bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Morphologic Grading and COS Protocol on the Outcome of Day 5 Versus Day 6 Single Fresh Blastocyst Transfers: a Retrospective Analysis of Clinical Outcomes
Authors: Chen Zhilan , Li Wei , Xiao Cong , Li Yanmin , Lv Liqun , Huang Kecheng , Gong Aidong
Published: October 2021

Background: This study aimed to compare the clinical outcomes after day 5 (D5) blastocyst-stage single embryo transfers (SET) versus day 6 (D6) SET following fresh embryo transfer cycle and to evaluate whether the blastocyst morphologic grading and the protocol of controlled ovarian stimulation (COS) would influence effect estimates, aiming to provide guidance when choosing blastocyst transfer.Method: The clinical data of 612 patients who underwent single fresh blastocyst transplantation, as well as the data of 217 patients who had already delivered were analyzed retrospectively. The patients were divided into two groups according to blastocyst formation time (D5 or D6). The following subgroup analyses were performed: (i) the protocol of COS and (ii) the morphologic grading of blastocyst. Results: We observed that D6 SET were associated with lower clinical pregnancy rate (CPR, 31.7% vs 59.8%, P < 0.001) and live birth rate (LBR, 22.1% vs 38.2%, P = 0.002) than D5 SET following fresh cycle. Patients in D5 group experienced more good blastocysts transfer (45.7% vs 13.5%, P < 0.001) and less poor blastocysts transfer (9.7% vs 45.2%, P < 0.001) than patients in D6 group (Table 3). As to good quality blastocysts, the CPR（63.4% vs 50.0%, P = 0.33）and LBR（40.9% vs 42.9%, P = 1.0）were similar between D5 and D6 group. Conclusion: In conclusion, the CPR and LBR in the D5 group were significantly higher than those in the D6 group. The difference in neonatal outcomes between the two groups was not statistically significant. The subgroup analysis found that the superiority of day 5 SET compared with day 6 SET is influenced by the quality of blastocyst transferred and the COS protocols.
Tracking the kinetics and phenotype of spike epitope-specific CD4 T cell immunity in the context of SARS-CoV-2 infection and vaccination
Authors: Juno Jennifer , Wragg Kathleen , Lee Wen Shi , Amarasena Thakshila , Reynaldi Arnold , Koutsakos Marios , Konstandopoulos Penny , Field Kirsty , Esterbauer Robyn , Tan Hyon-Xhi , Kent Helen , Davenport Miles , Wheatley Adam , Kent Stephen
Published: October 2021

CD4+ T cells play a critical role in the immune response to viral infection. SARS-CoV-2 infection and vaccination elicit strong CD4+ T cell responses to the viral spike protein, including circulating T follicular helper (cTFH) cells that correlate with the development of neutralising antibodies. Here we use a novel HLA-DRB1*15:01/S751 tetramer to precisely track spike-specific CD4+ T cells following recovery from mild/moderate COVID-19, or after vaccination with spike-encoding vaccines. SARS-CoV-2 infection induces robust S751-specific responses with both CXCR5- and cTFH phenotypes that are maintained for at least 12 months in a stable, CXCR3-biased, central memory pool. Vaccination of immunologically naïve subjects similarly drives expansion of S751-specific T cells with a highly restricted TCR repertoire comprised of both public and private clonotypes. Vaccination of convalescent individuals drives recall of CD4+ T cell clones established during infection, which are shared between the CXCR5- and cTFH compartments. This recall response is evident 5 days after antigen exposure and includes a population of spike-specific cTFH that persist in the periphery after losing expression of PD-1. Overall this study demonstrates the generation of a stable pool of cTFH and memory CD4+ T cells that can be recalled upon spike antigen re-exposure, which may play an important role in long-term protection against SARS-CoV-2 infection.
CD82 Protects Against Glaucomatous Axonal Transport Deficits via mTORC1 Activation in Mice
Authors: Ye Meng , Huang Jingqiu , Mou Qianxue , Luo Jing , Hu Yuanyuan , Lou Xiaotong , Yao Ke , Zhao Bowen , Duan Qiming , Li Xing , Zhang Hong , Zhao Yin
Published: October 2021

