bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Pendidikan Kesehatan Asupan Cairan terhadap Kepatuhan Pembatasan Cairan Pasien Hemodialisis
Authors: Widhawati Riswahyuni , Fitriani Fitriani
Published: August 2021

Pasien Chronic Kidney Disease (CKD) yang rutin menjalani hemodialisis dua hingga tiga kali seminggu cenderung mengalami kelebihan volume cairan karena penurunan fungsi ginjal. Asupan volume cairan yang berlebih merupakan salah satu penyebab kematian pada pasien CKD. Tujuan penelitian ini adalah untuk mengetahui adanya pengaruh pendidikan kesehatan terhadap kepatuhan pembatasan asupan cairan pasien hemodialisis di Rumah Sakit Ichsan Medical Centre (IMC) Bintaro Tangerang Selatan. Penelitian ini menggunakan pendekatan kuantitatif dengan menggunakan metode quasi eksperimen dengan pendekatan pretest and post test non-equivalent control group design. Sampel penelitian berjumlah 40 pasien hemodialisis (20 pasien eksperimen dan 20 pasien kontrol). Intervensi pada kelompok eksperimen berupa pendidikan kesehatan tentang pembatasan asupan cairan. Pengumpulan data menggunakan kuisioner. Analisis yang digunakan adalah analisis univariat dan bivariat dengan uji paired sample T test dan independent T test. Hasil analisis data menunjukkan ada pengaruh pemberian pendidikan kesehatan pada kelompok eksperimen (p = 0,000), tetapi tidak ada perbedaan kepatuhan pembatasan cairan (p = 0,330) pada kelompok kontrol yang tidak diberikan pendidikan kesehatan. Peneliti menyimpulkan bahwa ada pengaruh pemberian pendidikan kesehatan terhadap tingkat kepatuhan pembatasan cairan pada pasien CKD.
Mechanisms Underlying the Anti-Suicidal Treatment Potential of Buprenorphine
Authors: Cameron Courtney M. , Nieto Steven , Bosler Lucienne , Wong Megan , Bishop Isabel , Mooney Larissa , Cahill Catherine M.
Published: August 2021

Death by suicide is a global epidemic with over 800 K suicidal deaths worlwide in 2012. Suicide is the 10th leading cause of death among Americans and more than 44 K people died by suicide in 2019 in the United States. Patients with chronic pain, including, but not limited to, those with substance use disorders, are particularly vulnerable. Chronic pain patients have twice the risk of death by suicide compared to those without pain, and 50% of chronic pain patients report that they have considered suicide at some point due to their pain. The kappa opioid system is implicated in negative mood states including dysphoria, depression, and anxiety, and recent evidence shows that chronic pain increases the function of this system in limbic brain regions important for affect and motivation. Additionally, dynorphin, the endogenous ligand that activates the kappa opioid receptor is increased in the caudate putamen of human suicide victims. A potential treatment for reducing suicidal ideation and suicidal attempts is buprenorphine. Buprenorphine, a partial mu opioid agonist with kappa opioid antagonist properties, reduced suicidal ideation in chronic pain patients with and without an opioid use disorder. This review will highlight the clinical and preclinical evidence to support the use of buprenorphine in mitigating pain-induced negative affective states and suicidal thoughts, where these effects are at least partially mediated via its kappa antagonist properties.
The Tyrosine Kinase-Driven Networks of Novel Long Non-coding RNAs and Their Molecular Targets in Myeloproliferative Neoplasms
Authors: Wong Nonthaphat Kent , Luo Shumeng , Chow Eudora Y. D. , Meng Fei , Adesanya Adenike , Sun Jiahong , Ma Herman M. H. , Jin Wenfei , Li Wan-Chun , Yip Shea Ping , Huang Chien-Ling
Published: August 2021

Recent research has focused on the mechanisms by which long non-coding RNAs (lncRNAs) modulate diverse cellular processes such as tumorigenesis. However, the functional characteristics of these non-coding elements in the genome are poorly understood at present. In this study, we have explored several mechanisms that involve the novel lncRNA and microRNA (miRNA) axis participating in modulation of drug response and the tumor microenvironment of myeloproliferative neoplasms (MPNs). We identified novel lncRNAs via mRNA sequencing that was applied to leukemic cell lines derived from BCR-ABL1-positive and JAK2-mutant MPNs under treatment with therapeutic tyrosine kinase inhibitors (TKI). The expression and sequence of novel LNC000093 were further validated in both leukemic cells and normal primary and pluripotent cells isolated from human blood, including samples from patients with chronic myelogenous leukemia (CML). Downregulation of LNC000093 was validated in TKI-resistant CML while a converse expression pattern was observed in blood cells isolated from TKI-sensitive CML cases. In addition to BCR-ABL1-positive CML cells, the driver mutation JAK2-V617F-regulated lncRNA BANCR axis was further identified in BCR-ABL1-negative MPNs. Further genome-wide validation using MPN patient specimens identified 23 unique copy number variants including the 7 differentially expressed lncRNAs from our database. The newly identified LNC000093 served as a competitive endogenous RNA for miR-675-5p and reversed the imatinib resistance in CML cells through regulating RUNX1 expression. The extrinsic function of LNC000093 in exosomal H19/miR-675-induced modulation for the microenvironment was also determined with significant effect on VEGF expression.
NAD+ in Alzheimer’s Disease: Molecular Mechanisms and Systematic Therapeutic Evidence Obtained in vivo
Authors: Wang Xinshi , He Hai-Jun , Xiong Xi , Zhou Shuoting , Wang Wen-Wen , Feng Liang , Han Ruiyu , Xie Cheng-Long
Published: August 2021

