Bacteria-derived extracellular vesicles: endogenous roles, therapeutic potentials and their biomimetics for the treatment and prevention of sepsis.

Sepsis is one of the medical conditions with a high mortality rate and lacks specific treatment despite several years of extensive research. Bacterial extracellular vesicles (bEVs) are emerging as a focal target in the pathophysiology and treatment of sepsis. Extracellular vesicles (EVs) derived from pathogenic microorganisms carry pathogenic factors such as carbohydrates, proteins, lipids, nucleic acids, and virulence factors and are regarded as "long-range weapons" to trigger an inflammatory response. In particular, the small size of bEVs can cross the blood-brain and placental barriers that are difficult for pathogens to cross, deliver pathogenic agents to host cells, activate the host immune system, and possibly accelerate the bacterial infection process and subsequent sepsis. Over the years, research into host-derived EVs has increased, leading to breakthroughs in cancer and sepsis treatments. However, related approaches to the role and use of bacterial-derived EVs are still rare in the treatment of sepsis. Herein, this review looked at the dual nature of bEVs in sepsis by highlighting their inherent functions and emphasizing their therapeutic characteristics and potential. Various biomimetics of bEVs for the treatment and prevention of sepsis have also been reviewed. Finally, the latest progress and various obstacles in the clinical application of bEVs have been highlighted.

A blastic plasmacytoid dendritic cell neoplasm-like immunophenotype is negatively associated with CEBPA bZIP mutation and predicts unfavorable prognosis in acute myeloid leukemia.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy which characteristically expresses an atypical phenotype including CD123+, CD56+, and CD4+. We are aimed to investigate the clinical and prognostic characteristics of AML patients exhibiting BPDCN-like immunophenotype and provide additional insights for risk stratification of AML. A total of 241 newly diagnosed AML patients were enrolled in this retrospective study and categorized into BPDCN-like positive (n = 125)/negative (n = 116) groups, determined by the present with CD123+ along with either CD56+ or CD4+, or both. Subsequently, an analysis was conducted to examine the general clinical characteristics, genetic profiles, and prognosis of the two respective groups. Patients with BPDCN-like immunophenotype manifested higher frequencies of acute myelomonocytic leukemia and acute monoblastic leukemia. Surprisingly, the presence of the BPDCN-like immunophenotype exhibited an inverse relationship with CEBPA bZIP mutation. Notably, patients with BPDCN-like phenotype had both worse OS and EFS compared to those without BPDCN-like phenotype. In the CN-AML subgroups, the BPDCN-like phenotype was associated with worse EFS. Similarly, a statistically significant disparity was observed in both OS and EFS within the favorable-risk subgroup, while only OS was significant within the adverse-risk subgrouMoreover, patients possessing favorable-risk genetics without BPDCN-like phenotype had the longest survival, whereas those who had both adverse-risk genetics and BPDCN-like phenotype exhibited the worst survival. Our study indicated that BPDCN-like phenotype negatively associated with CEBPA bZIP mutation and revealed a significantly poor prognosis in AML. Moreover, the 2022 ELN classification, in combination with the BPDCN-like phenotype, may better distinguish between different risk groups.

Microbial infections as potential risk factors for lung cancer: Investigating the role of human papillomavirus and chlamydia pneumoniae.

Background: Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods: Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model. Results: The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (OR = 2.33, 95% CI = 1.57-3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33-17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27-11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02-1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57-1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61-1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30-2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10-2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42-1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42-105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions: Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer.

Macrophages facilitate tumor cell PD-L1 expression via an IL-1ß-centered loop to attenuate immune checkpoint blockade.

Tumor-associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleukin (IL)-1ß was among the most abundant cytokines within the in vitro tumor-macrophage coculture system, and enhanced IL-1ß expression was associated with impaired cytotoxicity of CD8+ T cells in human ovarian cancer, indicating the possibility that IL-1ß mediated immunosuppression during tumor-TAMs crosstalk. Mechanistically, we demonstrated that IL-1ß significantly boosted programmed death-ligand 1 (PD-L1) expression in tumor cells via the activation of the nuclear factor-κb signaling cascade. Specifically, IL-1ß released from TAMs was triggered by lactate, the anaerobic metabolite of tumor cells, in an inflammasome activation-dependent manner. IL-1ß sustained and intensified immunosuppression by promoting C-C motif chemokine ligand 2 secretion in tumor cells to fuel TAMs recruitment. Importantly, IL-1ß neutralizing antibody significantly curbed tumor growth and displayed synergistic antitumor efficacies with anti-PD-L1 antibody in tumor-bearing mouse models. Together, this study presents an IL-1ß-centered immunosuppressive loop between TAMs and tumor cells, highlighting IL-1ß as a candidate therapeutic target to reverse immunosuppression and potentiate immune checkpoint blockade.