Background: Glaucoma is a leading cause of irreversible blindness worldwide characterized by progressive optic nerve degeneration and retinal ganglion cell (RGC) loss. Axonal transport deficits have been demonstrated to be the earliest crucial pathophysiological changes underlying axonal degeneration in glaucoma. The critical feature of this pathological process and the significance of early intervention remain to be further explored. Here, we explore the role of a tetraspanin superfamily member CD82 in protection of glaucomatous neurodegeneration in an acute ocular hypertension mouse model. Methods:Expression level of CD82 in retina was examined before and after an acute ocular hypertension (AOHT) model in mouse. Overexpression of CD82 was achieved by intraocular injection of adeno-associated virus vector expressing CD82. Axonal transport deficits were evaluated by intravitreally injected Cholera toxin B (CTB) from eyes to superior colliculus and the distribution of endogenous synaptophysin. Subsequent optic nerve (ON) degeneration phenotypes were also examined including axon loss, myelin damage, and Aβ accumulation. In vitro neurite outgrowth assay was performed in SH-SY5Y cells with Cd82-plasmid transfection. Another optic nerve crush (ONC) model was taken to further validate the neuroprotective effects of CD82 by evaluation of axonal regeneration, RGC survival, and visual function of mice. Downstream pathway of CD82 was analyzed by qPCR examination and western blotting analysis as well as phenotype detection.Results:We found a transient downregulation of CD82 after acute IOP elevation, with parallel emergence of axonal transport deficits. Overexpression of CD82 with AAV2/9 vector in mouse retina improved optic nerve (ON) axonal transport and ameliorated subsequent axon degeneration. In vitro neurite outgrowth assay displayed longer neurite length of SH-SY5Y cells with transfection of Cd82-plasmid. Moreover, CD82 overexpression could stimulate ON regeneration and restore mouse vision after an optic nerve crush model. CD82 exerted protective effect through upregulation of TRAF2, which was an E3 ubiquitin ligase and activated mTORC1 through K63-linked ubiquitylation and intracellular repositioning of Raptor. Conclusions:These findings indicate that CD82 overexpression protects against glaucomatous axonal transport deficits through TRAF2-dependent activation of mTORC1 pathway, which offers deeper insights into tetraspanins superfamily and demonstrated potential neuroprotective strategy in glaucoma treatments.
Effects of Indocyanine Green on Apoptosis, Proliferation, Migration, Invasion and Transdifferentiation of Human Lens Epithelial Cells Line SRA01/04
Authors: Liu Ya jun , Zhao Yingdi , Zhang Wenwen , Zhang Si , He Zifang , Chen Feifei , Xie Zhenggao
Published: October 2021

Background

To investigate the effect of indocyanine green (ICG) on apoptosis, proliferation, migration, invasion and transdifferentiation in cultured human lens epithelial cells line SRA01/04 (HLECs).
Methods

HLECs were exposed to ICG for 3 minutes at various concentrations of 0.5%, 1.5% and 2.5%. The apoptosis process was detected by flow cytometry, and apoptosis related proteins Bax, Bcl-2, caspase-3 and caspase-9 were detected by Western blot. Cell proliferation process was detected via the cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Wound healing assay was employed to determine cell migration. Transwell assays were performed to assess cell migration and invasion process. Transdifferentiation related proteins α-SMA, N-cadherin, Fibronectin and Vimentin were accessed by Western blot.
Results

ICG significantly increased HLECs apoptosis and decreased cell proliferation, migration, invasion and transdifferentiation after 3 minutes of exposure. Expression of Bax, caspase-3, and caspase-9 pro-apoptosis proteins were up-regulated after ICG exposure, while Bcl-2 anti-apoptosis protein was down-regulated. Transdifferentiation related proteins α-SMA, N-cadherin, Fibronectin and Vimentin expression were down-regulated.
Conclusions

ICG can promote HLECs apoptosis and inhibition HLECs proliferation, migration, invasion and transdifferentiation in a concentration-dependent manner.
Androgenic TRPM8 activity drives sexual dimorphism in a murine model of chronic migraine
Authors: Alarcón-Alarcón David , Cabañero David , de Andrés-López Jorge , Fernández-Ballester Gregorio , Fernández-Carvajal Asia , Ferrer-Montiel Antonio
Published: October 2021

The mechanisms contributing to the high prevalence of chronic migraine in females are yet elusive. Here, we used a mouse model of nitroglycerin-induced chronic migraine that displays a sexual dimorphic phenotype and unveiled a role of TRPM8 as a testosterone receptor that provides antinociceptive resilience exclusively in males. Nitroglycerin induced similar mechanosensitivity to both sexes trough activation of TRPA1 channels, but triggered persistent hypersensitivity solely in females, as males readily recovered from the migraine crisis. Notably, we found that testosterone exerted an antinociceptive activity through its interaction with the TRPM8 channel. Downregulation of this protective mechanism in males led to persistent mechanical hypersensitivity, whereas administration of testosterone to females favoured their recovery. Thus, our findings reveal a novel protective function of TRPM8 through pre-clinical models of acute and chronic pain and highlights the interest of molecular solutions mimicking the pain-relieving activity of testosterone on TRPM8.
Inflammatory Biomarkers after an Exercise Intervention in Acute Lymphoblastic Leukemia Survivors
Authors: Lähteenmäki Tuomas , Järvelä Liisa , Niinikoski Harri , Huurre Anu , Harila-Saari Arja
Published: October 2021

BackgroundCancer survivors show increased risk for non-communicable diseases and chronic low-grade inflammation characterizes the development of such diseases. We investigated inflammatory plasma protein profiles of survivors of acute lymphoblastic leukemia (ALL) in comparison to healthy controls and after an intervention with a home-based exercise program. ProcedureSurvivors of ALL aged 16-30 years (n=21) with a median time of 15.9 years from diagnosis, and sex- and age-matched healthy controls (n=21), were studied. Stored plasma samples were analyzed with Olink’s 92-protein-wide Inflammation panel in 21 ALL long-term survivors at baseline, after a 16-week home-based exercise intervention (n=17) and in 21 age- and sex-matched controls at baseline. Protein expression levels were compared between the groups. ResultsInflammatory protein levels did not differ between the survivors and controls at baseline. Significantly reduced levels after the intervention were found in 11 proteins related to either vascular inflammation, insulin resistance, or both: TNFSF14, OSM, MCP-1, MCP-2, FGF-21, CCL4, TGF-alpha, TRAIL, ADA, CXCL6, and LAP TGF-beta-1. ConclusionsThe ALL survivors were not significantly more affected by inflammation than controls at baseline. The survivors’ 16-week physical exercise intervention led to significant beneficial change in inflammation protein levels. Physical exercise should be promoted for survivors of cancer.
Knowledge of human papillomavirus vaccines among university students in Angola
Authors: Rocha Joao Wilson , Vasconcelos Ana Morais , Simões Honolfo Elves , Soqui Elizandra , Rosa Nilton Helibrando
Published: October 2021

