Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Simple Summary In prostate cancer, overdiagnosis and overtreatment is a common problem for clinicians. Accurate diagnosis and prognosis are essential to avoid unnecessary biopsy and to increases the effectiveness of treatment. A new, easy-to-use and non-invasive test based on liquid biopsy biomarkers such as Progensa PCA3, MyProstateScore, ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed to improve diagnosis, prognosis and to help guide the decision-making process. This article provides an overview of the above-mentioned commercial tests. The performance and financial aspects of the tests have been compared using available studies. Then the application of biomarker tests as an adjunct to multiparametric MRI in the diagnosis, prognosis and monitoring of prostate cancer has been discussed. Abstract Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.
Dysregulation of miRNA in Leukemia: Exploiting miRNA Expression Profiles as Biomarkers

Micro RNAs (miRNAs) are a class of small non-coding RNAs that have a crucial role in cellular processes such as differentiation, proliferation, migration, and apoptosis. miRNAs may act as oncogenes or tumor suppressors; therefore, they prevent or promote tumorigenesis, and abnormal expression has been reported in many malignancies. The role of miRNA in leukemia pathogenesis is still emerging, but several studies have suggested using miRNA expression profiles as biomarkers for diagnosis, prognosis, and response to therapy in leukemia. In this review, the role of miRNAs most frequently involved in leukemia pathogenesis is discussed, focusing on the class of circulating miRNAs, consisting of cell-free RNA molecules detected in several body fluids. Circulating miRNAs could represent new potential non-invasive diagnostic and prognostic biomarkers of leukemia that are easy to isolate and characterize. The dysregulation of some miRNAs involved in both myeloid and lymphoid leukemia, such as miR-155, miR-29, let-7, and miR-15a/miR-16-1 clusters is discussed, showing their possible employment as therapeutic targets.
In Vitro Assessment of Long-Term Fluoride Ion Release from Nanofluorapatite

The issue concerning the tooth decay is ongoing, therefore the study of materials with potential use in its prevention is crucial. This study aimed to analyze the long-term release of fluoride from synthesized nanofluorapatite in various in vitro environments for its potential use in dental materials. We placed 100 mg samples in 0.9% NaCl or deionized water and incubated them at 37 °C or 22 °C for 12 weeks. F− levels were read at 1, 3, 24, 48, 72, and 96 h, and thereafter weekly. The levels of F− released at specific time intervals, as well as their cumulative values were compared. In a solution of 0.9% NaCl at 22 °C, there were no significant differences in the amount of F− released in the assessed time intervals, while at 37 °C, the highest value was read after 24 h (0.0697 ppm + 0.0006; p < 0.05). In deionized water, the highest amount of F− at 22 °C was read after 4 weeks (0.0776 ppm + 0.0028; p < 0.05), and at 37 °C, it was also the highest after 4 weeks (0.0910 ppm + 0.0156; p < 0.05). Under the same conditions, after 5 weeks the cumulative level of F− released (0.6216 ppm + 0.0085) significantly increased (p < 0.05), when compared to the samples placed in 0.9% NaCl at 37 °C and 22 °C (0.5493 ppm + 0.0321 and 0.5376 ppm + 0.0234, respectively). FAp releases F− for a long period of time in all assessed environments, therefore it is advised to continue testing in vivo models. Due to the probable remineralization effect towards hard tooth tissues, fluorapatite can be used in the prevention and treatment of dental caries and dentin hypersensitivity.
Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review

Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients.
Validation and Inter-rater Reliability of the Modified Videofluoroscopic Dysphagia Scale (mVDS) in Dysphagic Patients with Multiple Etiologies

