High Lethality Rate Research Articles

Development of a Gene Risk Signature for Patients of Pancreatic Cancer.

Background Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

Prevalence and evolution of clinical cases of Yellow Fever in Brazil between the years 2007 to 2016

Yellow Fever (YF) is a non-contagious infectious disease of variable symptoms that occurs mainly in tropical forests regions of the Americas and Africa and is caused by a Flavivirus belonging to the Flaviviridae family. Its vectors are mosquitoes of the genus Haemagogus, Sabethes and Aedes, and these have non-human primates as the main source of infection. In Brazil, there has been no record of urban AF since 1942, although the increase in cases of the wild form combined with low vaccination coverage contribute to the risk of re-urbanization of the disease Material and methods: For the study, epidemiological data were obtained from confirmed cases of Yellow Fever reported in the Notification System for Health Disorders (SINAN) available at the Informatics Department of the Unified Health System (DATASUS). Results and discussion: A total of 177 cases of were reported in Brazil, the year with the highest notification was in 2016 (52). The region with the highest occurrence of cases were the Southeast (95). Regarding the clinical evolution, of the 177 cases, 68 affected patients were cured, while 89 died from the reported injury, evidencing a high rate of lethality (50.2%). Conclusion: YF remains a public health problem, over the years there was a decrease in cases, this was due to immunization campaigns in the country, however, there was a significant increase in notifications in 2016, this whole panorama reinforces the need intensifying surveillance and expanding vaccine coverage.

Identification of FEZ2 as a potential oncogene in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the common malignant tumors with high lethal rate and poor prognosis. Dysregulation of many genes have been reported to be involved in the occurrence and development of PDAC. However, as a highly conserved gene in eukaryotes, the role of Fasciculation and Elongation protein Zeta 2 (FEZ2) in pancreatic cancer progression is not clear. In this study, we identified the oncogenic effect of FEZ2 on PDAC. By mining of The Cancer Genome Atlas (TCGA) database, we found that FEZ2 was upregulated in PDAC tissues and FEZ2 expression was negatively regulated by its methylation. Moreover, high expression and low methylation of FEZ2 correlated with poor prognosis in PDAC patients. Besides, we found that FEZ2 could promote PDAC cells proliferation, migration and 5-FU resistance in vitro. Furthermore, Gene pathway enrichment analysis demonstrated a positive correlation between Wnt signaling activation and FEZ2 expression in PDAC patients. Western blot showed that FEZ2 knockdown significantly suppressed β-catenin expression. Collectively, our finding revealed that FEZ2 functioned as a potential oncogene on PDAC progression and migration, and the expression of FEZ2 had guidance value for the treatment and chemotherapy program of PDAC patients.

Incidence and risk factors for the development of cerebral metastasis in cervical cancer patients.

ObjectiveCerebral metastasis (CM) in cervical cancer (CC) cases, although rare, results in high lethality rates. The present study aimed to assess CM incidence in a Brazilian reference CC center and evaluate the risk factors for CM development. Retrospective observational study of patients diagnosed with CC between 2010 and 2017.MethodsCumulative CM incidence and incidence density were evaluated. Characteristics associated to CM development risks were identified using crude (cOR) or adjusted (aOR) odds ratios.ResultsA total of 3,397 patients were included in this study. Patient age ranged from 18 to 101 years, with a mean age of 48.8±14.0. After a mean follow-up time of 3.2±2.1 years, 51 CM cases were identified, resulting in a cumulative incidence of 1.5% (95% confidence intervals [CI]=1.12–1.97) and an incidence density at the end of the 6th year of 27.4 per 1,000 women/year. Advanced clinical stage (aOR=3.15; 95% CI=1.16–8.58; p=0.025), the presence of previous lung metastasis (aOR=4.04; 95% CI=1.82–8.94; p=0.001) and the adenocarcinoma (aOR=2.90; 95% CI=1.46–5.76; p=0.002), adenosquamous carcinoma (aOR=7.33; 95% CI=2.87–18.73; p<0.001), undifferentiated carcinoma (aOR=14.37; 95% CI=3.77–54.76; p<0.001) and neuroendocrine carcinoma (aOR=21.31; 95% CI=6.65–68.37, p<0.001) histological types were associated with a higher risk for CM development. CM risk was higher in the first years of follow-up, with no cases observed after the 6th year.ConclusionCC patients in advanced clinical stages, displaying previous lung metastasis and non-squamous histological types are at high risk of developing CM.

