Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia.

BACKGROUND: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. METHODS: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. RESULTS: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. CONCLUSIONS: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

The Influence of Tumor-Specific Markers in Breast Cancer on Other Blood Parameters.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer among women, responsible for the highest number of cancer-related deaths worldwide. There is limited data available related to serum tumor markers in breast cancer and other blood parameters or other glandular laboratory parameters. This study aims to evaluate the correlation of tumor-specific markers for breast cancer with other blood parameters and how these correlations could impact clinical management. MATERIAL AND METHOD: This retrospective study represents a data analysis from 1 January 2020 to 31 May 2023, in the County Hospital of Timisoara, Romania. We reviewed all the cases where, in the laboratory analyses, the serum tumor specific biomarkers for breast cancer were analyzed. RESULTS: A statistical analysis was performed in order to identify a possible relationship between CA 15-3 and the various biomarkers and blood parameters included in the present study. Values were classified according to reference ranges. The tests revealed no statistically significant associations between CA 15-3 values and the levels of CA125 (χ2(1) = 1.852, p = 0.174), CEA (χ2(1) = 1.139, p = 0.286), AFP (Fisher's exact test, p = 0.341), fT4 (Fisher's exact test, p = 0.310), TSH (Fisher's exact test, p = 0.177), or PTH (Fisher's exact test, p = 0.650). CONCLUSION: The findings indicate a lack of strong correlation between CA 15-3 and CA125, CEA, AFP, thyroid function markers, or PTH within this cohort.

Systematic Review on the Effectiveness and Outcomes of Nivolumab Treatment Schemes in Advanced and Metastatic Cervical Cancer.

Advanced and metastatic cervical cancer remains a formidable challenge in oncology, with immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab emerging as a potential therapeutic option. This systematic review rigorously assesses the effectiveness and outcomes of various nivolumab treatment regimens within this patient cohort, drawing from clinical trials and real-world evidence up to December 2023. Following a comprehensive search across PubMed, Scopus, and Embase, four studies were deemed eligible, involving a collective total of 80 patients. One preliminary trial data were excluded from the final analysis, as well as four other proceedings and abstracts on the efficacy and safety of nivolumab on advanced cervical cancer. The patients' average age across these studies was 48 years, with an average of 38% having an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Notably, 64% of all patients were positive for high-risk HPV, and 71% exhibited PD-L1 positivity, indicating a substantial target population for nivolumab. The analysis revealed a pooled objective response rate (ORR) of 48%, with a disease control rate (DCR) averaging 71%. Moreover, progression-free survival (PFS) at 6 months was observed at an average rate of 50%, reflecting the significant potential of nivolumab in managing advanced stages of the disease. The review highlights the influence of PD-L1 status on response rates and underscores the enhanced outcomes associated with combination therapy approaches. By delineating the variability in treatment efficacy and pinpointing key factors affecting therapeutic response and survival, this systematic review calls for further investigations to refine nivolumab's clinical application, aiming to improve patient outcomes in advanced and metastatic cervical cancer.

3D-CFD Modeling of Hollow-Fiber Membrane Contactor for CO2 Absorption Using MEA Solution.

Membrane technology is considered an innovative and promising approach due to its flexibility and low energy consumption. In this work, a comprehensive 3D-CFD model of the Hollow-Fiber Membrane Contactor (HFMC) system for CO2 capture into aqueous MEA solution, considering a counter-current fluid flow, was developed and validated with experimental data. Two different flow arrangements were considered for the gas mixture and liquid solution inside the HFMC module. The simulation results showed that the CO2 absorption efficiency was considerably higher when the gas mixture was channeled through the membranes and the liquid phase flowed externally between the membranes, across a wide range of gas and liquid flow rates. Sensitivity studies were performed in order to determine the optimal CO2 capture process parameters under different operating conditions (flow rates/flow velocities and concentrations) and HFMC geometrical characteristics (e.g., porosity, diameter, and thickness of membranes). It was found that increasing the membrane radius, while maintaining a constant thickness, positively influenced the efficiency of CO2 absorption due to the higher mass transfer area and residence time. Conversely, higher membrane thickness resulted in higher mass transfer resistance. The optimal membrane thickness was also investigated for various inner fiber diameters, resulting in a thickness of 0.2 mm as optimal for a fiber inner radius of 0.225 mm. Additionally, a significant improvement in CO2 capture efficiency was observed when increasing membrane porosity to values below 0.2, at which point the increase dampened considerably. The best HFMC configuration involved a combination of low porosity, moderate thickness, and large fiber inner diameter, with gas flow occurring within the fiber membranes.