Cervical cancer is the first most common cancer among women in Angola and accounts for 37.6% of cancers among women in Angola. The human papillomavirus (HPV) is a causative agent of the disease. Recent advances in technology have led to the introduction of vaccines to prevent HPV infection. This study aims to assess the awareness of university students about HPV infection as a causal factor for cervical cancer and their knowledge about HPV vaccination. Assessing knowledge about vaccination among university students helps us to understand the level of awareness about it. Methods:A questionnaire-based study was carried out on 106 university students, from May 10th to July 26th, 2021. The questionnaire consisted of 10 multiple-choice questions and the results were analyzed using percentages. Results:Knowledge about HPV as a causative agent of cervical cancer was found in 84.2% of students.Awareness of the availability of the HPV vaccine was observed in 55.3%. Complete vaccination status was verified in 0% male students and 13% female students. No male students and 13 female students received incomplete vaccination. 33 men and 73 women were willing to be vaccinated with the HPV vaccine. Conclusion:The present study concludes that there is not a good knowledge of university students about cervical cancer and its prevention. There is also little knowledge about the HPV vaccine, meaning the availability of the vaccine, the right age group for vaccination and the recommended vaccination for men need to be improved. Vaccination status is poor among men and women because it is not on the national vaccination calendar. The desire to get vaccinated in male students was lower compared to female students. Thus, there seems to be a need to motivate male students for vaccination. Therefore, more awareness should be created about the HPV vaccine among students. The government through the Ministry of Health must incorporate the HPV vaccine in the vaccination calendar.
Select the Optimal Development Strategy for Layered Sandstone Reservoir by Creating System Economic Model and the Accumulated Oil Production Prediction Method
Authors: wang fulin , zhao yunfei , fang yanjun
Published: October 2021

To determine the development mode of different oil field in layered sandstone reservoir, a system economic model was established, including the primary production layer section and the upper layer. The cumulative oil production limits of the primary layer were described under different oil prices, using the existing well method (UEWM) and drilling new well method (DNWM). The first layer’s oil production limit for DNWM and UEWM was determined. The established economic ultimate water cut (EUWC) model, the solution prediction model of water cut arctangent, and the water drive curve were combined, to calculate the accumulative oil production from planning time of the upper layer production to the economic limited water cut of block. When the oil price is 40$/BBL, the SME block should be developed by UEWM method. While for 70$/BBL, DNWM should be adopted. This work provides theoretical support for the optimization of up (down) layer return development mode. It is of great significance to guide the development of layered sandstone reservoir.
Anti-UBE2T antibody: a novel biomarker of progressive-fibrosing interstitial lung disease
Authors: Hikichi Mari , Gon Yasuhiro , Mizumura Kenji , Hashimoto Shu , Ph.D. M.D. M Shuichiro
Published: October 2021

Background

Antifibrotic therapy has demonstrated efficacy against progressive-fibrosing interstitial lung disease (PF-ILD); therefore, it has become a priority to identify disease behavior before disease presentation. As autoimmunity is implicated in the pathogenesis of various ILDs, we explored the possibility of a circulating biomarker that can predict the chronic progressive behavior of ILDs.
Methods

A single-center retrospective cohort study was conducted to investigate a biomarker of PF-ILD. Circulating autoantibodies against 9,483 purified full-length human recombinant proteins of patients with interstitial pneumonia were screened by microarray analysis. The candidate auto-antibodies were verified their existence by multiples solution assay. In addition, enzyme-linked immunosorbent assay (ELISA) was performed in larger sample sets to evaluate accurate sensitivity, specificity and clinical significance in ILDs.
Results

In total, 61 healthy subjects and 87 patients with various ILDs enrolled in this study. Anti-UBE2T antibody was discovered by performing protein microarray and multiplex solution assay as a candidate biomarker of ILDs. By measuring its concentration by ELISA, anti-ubiquitin-conjugating enzyme E2T (UBE2T) antibody levels were significantly higher in patients with idiopathic interstitial pneumonias (IIPs), especially in those with PF-ILDs, than in healthy participants. The receiver operating characteristic analysis of anti-UBE2T antibody in diagnosing PF-ILD was calculated. The area under the curve was 0.85 and yielded a cut-off value of 238.1 ng/mL. Anti-UBE2T antibody-positive IIP patients demonstrated significantly higher ILD-gender age physiology scores, PF-ILD diagnosis rates and were more likely to develop honeycomb structures than anti-UBE2T-negative IIP patients after two years of follow up. The anti-UBE2T antibody positivity did not correlate with other commercial biomarkers such as KL-6 and commercial autoantibodies, suggesting the presence of anti-UBE2T antibody was independent of the others. Immunohistochemical staining of UBE2T in normal lungs was observed sparsely in the bronchiole epithelium and macrophages. Controversially, idiopathic pulmonary fibrosis lung tissue showed robust expression of the UBE2T protein in the lining epithelium of honeycomb structures.
Conclusion