NOVA1 promotes SMN2 exon 7 splicing by binding the UCAC motif and increases SMN protein expression.

Spinal muscular atrophy (SMA) is a rare hereditary neuromuscular disease with a high lethality rate in infants. Variants in the homologous genes survival of motor neuron (SMN)1 and SMN2 have been reported to be SMA pathogenic factors. Previous studies showed that a high inclusion rate of SMN2 exon 7 increased SMN expression, which in turn reduced the severity of SMA. The inclusion rate of SMN2 exon 7 was higher in neural tissues than in non-neural tissues. Neuro-oncological ventral antigen (NOVA) is a splicing factor that is specifically and highly expressed in neurons. It plays a key role in nervous system development and in the induction of nervous system diseases. However, it remains unclear whether this splicing factor affects SMA. In this study, we analyzed the inclusion of SMN2 exon 7 in different tissues in a mouse model of SMA (genotype smn-/-SMN22tg/0) and littermate controls (genotype smn+/-SMN22tg/0). We found that inclusion level of SMN2 exon 7 was high in the brain and spinal cord tissue, and that NOVA1 was also highly expressed in nervous system tissues. In addition, SMN2 exon 7 and NOVA1 were expressed synchronously in the central nervous system. We further investigated the effects of NOVA1 on disease and found that the number of neurons in the anterior horn of spinal cord decreased in the mouse model of SMA during postnatal days 1-7, and that NOVA1 expression levels in motor neurons decreased simultaneously as spinal muscular atrophy developed. We also found that in vitro expression of NOVA1 increased the inclusion of SMN2 exon 7 and expression of the SMN2 protein in the U87MG cell line, whereas the opposite was observed when NOVA1 was knocked down. Finally, point mutation and RNA pull-down showed that the UCAC motif in SMN2 exon 7 plays a critical role in NOVA1 binding and promoting the inclusion of exon 7. Moreover, CA was more essential for the inclusion of exon 7 than the order of Y residues in the motif. Collectively, these findings indicate that NOVA1 interacts with the UCAC motif in exon 7 of SMN2, thereby enhancing inclusion of exon 7 in SMN2, which in turn increases expression of the SMN protein.

Whole blood circular RNA hsa_circ_0002171 serves as a potential diagnostic biomarker for human adenovirus pneumonia in children.

Severe pneumonia related to human adenoviruses (HAdVs) has a high lethality rate in children and its early diagnosis and treatment remain a major challenge. Circular RNAs (circRNAs) are novel long noncoding RNAs that play important roles in gene regulation and disease pathogenesis. To investigate the roles of circRNAs in HAdV pneumonia, we analyzed the circRNA profiles of healthy children and children with HAdV pneumonia, including both mild and severe cases, and identified 139 significantly upregulated circRNAs in children with HAdV pneumonia vs healthy controls and 18 significantly upregulated circRNAs in children with severe HAdV pneumonia vs mild HAdV pneumonia. In particular, hsa_circ_0002171 was differentially expressed in both groups and might thus be useful as a diagnostic biomarker of HAdV pneumonia and severe HAdV pneumonia. To identify the underlying mechanisms of circRNAs in HAdV pneumonia, we analyzed the transcriptome of children with HAdV pneumonia and established a circRNA-mRNA regulatory network. Enrichment analysis of differentially expressed target mRNAs demonstrated that the differentially expressed genes between healthy controls and HAdV pneumonia patients were mainly involved in RNA splicing while the differentially expressed genes between children with mild and severe HAdV pneumonia were mainly involved in regulating lymphocyte activation. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0002171 had a significant value in the diagnosis of HAdV pneumonia and of severe HAdV pneumonia. Taken together, the circRNA expression profile was altered in children with HAdV pneumonia. These results demonstrated that hsa_circ_0002171 is a potential diagnostic biomarker of HAdV pneumonia.