Mitochondria in neurons generate adenosine triphosphate (ATP) to provide the necessary energy required for constant activity. Nicotinamide adenine dinucleotide (NAD+) is a vital intermediate metabolite involved in cellular bioenergetics, ATP production, mitochondrial homeostasis, and adaptive stress responses. Exploration of the biological functions of NAD+ has been gaining momentum, providing many crucial insights into the pathophysiology of age-associated functional decline and diseases, such as Alzheimer’s disease (AD). Here, we systematically review the key roles of NAD+ precursors and related metabolites in AD models and show how NAD+ affects the pathological hallmarks of AD and the potential mechanisms of action. Advances in understanding the molecular roles of NAD+-based neuronal resilience will result in novel approaches for the treatment of AD and set the stage for determining whether the results of exciting preclinical trials can be translated into the clinic to improve AD patients’ phenotypes.
Metabolic Alterations in Preneoplastic Development Revealed by Untargeted Metabolomic Analysis
Authors: Myllymäki Henna , Astorga Johansson Jeanette , Grados Porro Estefania , Elliot Abigail , Moses Tessa , Feng Yi
Published: August 2021

Metabolic rewiring is a critical hallmark of tumorigenesis and is essential for the development of cancer. Although many key features of metabolic alteration that are crucial for tumor cell survival, proliferation and progression have been identified, these are obtained from studies with established tumors and cancer cell lines. However, information on the essential metabolic changes that occur during pre-neoplastic cell (PNC) development that enables its progression to full blown tumor is still lacking. Here, we present an untargeted metabolomics analysis of human oncogene HRASG12V induced PNC development, using a transgenic inducible zebrafish larval skin development model. By comparison with normal sibling controls, we identified six metabolic pathways that are significantly altered during PNC development in the skin. Amongst these altered pathways are pyrimidine, purine and amino acid metabolism that are common to the cancer metabolic changes that support rapid cell proliferation and growth. Our data also suggest alterations in post transcriptional modification of RNAs that might play a role in PNC development. Our study provides a proof of principle work flow for identifying metabolic alterations during PNC development driven by an oncogenic mutation. In the future, this approach could be combined with transcriptomic or proteomic approaches to establish the detailed interaction between signaling networks and cellular metabolic pathways that occur at the onset of tumor progression.
Two Similar Signatures for Predicting the Prognosis and Immunotherapy Efficacy of Stomach Adenocarcinoma Patients
Authors: Yue Taohua , Zuo Shuai , Zhu Jing , Guo Shihao , Huang Zhihao , Li Jichang , Wang Xin , Liu Yucun , Chen Shanwen , Wang Pengyuan
Published: August 2021

Background

Globally, stomach adenocarcinoma (STAD)’s high morbidity and mortality should arouse our urgent attention. How long can STAD patients survive after surgery and whether novel immunotherapy is effective are questions that our clinicians cannot escape.

Methods

Various R packages, GSEA software, Metascape, STRING, Cytoscape, Venn diagram, TIMER2.0 website, TCGA, and GEO databases were used in our study.

Results

In the TCGA and GEO, macrophage abundance of STAD tissues was significantly higher than that of adjacent tissues and was an independent prognostic factor, significantly related to the overall survival (OS) of STAD patients. Between the high- and low- macrophage abundance, we conducted differential expression, univariate and multivariate Cox analysis, and obtained 12 candidate genes, and finally constructed a 3-gene signature. Both low macrophage abundance group and group D had higher TMB and PD-L1 expression. Furthermore, top 5 common gene-mutated STAD tissues had lower macrophage abundance. Macrophage abundance and 3 key genes expression were also lower in the Epstein-Barr Virus (EBV) and HM-indel STAD subtypes and significantly correlated with the tumor microenvironment score. The functional enrichment and ssGSEA revealed 2 signatures were similar and closely related to BOQUEST_STEM_CELL_UP, including genes up-regulated in proliferative stromal stem cells. Hsa-miR-335-5p simultaneously regulated 3 key genes and significantly related to the expression of PD-L1, CD8A and PDCD1.

