bluuebunny/crossref_metadata_2025 huggingface dataset:
The curious case of genome packaging and assembly in RNA viruses infecting plants
Authors: Ranjan Tushar , Ranjan Kumar Ravi , Ansar Mohammad , Kumar Jitesh , Mohanty Auroshikha , Kumari Anamika , Jain Khushbu , Rajani Kumari , Dei Sailabala , Ahmad Mohammad Feza
Published: June 2023

Genome packaging is the crucial step for maturation of plant viruses containing an RNA genome. Viruses exhibit a remarkable degree of packaging specificity, despite the probability of co-packaging cellular RNAs. Three different types of viral genome packaging systems are reported so far. The recently upgraded type I genome packaging system involves nucleation and encapsidation of RNA genomes in an energy-dependent manner, which have been observed in most of the plant RNA viruses with a smaller genome size, while type II and III packaging systems, majorly discovered in bacteriophages and large eukaryotic DNA viruses, involve genome translocation and packaging inside the prohead in an energy-dependent manner, i.e., utilizing ATP. Although ATP is essential for all three packaging systems, each machinery system employs a unique mode of ATP hydrolysis and genome packaging mechanism. Plant RNA viruses are serious threats to agricultural and horticultural crops and account for huge economic losses. Developing control strategies against plant RNA viruses requires a deep understanding of their genome assembly and packaging mechanism. On the basis of our previous studies and meticulously planned experiments, we have revealed their molecular mechanisms and proposed a hypothetical model for the type I packaging system with an emphasis on smaller plant RNA viruses. Here, in this review, we apprise researchers the technical breakthroughs that have facilitated the dissection of genome packaging and virion assembly processes in plant RNA viruses.
Knowledge of fertility and perception of fertility treatment among adults with sickle cell disease (KNOW FERTILITY)
Authors: Carrithers Bria , Raja Maidah , Gemmill Alison , Cayton Vaught Kamaria C. , Christianson Mindy S. , Lanzkron Sophie , Pecker Lydia H.
Published: June 2023

Introduction

This study assessed fertility knowledge in adults with sickle cell disease using the Cardiff Fertility Knowledge Scale and Fertility Treatment Perception Survey and compared knowledge scores in respondents with sickle cell disease to previously reported unaffected cohorts.

Methods

This cross-sectional study surveyed adults over age 18 with sickle cell disease at an adult sickle cell disease center using a 35-question survey addressing infertility risk factor knowledge and perceptions of fertility treatment. Analyses included summary statistics for continuous and categorical variables, univariate linear regression, and Mann-Whitney U tests for group comparisons of Fertility Knowledge Scale scores. Fertility Treatment Perception Survey scores were measured by medians of the two positive statements and four negative statements to generate separate positive and negative treatment belief scores. Statistical significance was set at p < 0.05 for all analyses.

Results

Ninety-two respondents (71 female, 21 male) with median age of 32 years (IQR: 25.0, 42.5) completed the survey between October 2020-May 2021. Sixty-five percent of respondents reported taking sickle cell disease treatment and 18% reported refusing at least one sickle cell disease treatment due to fertility concerns. The mean Fertility Knowledge Score was 49% (SD: 5.2), lower than reported in an international cohort (57% vs. 49%, p = 0.001), and higher than in a cohort of reproductive-aged Black women in the USA (49% vs. 38%, p = 0.001). Less than 50% of respondents correctly identified common infertility risk factors including sexually transmitted infections, advanced age, and obesity. Mean positive fertility perception score was 3 (IQR 3, 4), and negative fertility perception score was 3.5 (IQR 3, 4). Factors associated with agreement with negative fertility perception statements included: trying to conceive, refusing sickle cell disease treatment, and undergoing fertility treatment.

Discussion

Opportunities exist to improve knowledge of infertility risk factors among adults with sickle cell disease. This study raises the possibility that nearly one in five adults with sickle cell disease refuse SCD treatment or cure due to infertility concerns. Education about common infertility risks factors needs to be addressed alongside disease- and treatment- associated fertility risks.
Genetic insights into immune mechanisms of Alzheimer’s and Parkinson’s disease
Authors: Nott Alexi , Holtman Inge R.
Published: June 2023