Understanding the Impact of COVID-19 on Roma Vulnerable Communities in Western Romania: Insights and Predictive Factors from a Retrospective Study.

BACKGROUND: The COVID-19 pandemic disproportionately affected vulnerable populations like Roma patients in Western Romania due to marginalization and limited healthcare access. METHODS: A retrospective study analyzed COVID-19 cases between March 2020 and August 2022 using data from the Directorate of Public Health in Timis county. Demographic, epidemiological, clinical, and laboratory data were assessed, along with risk factors and biomarkers for ICU admission and mortality prediction. The following biomarkers were assessed: C-reactive protein (CRP), ferritin (FER), IL-6, D-dimers, lactate dehydrogenase (LDH), high density lipoprotein cholesterol (HDL), and 25-OH vitamin D (25-OHD). RESULTS: In comparison with the general population (GP), Roma patients were more overweight (p = 0.0292), came from rural areas (p = 0.0001), could not recall transmission source (p = 0.0215), were admitted to the intensive care unit (ICU, p = 0.0399) more frequently, had worse symptomatology (p = 0.0490), showed more elevated levels of CRP (p = 0.0245) and IL-6 (p < 0.0001) and lower levels of HDL (p = 0.0008) and 25-OHD (p = 0.0299). A stronger, significant correlation was observed between CRP and severity (rho = 0.791 vs. 0.433 in GP), and an inverse stronger significant one was observed between HDL and severity (rho = -0.850 vs. -0.734 in GP) in the Roma patients. The male sex continues to be an important risk factor for ICU admission (OR = 2.379) and death (OR = 1.975), while heavy smoking was more important in relation to ICU admission (OR = 1.768). Although the Roma ethnicity was 1.454 times more at risk of ICU admission than the GP, this did not prove statistically significant (p = 0.0751). CRP was the most important predictive factor in regards to admission to the ICU for both Roma (OR = 1.381) and the GP (OR = 1.110) and in regards to death (OR = 1.154 for Roma, OR = 1.104 for GP). A protective effect of normal values of HDL and 25-OHD was observed in the GP for both ICU admission (OR = 0.947, 0.853, respectively) and death (OR = 0.920, 0.921, respectively), while for the Roma group, normal 25-OHD values were only considered protective in regards to death (OR = 0.703). Cutoff values for ICU admission were 28.98 mg/L for Roma and 29.03 mg/L for GP patients, with high specificity for both groups (over 95). CONCLUSIONS: Higher rates of ICU admissions, severe symptomatology, and distinct laboratory biomarker profiles among Roma patients emphasize the critical importance of personalized care strategies and targeted interventions to mitigate the disproportionate burden of COVID-19 on vulnerable communities. CRP values at admission have had a clear impact as a risk assessment biomarker for Roma patients, while the significance of IL-6, HDL, and 25-OHD should also not be overlooked in these patients.

TP53 gene implications in prostate cancer evolution: potential role in tumor classification.

Background and aims: Prostate adenocarcinoma (PRAD) is a complex disease that can be driven by alterations in both coding and noncoding genes. Recent research has identified coding and non-coding genes that are considered to play important roles in prostate cancer evolution and which may be used as biomarkers for disease diagnosis, prognosis, and treatment. TP53 is a critical hub gene in prostate cancer. Advanced studies have demonstrated the crosstalk between coding and non-coding RNAs, particularly microRNAs (miRNAs). Methods: In this study, we investigated the roundabout of TP53 and their regulatory miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) based on the TCGA data set. We validated an additional patient cohort of 28 matched samples of patients with PRAD at tissue and plasma level. Results: Therefore, using the UALCAN online database, we evaluated the expression level in PRAD of these genes revealing overexpression of TP53. qRT-PCR validation step endorsed the expression level for these genes. Additionally, we evaluated the expression level of the four key miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) interconnected as a network at tissue and plasma levels. Conclusions: Through these results, we demonstrated the essential function of TP53 and its associated miRNAs that play a significant role in tumor control, highlighting miRNAs' potential as future therapeutic targets and biomarkers with important implications in managing prostate cancer.