Conclusion

macrophage abundance and 3-gene signature could simultaneously predict the OS and immunotherapy efficacy, and both 2 signatures had remarkable similarities. Hsa-miR-335-5p and BOQUEST_STEM_CELL_UP might be novel immunotherapy targets.
Interleukin 32 Promotes Foxp3+ Treg Cell Development and CD8+ T Cell Function in Human Esophageal Squamous Cell Carcinoma Microenvironment
Authors: Han Li , Chen Shiyu , Chen Zheyi , Zhou Bingqian , Zheng Yingxia , Shen Lisong
Published: August 2021

Proinflammatory cytokine interleukin 32 (IL-32) is involved in infectious diseases and cancer, but what subtypes of immune cells express IL-32 and its roles in tumor microenvironment (TME) have not been well discussed. In this study, we applied bioinformatics to analyze single-cell RNA sequencing data about tumor-infiltrating immune cells from esophageal squamous cell carcinoma (ESCC) TME and analyzed IL-32 expression in different immune cell types. We found CD4+regulatory T cells (Treg cells) express the highest level of IL-32, while proliferating T and natural killer cells expressed relatively lower levels. Knocking down of IL-32 reduced Foxp3 and interferon gamma (IFNγ) expressions in CD4+and CD8+T cells, respectively. IL-32 was positively correlated with Foxp3, IFNG, and GZMB expression but was negatively correlated with proliferation score. IL-32 may have a contradictory role in the TME such as it promotes IFNγ expression in CD8+T cells, which enhances the antitumor activity, but at the same time induces Foxp3 expression in CD4+T cells, which suppresses the tumor immune response. Our results demonstrate different roles of IL-32 in Treg cells and CD8+T cells and suggest that it can potentially be a target for ESCC cancer immunosuppressive therapy.
The Potential Role of RP105 in Regulation of Inflammation and Osteoclastogenesis During Inflammatory Diseases
Authors: Fan Zhou , Pathak Janak L. , Ge Linhu
Published: August 2021

Inflammatory diseases have a negative impact on bone homeostasis via exacerbated local and systemic inflammation. Bone resorbing osteoclasts are mainly derived from hematopoietic precursors and bone marrow monocytes. Induced osteoclastogenesis during inflammation, autoimmunity, metabolic diseases, and cancers is associated with bone loss and osteoporosis. Proinflammatory cytokines, pathogen-associated molecular patterns, or endogenous pathogenic factors induce osteoclastogenic differentiation by binding to the Toll-like receptor (TLR) family expressed on surface of osteoclast precursors. As a non-canonical member of the TLRs, radioprotective 105 kDa (RP105 or CD180) and its ligand, myeloid differentiation protein 1 (MD1), are involved in several bone metabolic disorders. Reports from literature had demonstrated RP105 as an important activator of B cells, bone marrow monocytes, and macrophages, which regulates inflammatory cytokines release from immune cells. Reports from literature had shown the association between RP105 and other TLRs, and the downstream signaling mechanisms of RP105 with different “signaling-competent” partners in immune cells during different disease conditions. This review is focused to summarize: (1) the role of RP105 on immune cells’ function and inflammation regulation (2) the potential regulatory roles of RP105 in different disease-mediated osteoclast activation and the underlying mechanisms, and (3) the different “signaling-competent” partners of RP105 that regulates osteoclastogenesis.
Gut Microbiota and Atherosclerosis—Focusing on the Plaque Stability
Authors: Shen Xinyi , Li Lihua , Sun Zhen , Zang Guangyao , Zhang Lili , Shao Chen , Wang Zhongqun
Published: August 2021

Cardiovascular diseases (CVDs) are major causes of mortality and morbidity in the modern society. The rupture of atherosclerotic plaque can induce thrombus formation, which is the main cause of acute cardiovascular events. Recently, many studies have demonstrated that there are some relationships between microbiota and atherosclerosis. In this review, we will focus on the effect of the microbiota and the microbe-derived metabolites, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS), on the stability of atherosclerotic plaque. Finally, we will conclude with some therapies based on the microbiota and its metabolites.
A New Inclusive Volcanic Risk Ranking, Part 1: Methodology
Authors: Nieto-Torres Amiel , Guimarães Leticia Freitas , Bonadonna Costanza , Frischknecht Corine
Published: August 2021

The ever-increasing population living near active volcanoes highlights the need for the implementation of effective risk reduction measures to save lives and reduce the impact of volcanic unrest and eruptions. To help identify volcanic systems associated with potential high risk and prioritize risk reduction strategies, we introduce a new Volcanic Risk Ranking (VRR) methodology that integrates hazard, exposure, and vulnerability as factors that increase risk, and resilience as a factor that reduces risk. Here we present a description of the methodology using Mexican volcanoes as a case study, while a regional application to Latin American volcanoes is presented in a companion paper (Guimarães et al., submitted). With respect to existing strategies, the proposed VRR methodology expands the parameters associated with hazard and exposure and includes the analysis of 4 dimensions of vulnerability (physical, systemic, social, economic) and of resilience. In particular, we propose 41 parameters to be analyzed, including 9 hazard parameters, 9 exposure parameters, 10 vulnerability parameters and 13 resilience parameters. Since the number of parameters evaluated for each risk factor is different, they are normalized to have the same weight based on dedicated sensitivity analyses. In order to best illustrate the methodology, the proposed VRR is here applied to 13 Mexican volcanoes and compared with other approaches. We found that the volcanoes associated with the highest combination of hazard, exposure and vulnerability (3-factor VRR) for this geographic area are Tacaná and El Chichón regardless of the analyzed time window of eruption occurrence (i.e., <1 and <10 ka). Nonetheless, the volcanoes with eruption <1 ka that require the most urgent actions as associated with no or few resilience measures in place are Michoacán-Guanajuato Volcanic Field and San Martín Tuxtla (4-factor VRR); the top volcanoes in the 4-factor VRR with eruption <10 ka are Michoacán-Guanajuato Volcanic Field and Las Cumbres.
Teaching in Times of COVID-19: The Evaluation of Distance Teaching in Elementary and Secondary Schools in Germany
Authors: Schneider Rebecca , Sachse Karoline A. , Schipolowski Stefan , Enke Florian
Published: August 2021

