-free survival time in SKCM, and the expression levels of ITGA6, ITGA10, ITGB2, ITGB3, ITGB6, ITGB7, and ITGB8 were markedly associated with overall survival in SKCM. We also found significant correlations between the expression of integrin subunits and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells). Finally, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and protein-protein interaction (PPI) networks were constructed. We have identified abnormally-expressed genes and gene regulatory networks associated with SKCM, improving understanding of the underlying pathogenesis of SKCM.
Decreased Incidence of Intraventricular Hemorrhage in Extremely Low Birth Weight Infants Using Customized Circulatory Management to Evaluate the Hemodynamic Change of Patent Ductus Arteriosus
Authors: Huang Wan-Heng , Li De-Ming , Hsu Chung-Ting , Lin Yi-Hsuan , Hsu Ya-Chi , Wang Teh-Ming , Lin Ming-Chih
Published: September 2021

Background:In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants.

Methods:We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia.

Results:A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 (p= 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration (p= 0.017).

Conclusion:The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective “early target therapy” for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications.
Parental Stress, Depression, and Participation in Care Before and During the COVID-19 Pandemic: A Prospective Observational Study in an Italian Neonatal Intensive Care Unit
Authors: Bua Jenny , Mariani Ilaria , Girardelli Martina , Tomadin Murphy , Tripani Antonella , Travan Laura , Lazzerini Marzia
Published: September 2021

Background: Recent studies reported, during the COVID-19 pandemic, increased mental distress among the general population and among women around the childbirth period. COVID-19 pandemic may undermine the vulnerable well-being of parents in Neonatal Intensive Care Units (NICUs).

Objective: Our study aimed to explore whether parental stress, depression, and participation in care in an Italian NICU changed significantly over three periods: pre-pandemic (T0), low (T1), and high COVID-19 incidence (T2).

Methods: Enrolled parents were assessed with the Parental Stressor Scale in the NICU (PSS:NICU), Edinburgh Postnatal Depression Scale (EPDS), and Index of Parental Participation (IPP). Stress was the study primary outcome. A sample of 108 parents, 34 for each time period, was estimated to be adequate to detect a difference in PSS:NICU stress occurrence level score (SOL) of 1.25 points between time periods. To estimate score differences among the three study periods a non-parametric analysis was performed. Correlation among scores was assessed with Spearman rank coefficient.

Results: Overall, 152 parents were included in the study (62 in T0, 56 in T1, and 34 in T2). No significant differences in the median PSS:NICU, EPDS, and IPP scores were observed over the three periods, except for a slight increase in the PSS:NICU parental role sub-score in T2 (T0 3.3 [2.3–4.1] vs. T2 3.9 [3.1–4.3]; p = 0.038). In particular, the question regarding the separation from the infant resulted the most stressful aspect during T2 (T0 4.0 [4.0–5.0] vs. T2 5.0 [4.0–5.0], p = 0.008). The correlation between participation and stress scores (r = 0.19–022), and between participation and depression scores (r = 0.27) were weak, while among depression and stress, a moderate positive correlation was found (r = 0.45–0.48).

Conclusions: This study suggests that parental stress and depression may be contained during the COVID-19 pandemic, while participation may be ensured.
Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis
Authors: Puzzovio Pier Giorgio , Levi-Schaffer Francesca
Published: September 2021

In the last years, the understanding of the pathologic mechanisms of asthma and atopic dermatitis, both characterized by allergic inflammation, has greatly improved. However, it is evident that both diseases present with high heterogeneity, which complicates the diagnosis and the therapeutic approach of the patients. Moreover, some of the currently available strategies to treat asthma and atopic dermatitis are still mostly controlling the symptoms, but not to lead towards full healing, thus having these two diseases labelled as unmet clinical needs by WHO. Therefore, the “one-size-fits-all” strategy is outdated for asthma and atopic dermatitis, and there is the need of better methods to clearly diagnose the disease and tailor the therapy according to the specific symptomatology. In this regard, the use of biomarkers has been advanced in order to characterize both diseases according to their clinical signs and to facilitate the subsequent treatment. Despite the advancements made in this regard, there is still need for better and more sensitive biomarkers and for less invasive sampling methodologies, with the aim to diagnose specifically each manifestation of asthma and atopic dermatitis and to provide the best treatment with the least suffering for the patients.
Eicosanoid Metabolomic Profile of Remdesivir Treatment in Rat Plasma by High-Performance Liquid Chromatography Mass Spectrometry
Authors: Du Ping , Wang Guo-yong , Zhao Rui , An Zhuo-ling , Liu Li-hong
Published: September 2021