Environmental impact assessment of green ammoniacoupled with urea and ammonium nitrate production.

This study aims to explore more sustainable ammonia production routes for urea and ammonium nitrate fertilizers to support the rising global food demand and help achieve the Net Zero Emissions scenario by 2050. The research uses process modelling tools and Life Cycle Assessment methodology to evaluate the technical and environmental performance of green ammonia production compared to blue ammonia production, both pathways coupled with urea and ammonium nitrate production processes. The blue ammonia scenario uses steam methane reforming for H2 production, while the sustainable approach scenarios consider water electrolysis with renewable resources (i.e., wind, hydro and photovoltaics) and nuclear power as a carbon-free source for H2 generation. The study assumes an annual productivity of 450,000 tons for both urea and ammonium nitrate. The environmental assessment uses mass and energy balance data derived from process modelling and simulation. A cradle-to-gate environmental evaluation is conducted using GaBi software and the Recipe 2016 impact assessment method. Results show that green ammonia production requires less raw materials but has higher energy consumption due to electrolytic H2 production (i.e., >90% of total energy requirements). The use of nuclear power achieves the highest reduction in global warming potential (i.e., 5.5 times for urea and 2.5 times for ammonium nitrate production processes), while hydro power coupled with electrolytic H2 production shows lower environmental impacts in most categories (i.e., six out of ten impact categories). Overall, the sustainable scenarios prove to be suitable alternatives for fertilizer production towards achieving a more sustainable future.

Insights into the Human Microbiome and Its Connections with Prostate Cancer.

The human microbiome represents the diversity of microorganisms that live together at different organ sites, influencing various physiological processes and leading to pathological conditions, even carcinogenesis, in case of a chronic imbalance. Additionally, the link between organ-specific microbiota and cancer has attracted the interest of numerous studies and projects. In this review article, we address the important aspects regarding the role of gut, prostate, urinary and reproductive system, skin, and oral cavity colonizing microorganisms in prostate cancer development. Various bacteria, fungi, virus species, and other relevant agents with major implications in cancer occurrence and progression are also described. Some of them are assessed based on their values of prognostic or diagnostic biomarkers, while others are presented for their anti-cancer properties.

New Insights into the Multivariate Analysis of SER Spectra Collected on Blood Samples for Prostate Cancer Detection: Towards a Better Understanding of the Role Played by Different Biomolecules on Cancer Screening: A Preliminary Study.

It is possible to obtain diagnostically relevant data on the changes in biochemical elements brought on by cancer via the use of multivariate analysis of vibrational spectra recorded on biological fluids. Prostate cancer and control groups included in this research generated almost similar SERS spectra, which means that the values of peak intensities present in SERS spectra can only give unspecific and limited information for distinguishing between the two groups. Our diagnostic algorithm for prostate cancer (PCa) differentiation was built using principal component analysis and linear discriminant analysis (PCA-LDA) analysis of spectral data, which has been widely used in spectral data management in many studies and has shown promising results so far. In order to fully utilize the entire SERS spectrum and automatically determine the most meaningful spectral features that can be used to differentiate PCa from healthy patients, we perform a multivariate analysis on both the entire and specific spectral intervals. Using the PCA-LDA model, the prostate cancer and control groups are clearly distinguished in our investigation. The separability of the following two data sets is also evaluated using two alternative discrimination techniques: principal least squares discriminant analysis (PLS-DA) and principal component analysis-support vector machine (PCA-SVM).

SARS-CoV-2: An Overview of the Genetic Profile and Vaccine Effectiveness of the Five Variants of Concern.

