bluuebunny/crossref_metadata_2025 huggingface dataset:
KN026, a Bispecific Anti-HER2 Antibody, Combined with KN046, an Anti-CTLA-4/PD-L1 Antibody, in Patients with HER2-positive Advanced Gastrointestinal Cancer: a multicenter, open-label, nonrandomized, phase Ib study
Authors: Dong Zhi , Gong Jifang , Liu Dan , Zhang Xiaotian , Luo Suxia , Peng Zhi , Wang Yankun , Qi Changsong , Wang Zhenghang , Li Jian , Wang Xicheng , Lu Ming , Lu Zhihao , Zhou Jun , Cao Yansuo , Yuan Jiajia , Shen Lin
Published: May 2022

Background
Anti-HER2 antibodies combined with immune checkpoint inhibitors exert synergistic effects on innate and adaptive immunity. This phase Ib study assessed the safety and efficacy of KN026 plus KN046 in patients with HER2-positive gastrointestinal cancer.
Methods
Treatment naïve or pretreated locally advanced or metastasis, gastrointestinal cancer patients with HER2 alterations were enrolled. Four dose combinations of KN026 (20 mg/kg Q2W or 30 mg/kg Q3w) and KN046 (3 mg/kg Q2w or 5 mg/kg Q2w/Q3w) were designed. The primary objective was to assess dose-limiting toxicity (DLT) and preliminary efficacy.
Results
Overall, 47 patients were enrolled. No DLTs were observed. Any-grade treatment-related adverse events (TRAEs) were observed in 42 patients (89.4%). Anemia (40.4%), infusion-related reactions (36.2%), and elevated alanine transaminase (ALT) (27.7%) were the most common TRAEs. Grade 3 or worse TRAEs occurred in 17% of the patients. Twenty-four of the 47 patients suffered immune-related adverse events (irAEs). Rash (14.9%), hypothyroidism (6.4%) and interstitial lung disease (6.4%) were most commonly observed. Forty of 47 patients were included in efficacy assessment. The objective response rates (ORRs) in the patients with HER2-positive gastric cancer and gastroesophageal junction (GC/GEJ) adenocarcinoma in the first-line and late-line settings were 71.4% and 37.5%, respectively. No disease remission was observed in the patients with low HER2 expression or HER2 mutation. Notably, half of the patients (2/4) pretreated with trastuzumab and a programmed cell death-1 (PD-1) blockade achieved partial response (PR).
Conclusions and Relevance
: KN026 combined with KN046 exhibited acceptable safety profiles and encouraging efficacy in patients with HER2-positive gastrointestinal cancer.
Trial registration:
ClinicalTrials.gov, NCT NCT04040699, Registered August 1,2019.
Analysis of key genes and immune infiltration in ruptured intracranial aneurysms based on artificial neural networks and bioinformatics
Authors: Jia Qi , Shi Wei-Hua , Lu Xiao-Jian , Sun Shu-Qing , Shao Jun-Jie , Huang Qing-Feng
Published: May 2022

Background: Intracranial aneurysm (IA) is a potentially devastating cerebrovascular disease, and its rupture leads to subarachnoid hemorrhage with high mortality and disability rates. This study aimed to predict the potential biomarkers of ruptured intracranial aneurysms (RIAs) and explore the correlation between RIAs and immune infiltration through artificial neural networks and bioinformatics analysis.Method: Three RIA gene microarray data sets were obtained from the gene expression profile (GEO) database, with GSE13353 and GSE36791 as the training sets and GSE54083 as the validation set. Differentially expressed genes (DEGs) were obtained after the analysis. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Metascape databases were used for functional enrichment analysis. A random forest tree was used to screen for disease signature genes, while a neural network model was built afterward. The accuracy was also confirmed in the validation set. Finally, immune cell infiltration in the unruptured IAsand RIAs groups was analyzed using CIBERSORT.Results: A total of 27 DEGs were identified by the analysis, 1 of which was a downregulated gene and 26 were upregulated genes. The functional enrichment associated with RIAs was closely related to inflammation and immune function. Hexokinase 3, matrix metalloproteinase 9, CST7, NCF2, and uridine phosphorylase 1 were disease signature genes for RIAs and could be used as potential markers for predicting RIAs. The numbers of CD8+ T cells, CD4+ memory T cells, activated natural killer cells, macrophages M0, and neutrophils were high in the RIA group in immune cell infiltration analysis.Conclusion: The analysis revealed disease signature genes and immune cell infiltration types that predicted RIAs and had important effects on inflammatory and immune responses.
Dorsal raphe serotonergic neurons mediate depression in a mouse model of loss of control over stress
Authors: Yongfeng li , Yao Li , Zheng Qiaohua , Qian Zhaoqiang , Li Ningrao , Wei Chunling , Han Jing , Liu Zhiqiang , Ren Wei , Qiao Haifa
Published: May 2022