To depict the situation during the school closures in spring 2020 that were implemented to contain the spread of COVID-19, we conducted a self-constructed online survey on distance teaching among teachers regarding their teaching practices in this new situation, the challenges they experienced, and the prerequisites for successful distance teaching. The sample consisted of voluntarily participating German elementary (n= 857) and secondary school teachers (n= 1,590) from a sample of randomly drawn schools in four federal states in Germany. We describe the main survey findings and examine the importance of different distance teaching aspects for teacher reports of students attaining their learning objectives and students’ learning progress during distance teaching. Our results particularly highlight the necessity for students and teachers to remain in contact in all the surveyed school types. In elementary school, regular contact between teachers and parents is similarly important. The key challenges highlighted inadequate digitalization, the participation of all students, and students’ motivation. Correspondingly, adequate technical equipment for schools, teachers, and students, together with teachers’ and students’ competence to use technical devices and digital media as well as students’ motivation to participate in distance learning were found to be necessary prerequisites for successful distance teaching. We conclude that efforts should be devoted to enabling teachers and students to better communicate using digital devices, for example, expanding the digital infrastructure in combination with training teachers and students in the use of technical devices and digital media.
Lockdown Learning: Changes in Online Foreign-Language Study Activity and Performance of Dutch Secondary School Students During the COVID-19 Pandemic
Authors: van der Velde Maarten , Sense Florian , Spijkers Rinske , Meeter Martijn , van Rijn Hedderik
Published: August 2021

The COVID-19 pandemic caused lockdowns and sudden school closures around the world in spring 2020, significantly impacting the education of students. Here, we investigate how the switch to distance learning affected study activity and performance in an online retrieval practice tool used for language learning in Dutch secondary education. We report insights from a rich data set consisting of over 115 million retrieval practice trials completed by more than 133 thousand students over the course of two consecutive school years. Our findings show that usage of the tool increased substantially at the start of lockdown, with the bulk of study activity occurring on weekday mornings. In general, students’ progress through the material was largely unaffected by lockdown, although students from the highest educational track were somewhat more likely to be on or ahead of schedule than students from lower tracks, compared to the previous year. Performance on individual study trials was generally stable, but accuracy and response time on open answer questions went up, perhaps as a result of students being more focused at home. These encouraging findings contribute to a growing literature on the educational ramifications of distance learning during lockdown.
Psychological Stress and Functional Endometrial Disorders: Update of Mechanism Insights
Authors: Wu Jin-xiang , Lin Shu , Kong Shuang-bo
Published: August 2021

The human endometrium plays a vital role in providing the site for embryo implantation and maintaining the normal development and survival of the embryo. Recent studies have shown that stress is a common factor for the development of unexplained reproductive disorders. The nonreceptive endometrium and disturbed early maternal-fetal interaction might lead to infertility including the repeated embryo implantation failure and recurrent spontaneous abortion, or late pregnancy complications, thereby affecting the quality of life as well as the psychological status of the affected individuals. Additionally, psychological stress might also adversely affect female reproductive health. In recent years, several basic and clinical studies have tried to investigate the harm caused by psychological stress to reproductive health, however, the mechanism is still unclear. Here, we review the relationship between psychological stress and endometrial dysfunction, and its consequent effects on female infertility to provide new insights for clinical therapeutic interventions in the future.
Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing
Authors: Lv Yong , Xie Xiaolong , Pu Lihui , Wang Qi , Yang Jiayin , Pu Siyu , Ai Chengbo , Liu Yi , Chen Jing , Xiang Bo
Published: August 2021

A choledochal cyst (CC) is a common congenital biliary disease in children, yet the underlying molecular bases for the cystic and fusiform clinical subtypes are unknown. RNA sequencing (RNA-seq) has been performed on 22 high-quality CC samples, including 12 cystic CC and 10 fusiform CC samples, to search for molecular features. Weighted gene co-expression network analysis (WGCNA) was performed to identify key modules associated with clinical subtypes. Bioinformatic analyses were conducted to elucidate potential mechanisms. Then, we constructed protein–protein interaction (PPI) networks to identify candidate hub genes related to CC. Finally, we used the support vector machine (SVM) to eliminate redundant features and screen out the hub genes. The selected gene expression was determined in CC patients through quantitative real-time polymerase chain reaction (PCR). A total of 6,463 genes were found to be aberrantly expressed between cystic CC and fusiform CC. Twelve co-expression modules that correlated with clinical subtypes of CC were identified and assigned representative colors. Among the 12 modules, the blue module was considered the key module. Two functionally distinct sets of dysregulated genes have been identified in two major subtypes, metabolism-related genes in cystic CC and immune-related genes in fusiform CC. A total of 20 candidate hub genes that were correlated with clinical subtypes were found in the blue module. In addition, we found ERBB2 and WNT11 that have not been studied in CC and verified their differential expression in CC through quantitative real-time PCR experiments. For the first time, we have described the transcriptome characteristics of CC. These results suggest that cystic CC and fusiform CC have different molecular mechanisms. The bi-omics-identified novel candidate genes and pathways might be helpful for personalized treatment and are of great clinical significance for CC.
BMP4 Moderates Glycolysis and Regulates Activation and Interferon-Gamma Production in CD4+ T Cells
Authors: Huang Feng , Hu Lei , Zhang Yuanmin , Qu Xingmin , Xu Junji
Published: August 2021

