bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and Verification of a Combined Hypoxia and Immune Index for Clear Cell Renal Cell Carcinoma
Authors: Wang Bin , Liu Lixiao , Wu Jinting , Mao Xiaolu , Fang Zhen , Chen Yingyu , Li Wenfeng
Published: February 2022

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive malignancies in humans. Hypoxia-related genes are now recognized as a reflection of poor prognosis in cancer patients with cancer. Meanwhile, immune-related genes play an important role in the occurrence and progression of ccRCC. Nevertheless, reliable prognostic indicators based on hypoxia and immune status have not been well established in ccRCC. The aims of this study were to develop a new gene signature model using bioinformatics and open databases and to validate its prognostic value in ccRCC. The data used for the model structure can be accessed from The Cancer Genome Atlas database. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the hypoxia- and immune-related genes associated with prognostic risk, which were used to develop a characteristic model of prognostic risk. Kaplan-Meier and receiver-operating characteristic curve analyses were performed as well as independent prognostic factor analyses and correlation analyses of clinical characteristics in both the training and validation cohorts. In addition, differences in tumor immune cell infiltrates were compared between the high and low risk groups. Overall, 30 hypoxia- and immune-related genes were identified, and five hypoxia- and immune-related genes (EPO, PLAUR, TEK, TGFA, TGFB1) were ultimately selected. Survival analysis showed that the high-risk score on the hypoxia- and immune-related gene signature was significantly associated with adverse survival outcomes. Furthermore, clinical ccRCC samples from our medical center were used to validate the differential expression of the five genes in tumor tissue compared to normal tissue through quantitative real-time polymerase chain reaction (qRT-PCR). However, more clinical trials are needed to confirm these results, and future experimental studies must verify the potential mechanism behind the predictive value of the hypoxia- and immune-related gene signature.
Identification of CCL19 as a Novel Immune-Related Biomarker in Diabetic Nephropathy
Authors: Chen Hanzhi , Zhang Zhijian , Zhou Leting , Cai Ting , Liu Bin , Wang Liang , Yang Junwei
Published: February 2022

Diabetic nephropathy (DN) is one of the major microvascular complications in diabetic patients and the leading cause of end-stage renal disease (ESRD). Previous studies found that immune-related genes and immune cell infiltration play important roles in the pathogenesis and development of DN. Therefore, this study aimed to explore immune-related biomarkers in DN. In this research, three microarray datasets that included 18 DN and 28 healthy tubule samples were downloaded and integrated as the training set to identify differentially expressed immune-related genes (DEIGs). A total of 63 DEIGs were identified, and most upregulated DEIGs were primarily involved in the inflammatory response and chemokine-mediated signaling pathways. The Microenvironment Cell Populations-counter (MCP-counter) algorithm was then used to estimate the abundance of infiltrated immune and stromal cell populations. According to DEIG, weighted gene coexpression network and protein–protein network analyses, CCL19 was identified as the hub immune-related biomarker. Moreover, the upregulated level of CCL19 was confirmed in other independent datasets as well as in in vitro experiments with high glucose. In summary, this study provides novel insights into the pathogenesis of diabetic nephropathy and identifies CCL19 as a potential critical gene of DN.
Determining Sex-Based Differences in Inflammatory Response in an Experimental Traumatic Brain Injury Model
Authors: Scott Michael C. , Prabhakara Karthik S. , Walters Andrew J. , Olson Scott D. , Cox Charles S.
Published: February 2022

Introduction

Traumatic brain injury is a leading cause of injury-related death and morbidity. Multiple clinical and pre-clinical studies have reported various results regarding sex-based differences in TBI. Our accepted rodent model of traumatic brain injury was used to identify sex-based differences in the pathological features of TBI.

Methods

Male and female Sprague-Dawley rats were subjected to either controlled-cortical impact (CCI) or sham injury; brain tissue was harvested at different time intervals depending on the specific study. Blood-brain barrier (BBB) analysis was performed using infrared imaging to measure fluorescence dye extravasation. Microglia and splenocytes were characterized with traditional flow cytometry; microglia markers such as CD45, P2Y12, CD32, and CD163 were analyzed with t-distributed stochastic neighbor embedding (t-SNE). Flow cytometry was used to study tissue cytokine levels, and supplemented with ELISAs of TNF-⍺, IL-17, and IL-1β of the ipsilateral hemisphere tissue.

Results

CCI groups of both sexes recorded a higher BBB permeability at 72 hours post-injury than their respective sham groups. There was significant difference in the integrated density value of BBB permeability between the male CCI group and the female CCI group (female CCI mean = 3.08 x 108 ± 2.83 x 107, male CCI mean = 2.20 x 108 ± 4.05 x 106, p = 0.0210), but otherwise no differences were observed. Traditional flow cytometry did not distinguish any sex-based difference in regards to splenocyte cell population after CCI. t-SNE did not reveal any significant difference between the male and female injury groups in the activation of microglia. Cytokine analysis after injury by flow cytometry and ELISA was limited in differences at the time point of 6 hours post-injury.

