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Frontiers in Oncology 2024Squamous cell carcinoma (SCC) is a prevalent malignancy affecting multiple organs in the human body, including the oral cavity, esophagus, cervix, and skin. Given its... (Review)
Review
Squamous cell carcinoma (SCC) is a prevalent malignancy affecting multiple organs in the human body, including the oral cavity, esophagus, cervix, and skin. Given its significant incidence and mortality rates, researchers are actively seeking effective diagnostic and therapeutic strategies. In recent years, exosomes and their molecular cargo, particularly circular RNA (circRNA), have emerged as promising areas of investigation in SCC research. Exosomes are small vesicles released into the extracellular environment by cells that contain biomolecules that reflect the physiological state of the cell of origin. CircRNAs, known for their unique covalently closed loop structure and stability, have garnered special attention in oncology and are closely associated with tumorigenesis, progression, metastasis, and drug resistance. Interestingly, exosomal circRNAs have been identified as ideal biomarkers for noninvasive cancer diagnosis and prognosis assessment. This article reviews the progress in research on exosomal circRNAs, focusing on their expression patterns, functions, and potential applications as biomarkers in SCC, aiming to provide new insights and strategies for the diagnosis and treatment of SCC.
PubMed: 38933443
DOI: 10.3389/fonc.2024.1430684 -
The Pan African Medical Journal 2024Placenta accreta is a rare but serious placental attachment abnormality. The aim of this study is to analyze the epidemiological, clinical, para-clinical and...
[Placenta accreta: a retrospective descriptive study of 46 patients treated in the Obstetrics and Gynaecology Department of the Farhat Hached University Hospital in Sousse, Tunisia].
Placenta accreta is a rare but serious placental attachment abnormality. The aim of this study is to analyze the epidemiological, clinical, para-clinical and evolutionary features of placenta accreta, to investigate the therapeutic management and to assess maternal and neonatal morbidity and mortality. We conducted a retrospective, descriptive study of patients with histologically confirmed placenta accreta in the obstetrics and gynaecology department of the Farhat Hached University Hospital in Sousse, over a 4-year period from 1 January 2015 to 31 December 2019. The epidemiological, clinical, paraclinical, therapeutic and evolutionary data were collected from patients´ medical records and operative reports. In our series, we identified 46 cases of placenta accreta. The average age of our patients was 35±4.61 years. Each of our patients had a scarred uterus. The average term of delivery was 34 weeks of amenorrhoea and the mode of delivery was caesarean section for all our patients. First-line hysterectomy was performed in 40 patients and conservative treatment in 6. Sixteen patients developed maternal complications. No maternal death was observed. Placenta accreta is a rare condition associated with significant maternal and foetal morbidity.
Topics: Humans; Female; Retrospective Studies; Tunisia; Placenta Accreta; Adult; Pregnancy; Hospitals, University; Hysterectomy; Cesarean Section; Young Adult; Infant, Newborn; Conservative Treatment
PubMed: 38933434
DOI: 10.11604/pamj.2024.47.147.38111 -
The Pan African Medical Journal 2024Lymphatic filariasis is a neglected tropical disease that affects the lymphatic system of humans. The major etiologic agent is a nematode called Wuchereria bancrofti,... (Review)
Review Meta-Analysis
Lymphatic filariasis is a neglected tropical disease that affects the lymphatic system of humans. The major etiologic agent is a nematode called Wuchereria bancrofti, but Brugia malayi and Brugia timoriare sometimes encountered as causative agents. Mosquitoes are the vectors while humans the definitive hosts respectively. The burden of the disease is heavier in Nigeria than in other endemic countries in Africa. This occurs with increasing morbidity and mortality at different locations within the country, the World Health Organization recommended treatments for lymphatic filariasis include the use of Albendazole (400mg) twice per year in co-endemic areas with loa loa, Ivermectin (200mcg/kg) in combination with Albendazole (400mg) in areas that are co-endemic with onchocerciasis, ivermectin (200mcg/kg) with diethylcarbamazine citrate (DEC) (6mg/kg) and albendazole (400mg) in areas without onchocerciasis. This paper covered a systematic review, meta-analysis, and scoping review on lymphatic filariasis in the respective geopolitical zones within the country. The literature used was obtained through online search engines including PubMed and Google Scholar with the heading "lymphatic filariasis in the name of the state", Nigeria. This review revealed an overall prevalence of 11.18% with regional spread of Northwest (1.59%), North Central and North East, (4.52%), South West (1.26%), and South-South with South East (3.81%) prevalence. The disease has been successfully eliminated in Argungu local government areas (LGAs) of Kebbi State, Plateau, and Nasarawa States respectively. Most clinical manifestations (31.12%) include hydrocele, lymphedema, elephantiasis, hernia, and dermatitis. Night blood samples are appropriate for microfilaria investigation. Sustained MDAs, the right testing methods, early treatment of infected cases, and vector control are useful for the elimination of lymphatic filariasis for morbidity management and disability prevention in the country. Regional control strategies, improved quality monitoring of surveys and intervention programs with proper records of morbidity and disability requiring intervention are important approaches for the timely elimination of the disease in Nigeria.