BMP4 is a key growth factor well known in promoting bone regeneration and has been reported to be able to regulate T cell development in the thymus. Here, we showed that BMP4 downregulates the activation of naïve CD4+ T cells and the IFN-γ production of CD4+ T cells without increasing regulatory T cells. BMP4 could also moderate glycolysis of T cells and regulate Hif1α expression. Furthermore, BMP4 showed a suppressive function on the IFN-γ production of CD4+ T cells in vivo. These findings indicating a mechanism by which BMP-4 may regulate activation and IFN-γ production in CD4+ T cells via metabolism moderation and suggests that BMP4 may be a potential therapeutic supplement in autoinflammatory diseases.
Herbivory on the Invasive Alga Caulerpa cylindracea: The Role of Omnivorous Fishes
Authors: Santamaría Jorge , Tomas Fiona , Ballesteros Enric , Cebrian Emma
Published: August 2021

Herbivory has long been considered an important component of biotic resistance against macroalgae invasions in marine habitats. However, most of the studies on herbivory of invasive algae refer only to consumption by strictly herbivorous organisms, whereas consumption by omnivorous species has been largely ignored and rarely quantified. In this study, we assess whether the commonest omnivorous sparid species in the Mediterranean Sea are consuming the highly invasive alga, Caulerpa cylindracea, and determine both, its importance in their diet and their electivity toward it as a source of food. Our results confirm that three of the four fish species studied regularly consume C. cylindracea, but in most cases, the importance of C. cylindracea in the diet is low. Indeed, the low electivity values indicate that all species avoid feeding on the invasive alga and that it is probably consumed accidentally. However, despite animals and detritus being the main food for these sparid species, several individual specimens were found to have consumed high amounts of C. cylindracea. This suggests a potential role that these fish species, being really abundant in shallow rocky bottoms, may play in controlling, to some extent, the abundance of the invader.
Ten Considerations for Research Funders Seeking to Enhance Knowledge Exchange and the Impact of Marine Science on Policy and Practice
Authors: Cvitanovic Christopher , Wyborn Carina , Glenn Evora , Kelly Rachel , Louder Elena , van Putten Elizabeth I. , Bednarek Angela
Published: August 2021

Research funders can play an important role in supporting the integration of marine science into policy and practice to enable evidence-informed decision-making. However, to date, there is a paucity of guidance available to help research funders understand the specific actions they can take to support knowledge exchange among the researchers that they fund and relevant stakeholders, particularly within marine contexts. This Brief Research Report aims to begin to fill this gap through an in-depth case study of the Lenfest Ocean Program (LOP). Specifically, through qualitative interviews with 32 participants across eight LOP funded research projects (i.e., case studies) we sought to: (i) understand the types of impacts that have resulted from the LOP funded research, (ii) determine which activities undertaken by the LOP enabled funded research projects to achieve these impacts, and (iii) synthesize findings to articulate the core lessons that have emerged from our examination of these research projects. Results show that the concept of “research impact” is complex and can be interpreted in a number of ways including: (i) raising awareness of research among end-users, (ii) development and expansion of social networks, (iii) the provision of information to decision-makers, (iv) the development of decision-support tools, and (v) a direct contribution to policy change. We highlight the ways by which the LOP has supported the attainment of these impacts, as well as 10 general considerations that research funders should consider when seeking to enhance the impact of the research that they fund on marine policy and practice.
Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model
Authors: Yeung Chun-Yan , Chiang Chiau Jen-Shiu , Cheng Mei-Lein , Chan Wai-Tao , Jiang Chuen-Bin , Chang Szu-Wen , Liu Chia-Yuan , Chang Ching-Wei , Lee Hung-Chang
Published: August 2021

Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression.

Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated.

Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group.

Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.
Estimating the Transmissibility of Mumps: A Modelling Study in Wuhan City, China
Authors: Peng Ying , Yang Tianlong , Zhu Yuanzhao , Hu Qingqing , Wang Yao , Zhao Zeyu , Rui Jia , Lin Shengnan , Liu Xingchun , Xu Jingwen , Yang Meng , Deng Bin , Huang Jiefeng , Liu Weikang , Luo Li , Liu Chan , Li Zhuoyang , Li Peihua , Kong Deguang , Yang Xiaobing , Chen Tianmu
Published: August 2021

Despite the adoption of a national immunization program in China, the incidence of mumps remains high. This study aimed to describe the epidemiological characteristics, including the time, region, occupation, and age, of mumps in Wuhan from 2005 to 2018 and to evaluate its transmissibility. In this study, the susceptible–exposed–infectious–asymptomatic–recovered (SEIAR) model fitted the actual incidence data of mumps. The effective reproduction number (Rt) was used to evaluate and compare the transmission capacity in different areas. From 2005 to 2018, there were 36,415 cases. The incidence of mumps was highest among people aged 5–10 years (460.02 per 100,000). The SEIAR model fitted the reported mumps data well (P < 0.01). The median transmissibility (Rt) was 1.04 (range = 0–2.50). There were two peak spreads every year (from March to May and from October to December). The Rt peak always appeared in the first 2 months of the peak incidence rate. The peak time of the epidemic spread of mumps was 1–2 months earlier than the peak incidence rate. The prevention and control measures of vaccination for children aged 5–10 years should be taken before the peak transmission capacity each year, 2 months before the peak of the outbreak, to reduce the spread of mumps.
Impact of the Internal Carotid Artery Morphology on in silico Stent-Retriever Thrombectomy Outcome
Authors: Bridio Sara , Luraghi Giulia , Rodriguez Matas Jose F. , Dubini Gabriele , Giassi Giorgia G. , Maggio Greta , Kawamoto Julia N. , Moerman Kevin M. , McGarry Patrick , Konduri Praneeta R. , Arrarte Terreros Nerea , Marquering Henk A. , van Bavel Ed , Majoie Charles B. L. M. , Migliavacca Francesco
Published: August 2021

The aim of this work is to propose a methodology for identifying relationships between morphological features of the cerebral vasculature and the outcome of in silico simulations of thrombectomy, the mechanical treatment for acute ischemic stroke. Fourteen patient-specific cerebral vasculature segmentations were collected and used for geometric characterization of the intracranial arteries mostly affected by large vessel occlusions, i.e., internal carotid artery (ICA), middle cerebral artery (MCA) and anterior cerebral artery (ACA). First, a set of global parameters was created, including the geometrical information commonly provided in the clinical context, namely the total length, the average diameter and the tortuosity (length over head-tail distance) of the intracranial ICA. Then, a more exhaustive geometrical analysis was performed to collect a set of local parameters. A total of 27 parameters was measured from each patient-specific vascular configuration. Fourteen virtual thrombectomy simulations were performed with a blood clot with the same length and composition placed in the middle of the MCA. The model of TREVO ProVue stent-retriever was used for all the simulations. Results from simulations produced five unsuccessful outcomes, i.e., the clot was not removed from the vessels. The geometric parameters of the successful and unsuccessful simulations were compared to find relations between the vascular geometry and the outcome. None of the global parameters alone or combined proved able to discriminate between positive and negative outcome, while a combination of local parameters allowed to correctly identify the successful from the unsuccessful simulations. Although these results are limited by the number of patients considered, this study indicates a promising methodology to relate patient-specific geometry to virtual thrombectomy outcome, which might eventually guide decision making in the treatment of acute ischemic stroke.
The Elevated Endogenous Reactive Oxygen Species Contribute to the Sensitivity of the Amphotericin B-Resistant Isolate of Aspergillus flavus to Triazoles and Echinocandins
Authors: Liang Tianyu , Chen Wei , Yang Xinyu , Wang Qiqi , Wan Zhe , Li Ruoyu , Liu Wei
Published: August 2021

Aspergillus flavus has been frequently reported as the second cause of invasive aspergillosis (IA), as well as the leading cause in certain tropical countries. Amphotericin B (AMB) is a clinically important therapy option for a range of invasive fungal infections including invasive aspergillosis, and in vitro resistance to AMB was associated with poor outcomes in IA patients treated with AMB. Compared with the AMB-susceptible isolates of A. terreus, the AMB-resistant isolates of A. terreus showed a lower level of AMB-induced endogenous reactive oxygen species (ROS), which was an important cause of AMB resistance. In this study, we obtained one AMB-resistant isolate of A. flavus, with an AMB MIC of 32 μg/mL, which was sensitive to triazoles and echinocandins. This isolate presented elevated endogenous ROS levels, which strongly suggested that no contribution of decreased AMB-induced endogenous ROS for AMB-resistance, opposite to those observed in A. terreus. Further, we confirmed that the elevated endogenous ROS contributed to the sensitivity of the AMB-resistant A. flavus isolate to triazoles and echinocandins. Further investigation is needed to elucidate the causes of elevated endogenous ROS and the resistance mechanism to AMB in A. flavus.
The Small Protein YmoA Controls the Csr System and Adjusts Expression of Virulence-Relevant Traits of Yersinia pseudotuberculosis
Authors: Böhme Katja , Heroven Ann Kathrin , Lobedann Stephanie , Guo Yuzhu , Stolle Anne-Sophie , Dersch Petra
Published: August 2021