Our previous study found that, in a triadic experiment, helplessness exhibited in mice in the loss of control over stress (LOC) group in response to aversive events was more prominent than that seen in the yoked (Yoked) group of mice. However, the mechanisms responsible for such phenomena are poorly understood. Increasing evidence has demonstrated that 5-hydroxytryptamine (5-HT) plays a critical role in emotional behaviours. Therefore, we hypothesized that the serotonergic system might mediate depression induced by the loss of control over stress. Our results showed that the activity level of 5-HT neurons of mice in the LOC group was significantly higher than that of mice in the Yoked and Control groups. Additionally, optogenetic inhibition of 5-HT neuron projections from the dorsal raphe nucleus (DRN) to the ventral hippocampus (VH) significantly reduced escape latency and freezing time, improved escape defect behaviour of mice in the LOC/Yoked group, and downregulated the expression of DRN 5-HT1A autoreceptor (DRN 5-HT1AR) of mice in the LOC group. These results provide compelling evidence that the sensitization of dorsal raphe 5-HT neurons mediates depression in a mouse model of loss of control over stress.
Clinicopathological Characteristics of Low to Intermediate Grade Neuroendocrine Tumors with Oncocytic Features
Authors: Cui Shengjie , Liu Bella L , Mijares Kevin , Han Jing , Paulsen John D , Sun Jihong
Published: May 2022

Neuroendocrine tumors (NETs) with oncocytic features are rare. To date, few studies have described the metastatic characteristics of these tumors, most of which were limited by the low number of cases. One article characterized intermediate to high grade (G2 and G3) oncocytic NETs of the pancreas as having an ominous outcome; however, metastatic features of low grade oncocytic NETs have, to our knowledge, been hitherto unexplored. Our study characterized the clinicopathological and metastatic features of 32 low to intermediate grade oncocytic NETs of various organs. The most frequent metastatic site was the liver (63%). Metastatic rate of our cases was compared with Riihimaki’s study (metastatic rate of G1/G2 NETs was reported), as well as Heetfeld’s study and Lithgow’s study (metastatic rate of G3 NETs was reported). The overall metastatic rate of our cases is 84.4%, which is significantly higher than that of the G1/2 NETs from Riihimaki’s study (84.4% vs 25%, p < 0.0001), while similar to that of the G3 NETs from Heetfeld’s study (84.4% vs 86.5%, p>0.05) and Lithgow’s study (84.4% vs 80.8%, p>0.05). These data indicate that oncocytic features could potentially be characterized as a high risk feature in addition to high Ki-67 index, mitotic count and necrosis. Thus, imaging studies such as liver magnetic resonance imaging may be warranted to detect liver metastases in NETs with distinctive oncocytic cytologic features even in the absence of other high risk features.
WITHDRAWN: High-throughput preclinical screening of CD123 scFv to design 3rd generation of CAR T-cell in the treatment of BPDCN patient
Authors: Fredon Maxime , Poussard Margaux , Biichle Sabeha , Bonnefoy Francis , Seffar Evan , Bôle-Richard Elodie , Renosi Florian , Boidot Romain , Anna François , Loustau Maria , Caumartin Julien , Saas Philippe , Deconinck Eric , Daguindeau Etienne , Roussel Xavier , Adotevi Olivier , Angelot-Delettre Fanny , Galaine Jeanne , Garnache-Ottou Francne
Published: May 2022

Background: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive malignant hemopathy characterized by constant overexpression of the CD123 antigen on 100% of blasts identifying CD123 as an antigenic target for the development of adoptive cell therapy. Chimeric Antigen Receptor-T (CAR-T) are composed of an extracellular domain consisting of a single-chain fragment variable (scFv) targeting a surface antigen expressed on tumor cells. In view of the low expression of CD123 on hematopoietic stem cells, monocytes and endothelial cells, it is necessary to evaluate and select the CD123 CAR-T allowing the best cytotoxicity differential between leukemic and healthy cells. Methods: We developed five third-generation CD123 CAR-T by substituting scFv, in order to assess changes in efficacy and on-target/off-tumor side effects. Using various in vitro and in vivo BPDCN models, we evaluated the functionality on BPDCN and the on-target/off-tumor effect on endothelial cell line, monocytes and hematopoietic stem cell (HSC). Results: Using Incucyte, we confirmed the low cytotoxicity on endothelial cells. We showed an increase in CD123 expression on endothelial cells, dependent on the activation of CAR-T through cytokine secretion. Evaluated by CFU-GM culture, we show that two CAR-T are less cytotoxic against hematopoietic stem cells and these two CAR-T significantly reduce tumor infiltration and increase overall survival of mice in three in vivo BPDCN models. Finally, we demonstrate in bulk RNA-sequencing that the most effective CAR-T in an aggressive BPDCN model, upregulates genes associated with cytotoxicity and activation/exhaustion at day 34, with fewer regulatory signaturesConclusions: Together, these results emphasize the importance of evaluating different scFv for the development of CAR-T, to select the best one, with high cytotoxicity potential and the best safety profile for clinical development.
Bioinformatic Analyses of Potential Key Genes in the Pathogenesis of Idiopathic Pulmonary Fibrosis
Authors: Wang Peijie , Shu Wanhong , Yin Fei , Zhang Qiwei , Yin Yin , Deng Qiying , Zeng Feifei , Li Yun , Zhang Junhang
Published: May 2022