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.
Protease-Activated Receptor-1 Antagonist Protects Against Lung Ischemia/Reperfusion Injury
Authors: Chu Shi-Jye , Tang Shih-En , Pao Hsin-Ping , Wu Shu-Yu , Liao Wen-I
Published: September 2021

Protease-activated receptor (PAR)-1 is a thrombin-activated receptor that plays an essential role in ischemia/reperfusion (IR)-induced acute inflammation. PAR-1 antagonists have been shown to alleviate injuries in various IR models. However, the effect of PAR-1 antagonists on IR-induced acute lung injury (ALI) has not yet been elucidated. This study aimed to investigate whether PAR-1 inhibition could attenuate lung IR injury. Lung IR was induced in an isolated perfused rat lung model. Male rats were treated with the specific PAR-1 antagonist SCH530348 (vorapaxar) or vehicle, followed by ischemia for 40 min and reperfusion for 60 min. To examine the role of PAR-1 and the mechanism of SCH530348 in lung IR injury, western blotting and immunohistochemical analysis of lung tissue were performed. In vitro, mouse lung epithelial cells (MLE-12) were treated with SCH530348 or vehicle and subjected to hypoxia-reoxygenation (HR). We found that SCH530348 decreased lung edema and neutrophil infiltration, attenuated thrombin production, reduced inflammatory factors, including cytokine-induced neutrophil chemoattractant-1, interleukin-6 and tumor necrosis factor-α, mitigated lung cell apoptosis, and downregulated the phosphoinositide 3-kinase (PI3K), nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in IR-injured lungs. In addition, SCH530348 prevented HR-induced NF-κB activation and inflammatory chemokine production in MLE12 cells. Our results demonstrate that SCH530348 exerts protective effects by blocking PAR-1 expression and modulating the downstream PI3K, NF-κB and MAPK pathways. These findings indicate that the PAR-1 antagonist protects against IR-induced ALI and is a potential therapeutic candidate for lung protection following IR injury.
Actuators for MRE: New Perspectives With Flexible Electroactive Materials
Authors: Gnanago Jean-Lynce , Capsal Jean-Fabien , Gerges Tony , Lombard Philippe , Semet Vincent , Cottinet Pierre-Jean , Cabrera Michel , Lambert Simon Auguste
Published: September 2021

Since 1995, Magnetic Resonance Elastography (MRE) has been constantly developed as a non-invasive diagnostic tool for quantitative mapping of mechanical properties of biological tissues. Indeed, mechanical properties of tissues vary over five orders of magnitude (the shear stiffness is ranging from 102 Pa for fat to 107 Pa for bones). Additionally, these properties depend on the physiological state which explains the granted benefit of MRE for staging liver fibrosis and its potential in numerous medical and biological domains. In comparison to the other modalities used to perform such measurement, Magnetic Resonance (MR) techniques offer the advantages of acquiring 3D high spatial resolution images at high penetration depth. However, performing MRE tissue characterization requires low frequency shear waves propagating in the tissue. Inducing them is the role of a mechanical actuator specifically designed to operate under Magnetic Resonance Imaging (MRI) specific restrictions in terms of electromagnetic compatibility. Facing these restrictions, many different solutions have been proposed while keeping a common structure: a vibration generator, a coupling device transmitting the vibration and a piston responsible for the mechanical coupling of the actuator with the tissue. The following review details the MRI constraints and how they are shaping the existing actuators. An emphasis is put on piezoelectric solutions as they solve the main issues encountered with other actuator technologies. Finally, flexible electroactive materials are reviewed as they could open great perspectives to build new type of mechanical actuators with better adaptability, greater ease-of-use and more compactness of dedicated actuators for MRE of small soft samples and superficial organs such as skin, muscles or breast.
Immersive Virtual Reality Influences Physiologic Responses to Submaximal Exercise: A Randomized, Crossover Trial
Authors: Rutkowski Sebastian , Szary Patryk , Sacha Jerzy , Casaburi Richard
Published: September 2021

Objectives: This cross-sectional, randomly assigned study aimed to assess the influence of immersive virtual reality (VR) on exercise tolerance expressed as the duration of a submaximal exercise test (ET) on a cycle ergometer.

