bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Validation of Hub Genes Associated with Bladder Cancer by Integrated Bioinformatics and Experimental Assays
Authors: Chen Kang , Xing Ji , Yu Weimin , Xia Yuqi , Zhang Yunlong , Cheng Fan , Rao Ting
Published: December 2021

Bladder cancer (BC) is the most common malignant tumor of the urinary system and is associated with high morbidity and mortality; however, the molecular mechanism underlying its occurrence is not clear. In this study, the gene expression profile and related clinical information of GSE13507 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Overlapping genes were identified by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Then, we carried out functional enrichment analysis to understand the potential biological functions of these co-expressed genes. Finally, we performed a protein–protein interaction (PPI) analysis combined with survival analysis. Using the CytoHubba plug-in of Cytoscape, TROAP, CENPF, PRC1, AURKB, CCNB2, CDC20, TTK, CEP55, ASPM, and CDCA8 were identified as candidate central genes. According to the survival analysis, the high expression of TTK was related to the poor overall survival (OS) of patients with BC. TTK may also affect the bladder tumor microenvironment (TME) by affecting the number of immune cells. The expression level of TTK was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of TTK in BC cells was confirmed in vitro. Our results also identified the MSC-AS1/hsa-miR-664b-3p/TTK regulatory axis, which may also play an important role in the progression of BC, but further research is needed to verify this result. In summary, our results provide a new idea for accurate early diagnosis, clinical treatment, and prognosis of BC
Review of Immunohistochemistry Biomarkers in Pancreatic Cancer Diagnosis
Authors: Luu Tuan Trong
Published: December 2021

Pancreatic cancer is one of the cancer types with poor prognosis and high rate of mortality. Diagnostic modalities for early detection of pancreatic cancer have been among the academic concerns. On account of the potential role of immunohistochemistry (IHC) biomarkers in overcoming certain limitations of imaging diagnostic tools in discriminating pancreatic cancer tissues from benign ones, a growing scholarly attention has been given to the diagnostic efficacy of IHC biomarkers for pancreatic cancer. This review will analyze and synthesize published articles to provide an insight into potential IHC biomarkers for pancreatic cancer diagnosis.
Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score
Authors: Brisca Giacomo , Consolaro Alessandro , Caorsi Roberta , Pirlo Daniela , Tuo Giulia , Campanello Claudia , Castagnola Elio , Moscatelli Andrea , Gattorno Marco , Ravelli Angelo
Published: December 2021

In this observational study, we report the clinical, therapeutics and outcome features of 23 patients with multisystem inflammatory syndrome (MIS-C) who have been treated in Gaslini Children Hospital (Genoa, Italy) with a multistep antinflammatory treatment protocol, based on disease severity at admission. Patients were initially assigned to four severity classes on admission and treated accordingly. The therapeutic options ranged from IV immunoglobulin alone to a combination of IVIG plus pulses of methylprednisolone plus anakinra for patients with marked cardiac function impairment or signs of macrophage activation syndrome, with rapid treatment escalation in case of inadequate therapeutic response. With the application of this therapeutic strategy, no patient required admission to Intensive Care Unit (ICU) or invasive mechanical ventilation, and no inotropic drugs administration was required. Early aggressive treatment of MIS-C, with therapeutic interventions modulated based on the severity of clinical manifestations may help to prevent the progression of the inflammatory process and to avoid the need of admission to the ICU. A timely intervention with anti-IL-1 blockers can play a pivotal role in very severe patients that are at risk to have an incomplete response to immunoglobulins and steroids.
Neurological Outcome Following Newborn Encephalopathy With and Without Perinatal Infection: A Systematic Review
Authors: Andersen Mads , Pedersen Mette Vestergård , Andelius Ted Carl Kejlberg , Kyng Kasper Jacobsen , Henriksen Tine Brink
Published: December 2021

Background: Studies have suggested that neurological outcome may differ in newborns with encephalopathy with and without perinatal infection. We aimed to systematically review this association.

Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies were obtained from four databases including Pubmed, Embase, Web of Science, and The Cochrane Database. Newborns with encephalopathy with and without markers of perinatal infection were compared with regard to neurodevelopmental assessments, neurological disorders, and early biomarkers of brain damage. Risk of bias and quality of evidence were assessed by the Newcastle-Ottawa scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results: We screened 4,284 studies of which eight cohort studies and one case-control study met inclusion criteria. A narrative synthesis was composed due to heterogeneity between studies. Six studies were classified as having low risk of bias, while three studies were classified as having high risk of bias. Across all outcomes, the quality of evidence was very low. The neurological outcome was similar in newborns with encephalopathy with and without markers of perinatal infection.

Conclusions: Further studies of higher quality are needed to clarify whether perinatal infection may affect neurological outcome following newborn encephalopathy.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42020185717.
Eliminating Contamination in Umbilical Cord Blood Culture Sampling for Early-Onset Neonatal Sepsis
Authors: Quinones Cardona Vilmaris , Lowery Vanessa , Cooperberg David , Anday Endla K. , Carey Alison J.
Published: December 2021

Introduction: Despite the advantages of umbilical cord blood culture (UCBC) use for diagnosis of early onset sepsis (EOS), contamination rates have deterred neonatologists from its widespread use. We aimed to implement UCBC collection in a level III neonatal intensive care unit (NICU) and apply quality improvement (QI) methods to reduce contamination in the diagnosis of early onset sepsis.