Purpose: Idiopathic pulmonary fibrosis (IPF) is an advancing, chronic and fatal interstitial lung disease with a poor prognosis and increasing incidence. Our study aimed to learn the molecular mechanisms of IPF progression to gain a better comprehension of IPF at the biological level.Methods: In our study, we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE15197 and GSE48149 to identify differentially expressed genes (DEGs) between IPF patients and normal controls. Then, tissue-specific gene expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed.Results: In total, 183 DEGs were identified in the differential expression analysis, including 56 downregulated genes and 127 upregulated genes. The PPI network analysis and manual screening of tissue-specific gene expression resulted in the identification of 51 tissue-specific expressed DEGs, among which 25 were tissue-specifically expressed in the respiratory system. In addition, functional enrichment and biological process analysis identified 7 upregulated genes (SERPINB5, COL17A1, CLCA2, KRT17, KRT5, CDH3) and 6 downregulated genes (CLDN18, CRTAC1, AGER, SFTPA2, SFTPA1, ABCA3) specifically expressed in the respiratory system and indicated that the processes of extracellular matrix organization, protein digestion, and absorption signaling pathway and hemidesmosome assembly played main roles in the pathogenesis of IPF.Conclusions: This bioinformatic analysis may provide useful information for elucidating novel mechanisms underlying IPF. 13 main DEGs specifically expressed in the respiratory system, which are involved in processes of hemidesmosome assembly, cell-substrate junction assembly, and cell junction assembly, may play main roles in the pathogenesis of progression of IPF.
Low Temperature Plasma Suppresses Proliferation, Invasion, Migration and Survival of SK-BR-3 Breast Cancer Cells
Authors: Li Xiang , Sun Tao , Zhang Xinru , Hou Chao , Shen QiYing , Wang Dong , Ni Guohua
Published: May 2022

Low temperature plasma (LTP) is a developing field in recent years to play important roles of sterilization, material modification and wound healing. Breast cancer is a common gynecological malignant tumor. Recent studies have shown that LTP is a promising selective anti-cancer treatment, because some cancer cells are highly sensitive to reactive oxygen species (ROS) produced by LTP, but non-tumor cells are highly resistant to it, which indicates that the main effect of LTP is mediated through the generation of ROS. The effect of LTP on breast cancer is still unclear. In this study, We treated breast cancer cell lines with low temperature plasma for different periods of time and analyzed the relevant differences. we found that LTP was able to suppress cell vitality, proliferation, invasion and migration of SK-BR-3 cells. Also, SK-BR-3 apoptosis was induced by LTP in a time-dependent manner. These evidences suggest the negative effect of LTP on malignant development of SK-BR-3 cells, and LTP has the potential clinical application for breast cancer treatment.
Room temperature synthesis of water-soluble spherical particles of a uniform diameter composed of carbon nanobelts and C60 molecules
Authors: Choi Sieun , Kurosu Shunji , Marieshiko Yuta , Maekawainakawa Takanobu , Maekawa Toru
Published: May 2022

A carbon nanobelt (CNB) is a loop of fused benzene rings and in a sense a cutout of a single-walled carbon nanotube. Various types of CNBs have been successfully synthesized in recent years and CNBs have been utilized for the development of practical devices. In this study, we investigate secondary structures formed by (6,6)CNBs and C60 molecules, which are dissolved in 1,2-dichlorobenzene. We find that uniform spherical particles are formed by (6,6)CNBs and C60 molecules in 1,2-dichlorobenzene at room temperature via bottom-up self-assembly, setting the molar concentrations of (6,6)CNBs and C60 molecules at appropriate values, and furthermore those particles are monodisperse even in water. The present facile room temperature synthetic methodology can be applied to the creation of nano/micro structures/materials using basic carbon nano units such as cycloparaphenylene (CPP, carbon nanorings) and fullerenes; e.g., C60, C70 and C59N.
Validation of the Death Literacy Index and benchmarking of death literacy level in a representative UK population sample
Authors: Graham-Wisener Lisa , Toner Paul , Leonard Rosemary , Groarke Jenny M.
Published: May 2022

BackgroundDeath literacy includes the knowledge and skills that people need to gain access to, understand, and make informed choices about end of life and death care options. The Death Literacy Index (DLI) can be used to determine levels of death literacy across multiple contexts, including at a community/national level, and to evaluate the outcome of public health interventions. As the first measure of death literacy, the DLI has potential to significantly advance public health approaches to palliative care. The current study aimed to provide the first assessment of the psychometric properties of the DLI in the UK, alongside population-level benchmarks. MethodsA large nationally representative sample of 399 participants, stratified by age, gender and ethnicity, were prospectively recruited via an online panel. The factor structure of the 29-item DLI was investigated using confirmatory factor analysis. Internal consistency of subscales was assessed alongside interpretability. Hypothesised associations with theoretically related/unrelated constructs were examined to assess convergent and discriminant validity. Descriptive statistics were used to provide scaled mean scores on the DLI.ResultsConfirmatory factor analysis supported the original higher-order 8 factor structure, with the best fitting model including one substituted item developed specifically for UK respondents. The subscales reported high internal consistency. Good convergent and discriminant validity was evidenced in relation to objective knowledge of the death system, death competency, actions relating to death and dying in the community and loneliness. Good known-groups validity was achieved with respondents with professional/lived experience of end-of-life care reporting higher levels of death literacy. There was little socio-demographic variability in DLI scores. Scaled population-level mean scores were near the mid-point of DLI subscale/total, with comparatively high levels of experiential knowledge and the ability to talk about death and dying. ConclusionsPsychometric evaluations suggest the DLI is a reliable and valid measure of death literacy for use in the UK, with population level benchmarks suggesting the UK population could strengthen capacity in factual knowledge and accessing help. International validation of the DLI represents a significant advancement in outcome measurement for public health approaches to palliative care. Pre-registrationhttps://osf.io/fwxkh/
Indicators of climate change and violence against women predict estimated prevalence of modern slavery: An Ecofeminist Perspective
Authors: Cameron Erinn , Trend-Cunningham Fiona , Ray Janine M. , Jacquin Kristine M.
Published: May 2022