Background: the Videofluoroscopic Dysphagia Scale (VDS) is used to interpret and predict the long-term prognosis of patients with dysphagia. However, the inter-rater agreement of the VDS was shown to be lower in a previous study. To overcome the mentioned limitation of the VDS, a modified version (mVDS) was created and applied clinically. We aimed to validate its usefulness in determining the appropriate feeding method and predicting the prognosis of dysphagia. Methods: the videofluroscopic swallowing study (VFSS) data of 50 patients with dysphagia were collected retrospectively. The VFSS data were evaluated using the mVDS, and the inter-rater reliability was calculated. We also evaluated the association between the mVDS and type of feeding method selected, and between the mVDS and presence of aspiration pneumonia in patients with dysphagia. Results: among the different parameters of mVDS, “aspiration” showed the highest reliability (k = 0.767), followed by “mastication” and “lip closure” (k = 0.648 and k = 0.634, respectively). Conversely, “triggering pharyngeal swallow” and “pyriformis residue” demonstrated the lowest reliabilities (k = 0.312 and k = 0.324, respectively). The intraclass correlation coefficient (ICC), which is used as a measure of the reliability of the total mVDS score, was 0.876. In all patients with dysphagia, the mVDS score correlated significantly with the type of feeding method selected (p < 0.05), and the presence of aspiration pneumonia (p < 0.05). Conclusion: the ICC of the total mVDS score was 0.876. Therefore, the mVDS could be a useful tool for quantifying the severity of dysphagia. It could be helpful in the analysis of the VFSS findings among patients with dysphagia in clinical settings and research.
Comparison of the Effect of Cardiac Rehabilitation on Functional Capacity of Diabetic and Nondiabetic Patients after CABG

Background: After a coronary artery bypass graft (CABG), diabetic patients deal with various hemodynamic disorders. This study aimed to compare the effect of cardiac rehabilitation (CR) on the functional capacity of diabetic and nondiabetic patients following CABG. Methods: This descriptive-analytical study was performed on 40 diabetic and nondiabetic patients attending a similar CR program following CABG. The subjects were selected by convenience sampling and were divided into two diabetes and nondiabetes groups. All patients attended 24 exercise sessions held 3 days a week. The functional capacity of patients was measured and recorded with the metabolic equivalent of Task criterion before and after the CR program. In addition, data analysis was performed in SPSS version 19. Results: In this study, the mean age of the diabetic and nondiabetic patients was 54.45 ± 5.82 and 56.85 ± 5.36 years, respectively. There was no significant difference between the research groups regarding the systolic and diastolic blood pressure (P > 0.05). The mean functional capacity in the diabetes and nondiabetes groups was 4.5 ± 0.79 and 5.2 ± 1.7 before the rehabilitation, respectively. However, the results of Mann–Whitney U-test were indicative of a lack of a significant difference in this respect (P > 0.05). After the CR program, the mean functional capacity in the diabetes and nondiabetes groups was 5.7 ± 1.31 and 6.3 ± 1.7, respectively, demonstrating an insignificant difference in this regard (P > 0.05). Conclusions: According to the results of the study, there was no significant difference between the diabetic and nondiabetic patients, who underwent CABG, after a CR program. However, replication of the study is warranted.
Probing the peripheral immune response in mouse models of oxaliplatin-induced peripheral neuropathy highlights their limited translatability

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of various chemotherapeutic agents, including oxaliplatin. It is highly prevalent amongst cancer patients, causing sensory abnormalities and pain. Unfortunately, as the underlying mechanisms remain poorly understood, effective therapeutics are lacking. Neuro-immune interactions have been highlighted as potential contributors to the development and maintenance of CIPN, however, whether this is the case in oxaliplatin-induced peripheral neuropathy (OIPN) is yet to be fully established. Methods: In this study we used flow cytometry to examine the peripheral immune response of male C57BL/6 mice following both single and repeated oxaliplatin administration. In animals exposed to repeated dosing, we also undertook mechanical and thermal behavioural assays to investigate how oxaliplatin alters phenotype, and conducted RT-qPCR experiments on bone marrow derived macrophages in order to further inspect the effects of oxaliplatin on immune cells. Results: In contrast to other reports, we failed to observe substantial changes in overall leukocyte, lymphocyte or myeloid cell numbers in dorsal root ganglia, sciatic nerves or inguinal lymph nodes. We did however note subtle, tissue-dependant alterations in several myeloid subpopulations following repeated dosing. These included a significant reduction in MHCII antigen presenting cells in the sciatic nerve and an increase in infiltrating cell types into the inguinal lymph nodes. Though repeated oxaliplatin administration had a systemic effect, we were unable to detect a pain-like behavioural phenotype in response to either cold or mechanical stimuli. Consequently, we cannot comment on whether the observed myeloid changes are associated with OIPN. Conclusions: Our discussion puts these results into the wider context of the field, advocating for greater transparency in reporting, alignment in experimental design and the introduction of more clinically relevant models. Only through joint concerted effort can we hope to increase our understanding of the underlying mechanisms of CIPN, including any immune contributions.
Estimating the Acute Health Impacts of Fire‐Originated PM2.5 Exposure During the 2017 California Wildfires: Sensitivity to Choices of Inputs