Methods: The study enrolled 70 healthy volunteers aged 22–25years. Each participant performed an ET with and without VR. Time- and frequency-domain heart rate variability (HRV) parameters were analyzed for the first 3min (T1), the last 3min (T2), and the time at which the shorter of the two tests terminated (Tiso). In the time domain, a SD of R–R intervals (SDNN) and a root mean square of successive R–R interval differences (RMSSD) in milliseconds were computed. The following spectral components were considered: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio. The study was registered in ClinicalTrials.gov (NCT04197024).

Results: Compared to standard ET, tests in immersive VR lasted significantly longer (694 vs. 591s, p<0.00001) and were associated with lower HR response across the range of corresponding exercise levels, averaging 5–8 beats/min. In the multiple regression analysis, the ET duration was positively determined by male sex, immersion in VR, and negatively determined by HRT1 and RMSSDT1.

Conclusion: Exercising in VR is associated with lower HR which allowed subjects to exercise for a longer time before reaching target heart rate (HR). In addition, the increase in exercise duration was found to be related to an adjustment in autonomic nervous activity at a given work rate favoring parasympathetic predominance.
Molecular Identification of Anion Exchange Protein 3 in Pacific White Shrimp (Litopenaeus vannamei): mRNA Profiles for Tissues, Ontogeny, Molting, and Ovarian Development and Its Potential Role in Stress-Induced Gill Damage
Authors: Zhang Xin , Yang Hao , Li Hongmei , Chen Ting , Ruan Yao , Ren Chunhua , Luo Peng , Wang Yanhong , Liu Bing , Li Huo , Zhong Ping , Zhang Jiquan , Jiang Xiao , Hu Chaoqun
Published: September 2021

Bicarbonate (HCO3–) transport mechanisms play an essential role in the acid-base homeostasis of aquatic animals, and anion exchange protein 3 (AE3) is a membrane transport protein that exchanges Cl–/HCO3– across the cell membrane to regulate the intracellular pH. In this study, the full-length cDNA of AE3 (Lv-AE3) was obtained from the Pacific white shrimp (Litopenaeus vannamei). The Lv-AE3 cDNA is 4,943 bp in length, contains an open reading frame of 2,850 bp, coding for a protein of 949 amino acids with 12 transmembrane domains. Lv-AE3 shows high sequence homology with other AE3 at the protein level. Lv-AE3 mRNA was ubiquitously detected in all tissues selected, with the highest expression level in the gill, followed by the ovary, eyestalk and brain. By in situ hybridization, Lv-AE3-positive cells were shown predominant localization in the secondary gill filaments. The expression levels of Lv-AE3 were further investigated during the essential life processes of shrimp, including ontogeny, molting, and ovarian development. In this case, the spatiotemporal expression profiles of Lv-AE3 in L. vannamei were highly correlated with the activities of water and ion absorption; for example, increased mRNA levels were present after hatching, during embryonic development, after ecdysis during the molt cycle, and in the stage IV ovary during gonadal development. After low/high pH and low/high salinity challenges, the transcript levels of Lv-AE3 were reduced in the gill, while the cell apoptosis rate increased. In addition, knockdown of Lv-AE3 mRNA expression induced cell apoptosis in the gill, indicating a potential link between Lv-AE3 and gill damage. Altogether, this study thoroughly investigated the relationship between the mRNA expression profiles of Lv-AE3 and multiple developmental and physiological processes in L. vannamei, and it may benefit the protection of crustaceans from fluctuated aquatic environments.
Stroke-Related Mortality at Different Altitudes: A 17-Year Nationwide Population-Based Analysis From Ecuador
Authors: Ortiz-Prado Esteban , Espinosa Patricio S. , Borrero Alfredo , Cordovez Simone P. , Vasconez Jorge E. , Barreto-Grimales Alejandra , Coral-Almeida Marco , Henriquez-Trujillo Aquiles R. , Simbaña-Rivera Katherine , Gomez-Barreno Lenin , Viscor Gines , Roderick Paul
Published: September 2021

Introduction: Worldwide, more than 5.7% of the population reside above 1,500 m of elevation. It has been hypothesized that acute short-term hypoxia exposure could increase the risk of developing a stroke. Studies assessing the effect of altitude on stroke have provided conflicting results, some analyses suggest that long-term chronic exposure could be associated with reduced mortality and lower stroke incidence rates.