Conclusion

In our rodent model of traumatic brain injury, sex-based differences in pathology and neuroinflammation at specified time points are limited, and only noted in one specific analysis of BBB permeability.
ATG Ubiquitination Is Required for Circumsporozoite Protein to Subvert Host Innate Immunity Against Rodent Malaria Liver Stage
Authors: Zheng Hong , Lu Xiao , Li Kai , Zhu Feng , Zhao Chenhao , Liu Taiping , Ding Yan , Fu Yong , Zhang Kun , Zhou Taoli , Dai Jigang , Wu Yuzhang , Xu Wenyue
Published: February 2022

Although exo-erythrocytic forms (EEFs) of liver stage malaria parasite in the parasitophorous vacuole (PV) are encountered with robust host innate immunity, EEFs can still survive and successfully complete the infection of hepatocytes, and the underlying mechanism is largely unknown. Here, we showed that sporozoite circumsporozoite protein (CSP) translocated from the parasitophorous vacuole into the hepatocyte cytoplasm significantly mediated the resistance to the killing of EEFs by interferon-gamma (IFN-γ). Attenuation of IFN-γ-mediated killing of EEFs by CSP was dependent on its ability to reduce the levels of autophagy-related genes (ATGs) in hepatocytes. The ATGs downregulation occurred through its enhanced ubiquitination mediated by E3 ligase NEDD4, an enzyme that was upregulated by CSP when it translocated from the cytoplasm into the nucleus of hepatocytesviaits nuclear localization signal (NLS) domain. Thus, we have revealed an unrecognized role of CSP in subverting host innate immunity and shed new light for a prophylaxis strategy against liver-stage infection.
Inflammatory Markers, Pulmonary Function, and Clinical Symptoms in Acute COVID-19 Among Non-Hospitalized Adolescents and Young Adults
Authors: Lund Berven Lise , Selvakumar Joel , Havdal Lise , Stiansen-Sonerud Tonje , Einvik Gunnar , Leegaard Truls Michael , Tjade Trygve , Michelsen Annika E. , Mollnes Tom Eirik , Wyller Vegard Bruun Bratholm
Published: February 2022

Mild, subacute COVID-19 in young people show inflammatory enhancement, but normal pulmonary function. Inflammatory markers are associated with age and male sex, whereas clinical symptoms are associated with age and female sex, but not with objective disease markers.

Background

Coronavirus Disease 2019 (COVID-19) is widespread among adolescents and young adults across the globe. The present study aimed to compare inflammatory markers, pulmonary function and clinical symptoms across non-hospitalized, 12 – 25 years old COVID-19 cases and non-COVID-19 controls, and to investigate associations between inflammatory markers, clinical symptoms, pulmonary function and background variables in the COVID-19 group.

Methods

The present paper presents baseline data from an ongoing longitudinal observational cohort study (Long-Term Effects of COVID-19 in Adolescents, LoTECA, ClinicalTrials ID: NCT04686734). A total of 31 plasma cytokines and complement activation products were assayed by multiplex and ELISA methodologies. Pulmonary function and clinical symptoms were investigated by spirometry and questionnaires, respectively.

Results

A total of 405 COVID-19 cases and 111 non-COVID-19 controls were included. The COVID-19 group had significantly higher plasma levels of IL-1β, IL-4, IL-7, IL-8, IL-12, TNF, IP-10, eotaxin, GM-CSF, bFGF, complement TCC and C3bc, and significantly lower levels of IL-13 and MIP-1α, as compared to controls. Spirometry did not detect any significant differences across the groups. IL-4, IL-7, TNF and eotaxin were negatively associated with female sex; eotaxin and IL-4 were positively associated with age. Clinical symptoms were positively associated with female sex and age, but not with objective disease markers.

Conclusions

Among non-hospitalized adolescents and young adults with COVID-19 there was significant alterations of plasma inflammatory markers in the subacute stage of the infection. Still, pulmonary function was normal. Clinical symptoms were independent of inflammatory and pulmonary function markers, but positively associated with age and female sex.
The Relationship Between Successful Aging and All-Cause Mortality Risk in Older Adults: A Systematic Review and Meta-Analysis of Cohort Studies
Authors: Mao Lifen , Yin Rulan , Cai Jianzheng , Niu Mei'e , Xu Lan , Sui Wenjie , Shi Xiaoqing
Published: February 2022

Background

This meta-analysis aimed to explore the effect of successful aging (SA) on all-cause mortality risk in older people to provide a theoretical basis for promoting SA.

Methods

PubMed, Embase, CINAHL, CNKI, and WanFang databases (inception to March 4, 2021) were searched for cohort studies to evaluate the relationship between SA and mortality in older people. A random-effects model was used to synthesis hazard ratio and 95% confidence intervals. Quality assessment was performed using the Newcastle–Ottawa scale. All statistical analyses were conducted in STATA 16.0.

Results

In total, 21,158 older adults from 10 studies were included in the current systematic review and meta-analysis. The SA group tended to have 50% lower risk of all-cause mortality than the non-SA group (pooled hazard ratio = 0.50, 95% confidence intervals: 0.35–0.65, P < 0.001; I2 = 58.3%). The risk of all-cause mortality in older people increased by 17% for each unit increment in the healthy aging index (HAI) (I2 = 0%, P = 0.964). Compared with the reference group (HAI 0-2), older people with HAI 3-4, HAI 5-6, and HAI 7-10 had 1.31-fold, 1.73-fold, and 2.58-fold greater risk of all-cause mortality, respectively. Subgroup analysis did not reveal possible sources of heterogeneity.

