bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Natural and BNT162b2 Vaccine-induced Immunity, with and without an Enhancer or Booster Dose, on the Risk of COVID-19-Related Hospitalization in Israel
Authors: Waxman Jacob , Makov-Assif Maya , Reis Ben , Nezer Doron , Balicer Ran , Dagan Noa , Barda Noam
Published: January 2022

Introduction:
With the COVID-19 pandemic ongoing, accurate assessment of population immunity and the effectiveness of booster and enhancer vaccines is critical.
Methods
We compare COVID-19-related hospitalization incidence rate ratios, adjusted for potential demographic, clinical and health-seeking-behavior confounders, in 2,412,755 individuals (235,552,274 person-days), across four exposures: 2 BNT162b2 doses, 5 or more months prior ("non-recent vaccine immunity"); 3 BNT162b2 doses (“boosted vaccine immunity”); previous COVID-19, with or without a subsequent BNT162b2 dose (“natural immunity” and “enhanced natural immunity” respectively).
Results
Compared with non-recent vaccine immunity, COVID-19-related hospitalization incidence rate ratios are 11% (9%-13%) for boosted vaccine immunity, 34% (23%-50%) for natural immunity and 25% (17%-39%) for enhanced natural immunity.
Conclusion
We demonstrate that natural immunity (enhanced or not) provides better protection against COVID-19-related hospitalization than non-recent vaccine immunity, but less protection than that attained from booster vaccination. Additionally, our results suggest that vaccinating individuals with natural immunity further enhances their protection.
High Times and Dry Times In a Salt Marsh: Budgeting For Supplemental Freshwater Needs at the Big Boggy National Wildlife Refuge, USA
Authors: Madewell Matthew , Feagin Rusty , Huff Thomas , Balboa Bill
Published: January 2022

Salt marshes can be vulnerable to reduced freshwater input. Reduced freshwater inflows, particularly during a hot or dry summer season, can be catastrophic for vegetation productivity, organic accretion and inorganic sedimentation, and the ability of a marsh to maintain a sustainable elevation facing relative sea level rise (RSLR). Unfortunately, it is challenging for scientists to obtain inflow records for ungauged watersheds and link them with historical trends of salt marsh loss. We sought to address this challenge in Big Boggy National Wildlife Refuge (NWR), a small watershed in East Matagorda Bay, Texas. Our objective was to link the quantity of freshwater inflow with salt marsh sustainability and recommend management actions for the NWR. We first explored land cover trends and found that this watershed lost more than one-third of its low marsh since 1953. We then measured the streamflow into and out of the watershed, created a water budget, and modeled historical and future inflows from 1953 to 2100. Freshwater inflows have been increasing on average since 1953, but a combination of RSLR, sediment starvation, and punctuated seasonal droughts are likely responsible for the loss of salt marsh. We also estimated supplemental water needs during potential droughts out to 2100. We conclude that managers cannot fundamentally alter the accretion versus RSLR balance in this basin except by modifying freshwater input. Thus, during droughts, they should focus on providing these inputs and avoiding vegetation loss. Our work points to both water purchases and land management options that can achieve this goal.
Diatomite Modified With Alkyl Ketene Dimer For Hydrophobicity of Cellulosic Paper
Authors: Chen Zicheng , Fan Guangyuan , He Xiangyang , Xu Lei , Zhang Xuefeng , Zhang Lanhe
Published: January 2022

Multi-functionalization of papermaking chemicals is one of its main developing strategies. Fillers and internal sizing agents are often mutually restricted in practice. Therefore, it is feasible to prepare a new papermaking chemical by combining its functions. A process of diatomite modified with Alkyl ketene dimer (AKD) was developed in this study. The modified diatomite (AD) can concurrently play the role of mineral filler and sizing agent in the papermaking process. With the equal dosage of AKD, the AD had better sizing and retention performance than the commercial AKD emulsion in the case of cationic polyacrylamide (CPAM) and the CPAM/ bentonite retention system. The sizing mechanism of the AD can be interpreted as numerous hydrophobic sites and micro-surface structure of the paper sheet caused by the AD. Since the ester linkages were not detected in FT-IR spectra of the paper sheet filled by the AD, the chemical reaction may not be indispensable for its sizing performance. What’s more, an interesting “sticky” hydrophobicity phenomenon was observed when filling with AD. The approach in this study to prepare the “sticky” hydrophobic paper sheet can find its applications in some non-traditional application fields of cellulosic paper.
Prognostic Value of The Ratio of Maximum To Minimum Diameter of Primary Tumor In Metastatic Clear Cell Renal Cell Carcinoma
Authors: Shi Hongzhe , Cao Chuanzhen , Wen Li , Zhang Lianyu , Zhang Jin , Ma Jianhui , Shou Jianzhong , Li Changling
Published: January 2022