Methods: Single-center implementation study utilizing quality improvement methodology to achieve 0% contamination rate in UCBC samples using the Plan-Do-Study-Act (PDSA) model for improvement. UCBC was obtained in conjunction with peripheral blood cultures (PBC) in neonates admitted to the NICU due to maternal chorioamnionitis. Maternal and neonatal characteristics between clinical sepsis and asymptomatic groups were compared. Process, outcome, and balancing measures were monitored.

Results: Eighty-two UCBC samples were collected in addition to peripheral blood culture from neonates admitted due to maternal chorioamnionitis. Ten (12%) neonates had a diagnosis of clinical sepsis. All PBCs were negative and 5 UCBCs were positive in the study period. After 2 PDSA cycles, there was special cause variation with improvement in the percent of contaminated samples from 7.3 to 0%. There was no change in antibiotic duration among asymptomatic neonates.

Conclusions: Implementation of UCBC for the diagnosis of EOS in term infants is feasible and contamination can be minimized with the implementation of a core team of trained providers and a proper sterile technique without increasing antibiotic duration.
The Roles of Cardiovascular H2-Histamine Receptors Under Normal and Pathophysiological Conditions
Authors: Neumann Joachim , Kirchhefer Uwe , Dhein Stefan , Hofmann Britt , Gergs Ulrich
Published: December 2021

This review addresses pharmacological, structural and functional relationships among H2-histamine receptors and H1-histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential clinical role of cardiac H2-histamine-receptors in cardiac diseases will be examined. The use of H2-histamine receptor agonists to acutely increase the force of contraction will be discussed. Special attention will be paid to the potential role of cardiac H2-histamine receptors in the genesis of cardiac arrhythmias. Moreover, novel findings on the putative role of H2-histamine receptor antagonists in treating chronic heart failure in animal models and patients will be reviewed. Some limitations in our biochemical understanding of the cardiac role of H2-histamine receptors will be discussed. Recommendations for further basic and translational research on cardiac H2-histamine receptors will be offered. We will speculate whether new knowledge might lead to novel roles of H2-histamine receptors in cardiac disease and whether cardiomyocyte specific H2-histamine receptor agonists and antagonists should be developed.
Ferroptosis-Inducing Nanomedicine for Cancer Therapy
Authors: Wang Yang , Liu Tianfu , Li Xiang , Sheng Hui , Ma Xiaowen , Hao Liang
Published: December 2021

Ferroptosis, a new iron- and reactive oxygen species–dependent form of regulated cell death, has attracted much attention in the therapy of various types of tumors. With the development of nanomaterials, more and more evidence shows the potential of ferroptosis combined with nanomaterials for cancer therapy. Recently, there has been much effort to develop ferroptosis-inducing nanomedicine, specially combined with the conventional or emerging therapy. Therefore, it is necessary to outline the previous work on ferroptosis-inducing nanomedicine and clarify directions for improvement and application to cancer therapy in the future. In this review, we will comprehensively focus on the strategies of cancer therapy based on ferroptosis-inducing nanomedicine currently, elaborate on the design ideas of synthesis, analyze the advantages and limitations, and finally look forward to the future perspective on the emerging field.
SlpB Protein Enhances the Probiotic Potential of L. lactis NCDO 2118 in Colitis Mice Model
Authors: Belo Giovanna A. , Cordeiro Bárbara F. , Oliveira Emiliano R. , Braga Marina P. , da Silva Sara H. , Costa Bruno G. , Martins Flaviano dos S. , Jan Gwénaël , Le Loir Yves , Gala-García Alfonso , Ferreira Enio , Azevedo Vasco , do Carmo Fillipe L. R.
Published: December 2021

Bacteria used in the production of fermented food products have been investigated for their potential role as modulators of inflammation in gastrointestinal tract disorders such as inflammatory bowel diseases (IBD) that cause irreversible changes in the structure and function of gut tissues. Ulcerative colitis (UC) is the most prevalent IBD in the population of Western countries, and it is marked by symptoms such as weight loss, rectal bleeding, diarrhea, shortening of the colon, and destruction of the epithelial layer. The strain Propionibacterium freudenreichii CIRM-BIA 129 recently revealed promising immunomodulatory properties that greatly rely on surface-layer proteins (Slp), notably SlpB. We, thus, cloned the sequence encoding the SlpB protein into the pXIES-SEC expression and secretion vector, and expressed the propionibacterial protein in the lactic acid bacterium Lactococcus lactis NCDO 2118. The probiotic potential of L. lactis NCDO 2118 harboring pXIES-SEC:slpB (L. lactis-SlpB) was evaluated in a UC-mice model induced by Dextran Sulfate Sodium (DSS). During colitis induction, mice receiving L. lactis-SlpB exhibited reduced severity of colitis, with lower weight loss, lower disease activity index, limited shortening of the colon length, and reduced histopathological score, with significant differences, compared with the DSS group and the group treated with L. lactis NCDO 2118 wild-type strain. Moreover, L. lactis-SlpB administration increased the expression of genes encoding tight junction proteins zo-1, cln-1, cln-5, ocln, and muc-2 in the colon, increased IL-10 and TGF-β, and decreased IL-17, TNF-α, and IL-12 cytokines in the colon. Therefore, this work demonstrates that SlpB recombinant protein is able to increase the probiotic potential of the L. lactis strain to alleviate DSS-induced colitis in mice. This opens perspectives for the development of new approaches to enhance the probiotic potential of strains by the addition of SlpB protein.
Molecular Mechanism of the Regulatory Effect of Schisandrol A on the Immune Function of Mice Based on a Transcription Factor Regulatory Network
Authors: Xu Guangyu , Feng Yanbo , Li Han , Chen Cong , Li He , Wang Chunmei , Chen Jianguang , Sun Jinghui
Published: December 2021