Epigenetic compounds targeting pharmacological target lysine specific demethylase 1 and its impact on immunotherapy, chemotherapy and radiotherapy for treatment of tumor recurrence and resistance.

It has been proven that metastatic recurrence and therapeutic resistance are linked. Due to the variability of individuals and tumors, as well as the tumor's versatility in avoiding therapies, therapy resistance is more difficult to treat. Therapy resistance has significantly restricted the clinical feasibility and efficacy of tumor therapy, despite the discovery of novel compounds and therapy combinations with increasing efficacy. In several tumors, lysine specific demethylase 1 (LSD1) has been associated to metastatic recurrence and therapeutic resistance. For researchers to better comprehend how LSD1-mediated tumor therapy resistance occurs and how to overcome it in various tumors, this study focused on the role of LSD1 in tumor recurrence and therapeutic resistance. The importance of therapeutically targeted LSD1 was also discussed. Most gene pathway signatures are related to LSD1 inhibitor sensitivity. However, some gene pathway signatures, especially in AML, negatively correlate with LSD1 inhibitor sensitivity, but targeting LSD1 makes the therapy-resistant tumor sensitive to physiological doses of conventional therapy. We propose that combining LSD1 inhibitor with traditional tumor therapy can help patients attain a complete response and prevent cancer relapse.

Cervical cancer survival times in Africa.

Objective: Accessibility to quality healthcare, histopathology of tumor, tumor stage and geographical location influence survival rates. Comprehending the bases of these differences in cervical cancer survival rate, as well as the variables linked to poor prognosis, is critical to improving survival. We aimed to perform the first thorough meta-analysis and systematic review of cervical cancer survival times in Africa based on race, histopathology, geographical location and age. Methods and materials: Major electronic databases were searched for articles published about cervical cancer survival rate in Africa. The eligible studies involved studies which reported 1-year, 3-year or 5-year overall survival (OS), disease-free survival (DFS) and/or locoregional recurrence (LRR) rate of cervical cancer patients living in Africa. Two reviewers independently chose the studies and evaluated the quality of the selected publications, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P). We used random effects analysis to pooled the survival rate across studies and heterogeneity was explored via sub-group and meta-regression analyses. A leave-one-out sensitivity analysis was undertaken, as well as the reporting bias assessment. Our findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P). Results: A total of 16,122 women with cervical cancer were covered in the 45 articles (59 studies), with research sample sizes ranging from 22 to 1,059 (median = 187.5). The five-year overall survival (OS) rate was 40.9% (95% CI: 35.5-46.5%). The five-year OS rate ranged from 3.9% (95% CI: 1.9-8.0%) in Malawi to as high as 76.1% (95% CI: 66.3-83.7%) in Ghana. The five-year disease-free survival rate was 66.2% (95% CI: 44.2-82.8%) while the five-year locoregional rate survival was 57.0% (95% CI: 41.4-88.7%). Conclusion: To enhance cervical cancer survival, geographical and racial group health promotion measures, as well as prospective genetic investigations, are critically required.

Correlates of dietary diversity among children aged 6-23 months of head porters in Ghana.

Objective: In many developing countries, most children cannot meet minimum dietary diversity (MDD), defined as the consumption of four or more of the seven food groups. In Ghana, only 35% of children met MDD nationwide in 2017, but rates are worse among the rural poor and resource-constrained individuals like Head Porters (HPs). The current study investigated the correlates of MDD in children of HPs aged 6-23 months old in Ghana. Methods and materials: A cross-sectional survey was carried out in 2021 among 423 HPs selected purposively from eight market centers in two commercial cities. A multi-stage sampling method was used in obtaining the sample, while a structured interview guide was used to collect data from the caregivers. Stata version 15.1 and descriptive and inferential statistics like frequency, percentage, chi-square and logistic regression were used to analyze the data. All results were deemed significant if the p-value was < 0.05 and the odds ratios with a 95% confidence interval. Results: The children had a mean age of 14.3 (±4.9) months, while half of the caregivers (48.2%) were between 15 and 25 years. Approximately 59% (251) had good knowledge of infant and young child feeding practices (IYCF). About 45% of the children consumed a diversified diet. The number of postnatal care (PNC) visits, delivery in a health facility, meeting minimum meal frequency (MMF), and the child's age was independently associated with MDD at the multivariate level. Conclusion: Over a third of the caregivers had poor knowledge of IYCF practices. Furthermore, less than half of the children achieved MDD reflecting the need for more education by the stakeholders. Regular PNC visits and delivery in health facilities were independently associated with MDD; therefore, interventions to combat low MDD should prioritize the relevance of these predictors.