Background: Several models and markers were developed and found to predict outcome of advanced renal cell carcinoma. This study aimed to evaluate the prognostic value of the ratio of maximum to minimum tumor diameter (ROD) in metastatic clear cell renal cell carcinoma (mccRCC).Methods: Patients with mccRCC (n=213) treated with sunitinib from January 2008 to December 2018 were identified. Cut-off value for ROD was determined using receiver operating characteristic. Patients with different ROD scores were grouped and evaluated. Survival outcomes were estimated by Kaplan-Meier method.Results: The optimal ROD cutoff value of 1.34 was determined for progression free survival (PFS) and overall survival (OS). Patients in ROD≥1.34 group had shorter PFS (9.6 versus 17.7 months, p<0.001) and OS (25.5 versus 32.6 months, p<0.001) than patients in ROD<1.34 group. After adjustment for other factors, multivariate analysis showed ROD≥1.34 was an independent prognostic factor for PFS (p<0.001) and OS (p=0.006). Patients in ROD³1.34 group presented higher proportions of T3/4 stage (92.9% versus 7.1%, p=0.012), WHO/ISUP grade III/IV (72.0% versus 28.0%, p=0.010), tumor necrosis (71.0% versus 29.0%, p=0.039), sarcomatoid differentiation (79.1% versus 20.9%, p=0.007), poor MSKCC risk score (78.4% versus 21.6%, p<0.001) and poor IMDC risk score (74.4% versus 25.6%, p<0.001) than ROD<1.34 group.Conclusion: Primary tumor with higher ROD was an independently prognostic factor for both PFS and OS in patients with mccRCC who received targeted therapy. Higher ROD was also associated with high T stage, high WHO/ISUP grade, sarcomatoid features, tumor necrosis, poor MSKCC and IMDC risk score.
Analysis of the Efficacy of Metformin Against Doxorubicin Cardiotoxicity and Exploration of its Molecular Mechanism
Authors: Wei Jia , Wei Jin
Published: January 2022

Doxorubicin is a very effective broad-spectrum anti-tumor drug, but it can cause dose-dependent cardiotoxicity and ultimately lead to heart failure. Previous studies have found that metformin exerts a cardioprotective effect through AMP-activated protein kinase (AMPK), but its effect on doxorubicin cardiotoxicity is still unclear. In order to investigate whether and how AMPK affects the ability of metformin to regulate the cardiotoxicity of doxorubicin, we have conducted two parts: clinical research and basic research. We found that metformin can reduce doxorubicin cardiotoxicity through clinical retrospective case-control study. Based on this, animal experiments were conducted to explore the molecular mechanism, and it was found that metformin was not associated with AMPK pathway, an important pathway of energy metabolism in the body, and this pathway did not play a protective role in doxorubicin induced cardiotoxicity. The reason may be related to decreased glucose utilization and mitochondrial autophagy of cardiomyocytes.
Psychometric Validation of The Cognitive Abilities Screening Instrument Using Rasch Analysis In People With Dementia
Authors: Hsu Fang-Hsiao , Lee Ya-Chen , Chiu En-Chi
Published: January 2022

Background: The Cognitive Abilities Screening Instrument (CASI) is one of the most commonly used cognitive screening tools to assess overall cognitive function in people with dementia. However, the unidimensionliaty of the CASI using Rasch analysis has not been evaluated in people with dementia, limiting its utility in clinical and research settings. Unidimensionality verifies whether all items of a measure reflect a single theoretical construct, which is necessary to determine whether clinicians and researchers can appropriately use the sum scores of the CASI to describe overall cognitive function. This study aimed to examine unidimensionality of the CASI using Rasch analysis and estimate Rasch person reliability in people with dementia. Methods: CASI data of people with dementia was collected from medical records of one general hospital in northern Taiwan. A total of 506 people with dementia were recruited from the Department of Neurology. Unidimensionality was confirmed through two assumptions: (1) the infit and outfit mean square (MnSq) were 0.6-1.4, and (2) residual variance of the first principal component in principal component analysis was ≤ 20%. Rasch person reliability was estimated after undimensionality was supported. Results: One item from the list-generating fluency dimension was misfitted (outfit MnSq=1.42) and was deleted. The unidimensionality of the remaining 45 items (referred to as the CASI-45) was supported with an infit and outfit MnSq (0.85-1.24 and 0.84-1.28, respectively) and low residual variance of the first principal component (12.8%). The Rasch person reliability of the CASI-45 was 0.62. Conclusion: The CASI-45 showed a unidimensional construct and had acceptable Rasch person reliability in people with dementia.
Investigating Orthorexia Nervosa With The ORTO-R in a Sample of University Students With Or Without Subthreshold Autism Spectrum: Focus On Dietary Habits and Sex Differences
Authors: Dell’Osso Liliana , Cremone Ivan Mirko , Chiarantini Ilaria , Arone Alessandro , Casagrande Danila , Massimetti Gabriele , Carmassi Claudia , Carpita Barbara
Published: January 2022

Purpose: The aim of the present study was to investigate the presence of ON symptoms, measured by means of the ORTO-R, in a sample of University students with or without AT, specifically focusing on evaluating the role of sex and of dietary habits in the association between ON and autism spectrum. Methods: Subjects were requested to anonymously fulfil the ORTO-R and the Adult Autism Subthreshold Autism Spectrum (AdAS Spectrum) through an online form. Results: 2140 students participated in the study. Subjects with significant AT reported significantly higher ORTO-R scores than subjects without AT. Females and subjects following a vegetarian/vegan diet reported significantly higher ORTO-R scores than males and than subjects following an omnivorous diet, respectively. Significant positive correlations were found between ORTO-R and AdAS Spectrum scores. A decision tree model, with sex, type of diet and presence of AT as independent variables and ORTO-R score as dependent variable, showed in the first step the presence of significantly higher ORTO-R scores among females than among males, and in the second step showed in both sexes the presence of higher ORTO-R scores among subjects with AT than in those without. A significant interaction of sex and presence/absence of AT was reported on ORTO-R score, with a higher increasing trend of ORTO-R score with the increase of AdAS Spectrum score among females than among males. Conclusions: Our results further highlighted the association between AT and ON, in particular among females.
Probing Perovskite Carrier Dynamics under Sunlight
Authors: Li Bo-Han , Li Huang , Xuan Zhipeng , Zeng Wen , Wang Jia-Cheng , Zhou Chuanyao , Wang Xingan , Zhang Jingquan , Ren Zefeng , Yang Xueming
Published: January 2022