Climate change, violence against women (VAW), and modern slavery are significant human rights crises to which women are disproportionately vulnerable. Our research examined the complex relationship between indicators of climate change, VAW, and the estimated prevalence of modern slavery across 180 countries. Regression analysis revealed significant results suggesting that countries where climate change and VAW are prevalent may support conditions that exacerbate vulnerability to exploitation. Results are placed within a gender framework, highlighting ecofeminism theory for an examination of patriarchal and capitalistic systems and their relationship to the oppression of women, the degradation of the environment, and modern slavery.
Chemical constituents from the rhizome of Dioscorea bulbifera L.
Authors: Zhang Yunqiang , Han Tingting , Wang Hongpeng , Li Meichen , Xia Feiruo , Liu Jianyu , Xu Yongnan
Published: May 2022

A phytochemical investigation of the rhizome of Dioscorea bulbifera L. led to the isolation of twenty compounds, including eight phenanthrenes (1–8), eight flavonoids (9-16), two diterpenes (17, 18), one bibenzyl derivatives (19), and one acid (20). The structures of these compounds were elucidated on the basis of spectroscopic analysis and comparison with previous literature data. Among them, 1 and 16 were isolated from the rhizome of Dioscorea bulbifera L. for the first time and compounds 16 first reported from the genus Dioscorea. They were tested in vitro for cytotoxic activities against CT26 cell lines and Compound 1 exhibits cytotoxic activity with IC50 value of 83.23 μM.
Cyberbullying among Adolescents in Saint Vincent and the Grenadines: Psychosocial Correlates for School-Based Health Promotion Interventions
Authors: Mireku Dickson Okoree , Sarfo Jacob Owusu , Seidu Abdul-Aziz , Ahinkorah Bright Opoku
Published: May 2022

Background This study aimed to investigate the prevalence and psychosocial correlates of cyberbullying among in-school adolescents in Saint Vincent and the Grenadines. MethodWe explored the 2018 Saint Vincent and the Grenadines’ Global School-based Health Survey with a sample size of 1,877 in-school teenagers (aged 11 - 18 years old). Using a binomial logistic regression modelling, statistically estimated Adjusted Odds Ratios (AOR) at a 95% confidence interval were utilised to determine the predictors of cyberbullying. ResultsResults showed a 15.7% (10.8% males vs. 20.5% females) prevalence of cyberbullying among in-school teenagers. Also, psychosocial correlates like being a female (AOR 2.387, 95% CI 1.694 – 3.362), being physically attacked (AOR 0.702, 95% CI 0.494 –0.997), being involved in a physical fight (AOR .702, 95% CI 0.499 – 0.988), being bullied on a school property (AOR 0.458, 95% CI 0.326 – 0.645), being bullied off a school property (AOR 0.261, 95% CI 0.185 – 0.368), having ever considered suicide (AOR 0.577, 95% CI 0.418–0.796), and having ever had sex (AOR 0.484, 95% CI 0.350–0.669) significantly predicted cyberbullying. ConclusionFurther, school-based health interventions focusing on the identified psychosocial correlates are required to mitigate cyberbullying in Saint Vincent and the Grenadines.Trail Registration: Global School-Based Student Health Survey 2018 (VCT_2018_GSHS_v01) Registered August 20, 2021, https://extranet.who.int/ncdsmicrodata/index.php/catalog/878.
Can mobile-bearing unicompartmental knee arthroplasty achieve natural gap-balancing： an observational study with novel pressure sensor
Authors: Nan Shaokui , Cao Zheng , Song Yue , Kong Xiangpeng , Li Haifeng , Chai Wei
Published: May 2022

BackgroundMobile-bearing unicompartmental knee arthroplasty (MB-UKA) is an effective treatment for anteromedial knee osteoarthritis. Meticulous intraoperative soft tissue balancing remains challenging yet consequential for a successful operation. Currently, surgeons rely mostly on their experience during soft tissue balancing, yielding unreproducible results. This study aimed to further optimize clinical results of MB-UKA through quantitative measurements of intraoperative medial compartment soft tissue tension and determination of target tension values most consistent with the natural state.MethodsThis was an observational study of 24 consecutive patients. All 30 UKAs were performed by a single surgeon. The piezoresistive sensor was custom designed to fit in the medial compartment gap. Contact pressures were measured at 5 angular positions of the knee intraoperatively: 0°, 20°, 45°, 90°, and 110° of flexion. The change in pressure from extension (20° position) and flexion (110° position) was also calculated (E-FPD). Data on age, sex, body mass index, operative side, and bearing size were collected. Outcome measures were measured at baseline and at the 6-month postoperative follow-up; Oxford Knee Score, visual analog scale score, and range of motion were compared to evaluate clinical outcomes. Results There was a significant improvement in patients in all measured outcomes at 6 months from baseline. The E-FPD of 14.9 N (8.9, 24.6) was indicative of appropriate soft tissue balancing throughout the functional range of knee motion. Of 30 knees, 22 were 3-mm bearing and 8 were 4- or 5-mm bearing. The pressure data of the 3-mm bearing group was larger than that of the non-3-mm bearing group for each knee flexion degree, but the difference was not statistically significant.Conclusions Objective data from sensor output may assist surgeons in decreasing loading variability during MB-UKA. The data suggested that MB-UKA could not accurately restore soft tissue tension to the natural state, which was related to the inability of MB-UKA surgical instruments to fine adjust the bone cut and soft tissue release. We suggest designing a new type of 3.5 G-clamp to help better obtain the soft tissue tension close to the natural tension.Study registration:Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR1900024146.
Bacterial infection is a risk factor for progression to acute-on-chronic liver failure in patients with severe hepatitis flare of HBV-related compensated liver cirrhosis
Authors: Lin Shide
Published: May 2022