This is the first report to describe anti-UBE2T antibody, a new biomarker that is significantly elevated in idiopathic PF-ILDs. This new antibody may constitute a sensitive biomarker to detect cases of PF-ILDs that are not currently detected by commercially available biomarkers.
Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia
Authors: Sha Hong Xi , Veerapen Kumar , Chow Sook Khuan , Gun Suk Chyn , Lau Ing Soo , Lim Renee Lay Hong , Zulkifli Zaliha , Yow Yoon Yen , Peh Suat Cheng , Hwang Jung Shan
Published: October 2021

Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR=0.5478, 95%CI=0.3396-0.8835, p=0.01321) and ATIC T675C (rs4673993) (OR=0.5247, 95%CI=0.3248-0.8478, p=0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene-gene and gene-environment interactions.
A higher rate of adverse pregnancy outcome in HBsAg-positive pregnant woman
Authors: Huang Zhi-Hao , Peng Ting-Ting , Yan Sheng-Guang , Yan Hao-Zhen , Yu Dong-Dong , Qiu Jun-Chao , Liu Mei-Ling , Huang Xin-Yue , Xu Guo-Jun , Ouyang Shi
Published: October 2021

Objective

The aim of this study was to study the relationship between adverse pregnant outcomes(APO) with chronic hepatitis B virus (HBV) infection in pregnant women.
Method

From 2017 to 2019, we studied HBsAg (+) pregnant women and HBsAg (-) who gave birth at our hospital in Guangzhou City, China. We compared of the outcomes of pregnant women with HBsAg(+) or HBsAg(-). Further, among HBsAg(+) pregnant women, We compared of the outcomes of pregnant women with HBeAg(+) group or HBeAg(-) group, HBV DNA above 2×10e5IU/mL group or HBV DNA below 2×10e5IU/mL) group, respectively. Finally, multivariate logistic regression analysis was used to evaluate the independent association between HBV infection and the risk of developing APO.
Result

First, Our research Indicates that the rates of gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), premature rupture of membrane (PROM), Fetal distress (FD), Oligohydramnios, Premature delivery (PD), Low birth weight (LBW), Meconium contamination (MC), Neonatal hyperbilirubinemia(NH) in HBsAg(+) group were higher than those in HBsAg(-) group (P<0.05). Second, among 711 HBsAg(+) pregnant women, the rates of GDM and ICP in HBV DNA above 2ⅹ10e5 IU/mL were higher than those in HBV DNA below 2×10e5 IU/mL group (P<0.05). Similarly, The rates of ICP in HBeAg(+) group were higher than those in HBeAg(-) group. Further, through multivariable logistical regression model analysis, we observed maternal HBsAg carrier (OR, 6.758; 95% CI, 2.358-19.369) had an independent risk for ICP. Similarly, HBsAg carrier(OR, 1.101; 95% CI, 1.066-1.137) ,advanced age (OR, 1.407; 95% CI,1.033-1.917) and abortion(OR,1.446; 95% CI, 1.062-1.969) had independent risk for GDM.
Conclusions

Chronic HBV infection can increase the rate of host adverse pregnancy outcomes (APO). The maternal viral load and HBeAg status were significantly associated with the appearance of GDM and ICP. Maternal HBsAg carrier had an independent risk for GDM and ICP.
Detection and Validation of Novel Human Targets for EBV-miR-BART10-3p
Authors: Jerud Julie Tro , Sognnes Vibeke , Hofsli Eva , Mjelle Robin
Published: October 2021

Epstein-Barr virus (EBV) miRNAs are expression in various human tissues, including the human colon. We have previously shown that the EBV miRNA miR-BART10-3p is higher expressed in colon cancer tissue compared to adjacent normal tissue. Here, we aim to identify and validate novel human targets of miR-BART10-3p. MiR-BART10-3p mimics were transfected into the two colon cancer cell lines, SW620 and LS411N, and changes in RNA expression were evaluated by RNA-seq. Several genes showed significant changes in gene expression upon miR-BART10-3p transfection, and genes that were significantly differentially expressed in both cell lines were more often down-regulated in miR-BART10-3p transfected cells, indicating regulation by miR-BART10-3p. Candidate human targets of miR-BART10-3p were predicted using TargetScan, and two genes with predicted target sites, MAT2B and CCND1, were functionally validated as miR-BART10-3p targets. Together, we here present several novel candidate human targets of miR-BART10-3p, thereby increasing the understanding of miR-BART10-3p in colon cancer.
A miR-205-5p/GGCT/CD44 axis controls the progression of papillary thyroid cancer
Authors: Li Han-ning , Zhang Hui-min , Li Xing-rui , Wang Jun , Xu Tao , Li Shu-yu , Dong Meng-lu , Wang Ge , Cui Xiao-qing , Yang Xue , Wu Yong-lin , Liao Xing-hua , Du Ya-ying
Published: October 2021