COVID-19 IN ADOLESCENT PATIENTS IN THE BRAZILIAN POPULATION WITH SICKLE CELL ANEMIA

Introduction: Sickle cell anemia due to recent scientific evidence suggests that individuals with disease are considered a risk group and SARS-CoV-2 and spreads rapidly in this group of patients with diseases due to lack of inherited immunity, has a high lethality rate among young people and children and patients with associated comorbidities such as Diabetes Mellitus. Objective: to analyze the profile of patients with sickle cell anemia and their immunological motivations for worsening in positive cases of COVID-19 from a systematic review. Results: Initially, 217 articles were identified, of which 213 were removed because they were not related to the theme of the review, or because they were duplicated or did not have the abstract. The 04 selected articles were classified into two thematic axes to be performed the analysis. Discussion: This systematic review study is the first with sickle cell anemia and COVID-19 in the adolescent population with a limited resource configuration that shows the inherent need in the management of both diseases. However, in this systematic review, the four included studies showed a favorable evolution of the infectious process by COVID-19, and deaths occurred in adolescent patients who concomitantly had multiple comorbidities, for example, DM. Conclusion: It was found in this systematic review study that COVID-19 infection may accentuate the presence of vasculopathy in patients with sickle cell anemia and may increase pain to varying degrees.

Survival of patients with diabetes mellitus hospitalized for acute respiratory syndrome due to COVID-19.

Given the magnitude of COVID-19 and the increase in hospitalization cases for severe acute respiratory syndrome (SARS), especially among patients with diabetes mellitus, it is essential to understand the epidemiological aspects inherent to the disease and the worsening of cases. Thus, this study aimed to analyze the survival of patients with diabetes mellitus hospitalized for SARS due to COVID-19 in different regions of Brazil. This is a longitudinal study, carried out based on data reported in the Influenza Epidemiological Surveillance Information System during the year 2020. The number of patients with diabetes mellitus among the hospitalized cases of SARS due to COVID-19 in the different regions of Brazil and the lethality rate among them were identified. A comparison of patient profiles of those who survived or did not survive and the Cox regression analysis were performed to evaluate the factors associated with shorter survival of patients. It was found that 51.4% of patients hospitalized with SARS due to COVID-19 had diabetes, and the case lethality rate among them was 45.0%. The Northeastern and Northern regions presented a higher proportion of patients with diabetes mellitus (56.5% and 54.3%, respectively) and a higher lethality rate (53.8% and 59.9%, respectively). The mean survival time of cases with diabetes mellitus hospitalized for SARS due to COVID-19 was estimated to be 35.7 days (0.5 days). A lower survival rate was observed among residents of the Northeastern and Northern regions with skin color reported as non-white, who required admission to Intensive Care Units and invasive mechanical ventilation, and presented respiratory symptoms such as dyspnea, respiratory distress and an oxygen saturation lower than 95%. It is concluded that diabetes mellitus was responsible for the high occurrence and lethality, mainly in the Northeastern and Northern regions, among non-white patients and those with greater clinical severity, which reinforces the importance of taking measures aimed at supporting this population.

High lethality rate of carbapenem-resistant Acinetobacter baumannii in Intensive Care Units of a Brazilian hospital: An epidemiologic surveillance study.

ABSTRACTBackground: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a growing threat to public health. Methods: A 3-year retrospective study was conducted to evaluate the prevalence and lethality of multidrug-resistant (MDR) A. baumannii isolated from Brazilian patients. Results: In this study, 219 Acinetobacter baumannii isolates were identified, of which 70.8% (155/219) were isolated from patients hospitalized in intensive care units. Of these, 57.4% (n = 89/155) were assessed, of which 92.1% (82/89) were carbapenem-resistant, and 49 were classified as infected. The lethality rate was 79.6% (39/49). Conclusions: We highlight the need of an effective epidemiological surveillance measure to contain the dissemination of CRAB in the hospital environment.

Three-phase interface photocatalysis for the enhanced degradation and antibacterial property