Aims
The aims of this study were to investigate the risk factors for bacterial infection (BI) and the association of BI with progression to acute-on-chronic liver failure (ACLF) in patients with severe hepatitis flare of hepatitis B virus (HBV)-related compensated liver cirrhosis.
Methods
237 patients with HBV-related compensated liver cirrhosis and severe hepatitis flare were retrospectively reviewed. Baseline demographics characteristics, biochemical were compared between patients with and without occurring of BIs and progression to ACLF. Univariate and multivariate logistic regression were used to identify independent risk factors associated with development of BI and ACLF.
Results
48 (20.3%) patients progressed to ACLF after admission. 101 (42.6%) patients progressed to hepatic decompensation (HD) and 52 (20.3%) patients had BIs before development of ACLF. Patients with BIs had significantly higher incidence of HD (73.1%) and ACLF (46.2%) than those without BIs (34.1% and 13.0%, respectively, P < 0.01). Total bilirubin (TBil, OR = 1.003, 95% CI: 1.000-1.006) and Child-turcotte-pugh (CTP) score (OR = 1.745, 95% CI: 1.345–2.265) were identified as independent risk factors associated with BI. BI (OR = 7.113, 95% CI: 2.714–18.644), gamma-glutamyl transpeptidase (OR = 0.094, 95% CI: 0.988–0.999), TBil (OR = 1.004, 95% CI: 1.001–1.007), international normalized ratio (OR = 114.05, 95% CI:17.4-746.3) and platelet (OR = 0.984, 95% CI: 0.972–0.996) were independent risk factors associated with progression to ACLF.
Conclusion
High level of TBil and CTP score are risk factors associated with occurring of BI and BI is a risk factor related with progression to ACLF in patients with HBV-related compensated liver cirrhosis and severe hepatitis flare.
A Systematic Review on Evolving the Bowel Cancer Screening Programme in England: Targeted Screening for Individuals with First-Degree Family History of Bowel Cancer
Authors: Chigonda Rutendo Lisa
Published: May 2022

First-degree relatives of bowel cancer cases have an approximately twofold risk of the disease compared with those without a family history. The more affected first-degree relatives an individual has the higher the absolute and relative risk for developing bowel cancer. At present, widespread screening of average-risk individuals for bowel cancer occurs in England, however, the Bowel Cancer Screening Programme does not currently provide a framework for the identification of a family history of bowel cancer. The aim is to determine the cost effectiveness and benefits of offering targeted screening to individuals with a first-degree family history of bowel cancer. The primary outcomes examined the prevalence of developing bowel cancer and estimated the cost effectiveness to inform screening policy decisions. The secondary outcome evaluated the possible screening barriers in the adoption of bowel screening of first-degree relatives. Data presented suggests that screening first-degree relatives of patients with bowel cancer is likely to be cost effective to the NHS, and that compared with the average-risk group using colonoscopy, advanced neoplasia was significantly more prevalent in those with first-degree relatives with bowel cancer. Targeted screening would mean less long-term health costs however, given the limited resources on NHS cost analysis data, cost savings associated with targeted screening are largely unknown; although data presented from European studies strongly suggests that it may be optimistic. Opportunities for this review include its recommendation to modify the screening criteria to extend to first-degree relatives of bowel cancer patients and for the National Screening Committee to implement this protocol nationwide.
Vascular Density Changes in Retina and Optic Nerve in OSAS Patients Using and Not Using CPAP
Authors: Oba Turker , Arman Berkay Hasan , Cicek Feyza , Onder Feyza
Published: May 2022

Background To compare optic disc and macular vascular density (VD) between the control group and severe obstructive sleep apnea syndrome (OSAS) patients with using CPAP or not.Methods Evaluation was made of 60 eyes of patients with severe OSAS using CPAP, 60 eyes of patients with severe OSAS not using CPAP, and 30 control groups, using OCTA RT XR Avanti (AngioVue software, Optovue Inc., Fremont, CA). Optic nerve head (ONH) and macular VD were measured in 4 quadrants. Retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (mGCC) thickness were evaluated with Spectral Domain OCT for all patients. Results In OSAS patients using CPAP, there was no significant thinning in the RNFL and mGCC thickness compared to the control group (p>0.05). Peripapillary VD was significantly different in superior-inferior-nasal quadrants in patients using CPAP (p<0.001, p=0.001, p=0.004, respectively) and was affected in the nasal quadrant in patients not using CPAP when compared with the control group (p=0.012). In eyes with no use of CPAP, macular superficial and perifoveal deep vascular density differed from control in all sectors (all, p<0.05), while only deep VD was reduced in patients using CPAP (p=0.005, p>0.05, respectively).Conclusion Although OSAS causes a significant decrease in macular vessel density, it does not cause significant damage to structural elements such as RNFL and mGCC. While the use of CPAP has a positive effect by providing oxygenation to the macular superficial perfusion, it significantly reduces the peripapillary perfusion by causing an increase in IOP. Severe cases using CPAP may have a significant risk for glaucoma. Therefore, OCTA may be an ideal method to evaluate the changes in the retinal vascular system, which could be an effective parameter for the early evaluation of severe OSAS patients.
Activation of LRP1 ameliorates cerebral ischemia/reperfusion injury and cognitive decline by suppressing neuroinflammation and oxidative stress through TXNIP/NLRP3 signaling pathway in mice
Authors: Yang Chengjie , Chen Ye , Li Xin , Feng Xiaoqing , Feng Jianguo , Jia Jing , Wei Jicheng , Zhou Jun
Published: May 2022