Background

Papillary thyroid cancer (PTC) is the most common endocrine malignancy, despite marked achieves in recent decades, the mechanisms underlying the pathogenesis and progression for PTC are incomplete. Accumulating evidence shows that γ-glutamylcyclotransferase (GGCT), an enzyme participated in glutathione homeostasis that is elevated in multiple types of tumors, represents an attractive therapeutic target.
Methods

Bioinformatics, immunohistochemistry (IHC), qRT-PCR and western blot (WB) assays were used to determine the elevation of GGCT in PTC. The biological functions of GGCT were examined using CCK8, wound healing and transwell assays. Subcutaneous xenograft and tail vein pulmonary metastatic mouse models were constructed to determine the effect of GGCT on tumorigenicity and metastasis in vivo. The effect of miR-205-5p on GGCT and the relationship between these two molecules were examined by dual luciferase reporter assay, RNA-RNA pull down assay as well as the rescue experiments both in vitro and in vivo. The interaction between GGCT and CD44 was assessed by co-immunoprecipitation (Co-IP) and IHC assays.
Results

Our results showed that GGCT expression is upregulated in PTC, correlates with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the cell proliferation, migratory and invasion ability of PTC cells and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP-2 and MMP9) while increased epithelial marker (E-cadherin) in PTC cells. We confirmed binding of miR-205-5p on the 3’-UTR regions of GGCT and delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found GGCT interacted with and stabilized CD44 in PTC cells.
Conclusions

Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.
Do COVID-19 Pandemic-Related Behavior Changes Affect Perioperative Respiratory Adverse Events in Children Undergoing Cardiac Interventional Catheterization?
Authors: Ji Wei , Zhang Kan , Li Mengqi , Wang Siyuan , Sun Liping , Huang Yue , Bai Jie , Zhang Mazhong , Zheng Jijian
Published: October 2021

Background: The Novel Coronavirus Disease (COVID-19) pandemic-related behavior changes could affect the perioperative respiratory adverse events in children with congenital heart disease (CHD). This study was designed to compare the incidence of perioperative respiratory adverse events (PRAEs) in children with and without upper respiratory infection (URI) undergoing the cardiac catheterization before and during COVID-19 pandemic.Methods：COVID-19 was outbreak in January 2020 in China. 260 pediatric patients scheduled for elective therapeutic cardiac catheterization were included from January 2019 to March 2021 and 154 were completed during the pandemic. Recent URI was diagnosed by the attending anesthesiologist owing to different PRAEs incidence in non-URI and URI children. The overall incidence of PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) in non-URI and URI children undergoing the elective cardiac catheterization were compared before and during the COVID-19 pandemic. Logistic regression model was fitted to identify the potential risk factors associated with PRAEs.Results: Of 564 children enrolled, 359 completed the study and was analyzed finally. URI incidence decreased substantially during the COVID-19 pandemic (14% vs. 41%, P<0.001). Meanwhile, the overall PRAEs also significantly declined no matter whether or not the child had recent URI (22.3% vs. 42.3%, P=0.001 for non-URI and 29.2% vs. 58.7%, P=0.012 for URI respectively). Post-operative agitation in non-URI children occurred less frequently during the pandemic than before (2.3% vs. 16.2%, P=0.001). Behaviors before the COVID-19 pandemic (odd ratio=2.84, 95%CI 1.76 to 4.58) and recent URI (odd ratio =1.79, 95%CI 1.09 to 2.92) were associated with the PRAEs.Conclusions: COVID-19 pandemic-related behavior changes were associated with the reduction of PRAEs in non-URI and URI children undergoing elective therapeutic cardiac catheterization.
Modification of Mesenchymal Stem Cells by HMGB1 Promotes the Activity of Cav3.2 T-type Calcium Channel via PKA/β-catenin/γ-cystathionase Pathway
Authors: Wu Hao , Xie Xiaodong , Sun Mingyang , Chen Min , Tao Xuan , Fang Xin , Meng Xiaohu , Wei Wei , Yu Min
Published: October 2021