Conclusions

This meta-analysis suggests that older adults with SA reduced the risk of all-cause mortality by 50%. However, few interventional studies have been conducted. Therefore, healthcare providers must be aware of the relationship between SA and mortality risk and actively develop intervention methods for helping old people achieve SA.
Adherence, Safety, and Effectiveness of Medical Cannabis and Epidemiological Characteristics of the Patient Population: A Prospective Study
Authors: Bar-Lev Schleider Lihi , Mechoulam Raphael , Sikorin Inbal , Naftali Timna , Novack Victor
Published: February 2022

Background

Despite the absence of rigorous prospective studies, there has been an increase in the use of cannabis-based medicinal products. During the study period, the use of medical cannabis in Israel was tightly regulated by national policy. Through a prospective study of approximately 10,000 patients, we aimed to characterize the medical cannabis patient population as well as to identify treatment adherence, safety, and effectiveness.

Methods and Findings

In this study of prescribed medical cannabis patients, adherence, safety, and effectiveness were assessed at 6 months. Treatment adherence was assessed by the proportion of patients purchasing the medication out of the total number of patients (excluding deceased cases and patients transferred to another cannabis clinic). Safety was assessed by the frequency of the side-effects, while effectiveness was defined as at least moderate improvement in the patient condition without treatment cessation or serious side-effects. The most frequent primary indications requiring therapy were cancer (49.1%), followed by non-specific pain (29.3%). The average age was 54.6 ± 20.9 years, 51.1% males; 30.2% of the patients reported prior experience with cannabis. During the study follow-up, 1,938 patients died (19.4%) and 1,735 stopped treatment (17.3%). Common side-effects, reported by 1,675 patients (34.2%), were: dizziness (8.2%), dry mouth (6.7%), increased appetite (4.7%), sleepiness (4.4%), and psychoactive effect (4.3%). Overall, 70.6% patients had treatment success at 6 months. Multivariable logistic regression analysis revealed that the following factors were associated with treatment success: cigarette smoking, prior experience with cannabis, active driving, working, and a young age. The main limitation of this study was the lack of data on safety and effectiveness of the treatment for patients who refused to undergo medical assessment even at baseline or died within the first 6 months.

Conclusions

We observed that supervised medical-cannabis treatment is associated with high adherence, improvement in quality of life, and a decrease in pain level with a low incidence of serious adverse events.
Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology
Authors: Cosgrove Dominic , Madison Jacob
Published: February 2022

Alport syndrome results from a myriad of variants in the COL4A3, COL4A4, or COL4A5 genes that encode type IV (basement membrane) collagens. Unlike type IV collagen α1(IV)2α2(IV)1 heterotrimers, which are ubiquitous in basement membranes, α3/α4/α5 have a limited tissue distribution. The absence of these basement membrane networks causes pathologies in some, but not all these tissues. Primarily the kidney glomerulus, the stria vascularis of the inner ear, the lens, and the retina as well as a rare link with aortic aneurisms. Defects in the glomerular basement membranes results in delayed onset and progressive focal segmental glomerulosclerosis ultimately requiring the patient to undergo dialysis and if accessible, kidney transplant. The lifespan of patients with Alport syndrome is ultimately significantly shortened. This review addresses the consequences of the altered glomerular basement membrane composition in Alport syndrome with specific emphasis on the mechanisms underlying initiation and progression of glomerular pathology.
SARS-CoV-2 Variant Determination Through SNP Assays in Samples From Industry Workers From Rio de Janeiro, Brazil
Authors: Henriques-Santos Bianca Monteiro , Farjun Bruna , Corrêa Isadora Alonso , Figueiredo Janaina de Barros , Fidalgo-Neto Antonio Augusto , Kuriyama Sergio Noboru
Published: February 2022

Since the first reported case in December 2019, SARS-CoV-2 infections have become a major public health worldwide. Even with the increasing vaccination in several countries and relaxing of social distancing measures, the pandemic remains a threat especially due to the emergence of new SARS-CoV-2 variants. Despite the presence of an enzyme capable of proofreading its genome, high rates of replication provide a source of accumulation of mutations within the viral genome. In this retrospective study, samples from a cohort of industry workers tested by the SESI’s COVID-19 mass testing program from September 2020 to May 2021 were analyzed using a mutation panel in order to describe the circulation of currently identified SARS-CoV-2 variants within the samples obtained in Rio de Janeiro State. Our results demonstrated that the variant of interest (VOI) Zeta has been in circulation since October 2020 and reached 87% of prevalence in February 2021 followed by a decrease due to the emergence of Gamma variant of concern (VOC). Gamma was detected in January 2021 in our studied population, and its prevalence increased during the following months, reaching absolute prevalence within positive samples in May. The Alpha variant was detected only in 4–7% of samples during March and April while Beta VOC was not detected in our study. Our data agree with sequencing genomic surveillance databases and highlight the importance of continuous mass testing programs and variant detection in order to control viral spread and guide public health measures.
Endogenous CRISPR-Cas Systems in Group I Clostridium botulinum and Clostridium sporogenes Do Not Directly Target the Botulinum Neurotoxin Gene Cluster
Authors: Wentz Travis G. , Tremblay Benjamin J. M. , Bradshaw Marite , Doxey Andrew C. , Sharma Shashi K. , Sauer John-Demian , Pellett Sabine
Published: February 2022