Methods: An ecological analysis of all stroke hospital admissions, mortality rates, and disability-adjusted life years in Ecuador was performed from 2001 to 2017. The cases and population at risk were categorized in low (<1,500 m), moderate (1,500–2,500 m), high (2,500–3,500 m), and very high altitude (3,500–5,500 m) according to the place of residence. The derived crude and direct standardized age-sex adjusted mortality and hospital admission rates were calculated.

Results: A total of 38,201 deaths and 75,893 stroke-related hospital admissions were reported. High altitude populations (HAP) had lower stroke mortality in men [OR: 0.91 (0.88–0.95)] and women [OR: 0.83 (0.79–0.86)]. In addition, HAP had a significant lower risk of getting admitted to the hospital when compared with the low altitude group in men [OR: 0.55 (CI 95% 0.54–0.56)] and women [OR: 0.65 (CI 95% 0.64–0.66)].

Conclusion: This is the first epidemiological study that aims to elucidate the association between stroke and altitude using four different elevation ranges. Our findings suggest that living at higher elevations offers a reduction or the risk of dying due to stroke as well as a reduction in the probability of being admitted to the hospital. Nevertheless, this protective factor has a stronger effect between 2,000 and 3,500 m.
Analyzing the Role of Repolarization Gradients in Post-infarct Ventricular Tachycardia Dynamics Using Patient-Specific Computational Heart Models
Authors: Sung Eric , Prakosa Adityo , Trayanova Natalia A.
Published: September 2021

Aims: Disease-induced repolarization heterogeneity in infarcted myocardium contributes to VT arrhythmogenesis but how apicobasal and transmural (AB-TM) repolarization gradients additionally affect post-infarct VT dynamics is unknown. The goal of this study is to assess how AB-TM repolarization gradients impact post-infarct VT dynamics using patient-specific heart models.

Method: 3D late gadolinium-enhanced cardiac magnetic resonance images were acquired from seven post-infarct patients. Models representing the patient-specific scar and infarct border zone distributions were reconstructed without (baseline) and with repolarization gradients along both the AB-TM axes. AB only and TM only models were created to assess the effects of each ventricular gradient on VT dynamics. VTs were induced in all models via rapid pacing.

Results: Ten baseline VTs were induced. VT inducibility in AB-TM models was not significantly different from baseline (p>0.05). Reentry pathways in AB-TM models were different than baseline pathways due to alterations in the location of conduction block (p<0.05). VT exit sites in AB-TM models were different than baseline VT exit sites (p<0.05). VT inducibility of AB only and TM only models were not significantly different than that of baseline (p>0.05) or AB-TM models (p>0.05). Reentry pathways and VT exit sites in AB only and TM only models were different than in baseline (p<0.05). Lastly, repolarization gradients uncovered multiple VT morphologies with different reentrant pathways and exit sites within the same structural, conducting channels.

Conclusion: VT inducibility was not impacted by the addition of AB-TM repolarization gradients, but the VT reentrant pathway and exit sites were greatly affected due to modulation of conduction block. Thus, during ablation procedures, physiological and pharmacological factors that impact the ventricular repolarization gradient might need to be considered when targeting the VTs.
An Open-Access Database for the Evaluation of Cardio-Mechanical Signals From Patients With Valvular Heart Diseases
Authors: Yang Chenxi , Fan Foli , Aranoff Nicole , Green Philip , Li Yuwen , Liu Chengyu , Tavassolian Negar
Published: September 2021