Background: Mesenchymal stem cells (MSC) hold great promise for treating cardiovascular disease. Recently, we genetically modified MSCs with high mobility group box 1 (HMGB1), and these cells demonstrated high mobility by efficient migrating and homing to target neointima. The possible mechanism was investigated in the current study. Methods: Rat MSCs were transfected with lentivirus containing HMGB1 cDNA to yield MSC-H cell line stably overexpressing HMGB1. The MSC-C cells which were transfected with empty lentivirus served as negative control, and the differentially expressed genes were analyzed by microarray. The cell mobility was determined by transwell migration assay. Intracellular free calcium and the expression of Cav3.2 T-type calcium channel (CACNA1H) were assayed to analyze activity of CACNA1H-mediated calcium influx. H2S production and γ-cystathionase expression were examined to assess the activity of γ-cystathionase/H2S signaling. The interaction of HMGB1 with γ-cystathionase in MSC-H cells was analyzed by co-immunoprecipitation. Luciferase reporter assay was performed to determine whether the promoter activity of γ-cystathionase was regulated by interaction of β-catenin and TCF/LEF binding site. Intercellular cAMP, PKA activity, phosphorylation of β-catenin and GSK3β were investigated to reveal cAMP/PKA mediated β-catenin activation. Result: Microarray analysis revealed that differentially expressed genes were enriched in cAMP signaling and calcium signaling. CACNA1H was upregulated to increase intracellular free calcium and MSC-H cell migration. Blockage of CACNA1H by ABT-639 significantly reduced intracellular free calcium and cell migration. The γ-cystathionase/H2S signaling was responsible for CACNA1H activation. H2S production was increased with high expression of γ-cystathionase in MSC-H cells, which was blocked by γ-cystathionase inhibitor DL-propargylglycine. Upregulation of γ-cystathionase was not attributed to interaction with HMGB1 overexpressed in MSC-H cells although γ-cystathionase was suggested to co-immunoprecipitate with oxidized HMGB1. Bioinformatics analysis identified a conserved TCF/LEF binding site in the promoter of γ-cystathionase gene. Luciferase reporter assay confirmed that the promoter had positive response to β-catenin which was activated in MSC-H cells. Finally, cAMP/PKA was activated to phosphorylate β-catenin at Ser657 and GSK3β, enabling persisting activation of Wnt/β-catenin signaling in MSC-H cells. Conclusion: Our study revealed that modification of MSCs with HMGB1 promoted CACNA1H-mediated calcium influx via PKA/β-catenin/γ-cystathionase pathway. This was a plausible mechanism for high mobility of MSC-H cell line.
Assessment of neutrophil-lymphocyte ratios in patients with dry age-related macular degeneration
Authors: SANNAN NAIF , Ramadhan Majed , Elsayid Mohieldin Abass , Ghamdi Hanan Khalid Ahmad Al , Alghamdi Lamis Abdulkhaliq A , Alqahtani Maha Badr
Published: October 2021

Purpose

To assess the significance of neutrophil-lymphocyte ratio (NLR) as an indicator of inflammation in Saudi patients with dry age-related macular degeneration (AMD).
Study design:
A retrospective case-control study.
Methods

Clinical diagnosis along with complete blood count (CBC) results were extracted from hospital and laboratory information systems for patients with dry AMD and age- gender- matched controls attending the ophthalmology clinic at King Abdulaziz medical city, Jeddah, between January 2018 and December 2020. NLR was calculated by dividing the neutrophil by the lymphocyte count.
Results

This study captured 90 patients diagnosed with dry AMD and 270 control subjects without AMD. The mean of ages 70 and 71 years old for cases and controls, respectively. In univariate analysis, there were no significant differences in CBC results between cases and control. In NLR, dry AMD patients have a slightly higher mean than the control group; however, this increase was not statistically significant (P-value 0.8). In the NLR model, age and gender were statistically significant factors affecting the NLR values in dry AMD (P-value 0.03, 0.01 respectively).
Conclusion

as a systemic inflammatory biomarker, NLR alone could not predict dry AMD. However, the slight increase in the NLR values may be helpful if augmented with other laboratory measurements to aid in early disease prediction.
Circulating noncoding RNAs as early predictive biomarkers in preeclampsia: A diagnostic meta-analysis
Authors: Su Sha , Yang Fang , Zhong Linlin , Pang lihong
Published: October 2021

Background
We designed a meta-analysis to evaluate the clinical significance and efficacy of circulating noncoding RNAs (ncRNAs) in the early prediction of preeclampsia.
Methods
PubMed, Embase and the Cochrane Library were used to search for literature. The combined prediction performance was evaluated by calculating the area under the summary receiver operator characteristic (SROC) curve. The potential sources of heterogeneity were analysed by meta-regression analysis and subgroup analysis. All statistical analyses and mapping were performed by RevMan 5.3 and Stata 12.0.
Results
A total of 41 studies from 14 articles, including 557 preeclampsia patients and 842 controls, were included in our meta-analysis. All studies collected blood before onset. NcRNAs in blood performed relatively well in predicting preeclampsia. The combined sensitivity was 0.71, the specificity was 0.84, and the area under the SROC curve (AUC) was 0.86. Peripheral blood mononuclear cells (PBMC) samples showed the best diagnostic accuracy. The combined AUC was 0.93. Combined detection was better than single detection, and miRNA was better than circRNA. The heterogeneity of the study was determined by sample size, lncRNA characteristics, lncRNA source and race.
Conclusion
Circulating ncRNAs can be used as noninvasive early predictive biomarkers of preeclampsia and have great clinical application prospects. Its clinical value needs to be tested by further multicentre, comprehensive and prospective studies, and the test criteria should be established.
Assessment of Estradiol, Progesterone and Lipid Profile among Breast Cancer Patients in Ethiopia: Hospital-based Comparative Cross-Sectional Study
Authors: Tadesse Etagegn , Seifu Daniel , Menon Menakath , Tigeneh Wondmagegnehu , Obsa Teka , Neges Bikila , Mehdi Mohammed
Published: October 2021

Background

Breast cancer is the most often diagnosed type of cancer and the leading cause of death worldwide. Estrogen, also known as estradiol, influences progesterone metabolism and modifies lipid metabolism. Thus, steroid hormone and lipid profile levels for breast cancer patients must be evaluated. However, this has yet to be explored and used for therapy in Ethiopia. As a result, the present study at Tikur Anbessa Specialized Hospital attempted to assess serum estrogen, progesterone, and lipid profile levels in breast cancer patients and healthy controls.
Methods