Microglia, the macrophages of the brain, are vital for brain homeostasis and have been implicated in a broad range of brain disorders. Neuroinflammation has gained traction as a possible therapeutic target for neurodegeneration, however, the precise function of microglia in specific neurodegenerative disorders is an ongoing area of research. Genetic studies offer valuable insights into understanding causality, rather than merely observing a correlation. Genome-wide association studies (GWAS) have identified many genetic loci that are linked to susceptibility to neurodegenerative disorders. (Post)-GWAS studies have determined that microglia likely play an important role in the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The process of understanding how individual GWAS risk loci affect microglia function and mediate susceptibility is complex. A rapidly growing number of publications with genomic datasets and computational tools have formulated new hypotheses that guide the biological interpretation of AD and PD genetic risk. In this review, we discuss the key concepts and challenges in the post-GWAS interpretation of AD and PD GWAS risk alleles. Post-GWAS challenges include the identification of target cell (sub)type(s), causal variants, and target genes. Crucially, the prediction of GWAS-identified disease-risk cell types, variants and genes require validation and functional testing to understand the biological consequences within the pathology of the disorders. Many AD and PD risk genes are highly pleiotropic and perform multiple important functions that might not be equally relevant for the mechanisms by which GWAS risk alleles exert their effect(s). Ultimately, many GWAS risk alleles exert their effect by changing microglia function, thereby altering the pathophysiology of these disorders, and hence, we believe that modelling this context is crucial for a deepened understanding of these disorders.
Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation
Authors: Yin Run , Zhang Kailing , Li Yingming , Tang Zilei , Zheng Ruiyu , Ma Yue , Chen Zonghan , Lei Na , Xiong Lei , Guo Peixin , Li Gang , Xie Yuhuan
Published: June 2023

Depression is a complex and biologically heterogeneous disorder. Recent studies have shown that central nervous system (CNS) inflammation plays a key role in the development of depression. Lipopolysaccharide (LPS)-induced depression-like model in mice is commonly used to studying the mechanisms of inflammation-associated depression and the therapeutic effects of drugs. Numerous LPS-induced depression-like models in mice exist and differ widely in animal characteristics and methodological parameters. Here, we systematically reviewed studies on PubMed from January 2017 to July 2022 and performed cardinal of 170 studies and meta-analyses of 61 studies to support finding suitable animal models for future experimental studies on inflammation-associated depression. Mouse strains, LPS administration, and behavioral outcomes of these models have been assessed. In the meta-analysis, forced swimming test (FST) was used to evaluate the effect size of different mouse strains and LPS doses. The results revealed large effect sizes in ICR and Swiss mice, but less heterogeneity in C57BL/6 mice. For LPS intraperitoneal dose, the difference did not affect behavioral outcomes in C57BL/6 mice. However, in ICR mice, the most significant effect on behavioral outcomes was observed after the injection of 0.5 mg/kg LPS. Our results suggests that mice strains and LPS administration play a key role in the evaluation of behavioral outcomes in such models.
DNAM-1 chimeric receptor-engineered NK cells: a new frontier for CAR-NK cell-based immunotherapy
Authors: Cifaldi Loredana , Melaiu Ombretta , Giovannoni Roberto , Benvenuto Monica , Focaccetti Chiara , Nardozi Daniela , Barillari Giovanni , Bei Roberto
Published: June 2023

DNAM-1 is a major NK cell activating receptor and, together with NKG2D and NCRs, by binding specific ligands, strongly contributes to mediating the killing of tumor or virus-infected cells. DNAM-1 specifically recognizes PVR and Nectin-2 ligands that are expressed on some virus-infected cells and on a broad spectrum of tumor cells of both hematological and solid malignancies. So far, while NK cells engineered for different antigen chimeric receptors (CARs) or chimeric NKG2D receptor have been extensively tested in preclinical and clinical studies, the use of DNAM-1 chimeric receptor-engineered NK cells has been proposed only in our recent proof-of-concept study and deserves further development. The aim of this perspective study is to describe the rationale for using this novel tool as a new anti-cancer immunotherapy.
Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells
Authors: Busch Catharina , Rau Saskia , Sekulic Andjela , Perie Luce , Huber Christian , Gehrke Miranda , Joussen Antonia M. , Zipfel Peter F. , Wildner Gerhild , Skerka Christine , Strauß Olaf
Published: June 2023

Purpose

Polymorphisms in complement genes are risk-associated for age-related macular degeneration (AMD). Functional analysis revealed a common deficiency to control the alternative complement pathway by risk-associated gene polymorphisms. Thus, we investigated the levels of terminal complement complex (TCC) in the plasma of wet AMD patients with defined genotypes and the impact of the complement activation of their plasma on second-messenger signaling, gene expression, and cytokine/chemokine secretion in retinal pigment epithelium (RPE) cells.

Design

Collection of plasma from patients with wet AMD (n = 87: 62% female and 38% male; median age 77 years) and controls (n = 86: 39% female and 61% male; median age 58 years), grouped for risk factor smoking and genetic risk alleles CFH 402HH and ARMS2 rs3750846, determination of TCC levels in the plasma, in vitro analysis on RPE function during exposure to patients’ or control plasma as a complement source.

Methods

Genotyping, measurement of TCC concentrations, ARPE-19 cell culture, Ca2+ imaging, gene expression by qPCR, secretion by multiplex bead analysis of cell culture supernatants.

Main outcome measures

TCC concentration in plasma, intracellular free Ca2+, relative mRNA levels, cytokine secretion.