The molecular mechanism of the regulatory effed of schizandrol A (SA) on the immune function of cyclophosphamide-induced immunosuppressive mice was explored in this study. On the basis of 1619 differentially expressed genes related to the regulatory effect of SA on the immune function of mice screened in our previous study, transcription factors and their corresponding target genes were screened in the Transcriptional Regulatory Element Database (TRED), and a transcription factor target gene regulatory network was constructed. The key nodes of the network were statistically analyzed to clarify the role of transcription factors in the regulatory network. The correlation of network genes with diseases was analyzed with an online annotation tool through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, the key factors related to the regulatory effect of SA on the immune function of mice were screened and verified by animal experiments and the detection of related protein expression by western blot analysis. The results showed that SA could alleviate the immunosuppression induced by cyclophosphamide in mice and regulate the protein expression of Jun, Trp53, and Creb1 in the spleen tissue of mice, together with the transcription factors Atf4 and E2f2. SA may thus play a role in the alleviation of some immunity-related diseases (such as cancer) by regulating the immune function of mice through multiple genes and their transcription factors.
Surface and Subsurface Quality Assessment of Polished Lu2O3 Single Crystal Using Quasi-Brewster Angle Technique
Authors: Yao Chengyuan , Shen Wanfu , Hu Xiaodong , Hu Chunguang
Published: December 2021

The sesquioxide Lu2O3 single crystal has attracted tremendous attention as potential host material for high-power solid-state lasers. As polishing is the terminal process of conventional ultra-precision machining, the quality of polished crystal directly impacts the crucial performance indicators of optics. The high melting point of Lu2O3 single crystal makes crystal preparation difficult. Therefore, investigations on the surface/subsurface quality inspection of polished Lu2O3 single crystal are scarce. In this paper, we utilize the quasi-Brewster angle technique (qBAT) based on ellipsometry to inspect the quality of polished Lu2O3 single crystal, achieving fast, non-destructive, and high-sensitive surface/subsurface damage assessment. A systematic crystal processing scheme is designed and polished Lu2O3 crystal samples are obtained. To verify the results of qBAT, the surface and subsurface quality are tested using optical profilometer and transmission electron microscope, respectively. The consistency of the test results demonstrates the feasibility, high sensitivity, and accuracy of the qBAT. To our knowledge, this is the first time that the qBAT is applied to investigate the polished surface/subsurface quality of Lu2O3 single crystal. In conclusion, this method provides a powerful approach to the high-precision characterization of the surface/subsurface quality of Lu2O3 single crystal, and has significant potential for material property study and process optimization during ultra-precision machining.
Hydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis
Authors: Tian Yan , Zhang Yafang , Wang Yu , Chen Yunxi , Fan Weiping , Zhou Jianjun , Qiao Jing , Wei Youzhen
Published: December 2021

Molecular hydrogen (H2) is a colorless and odorless gas. Studies have shown that H2 inhalation has the therapeutic effects in many animal studies and clinical trials, and its application is recommended in the novel coronavirus pneumonia treatment guidelines in China recently. H2 has a relatively small molecular mass, which helps it quickly spread and penetrate cell membranes to exert a wide range of biological effects. It may play a role in the treatment and prevention of a variety of acute and chronic inflammatory diseases, such as acute pancreatitis, sepsis, respiratory disease, ischemia reperfusion injury diseases, autoimmunity diseases, etc.. H2 is primarily administered via inhalation, drinking H2-rich water, or injection of H2 saline. It may participate in the anti-inflammatory and antioxidant activity (mitochondrial energy metabolism), immune system regulation, and cell death (apoptosis, autophagy, and pyroptosis) through annihilating excess reactive oxygen species production and modulating nuclear transcription factor. However, the underlying mechanism of H2 has not yet been fully revealed. Owing to its safety and potential efficacy, H2 has a promising potential for clinical use against many diseases. This review will demonstrate the role of H2 in antioxidative, anti-inflammatory, and antiapoptotic effects and its underlying mechanism, particularly in coronavirus disease-2019 (COVID-19), providing strategies for the medical application of H2 for various diseases.
Systemic Identification and Functional Characterization of Common in Fungal Extracellular Membrane Proteins in Lasiodiplodia theobromae
Authors: Peng Junbo , Wu Linna , Zhang Wei , Zhang Qi , Xing Qikai , Wang Xuncheng , Li Xinghong , Yan Jiye
Published: December 2021