Cerebral ischemia/reperfusion (I/R) injury is a clinical event associated with high morbidity and mortality. Neuroinflammation plays a crucial role in the pathogenesis of I/R-induced brain injury and cognitive decline. Low-density lipoprotein receptor-related protein-1 (LRP1) can exert strong neuroprotection in experimental intracerebral hemorrhage. However, whether LRP1 can confer neuroprotective effects after cerebral I/R is yet to be elucidated. The present study aimed to investigate the effects of LRP1 activation on cerebral I/R injury and deduce the underlying mechanism involving TXNIP/NLRP3 signaling pathway. Cerebral I/R injury was induced in mice by bilateral common carotid arteries occlusion. LPR1 ligand, apoE-mimic peptide COG1410 was administered intraperitoneally. To elucidate the underlying mechanism, overexpression of TXNIP was achieved via the hippocampal injection of AAV-TXNIP before COG1410 treatment. Neurobehavioral tests, brain water content, immunofluorescence, western blot, enzyme-linked immunosorbent assay, HE and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were performed. Our results showed that the expressions of endogenous LRP1, TXNIP, NLRP3, and cleaved caspase-1 were increased after cerebral I/R. COG1410 significantly ameliorated cerebral I/R-induced neurobehavioral deficits, brain edema, histopathological damage, and poor survival rate. Interestingly, COG1410 inhibited microglia pro-infammatory polarization and promoted anti-infammatory polarization, decreased oxidative stress, attenuated apoptosis, and inhibited the expression of the TXNIP/NLRP3 signaling pathway. However, the benefits of COG1410 were abolished by TXNIP overexpression. Thus, our study suggested that LRP1 activation with COG1410 attenuated cerebral I/R injury at least partially related to modulating microglial polarization through TXNIP/NLRP3 signaling pathway in mice. Thus, COG1410 treatment might serve as a promising therapeutic approach in the management of cerebral I/R patients.
Enterococcus faecalis rnc gene modulates its susceptibility to disinfection agents: a novel approach against biofilm
Authors: Xia Mengying , Zhuo Niya , Ren Shirui , Zhang Hongyu , Yang Yingming , Lei Lei , Hu Tao
Published: May 2022

Background: Enterococcus faecalis (E. faecalis) plays an important role in the failure of root canal treatment and refractory periapical periodontitis. As an important virulence factor of E. faecalis, extracellular polysaccharide (EPS) serves as a matrix to wrap bacteria and form biofilms. The homologous rnc gene, encoding Ribonuclease III, has been reported as a regulator of EPS synthesis. Searching the novel anti-biofilm targets, the effects of the rnc gene on the biological characteristics of E. faecalis were investigated and the biofilm tolerance towards the typical root canal irrigation agents and traditional Chinese medicine fluid Pudilan was compared.Methods: E. faecalis rnc gene overexpression (rnc+) and low-expression (rnc-) strains were constructed. The growth curves of E. faecalis ATCC29212, rnc+, and rnc- strains were identified to study the regulatory effect of the rnc gene on E. faecalis. Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and crystal violet staining assays were performed to evaluate the morphology and composition of E. faecalis biofilms. Furthermore, the wild-type and mutant biofilms were treated with 5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), and Pudilan. The residual viabilities of E. faecalis biofilms were evaluated using crystal violet staining and colony counting assays.Results: The results demonstrated that the rnc gene could suppress bacterial growth and EPS synthesis, causing the EPS-barren biofilm morphology and low EPS/bacteria ratio. Both the rnc+ and rnc- biofilms showed increased susceptibility to the root canal irrigation agents. 5% NaOCl showed the highest biofilm removing effect followed by Pudilan and 2% CHX. The colony counting results showed almost complete removal of bacteria in the 5% NaOCl, 2% CHX, and Chinese medicine agents’ groups.Conclusions: This study concluded that the rnc gene could positively regulate bacterial proliferation, EPS synthesis, and biofilm formation in E. faecalis. The rnc mutation caused an increase in the disinfectant sensitivity of biofilm, indicating a potential anti-biofilm target. In addition, Pudilan exhibited an excellent ability to remove E. faecalis biofilm.
Identification of Intracranial Aneurysm Inflammatory Hub Genes by Machine Learning
Authors: Dai Penggao , Lin Qi , Chen Jianping
Published: May 2022