Understanding the nature of photogenerated carriers and their subsequent dynamics in perovskites is important for the development of related materials and devices. Most ultrafast dynamic measurements on the perovskite materials were conducted under high carrier densities, which likely obscures the genuine dynamics at low carrier densities under solar illumination conditions. In this study, we presented a detailed experimental study of the carrier density-dependent dynamics in hybrid lead iodide perovskites using a highly sensitive transient absorption spectrometer. We found that the carrier lifetime was about a hundred nanosecond in the linear response range, representing sunlight excitation, which was much longer than under high carrier densities. We also elucidated that the fast carrier decay (<1 ps) and the medium decay processes (tens of ps) occurred via the defect state trapping, and we determined its effects on the utilization percentage of photogenerated carriers through quantitative analysis. Furthermore, we obtained the Shockley-Queisser limit that took into account the carrier trapping effect, which directly reflected the material performance.
NEAT1 Enhances MPP+-Induced Pyroptosis In SH-SY5Y Cells Via Targeting Mir-5047/YAF2 Signaling
Authors: Shen Hong , Song Hui , Wang Songlin , Su Daojing , Sun Qiang
Published: January 2022

Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. The aim of our study is to explore the role and regulatory mechanism of long non-coding RNA (lncRNA) NEAT1 in the MPP+-induced neuron pyroptosis. The levels of miR-5047 and YAF2 mRNA were determined through qRT-PCR. TUNEL staining was carried out to analyze neuronal apoptosis. Luciferase activity assay was accomplished to analyze the combination of miR-5047 and NEAT1 and YAF2 3’-UTR. Besides, the concentrations of IL-1β and IL-18 in supernatant were analyzed by ELISA assay. The levels of protein were examined through Western blot. NEAT1 and YAF2 expression were increased, while miR-5047 level was declined in the SH-SY5Y cells treated with MPP+. NEAT1 was a positively regulator for the SH-SY5Y cells pyroptosis induced by MPP+. In addition, YAF2 was a downstream target of miR-5047. NEAT1 promoted YAF2 expression via inhibiting miR-5047. Importantly, the promotion of NEAT1 to SH-SY5Y cells pyroptosis induced by MPP+ was recused by miR-5047 mimic transfection and YAF2 downregulation. In conclusion, NEAT1 was increased in the SH-SY5Y cells treated with MPP+, and it promoted the MPP+-induced pyroptosis through facilitating YAF2 expression by sponging miR-5047.
LAMTOR1 Phosphorylation of Exo70 Facilitates Tumor-Associated Macrophage Polarization to Restrain CD8+ T Cell Function in HCC
Authors: Wu Bo , Wang Qian , Li Bowen , Wang Xiaonan , Zhan Xiaoni , Shi Xiang , Wen Gehua , Wu Lingli , Liu Mei , Jiang Meixi
Published: January 2022

The tumor microenvironment controls the progression of tissue homeostasis leading to cancer.Accumulation of anti-inflammatory tumor-associated macrophages (TAM) has also been linked to worsening clinical outcomes as well as resistance to treatment in hepatocellular carcinoma(HCC).The current immune landscape for regulation by the presence of TAMs has been studies.It is known that LAMTOR1 undergoes phosphorylation to bind to Exo70 and other exocyst components and is enhancing the secretion of TGFB1 to facilitate the polarization of TAMs.The tumor-conditioned macrophages(TCM) numbers also correlated with enhanced number of regulatory T cells(Tregs) and decreased CD8+T cells in HCC.Mechanistically,TCM enhanced IL-10 production to diminished CD8+T cell activities.Our data demonstrate a novel immune therapeutic approach targeting TAMs immune suppression of T cell anti-tumor activities.
Posterior Laminectomy and Lateral Mass Screw Fixation for the Treatment of Severe Cervical Spondylotic Myelopathy
Authors: Li Chuang , Wu Bin , Wu Yongchao , Pan Haitao , Zheng Qixin
Published: January 2022

Background
Severe and complex cervical spondylotic myelopathy(CSM) requires surgical treatment. The common methods of posterior cervical spine surgery are laminoplasty and laminectomy with lateral mass screw internal fixation. However, the operative effect of this surgical approach is unclear owing to the complexity and severity of CSM in patients who undergo this surgical treatment.Therefore, we aimed to evaluate the clinical effects of posterior cervical laminectomy and lateral mass screw internal fixation in patients with severe and complex CSM.
Methods
We retrospectively analysed 60patients (48men,12women; mean age59.7 years) with severe and complex CSM who underwent posterior cervical laminectomy and lateral mass screw internal fixation from May 2013 to June 2020. Forty-eight patients underwent laminectomy and lateral mass screw internal fixation;12 patients underwent laminectomy and lateral mass screw internal fixation with 1–2 segmental laminoplasty. C-spine radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) were used to detect any curvature and fusion of the cervical spine, restenosis, and loose/broken internal fixation screws.Clinical efficacy was evaluated using Japanese Orthopaedic Association (JOA)scores, neck disability index(NDI), Odom’s classification, and the visual analogue scale(VAS) for pain.
Results
Overall effect was satisfactory at the last follow-up (average, 3.6 years [range, 6 months–6 years]), with no restenosis or loosened, slipped, or broken internal fixations. The anterior curvature angle of lordosis (n=46)was not significantly different from baseline at the last follow-up(P>0.05). The cervical kyphosis angle (n=14)was significantly improved at the last follow-up compared with the baseline value (P<0.05), as were the JOA, NDI, and VAS scores(all P<0.05). Odom’s classifications at the last follow-up were excellent, good, and fair in 45, 12, and three patients, respectively.
Conclusions
Posterior cervical laminectomy and lateral mass screw internal fixation achieved satisfactory clinical results in severe and complex CSM cases.Combining this surgical method with laminoplasty of 1–2 spinal segments stabilised the cervical spine and provided spinal decompression while preventing excessive backward drift of the cervical spinal cord, resulting in fewer complications.
NCoR1 and SMRT Fine-Tune Inflammatory Versus Tolerogenic Balance in Dendritic Cells By Differentially Regulating STAT3 Signaling
Authors: Jha Atimukta , Ahad Abdul , Mishra Gyan Prakash , Sen Kaushik , Smita Shuchi , Minz Aliva P , Biswas Viplov Kumar , Tripathy Archana , Senapati Shantibhushan , Gupta Bhawna , Orbea Hans Acha , Raghav Sunil Kumar
Published: January 2022