Plant pathogenic fungi deploy secreted proteins into apoplastic space or intracellular lumen to promote successful infections during plant-pathogen interactions. In the present study, fourteen CFEM domain-containing proteins were systemically identified in Lasiodiplodia theobromae and eight of them were functionally characterized. All eight proteins were confirmed to be secreted into extracellular space by a yeast signal peptide trapping system. The transcriptional levels of most CFEM genes, except for LtCFEM2 and LtCFEM6, were significantly elevated during infection. In addition, almost all LtCFEM genes, apart from LtCFEM2, LtCFEM3, and LtCFEM6, were transcriptionally up-regulated at 35°C in contrast to that at 25°C and 30°C. As two elicitors, LtCFEM1 induced local yellowish phenotype and LtCFEM4 triggered cell death in Nicotiana benthamiana leaves. Furthermore, these proteins displayed distinct subcellular localizations when expressed transiently in N. benthamiana. Moreover, two genes, LtCFEM7 and LtCFEM8, were found to be spliced alternatively by RT-PCR and sequencing. Therefore, our data suggest that LtCFEM proteins play important roles in multiple aspects, including pathogenicity and plant immune response, which will enhance our understanding of the sophisticated pathogenic mechanisms of plant opportunistic pathogen L. theobromae.
Effects of Leader Narcissism on Career Success of Employees: An Interpersonal Relationship Perspective
Authors: Wang Huaqiang , Li Dan , Wu Lei , Ding Zhihui
Published: December 2021

Previous studies have shown that leader narcissism has a significant impact on the effectiveness of a leader and employee behaviors; however, research on career outcomes of employees is still inadequate. This study explores the effects of leader narcissism on the career success of employees from an interpersonal relationship perspective and examines the mediating role of supervisor-subordinate conflict and the moderating role of dominant personality traits of employees. Data from 291 employees in Chinese companies have revealed that leader narcissism, directly and indirectly, affects the career success of employees through supervisor-subordinate relationship conflict. However, dominant personality traits of employees strengthen the impact of leader narcissism on supervisor-subordinate relationship conflict. The theoretical and practical implications of the findings of this study are further discussed.
Digital Nudging for Online Food Choices
Authors: Jesse Mathias , Jannach Dietmar , Gula Bartosz
Published: December 2021

When people search for what to cook for the day, they increasingly use online recipe sites to find inspiration. Such recipe sites often show popular recipes to make it easier to find a suitable choice. However, these popular recipes are not always the healthiest options and can promote an unhealthy lifestyle. Our goal is to understand to what extent it is possible to steer the food selection of people through digital nudging. While nudges have been shown to affect humans' behavior regarding food choices in the physical world, there is little research on the impact of nudges on online food choices. Specifically, it is unclear how different nudges impact (i) the behavior of people, (ii) the time they need to make a decision, and (iii) their satisfaction and confidence with their selection. We investigate the effects of highlighting, defaults, social information, and warnings on the decision-making of online users through two consecutive user studies. Our results show that a hybrid nudge, which both involves setting a default and adding social information, significantly increases the likelihood that a nudged item is selected. Moreover, it may help decreasing the required decision time for participants while having no negative effects on the participant's satisfaction and confidence. Overall, our work provides evidence that nudges can be effective in this domain, but also that the type of a digital nudge matters. Therefore, different nudges should be evaluated in practical applications.
Job Demands and Resources and Employee Well-Being in the Chinese Nonprofit Sector
Authors: Deng Guosheng , Huang Chienchung , Cheung Shannon P. , Zhu Shaoming
Published: December 2021

Although the nonprofit sector in China has grown substantially in past decades, its future is threatened by high turnover and burnout. It is thus necessary to investigate the factors that contribute to employee well-being (EWB) among nonprofit employees in China. This study used 233 foundation employees in China to examine the effects of job demands and resources (JD-R) on EWB. Estimates produced by regression analyses indicated that job resources (JR) have a strong effect on EWB (Beta = 0.53), as well as on the three EWB subscales (workplace, psychological, and life well-being). While job demands (JD) had no effects on overall well-being, they were negatively associated with workplace well-being (WWB) (Beta = −0.12). Robustness tests were conducted to further examine how JD and JR dimensions affect EWB and its subscales. Based on the findings, we underscore the importance of JR for EWB among foundation employees in China as well as that of implementing interventions that may alleviate the cost of emotional workload as a JD.
Latent Structure of Combined Autistic and ADHD Symptoms in Clinical and General Population Samples: A Scoping Review
Authors: Krakowski Aneta D. , Szatmari Peter , Crosbie Jennifer , Schachar Russell , Duku Eric , Georgiades Stelios , Anagnostou Evdokia
Published: December 2021

Background: Many phenotypic studies have estimated the degree of comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), but few have examined the latent, or unobserved, structure of combined ASD and ADHD symptoms. This is an important perquisite toward better understanding the overlap between ASD and ADHD.