Most strains of proteolytic group I Clostridium botulinum (G1 C. botulinum) and some strains of Clostridium sporogenes possess genes encoding botulinum neurotoxin (BoNT), a potent neuroparalytic agent. Within G1 C. botulinum, conserved bont gene clusters of three major toxin serotypes (bont/A/B/F) can be found on conjugative plasmids and/or within chromosomal pathogenicity islands. CRISPR-Cas systems enable site-specific targeting of previously encountered mobile genetic elements (MGE) such as plasmids and bacteriophage through the creation of a spacer library complementary to protospacers within the MGEs. To examine whether endogenous CRISPR-Cas systems restrict the transfer of bont gene clusters across strains we conducted a bioinformatic analysis profiling endogenous CRISPR-Cas systems from 241 G1 C. botulinum and C. sporogenes strains. Approximately 6,200 CRISPR spacers were identified across the strains and Type I-B, III-A/B/D cas genes and CRISPR array features were identified in 83% of the strains. Mapping the predicted spacers against the masked strain and RefSeq plasmid dataset identified 56,000 spacer–protospacer matches. While spacers mapped heavily to targets within bont(+) plasmids, no protospacers were identified within the bont gene clusters. These results indicate the toxin is not a direct target of CRISPR-Cas but the plasmids predominantly responsible for its mobilization are. Finally, while the presence of a CRISPR-Cas system did not reliably indicate the presence or absence of a bont gene cluster, comparative genomics across strains indicates they often occupy the same hypervariable loci common to both species, potentially suggesting similar mechanisms are involved in the acquisition and curation of both genomic features.
Genome-Based Classification of Strain 16-SW-7, a Marine Bacterium Capable of Converting B Red Blood Cells, as Pseudoalteromonas distincta and Proposal to Reclassify Pseudoalteromonas paragorgicola as a Later Heterotypic Synonym of Pseudoalteromonas distincta
Authors: Nedashkovkaya Olga I. , Kim Song-Gun , Balabanova Larissa A. , Zhukova Natalia V. , Son Oksana M. , Tekutyeva Liudmila A. , Mikhailov Valery V.
Published: February 2022

A strictly aerobic, Gram-stain-negative, rod-shaped, and motile bacterium, designated strain 16-SW-7, isolated from a seawater sample, was investigated in detail due to its ability to produce a unique α-galactosidase converting B red blood cells into the universal type blood cells. The phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain 16-SW-7 is a member of the Gammaproteobacteria genus Pseudoalteromonas. The closest relatives of the environmental isolate were Pseudoalteromonas distincta KMM 638T and Pseudoalteromonas paragorgicola KMM 3548T, with the plural paralogous 16S rRNA genes of 99.87–100% similarity. The strain 16-SW-7 grew with 1–10% NaCl and at 4–34°C, and hydrolyzed casein, gelatin, tyrosine, and DNA. The genomic DNA G+C content was 39.3 mol%. The prevalent fatty acids were C16:1 ω7c, C16:0, C17:1 ω8c, C18:1 ω7c, C17:0, and C12:0 3-OH. The polar lipid profile was characterized by the presence of phosphatidylethanolamine, phosphatidylglycerol, two unidentified amino lipids, and three unidentified lipids. The major respiratory quinone was Q-8. The finished genome of the strain 16-SW-7 (GenBank assembly accession number: GCA_005877035.1) has a size of 4,531,445 bp and comprises two circular chromosomes L1 and S1, deposited in the GenBank under the accession numbers CP040558 and CP040559, respectively. The strain 16-SW-7 has the ANI values of 98.2% with KMM 638T and KMM 3548T and the DDH values of 84.4 and 83.5%, respectively, indicating clearly that the three strains belonged to a single species. According to phylogenetic evidence and similarity for the chemotaxonomic and genotypic properties, the strain 16-SW-7 (= KCTC 52772 = KMM 701) represents a novel member of the species Pseudoalteromonas distincta. Also, we have proposed to reclassify Pseudoalteromonas paragorgicola as a later heterotypic synonym of P. distincta based on the rules of priority with the emendation of the species.
Revealing the Yeast Diversity of the Flor Biofilm Microbiota in Sherry Wines Through Internal Transcribed Spacer-Metabarcoding and Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry
Authors: Carbonero-Pacheco Juan , Moreno-García Jaime , Moreno Juan , García-Martínez Teresa , Mauricio Juan Carlos
Published: February 2022