Results

TCC levels in the plasma of AMD patients were five times higher than in non-AMD controls but did not differ in plasma from carriers of the two risk alleles. Complement-evoked Ca2+ elevations in RPE cells differed between patients and controls with a significant correlation between TCC levels and peak amplitudes. Comparing the Ca2+ signals, only between the plasma of smokers and non-smokers, as well as heterozygous (CFH 402YH) and CFH 402HH patients, revealed differences in the late phase. Pre-stimulation with complement patients’ plasma led to sensitization for complement reactions by RPE cells. Gene expression for surface molecules protective against TCC and pro-inflammatory cytokines increased after exposure to patients’ plasma. Patients’ plasma stimulated the secretion of pro-inflammatory cytokines in the RPE.

Conclusion

TCC levels were higher in AMD patients but did not depend on genetic risk factors. The Ca2+ responses to patients’ plasma as second-messenger represent a shift of RPE cells to a pro-inflammatory phenotype and protection against TCC. We conclude a substantial role of high TCC plasma levels in AMD pathology.
A novel predictive model for the recurrence of pediatric alopecia areata by bioinformatics analysis and a single-center prospective study
Authors: Zheng Yuanquan , Nie Yingli , Lu Jingjing , Yi Hong , Fu Guili
Published: June 2023

Background

Alopecia areata (AA) is a disease featured by recurrent, non-scarring hair loss with a variety of clinical manifestations. The outcome of AA patients varies greatly. When they progress to the subtypes of alopecia totalis (AT) or alopecia universalis (AU), the outcome is unfavorable. Therefore, identifying clinically available biomarkers that predict the risk of AA recurrence could improve the prognosis for AA patients.

Methods

In this study, we conducted weighted gene co-expression network analysis (WGCNA) and functional annotation analysis to identify key genes that correlated to the severity of AA. Then, 80 AA children were enrolled at the Department of Dermatology, Wuhan Children’s Hospital between January 2020 to December 2020. Clinical information and serum samples were collected before and after treatment. And the serum level of proteins coded by key genes were quantitatively detected by ELISA. Moreover, 40 serum samples of healthy children from the Department of Health Care, Wuhan Children’s Hospital were used for healthy control.

Results

We identified four key genes that significantly increased (CD8A, PRF1, and XCL1) or decreased (BMP2) in AA tissues, especially in the subtypes of AT and AU. Then, the serum levels of these markers in different groups of AA patients were detected to validate the results of bioinformatics analysis. Similarly, the serum levels of these markers were found remarkedly correlated with the Severity of Alopecia Tool (SALT) score. Finally, a prediction model that combined multiple markers was established by conducting a logistic regression analysis.

Conclusion

In the present study, we construct a novel model based on serum levels of BMP2, CD8A, PRF1, and XCL1, which served as a potential non-invasive prognostic biomarker for forecasting the recurrence of AA patients with high accuracy.
Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo
Authors: Meng Shuai , Xu Zengping , Wang Xueming , Liu Yang , Li Bole , Zhang Jie , Zhang Xiaolong , Liu Tianjun
Published: June 2023

For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.
Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis
Authors: Spain Rebecca I. , Hildebrand Andrea , Waslo Carin S. , Rooney William D. , Emmons Joshua , Schwartz Daniel L. , Freedman Mark S. , Paz Soldan M. Mateo , Repovic Pavle , Solomon Andrew J. , Rinker John , Wallin Mitchell , Haselkorn Jodie K. , Stuve Olaf , Gross Robert H. , Turner Aaron P.
Published: June 2023

Background

Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates.

Objectives

This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes.

Design

The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028).

Methods

Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts.

Results

Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0–6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses.

Conclusion

Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.
Ultrasound radiomics nomogram for predicting large-number cervical lymph node metastasis in papillary thyroid carcinoma
Authors: Zhang Meiwu , Zhang Yan , Wei Huilin , Yang Liu , Liu Rui , Zhang Baisong , Lyu Shuyi
Published: June 2023

Purpose

To evaluate the value of preoperative ultrasound (US) radiomics nomogram of primary papillary thyroid carcinoma (PTC) for predicting large-number cervical lymph node metastasis (CLNM).

Materials and methods

A retrospective study was conducted to collect the clinical and ultrasonic data of primary PTC. 645 patients were randomly divided into training and testing datasets according to the proportion of 7:3. Minimum redundancy-maximum relevance (mRMR) and least absolution shrinkage and selection operator (LASSO) were used to select features and establish radiomics signature. Multivariate logistic regression was used to establish a US radiomics nomogram containing radiomics signature and selected clinical characteristics. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was assessed by decision curve analysis (DCA). Testing dataset was used to validate the model.

Results

TG level, tumor size, aspect ratio, and radiomics signature were significantly correlated with large-number CLNM (all P< 0.05). The ROC curve and calibration curve of the US radiomics nomogram showed good predictive efficiency. In the training dataset, the AUC, accuracy, sensitivity, and specificity were 0.935, 0.897, 0.956, and 0.837, respectively, and in the testing dataset, the AUC, accuracy, sensitivity, and specificity were 0.782, 0.910, 0.533 and 0.943 respectively. DCA showed that the nomogram had some clinical benefits in predicting large-number CLNM.