Methods: We conducted a scoping review of studies that examined the factor or latent class structure of ASD and ADHD symptoms within the same clinical or general population sample.

Results: Eight studies met final inclusion criteria. Four factor analysis studies found that ASD and ADHD domains loaded separately and one found that some ASD and ADHD domains loaded together. In the three latent class studies, there were evidence of profiles with high levels of co-occurring ASD and ADHD symptoms.

Conclusions: Our scoping review provides some evidence of phenotypic overlap between ASD and ADHD at the latent, or unobserved, level, particularly when using a “person-centered” (latent class analysis) vs. a “variable-centered” (factor analysis) approach.
Impact of Air Pollution on Residents' Medical Expenses: A Study Based on the Survey Data of 122 Cities in China
Authors: Liu Huan , Hu Tiantian , Wang Meng
Published: December 2021

Background: With the development of the social economy, air pollution has resulted in increased social costs. Medical costs and health issues due to air pollution are important aspects of environmental governance in various countries.

Methods: This study uses daily air pollution monitoring data from 122 cities in China to empirically investigate the impact of air pollution on residents' medical expenses using the Heckman two-stage and instrumental variable methods, matching data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) survey.

Results: The study found that poor air quality, measured by the air quality index (AQI), significantly increased the probability of chronic lung disease, heart disease, and self-rated poor health. Additionally, the AQI (with an effect of 4.51%) significantly impacted health-seeking behavior and medical expenses. The medical expenditure effects of mild, moderate, severe, and serious pollution days were 3.27, 7.21, 8.62, and 42.66%, respectively.

Conclusion: In the long run, residents' health in areas with a higher air pollution index, indicating poor air quality, is negatively impacted. The more extreme the pollution, the higher the probability of residents' medical treatment and the subsequent increase in medical expenses. Group and regional heterogeneity also play a role in the impact of air pollution on medical expenses. Compared with the existing literature, this study is based on individuals aged 15 years and above and produces reliable research conclusions.
Multimorbidity in Hospitalized Patients Admitted to General Practice Departments and Its Implications for the General Practice Healthcare System: A Four-Year Longitudinal Study in China
Authors: Zhou Zhihan , Shi Meng , Liu Mengzhu , Gu Jianqin , Silver Tarimo Clifford , Wu Jian , Miao Yudong
Published: December 2021

Objective: China and many developing countries has placed high expectations on the general practice healthcare system in terms of lowering medical costs and improving the health status of the multimorbid population in recent years. However, the prevalence of multimorbidity among inpatients attending the general practice department of hospitals and its policy implications are largely unknown. The current study aimed to analyze the prevalence of comorbidities among inpatients attending the general practice department of the tertiary Grade-A Hospitals in China, and put forward evidence-based policy recommendations.

Methods: Between December 2016 and November 2020, 351 registered general practitioners from 27 tertiary hospitals were selected, and their direct admissions were evaluated. The rate and composition ratio were used for descriptive analysis of the clinical and epidemiological characteristics of multimorbidity. A backward stepwise algorithm was used to explore independent variables. The absence of multicollinearity and plausible interactions among variables were tested to ensure the robustness of the logistic regression model. The pyramid diagram was used to show the link between gender and the involved human body system in multimorbidity.

Results: Multimorbidity was present in 93.1% of the 64, 395 patients who were admitted directly. Multimorbidity was significantly more prevalent in patients aged 45–59 years (OR=3.018, 95% CI=1.945–4.683), 60–74 years (OR = 4.349, 95% CI = 2.574–7.349), ≥75 years (OR = 7.804, 95% CI = 3.665–16.616), and those with body mass index (BMI) ≥ 28 kg/m2 (OR = 3.770, 95% CI = 1.453–9.785). The circulatory system was found to be the most commonly involved human body system in multimorbidity, accounting for 79.2% (95% CI = 78.8–79.5%) of all cases. Significant gender inequity was further observed in the involved human body system in multimorbidity.

Conclusion: Multimorbidity is likely common among the inpatients attending the general practice department of hospitals in China and many developing countries, with significant gender inequity in the involved human body systems. Effective countermeasures include establishing a GP-PCIC multimorbidity prevention and control model and enhancing the multimorbidity of elderly and obese patients at both the clinical and healthy lifestyle levels. The diagnosis and treatment capabilities of GPs on the circulatory, endocrine, metabolic, digestive, and respiratory systems should be prioritized.
21st Century Good Neighbor Program: An Easily Generalizable Program to Reduce Social Isolation in Older Adults
Authors: Sandu Shashank , Sreedhar Siva , Chang Linda , Cohen Lindsay , Cruz Andrea , Olson Heidi R. , Sreedhar Radhika , Gomez Kayeromi , Carrion Alberto
Published: December 2021

Aim: In this once-in-a-lifetime humanitarian crisis, what does it mean to be a good neighbor? It means that as a community, we must address loneliness and barriers to care faced by vulnerable populations such as older adults. We share an inexpensive longitudinal experiential service-learning program implemented by health professions and undergraduate student volunteers that aims to help alleviate loneliness in older adults while imparting meaningful experiences to volunteers.

