Markers For Discrimination Research Articles

Analysis of alkyl-anthraquinone derivatives from hydrogen peroxide industrial process, using LC × LC-HRMS with shifting gradients.

The characterization of industrial working solutions containing numerous structurally related compounds and isomers requires the use of two-dimensional liquid chromatography coupled with high-resolution mass spectrometry (LC × LC-HRMS). The separation of alkyl-anthraquinone derivatives produced during hydrogen peroxide production was achieved by coupling a biphenyl and a C18 in the first and second dimensions, combined with the use of continuous shifting gradients in the second dimension (2D). The use of shifting gradients offers a significant advantage over regular gradients, with a 20% increase in occupancy and better separation of isomers eluted within the same modulation. Additionally, MS spectra were improved by reducing ion suppression in the source. The analysis of the industrial solutions produced a list of 226 peaks with 75 different molar masses, thereby confirming the presence of many isomers. The excellent repeatability of the retention times (within ±0.28 s in the second dimension) enabled the method to be used to study the differences between production batches, which were divided into two groups according to their measured hydrogen peroxide yield. Using multivariate statistical tools on the area of each peak, a total of 191 variables, including 11 clusters of insufficiently resolved isomers, were studied by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). A simple Wilcoxon test performed on the most pertinent variables was able to confirm that 28 peaks could be used to monitor the industrial process. This work highlighted the efficacy of combining a very powerful separation technique with the implementation of two simple statistical tests to rapidly identity a set of discriminant markers in a highly complex industrial mixture.

RACISM AGAINST INDIGENOUS PEOPLE AND AFRO-DESCENDANTS IN SWEDEN, BRAZIL, AND MEXICO

This article explores how racism and stigmatizing discourses and practices are articulated and normalized in colonizer and colonized countries. The research compares the cases of Sweden, Brazil, and Mexico from a combination of frameworks -- the Critical Race Theory (Walton, 2019; Ansley, 1997), the neo-Marxist concept of institutional racism and racialization (Cole, 2016 and 2020), and a decolonial framework and methodology (Fanon, 1968; Tynan and Bishop, 2022). Racism has been structural and systemic in Latin American societies since colonization when religious and royal authorities legitimated Indigenous and African slavery in the colonies. After independence, modern free republics converted religious legitimation of racism in pseudoscientific Eugenics and the invention of human races and racism continue oppressing Indigenous and African descendants. Currently structural racism continues to be the normal behavior in Western societies, not an exception. The objective of this research is to identify and compare racism reveled in behaviors and the speeches behind them in two colonized societies – Brazil and Mexico – and Sweden, a colonizing society. The question orienting the comparative research is how and in which ways racism and stigmatizing discourses and practices are articulated and normalized in colonizer and colonized countries. Understanding the main persistent trends in these societies on eugenic somatic characteristics such as hair type, body part sizes (e.g. head), as well as other collective social and religious symbols, behaviors, attitudes and cultural customs, used as discriminatory markers. The qualitative methodology includes 69 interviews and six focus groups in the three countries. Results were analyzed form a critical reflexivity about how colonialism and eugenics impact the lived experiences and realities of both groups in colonized and colonizer countries, through historic and current practices. racism has the same routes of functioning, structuring unequal relationships, distortions in the perception of the other, marginalization and suffering.

Chemical profiling and clustering of various dried cannabis flowers revealed by volatilomics and chemometric processing

Cannabis flower scent is one of the key characteristics of the cannabis plant. The diverse scents impact user experiences and offer medicinal benefits. These scents originate from volatile compounds, particularly terpenes and terpenoids. This study characterized the volatile profile of 19 different dried cannabis flowers using gas chromatography-mass spectrometry coupled with headspace-solid phase microextraction (HS-SPME-GC-MS). A total of 75 compounds were identified, including alcohols, aldehydes, benzenes, esters, ketone, monoterpenes, monoterpenoids, sesquiterpenes, and sesquiterpenoids. Cluster analysis was able to group the 19 cannabis cultivars into five clusters based on volatile chemotypes using chemometric techniques of hierarchical cluster analysis (HCA) and principal component analysis (PCA). Potential discriminant markers of each cultivar were then analyzed using a supervised partial least squares discriminant analysis (PLS-DA) verified through Variable Importance in Projection values (VIP), identifying twenty discriminant markers. In addition, the correlations among 75 volatile compounds were also obtained. The findings of this study provide a valuable database of single cannabis cultivars, useful for identifying individual strains and verifying their quality. Clustering the cultivars by volatile chemotype can be used for the classification of cannabis in the market. The results of this study are expected to be a starting point for further cannabis breeding programs to expand knowledge of this plant. Furthermore, the proposed method is applicable to other aroma plants in the future.