Conclusion

We have developed an easy-to-use and non-invasive US radiomics nomogram for predicting large-number CLNM with PTC, which combines radiomics signature and clinical risk factors. The nomogram has good predictive efficiency and potential clinical application value.
Feasibility study of adaptive radiotherapy for esophageal cancer using artificial intelligence autosegmentation based on MR-Linac
Authors: Wang Huadong , Liu Xin , Song Yajun , Yin Peijun , Zou Jingmin , Shi Xihua , Yin Yong , Li Zhenjiang
Published: June 2023

Objective

We proposed a scheme for automatic patient-specific segmentation in Magnetic Resonance (MR)-guided online adaptive radiotherapy based on daily updated, small-sample deep learning models to address the time-consuming delineation of the region of interest (ROI) in the adapt-to-shape (ATS) workflow. Additionally, we verified its feasibility in adaptive radiation therapy for esophageal cancer (EC).

Methods

Nine patients with EC who were treated with an MR-Linac were prospectively enrolled. The actual adapt-to-position (ATP) workflow and simulated ATS workflow were performed, the latter of which was embedded with a deep learning autosegmentation (AS) model. The first three treatment fractions of the manual delineations were used as input data to predict the next fraction segmentation, which was modified and then used as training data to update the model daily, forming a cyclic training process. Then, the system was validated in terms of delineation accuracy, time, and dosimetric benefit. Additionally, the air cavity in the esophagus and sternum were added to the ATS workflow (producing ATS+), and the dosimetric variations were assessed.

Results

The mean AS time was 1.40 [1.10–1.78 min]. The Dice similarity coefficient (DSC) of the AS model gradually approached 1; after four training sessions, the DSCs of all ROIs reached a mean value of 0.9 or more. Furthermore, the planning target volume (PTV) of the ATS plan showed a smaller heterogeneity index than that of the ATP plan. Additionally, V5 and V10 in the lungs and heart were greater in the ATS+ group than in the ATS group.

Conclusion

The accuracy and speed of artificial intelligence–based AS in the ATS workflow met the clinical radiation therapy needs of EC. This allowed the ATS workflow to achieve a similar speed to the ATP workflow while maintaining its dosimetric advantage. Fast and precise online ATS treatment ensured an adequate dose to the PTV while reducing the dose to the heart and lungs.
Diagnostic and prognostic role of circRNAs in pancreatic cancer: a meta-analysis
Authors: Zhao Ruihua , Han Zhuo , Zhou Haiting , Xue Yaru , Chen Xiaobing , Cao Xinguang
Published: June 2023

Background

Circular RNAs (circRNAs) are types of endogenous noncoding RNAs produced by selective splicing that are expressed highly specifically in various organisms and tissues and have numerous clinical implications in the regulation of cancer development and progression. Since circRNA is resistant to digestion by ribonucleases and has a long half-life, there is increasing evidence that circRNA can be used as an ideal candidate biomarker for the early diagnosis and prognosis of tumors. In this study, we aimed to reveal the diagnostic and prognostic value of circRNA in human pancreatic cancer (PC).

Methods

A systematic search for publications from inception to 22 July 2022 was conducted on Embase, PubMed, Web of Science (WOS), and the Cochrane Library databases. Available studies that correlated circRNA expression in tissue or serum with the clinicopathological, diagnostic, and prognostic values of PC patients were enrolled. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to evaluate clinical pathological characteristics. Area under the curve (AUC), sensitivity, and specificity were adopted to assess diagnostic value. Hazard ratios (HRs) were utilized to assess disease-free survival (DFS) and overall survival (OS).

Results

This meta-analysis enrolled 32 eligible studies, including six on diagnosis and 21 on prognosis, which accounted for 2,396 cases from 245 references. For clinical parameters, high expression of carcinogenic circRNA was significantly associated with degree of differentiation (OR = 1.85, 95% CI = 1.47–2.34), TNM stage (OR = 0.46, 95% CI = 0.35–0.62), lymph node metastasis (OR = 0.39, 95% CI = 0.32–0.48), and distant metastasis (OR = 0.26, 95% CI = 0.13–0.51). As for clinical diagnostic utility, circRNA could discriminate patients with pancreatic cancer from controls, with an AUC of 0.86 (95% CI: 0.82–0.88), a relatively high sensitivity of 84%, and a specificity of 80% in tissue. In terms of prognostic significance, carcinogenic circRNA was correlated with poor OS (HR = 2.00, 95% CI: 1.76–2.26) and DFS (HR = 1.96, 95% CI: 1.47–2.62).

Conclusion

In summary, this study demonstrated that circRNA may act as a significant diagnostic and prognostic biomarker for pancreatic cancer.
Breast self-examination practice and associated factors among women of reproductive age in southeast Ethiopia
Authors: Hussen Abduljewad , Kumbi Musa , Bedewi Jemal , Lette Abate , Nuriye Shemsu
Published: June 2023

Regular breast self-examination is the most cost-effective method for early detection of breast cancer, especially in resource-limited countries. However, breast self-examination practice was low among reproductive-age women.