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by down-regulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.
Design, Synthesis, and Docking Studies of Arylhydrazone Compounds and Evaluation of Their Platelet Aggregation Inhibitory Effect and Cytotoxicity
Authors: Klidsar Maryam H. , Esfahanizadeh Marjan , Haghverdi Pantea , Amidi Salimeh , Kobarfard Farzad
Published: January 2022

In view of proven antiplatelet activity of hydrazone group containing compounds, two series of hydrazone derivatives were synthesized by coupling appropriate aldehydes with phenyl hydrazine and Isonicotinic acid in the presence of distilled water and a catalytic amount of glacial acetic acid. All synthesized compounds were screened for their antiplatelet activity against induced aggregation by adenosine diphosphate (ADP) and arachidonic acid (AA). The results indicate that compounds in arylhydrazone group had shown satisfactory activity. Among them, 1-(3-methoxybenzylidene)-2-phenylhydrazine (1c), 2-methoxy-4-(2-phenylhydrazono) methyl phenol (1g), and 2-((2-phenylhydrazono) methyl)-1H-pyrrole (1h) were found to be the most potent antiplatelet compounds with IC50 less than 39 μM. Furthermore, the cell toxicity assay, (MTT test) indicates their noncytotoxic in various cell lines. None of the synthesized N-isonicotinohydrazide derivatives in this study excreted sufficient antiplatelet activity.
Electromechanical Coupling Characteristics Analysis and Research of Rotation-Parallel Flexible Robot Manipulator
Authors: xiao zhi , Zhang Wenhui
Published: January 2022

RP(Rotation-Parallel) flexible robot as a typical electromechanical system. The complex electromechanical coupling effect in the system has a significant impact on the dynamic characteristics and stability of the flexible manipulator. This article investigates the electromechanical coupling dynamics and vibration response characteristics of flexible robot manipulator driven by AC(Alternating Current) servo motor with considering the start-up dynamic characteristics of the motor. Firstly, the physical model including the coupling of electromagnetic and mechanical system is established, and the dynamic model of the whole system is derived based on the global electromechanical coupling effect and Lagrange-Maxwell equations. Secondly, the virtual simulation platform is constructed with the help of MATLAB/Simulink, and the output speed characteristics of the motor drive end and the motion of the moving base are analyzed. Finally, through the joint simulation of MATLAB/Simulink dynamic simulation model and ADAMS/Controls virtual prototype model, the vibration characteristics of flexible manipulator under electromechanical coupling are obtained. The result demonstrates that the electromechanical coupling effect at the motor driving end has an obvious influence on the dynamic characteristics of the flexible manipulator, which is manifested in the increase of the vibration displacement amplitude of the flexible manipulator. With the increase of motor speed, the change of elastic vibration of flexible manipulator becomes larger, which shows that the electromechanical coupling effect of motor driving end has a greater impact on the dynamic characteristics of flexible manipulator at high speed. The analysis results are of great significance to improve the dynamic performance of motor-driven flexible robot manipulator.
Using Variational Autoencoder to Develop and Validate a Compact, Deep Representation of Digital Clock Drawing Test for Classifying Dementia
Authors: Bandyopadhyay Sabyasachi , Dion Catherine , Libon David J. , Tighe Patrick , Price Catherine , Rashidi Parisa
Published: January 2022

The Clock Drawing Test (CDT) is an inexpensive tool to screen for dementia. In this study, we examined if a semi-supervised deep learning (DL) system using Variational Autoencoder (VAE) can extract atypical clock features from a large dataset of unannotated CDTs (n=13,580) and use them to classify dementia (n=18) from non-dementia (n=20) peers. The classification model built with VAE latent space features adequately classified dementia from non-dementia (0.78 Area Under Receiver Operating Characteristics (AUROC)). The VAE-identified atypical clock features were then reviewed by domain experts and compared with existing literature on clock drawing errors. This study shows that a semi-supervised deep learning (DL) analysis of the CDT can extract important clock drawing anomalies that are predictive of dementia.
Damage to School Buildings During the 2015 Nepal Earthquake and Reconstruction Strategy
Authors: Paudyal Youb Raj , Bhandary Netra Prakash
Published: January 2022