Topics: Elephantiasis, Filarial; Humans; Nigeria; Animals; Wuchereria bancrofti; Filaricides; Albendazole; Neglected Diseases; Ivermectin; Brugia malayi
PubMed: 38933431
DOI: 10.11604/pamj.2024.47.142.39746 -
Health Science Reports Jun 2024Lung cancer is ranked as the second most prevalent form of cancer worldwide. Nonsmall cell lung cancer (NSCLC) represents the predominant histological subtype. Research...
BACKGROUND AND AIMS
Lung cancer is ranked as the second most prevalent form of cancer worldwide. Nonsmall cell lung cancer (NSCLC) represents the predominant histological subtype. Research suggests that one-third of lung cancer patients also experiencing depression. Antidepressants play an indispensable role in the management of NSCLC. Despite significant advancements in treatment, lung cancer patients still face a high mortality rate. Major depressive disorder (MDD) and related antidepressants involved in treatment efficacy and prognosis of NSCLC. However, there has been a lack of screening and analysis regarding genes and networks associated with both NSCLC and MDD.
METHODS
To investigate the correlation between MDD and NSCLC, our discovery and validation analysis included four datasets from the Gene Expression Omnibus database from NSCLC or MDD. Differential gene expression (DEGs) analysis, GO and KEGG Pathway, and protein-protein interaction network analyzes to identify hub genes, networks, and associated observations link between MDD and NSCLC.
RESULTS
The analysis of two datasets yielded a total of 84 downregulated and 52 upregulated DEGs. Pathway enrichment analyzes indicated that co-upregulated genes were enriched in the regulation of positive regulation of cellular development, collagen-containing extracellular matrix (ECM), cytokine binding, and axon guidance. We identified 20 key genes, which were further analyzed using the MCODE plugin to identify two core subnetworks. The integration of functionally similar genes provided valuable insights into the potential involvement of these hub genes in diverse biological processes including angiogenesis humoral immune response regulation inflammatory response organization ECM network.
CONCLUSION
We have identified a total of 136 DEGs that participate in multiple biological signaling pathways. A total of 20 hub genes have demonstrated robust associations, potentially indicating novel diagnostic and therapeutic targets for both diseases.
PubMed: 38933422
DOI: 10.1002/hsr2.2167 -
Health Science Reports Jun 2024Stroke is the leading cause of disability and the second most common cause of death after ischemic heart disease worldwide. Understanding predictors of early poststroke...
Predictors of 30-day mortality following the first episode of stroke among patients admitted at referral hospitals in Dodoma, central Tanzania: A prospective longitudinal observational study.
BACKGROUND AND AIMS
Stroke is the leading cause of disability and the second most common cause of death after ischemic heart disease worldwide. Understanding predictors of early poststroke mortality provides opportunities for interventions and favorable outcomes. This study aimed to determine the incidence and predictors of 30-day mortality among patients admitted with the first stroke at referral hospitals in Dodoma.
METHODS
A prospective longitudinal observational design enrolled patients with acute stroke confirmed by CT scan or MRI admitted at referral hospitals in Dodoma. The National Institute of Health Stroke Scale was used to assess stroke severity at baseline. A comparison of risk factors, clinical profiles, and mortality was done using the Chi-square test. A logistic regression model was used to determine the predictors of 30-day mortality in patients with the stroke while the 30-day probability of survival was estimated using Kaplan-Meier analysis.
RESULTS
Out of 226 patients with first-ever stroke, 121(54%) were males, and the population mean age was 63(15) years. The 140(62%) had Ischemic stroke, and 154(68%) survived at the 30th day. Patients with a history of smoking 2.4 [95% confidence interval (CI) (1.0-5.6), = 0.048], loss of consciousness 2.7 [95% CI (1.2-6.4; = 0.019] and unequal pupil size 13.7 [95% CI (4.1-58.1, < 0.001 were significantly more associated with mortality within 30 days. The median survival was 7 (3-9) days, whereas alcohol drinkers and those aged above 60 years had a shorter time to mortality compared to non-alcohol drinkers and those aged <60 years.
CONCLUSION
The study showed a high incidence of mortality within 30 days after the first stroke episode, with the highest proportion dying within 7 days of being hospitalized. Advanced age of ≥60 years, smoking, alcohol use, and severe stroke at admission warrant special attention.