With the onset of the COVID-19 pandemic, enormous efforts have been made to understand the genus SARS-CoV-2. Due to the high rate of global transmission, mutations in the viral genome were inevitable. A full understanding of the viral genome and its possible changes represents one of the crucial aspects of pandemic management. Structural protein S plays an important role in the pathogenicity of SARS-CoV-2, mutations occurring at this level leading to viral forms with increased affinity for ACE2 receptors, higher transmissibility and infectivity, resistance to neutralizing antibodies and immune escape, increasing the risk of infection and disease severity. Thus, five variants of concern are currently being discussed, Alpha, Beta, Gamma, Delta and Omicron. In the present review, a comprehensive summary of the following critical aspects regarding SARS-CoV-2 has been made: (i) the genomic characteristics of SARS-CoV-2; (ii) the pathological mechanism of transmission, penetration into the cell and action on specific receptors; (iii) mutations in the SARS-CoV-2 genome; and (iv) possible implications of mutations in diagnosis, treatment, and vaccination.

Gastric Pull-up: A Back-up Surgical Solution in the Treatment of Large Hiatal Hernias.

The laparoscopic treatment of the hiatal hernias is nowadays the standard procedure. However, due to the volume and the age of the affliction, there are some situations in which the classical approach is indicated. The latter is associated with specific risks. The appearance of some intra-operatory incidents or accidents could lead to changes in the tactics and the techniques, moreover the abandon of the classical procedure and the use of alternative solutions. These procedures are meant to solve the case with minimum negative effects on the patient. This article presents the case of a 62 year-old female patient, diagnosed with a large type II hiatal hernia on which the surgical team had to intervene through a median xypho-umbilical laparotomy. During the attempt to perform the Nissen procedure, the irreversible lesion of the abdominal esophagus occurred, the esophageal wall having already suffered because of the esophagitis. This led to the restoring of the gastric continuity using the gastric pull-up technique and a cervical anastomosis. The remaining esophagus was removed during the second procedure, 3 moths later. The immediate and the late evolution of the patient was excellent.

MicroRNA Dysregulation in Prostate Cancer.

Prostate cancer biology is complex, and needs to be deciphered. The latest evidence reveals the significant role of non-coding RNAs, particularly microRNAs (miRNAs), as key regulatory factors in cancer. Therefore, the identification of altered miRNA patterns involved in prostate cancer will allow them to be used for development of novel diagnostic and prognostic biomarkers. PATIENTS AND METHODS: We performed a miRNAs transcriptomic analysis, using microarray (10 matched pairs tumor tissue versus normal adjacent tissue, selected based on inclusion criteria), followed by overlapping with TCGA data. A total of 292 miRNAs were differentially expressed, with 125 upregulated and 167 downregulated in TCGA patients' cohort with PRAD (prostate adenocarcinoma), respectively for the microarray experiments; 16 upregulated and 44 downregulated miRNAs were found in our cohort. To confirm our results obtained for tumor tissue, we performed validation with qRT-PCR at the tissue and plasma level of two selected transcripts, and finally, we focused on the identification of altered miRNAs involved in key biological processes. RESULTS: A common signature identified a panel of 12 upregulated and 1 downregulated miRNA, targeting and interconnected in a network with the TP53, AGO2, BIRC5 gene and EGFR as a core element. Among this signature, the overexpressed transcripts (miR-20b-5p, miR-96-5p, miR-183-5p) and the downregulated miR-542-5p were validated by qRT-PCR in an additional patients' cohort of 34 matched tumor and normal adjacent paired samples. Further, we performed the validation of the expression level for miR-20b-5p, miR-96-5p, miR-183-5p plasma, on the same patients' cohort versus a healthy control group, confirming the overexpression of these transcripts in the PRAD group, demonstrating the liquid biopsy as a potential investigational tool in prostate cancer. CONCLUSION: In this pilot study, we provide evidence on miRNA dysregulation and its association with key functional components of the PRAD landscape, where an important role is acted by miR-20b-5p, miR-542-5p, or the oncogenic cluster miR-183-96-182.

Impact of COVID-19 prevention measures on Clostridioides difficile infections in a regional acute care hospital.

Clostridioides difficile (C. difficile) is a common cause of nosocomial diarrhea. The multi-modal infection control strategies designed to contain the COVID-19 pandemic have had an unintended positive effect on other hospital-acquired infections. The aim of the present study was to analyze the impact of the COVID-19 prevention measures on healthcare-associated C. difficile infections in a large regional acute care center. Electronic databases were reviewed from the start of the pandemic (March) up to November 2020. Average values from the same months from 2019 and 2018 were used as controls. Using the ICD-10 discharge coding, 65 C. difficile cases per 25,124 patients were identified in 2020 compared to 151/43,126 from the 2018 and 2019 averages (P=0.0484). The C. difficile cases were found to be decreased after the implementation of COVID-19 infection control strategies compared to previous years, despite an increase in antibiotic use. Subset analysis during lockdown showed a clear decrease but the difference was not statistically significant. For the months of recovery after lockdown, the number of cases was comparable to previous years.

PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer.

Prostate cancer represents the most encountered urinary malignancy in males over 50 years old, and the second most diagnosed after lung cancer globally. Digital rectal examination and prostatic specific antigen were the long-time standard tools for diagnosis but with a significant risk of overdiagnosis and overtreatment. Magnetic resonance imaging recently entered the diagnosis process, but to this date, there is no specific biomarker that accurately indicates whether to proceed with the prostate biopsy. Research in this area has gone towards this direction, and recently, serum, urine, imagistic, tissue biomarkers, and Risk Calculators promise to help better diagnose and stratify prostate cancer. In order to eliminate the comorbidities that appear along with the diagnosis and treatment of this disease, there is a constant need to implement new diagnostic strategies. Important uro-oncology associations recommend the use of novel biomarkers in the grey area of prostate cancer, to better distinguish the next step in the diagnostic process. Although it is not that simple, they should be integrated according to the clinical policies, and it should be considered that statistical significance does not always equal clinical significance. In this review, we analyzed the contribution of prostate-specific antigen (PSA)-based biomarkers (PHI, PHID, 4Kscore, STHLM3), imagistic techniques (mp-MRI and mp-US), and combined tests in the early diagnosis process of localized prostate cancer.

Spontaneous and Induced Animal Models for Cancer Research.

Considering the complexity of the current framework in oncology, the relevance of animal models in biomedical research is critical in light of the capacity to produce valuable data with clinical translation. The laboratory mouse is the most common animal model used in cancer research due to its high adaptation to different environments, genetic variability, and physiological similarities with humans. Beginning with spontaneous mutations arising in mice colonies that allow for pursuing studies of specific pathological conditions, this area of in vivo research has significantly evolved, now capable of generating humanized mice models encompassing the human immune system in biological correlation with human tumor xenografts. Moreover, the era of genetic engineering, especially of the hijacking CRISPR/Cas9 technique, offers powerful tools in designing and developing various mouse strains. Within this article, we will cover the principal mouse models used in oncology research, beginning with behavioral science of animals vs. humans, and continuing on with genetically engineered mice, microsurgical-induced cancer models, and avatar mouse models for personalized cancer therapy. Moreover, the area of spontaneous large animal models for cancer research will be briefly presented.

MiRNA-Based Inspired Approach in Diagnosis of Prostate Cancer.

Prostate cancer is one of the most encountered cancer diseases in men worldwide and in consequence it requires the improvement of therapeutic strategies. For the clinical diagnosis, the standard approach is represented by solid biopsy. From a surgical point of view, this technique represents an invasive procedure that may imply several postoperative complications. To overcome these impediments, many trends are focusing on developing liquid biopsy assays and on implementing them in clinical practice. Liquid samples (blood, urine) are rich in analytes, especially in transcriptomic information provided by genetic markers. Additionally, molecular characterization regarding microRNAs content reveals outstanding prospects in understanding cancer progression mechanisms. Moreover, these analytes have great potential for prostate cancer early detection, more accurate prostate cancer staging and also for decision making respecting therapy schemes. However, there are still questionable topics and more research is needed to standardize liquid biopsy-based techniques.

Oral lichen planus - case report.

This paper presents the case of a 58-year-old heavy smoker female who came to our clinic with acute pain, as well as mastication and feeding difficulties. The macroscopic examination revealed oral erosive lesions and ulcerations. The polymorphic aspect of the lesions required the differential diagnosis of oral erythroplakia or carcinoma, which were excluded by biopsy. At the same time, we assessed the expression of S100 protein, Ki67 and the cluster of differentiation (CD) 4, CD8 (T-cell) and CD20 (B-cell) immune cell markers by immunohistochemical analysis. As a result, after the clinical and pathological assessment, the diagnosis of oral lichen planus was established, and a therapy plan was conducted. We observed a favorable clinical evolution after the administration of corticosteroids and immunomodulatory agents.