This paper describes an open-access database for seismo-cardiogram (SCG) and gyro-cardiogram (GCG) signals. The archive comprises SCG and GCG recordings sourced from and processed at multiple sites worldwide, including Columbia University Medical Center and Stevens Institute of Technology in the United States, as well as Southeast University, Nanjing Medical University, and the first affiliated hospital of Nanjing Medical University in China. It includes electrocardiogram (ECG), SCG, and GCG recordings collected from 100 patients with various conditions of valvular heart diseases such as aortic and mitral stenosis. The recordings were collected from clinical environments with the same types of wearable sensor patch. Besides the raw recordings of ECG, SCG, and GCG signals, a set of hand-corrected fiducial point annotations is provided by manually checking the results of the annotated algorithm. The database also includes relevant echocardiogram parameters associated with each subject such as ejection fraction, valve area, and mean gradient pressure.
Arabidopsis thaliana eIF4E1 and eIF(iso)4E Participate in Cold Response and Promote Translation of Some Stress-Related mRNAs
Authors: Salazar-Díaz Kenia , Aquino-Luna Mayra , Hernández-Lucero Eloísa , Nieto-Rivera Brenda , Pulido-Torres Marlon A. , Jorge-Pérez Jesús H. , Gavilanes-Ruiz Marina , Dinkova Tzvetanka D.
Published: September 2021

Plant defense and adaptation to adverse environmental conditions rely on gene expression control, such as mRNA transcription, processing, stability, and translation. Sudden temperature changes are common in the era of global warming; thus, understanding plant acclimation responses at the molecular level becomes imperative. mRNA translation initiation regulation has a pivotal role in achieving the synthesis of the appropriate battery of proteins needed to cope with temperature stress. In this study, we analyzed the role of translation initiation factors belonging to the eIF4E family in Arabidopsis acclimation to cold temperatures and freezing tolerance. Using knockout (KO) and overexpressing mutants of AteIF4E1 or AteIF(iso)4E, we found that AteIF4E1 but not AteIF(iso)4E overexpressing lines displayed enhanced tolerance to freezing without previous acclimation at 4°C. However, KO mutant lines, eif(iso)4e-1 and eif4e1-KO, were more sensitive to the stress. Cold acclimation in wild-type plants was accompanied by increased levels of eIF4E1 and eIF(iso)4E transcript levels, polysomes (P) enrichment, and shifts of these factors from translationally non-active to active fractions. Transcripts, previously found as candidates for eIF(iso)4E or eIF4E1 selective translation, changed their distribution in both P and total RNA in the presence of cold. Some of these transcripts changed their polysomal distribution in the mutant and one eIF4E1 overexpressing line. According to this, we propose a role of eIF4E1 and eIF(iso)4E in cold acclimation and freezing tolerance by regulating the expression of stress-related genes.
Fungal Endophyte: An Interactive Endosymbiont With the Capability of Modulating Host Physiology in Myriad Ways
Authors: Sarkar Sohini , Dey Abhijit , Kumar Vinay , Batiha Gaber El-Saber , El-Esawi Mohamed A. , Tomczyk Michał , Ray Puja
Published: September 2021

Endophytic fungi ubiquitously dwell inside the tissue-spaces of plants, mostly asymptomatically. They grow either intercellularly or intracellularly in a particular host plant to complete the whole or part of their life cycle. They have been found to be associated with almost all the plants occurring in a natural ecosystem. Due to their important role in the survival of plants (modulate photosynthesis, increase nutrient uptake, alleviate the effect of various stresses) they have been selected to co-evolve with their hosts through the course of evolution. Many years of intense research have discovered their tremendous roles in increasing the fitness of the plants in both normal and stressed conditions. There are numerous literature regarding the involvement of various endophytic fungi in enhancing plant growth, nutrient uptake, stress tolerance, etc. But, there are scant reports documenting the specific mechanisms employed by fungal endophytes to manipulate plant physiology and exert their effects. In this review, we aim to document the probable ways undertaken by endophytic fungi to alter different physiological parameters of their host plants. Our objective is to present an in-depth elucidation about the impact of fungal endophytes on plant physiology to make this evolutionarily conserved symbiotic interaction understandable from a broader perspective.
Characterization of the Durum Wheat-Aegilops tauschii 4D(4B) Disomic Substitution Line YL-443 With Superior Characteristics of High Yielding and Stripe Rust Resistance
Authors: Yang Fan , Liu Qier , Wang Qin , Yang Ning , Li Jun , Wan Honshen , Liu Zehou , Yang Sujie , Wang Ying , Zhang Jie , Liu Hang , Fan Xing , Ma Wujun , Yang Wuyun , Zhou Yonghong
Published: September 2021