Intervention Design and Setting: The 21st Century Good Neighbor Program is an observational cohort study of an experiential service-learning program started in May 2020, and this article shares the results collected after 1 year. This longitudinal, weekly phone call program was conducted in a single community setting in the Midwestern part of the United States. Older adults over the age of 60 served by a local community service agency (CSA) were invited to participate. Volunteers consisted of students 18 or older. Student volunteers made regular phone calls to a pair of older adults throughout the course of 1 year following standardized call scripts. The loneliness of the older adults was measured by volunteers using the 3-item UCLA Loneliness Assessment.

Results: 261 older adults were engaged in conversations with a volunteer. A total of 1,391 calls were accepted by older adults and the median length of a welcomed call was 11 min. The average baseline loneliness score was 4.156 ± 1.41 and the prevalence of social isolation was 19.5%. There was no significant change in the UCLA loneliness score in the first year of follow up. However, a majority of volunteers (88%) agreed or strongly agreed that the program had a positive impact on them. In addition, the program identified 257 issues older adults faced that required follow-up. The most prevalent concerns referred to the community service agency by volunteers were issues related to utilities, food and transportation access.

Conclusion: The 21st Century Good Neighbor Program is a unique intervention in which student volunteers and older adults paired by a community service agency forge relationships though a longitudinal phone call-based program. This easy-to-implement program provides another layer of support to identify and refer issues that impact social determinants of health. The added benefit of volunteer satisfaction in the setting of COVID 19 pandemic is heartening. We hope to continue to study the impact of this intervention on social isolation in this vulnerable population.
EQ-5D-3L Health Status Among Homeless People in Stockholm, Sweden, 2006 and 2018
Authors: Burström Bo , Irestig Robert , Burström Kristina
Published: December 2021

Background: Homeless people are a socially excluded group whose health reflects exposures to intersecting social determinants of health. The aim of this study was to describe and compare the demographic composition, certain social determinants of health, and self-reported health among homeless people in Stockholm, Sweden, in 2006 and 2018.

Methods: Analysis of data from face-to-face interviews with homeless people in Stockholm 2006 (n = 155) and 2018 (n = 148), based on a public health survey questionnaire adapted to the group, including the EQ-5D-3L instrument. The chi-squared test was employed to test for statistical significance between groups and the independent t-test for comparison of mean scores and values. Ordinary Least Squares (OLS) regression, with Robust Standard Errors (RSE) was performed on merged 2006 and 2018 data with mean observed EQ VAS score as outcome variable.

Results: In 2018 more homeless people originated from countries outside Europe, had temporary social assistance than long-term social insurance, compared to in 2006. In 2018 more respondents reported lack of social support, exposure to violence, and refrained from seeking health care because of economic reasons. Daily smoking, binge drinking, and use of narcotic drugs was lower 2018 than 2006. In 2018 a higher proportion reported problems in the EQ-5D-3L dimensions, the mean TTO index value and the VAS index value was significantly lower than in 2006. In the regression analysis of merged data there was no significant difference between the years.

Conclusions: Homeless people are an extremely disadvantaged group, have high rates of illness and disease and report poor health in all EQ-5D-3L dimensions. The EQ VAS score among the homeless people in 2018 is comparable to the score among persons aged 95–104 years in the general Swedish population 2017. The EQ-5D-3L instrument was easily administered to this group, its use allows comparison with larger population groups. Efforts are needed regarding housing, but also intensified collaboration by public authorities with responsibilities for homeless people's health and social welfare. Further studies should evaluate the impact of such efforts by health and social care services on the health and well-being of homeless people.
Velocity Distribution Associated With EUV Disturbances Caused by Eruptive MFR
Authors: Mei Zhixing , Cai Qiangwei , Ye Jing , Li Yan , Zhu Bojing
Published: December 2021

Extreme ultraviolet (EUV) disturbances are ubiquitous during eruptive phenomena like solar flare and Coronal Mass Ejection (CME). In this work, we have performed a three-dimensional (3D) magnetohydrodynamic numerical simulation of CME with an analytic magnetic fluxrope (MFR) to study the complex velocity distribution associated with EUV disturbances. When the MFR erupts upward, a fast shock (FS) appears as a 3D dome, followed by outward moving plasma. In the center of the eruptive source region, an expanding CME bubble and a current sheet continuously grow, both of which are filled by inward moving plasma. At the flanks of the CME bubble, a complex velocity distribution forms because of the dynamical interaction between inward and outward plasma, leading to the formation of slow shock (SS) and velocity separatrix (VS). We note two types of vortices near the VS, not mentioned in the preceding EUV disturbance simulations. In first type of vortex, the plasma converges toward the vortex center, and in the second type, the plasma spreads out from the center. The forward modeling method has been used to create the synthetic SDO/AIA images, in which the eruptive MFR and the FS appear as bright structures. Furthermore, we also deduce the plasma velocity field by utilizing the Fourier local correlation tracking method on the synthetic images. However, we do not observe the VS, the SS, and the two types of vortices in this deduced velocity field.
Insight into Yeast–Mycotoxin Relations
Authors: Papp László Attila , Horváth Enikő , Peles Ferenc , Pócsi István , Miklós Ida
Published: December 2021