Exposure to wildfire smoke increases the risk of respiratory and cardiovascular hospital admissions. Health impact assessments, used to inform decision‐making processes, characterize the health impacts of environmental exposures by combining preexisting epidemiological concentration–response functions (CRFs) with estimates of exposure. These two key inputs influence the magnitude and uncertainty of the health impacts estimated, but for wildfire‐related impact assessments the extent of their impact is largely unknown. We first estimated the number of respiratory, cardiovascular, and asthma hospital admissions attributable to fire‐originated PM2.5 exposure in central California during the October 2017 wildfires, using Monte Carlo simulations to quantify uncertainty with respect to the exposure and epidemiological inputs. We next conducted sensitivity analyses, comparing four estimates of fire‐originated PM2.5 and two CRFs, wildfire and nonwildfire specific, to understand their impact on the estimation of excess admissions and sources of uncertainty. We estimate the fires accounted for an excess 240 (95% CI: 114, 404) respiratory, 68 (95% CI: −10, 159) cardiovascular, and 45 (95% CI: 18, 81) asthma hospital admissions, with 56% of admissions occurring in the Bay Area. Although differences between impact assessment methods are not statistically significant, the admissions estimates' magnitude is particularly sensitive to the CRF specified while the uncertainty is most sensitive to estimates of fire‐originated PM2.5. Not accounting for the exposure surface's uncertainty leads to an underestimation of the uncertainty of the health impacts estimated. Employing context‐specific CRFs and using accurate exposure estimates that combine multiple data sets generates more certain estimates of the acute health impacts of wildfires.
Formulae derived from Anthropometric Measurements to Estimate Ideal Tibial Nail Length

ABSTRACT Introduction: Ideal Nail Length (INL) provides better outcomes after Intramedullary Nailing (IMN) of Tibia Shaft Fractures (TSF). Intraoperative methods do not allow for preoperative planning. Changing the nail may cause complications. X-rays are commonly used, but displacement or magnification errors may occur. Forearm measurements may be benefical in bilateral TSF. We aim to examine correlations of anthropometric measurements (AMs) and INL and use them to obtain formulae. Materials and methods: Tuberositas Tibia-Medial Malleolus (TM), Tuberositas Tibia-Ankle joint (TA), knee-ankle joint (JJ), and olecranon tip-5th Metacarpal head (OM) distances were evaluated in 76 IMN patients. Correlation analyses were performed and the results used to create formulae. Results: The correlations between INL and TM-left, TM-right, TA-left, TA-right, OM-left, OM-right, JJ-left, JJ-right were 0.81, 0.83, 0.77, 0.77, 0.82, 0.80, 0.90, 0.91 respectively for males; and 0.93, 0.89, 0.88, 0.86, 0.80, 0.82, 0.90, 0.89 respectively for females. AMs show excellent correlation in both sexes (p<0.0001). Regression analysis was statistically significant in all formulae. The most compatible correlations in males were JJ-right and JJ-left; and in females, TM-left, TM-right, and JJ-right. Conclusion: The most compatible correlations wth INL were JJ in males, and TM and JJ in females. OM can be used in the presence of bilateral TSF, edema, wounds and obesity. AMs are useful preoperatively. The formulae can be used to ensure INL and reduce errors, time and radiation. Level of Evidence: Level I, Testing of previously developed diagnostic criteria on consecutive patients (with the universally applied reference gold standard).
Differential Regulation of Lacto-/Neolacto- Glycosphingolipid Biosynthesis Pathway Reveals Transcription Factors as Potential Candidates in Triple-Negative Breast Cancer