Semiconductor photocatalysis, as a means of utilizing stranded renewable solar resources, is now emerging as a viable and promising approach for increasingly severe water pollution. In this work, a high-performance photocatalytic system has been fabricated by immobilizing spiky TiO2/Au nanohybrids on one side of hydrophobic nanoPE substrate (PE-TiO2/Au) that forces the enabling of air–liquid–solid triphase photocatalytic interface. Such a triphase system allows efficient oxygen access to the photocatalyst surface, which is feasible for charge separation and reactive oxygen species (ROS) production. Two modes of triphase systems with different gas flow paths were constructed, in which PE-TiO2/Au was floating on the aqueous solution surface (exposed mode) or immersing in aqueous phase (immersed mode). It is worth mentioning that the exposed PE-TiO2/Au enables a more efficient oxygen supply, thus leading to a 5.5-fold and 1.8-fold higher reaction kinetics as compared to normal liquid–solid diphase system and immersed PE-TiO2/Au. Meanwhile, PE-TiO2/Au also exerts bactericidal effect under visible light irradiation, which effectively inactivates S.aureus (>99.9%) in a lean period of 30 min. The qualities of high lethality rate and short reaction time are endowed to PE-TiO2/Au due to the co-effect of unique triphase interface microenvironment and elaborate heterojunction of spiky TiO2/Au nanohybrids. In this paper, we have revealed for the first time that the antibacterial efficiency can be effectively improved by increasing the oxygen supply with the construction of three-phase interface, which represents a promising option in designing highly efficient photocatalytic systems for sewage purification applications.

Epidemiological characterization and spatial distribution of visceral leishmaniasis cases in Três Lagoas - MS, Brazil in the period of 2007-2021

This retrospective observational cross-sectional study aimed to analyze the distribution of visceral leishmaniasis (VL) cases in Três Lagoas registered between January 2007 and August 2021, through data processed by the Epidemiological Surveillance Service based on the notification of the National System of Diseases and Notifications. In this period, 231 cases were confirmed, being 137 male (59.3%) and 94 female (40.7%). Was observed a higher prevalence of cases between ages 0-4 years (30.8%), 20-39 (22.5%) and 40-59 (19.9%). Also was observed a higher percentage of infected Caucasian individuals (45.4%) and individuals with low education: elementary school II (22.1%). The most prevalent clinical manifestations were fever (85.3%), splenomegaly (76.6%), weakness (67.1%), weight loss (65.8%) and hepatomegaly (62.8%). It was found that 80.1% of patients received pharmacological treatment, mainly using pentavalent antimonials (56.7%), and that 26 patients (11.3%) died during the period due to complications caused by VL. The spatial analysis showed a homogeneous distribution of VL cases in the city's urban perimeter without predominant regions. Finally, it was observed that the incidence and mortality by VL has been decreasing in recent years, however maintaining high rates of lethality and transmissibility, placing the municipality in the third with the highest transmission rate in the state. In view of these aspects, we conclude that VL is still a serious public health problem in the city and that despite the slight drop in incidence and mortality rates, it still presents values higher than the national average and high dissemination of the disease in the urban area.

Evolution of mortality and lethality due to covid-19 in the state of Roraima, Brazil, from march 2020 to july 2021

Introduction: the context of the Covid-19 pandemic in the Brazilian North region is worrying. There is a lack of resources for Public Health, a low human development index, and poverty indicators above the national average. Objective: to analyze mortality and lethality from COVID-19 in the State of Roraima, Brazil. Methods: this is an ecological time-series study of secondary data on COVID-19 in Roraima, Northern Brazil, from March 2020 to July 2021. The incidence, mortality, and lethality rates due to COVID-19 were calculated. The Prais-Winsten regression model was used to calculate the time series trends. Trends were classified as increasing, decreasing, or stationary. The trend was considered static when the p-value was not significant (p&gt;0.05). Results: in the state of Roraima, from March 2020 to July 2021, there were 123,125 cases and 1,903 accumulated deaths due to COVID-19. The first wave (March 2020 to October 2021) of COVID-19 recorded the incidence rate (2,995.30 new cases per 100,000 inhabitants - July 2020) and mortality (56.32 deaths per 100,000 inhabitants - June 2020) higher lethality. However, in the second wave (November 2020 to July 2021), the highest lethality rate was observed (3.47% - February 2021). It was observed that during the first wave, the incidence rate of COVID-19 showed increasing trends. During this period, the mortality rate had a stationary tendency (p&gt;0.05) and the percentage lethality with a decreasing trend (p&lt;0.05). During the second wave, there was a more aggravating scenario for lethality, which changed from a daily reduction rate of 0.90% to stationary trends. Conclusion: the pandemic in the state of Roraima is not yet under control, so it is necessary to strengthen strategies to mitigate the spread of the pandemic in the region and prevent the formation of new waves.