Machine learning-assisted prediction of pneumonia based on non-invasive measures.

Background: Pneumonia is an infection of the lungs that is characterized by high morbidity and mortality. The use of machine learning systems to detect respiratory diseases via non-invasive measures such as physical and laboratory parameters is gaining momentum and has been proposed to decrease diagnostic uncertainty associated with bacterial pneumonia. Herein, this study conducted several experiments using eight machine learning models to predict pneumonia based on biomarkers, laboratory parameters, and physical features. Methods: We perform machine-learning analysis on 535 different patients, each with 45 features. Data normalization to rescale all real-valued features was performed. Since it is a binary problem, we categorized each patient into one class at a time. We designed three experiments to evaluate the models: (1) feature selection techniques to select appropriate features for the models, (2) experiments on the imbalanced original dataset, and (3) experiments on the SMOTE data. We then compared eight machine learning models to evaluate their effectiveness in predicting pneumonia. Results: Biomarkers such as C-reactive protein and procalcitonin demonstrated the most significant discriminating power. Ensemble machine learning models such as RF (accuracy = 92.0%, precision = 91.3%, recall = 96.0%, f1-Score = 93.6%) and XGBoost (accuracy = 90.8%, precision = 92.6%, recall = 92.3%, f1-score = 92.4%) achieved the highest performance accuracy on the original dataset with AUCs of 0.96 and 0.97, respectively. On the SMOTE dataset, RF and XGBoost achieved the highest prediction results with f1-scores of 92.0 and 91.2%, respectively. Also, AUC of 0.97 was achieved for both RF and XGBoost models. Conclusions: Our models showed that in the diagnosis of pneumonia, individual clinical history, laboratory indicators, and symptoms do not have adequate discriminatory power. We can also conclude that the ensemble ML models performed better in this study.

Exploration of Different Hypoxia Patterns and Construction of a Hypoxia-Related Gene Prognostic Index in Colorectal Cancer.

Introduction: Immune checkpoint inhibitor (ICI) therapy has been proven to be a highly efficacious treatment for colorectal adenocarcinoma (COAD). However, it is still unclear how to identify those who might benefit the most from ICI therapy. Hypoxia facilitates the progression of the tumor from different aspects, including proliferation, metabolism, angiogenesis, and migration, and improves resistance to ICI. Therefore, it is essential to conduct a comprehensive understanding of the influences of hypoxia in COAD and identify a biomarker for predicting the benefit of ICI. Methods: An unsupervised consensus clustering algorithm was used to identify distinct hypoxia-related patterns for COAD patients from TCGA and the GEO cohorts. The ssGSEA algorithm was then used to explore the different biological processes, KEGG pathways, and immune characteristics among distinct hypoxia-related clusters. Some hypoxia-related hub genes were then selected by weighted gene coexpression network analysis (WGCNA). Subsequently, univariate Cox regression analysis, multivariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) regression were utilized to construct a hypoxia-related gene prognostic index (HRGPI). Finally, validation was also conducted for HRGPI in prognostic value, distinguishing hypoxia-related characteristics and benefits of ICI. Results: We identified four hypoxia-related clusters and found that different hypoxia response patterns induced different prognoses significantly. Again, we found different hypoxia response patterns presented distinct characteristics of biological processes, signaling pathways, and immune features. Severe hypoxia conditions promoted activation of some cancer-related signaling pathways, including Wnt, Notch, ECM-related pathways, and remodeled the tumor microenvironment of COAD, tending to present as an immune-excluded phenotype. Subsequently, we selected nine genes (ANO1, HOXC6, SLC2A4, VIP, CD1A, STC2, OLFM2, ATP6V1B1, HMCN2) to construct our HRGPI, which has shown an excellent prognostic value. Finally, we found that HRGPI has an advantage in distinguishing immune and molecular characteristics of hypoxia response patterns, and it could also be an excellent predictive indicator for clinical response to ICI therapy. Conclusion: Different hypoxia response patterns activate different signaling pathways, presenting distinct biological processes and immune features. HRGPI is an independent prognostic factor for COAD patients, and it could also be used as an excellent predictive indicator for clinical response to ICI therapy.