Rupture of intracranial aneurysm (IA) has a very high mortality and disability rate, so it is very important to explore the mechanism of IA formation and to find potential drug therapy targets. Inflammatory responses have now been shown to play an important role in the formation and development of IA. The diagnosis, therapeutic target and prognostic marker research of various diseases through machine learning has superior performance, but it has not been reported in IA. In this study, we searched for the core inflammatory genes in the formation of IA through the GEO database, and identified the interaction relationship of these genes and the core regulated gene (TLR4) through the string database. The results of enrichment analysis indicated that our obtained inflammatory genes were associated with inflammatory response, immune response and vascular disease. Then, three key genes (CLEC7A, RTP4, SOX11) were found by two machine learning algorithms. The ROC curve results showed that key genes had high clinical value. In addition, by analyzing the correlation between key genes and immune cell infiltration, we found that inflammatory cells positively correlated with the expression of key genes play an important role in the formation and development of IA. This study is the first time to find the key genes of IA formation by machine learning method. The hub genes obtained in this study can provide new ideas for the formation and molecular mechanism of IA in the future, and provide a new direction for the non-surgical treatment of IA.
A new hereditary PROS1 mutation caused isolated cortical venous thrombosis: a case report and literature review
Authors: Huang Jieming , Zeng Yuqi , Sun Bin , Xin Jiawei , Yu Erhan , Chen Xiaochun , Ye Qinyong , Chen Ying
Published: May 2022

Background: Protein S Deficiency is a rare inherited disease. We report a disease process that a young man with a new PROS1(OMIM:176880) mutation suddenly occurred Isolated cortical vein thrombosis(ICoVT).Case presentation: The patient suffered from headaches and Paroxysmal convulsion without obvious inducement. Physical examination, coagulation function test were generally normal. The activity of protein S was 21.2%, which was significantly lower than the normal value. MRI (magnetic resonance imaging) showed right parietal cerebral hemorrhage, right parietal cortex vein thickening, cord-like. When we reviewed the patient's family history, we found that his father had successively suffered from mesenteric venous thrombosis, Portal venous thrombosis, and cerebral venous sinus thrombosis. Genetic analysis revealed a new PROS1 mutation in the patient and his father. In addition, there is a duplication about 403.6Kb in the patient's chromosome 3q26.32-33. And we summarized the characteristics of cases with PROS1 LG2 subunit mutation.Conclusions: This is a novel case report that a new PROS1 gene missense mutation caused ICoVT. It provides information for us to understand the functional information of PROS1. When come to unexplained ICoVT, we need to consider the possibility of PROS1 gene mutation.
Effect of smoking on retinal ganglion cell-inner plexiform layer complex in diabetes
Authors: li lu , Zhang Lina , Zheng Zhaoxia , Zhang Duo , Yan Meng
Published: May 2022

PurposeThe aim of this study is to show the effect of smoking on retina layers measured by spectral domain optical coherence tomography (OCT) in diabetes, especially retinal ganglion cell complex and inner plexiform layer (GC-IPL) thickness.Materials and MethodsThe 92 smoking and 92 never-smoking subjects were divided into six groups­—healthy smokers group (HS), healthy nonsmokers group (HNS), diabetic smokers group (DS), diabetic nonsmokers group(DNS), diabetic retinopathy smokers(DRS) group, diabetic retinopathy nonsmokers group(DRNS), based on whether they were diagnosed as diabetes and the ET-DRS classification. After full ophthalmologic examination, retinal ganglion cell-inner plexiform layer complex(GC-IPL) thickness, and central macular thickness (CMT) were measured by OCT. Statistical analysis was performed to compare GC-IPL thickness and CMT values between groups. ResultsThere were no significant differences in GC-IPL thickness and CMT between the healthy smokers and healthy nonsmokers group. All quadrants of GC-IPL and mean GC-IPL were thinner in the diabetic smokers than diabetic nonsmokers group except that of inferotemporal GC-IPL thickness and CMT. Superonasal, superior GC-IPL and mean GC-IPL were thinner in the diabetic retinopathy smokers than diabetic retinopathy nonsmokers group. On the contrary, there were no statistically significant difference in other quadrants of GC-IPL and CMT. Multiple regression analysis demonstrated that advancing age and smoking behaviors are the most important determinants for mean GC-IPL. ConclusionSmoking may affect GC-IPL thickness in diabetes but not in the healthy people.
NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Feasibility Trial
Authors: Lim Grace , Nowakowski Emma , LaSorda Kelsea R. , Altamirano Valeria , Morgan Madison , Makeen Mutasim , Beck Stacy , Krans Elizabeth , Chelly Jacques E.
Published: May 2022

Introduction
Percutaneous auricular nerve stimulation has been used for the treatment of symptoms associated with opioid withdrawal, including abdominal pain, nausea, and general discomfort. However, its potential utility for pain management and opioid minimization after surgery has not been investigated. The purpose of this study was to test the feasibility and acceptability of a trial protocol designed to assess the effectiveness of the NSS2-Bridge device as a non-pharmacologic alternative to opioids after cesarean delivery.
Methods
In a randomized control design, healthy women receiving cesarean delivery were randomized in a 1:1:1 allocation to receive the active device, placebo device, or no device. Devices were placed on the ear following cesarean delivery and left in place for 5 days. Feasibility and acceptability of the device was assessed by patient reports of device tolerability (rated on a 100mm visual analog scale where 0 is not tolerable at all and 100 is the most tolerable) as well as qualitative reporting. Additional outcomes assessed included proportion of patients not using opioids in hospital, as well as pain at rest, pain with movement, and total opioid consumption in the hospital and for the first 5 days after surgery.
Results
There were 60 patients included in the final analysis. Device tolerability was rated highly, with an average daily score of > 75 mm on the visual analog scale. The trial retention rate was 89.7% with most exclusions (42.9%) occurring due to unanticipated development of care complexity (e.g., hemorrhage and additional surgical procedures), with only 1 exclusion (14.3%) due to device discomfort. The active device group achieved the highest proportion of opioid-free hospitalizations (40%) compared to placebo (20%) and no device groups (30%). Pain at rest and with movement was similar between treatment groups.
Conclusions
The NSS2-Bridge device for post-cesarean pain management is feasible and acceptable to patients. Larger proportions of patients not using opioids in the active device group justifies additional investigation on device effectiveness in the context of opioid use disorders in pregnant and postpartum people.
WITHDRAWN: Computational fluid dynamics modeling of microstructured steam reforming reactors for hydrogen production
Authors: Chen Junjie , Ge Wei
Published: May 2022