The 2015 Nepal Earthquake (Mw7.8) affected more than 9,000 schools in the country. Damage distribution in the 14 most-affected administrative districts shows that the construction practices were an important determent for the level of damage extended. Use of improper construction materials, lack of construction supervision, and non-compliance with the existing building codes during design and construction probably contributed to the severe damage of most of the school buildings. Preliminary damage assessment results show that in the most-affected districts, about 86% schools were affected by the earthquake and about one million students were out of their schools for a long time. The damage survey data indicate that about 30% classrooms collapsed, about 13% classrooms sustained major damage, and about 17% classrooms sustained minor damage within the 14 districts. Such evidence of loss and damage in the earthquake disasters provides an opportunity to learn lessons for the future preparedness and to encounter the disaster challenges. Based on the damage analysis data and experience of reconstruction process after the 2015 Nepal Earthquake, this paper highlights the steps to be considered during reconstruction strategy planning for school buildings after an earthquake disaster.
Geraniol Attenuates Oxidative Stress and Neuro-inflammation Mediated Cognitive Impairment in D‑galactose‑induced Mouse Aging Model
Authors: Rajendran Peramaiyan , Ammar Rebai Ben , Al-Saeedi Fatma J , AlRamadan Saeed Y. , Ismail Mohammad Bani , Veeraraghavan Vishnu Priya , Alamer Sarah Abdulaziz , Alawwad Nasir , Moqbel Mohammed Salem , Ahmed Emad A
Published: January 2022

D-galactose (D-gal) is a reducing sugar drug can induce artificial senescence and aging process that mimic natural aging along with the accompanying brain and liver injury in experimental animals. Therefore, chronic D-gal administration is widely used to induce cognitive impairment, Alzheimer disease and aging in rodents' models. Aging is a phenomenon in which oxidative stress and apoptosis play a vital role. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes, presents in essential oils such as those from Cinnamomum tenuipilum and Valeriana officinalis. In the present study, we examined the effects of GNL on D-gal-induced oxidative stress and neuro-inflammation mediated memory loss in mice. Analyzing the behavioral differences between control and treated groups, including the elderly mice, revealed that GNL significantly improved memory in mice treated with D-gal-induced memory loss (supplementary videos are provided). The anti-inflammatory and the anti-oxidative role of GNL were confirmed by both histopathological investigations and biochemical analyses. Mechanistically, GNL appears to activate PI3K/Akt and thus upregulates the nuclear factor erythroid 2-related factor 2 (Nrf2) and the heme oxygenase 1 (HO-1) to reduce the oxidative stress and apoptosis induced after D-gal treatment leading to easing of neurological deficits and cognitive dysfunction in D-gal-induced aging mouse models. Accordingly, our comprehensive behavioral analysis and bioassays suggest GNL as a promising agent preventing cognitive impairment and neurological deficits associated with aging.
The AGT Epistasis Pattern Proposed a Novel Role for ZBED9 In Regulating Blood Pressure: Tehran Cardiometabolic Genetic Study (TCGS)
Authors: Akbarzadeh Mahdi , Riahi Parisa , Kolifarhood Goodarz , Lanjanian Hossein , Alipour Nadia , Bonab Leila Najd Hassan , Moghadas Mohammad Reza , Sabour Siamak , Azizi Fereidoun , Daneshpour Maryam S
Published: January 2022

Backgroung: Hypertension is typically considered as the leading risk factor for cardiovascular disease. Epistasis studies may add another layer of complexity to our understanding of the genetic basis of hypertension. Methods: A nested case-control design was used on 4214 unrelated Tehran Cardiometabolic Genetic Study (TCGS) adults to evaluate 65 SNPs of previously associated genes, including ZBED9, AGT, and TNXB. The integrated effect of each gene was determined using the Sequence-based Kernel Association Test (SKAT). We used model-based multifactor dimension reduction (Mb-MDR) and entropy-based gene-gene interaction (IGENT) methods to determine interaction and epistasis patterns. Results: The integrated effect of each gene has a statistically significant association with blood pressure traits (P-value < 0.05). Single-locus analysis identified two missense variants in ZBED9 (rs450630) and AGT (rs4762) that are associated with hypertension. In the ZBED9 gene, significant local interactions were discovered. The G allele in rs450630 showed an antagonistic effect on hypertension, but interestingly, IGENT analysis revealed significant epistasis effects for different combinations of ZBED9, AGT, and TNXB loci. Conclusion: We discovered a novel interaction effect between a significant variant in an essential gene for hypertension (AGT) and a missense variant in ZBED9, which has shifted our focus to ZBED9's role in blood pressure regulation.
Impact of gene polymorphisms on toxicity and response rate in head and neck squamous cell carcinoma: a literature review
Authors: abbaszadeh hamid , Rajabi-Moghaddam Mahdieh
Published: January 2022

Advanced head and neck squamous cell carcinoma (HNSCC) is treated with radiotherapy, chemotherapy, targeted therapy or a combination of these treatments. Variations in toxicity and response to therapy are observed among patients despite similar clinicopathologic characteristics which are attributed to single nucleotide polymorphisms (SNPs). The aim of this review was to evaluate the impact of SNPs on toxicity and response to therapy in HNSCCs. A web-based search of all original articles about the impact of gene polymorphisms on toxicity and response to therapy in HNSCCs was done until September 2021 using international English language databases including Google Scholar, Scopus, PubMed and Web of science. Findings were categorized by type of treatment (radiotherapy, chemotherapy, targeted therapy, or combination therapy). In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. Among studied SNPs with probable impact on toxicity and response to therapy are XRCC1, XRCC3, RAD51, Ku70, NBN, CAT, GSTP1, GSTT1, GSTM1, XPD, XPC, ERCC1, MMP3, ACSL6, EXO1, CXP2D6, FcγRIIIa, AurkA, and EGFR. Understanding gene polymorphisms will help us move toward personalized medicine and determine which patients will actually benefit from therapies for HNSCCs. By examining the SNPs, it is possible to make predictions about the patient's response to treatment or development of toxicity after treatment, and if necessary, make changes in the patient's treatment regimen.
Bone Sarcoma Of The Pelvis: A Multicentric Retrospective Study Of One Hundred-Fourteen Cases
Authors: Nouri Habib , Makhlouf Hassan , Maitigue Mahmoud Ben , Hassini Lassaad , Msekni Ahmed , Mihoubi Maamoun , Triki Fakhreddine Elyes , Othman Youssef , Nfiss Mouadh , Bellil Mehdi , Mallat Youssef , Trigui Moez , Meddeb Khadija , Messai Taha
Published: January 2022