Building a predictive model to assist in the diagnosis of cervical cancer.

Aim: Cervical cancer is still one of the most common gynecologic cancers in the world. Since cervical cancer is a potentially preventive cancer, earlier detection is the most effective technique for decreasing the worldwide incidence of the illness. Materials and methods: This research presents a novel ensemble technique for predicting cervical cancer risk. Specifically, the authors introduce a voting classifier that aggregates prediction probabilities from multiple machine-learning models: logistic regression, K-nearest neighbor, decision tree, XGBoost and multilayer perceptron. Results: The average accuracy, precision, recall and f1-score of the voting classifier were 96.6, 97.4, 95.9 and 96.6, respectively. Furthermore, the voting algorithm gains average high values for all evaluation metrics (accuracy, precision, recall and f1-score). The f1-score of the algorithm is 96%, which demonstrates the robustness of the model. Conclusion: The findings suggest that the probability of having cervical cancer can be accurately predicted utilizing the voting technique.

Neutrophil-Dependent Immunity During Pulmonary Infections and Inflammations.

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.

Evaluation of the Therapeutic Outcomes of Antibiotic Regimen Against Carbapenemase-Producing Klebsiella pneumoniae: A Systematic Review and Meta-Analysis.

Background: Carbapenemase-producing Klebsiella pneumoniae (CpKP) has been implicated as an increasing threat to public health. CpKP is a ubiquitous, opportunistic pathogen that causes both hospital and community acquired infections. This organism hydrolyzes carbapenems and other ß-lactams and thus, leading to multiple resistance to these antibiotics. Despite the difficult to treat nature of infections caused by CpKP, little has been discussed on the mortality, clinical response and microbiological success rates associated with various antibiotic regimen against CpKP. This meta-analysis was designed to fill the paucity of information on the clinical impact of various antibiotic therapeutic regimens among patients infected with CpKP. Materials and Methods: Literature in most English databases such as Medline through PubMed, Google Scholar, Web of Science, Cochrane Library and EMBASE, were searched for most studies published between the years 2015-2020. Data were analyzed using the R studio 2.15.2 statistical software program (metaphor and meta Package, Version 2) by random-effects (DerSimonian and Laird) model. Results: Twenty-one (21) studies including 2841 patients who had been infected with CpKP were analysed. The overall mortality rate was 32.2% (95%CI = 26.23-38.87; I 2 = 89%; p-value ≤ 0.01, Number of patients = 2716). Pooled clinical and microbiological success rates were 67.6% (95%CI = 58.35-75.64, I 2 = 22%, p-value = 0.25, Number of patients = 171) and 74.9% (95%CI = 59.02-86.09, I 2 = 53%, p-value = 0.05, Number of patients = 121), respectively. CpKP infected patients treated with combination therapy are less likely to die as compared to those treated with monotherapy (OR = 0.55, 95%CI = 0.35-0.87, p-value = 0.01, Number of patients = 1,475). No significant difference existed between the mortality rate among 60years and above patients vs below 60years (OR = 0.84, 95%CI = 0.28-2.57, p-value = 0.76, 6 studies, Number of patients = 1,688), and among patients treated with triple therapy vs. double therapy (OR = 0.50, 95%CI = 0.21-1.22, p-value = 0.13, 2 studies, Number of patients = 102). When compared with aminoglycoside-sparing therapies, aminoglycoside-containing therapies had positive significant outcomes on both mortality and microbiological success rates. Conclusion: New effective therapies are urgently needed to help fight infections caused by this organism. The effective use of various therapeutic options and the strict implementation of infection control measures are of utmost importance in order to prevent infections caused by CpKP. Strict national or international implementation of infection control measures and treatment guidelines will help improve healthcare, and equip governments and communities to respond to and prevent the spread of infectious diseases caused by CpKP.

The Impact of Video-Based Educational Interventions on Cervical Cancer, Pap Smear and HPV Vaccines.