Improvements in microstructured steam reforming reactors would be highly beneficial to the production of hydrogen. The present study relates to a catalytic process of steam-methanol reforming for the production of hydrogen in a microstructured heterogeneous reaction system. Computational fluid dynamics simulations were performed to investigate the effects of washcoat thickness and wall thermal conductivity on the efficiency and performance of a microstructured steam reforming reactor system. Design recommendations were made to improve the overall efficiency and performance of the microstructured heterogeneous reaction system. The results indicated that temperature uniformity can be maintained across the walls due to the small scale of the reactor system. The washcoat thickness and the inlet velocity are vital in determining the methanol conversion efficiency of the reactor system. The methanol conversion decreases with increasing flow velocity or with decreasing washcoat thickness. The hydrogen production rate increases with increasing the inlet velocity of the reforming stream. Copper and oxides of zinc and aluminum can be used effectively as a catalyst for methanol steam reforming in the reactor system. The wall thermal conductivity has a strong effect on the reforming efficiency of the reactor system. High wall thermal conductivity can offer performance advantages.
The Role of (De)bonding in the Legitimation of Violence in Extremists' Public Threatening Communication
Authors: Etaywe Awni
Published: May 2022

One aspect of threat of terrorist public communication is incitement to violence and legitimating it (Tsesis, 2017). This paper contributes to understanding how bonds tabled in discourse are exploited to legitimize 'Our' violence and to delegitimize ‘outgroups’. I argue that the inciting texts drive the strategic use of bonds to achieve a main rhetorical function: legitimizing violence. The patterns of bonds, geared as a basis for perception and (de)legitimation, are investigated as realized in a set of incitement texts communicated publicly by the former al-Qaeda leader, Osama bin Laden, and the far-rightist, Brenton Tarrant. The analytical approach mainly draws on Knight's (2010) social semiotic approach to bonding to identify the account of bonds as evidence of and entry points to (de)legitimation. The patterns of bonds across each terrorist's texts are then labelled thematically based on what is (de)legitimated. To identify reference to reasons of (de)legitimation, Van Leeuwen's (2007) semantic-functional strategies of critique and (de)legitimation are used. To map the rhetorical structure level-style of (de)legitimation, the classic appeal strategies – pathos (appeal to incitees' emotions), logos (rational arguments) and ethos (authority-based arguments) – are identified. Findings showed that both authors tended to deploy (i) communing bonds to legitimize 'Our' violence and (ii) condemning bonds to delegitimize outgroups (mainly, their actions, values, and membership), chiefly via moralization, rationalization and authorization, and by drawing on authors' ethos and logical reasoning.
Double window: definition of a new pseudo-color mapping scheme for medical imaging
Authors: Chen Chong , Huang Jia
Published: May 2022

The number of gray levels in medical images significantly exceeds the range of human eye recognition. In this paper, we propose a series of definitions for real-time pseudo-color enhancement based on the hue, saturation, and value (HSV) color space. First, the definitions of gray window and color window are given as follows: in the HSV color space, the gray window means mapping pixel values to value, and saturation is set to zero. Thereafter, the color window was defined by mapping pixel values to hue, with the maximum saturation and value. Moreover, pixel values greater than the upper bound of the gray window were converted to hues in the double window. The images in the double window display the details shown in the lung window, mediastinal window, and bone window for chest computed tomography and showed more details than the grayscale image in brain magnetic resonance imaging. The proposed method enhances the display effect in some cases; for example, when the image histogram has more than one peak, the information displayed white in a regular grayscale image is displayed in color.
Fostering empathy among preadolescents through stories: A Protocol for Scoping Review.
Authors: Odumegwu Joseph Chinwuba
Published: May 2022

BackgroundNo matter the age, everyone craves interaction and belonging, and storytelling creates this sense of belonging. Stories have the power to engage, influence, teach and inspire listeners.The emotional connection built when listening to a story, as opposed to reading raw facts or data, is far more stronger and pushes people to act in an altruistic, empathetic or prosocial manner. ObjectiveOverall, this study aims to identify all relevant quantitative and qualitative literature in the area of storytelling and empathy among preadolescents aged 5 to 12 years, by adopting the Arksey and O'Malley (2005) framework. MethodsFollowing the scoping review guidelines provided by Arksey and O'Malley, the underlisted electronic databases will be searched; MEDLINE, Scopus, PsycINFO, PsycArticles, CINAHL and Cochrane. Reference lists of articles, gray literature and journals would be screened to locate additional studies. Inclusion criteria will be strictly based on study aims and objectives. ResultsThe results of this review will be reported using the PRISMA-ScR (Tricco et al., 2018). The results will address the primary research question and describe a summary of the available literature on storytelling interventions on preadolescence's empathy. ConclusionsA scoping review of storytelling interventions and empathy outcomes for preadolescents has never been conducted due to a lack of literature. This report wants to fill this gap by summarizing what is known about this issue. Findings of this review will potentially inform future research into the effectiveness of storytelling interventions and point to the gaps in knowledge.