Virulence gene expression of Yersinia pseudotuberculosis changes during the different stages of infection and this is tightly controlled by environmental cues. In this study, we show that the small protein YmoA, a member of the Hha family, is part of this process. It controls temperature- and nutrient-dependent early and later stage virulence genes in an opposing manner and co-regulates bacterial stress responses and metabolic functions. Our analysis further revealed that YmoA exerts this function by modulating the global post-transcriptional regulatory Csr system. YmoA pre-dominantly enhances the stability of the regulatory RNA CsrC. This involves a stabilizing stem-loop structure within the 5′-region of CsrC. YmoA-mediated CsrC stabilization depends on H-NS, but not on the RNA chaperone Hfq. YmoA-promoted reprogramming of the Csr system has severe consequences for the cell: we found that a mutant deficient of ymoA is strongly reduced in its ability to enter host cells and to disseminate to the Peyer’s patches, mesenteric lymph nodes, liver and spleen in mice. We propose a model in which YmoA controls transition from the initial colonization phase in the intestine toward the host defense phase important for the long-term establishment of the infection in underlying tissues.
A Type I Restriction Modification System Influences Genomic Evolution Driven by Horizontal Gene Transfer in Paenibacillus polymyxa
Authors: Chen Ziyan , Shen Minjia , Mao Chengyao , Wang Chenyu , Yuan Panhong , Wang Tingzhang , Sun Dongchang
Published: August 2021

Considered a “Generally Recognized As Safe” (GRAS) bacterium, the plant growth–promoting rhizobacterium Paenibacillus polymyxa has been widely applied in agriculture and animal husbandry. It also produces valuable compounds that are used in medicine and industry. Our previous work showed the presence of restriction modification (RM) system in P. polymyxa ATCC 842. Here, we further analyzed its genome and methylome by using SMRT sequencing, which revealed the presence of a larger number of genes, as well as a plasmid documented as a genomic region in a previous report. A number of mobile genetic elements (MGEs), including 78 insertion sequences, six genomic islands, and six prophages, were identified in the genome. A putative lysozyme-encoding gene from prophage P6 was shown to express lysin which caused cell lysis. Analysis of the methylome and genome uncovered a pair of reverse-complementary DNA methylation motifs which were widespread in the genome, as well as genes potentially encoding their cognate type I restriction-modification system PpoAI. Further genetic analysis confirmed the function of PpoAI as a RM system in modifying and restricting DNA. The average frequency of the DNA methylation motifs in MGEs was lower than that in the genome, implicating a role of PpoAI in restricting MGEs during genomic evolution of P. polymyxa. Finally, comparative analysis of R, M, and S subunits of PpoAI showed that homologs of the PpoAI system were widely distributed in species belonging to other classes of Firmicute, implicating a role of the ancestor of PpoAI in the genomic evolution of species beyond Paenibacillus.
Gait Kinematic and Kinetic Characteristics of Older Adults With Mild Cognitive Impairment and Subjective Cognitive Decline: A Cross-Sectional Study
Authors: Zhong Qian , Ali Nawab , Gao Yaxin , Wu Han , Wu Xixi , Sun Cuiyun , Ma Jinhui , Thabane Lehana , Xiao Ming , Zhou Qiumin , Shen Ying , Wang Tong , Zhu Yi
Published: August 2021

Background

Older adults with mild cognitive impairment (MCI) have slower gait speed and poor gait performance under dual-task conditions. However, gait kinematic and kinetic characteristics in older adults with MCI or subjective cognitive decline (SCD) remain unknown. This study was designed to explore the difference in gait kinematics and kinetics during level walking among older people with MCI, SCD, and normal cognition (NC).

Methods

This cross-sectional study recruited 181 participants from July to December 2019; only 82 met the inclusion criteria and consented to participate and only 79 completed gait analysis. Kinematic and kinetic data were obtained using three-dimensional motion capture system during level walking, and joint movements of the lower limbs in the sagittal plane were analyzed by Visual 3D software. Differences in gait kinematics and kinetics among the groups were analyzed using multivariate analysis of covariance (MANCOVA) with Bonferroni post-hoc analysis. After adjusting for multiple comparisons, the significance level was p < 0.002 for MANCOVA and p < 0.0008 for post-hoc analysis.

Results

Twenty-two participants were MCI [mean ± standard deviation (SD) age, 71.23 ± 6.65 years], 33 were SCD (age, 72.73 ± 5.25 years), and 24 were NC (age, 71.96 ± 5.30 years). MANCOVA adjusted for age, gender, body mass index (BMI), gait speed, years of education, diabetes mellitus, and Geriatric Depression Scale (GDS) revealed a significant multivariate effect of group in knee peak extension angle (F = 8.77, p < 0.0001) and knee heel strike angle (F = 8.07, p = 0.001) on the right side. Post-hoc comparisons with Bonferroni correction showed a significant increase of 5.91° in knee peak extension angle (p < 0.0001) and a noticeable decrease of 6.21°in knee heel strike angle (p = 0.001) in MCI compared with NC on the right side. However, no significant intergroup difference was found in gait kinetics, including dorsiflexion, plantar flexion, knee flexion, knee extension, hip flexion, and hip extension(p > 0.002).