Background: Video-based interventions have the potential to contribute to long-lasting improvements in health-seeking behaviours. Ghana's upsurge rate of information and communication technology usage presents an opportunity to improve the awareness of HPV vaccination and screening rates of cervical cancer among women in Ghana. This research aimed to assess the impact of video-based educational intervention centred on the Health Belief and Transtheoretical Models of behavioural changes in promoting HPV vaccination, cervical carcinoma awareness and willingness to have Pap smear test (PST) among women in Ghana. Methods: To achieve the intended sample size, convenient, purposive and stratified random sampling techniques were used. SPSS v. 23.0 was used in the data analysis. Percentages and frequencies were used to represent participants' demographic characteristics, knowledge of (1) cervical carcinoma, (2) human papillomavirus vaccine, and (3) Pap smear test. The chi-square test by McNemar was employed to evaluate variations in the post- and pre-intervention responses. A p-value < 0.05 was considered statistically significant. The level of significance was adjusted owing to multiple comparisons by using the Bonferroni's correction. Results: Before the intervention, 84.2% of the participant had some knowledge or information about cervical cancer, but after the intervention, 100% of the participant became aware of cervical cancer which represents 15.8% increment at a P < .001. The willingness to have a pap smear test increased from 35.8% to 94.2% (df = 58.4%, P < .001) after the educational intervention. The willingness to be vaccinated increased from 47.5% to 81.7% (df = 34.2%, P < .001) after the educational intervention. Six months after the intervention, participants were followed-up. 253 (42.2%) participants had gone for cervical cancer screening (Pap smear test) while 347 (57.8%) participants had not been screened. In terms of HPV vaccination, 192 participants (32.0%) had begun their HPV vaccination cycle. Conclusion: The study results show that health education, using videos, may be influential in perception changing, self-efficacy improvement and the understanding of cervical carcinoma screening and HPV vaccination.

A higher percentage of leukemic blasts with vacuoles predicts unfavorable outcomes in patients with acute myeloid leukemia.

Cytoplasmic vacuoles, which are a morphological feature of dysplasia, can be observed under a microscope at initial diagnosis. Recently, this typical morphological feature has been found to be associated with impaired survival. To investigate the clinical significance of the grading of blasts with vacuoles in acute myeloid leukemia (AML), we retrospectively studied 152 patients newly diagnosed with non-M3 AML. The patients were categorized into three groups according to the percentage of blasts with vacuoles (>20 %, 11-20 %, 0-10 %). A high percentage of blasts with vacuoles (>20 %) was positively associated with the European Leukemia Net (2017-ELN) high-risk AML, a complex karyotype, TP53 and IDH1/2 mutations, and CD71 expression and negatively associated with the ELN low-risk category. Importantly, patients who had a higher percentage of blasts with vacuoles had a lower complete remission rate in response to first-cycle induction chemotherapy. The overall survival and event-free survival of patients who had a higher percentage of blasts with vacuoles were significantly shorter. Moreover, multivariate analysis showed that blast vacuolization was an independent high prognostic factor for AML. In conclusion, a higher percentage of leukemic blasts with vacuoles predicts worse outcomes in AML and may have potential as a prognostic marker.

Prognostic Variables of Younger-Aged Cervical Carcinoma Patients: A Retrospective Study.

PURPOSE: The prevalence of carcinoma of the cervix is increasing in younger women. This study aimed to evaluate the sociodemographic, pathological, and clinical features, prognosis, and treatment of women aged ≤35 years with carcinoma of the cervix (CC). METHODS AND MATERIALS: We retrospectively analysed the clinical information of 352 younger women with carcinoma of the cervix aged ≤35 years at the Gynaecological Oncology Department of Zhengzhou University People's Hospital from April 2000 to January 2018. The overall survival was evaluated with the Kaplan-Meier model, and the log-ranked analysis was compared with the univariate analysis to determine prognostic survival-related risk factors. Cox Proportional Hazards analysis was further used in analysing parameters correlated with survival after univariate analysis. A p value <0.05 was considered statistically significant. SPSS version 23.0 was used for the data analysis. RESULTS: The most frequent histopathological type observed in the selected 352 younger women was squamous cell carcinoma (SCC) (n = 221, 62.9%), adenocarcinoma (n = 125, 35.5%), and adenosquamous carcinoma (n = 6, 1.7%). The 5-year overall survival time was 80.5%. The prognostic risk factors discovered through univariate analysis were tumour stage (IA1-IIB vs. IIIA-IVA) (89.2% vs. 35.1%: p value = 0.002), histological type (SCC vs. non-SCC) (95.7% vs. 56.2%: p value = 0.001), surgical margin (negative vs. positive) (90.9% vs. 41.2%: p value = 0.001), and pelvic lymph node metastasis (no vs. yes) (93.4% vs. 39.2%: p value = .001). The Cox proportional hazards test demonstrated that lymph node metastases ([HR] = 2.924, 95% CI: 1.432-7.426; p=0.014), tumour stage IIIA-IVA ([HR] = 3.765, 95% CI: 1.398-9.765; p=0.016), and surgical margin ([HR] = 2.167, 95% CI: 1.987-9.554; p=0.019) were independent prognostic risk factors for overall survival in younger women with cervical carcinoma. CONCLUSION: In conclusion, the status of lymph node metastases, tumour stage, and surgical margin and the type of histopathology substantially influence the rate of survival.