Background: The aim of this study was to assess the oncologic outcome of pelvic bone sarcomas (PBS) and to identify prognosis factors.Methods: We report a multicentric cohort of patients treated for a PBS from 2000 to 2020. Data from 12 hospitals were analysed. Patients treated for primary PBS were included. Alive patients with less than 6 months of follow up were excluded. The primary outcome was survival.Results: One hundred and fourteen patients (67 males and 48 females) were reviewed with a mean follow up of 32±46,5 (1 to 216) months. The mean patient and doctor diagnosis delays were respectively 8,5±10,2 (1 to 60) and 3±4,3 (0 to 24) months. Sixty-eight patients (59,6%) died after a mean time from diagnosis of 15,9±22,8 (1 to 120) months. The overall survival rates at 5 and 10 years were respectively 38,4% and 27,6%. Chondrosarcoma histological type (HR=3,64), metastasis (HR=3,55) and surgery (HR=0,12) were identified as significant survival factors. Surgery was also associated to a decreased risk of metastasis (OR=0,03, 95% CI: 0,01 – 0,1). Among the 76 patients (66,7%) who underwent surgery, local recurrence was observed in 19 patients (25%) with a mean time from surgery to onset of 11,05 (±17,5) months. Conclusions: This nation-wide20-year-cohort study shows that surgery is the most effective treatment option in PBS regardless the histological type of the tumour. Efforts have to be done to decrease the diagnosis delay in order to start treatment when surgery is still feasible.
EnGAN: Enhancement Generative Adversarial Network in Medical Image Segmentation
Authors: Deng Erqiang , Qin Zhiguang , Chen Dajiang , Qin Zhen , Ding Yi , Geng Ji , Zhang Ning
Published: January 2022

Deep learning has been widely used in medical image segmentation, although the accuracy is affected by the problems of small sample space, data imbalance, and cross-device differences. Aiming at such issues, a enhancement GAN network is proposed by using the domain transferring of the adversarial generation network to enhance the original medical images. Specifically, based on retaining the transferability of the original GAN network, a new optimizer is added to generate a sample space with a continuous distribution, which can be used as the target domain of the original image transferring. The optimizer back-propagates the labels of the supervised data set through the segmentation network and maps the discrete distribution of the labels to the continuous image distribution, which has a high similarity to the original image but improves the segmentation efficiency.On this basis, the optimized distribution is taken as the target domain, and the generator and discriminator of the GAN network are trained so that the generator can transfer the original image distribution to the target distribution. extensive experiments are conducted based on MRI, CT, and ultrasound data sets. The experimental results show that, the proposed method has a good generalization effect in medical image segmentation, even when the data set has limited sample space and data imbalance to a certain extent.
Design Thinking to Reinvent Values in a Business Model: a 4-Step Approach Using Ideation Virtual Tools
Authors: Mikelsone Elina , Uvarova Inga , Segers Jean-Pierre
Published: January 2022

The purpose of this paper is to create and test design thinking approach sequence, to redefine the value proposition. This paper suggests a 4-step systematic design thinking approach sequence to reinvent values in a business model, which was researched by a case study method. Based on the idea management approach the authors describe idea generation and evaluation processes by applying the design thinking approach and their possible moderation elements. Originality/value: a created approach could be applied by the organisations that would like to create new values or reinvent the existing ones in their business models value propositions.
Performance of The Decarboxylation Index To Predict CO2 Removal And Mechanical Ventilation Reduction Under VV-ECMO Or High-Flow ECCO2R
Authors: Laumon Thomas , Courvalin Elie , Dagod Geoffrey , Deras Pauline , Girard Mehdi , Martinez Orianne , Maury Camille , Weber Hugues , Capdevila Xavier , Charbit Jonathan
Published: January 2022

Background: Optimal decarboxylation dose under extracorporeal respiratory support to ensure sufficient reduction of mechanical ventilation stress remains unclear and understudied. The aim of this study was to assess the interdependence of blood flow (BF) and gas flow (GF) in predicting CO2 removal and mechanical ventilation reduction (MVR) under extracorporeal respiratory support. Methods: All patients who benefited from veno-venous ECMO (HLS-maquet 7.0, 1.8 m²) and high-flow ECCO2R (HLS-maquet 5.0, 1.3 m²) in our intensive care unit over a period of 18 months were included. CO2 removal was calculated from inlet/outlet blood gases performed in clinical practice during the first 7 days of oxygenator use. The relationship between the BF × GF product and CO2 removal or MVR was studied using linear regression models. Results: Eighteen patients were analysed, corresponding to 24 oxygenators and 261 datasets. CO2 removal was 393 mL/min (IQR, 310–526 mL/min) for 1.8 m2 oxygenators and 179 mL/min (IQR, 165–235 mL/min) for 1.3 m2 oxygenators. The decarboxylation index was associated linearly with CO2 removal (R2 = 0.62 and R2 = 0.77 for the two oxygenators, respectively) and MVR (R2 = 0.72 and R2 = 0.62, respectively). Values in the range 20−30L2/min2 were associated with an MVR ratio between 38% and 58% for 1.8 m2 oxygenators, and between 37% and 55% for 1.3 m2 oxygenators. Conclusion: The decarboxylation index is a simple parameter to predict CO2 removal and MVR under extracorporeal respiratory support. A BF of 2 L2/min2 or more may be necessary to obtain a significant reduction of mechanical convection.Trial Registration: Being a retrospective study, no trial registration was made.
SCM-198 Prevents Endometriosis By Reversing Low Autophagy Levels Of Endometriotic Stromal Cells Via Inhibiting TNF-Α-Aromatase-Estrogen-Erα Pathway And Promoting PR Expression
Authors: Lin Yikong , Li Yunyun , Li Yue , Li Dajin , Wang Xiaolin , Wang Li , Yu Min , Zhu Yizhun , Cheng Jiajing , Du Meirong
Published: January 2022