PubMed: 38933419
DOI: 10.1002/hsr2.2198 -
Innovation (Cambridge (Mass.)) Jul 2024Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct...
Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct routes. Entomopathogenic fungi are primarily believed to infect host insects through external cuticle penetration. Here, we report a new variety, var. (Bbm), that can infect insects through the previously unrecognized foregut. Dual routes of infection significantly accelerate insect mortality. The pH-responsive transcription factor PacC in Bbm exhibits rapid upregulation and efficient proteolytic processing via PalC for alkaline adaptation in the foregut. Expression of is regulated by the adjacent downstream gene . Compared to non-enteropathogenic strains such as ARSEF252, in Bbm lacks a 249-bp fragment, resulting in its enhanced alkaline-induced expression. This induction promotes upregulation and facilitates PacC activation. Expressing the active form of BbmPacC in ARSEF252 enables intestinal infection. This study uncovers the pH-responsive Aia-PalC-PacC cascade enhancing fungal alkaline tolerance for intestinal infection, laying the foundation for developing a new generation of fungal insecticides to control destructive insect pests.
PubMed: 38933340
DOI: 10.1016/j.xinn.2024.100644 -
Frontiers in Neurology 2024Acute Ischemic Stroke (AIS) remains a leading cause of mortality and disability worldwide. Rapid and precise prognostication of AIS is crucial for optimizing treatment...
BACKGROUND
Acute Ischemic Stroke (AIS) remains a leading cause of mortality and disability worldwide. Rapid and precise prognostication of AIS is crucial for optimizing treatment strategies and improving patient outcomes. This study explores the integration of machine learning-derived radiomics signatures from multi-parametric MRI with clinical factors to forecast AIS prognosis.
OBJECTIVE
To develop and validate a nomogram that combines a multi-MRI radiomics signature with clinical factors for predicting the prognosis of AIS.
METHODS
This retrospective study involved 506 AIS patients from two centers, divided into training (n = 277) and validation ( = 229) cohorts. 4,682 radiomic features were extracted from T1-weighted, T2-weighted, and diffusion-weighted imaging. Logistic regression analysis identified significant clinical risk factors, which, alongside radiomics features, were used to construct a predictive clinical-radiomics nomogram. The model's predictive accuracy was evaluated using calibration and ROC curves, focusing on distinguishing between favorable (mRS ≤ 2) and unfavorable (mRS > 2) outcomes.
RESULTS
Key findings highlight coronary heart disease, platelet-to-lymphocyte ratio, uric acid, glucose levels, homocysteine, and radiomics features as independent predictors of AIS outcomes. The clinical-radiomics model achieved a ROC-AUC of 0.940 (95% CI: 0.912-0.969) in the training set and 0.854 (95% CI: 0.781-0.926) in the validation set, underscoring its predictive reliability and clinical utility.
CONCLUSION
The study underscores the efficacy of the clinical-radiomics model in forecasting AIS prognosis, showcasing the pivotal role of artificial intelligence in fostering personalized treatment plans and enhancing patient care. This innovative approach promises to revolutionize AIS management, offering a significant leap toward more individualized and effective healthcare solutions.
PubMed: 38933326
DOI: 10.3389/fneur.2024.1379031 -
Frontiers in Immunology 2024Extracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations...
BACKGROUND
Extracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.
METHODS
Plasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (<1 day after admission) and late mortality were assessed. Circulating EPs, cytokine profiles, and blood counts of platelets and leukocytes were determined. Receiver operating characteristic analyses were conducted.
RESULTS
Despite no significant differences in injury pattern or severity, non-survivors exhibited significantly elevated counts of circulating EPs compared to survivors. The optimal cut-off for EPs <200 nm indicating non-survivors was 17380/µl plasma, with a sensitivity of 77% and a specificity of 61% in predicting in-hospital mortality. Later non-survivors received significantly higher numbers of units of packed red blood cells [8.54 ± 5.45 vs. 1.29 ± 0.36 units], had higher serum lactate [38.00 ± 7.51 vs. 26.98 ± 1.58 mg/dL], significantly lower platelet counts [181.30 ± 18.06 vs. 213.60 ± 5.85 *10³/µL] and lower heart rates [74.50 ± 4.93 vs. 90.18 ± 2.06 beats/minute] upon arrival at the ED compared to survivors.
CONCLUSION
Our results demonstrate the high diagnostic potential of elevated concentrations of circulating EPs <200 nm for identifying patients at risk of mortality after severe trauma. This parameter shows comparable sensitivity to established clinical predictors. Early evaluation of EPs concentration could complement assessment markers in guiding early therapeutic decisions.