Analysis of COVID-19 mortality and case-fatality in a low- income region: an ecological time-series study in Tocantins, Brazilian Amazon

Introduction: Inserted in the vulnerable context of the Brazilian Amazon, the state of Tocantins has suffered damages with the dissemination of COVID-19 in its territory; however, little evidence is published from this state. &#x0D; Objective: This study aims to analyze the case-fatality, mortality, and incidence of COVID-19 in Tocantins. &#x0D; Methods: This is an ecological study, population-based, time-series analysis of COVID-19 cases and deaths in the state of Tocantins from March 2020 to August 2021. &#x0D; Results: During the examined period, 219,031 COVID-19 cases, and 3,594 deaths were registered due to disease. Two possible occurrence peaks were characterized in this time-series analysis. Remarkably, the Second Wave had the highest lethality rates (3.02% - April 2021), mortality (39.81 deaths per 100,000 inhabitants – March 2021), and incidence (1,938.88 cases per 100,000 inhabitants – March 2021). At the end of the period, mortality, incidence, and lethality showed flat trends, suggesting a positive outcome of the vaccination program. &#x0D; Conclusion: The prevention, surveillance, and control actions of COVID-19 cases in Tocantins State have been directed to mitigate the deleterious effects of the pandemic. Nevertheless, efforts are still needed to decrease lethality, mortality, and incidence trends, and ultimately to achieve control of the COVID-19 pandemic in the region.

The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells.

Glioblastoma multiforme (GBM) is one of the most aggressive and common types of brain tumor. Due to its high proliferation ability, a high lethality rate has been observed with this malignant glial tumor. Terminalia catappa L. (T. catappa) is currently known to have anti-inflammatory and anti-carcinogenesis effects. However, few studies have examined the mechanisms of the leaf extracts of T. catappa (TCE) on GBM cells. In the current study, we demonstrated that TCE can significantly inhibit the migration and invasion capabilities of GBM cell lines without showing biotoxic effects. Matrix metalloproteinases-2 (MMP-2) activity and protein expression were attenuated by reducing the p38 phosphorylation involved in the mitogen-activated protein kinase (MAPK) pathway. By treating with TCE and/or p38 inhibitor (SB203580), we confirmed that p38 MAPK is involved in the inhibition of cell migration. In conclusion, our results demonstrated that TCE inhibits human GBM cell migration and MMP-2 expression by regulating the p38 pathway. These results reveal that TCE contains potent therapeutic compounds which could be applied for treating GBM brain tumors.

Total Synthesis of the Tetrasaccharide Haptens of Vibrio vulnificus MO6-24 and BO62316 and Immunological Evaluation of Their Protein Conjugates.

Vibrio vulnificus is a human pathogen that can cause fatal septicemia and necrotizing infections with a high lethal rate exceeding 50%. V. vulnificus MO6-24 and BO62316 are two predominant virulent strains associated with approximately one-third of the clinical infections. The capsular polysaccharides (CPSs) of V. vulnificus consist of several structurally unique sugars and are excellent targets for developing effective glycoconjugate vaccines. This article describes the first total synthesis of the challenging tetrasaccharide repeating units of V. vulnificus MO6-24 and BO62316 CPSs. A key feature of this synthesis was the assembly of the tetrasaccharide skeleton using a 3,4-branched trisaccharide as the glycosyl donor. A modified TEMPO/BAIB oxidation protocol was developed to directly convert α-d-GalN into α-d-GalAN in not only disaccharides but also tri- and tetrasaccharides. The synthetic haptens were covalently coupled with CRM197 carrier protein via a bifunctional linker. Preliminary immunological studies of the resultant glycoconjugates in mice revealed their high efficacy to induce robust T-cell-dependent immune responses, and the IgG antibodies elicited by each glycoconjugate showed weak cross-reactivity with the other synthetic tetrasaccharide.