Flor yeast velum is a biofilm formed by certain yeast strains that distinguishes biologically aged wines such as Sherry wine from southern Spain from others. AlthoughSaccharomyces cerevisiaeis the most common species, 5.8 S-internal transcribed spacer (ITS) restriction fragment length polymorphism analyses have revealed the existence of non-Saccharomycesspecies. In order to uncover the flor microbiota diversity at a species level, we used ITS (internal transcribed spacer 1)-metabarcoding and matrix-assisted laser desorption/Ionization time of flight mass spectrometry techniques. Further, to enhance identification effectiveness, we performed an additional incubation stage in 1:1 wine:yeast extract peptone dextrose (YPD) before identification. Six species were identified:S. cerevisiae,Pichia manshurica,Pichia membranifaciens,Wickerhamomyces anomalus,Candida guillermondii, andTrichosporon asahii, two of which were discovered for the first time (C. guillermondiiandTrichosporon ashaii) in Sherry wines. We analyzed wines where non-Saccharomycesyeasts were present or absent to see any potential link between the microbiota and the chemical profile. Only 2 significant volatile chemicals (out of 13 quantified), ethanol and ethyl lactate, and 2 enological parameters (out of 6 quantified), such as pH and titratable acidity, were found to differ in long-aged wines. Although results show a low impact where the non-Saccharomycesyeasts are present, these yeasts isolated from harsh environments (high ethanol and low nutrient availability) could have a potential industrial interest in fields such as food microbiology and biofuel production.
The Role of c-Jun and Autocrine Signaling Loops in the Control of Repair Schwann Cells and Regeneration
Authors: Jessen Kristjan R. , Mirsky Rhona
Published: February 2022

After nerve injury, both Schwann cells and neurons switch to pro-regenerative states. For Schwann cells, this involves reprogramming of myelin and Remak cells to repair Schwann cells that provide the signals and mechanisms needed for the survival of injured neurons, myelin clearance, axonal regeneration and target reinnervation. Because functional repair cells are essential for regeneration, it is unfortunate that their phenotype is not robust. Repair cell activation falters as animals get older and the repair phenotype fades during chronic denervation. These malfunctions are important reasons for the poor outcomes after nerve damage in humans. This review will discuss injury-induced Schwann cell reprogramming and the concept of the repair Schwann cell, and consider the molecular control of these cells with emphasis on c-Jun. This transcription factor is required for the generation of functional repair cells, and failure of c-Jun expression is implicated in repair cell failures in older animals and during chronic denervation. Elevating c-Jun expression in repair cells promotes regeneration, showing in principle that targeting repair cells is an effective way of improving nerve repair. In this context, we will outline the emerging evidence that repair cells are sustained by autocrine signaling loops, attractive targets for interventions aimed at promoting regeneration.
Altered Spontaneous Brain Activity and Functional Integration in Hemodialysis Patients With End-Stage Renal Disease
Authors: Su Huanhuan , Fu Shishun , Liu Mengchen , Yin Yi , Hua Kelei , Meng Shandong , Jiang Guihua , Quan Xianyue
Published: February 2022

Purpose

Using the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) algorithm to study the alteration of brain function in hemodialysis patients with end-stage renal disease (ESRD).

Patients and Methods

We recruited 20 patients with ESRD on regular hemodialysis and 17 healthy controls (HCs). All of the participants underwent resting-state fMRI (rs-fMRI), neuropsychological tests, and blood biochemical examination. The individual ALFF values between the two groups were tested by an independent sample t-test. Then, we set the altered ALFF brain areas as seed regions of interest (ROIs), and FC analysis was used to investigate the functional integration patterns between the seed ROI and the voxels within the whole brain.

Results

The ALFF values of the right precuneus and angular gyrus (RAG) in the ESRD group were lower than those in the HC subjects, but the right precentral gyrus showed higher ALFF values in patients. Hemoglobin (Hb) was negatively correlated with the ALFF values of the right precentral gyrus, and the ALFF values of the right precuneus were negatively correlated with line-tracing test (LTT) scores in patients with ESRD. Patients with ESRD show decreased connectivity between the RAG and the left precuneus, right superior frontal gyrus (RSFG), and the connectivity within the RAG was weak. In addition, FC in the RAG-right cuneus, right precuneus-left supramarginal gyrus was enhanced in the patient group.

Conclusion

Our research suggested that, in hemodialysis patients with ESRD, the brain areas with abnormal spontaneous brain activity and FC are mainly located in the default mode network (DMN) regions. Hb and the LTT results were correlated with abnormal spontaneous brain activity. These findings provide additional evidence to understand the possible underlying neuropathological mechanisms in patients with ESRD.
A Multielement Prognostic Nomogram Based on a Peripheral Blood Test, Conventional MRI and Clinical Factors for Glioblastoma
Authors: Rao Changjun , Jin Jinghao , Lu Jianglong , Wang Chengde , Wu Zerui , Zhu Zhangzhang , Tu Ming , Su Zhipeng , Li Qun
Published: February 2022

Background

Glioblastoma (GBM) is one of the most malignant types of tumors in the central nervous system, and the 5-year survival remains low. Several studies have shown that preoperative peripheral blood tests and preoperative conventional Magnetic Resonance Imaging (MRI) examinations affect the prognosis of GBM patients. Therefore, it is necessary to construct a risk score based on a preoperative peripheral blood test and conventional MRI and develop a multielement prognostic nomogram for GBM.