Background: Endometriosis (EMS), an estrogen-dependent disease, is characterized by dysregulated inflammation and increased estrogen in ectopic lesions. However, the crosstalk and pathogenic mechanism of inflammation and estrogen has not been fully explored. SCM-198 is the synthetic form of leonurine with multiple pharmacological activities. Whether SCM-198 could inhibit the progress of EMS by regulating inflammation and estrogen signaling remains unknown. Methods: The therapeutic effects and potential mechanisms of SCM-198 on EMS were analyzed by establishing EMS mice models and performing RNA-seq assay. ELISA was performed to detect estrogen and TNF-α concentration in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs), with or without SCM-198 treatment. Western blotting, RNA silencing and plasmid overexpression were utilized to analyze the relationship among inflammation, endocrine and autophagy as well as the regulation of SCM-198 on inflammation-endocrine-autophagy axis. Results: Increased estrogen-ERα signaling and decreased PR expression co-led to the hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. Highly expressed TNF-α in eESCs enhanced low-autophagy mediated anti-apoptosis effect by activating aromatase-estrogen-ERα signaling. SCM-198 inhibited the growth of ectopic lesions in EMS mouse model and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptosis effect of SCM-198 on eESCs were realized by upregulating the autophagy level via inhibiting TNF-α activated aromatase-estrogen-ERα signaling and increasing PR expression. Conclusion: Inflammation facilitated the progress of EMS by disturbing estrogen regulatory axis. SCM-198 restrained the growth of EMS by regulating inflammation-endocrine-autophagy axis.
Optimization of Spatial Resolution and Image Reconstruction Parameters for the Small-Animal MetisTM PET/CT System
Authors: Zhao Jie , Liu Qiong , Li Chaofan , Song Yunfeng , Zhang Ying , Jose Mejia , Chen Jyh-Cheng
Published: January 2022

The aim of this study was to investigate the optimization of spatial resolution and image reconstruction parameters related to image quality in an iterative reconstruction algorithm for the small-animal MetisTM PET/CT system. We used a homemade Derenzo phantom to evaluate the image quality by visual assessment, signal-to-noise ratio, contrast, coefficient of variation, and contrast-to-noise ratio of the 0.8 mm hot rods of 8 slices in the centre of the phantom PET images. A healthy mouse study was performed to analyze the influence of optimal reconstruction parameters and Gaussian post-filter FWHM. In the phantom study, the best image quality was obtained by placing the phantom at one end, keeping the central axis parallel to X-axis of the system, selecting iterations between 30 and 40, with a reconstruction voxel of 0.314 mm and a Gaussian post-filter FWHM of 1.57 mm. The optimization of spatial resolution can reach 0.6-mm. In the animal study, it was suitable to choose a voxel size of 0.472-mm, iterations between 30 and 40, and 2.36-mm Gaussian post-filter FWHM. Our results indicate that optimal imaging conditions and reconstruction parameters are necessary to obtain high-resolution images and quantitative accuracy, especially for the high-precision identification of tiny lesions.
Association of Elevated Non-HDL-C and LDL-C with Carotid atherosclerosis among Tibetans Living at High Altitudes: A Cross-sectional Study
Authors: Hu Xianjin , Zhang Xin , Gou Qiling , Ye Runyu , Zhang Zhipeng , Li Xinran , Chen Xiaoping
Published: January 2022

Background: Hypoxic circumstances impair endothelial function and may contribute to carotid atherosclerosis. In high-altitude areas, there is a scarcity of data on the correlation between lipid particles and carotid atherosclerosis. Methods: A total of 587 patients who underwent carotid artery ultrasound and met the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants resided in Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China (mean altitude: 3,860 meters). We used questionnaires, physical examination, blood sample testing, and ultrasound in our investigation. Spearman correlation analysis and multiple linear regression analysis were performed to explore the association between lipid particles and carotid atherosclerosis. We compared the disparity between lipid particles in predicting atherosclerosis using the receiver operator characteristic curve.Results: We found a statistically significant association between lipid particles and carotid atherosclerosis. After adjustment for certain variables, including age, gender, mean arterial pressure, and fasting blood glucose, we discovered that non-high-density lipoprotein-cholesterol (non-HDL-C) was a risk factor for carotid intima-media thickness (β = 0.012, p = 0.032) but not for low-density lipoprotein cholesterol (LDL-C) (p = 0.073). In terms of lifestyle, non-HDL-C was also found to be a risk factor for atherosclerosis independent of cigarette smoking and vegetarian (β = 0.012, p = 0.049). The area under the curve (AUC) of non-HDL-C was 0.644 (CI: 0.583 – 0.706) while LDL-C was 0.599 (CI: 0.534 - 0.664) in predicting carotid atherosclerosis. The optimal cut-off value of non-HDL-C was 3.625 mmol/L in predicting carotid plaques. Conclusions: Among Tibetans living in high-altitude areas, non-HDL-C is a better biomarker than LDL-C for carotid artery atherosclerosis independent of conventional risk factors. It is crucial to resolve non-HDL-C dyslipidemia in order to mitigate carotid atherosclerosis in Tibetans living at high-altitude settings.
SARS-CoV-2 Humoral and Cellular Immune Responses in COVID-19 Convalescent Individuals With HIV
Authors: Giannone Denise , Vecchione Maria Belén , Czernikier Alejandro , Polo Maria Laura , Polo Virginia Gonzalez , Cruces Leonel , Ghiglione Yanina , Balinotti Silvia , Longueira Yesica , Turk Gabriela , Laufer Natalia , Quiroga Maria Florencia
Published: January 2022