A hospital-based comparative cross-sectional study was conducted on a total of 80 participants (40 newly diagnosed breast cancer patients and 40 healthy control females). A convenient sampling method was used to recruit the study participants. Steroid hormones and lipid profile were determined using immunoassays and an enzymatic colorimetric technique, respectively. SPSS version 20.0 was used for statistical analysis, and p-values of 0.05 were considered statistically significant.
Results

When compared to healthy controls, the mean serum progesterone, TC, and HDL-C levels in breast cancer patients were considerably lower, while estradiol, TG, and LDL-C levels were insignificantly higher.
Conclusions

Breast cancer may be to blame for changes in progesterone, estradiol, and lipid profile levels, which can lead to secondary problems.
Impacts of Microplastics on Marine Organisms and in Human Health
Authors: Bhuyan Md. Simul , Nabi Md. Rashed-Un , Alam Md. Wahidul , Islam Md. Nazrul , Cáceres-Farías Lenin , Bat Levent , Musthafa Mohamed Saiyad , Chung Sang Yong , Senapathi Venkatramanan , Alfaro-Núñez Alonzo
Published: October 2021

The ubiquitous presence of microplastics (MPs) across all oceans has emerged as a significant marine hazard as worldwide plastic production continues to grow. Now and during the next 20-30 years will be the time to confront the implications of the plastic industry's rise, which has resulted in the large-scale global production of millions of plastic-based items, varying from a single pen to automobiles. Inappropriate management, lack of awareness of the detrimental effects, reckless universal use, and the indiscriminate disposal of plastic based synthetic materials, has turned Earth into a "plastic planet”. It is critical to have a throughout understanding of MPs' potential from sink to source as well as the processes that govern their distribution and uptake and exchange in ecosystems, to properly comprehend their potential consequences and ecological harm. The goal of the present study was to identify the scenarios of microplastics structure, functions and subsequent impact to the marine organisms. Diversified origins of MPs in the oceans and their negative effects on marine animals have been discussed critically in this review. Because of their small size, these plastic particles are easily ingested by a wide range of marine life (e.g., fish, Mollusca, Arthropoda, Annelida, Echinodermata, Nematoda, phytoplankton, zooplankton, algae, birds, Mammalia, marine reptiles, and coral), putting their health at risk. The ability of MPs to absorb a variety of dangerous hydrophobic chemicals from the environment directly transfers these toxins into the food chain. As a result, many laws and rules have been created to address the major issue of MP pollution in the marine ecosystem and it must be improved and implemented worldwide. To avert future dangers, it is critical to stop producing it and replace it with environmentally suitable alternatives.
Prevalence and Predictors of Delayed Initiation of Breastfeeding Among Postnatal Women at a Tertiary Hospital in Eastern Uganda: a Cross-Sectional Study
Authors: Kusasira Loyce , Mukunya David , Samuel Obakiro , Kenedy Kiyimba , Rebecca Nekaka , Ssenyonga Lydia , Immaculate Mbwali , Agnes Napyo
Published: October 2021

BackgroundThe rates for the delayed initiation of breastfeeding in Uganda remain unacceptably high and reasons for this are not well understood. We aimed to determine the prevalence and predictors for the delayed initiation of breastfeeding in Eastern Uganda. MethodsThis study employed a cross-sectional study design. A total of 404 mother-infant pairs were enrolled onto the study between July and November, 2020 at Mbale regional referral hospital (MRRH). They were interviewed on socio-demographic related, infant-related, labour and delivery characteristics using a structured questionnaire. We estimated adjusted odds ratios using multivariable logistic regression models.Results. The rate of delayed initiation of breastfeeding was 70% (n=283/404, 95% CI: 65.3% – 74.4%). The factors that were associated with delayed initiation of breastfeeding were maternal charateristics including: being single (AOR=0.37; 95%CI: 0.19 – 0.74), receiving antenatal care for less than 3 times while pregnant (AOR=1.85, 95%CI: 1.07 – 3.19) undergoing a caesarean section (AOR= 2.07; 95%CI: 1.3 – 3.19) and having a difficult labour (AOR=2.05; 95%CI: 1.25 – 3.35). Infant characteristics included: having a health issue at birth (AOR=9.8; 95%CI: 2.94 – 32.98).Conclusions:The proportion of infants that do not achieve early initiation of breastfeeding in this setting remains high. Women at high risk of delaying the initiation of breastfeeding include those who: deliver by caesarean section, do not receive antenatal care and have labour difficulties. Infants at risk of not achieving early initiation of breastfeeding include those that have a health issue at birth. We recommend increased support for women who undergo caesarean section in the early initiation of breastfeeding. Breastfeeding support can be initiated in the recovery room after caesarean delivery or in the operating theatre. The importance of antenatal care attendance should be emphasized during health education classes.
The rhizosphere microbiota of the zinc and cadmium hyperaccumulators Arabidopsis halleri and Noccaea caerulescens is highly convergent in Prayon (Belgium)
Authors: Bertrand Amandine R. , Detry Emilie , Nouet Cécile , Hanikenne Marc , BAURAIN Denis
Published: October 2021