Simple Summary Triple-negative breast cancer (TNBC) tends to occur in younger women, is aggressive and has a poor outcome due to limited therapies. Recent drug trials have shown promise, but only improved TNBC survival by several months. To discover potential new therapeutic targets and pathways, we focused on the known alteration of glycosylation in cancer, and sought to discover TNBC-specific glycogenes and their regulatory pathways. Using an integrative bioinformatics approach, we discovered 34 TNBC-specific candidate glycogenes, and identified the lacto-/neolacto- glycosphingolipid biosynthesis pathway with seven candidate glycogenes as a novel target in TNBC. Furthermore, we identified three transcription factors as potential therapeutic targets: AR, GATA3 and ZNF622. Each TF target three glycogenes in this pathway. Together, this study revealed novel molecular features of TNBC, identifying potential new therapeutic targets. Abstract Triple-negative breast cancer (TNBC) is an aggressive breast cancer with limited treatment options. Glycosylation has been implicated in cancer development, but TNBC-specific glycosylation pathways have not been examined. Here, we applied bioinformatic analyses on public datasets to discover TNBC-specific glycogenes and pathways, as well as their upstream regulatory mechanisms. Unsupervised clustering of 345 glycogene expressions in breast cancer datasets revealed a relative homogenous expression pattern in basal-like TNBC subtype. Differential expression analyses of the 345 glycogenes between basal-like TNBC (hereafter termed TNBC) and other BC subtypes, or normal controls, revealed 84 differential glycogenes in TNBC. Pathway enrichment showed two common TNBC-enriched pathways across all three datasets, cell cycle and lacto-/neolacto- glycosphingolipid (GSL) biosynthesis, while a total of four glycosylation-related pathways were significantly enriched in TNBC. We applied a selection criterion of the top 50% differential anabolic/catabolic glycogenes in the enriched pathways to define 34 TNBC-specific glycogenes. The lacto-/neolacto- GSL biosynthesis pathway was the most highly enriched, with seven glycogenes all up-regulated in TNBC. This data led us to investigate the hypothesis that a common upstream mechanism in TNBC up-regulates the lacto-/neolacto-GSL biosynthesis pathway. Using public multi-omic datasets, we excluded the involvement of copy-number alteration and DNA methylation, but identified three transcription factors (AR, GATA3 and ZNG622) that each target three candidate genes in the lacto-/neolacto- GSL biosynthesis pathway. Interestingly, a subset of TNBC has been reported to express AR and GATA3, and AR antagonists are being trialed for TNBC. Our findings suggest that AR and GATA3 may contribute to TNBC via GSL regulation, and provide a list of candidate glycogenes for further investigation.
Gibberellin Oxidase Gene Family in L. chinense: Genome-Wide Identification and Gene Expression Analysis

GAox is a key enzyme for the transformation of gibberellins, and belongs to the 2-ketoglutarate dependent dioxygenase gene family (2ODD). However, a systematic analysis of GAox in the angiosperm L. chinense has not yet been reported. Here, we identified all LcGAox gene family members in L. chinense, which were classified into the three subgroups of GA20ox, C19GA2ox, and C20GA2ox. Comparison of the gene structure, conserve motifs, phylogenetic relationships, and syntenic relationships of gibberellin oxidase gene families in different species indicated that the gene functional differences may be due to the partial deletion of their domains during evolution. Furthermore, evidence for purifying selection was detected between orthologous GAox genes in rice, grape, Arabidopsis, and L. chinense. Analysis of the codon usage patterns showed that mutation pressure and natural selection might have induced codon usage bias in angiosperms; however, the LcGAox genes in mosses, lycophytes, and ambarella plants exhibited no obvious codon usage preference. These results suggested that the gibberellin oxidase genes were more primitive. The gene expression pattern was analyzed in different organs subjected to multiple abiotic stresses, including GA, abscisic acid (ABA), and chlormequat (CCC) treatment, by RNA-seq and qRT-PCR, and the stress- and phytohormone-responsive cis-elements were counted. The results showed that the synthesis and decomposition of GA were regulated by different LcGAox genes in the vegetative and reproductive organs of L. chinense, and only LcGA2ox1,4, and 7 responded to the NaCl, polyethylene glycol, 4 °C, GA, ABA, and CCC treatment in the roots, stems, and leaves of seedlings at different time periods, revealing the potential role of LcGAox in stress resistance.
The Ability of Metabolomics to Discriminate Non-Small-Cell Lung Cancer Subtypes Depends on the Stage of the Disease and the Type of Material Studied

Simple Summary The most commonly diagnosed lung cancer is non-small-cell lung cancer (NSCLC). In contrast, the most frequent subtypes of NSCLC, accounting for 80% of cases, are ADC and SCC. Nevertheless, subtype identification is based on the diagnosis of characteristic gene mutations occurring in each subtype. The aim of the study was the metabolomics analysis of the early stage of NSCLC and the determination of new biochemical pathways differentiating the subtypes. Our studies demonstrated that there are new potential significant changes in the biochemical pathways involved in N-acylethanolamine (NAE) biosynthesis that distinguish early-stage SCC from ADC. Moreover, the analysis of the plasma of patients with COPD and NSCLC allows the exclusion of metabolites related to inflammation in the lungs and the identification of compounds characteristic of cancer. Our research indicates new pathways that have not been explored in NSCLC so far, which may have diagnostic, prognostic, and therapeutic potential. Abstract Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.