Objective

This study aims to evaluate breast self-examination practice and associated factors among women of reproductive age in southeast Ethiopia.

Methods

A convergent parallel mixed-methods study design was conducted on 836 women of reproductive age. An interviewer-administered questionnaire was used for the quantitative part of the study and supplemented by focus group discussions. A database was created using Epi-info version 3.5.3, and analyzed using SPSS version 20. Bivariate and multivariable logistic regressions were done to examine the effect of explanatory variables. Variables with p-value <0.05 during multivariable logistic regressions were considered as significantly associated with the dependent variable. Thematic data analysis was carried out for the qualitative study.

Result

Out of 836 total participants, only 20.7% had ever heard about breast self-examination practice. Also, only 13.2% of the mothers had practiced breast self-examinations. Even though the majority of the participants during focused group discussions had knowledge about breast cancer screening, most of them stated that breast self-examination was not practiced among them. Maternal age, mother’s level of education, and previous history of breast examination by health professionals were significant predictors of breast self-examination practices.

Conclusion

This study reported a low prevalence of breast self-examination practice. Therefore, enhancing women’s education and encouraging breast examination by health professionals are essential to increase the proportion of women performing breast self-examination.
Reduced regional cerebral oxygen saturation increases risk for emergence delirium in pediatric patients
Authors: Li Lijing , Gao Zhengzheng , Zhang Jianmin , Zhang Fuzhou , Wang Fang , Wang Xiaoxue , Li Gan
Published: June 2023

Objectives

To assess whether decreased regional cerebral oxygen saturation (rScO2) is associated with the emergence delirium (ED) following general anesthesia in the pediatric population.

Methods

A retrospective observational cohort study was conducted on 113 children (ASA I–III) aged 2–14 years who underwent selective surgery under general anesthesia between 2022-01 and 2022-04. Intraoperatively, the rScO2 was monitored using a cerebral oximeter. The Pediatric Anesthesia Emergence Delirium (PAED) score was used to evaluate the patients for ED.

Results

The incidence of ED was 31%. Low rScO2 was reported in 41.6% of patients, who had a higher incidence of ED (P < 0.001) than those who did not experience desaturation. Logistic regression analysis revealed that decreased rScO2 was significantly associated with incident ED events [odds ratio (OR), 10.77; 95% confidence interval, 3.31–35.05]. Children under 3 years of age had a higher incidence of ED after rScO2 desaturation during anesthesia compared to older children (OR, 14.17 vs. 4.64).

Conclusion

Intraoperative rScO2 desaturation significantly increased the incidence of ED following general anesthesia. Monitoring should be enhanced to improve the oxygen balance in vital organs to improve the quality and safety of anesthesia.
Improved neonatal outcomes by multidisciplinary simulation—a contemporary practice in the demonstration area of China
Authors: Xu Chenguang , Zhang Qianshen , Xue Yin , Chow Chun-Bong , Dong Chunxiao , Xie Qian , Cheung Po-Yin
Published: June 2023

Background

Simulation-based training improves neonatal resuscitation and decreases perinatal mortality in low- and middle-income countries. Interdisciplinary in-situ simulation may promote quality care in neonatal resuscitation. However, there is limited information regarding the effect of multidisciplinary in-situ simulation training (MIST) on neonatal outcomes. We aimed to investigate the impact of MIST on neonatal resuscitation in reducing the incidence of neonatal asphyxia and related morbidities.

Methods

Weekly MIST on neonatal resuscitation has been conducted through neonatal and obstetrical collaboration at the University of Hong Kong-Shenzhen Hospital, China, since 2019. Each simulation was facilitated by two instructors and performed by three health care providers from obstetric and neonatal intensive care units, followed by a debriefing of the participants and several designated observers. The incidence of neonatal asphyxia, severe asphyxia, hypoxic-ischemic encephalopathy (HIE), and meconium aspiration syndrome (MAS) before (2017–2018) and after (2019–2020) the commencement of weekly MIST were analyzed.

Results

There were 81 simulation cases including the resuscitation of preterm neonates of different gestational ages, perinatal distress, meconium-stained amniotic fluid, and congenital heart disease with 1,503 participant counts (225 active participants). The respective incidence of neonatal asphyxia, severe asphyxia, HIE, and MAS decreased significantly after MIST (0.64%, 0.06%, 0.01%, and 0.09% vs. 0.84%, 0.14%, 0.10%, and 0.19%, respectively, all P < 0.05).