Methods

This study retrospectively analyzed 131 GBM patients. Determination of the association between peripheral blood test variables and conventional MRI variables and prognosis was performed by univariate Cox regression. The nomogram model, which was internally validated using a cohort of 56 GBM patients, was constructed by multivariate Cox regression. RNA sequencing data from Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA datasets were used to determine peripheral blood test-related genes based on GBM prognosis.

Results

The constructed risk score included the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), albumin/fibrinogen (AFR), platelet/lymphocyte ratio (PLR), and center point–to-ventricle distance (CPVD). A final nomogram was developed using factors associated with prognosis, including age, sex, the extent of tumor resection, IDH mutation status, radiotherapy status, chemotherapy status, and risk. The Area Under Curve (AUC) values of the receiver operating characteristic curve (ROC) curve were 0.876 (12-month ROC), 0.834 (24-month ROC) and 0.803 (36-month ROC) in the training set and 0.906 (12-month ROC), 0.800 (18-month ROC) and 0.776 (24-month ROC) in the validation set. In addition, vascular endothelial growth factor A (VEGFA) was closely associated with NLR and LMR and identified as the most central negative gene related to the immune microenvironment and influencing immune activities.

Conclusion

The risk score was established as an independent predictor of GBM prognosis, and the nomogram model exhibit appropriate predictive power. In addition, VEGFA is the key peripheral blood test-related gene that is significantly associated with poor prognosis.
Examining the Role of Food Form on Children's Self-Regulation of Energy Intake
Authors: Reigh Nicole A. , Rolls Barbara J. , Francis Lori A. , Buss Kristin A. , Hayes John E. , Hetherington Marion M. , Moding Kameron J. , Kling Samantha M. R. , Keller Kathleen L.
Published: February 2022

Increasing childhood obesity rates in both the United States and worldwide demonstrate a need for better prevention and intervention strategies. However, little is understood about what factors influence children's ability to sense and respond to hunger and fullness cues, a critical component of self-regulation of energy intake and maintenance of a healthy body weight. Research in adults suggests that food form may influence self-regulation of energy intake. More specifically, beverages are not as satiating as solid foods when matched for factors such as energy content, energy density, and volume and therefore elicit poorer energy intake self-regulation. However, much less is known about the impact of food form on children's ability to regulate their energy intake. This report describes a study that will examine the relationship between biological, cognitive, and psychological factors and children's appetite self-regulation (ASR). In this registered report, we will examine the influence of food form on children's short-term energy compensation, a proxy indicator of energy intake self-regulation. The study will employ a within-subjects, crossover design in which children (n = 78) ages 4.5–6 years will attend five laboratory visits, each ~1 week apart. During each visit, children will be presented with one of five possible preload conditions: apple slices, apple sauce, apple juice, apple juice sweetened with non-nutritive sweetener (NNS), or no preload. The order of preload conditions will be pseudorandomized and counterbalanced across participants. Following consumption of the preload (or no preload), children will consume a standardized ad libitum test meal of common foods for this age group. We hypothesize that children will demonstrate poorer short-term energy compensation (greater meal intake) in response to the liquid and semi-solid preloads compared to the solid preload. Understanding how energy in various forms affects children's ability to self-regulate intake has implications for dietary recommendations and will help identify those who are most at-risk for poor intake regulation and the development of obesity.
miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands
Authors: Naakka Erika , Barros-Filho Mateus Camargo , Adnan-Awad Shady , Al-Samadi Ahmed , Marchi Fábio Albuquerque , Kuasne Hellen , Korelin Katja , Suleymanova Ilida , Brown Amy Louise , Scapulatempo-Neto Cristovam , Lourenço Silvia Vanessa , Castilho Rogério Moraes , Kowalski Luiz Paulo , Mäkitie Antti , Araújo Vera Cavalcanti , Leivo Ilmo , Rogatto Silvia Regina , Salo Tuula , Passador-Santos Fabricio
Published: February 2022

Objectives

To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers.

Material and Methods

Gene and miRNA expression arrays were performed in 35 MECs and six NSGs.

Results

We found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT.

Conclusion

The in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.
Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength
Authors: Fanale Daniele , Corsini Lidia Rita , Brando Chiara , Dimino Alessandra , Filorizzo Clarissa , Magrin Luigi , Sciacchitano Roberta , Fiorino Alessia , Bazan Russo Tancredi Didier , Calò Valentina , Iovanna Juan Lucio , Francini Edoardo , Russo Antonio , Bazan Viviana
Published: February 2022

Lynch syndrome (LS) is an inherited genetic condition associated with increased predisposition to colorectal cancer (CRC) and other tumors and is caused by germline mutations in Mismatch Repair (MMR) or EPCAM genes. The identification of LS carriers is currently based on germline testing of subjects with MMR-deficient (dMMR) tumors or fulfilling clinical criteria, but the most efficient strategies to select patients who should be offered genetic testing are yet not well defined. In order to assess the most suitable selection mode to identify LS-related CRC patients, we retrospectively collected and analyzed all clinical and molecular information of 854 CRC patients, recruited from 2013 to 2021 at the University Hospital Policlinico “P. Giaccone” of Palermo (Italy), 100 of which were selected based on revised Bethesda guidelines, Amsterdam criteria II, or tissue MMR deficiency, and genetically tested for germline variants in LS-susceptibility genes. Our study showed that 32 out of 100 CRC patients harbored germline likely pathogenic/pathogenic variants in MMR genes. The analysis of tissue microsatellite instability (MSI) status according to the revised Bethesda guidelines has been to be the best selection approach. However, using different selection approaches as complementary strategies is useful to identify LS carriers, reducing underdiagnosis of this syndrome.
Prevalence and Risk Factors of Asthma in Preschool Children in Shanghai, China: A Cross-Sectional Study
Authors: Ren Jie , Xu Jing , Zhang Pingbo , Bao Yixiao
Published: February 2022