Topics: Humans; Male; Female; Middle Aged; Adult; Hospital Mortality; Biomarkers; Extracellular Vesicles; Injury Severity Score; Aged; Wounds and Injuries; Prognosis; Cytokines; Multiple Trauma; ROC Curve
PubMed: 38933277
DOI: 10.3389/fimmu.2024.1390380 -
Frontiers in Immunology 2024Nervous necrosis virus (NNV) is one of the greatest threats to Mediterranean aquaculture, infecting more than 170 fish species and causing mortalities up to 100% in...
Nervous necrosis virus (NNV) is one of the greatest threats to Mediterranean aquaculture, infecting more than 170 fish species and causing mortalities up to 100% in larvae and juveniles of susceptible species. Intensive aquaculture implies stressed conditions that affect the welfare of fish and their ability to fight against infections. In fact, a higher susceptibility to NNV has been related to poor welfare conditions. In order to analyze the physiological link between stressed conditions and increased susceptibility to NNV, as well as its possible role in the pathogenesis of this disease, we reared shi drum () juveniles (30.7 ± 3.10 g body weight), which are expected to be asymptomatic upon NNV infection, at three stocking densities (2, 15, and 30 kg/m) for 27 days and subsequently challenged them with NNV. We firstly characterized the stressed conditions of the specimens before and after infection and recorded the mortalities, demonstrating that stressed specimens reared at 30 kg/m suffered mortalities. However, the viral loads in different tissues were similar in all experimental groups, allowing horizontal and vertical transmission of the virus from asymptomatic specimens. All of these data suggest that shi drum tolerates wide ranges of culture densities, although high densities might be a setback for controlling NNV outbreaks in this species. In an attempt to understand the molecular pathways orchestrating this susceptibility change in stressed conditions, we performed a transcriptomic analysis of four tissues under mock- and NNV-infected conditions. In addition to the modification of the exceptive pathways such as cell adhesion, leukocyte migration, cytokine interaction, cell proliferation and survival, and autophagy, we also observed a heavy alteration of the neuroactive ligand-receptor pathway in three of the four tissues analyzed. Our data also point to some of the receptors of this pathway as potential candidates for future pharmacological treatment to avoid the exacerbated immune response that could trigger fish mortalities upon NNV infection.
Topics: Animals; Nodaviridae; Fish Diseases; RNA Virus Infections; Disease Susceptibility; Aquaculture; Viral Load
PubMed: 38933269
DOI: 10.3389/fimmu.2024.1304603 -
Frontiers in Immunology 2024This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize...
BACKGROUND
This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize the assessment of immunotherapy response.
METHODS
A training set comprising 305 HCC cases was obtained from The Cancer Genome Atlas (TCGA) database. Initially, a screening process was undertaken to identify prognostically significant immune-related genes (IRGs), followed by the application of logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods for gene modeling. Subsequently, the final model was constructed using support vector machines-recursive feature elimination (SVM-RFE). Following model evaluation, quantitative polymerase chain reaction (qPCR) was employed to examine the gene expression profiles in tissue samples obtained from our cohort of 54 patients with HCC and an independent cohort of 231 patients, and the prognostic relevance of the model was substantiated. Thereafter, the association of the model with the immune responses was examined, and its predictive value regarding the efficacy of immunotherapy was corroborated through studies involving three cohorts undergoing immunotherapy. Finally, the study uncovered the potential mechanism by which the model contributed to prognosticating HCC outcomes and assessing immunotherapy effectiveness.
RESULTS
SVM-RFE modeling was applied to develop an OS prognostic model based on six IRGs (CMTM7, HDAC1, HRAS, PSMD1, RAET1E, and TXLNA). The performance of the model was assessed by AUC values on the ROC curves, resulting in values of 0.83, 0.73, and 0.75 for the predictions at 1, 3, and 5 years, respectively. A marked difference in OS outcomes was noted when comparing the high-risk group (HRG) with the low-risk group (LRG), as demonstrated in both the initial training set (0.0001) and the subsequent validation cohort (0.0001). Additionally, the SVMRS in the HRG demonstrated a notable positive correlation with key immune checkpoint genes (CTLA-4, PD-1, and PD-L1). The results obtained from the examination of three cohorts undergoing immunotherapy affirmed the potential capability of this model in predicting immunotherapy effectiveness.
CONCLUSIONS
The HCC predictive model developed in this study, comprising six genes, demonstrates a robust capability to predict the OS of patients with HCC and immunotherapy effectiveness in tumor management.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Immunotherapy; Prognosis; Biomarkers, Tumor; Male; Female; Transcriptome; Middle Aged; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Support Vector Machine; Treatment Outcome
PubMed: 38933262
DOI: 10.3389/fimmu.2024.1371829