Conclusions

Weekly MIST on neonatal resuscitation decreased the incidence of neonatal asphyxia, severe asphyxia, HIE, and MAS. Implementation of regular resuscitation simulation training is feasible and may improve the quality of neonatal resuscitation with better neonatal outcomes in low- and middle-income countries.
Administration of protopine prevents mitophagy and acute lung injury in sepsis
Authors: Xiao Zhong , Long Juan , Zhang Jie , Qiu Zhimin , Zhang Chen , Liu Hongbing , Liu Xinyong , Wang Kang , Tang Yahui , Chen Longwang , Lu Zhongqiu , Zhao Guangju
Published: June 2023

Introduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an alkaloid with antiinflammatory and antioxidant properties. However, the function of PTP in septic ALI has not yet been documented. This work sought to investigate how PTP affected septic ALI and the mechanisms involved in septic lung damage, including inflammation, oxidative stress, apoptosis, and mitophagy.

Methods: Here, we established a mouse model induced by cecal ligation and puncture (CLP) and a BEAS-2B cell model exposed to lipopolysaccharide (LPS).

Results: PTP treatment significantly reduced mortality in CLP mice. PTP mitigated lung damage and reduced apoptosis. Western blot analysis showed that PTP dramatically reduced the expression of the apoptosis-associated protein (Cleaved Caspase-3, Cyto C) and increased Bcl-2/Bax. In addition, PTP decreased the production of inflammatory cytokines (IL-6, IL-1β, TNF-α), increased glutathione (GSH) levels and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels. Meanwhile, PTP significantly reduced the expression of mitophagy-related proteins (PINK1, Parkin, LC-II), and downregulated mitophagy by transmission electron microscopy. Additionally, the cells were consistent with animal experiments.

Discussion: PTP intervention reduced inflammatory responses, oxidative stress, and apoptosis, restored mitochondrial membrane potential, and downregulated mitophagy. The research shows that PTP prevents excessivemitophagy and ALI in sepsis, suggesting that PTP has a potential role in the therapy of sepsis.
Molecular mechanism of Hedyotis Diffusae Herba in the treatment of lupus nephritis based on network pharmacology
Authors: Yang Jinfei , Li Siying
Published: June 2023

Aims: To determine the bioactive components of Hedyotis Diffusae Herba (HDH) and the targets in treating lupus nephritis (LN), and so as to elucidate the protective mechanism of HDH against LN.

Methods and results: An aggregate of 147 drug targets and 162 LN targets were obtained from online databases, with 23 overlapped targets being determined as potential therapeutic targets of HDH against LN. Through centrality analysis, TNF, VEGFA and JUN were screened as core targets. And the bindings of TNF with stigmasterol, TNF with quercetin, and VEGFA with quercetin were further validated by molecular docking. By conducting Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses for drug targets, disease targets and the shared targets, TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway, etc., were found in all these three lists, indicating the potential mechanism of HDH in the treatment of LN.

Conclusion: HDH may ameliorate the renal injury in LN by targeting multi-targets and multi-pathways, including TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway and so on, which provided novel insights into further researches of the drug discovery in LN.
Safety and efficacy of stenting for symptomatic intracranial artery stenosis: a systematic reveiw and meta-analysis
Authors: Shi Ting , Chen ShiJian , Long YongPei , Gu ZhongDeng
Published: June 2023

Background: Stroke is currently the second-leading cause of death just behind ischaemic heart disease. Drug therapy is currently the standard of care for patients with symptomatic intracranial artery stenosis (sICAS). Stenting is an important treatment for the prevention and treatment of ischemic stroke. It has been suggested that vertebral artery stenting might reduce this risk, but operation-related complications limit the application of stenting in the treatment of ischemic stroke. The differences in the safety and efficacy of stenting combined with drugs and drugs alone in the treatment of sICAS are unclear. The aim of this study was to assess the impact of both treatment modalities on the prognosis of patients with sICAS through a systematic review and meta-analysis.

Methods: The Chinese databases (CNKI, Wanfang, VIP, CBM, DUXIU) and English databases (Pubmed, Embase, Ovid_medline, Cochrane library, Web of science)were searched to identify all studies describing sICAS. The “Risk of Bias Assessment” tool and the “Jadad Scale” provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Stata statistical software version 14.0.

Results: A total of 11 studies were included, comprising a total of 1,915 patients. The combined results of the study showed no significant difference between the incidence of transient cerebral ischemia (TIA)and stroke in patients with sICAS treated with drugs in combination with stents versus drugs alone. The incidence of death or stroke, cerebral haemorrhage, disabling stroke or death was significantly higher in patients receiving stent-combined drug therapy versus drug therapy alone for sICAS.