Fungal mycotoxins are secondary metabolites that can be present in green forage, hay, or silage. Consumption of contaminated plants or agricultural products can cause various animal and human diseases, which is why problems associated with mycotoxins have received particular attention. In addition, public pressure to produce healthy food and feed is also increasing. As the results of several surveys indicate that yeasts can decrease toxic effects by binding or converting secondary metabolites or control growth of harmful fungi, this article provides an overview of the yeast species that can have great potential in detoxification. The most important antagonistic yeast species against toxigenic fungi are described and the mode of their inhibitory mechanisms is also discussed. We provide an insight into toxin binding and biotransformation capacities of yeasts and examples of their use in silo. Issues requiring further study are also mentioned.
A Validated RP-HPLC Method for the Simultaneous Detection and Quantification of Pyridoxine and Terizidone in Pharmaceutical Formulations
Authors: Musafili Ngabo Yves , Samsodien Halima , Aucamp Marique Elizabeth
Published: December 2021

Tuberculosis (TB) remains a life-threatening infection, and it is well-known that effective TB treatment is associated with multiple drugs administered to infected patients on a daily basis. Terizidone (TZD) is an anti-TB drug used in the treatment of multi-drug resistant and extensively drug-resistant TB but presents with polyneuropathic adverse effects in some patients. To counteract these adverse effects, TZD is typically prescribed with pyridoxine (PDX), well known as Vitamin B6. As part of a pre-formulation study investigating the potential to co-formulate these two compounds, it became necessary to have a simple and reliable reversed-phase high-performance liquid chromatography (RP-HPLC) method. Optimal, simultaneous separation and detection of TZD and PDX were obtained using an isocratic mobile phase setup, consisting of ultrapure water and acetonitrile (30:70% v/v), with 1 mL glacial acetic acid added to the mobile phase mixture. A Discovery® C18, 150 × 4.6 mm, 5 μm column maintained at ambient temperature was utilized, with a detection wavelength of 260 nm. The method was validated in terms of linearity, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), specificity, robustness, and solution stability. Validation proved this method to be acceptable and reliable for the simultaneous accurate detection and quantification of TZD and PDX.
The Impact of COVID-19 on the Revenue of the Livestock Industry: A Case Study of China
Authors: Chen Jianxiong , Yang Chung-Cheng
Published: December 2021

The COVID-19 pandemic has affected social order and people’s health and has also caused a heavy blow to the livestock industry, affecting animal management and welfare. The livestock industry is one of the main contributors to economic growth in many regions, and it is of great significance to people’s lives and regional economic growth. COVID-19 has reduced the livestock industry’s market as well as consumers’ opportunities to purchase livestock products, resulting in no sales or low sales of livestock or their products. The main purpose of this study is to consider the impact of the pandemic on the revenue of the livestock industry, and to study the challenges arising from the pandemic to the livestock industry. Based on the perspective of financial statements, we estimate the impact of COVID-19 through the translog revenue function of listed Chinese livestock companies from 2015 to 2020, and the study results show that the COVID-19 pandemic has reduced the revenue of the livestock industry, but the decline in revenue of large livestock enterprises is lower than that of small and medium-sized livestock enterprises. In the last two parts of this study, we make policy recommendations to livestock enterprises and the authorities.
Disease Prevalence Matters: Challenge for SARS-CoV-2 Testing
Authors: Lau Chin-Shern , Aw Tar-Choon
Published: December 2021

While sensitivity and specificity are important characteristics for any diagnostic test, the influence of prevalence is equally, if not more, important when such tests are used in community screening. We review the concepts of positive/negative predictive values (PPV/NPV) and how disease prevalence affects false positive/negative rates. In low-prevalence situations, the PPV decreases drastically. We demonstrate how using two tests in an orthogonal fashion can be especially beneficial in low-prevalence settings and greatly improve the PPV of the diagnostic test results.
Anti-Herpes Simplex Virus Efficacy of Silk Cocoon, Silkworm Pupa and Non-Sericin Extracts
Authors: Jantakee Kanyaluck , Prangkio Panchika , Panya Aussara , Tragoolpua Yingmanee
Published: December 2021

Herpes simplex virus (HSV) infections are prevalent worldwide and are the cause of life- threatening diseases. Standard treatment with antiviral drugs, such as acyclovir, could prevent serious complications; however, resistance has been reported specifically among immunocompromised patients. Therefore, the development of an alternative approach is needed. The silk cocoon derived from silkworm, Bombyx mori, has been recognized for its broad-spectrum biological activity, including antiviral activity; however, its effects against HSV infection are unknown. In this study, we investigated the inhibitory effects of silk extracts derived from the cocoon shell, silk cocoon, silkworm pupa and non-sericin extract, on blocking HSV-1 and HSV-2 binding to host cells, resulting in the inhibition of the virus infection in Vero cells. Non-sericin extract demonstrated the greatest effectiveness on inhibiting HSV-1 and HSV-2 binding activity. Moreover, the virucidal effect to inactivate HSV-1 and HSV-2 was determined and revealed that non-sericin extract also exerted the highest potential activity. Using the treatment of non-sericin extract in HSV-2-infected HeLa cells could significantly lower the HSV-induced cell death and prevent inflammation via lowering the inflammatory cytokine gene expression. The non-sericin extract was analyzed for its bioactive compounds in which gallic acid, flavonoid and xanthophyll were identified, and might have partially contributed to its antiviral activity. The finding in our study suggested the potential of silk extract as an alternative therapeutic treatment for HSV infection.
The Role of Staphylococcus aureus YycFG in Gene Regulation, Biofilm Organization and Drug Resistance
Authors: Wu Shizhou , Zhang Junqi , Peng Qi , Liu Yunjie , Lei Lei , Zhang Hui
Published: December 2021