LSD1 as a Biomarker and the Outcome of Its Inhibitors in the Clinical Trial: The Therapy Opportunity in Tumor.

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Hence, it is of inordinate significance to ascertain novel biomarkers to forecast the prognosis and therapy targets for tumors. This review characterized LSD1 as a biomarker in different tumors. LSD1 inhibitors in clinical trials were also discussed. The recent pattern advocates that LSD1 is engaged at sauce chromatin zones linking with complexes of multi-protein having an exact DNA-binding transcription factor, establishing LSD1 as a favorable epigenetic target, and also gives a large selection of therapeutic targets to treat different tumors. This review sturdily backing the oncogenic probable of LSD1 in different tumors indicated that LSD1 levels can be used to monitor and identify different tumors and can be a useful biomarker of progression and fair diagnosis in tumor patients. The clinical trials showed that inhibitors of LSD1 have growing evidence of clinical efficacy which is very encouraging and promising. However, for some of the inhibitors such as GSK2879552, though selective, potent, and effective, its disease control was poor as the rate of adverse events (AEs) was high in tumor patients causing clinical trial termination, and continuation could not be supported by the risk-benefit profile. Therefore, we propose that, to attain excellent clinical results of inhibitors of LSD1, much attention is required in designing appropriate dosing regimens, developing in-depth in vitro/in vivo mechanistic works of LSD1 inhibitors, and developing inhibitors of LSD1 that are reversible, safe, potent, and selective which may offer safer profiles.

Eltrombopag Effectiveness and Tolerability in Chronic Immune Thrombocytopenia: A Meta-Analysis.

Eltrombopag is an orally administered, non-peptide, thrombopoietin receptor agonist which initiates thrombopoietin signaling and stimulates the production of normally functioning platelet. We aimed to do a systematic review and meta-analysis of currently available published data to verify whether eltrombopag treatment in patients with chronic immune-mediated thrombocytopenia can prolong survival. We searched for published, randomized, controlled trials in PubMed, Cochrane and Scopus databases using the following search strategy ("Eltrombopag" OR "Benzoates" OR "Hydrazines") AND ("Idiopathic Thrombocytopenic Purpura" OR "immune thrombocytopenia" OR "Idiopathic Thrombocytopenic Purpuras" OR "Immune Thrombocytopenia" OR "Autoimmune Thrombocytopenia" OR "Werlhof"). The pooled relative risk (RR) showed that eltrombopag group has significantly higher overall platelet response than placebo group (MD = 3.42, 95% CI [2.51, 4.65], P > .0001); pooled results were homogenous (P = .27, I2 = 22%). The pooled relative risk showed that eltrombopag group has lower incidence of any bleeding than placebo group (MD = 0.65, 95% CI [0.48, 0.87], P = .003); pooled results were heterogenous (P = .001, I2 = 75%) and the detected heterogeneity was best resolved after excluding Bussel et al (P = .10). Homogeneous results were still favored eltrombopag group (MD = 0.75, 95% CI [0.60, 0.93], P = .008).

Awareness of Cervical Cancer and Attitude Toward Human Papillomavirus and Its Vaccine Among Ghanaians.