Conclusion: Studies suggest that stenting combined with medication for patients with sICAS may increase the incidence of death or stroke, cerebral haemorrhage, stroke or death, but has no significant effect on the incidence of TIA and stroke. The studies report inadequate and conflicting data and therefore the safety and efficacy of stenting for sICAS should be interpreted with caution.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022377090, identifier CRD42022377090
Circular RNAs in gynecologic cancers: mechanisms and implications for chemotherapy resistance
Authors: Qin Meiying , Zhang Chunmei , Li Yang
Published: June 2023

Chemotherapy resistance remains a major challenge in the treatment of gynecologic malignancies. Increasing evidence suggests that circular RNAs (circRNAs) play a significant role in conferring chemoresistance in these cancers. In this review, we summarize the current understanding of the mechanisms by which circRNAs regulate chemotherapy sensitivity and resistance in gynecologic malignancies. We also discuss the potential clinical implications of these findings and highlight areas for future research. CircRNAs are a novel class of RNA molecules that are characterized by their unique circular structure, which confers increased stability and resistance to degradation by exonucleases. Recent studies have shown that circRNAs can act as miRNA sponges, sequestering miRNAs and preventing them from binding to their target mRNAs. This can lead to upregulation of genes involved in drug resistance pathways, ultimately resulting in decreased sensitivity to chemotherapy. We discuss several specific examples of circRNAs that have been implicated in chemoresistance in gynecologic cancers, including cervical cancer, ovarian cancer, and endometrial cancer. We also highlight the potential clinical applications of circRNA-based biomarkers for predicting chemotherapy response and guiding treatment decisions. Overall, this review provides a comprehensive overview of the current state of knowledge regarding the role of circRNAs in chemotherapy resistance in gynecologic malignancies. By elucidating the underlying mechanisms by which circRNAs regulate drug sensitivity, this work has important implications for improving patient outcomes and developing more effective therapeutic strategies for these challenging cancers.
ICD-related risk model predicts the prognosis and immunotherapy response of patients with liver cancer
Authors: Su Duntao , Zhang Zeyu , Xia Fada , Liang Qiuju , Liu Yuanhong , Liu Wei , Xu Zhijie
Published: June 2023

Immunogenic cell death (ICD) is a novel cell death mechanism that activates and regulates the immune system against cancer. However, its prognostic value in liver cancer remains unclear. Here, several algorithms such as correlation analysis, Cox regression analysis, and Lasso regression analysis were carried out to evaluate the prognostic value of ICD-related genes in patients with liver cancer. Three ICD-related prognostic genes, the prion protein gene (PRNP), dynamin 1-like gene (DNM1L), and caspase-8 (CASP8), were identified and used to construct a risk signature. Patients with liver cancer were categorized into high- and low-risk groups using the ICD-related signature. Subsequently, a multivariate regression analysis revealed that the signature was an independent risk factor in liver cancer [hazard ratio (HR) = 6.839; 95% confidence interval (CI) = 1.625–78.785]. Patient survival was also predicted using the risk model, with area under the curve values of 0.75, 0.70, and 0.69 for 1-, 3-, and 5-year survival, respectively. Finally, a prognostic nomogram containing the clinical characteristics and risk scores of patients was constructed. The constructed ICD-related signature could serve as a prognostic and immunotherapeutic biomarker in liver cancer.
Comparison of pharmacogenomic information for drug approvals provided by the national regulatory agencies in Korea, Europe, Japan, and the United States
Authors: Lee Mijin , Han Ji Min , Lee Jaeyeon , Oh Ju Young , Kim Jung Sun , Gwak Hye Sun , Choi Kyung Hee
Published: June 2023

Pharmacogenomics, which is defined as the study of changes in the properties of DNA and RNA associated with drug response, enables the prediction of the efficacy and adverse effects of drugs based on patients’ specific genetic mutations. For the safe and effective use of drugs, it is important that pharmacogenomic information is easily accessible to clinical experts and patients. Therefore, we examined the pharmacogenomic information provided on drug labels in Korea, Europe, Japan, and the United States (US). The selection of drugs that include pharmacogenomic information was based on the drug list that includes genetic information from the Korea Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) websites. Drug labels were retrieved from the sites of MFDS, FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Drugs were classified as per the Anatomical Therapeutic Chemical code, and the biomarkers, labeling sections, and necessity of genetic tests were determined. In total, 348 drugs were selected from 380 drugs with available pharmacogenomic information in Korea and the US after applying the inclusion and exclusion criteria. Of these drugs, 137, 324, 169, and 126 were with pharmacogenomics information in Korea, the US, Europe, and Japan, respectively. The most commonly represented drug class was antineoplastic and immunomodulating agents. Regarding the classification as per the mentioned biomarkers, the cytochrome P450 enzyme was the most frequently mentioned information, and the targeted anticancer drugs most commonly required genetic biomarker testing. The reasons for differences in drug labeling information based on country include differences in mutant alleles according to ethnicity, frequencies at which drug lists are updated, and pharmacogenomics-related guidelines. Clinical experts must continuously strive to identify and report mutations that can explain drug efficacy or side effects for safe drug use.
Malware propagation model of fractional order, optimal control strategy and simulations
Authors: Zhou Ying , Liu Ban-Teng , Zhou Kai , Shen Shou-Feng
Published: June 2023