Durum wheat is one of the important food and cash crops. The main goals in current breeding programs are improving its low yield potential, kernel characteristics, and lack of resistance or tolerance to some biotic and abiotic stresses. In this study, a nascent synthesized hexaploid wheat Lanmai/AT23 is used as the female parent in crosses with its AB genome donor Lanmai. A tetraploid line YL-443 with supernumerary spikelets and high resistance to stripe rust was selected out from the pentaploid F7 progeny. Somatic analysis using multicolor fluorescence in situ hybridization (mc-FISH) revealed that this line is a disomic substitution line with the 4B chromosome pair of Lanmai replaced by the 4D chromosome pair of Aegilops tauschii AT23. Comparing with Lanmai, YL-443 shows an increase in the number of spikelets and florets per spike by 36.3 and 75.9%, respectively. The stripe rust resistance gene Yr28 carried on the 4D chromosome was fully expressed in the tetraploid background. The present 4D(4B) disomic substitution line YL-443 was distinguished from the previously reported 4D(4B) lines with the 4D chromosomes from Chinese Spring (CS). Our study demonstrated that YL-443 can be used as elite germplasm for durum wheat breeding targeting high yield potential and stripe rust resistance. The Yr28-specific PCR marker and the 4D chromosome-specific KASP markers together with its unique features of pubescent leaf sheath and auricles can be utilized for assisting selection in breeding.
Single-Molecule Real-Time and Illumina Sequencing to Analyze Transcriptional Regulation of Flavonoid Synthesis in Blueberry
Authors: Tang Qi , Chi Fu-Mei , Liu Hong-Di , Zhang Hong-Jun , Song Yang
Published: September 2021

Blueberries (Vaccinium corymbosum) contain large amounts of flavonoids, which play important roles in the plant’s ability to resist stress and can also have beneficial effects on human health when the fruits are eaten. However, the molecular mechanisms that regulate flavonoid synthesis in blueberries are still unclear. In this study, we combined two different transcriptome sequencing platforms, single-molecule real-time (SMRT) and Illumina sequencing, to elucidate the flavonoid synthetic pathways in blueberries. We analyzed transcript quantity, length, and the number of annotated genes. We mined genes associated with flavonoid synthesis (such as anthocyanins, flavonols, and proanthocyanidins) and employed fluorescence quantitative PCR to analyze the expression of these genes and their correlation with flavonoid synthesis. We discovered one R2R3 MYB transcription factor from the sequencing library, VcMYB1, that can positively regulate anthocyanin synthesis in blueberries. VcMYB1 is mainly expressed in colored (mature) fruits. Experiments showed that overexpression and transient expression of VcMYB1 promoted anthocyanin synthesis in Arabidopsis, tobacco (Nicotiana benthamiana) plants and green blueberry fruits. Yeast one-hybrid (Y1H) assay, electrophoretic mobility shift assay, and transient expression experiments showed that VcMYB1 binds to the MYB binding site on the promoter of the structural gene for anthocyanin synthesis, VcMYB1 to positively regulate the transcription of VcDFR, thereby promoting anthocyanin synthesis. We also performed an in-depth investigation of transcriptional regulation of anthocyanin synthesis. This study provides background information and data for studying the synthetic pathways of flavonoids and other secondary metabolites in blueberries.
Shape–Trait Consistency: The Matching Effect of Consumer Power State and Shape Preference
Authors: Yao Feng , Jin Xiaotong , Wu Banggang , Zhao Taiyang , Ma Tiannv
Published: September 2021

Angular and rounded shapes are two important visual elements widely used in the design of product shapes and brand logos. By introducing the power state, a psychological variable that is inherently relevant to consumers' product choices, brand preferences, and decision-making, we propose that consumers' power state influences their shape preference. Specifically, compared to low-power consumers, high-power consumers respond more positively to angular as opposed to rounded shapes, because the angular shape facilitates the expression of competence (as opposed to warmth). Through four studies, we provide consistent support for our main predictions as well as the underlying processes. Studies 1 and 2 demonstrate that consumers experiencing higher power are more likely to prefer an angular shape over a rounded shape than those experiencing lower power through different research methods, research objects, and experimental materials. On this basis, studies 3 and 4 further explore the mechanisms underlying the observed effects. These findings contribute to sensory marketing and power research and provide important implications for visual design and advertisement development.