Conclusion

An increase of right knee peak extension angle and a decrease of right knee heel strike angle during level walking were found among older adults with MCI compared to those with NC.
Differentiation of Cerebellum-Type and Parkinson-Type of Multiple System Atrophy by Using Multimodal MRI Parameters
Authors: Cui Bin , Zheng Weimin , Ren Shan , Chen Zhigang , Wang Zhiqun
Published: August 2021

Recent studies have demonstrated the structural and functional changes in patients with multiple system atrophy (MSA). However, little is known about the different parameter changes of the most vulnerable regions in different types of MSA. In this study, we collected resting-state structure, perfusion, and patients with functional magnetic resonance imaging (fMRI) data of cerebellum-type of MSA (MSA-c) and Parkinson-type of MSA (MSA-p). First, by simultaneously using voxel-based morphology (VBM), arterial spin labeling (ASL), and amplitude of low-frequency fluctuation (ALFF), we analyzed the whole brain differences of structure, perfusion, and functional activation between patients with MSA-c and MSA-p. Second, we explored the relationships among structure, perfusion, function, and the clinical variables in patients with MSA. Finally, we extracted the MRI parameters of a specific region to separate the two groups and search for a sensitive imaging biomarker. As a result, compared with patients with MSA-p type, patients with MSA-c type showed decreased structure atrophy in several cerebella and vermis subregions, reduced perfusion in bilateral cerebellum_4_5 and vermis_4_5, and an decreased ALFF values in the right lingual gyrus (LG) and fusiform (FFG). Subsequent analyses revealed the close correlations among structure, perfusion, function, and clinical variables in both MSA-c and MSA-p. Finally, the receiver operating characteristic (ROC) analysis showed that the regional cerebral blood flow (rCBF) of bilateral cerebellum_4_5/vermis_4_5 could differentiate the two groups at a relatively high accuracy, yielding the sensitivity of 100%, specificity of 79.2%, and the area under the curve (AUC) value of 0.936. These findings have important implications for understanding the underlying neurobiology of different types of MSA and added the new evidence for the disrupted rCBF, structure, and function of MSA, which may provide the potential biomarker for accurately detecting different types of patients with MSA and new ideas for the treatment of different types of MSA in the future.
Adherence to Healthy Lifestyle and the Risk of Function Limitations in Late Life: The Atherosclerosis Risk in Communities Study
Authors: Li Dongze , Jia Yu , Yu Jing , Liu Yi , Li Fanghui , Liu Yanmei , Wu Qinqin , Liao Xiaoyang , Zeng Zhi , Zeng Rui , Wan Zhi
Published: August 2021

Background: Physiological function impairment is the main precursor of assisted living, movement disorder, and disability in the elderly. The relationship between a combination of healthy lifestyle factors and functional limitations is unclear. We investigated the association between healthy lifestyle scores and the risk of functional impairment in community residents.

Methods: A total of 10,602 participants (aged 40–64 years) of the Atherosclerosis Risk in Communities (ARIC) study with no history of cardiovascular events and tumors and who came for their fourth visit (1997–1999) were included in the final analysis. Primary outcomes were recorded during the fourth visit; these included impaired lower extremity function, activities of daily living, and instrumental activities of daily living. A logistic regression model was used to test the associations between healthy lifestyle scores and functional impairment. The lifestyle score comprised six factors: healthy diet, moderate alcohol consumption, coffee consumption, physical activity, normal body weight, and no smoking.

Results: Among the 10,602 participants with a median follow-up of 9 years, the prevalence rates of impaired lower extremity function, activities of daily living, and instrumental activities of daily living were 50.6%, 14.7%, and 21.6%, respectively. In the adjusted Cox regression model, participants with a healthy lifestyle score of 5 plus 6 had a significant lower risk of impaired lower extremity function (odds ratio = 0.252, 95% confidence interval: 0.184–0.344,P< 0.001), activities of daily living (odds ratio = 0.201, 95% confidence interval: 0.106–0.380,P< 0.001), and instrumental activities of daily living (odds ratio = 0.274, 95% confidence interval: 0.168–0.449,P< 0.001) than did participants with a score of 0. The association of healthy lifestyle scores with impaired activities of daily living and instrumental activities of daily living was stronger for individuals without diabetes than for those with it (Pfor interaction < 0.05). This can be partly explained by the fact that the lowest risk of functional impairment among the participants with diabetes was associated with being overweight.

Conclusion: Adherence to an overall healthy lifestyle was associated with a lower risk of physiological function limitation. This study highlights the importance of behavioral interventions in the prevention of disabilities.

Clinical Trial Registration:www.ClinicalTrials.gov; Unique identifier: NCT00005131.
Stimulus Driven Functional Transformations in the Early Olfactory System
Authors: Martelli Carlotta , Storace Douglas Anthony
Published: August 2021

Olfactory stimuli are encountered across a wide range of odor concentrations in natural environments. Defining the neural computations that support concentration invariant odor perception, odor discrimination, and odor-background segmentation across a wide range of stimulus intensities remains an open question in the field. In principle, adaptation could allow the olfactory system to adjust sensory representations to the current stimulus conditions, a well-known process in other sensory systems. However, surprisingly little is known about how adaptation changes olfactory representations and affects perception. Here we review the current understanding of how adaptation impacts processing in the first two stages of the vertebrate olfactory system, olfactory receptor neurons (ORNs), and mitral/tufted cells.