The Prayon site is known as a zinc-polluted area where two zinc and cadmium hyperaccumulator plant species currently coexist, although Arabidopsis halleri was introduced more recently than Noccaea caerulescens . While soil microorganisms may influence metal uptake, the microbial community present in the rhizosphere of hyperaccumulators remains poorly known. Plants of both species were sampled with their bulk and rhizosphere soil from different plots of the Prayon site. Soil components (ionome, pH, water composition, temperature) were analyzed, as well as shoot ionome and expression levels of metal transporter genes ( HMA3 , HMA4 , ZIP4 / ZNT1 , ZIP6 , MTP1 ). The taxonomic diversity of the microorganisms in soil samples was then determined by 16S rRNA metabarcoding and compared at the Operational Taxonomy Unit (OTU) level and across different taxonomic levels. Our elemental analyses confirmed that the site is still highly contaminated with zinc and cadmium and that both plant species indeed hyperaccumulate these elements in situ . Although the pollution is overall high, it is heterogenous at the site scale and correlates with the expression of some metal transporter genes. Metabarcoding analyses revealed a decreasing gradient of microbial diversity, with more OTUs discovered in the rhizosphere than in the soil bulk, especially at the bottom of the cores. However, the variability gradient increases with the distance from roots. Using an ad hoc pseudo-taxonomy to bypass the biases caused by a high proportion of unclassified and unknown OTUs, we identified Chloroflexi, Armatimonadetes, Pirellulaceae, Gemmatimonadetes and Chitinophagaceae as the drivers of the differences in the gradient along the cores. In contrast, no significant difference was identified between the rhizosphere composition of A. halleri and N. caerulescens . This suggests that, despite their distinct colonization history in Prayon, the two plant species have now recruited highly convergent microbial communities in the rhizosphere.
Complexity In The Context of Palliative Care: A Scoping Review
Authors: Ohinata Hironori , Aoyama Maho , Miyashita Mitsunori
Published: October 2021

Background: Understanding the factors of complexity of patients in palliative care is very important for healthcare providers in addressing the care needs of their patients. However, the healthcare providers’ perception of the factors of complexity in palliative care lacks a common understanding. This study aimed to determine the scope of research activities and specific factors of complexity in the context of palliative care.Methods: A scoping literature review was performed, following the methods described by the Joanna Briggs Institute. We conducted an electronic literature search in MEDLINE (Ovid), PsycINFO, Web of Science Core Collection, and CINAHL, examining literature from May 1972 to 2020.Results: We identified 32 peer-reviewed articles published in English before 2020. The target literature mainly originated in Europe and the United States. The research methods included quantitative studies (n=13), qualitative studies (n=12), case studies (n=3), and reviews (n=4). We reviewed 32 studies and summarized the factors of complexity into three levels: the patient’s level, the healthcare setting level, and the socio-cultural landscape level. We identified factors affecting patient-specific complexity, including sex, race, age, living situation, family burden, resources, treatment, decision-making, communication, prognosis, disease, and comorbidity/complexity. Other factors identified as contributing to patient complexity were the interaction of physical, psychological, social, and spiritual categories, as well as the healthcare providers’ confidence and skills, and the socio-cultural components.Conclusions: This scoping review shows specific factors of complexity and future challenges in the context of palliative care. Future research should include the factors of complexity identified in this review and conduct longitudinal studies on the interactions among them. In addition, it is necessary to examine specific complexity factors in patients from various social and ethnic backgrounds.
(Pre)Diabetes, Greater Glycemia, and Greater Daily Glucose Variability are Associated with Lower Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration and Precursor of Diabetic Retinopathy– The Maastricht Study
Authors: Heide Frank CT van der , Foreman Yuri , Franken Iris , Henry Ronald , Kroon Abraham , Dagnelie pieter , Eussen Simone , Berendschot Tos , Schouten Jan , Webers Carroll , Schram Miranda , kallen Carla van der , Greevenbroek Marleen van , Wesselius Anke , Schalkwijk Casper , Schaper Nicolaas , Brouwers Martijn , Stehouwer Coen
Published: October 2021

ObjectiveDiabetic retinopathy in type 2 diabetes is preceded by retinal nerve fiber layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), measures of glycemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance.Research design and methods We used cross-sectional data from The Maastricht Study (up to 5,455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycemia (fasting plasma glucose [FPG], 2-hour post-load glucose [2-h PG], HbA1c, advanced glycation endproducts [AGEs] assessed as skin autofluorescence [SAF]) and indices of daily GV (incremental glucose peak [IGP] and continuous glucose monitoring [CGM]-assessed standard deviation [SD]) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycemia. Results After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta [95%CI], respectively -0.16[-0.25;-0.08]; -0.05[-0.13;0.03]; Ptrend=0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP and CGM-assessed SD were also associated with lower RNFL thickness (per SD, respectively -0.05 [-0.08; -0.01]; -0.06 [-0.09; -0.02]; -0.05 [-0.08; -0.02]; -0.04 [-0.07; -0.01]; -0.06 [-0.12; -0.01]; and -0.07 [-0.21; 0.07]).Conclusion In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of diabetic retinopathy.