Background

Previous studies have shown the increasing prevalence of childhood asthma around the world as well as in China. Nevertheless, little is known about the epidemiology of asthma in preschool children. Thus, the present study investigated the prevalence and severity of asthma in Shanghai, China, and identified related risk factors for asthma in children at the age of 3–6.

Methods

Information was obtained through the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Risk factor analysis was carried out using univariate and multivariate logistic regression. The odds ratio (OR)/adjusted odds ratio (aOR) and the 95% confidence interval (CI) were determined.

Results

A total of 6,183 children (3,165 boys and 3,018 girls) covering 12 communities were included in our study, with an average age of 4.2 ± 0.7 years. The prevalence of ever asthma, current asthma, and physician-diagnosed asthma was 16.0, 11.2, and 5.3%, respectively. Parental allergic history, including rhinitis and asthma, was significantly associated with asthma symptoms. The strongest association with current asthma was paternal asthma (aOR = 5.91, 95% CI 3.87–9.01), and maternal asthma had the second strongest association with current asthma (3.85; 2.40–6.17). Among personal factors, allergic rhinitis history, eczema history, food allergy history, and antibiotic use in the first year of life were significantly associated with current asthma (aOR = 1.89, 95% CI 1.52–2.34; aOR = 1.34, 95% CI 1.09–1.64; aOR = 1.68, 95% CI 1.37–2.06; aOR = 1.53, 95% CI 1.25–1.87, respectively). More than once paracetamol use per year and per month were associated with current asthma in a dose–response manner. Additionally, female sex was an independent protective factor for ever asthma (0.82; 0.70–0.96). Among environmental factors, dampness or mildew at home was an independent risk factor for ever asthma (1.50; 1.15–1.97) and current asthma (1.63; 1.21–2.19). Floor heating system was significantly associated with ever asthma (1.57; 1.25–1.98) and current asthma (1.36; 1.04–1.78). Furthermore, dampness or mildew, infrequent house cleaning, and truck traffic in residential streets were significantly associated with asthma symptoms only in old communities, while paracetamol use in the first year of life and flooring materials were significant factors only in new communities.

Conclusion

The prevalence of asthma has increased among preschool children in Shanghai over the past three decades. The identified risk factors indicated the combined effects of genetic, personal, and environmental factors on asthma symptoms. Differentiated strategies should be taken for preventing asthma in old and new communities.
Electrocardiographic Characteristics and Catheter Ablation of Ventricular Arrhythmias Originating From the Moderator Band in Children
Authors: Jiang Diandong , Lv Jianli , Han Bo , Yang Xiaofei , Zhao Lijian , Yi Yingchun , Long Deyong , Sang Caihua
Published: February 2022

Aims

To investigate the electrocardiographic (ECG) characteristics and catheter ablation of ventricular arrhythmias (VAs) originating from the moderator band (MB) in children.

Methods

A total of six children who had VAs originating from the MB—as confirmed by electrophysiological study—and who underwent catheter ablation between January 2016 and December 2020 were retrospectively reviewed. During the procedure, a three-dimensional electroanatomic mapping system was used to facilitate three-dimensional anatomical reconstruction, mapping and ablation. Patients' clinical characteristics, ECG features and procedural data were collected and analyzed.

Results

The mean age was 8.4 ± 2.6 years (range: 5.3–11 years) and mean weight was 27.7 ± 11.4 kg (range: 17–47 kg). Four patients presented with frequent premature ventricular contraction (PVC), one patient presented with frequent PVC and non-sustained ventricular tachycardia, and one patient presented with sustained monomorphic ventricular tachycardia. The QRS duration averaged 126.3 ± 4.6 ms. In all patients, the VAs had left bundle branch block QRS with left superior frontal plane axes, rapid downstrokes of the QRS in the precordial leads, and late precordial transitions (>V4). During the same period, 10 cases of VAs originated from the posterior-lateral wall of the tricuspid annulus, with a mean QRS duration of 152.8 ± 6.4 ms. Compared to that, VAs of MB origin have narrower QRS widths, downstroke slopes in the inferior lead, sharper downstroke slopes in the precordial lead, and smaller R-wave amplitudes in the V6 lead. All patients experienced immediate ablation success with activations earlier than QRS by 26.0 ± 3.5 ms, and no procedural complications occurring. Only one case had recurrent PVC during a follow-up period ranging from 6 to 36 months.