Surgical treatment of ruptured right middle cerebral artery mycotic aneurysm and central nervous system aspergillosis: Clinical case and literature review

Background: Central nervous system (CNS) aspergillosis is more often met in patients with expressed immune suppression. Still, in 50% of cases of meningitis caused by Aspergillus spp., it is observed in patients without expressed immune suppression. The prognosis of CNS aspergillosis is unfavorable with the general rate of lethality around 70%.Case Description: Clinical case of a 58-year-old man who developed an Aspergillus abscess in the chiasmosellar region and an associated mycotic aneurysm of the right middle cerebral artery (MCA) and intracerebral hemorrhage. Microsurgical clipping of the fusiform-ectatic aneurysm of the right MCA in the conditions of rupture was performed. An extra-intracranial micro anastomosis was formed on the right. An open biopsy of the neoplasm in the chiasmosellar region was made. The neoplasm was yellow and destroyed the bone plate of the skull base. Biopsy results: Mycotic lesion (aspergillosis). The analysis of surgical treatment for mycotic aneurysms in the acute period of hemorrhage in patients with aspergillosis revealed a high rate of lethality. The issue of the feasibility and effectiveness of complicated revascularization interventions in the patients with hemorrhage and aspergillosis remains unsolved.Conclusion: The lack of generally accepted tactics of the treatment of this pathology requires further studies and systemic analysis. A high risk of the lethal outcome in patients with invasive mycotic infection and rupture of mycotic aneurysm highlight the importance of timely diagnostics and the beginning of antimycotic therapy. WThe issue of the evaluation of the revascularization methods effectiveness in patients after surgical treatment of a mycotic aneurysm associated with cerebral aspergillosis remains poor.

Systematic analysis of the long noncoding RNA (lncRNA)-miRNA-mRNA competing endogenous RNA network to identify prognostic biomarkers and the potential regulatory axis in glioblastoma multiforme.

BackgroundGlioblastoma (GBM) is an intracranial brain tumor characterized by a high final lethality rate and recurrence rate, and limited available therapies. With the development of high-throughput sequencing technology, the genomic and transcriptomic features of GBM have been fully characterized. Therefore, our study aimed to identify its underlying genetic mechanisms, thus facilitating the development of novel therapies for GBM.MethodsBased on the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, differential expression of RNAs in GBM and control group was analyzed. After constructing the long noncoding RNA (lncRNA)-miRNA-mRNA regulatory network of GBM, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) were performed to analyze related key nodes and the lncRNAs interacting with them. Further univariate Cox regression was conducted to explore independent factors, and then multivariate Cox regression was performed to construct risk prediction models.ResultsWe first constructed the lncRNA-miRNA-mRNA regulatory network of GBM and two effective prediction models that included 2 mRNAs [transcription factor 12 (TCF12) and discoidin, CUB and LCCL domain containing 2 (DCBLD2)] and 5 lncRNAs (C10orf25, LINC00343, HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1), FGF12 antisense RNA 2 (FGF12-AS2) and H19). Additionally, we identified several key molecules [TCF12, integrin β3 (ITGB3), high mobility group AT-hook 2 (HMGA2), C10orf25 and LINC00336] closely associated with GBM prognosis. C10orf25/miR-218/DCBLD2 may be an important regulatory pathway in GBM.ConclusionsKey molecules (TCF12, ITGB3, HMGA2, C10orf25, LINC00336 and H19) that are independent prognostic factors may be possible biomarkers to further optimize GBM prognosis. Two effective prognostic risk models that include 2 mRNAs (TCF12 and DCBLD2) and 5 lncRNAs (C10orf25, LINC00343, HOTAIRM1, FGF12-AS2 and H19) were constructed. C10orf25/miR-218/DCBLD2 may be an important regulatory pathway associated with the pathogenesis of GBM. Our findings contribute to further understanding the pathogenesis of GBM and finding possible candidate genes for prognostic and therapeutic usage with GBM.

Recent Advancements for the Management of Pancreatic Cancer: Current Insights

One of the most fatal forms of cancer includes cancer of the pancreas And the most rapid malignancy is observed in PDAC (pancreatic ductal adenocarcinoma). The high lethality rate is generally due to very late diagnosis and resistance to traditional chemotherapeutic agents. Desmoplastic stromal barrier results in resistance to immunotherapy. Other reasons for the high lethality rate include the absence of effective treatment and standard screening tests. Hence, there is a need for effective novel carrier systems. “A formulation, method, or device that allows the desired therapeutic substance to reach its site of action in such a manner that nontarget cells experience minimum effect is referred to as a drug delivery system”. The delivery system is responsible for introducing the active component into the body. They are also liable for boosting the efficacy and desirable targeted action on the tumorous tissues. Several studies, researches, and developments have yielded various advanced drug delivery systems, which include liposomes, nanoparticles, carbon nanotubules, renovoCath, etc. These systems control rate and location of the release. They are designed while taking into consideration characteristic properties of the tumor and tumor stroma. These delivery systems overcome the barriers in drug deliverance in pancreatic cancer. Alongside providing palliative benefits, these delivery systems also aim to correct the underlying reason for the defect. The following review article aims and focuses to bring out a brief idea about systems, methods, and technologies for futuristic drug deliverance in pancreatic cancer therapy.