In this paper, an improved SEIR model of fractional order is investigated to describe the behavior of malware propagation in the wireless sensor network. Firstly, the malware propagation model of fractional order is established based on the classical SEIR epidemic theory, the basic reproductive number is obtained by the next-generation method and the stability condition of the model is also analyzed. Then, the inverse approach for the uncertainty propagation based on the discrete element method and least square algorithm is presented to determine the unknown parameters of the propagation process. Finally, the optimal control strategy is also discussed based on the adaptive model. Simulation results show the proposed model works better than the propagation model of integer order. The error of proposed model is smaller than integer order models.
Changes in pontine and preBötzinger/Bötzinger complex neuronal activity during remifentanil-induced respiratory depression in decerebrate dogs
Authors: Palkovic Barbara , Mustapic Sanda , Saric Ivana , Stuth Eckehard A. E. , Stucke Astrid G. , Zuperku Edward J.
Published: June 2023

Introduction:In vivo studies using selective, localized opioid antagonist injections or localized opioid receptor deletion have identified that systemic opioids dose-dependently depress respiratory output through effects in multiple respiratory-related brainstem areas.

Methods: With approval of the subcommittee on animal studies of the Zablocki VA Medical Center, experiments were performed in 53 decerebrate, vagotomized, mechanically ventilated dogs of either sex during isocapnic hyperoxia. We performed single neuron recordings in the Pontine Respiratory Group (PRG, n = 432) and preBötzinger/Bötzinger complex region (preBötC/BötC, n = 213) before and during intravenous remifentanil infusion (0.1–1 mcg/kg/min) and then until complete recovery of phrenic nerve activity. A generalized linear mixed model was used to determine changes in Fn with remifentanil and the statistical association between remifentanil-induced changes in Fn and changes in inspiratory and expiratory duration and peak phrenic activity. Analysis was controlled via random effects for animal, run, and neuron type.

Results: Remifentanil decreased Fn in most neuron subtypes in the preBötC/BötC as well as in inspiratory (I), inspiratory-expiratory, expiratory (E) decrementing and non-respiratory modulated neurons in the PRG. The decrease in PRG inspiratory and non-respiratory modulated neuronal activity was associated with an increase in inspiratory duration. In the preBötC, the decrease in I-decrementing neuron activity was associated with an increase in expiratory and of E-decrementing activity with an increase in inspiratory duration. In contrast, decreased activity of I-augmenting neurons was associated with a decrease in inspiratory duration.

Discussion: While statistical associations do not necessarily imply a causal relationship, our data suggest mechanisms for the opioid-induced increase in expiratory duration in the PRG and preBötC/BötC and how inspiratory failure at high opioid doses may result from a decrease in activity and decrease in slope of the pre-inspiratory ramp-like activity in preBötC/BötC pre-inspiratory neurons combined with a depression of preBötC/BötC I-augmenting neurons. Additional studies must clarify whether the observed changes in neuronal activity are due to direct neuronal inhibition or decreased excitatory inputs.
The double-hit protocol induces HFpEF and impairs myocardial ubiquitin-proteasome system performance in FVB/N mice
Authors: Lira Jose R. , Guymon Andrew L. , Yang Liuqing , Sternburg Jack O. , Giri Samiksha , Wang Xuejun
Published: June 2023

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of death and disability, with its prevalence surpassing that of heart failure with reduced ejection fraction. Obesity and hypertension are often associated with HFpEF. HFpEF can be modeled through simultaneous metabolic and hypertensive stresses in male C57BL/6N mice provoked by a combination treatment of a high-fat diet (HFD) and constitutive nitric oxide synthase inhibition by Nω-nitro-L-arginine methyl-ester (L-NAME). Ubiquitin-proteasome system (UPS) dysfunction was detected in many forms of cardiomyopathy, but whether it occurs in HFpEF remains unknown. We report successful modeling of HFpEF in male FVB/N mice and, by taking advantage of a transgenic UPS reporter mouse, we have detected myocardial UPS functioning impairment during HFpEF, suggesting a pathogenic role for impaired protein degradation in the development and progression of HFpEF.
Research on Chemically Deuterated Cellulose Macroperformance and Fast Identification
Authors: Song Yan , Liu Shaoyang , Ben Haoxi , Zhang Yuanming , Han Guangting , Ragauskas Arthur J. , Jiang Wei
Published: June 2023

Chemically deuterated cellulose fiber was expected to provide novel applications due to its spectral, biological, and kinetic isotope effect. In this research, the performance of the chemically deuterated cotton fibers, including their mechanical property, enzymatic degradation performance, effect on bacterial treatment, and fast identification (near-infrared modeling) was investigated. The breaking tenacity of the deuterated cotton fibers was slightly lower, which might be attributed to the structural damage during the chemical deuteration. The glucose yield by enzymatic hydrolysis was less than that of the protonic cotton fibers, implying the deuterated fibers are less sensitive to enzymatic degradation. Furthermore, the deuterated fibers could promote the growth of bacteria such as Escherichia. coli, which was associated with the released low-level deuterium content. At last, the near-infrared technique combined with partial least squares regression successfully achieved a fast identification of the protiated and deuterated cotton fibers, which significantly promoted the potential application of deuterated cellulose as anticounterfeiting materials (e.g., special paper).