Background: Cervical cancer (CC) is the fourth most commonly diagnosed cancer among women. Ghana is a low-middle- income country with annual diagnosed cases of 3,151 and 2,119 deaths. The high prevalence rate of cervical cancer in Ghana is mainly due to ineffective preventive measures and insufficient knowledge about the disease. Therefore, our objective was to evaluate the level of knowledge and awareness of cervical cancer and attitude toward human papillomavirus and its vaccine among Ghanaians. Methods: This descriptive cross-sectional survey on the awareness of cervical cancer and attitude toward human papillomavirus and its vaccine was carried out from March 2019 to February 2020. SPSS v. 23.0 was used in the data analysis. The participants' demographic characteristics, knowledge of cervical carcinoma, human papillomavirus vaccine and HPV, and the likelihood to be vaccinated were represented as percentages and frequencies. The difference between males and females was assessed using the chi-square test. The logistic regression analysis was used to evaluate the relationship of possible related indicators with the willingness to receive the HPV vaccine. A p < 0.05 was considered statistically significant. Results: A total of 1,376 participants were involved in the final analysis. Among the 1,376 participants involved in this survey, 1,240 participants (90.1%) representing 456 males (33.1%) and 784 females (57.0%) were aware of the terminology "cervical cancer" with a significant p = 0.001. When stratified by gender, women had significantly greater knowledge, compared to men in terms of "cervical cancer being common in middle age (35-50) females" (75.5 vs. 67.5%, respectively, p ≤ 0.001). When stratified by gender, women had significantly greater knowledge of human papillomavirus (54.5 vs. 43.6%, respectively, p < 0.001) and the human papillomavirus vaccine (39.3 vs. 33.1%, respectively, p = 0.019) compared to men. Conclusion: Majority of the respondents had poor knowledge regarding cervical cancer risk factors, symptoms, HPV, and its vaccine. Hence, this indicates a wakeup call for government to increase the awareness and knowledge level via the media and health professionals.

Polymorphism in the Androgen Biosynthesis Gene (CYP17), a Risk for Prostate Cancer: A Meta-Analysis.

Gene polymorphism is one of the few factors that increases the risk of prostate cancer. T to C substitution in the 5' promoter region of the CYP17 gene is hypothesized to increase the rate of gene transcription, increase androgen production, and thereby increase the risk of prostate cancer. Nevertheless, the inconsistencies originating from studies on CYP17 polymorphism and prostate cancer prompted this meta-analysis, to decipher the association between CYP17 polymorphism and prostate cancer. Most case-control studies addressing CYP17 polymorphism and prostate cancer were exhaustively searched from Web of Science, Google Scholar, and PubMed. The various genotype distributions as well as the minor allele distributions were retrieved. Pooled odds ratios (ORs) with their 95% CI and estimates of the Hardy-Weinberg Equilibrium were calculated. Analyses were performed using the RevMan v.5.3 software and SPSS v.21. There was high-pooled heterogeneity (I2 = 87.0%, OR = .42, CI [.39, .45], and p < .001) among the A2 versus A1 allele. With the per-allele model (A2 versus A1), ethnicity was a major risk factor to prostate cancer, with Asians recording the highest risk (OR = 12.61, 95% CI [8.77, 18.12]). From the genotype models, A1/A1 versus A2/A2 (OR = 3.02, 95% CI [2.65, 3.44]) and A1/A2 versus A2/A2 (OR = 4.39, 95% CI [3.86, 5.00]) were all significantly associated with prostate cancer. Although some genotype models were associated with the risk of prostate cancer, we should be mindful when interpreting the results of this study because of the limited number of studies and the small sample size used.

The relationship between methionine synthase rs1805087 polymorphism and hematological cancers risk.

Background: The relationship between hematological cancer susceptibility and methionine synthase MTR A2756G (rs1805087) polymorphism is inconclusive based on data from past studies. Hence, this updated meta-analysis was conducted to investigate the relationship between methionine synthase reductase (MTR) rs1805087 polymorphism and hematological cancers. Method: We searched EMBASE, Google Scholar, Ovid and PubMed databases for possible relevant articles up to December 31, 2019. Results: The overall pooled outcome of our analysis showed lack of association between the risk of hematological malignancies and MTR A2756G polymorphism under the allele model (G vs A: odds ratio = 1.001, 95% CI: 0.944-1.061; p = 0.983), recessive model (GG vs GA + AA: odds ratio = 1.050, 95% CI: 0.942-1.170; p = 0.382). Conclusion: The findings in this study demonstrate a lack of relationship between hematological cancers and MTR A2756G.