Conclusion

MB VAs in children have distinctive ECG morphology and electrophysiological characteristics. Catheter ablation using a three-dimensional electroanatomic mapping system is safe and effective in these patients.
Apoptosis Triggering, an Important Way for Natural Products From Herbal Medicines to Treat Pancreatic Cancers
Authors: Li Meiyan , Tang Dandan , Yang Ting , Qian Die , Xu Runchun
Published: February 2022

Pancreatic cancer, a poor prognosis and high morbidity and mortality cancer, is a malignant tumor occurring in pancreatic exocrine glands. Currently, surgery and gemcitabine (Gem) are commonly used to treat pancreatic cancers. However, the high recurrence rate and resistance makes the therapeutic effects still unsatisfied. Apoptosis is comprehensively recognized as one of the major ways of the programmed cell death, refers to the autonomous and orderly death process of cells in order to maintain the stability of the body's environment after receiving a certain signal or stimulation. Currently, it has also been proven to be a promising way for the treatment of pancreatic cancer. Nowadays, some active ingredients from herbal medicine have been reported to be effective for the treatment of pancreatic cancer via inducing cells apoptosis. Therefore, this article reviews the current references regarding anti pancreatic cancer effects of natural products derived from herbal medicines via triggering apoptosis, and summarizes the related potential signal pathways, including death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, MAPK mediated apoptotic pathway, ERS mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other pathways such as JAK-STAT signal pathway, which can lay a certain foundation for the research and development of new natural products against pancreatic cancer.
Additional Use of Prostacyclin Analogs in Patients With Pulmonary Arterial Hypertension: A Meta-Analysis
Authors: Wang Pengwei , Deng Jiaxin , Zhang Quanying , Feng Hongyan , Zhang Yongheng , Lu Yizhong , Han Lizhu , Yang Pengfei , Deng Zhijian
Published: February 2022

Background: Combination therapy has become an attractive option in pulmonary arterial hypertension (PAH) treatment. The aim of this study was to investigate whether additional use of prostacyclin analogs could exert any additional benefits over background targeted therapies in PAH patients.

Methods: Searches were performed on PubMed, Embase, and ClinicalTrials.gov from inception to 1 October 2021. Randomized controlled trials were included if patients had been treated with prostacyclin analog-containing combination therapy and compared with the use of other PAH-specific background therapies. The bias risk and statistical analysis of the enrolled studies were performed with RevMan 5.1. Sensitivity analysis and funnel plot were used to evaluate the stability and publication bias, respectively. PROSPERO registered number CRD42021284196.

Results: Ten trials involving 1828 patients were included. Prostacyclin analog treatment was associated with greater improvement in clinical worsening (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.57–0.86), 6-min walk distance (mean difference [MD], 37.17 m; 95% CI, 3.01–71.33 m), NYHA/WHO functional class (RR, 1.58; 95% CI, 1.21–2.05), mean pulmonary artery pressure (MD, −9.23 mmHg; 95% CI, −17.44 to −1.03 mmHg), and cardiac index (MD, 0.41 L/min/m2; 95% CI, 0.26–0.55 L/min/m2) than the control group. No significant differences in pulmonary vascular resistance (MD, −137.22 dyn·s/cm5; 95% CI, −272.61 to −1.84 dyn·s/cm5) and all-cause mortality (RR, 0.96; 95% CI, 0.57–1.61) were found between the prostacyclin analog group and control group. Of note, more adverse events (RR, 1.07; 95% CI, 1.02–1.13) occurred in the prostacyclin analog group but no significant increase in serious adverse events (RR, 1.25; 95% CI, 0.75–2.11).

Conclusion: Additional prostacyclin analog treatment exerted benefits on clinical worsening, exercise capacity, functional class, mean pulmonary artery pressure, and cardiac index in PAH patients, but it was associated with overall risk of adverse events.

Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284196, identifier CRD42021284196.
The Effect of Chronic Intermittent Hypobaric Hypoxia on Sleep Quality and Melatonin Serum Levels in Chilean Miners
Authors: Calderon-Jofre Rodrigo , Moraga Daniel , Moraga Fernando A.
Published: February 2022

High-altitude mining is an important economic resource for Chile. These workers are exposed to chronic intermittent hypobaric hypoxia (CIHH), which reduces their sleep quality and increases the risk of accidents and long-term illnesses. Melatonin, a hormone produced by the pineal gland, is a sleep inducer that regulates the circadian cycle and may be altered in populations subjected to CIHH. This work aimed to assess the relationship between altitude, sleep quality, and plasma melatonin concentrations in miners with CIHH exposure. 288 volunteers were recruited from five altitudes (0, 1,600, 2,500, 3,500, and 4,500 m). All volunteers worked for 7 days at altitude, followed by 7 days of rest at sea level. We performed anthropometric assessments, nocturnal oximetry, sleep quality and sleepiness surveys, and serum melatonin levels upon awakening. Although oxygen saturation progressively decreased and heart rate increased at higher altitudes, subjective perception of sleep quality was not significantly different, and sleepiness increased in all groups compared to population at sea level. Similarly, melatonin levels increased at all assessed altitudes compared to the population at sea level. These data confirm that sleep disturbances associated with CIHH increase morning melatonin levels. Therefore, this hormone and could potentially serve as a biomarker of sleep quality.