Antibiotic resistance is a serious global health concern that may have significant social and financial consequences. Methicillin-resistant Staphylococcus aureus (MRSA) infection is responsible for substantial morbidity and leads to the death of 21.8% of infected patients annually. A lack of novel antibiotics has prompted the exploration of therapies targeting bacterial virulence mechanisms. The two-component signal transduction system (TCS) enables microbial cells to regulate gene expression and the subsequent metabolic processes that occur due to environmental changes. The YycFG TCS in S. aureus is essential for bacterial viability, the regulation of cell membrane metabolism, cell wall synthesis and biofilm formation. However, the role of YycFG-associated biofilm organization in S. aureus antimicrobial drug resistance and gene regulation has not been discussed in detail. We reviewed the main molecules involved in YycFG-associated cell wall biosynthesis, biofilm development and polysaccharide intercellular adhesin (PIA) accumulation. Two YycFG-associated regulatory mechanisms, accessory gene regulator (agr) and staphylococcal accessory regulator (SarA), were also discussed. We highlighted the importance of biofilm formation in the development of antimicrobial drug resistance in S. aureus infections. Data revealed that inhibition of the YycFG pathway reduced PIA production, biofilm formation and bacterial pathogenicity, which provides a potential target for the management of MRSA-induced infections.
Antifungal Mechanism of Vip3Aa, a Vegetative Insecticidal Protein, against Pathogenic Fungal Strains
Authors: Park Seong-Cheol , Kim Jin-Young , Lee Jong-Kook , Lim Hye Song , Son Hyosuk , Yoo Su-Hyang , Mun Seong-Eun , Jang Mi-Kyeong , Lee Jung Ro
Published: December 2021

Discovering new antifungal agents is difficult, since, unlike bacteria, mammalian and fungal cells are both eukaryotes. An efficient strategy is to consider new antimicrobial proteins that have variety of action mechanisms. In this study, a cDNA encoding Bacillus thuringiensis Vip3Aa protein, a vegetative insecticidal protein, was obtained at the vegetative growth stage; its antifungal activity and mechanism were evaluated using a bacterially expressed recombinant Vip3Aa protein. The Vip3Aa protein demonstrated various concentration- and time-dependent antifungal activities, with inhibitory concentrations against yeast and filamentous fungi ranging from 62.5 to 125 µg/mL and 250 to 500 µg/mL, respectively. The uptake of propidium iodide and cellular distributions of rhodamine-labeled Vip3Aa into fungal cells indicate that its growth inhibition mechanism involves its penetration within cells and subsequent intracellular damage. Furthermore, we discovered that the death of Candida albicans cells was caused by the induction of apoptosis via the generation of mitochondrial reactive oxygen species and binding to nucleic acids. The presence of significantly enlarged Vip3Aa-treated fungal cells indicates that this protein causes intracellular damage. Our findings suggest that Vip3Aa protein has potential applications in the development of natural antimicrobial agents.
Non-Invasive Measurement of Exercise-Induced Oxidative Stress in Response to Physical Activity. A Systematic Review and Meta-Analysis
Authors: Squillacioti Giulia , Guglieri Fulvia , Colombi Nicoletta , Ghelli Federica , Berchialla Paola , Gardois Paolo , Bono Roberto
Published: December 2021

Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses including the most frequently quantified biomarkers of oxidative stress, namely, urinary isoprostane and DNA oxidation products, were performed. Three electronic databases (PubMed, EMBASE and Cochrane CENTRAL) were interrogated. Among 4479 records, 43 original articles were included in the systematic review and 11 articles were included in meta-analysis I and II, respectively. We observed a pooled trend of increase of urinary isoprostanes in response to physical activity (+0.95, 95% CI: −0.18; 2.09). In comparison with aerobic exercise, anaerobic training determined a greater induction of isoprostanes (+5.21, 95% CI: 2.76; 7.66, p < 0.0001), which were markedly increased after vigorous physical activity (+6.01, 95% CI: 1.18; 10.84, p < 0.001) and slightly decreased in response to exercise interventions protracted over time (e.g., months) (−1.19, 95% CI: −2.25; −0.12, p < 0.001). We recommend the most integrative approach of oxidative stress multi-marker panels in response to physical activity instead of selecting one preferential biomarker to quantify physical activity-induced oxidative stress in humans.