Risk factors associated with the severity of COVID-19 in a region of the Brazilian Amazon

The Brazilian Northern region registered a high incidence of COVID-19 cases, particularly in the state of Pará. The present study investigated the risk factors associated with the severity of COVID-19 in a Brazilian Amazon region of 100,819 cases. An epidemiological, cross-sectional, analytical and demographic study, analyzing data on confirmed cases for COVID-19 available at the Brazilian Ministry of Health's surveillance platform, was conducted. Variables such as, municipalities of residence, age, gender, signs and symptoms, comorbidities were included and associated with COVID-19 cases and outcomes. The spatial distribution was performed using the ArcGIS program. A total of 100,819 cases were evaluated. Overall, patients had the mean age of 42.3 years, were female (51.2%) and with lethality reaching 4.79% of cases. Main symptoms included fever (66.5%), cough (61.9%) and sore throat (39.8%). Regarding comorbidities, most of the patients presented cardiovascular disease (5.1%) and diabetes (4.2%). Neurological disease increased risk of death by nearly 15 times, followed by obesity (5.16 times) and immunodeficiency (5.09 time). The municipalities with the highest incidence rate were Parauapebas, Canaã dos Carajás and Jacareacanga. Similarity between the Lower Amazon, Marajó and Southwest mesoregions of Pará state were observed concerning the highest morbidity rates. The obtained data demonstrated that the majority of cases occurred among young adults, females, with the classic influenza symptoms and chronic diseases. Finally, data suggest that the highest incidences were no longer in the metropolitan region of the state. The higher lethality rate than in Brazil may be associated with the greater impacts of the disease in this Amazonian population, or factors associated with fragile epidemiological surveillance in the notification of cases of cure.

Repetitive Transcranial Magnetic Stimulation Improves Neuropathy and Oxidative Stress Levels in Rats with Experimental Cerebral Infarction through the Nrf2 Signaling Pathway.

Ischemic stroke poses a serious threat to human health. Its high morbidity, disability, and lethality rates have led to it being a research hotspot. Cerebral ischemia reperfusion injury is a difficult point in the treatment of ischemic stroke. In recent years, studies have shown that repeated transcranial magnetic stimulation (rTMS) can enhance cerebral ischemic tolerance and have a significant protective effect on reperfusion injury after ischemia, but its specific mechanism is unknown. The Nrf2/pathway plays a vital role in ischemia-reperfusion injury in the body environment. Therefore, in this experiment, the middle cerebral artery occlusion (MCAO) reperfusion model of SD rats was made to simulate the occurrence of experimental cerebral infarction by the suture method. After treatment with rTMS, it was studied whether it can regulate the expression of Nrf2 and HO-1, affect the content of MDA and SOD activity, and then activate the Nrf2 pathway to exert its brain protection. The results showed that after MCAO reperfusion, the neurological deficit score of rats increased, and the time to remove the bilateral stickers and the time to cross the balance beam increased, suggesting the successful establishment of the experimental cerebral infarction model. Detecting the brain tissue of experimental cerebral infarction rats found that the expression of Nrf2 and HO-1 decreased, the content of MDA increased, and the activity of SOD decreased. After rTMS treatment, the neuromotor function of experimental cerebral infarction rats improved, the expression of Nrf2 and HO-1 in the brain tissue gradually increased, the content of MDA decreased, and the activity of SOD increased. It indicates that the expression of Nrf2 and HO-1 in experimental cerebral infarction rats is reduced. After treatment with rTMS, it can improve the neuromotor function damage of the rats and reduce the level of oxidative stress. The mechanism may be through promoting the activation of the Nrf2 signaling pathway, acting on the expression of antioxidant proteins, such as HO-1 and SOD1, reducing oxidative stress damage, and playing a protective effect on brain tissue.