Background

SARS-CoV-2-specific immune response features in people with HIV infection (PWH) remain to be fully elucidated. We aimed to evaluate the impact of HIV over humoral and cellular responses in COVID-19 convalescent PWH.
Methods

Blood samples from 29 PWH with preserved CD4+T-cell counts on ART and 29 HIV-negative (HIVneg) donors were included. SARS-CoV-2-specific IgG levels and IgG titers were determined by ELISA. Antibody neutralization capacity was evaluated against the reference B1 strain SARS-CoV-2. IFN-γ-secreting cells were detected by ELISpot using SARS-CoV-2 Spike, RBD, or Nucleocapsid protein or overlapping peptide pools. Frequency and phenotype of T, B and NK cells and levels of soluble cytokines and chemokines were assessed by flow cytometry.
Results

SARS-CoV-2-specific antibodies were detected on 65.5% of PWH and 79.3% of HIVneg individuals, with no differences in serum IgG levels and anti-SARS-CoV-2 neutralizing antibodies. All donors exhibited SARS-CoV-2-specific cellular immunity, including those with undetectable antibody responses. PWH showed diminished percentages of antibody-secreting cells compared to HIVneg cohort, with similar B cell proportions between groups. PWH presented an increment in T follicular helper (Tfh, CD4+CXCR5+) percentage, which negatively correlated with IgG titers. Additionally, CD4+PD1+ and CD8+HLA-DR+ cell frequencies were augmented in PWH. Moreover, PWH presented a high proportion of CD95+, CD25+, NKp46+, HLA-DR+, and CD38+/HLA-DR+ NK cells. Both groups displayed similar Tregs frequency, effector/memory, and T-helper profile for CD4TL, exhaustion and memory phenotypes for CD8TL and subtle differences in classical monocytes. Profile of circulating cytokines and chemokines was significantly different between both groups. Magnitude of IFN-γ responses to S or N proteins, and RBD was lower in PWH compared to HIVneg donors. Correlation analysis of immune and clinical parameters showed a distinct immune landscape in the PWH group.
Conclusions

PWH showed a distinctive immune profile although severity of COVID-19 was not exacerbated. PWH with conserved CD4+T-cell counts exerted both humoral and cellular responses against SARS-CoV-2. Even though cellular response was lower compared to HIVneg individuals, PWH achieved similar antibody responses with a high neutralization capacity. These data reinforce the impact of ART, not only in controlling HIV but also other infections.
Lelliottia Rebaudianalis Sp. Nov. Isolated From Wild Stevia Rebaudiana Bertoni
Authors: Lin Jing , Huang Ke , Huang Jing-Yu , Xiong Yuan-Ru , Wei Meng-Meng , Xiao Na , Gao Jia , Ding Xuan-Kai , Ma Zi-Yang , Sang Jun-Hao , Kong Ling-Xian , Hong Zhi-Yun , Li Ou
Published: January 2022

A Gram-stain-negative, aerobic, chemoheterotrophic bacterium, characterized with rod shape and mobility, designated as LST-1T, was isolated from wild Stevia rebaudiana Bertoni and subjected to polyphasic taxonomic analysis. The LST-1T strain grew optimally at 37 °C and pH 6.0–7.0 in the presence of 0.5 % (w/v) NaCl. Phylogenetic sequence analysis based on 16S rDNA from LST-1 indicated that it is close to Lelliottia jeotgali (99.85%), Lelliottia nimipressuralis (98.82%), and Lelliottia amnigena (98.54%). Multi-locus sequence typing analysis of concatenated partial recA, atpD, and infB was performed to improve resolution, and clear distinctions between the closest related type strains were exhibited. Meanwhile, the results from average nucleotide identify analyses and DNA–DNA hybridization with four species (16S rDNA similarity > 98.65%) were less than 90% and 40% respectively, verifying the distinct characteristics from other species of Lelliottia, The cellular fatty acid profile of the strain consisted of C16:0, Summed Feature3, and Summed Feature8 (may be 16:1 w6c/16:1 w7c and 18:1 w6c) as major components. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, aminophospholipid, three non-characteristic phospholipids, and a non-characteristic lipid. The genome of LST-1T is 4,611,055 bp, with a DNA G + C content of 55.02%. Combination of several phenotypic, chemotaxonomic, and genomic characteristics proved that the LST-1T strain does represent a novel genus, for which the name Lelliottia sp. LST-1 was proposed. The type strain is LST-1T (= CGMCC 1.19175T = JCM 34938T).