Mismatch negativity predicts age-related declines in memory precision

Does precision in auditory perception predict precision in subsequent memory (i.e., mnemonic discrimination) in aging? This study examined if the mismatch negativity (MMN), an electrophysiological marker of change detection and encoding, relates to age differences in mnemonic discrimination. The MMN was recorded in 92 adults (18–86 years, 47 females) in a passive oddball paradigm using tone sequences. Participants then completed a surprise recognition test for presented sequences (i.e., old targets) against novel sequences (i.e., similar lures and dissimilar foils). Across the adult lifespan, MMN amplitudes showed attenuation with increasing age, accompanied by worse performance discriminating targets from lures and foils. Across participants, smaller MMN amplitude predicted worse recognition performance. Notably, MMN amplitude partially explained age-related declines in target-lure discriminability, but not target-foil discriminability. Findings reinforce the MMN as a marker of mnemonic discrimination, and clarify how age-related declines in memory precision at retrieval may be explained by age differences at encoding.

Ultrasound Characteristics of Keratoacanthoma: Differentiation From Well-Differentiated Cutaneous Squamous Cell Carcinoma.

This study aims to describe the ultrasound characteristics of keratoacanthoma (KA), providing valuable insights for non-invasive diagnosis and differentiation from well-differentiated cutaneous squamous cell carcinoma (wcSCC). Ultrasound characteristics of 16 KA and 13 wcSCC conformed by surgical pathology were retrospective analyzed. KA patients were younger (mean age 63.13 years) compared with wcSCC patients (mean age 76.23 years). Ultrasound characteristics revealed that KA lesions were generally smaller, more frequently domed-shaped (87.50 vs 38.46%), exophytic (93.75 vs 30.77%), and well-defined (93.75 vs 53.85%) compared with wcSCC. Both lesion types predominantly showed hypoechoic internal echoes and inhomogeneous echotexture. The prevalence of hyperechoic superficial area was notably high in both groups (93.75 vs 84.62%), precluding the reliable use of this feature as a discriminatory marker between these two distinct neoplastic entities. KA lesions were mostly confined to the epidermis and superficial dermis (87.50%), while wcSCC cases frequently infiltrated into the subcutaneous fat layer (84.62%). Color Doppler imaging demonstrated higher vascularity in wcSCC lesions, with 61.5% showing Grade 3 flow, compared with KA lesions, where 62.5% exhibited Grade 2 flow. High-frequency ultrasound reveals distinct ultrasound characteristics differentiating KA from wcSCC, offering a promising non-invasive tool for preliminary diagnosis and treatment planning.

Comprehensive analysis identifies endocrine fibroblast growth factors as promising prognostic markers for colorectal carcinoma

Endocrine fibroblast growth factors (eFGFs) play essential roles in cellular signaling processes, including development and differentiation, and are implicated in various cancers. However, their precise involvement in colon neoplasia and colon adenocarcinoma (COAD) remains incompletely understood. Here, we conducted a comprehensive investigation utilizing multiple databases to explore the multifaceted characteristics of eFGFs. Through integrated analyses of diverse databases, including TIMER2.0, UALCAN, OncoDB, cBioPortal, LinkedOmics, STRING, htfTarget, mirTarBase, circBank, and DGIdb, we explored eFGFs’ gene expression, DNA methylation, prognostic significance, genetic alterations, gene regulatory networks, functional analysis, and drug interactions in COAD patients. Our findings revealed elevated expression levels of eFGFs in COAD, with aberrant gene expression potentially linked to promoter methylation. Importantly, hypermethylation of FGF21 and FGF23 and downregulation of FGF23 correlated with poor survival outcomes in COAD patients. Functional analyses highlighted the involvement of eFGF genes in Ras signaling, PI3K-Akt signaling, and cancer pathways. Furthermore, we validated our findings through a cross-sectional study by quantitative real-time polymerase chain reaction (qRT-PCR), confirming significant overexpression of FGF21 in colon polyps compared to normal mucosa. Additionally, we observed elevated RNA expression of FGF21 and FGF23 in adenomatous polyps compared to hyperplastic polyps. This study sheds new light on the critical roles of eFGFs in COAD tumorigenesis and underscores their potential as promising prognostic markers for COAD, as well as discriminative markers for distinguishing high-risk from low-risk polyps. These findings provide valuable insights into the complex molecular mechanisms underlying colorectal neoplasia and offer potential avenues for targeted therapeutic strategies.

The development of two fast genotyping assays for the differentiation of hemp from marijuana

AbstractThe legalization of hemp cultivation in the United States has raised the need for reliable methods to distinguish between legal hemp and illegal marijuana. Genetic analysis has emerged as a powerful tool, surpassing traditional chemical methods in specific aspects, such as analyzing trace amounts, aged samples, and different parts of the sample. Genetic differences in cannabinoid synthase genes offer promise for precise crop type determination, particularly focusing on genes like tetrahydrocannabinolic acid synthase (THCAS), cannabidiolic acid synthase (CBDAS), and cannabichromenic acid synthase (CBCAS). However, previous research faced several challenges in developing discriminatory genetic markers, including limited sample sizes, high similarity between the synthase genes, and the presence of pseudo synthase genes. A comprehensive study using Next‐Generation Sequencing (NGS) introduced a differentiation flowchart based on THCAS, CBDAS, and THCAS pseudogenes. To bridge the gap between NGS and the practical requirements of crime laboratories, two rapid genotyping assays were developed: a CE‐based SNaPshot™ assay and a TaqMan™ real‐time PCR assay. While the SNaPshot™ assay effectively differentiated various hemp and marijuana types, differentiation was limited with marijuana samples containing THC% close to the 0.3% legal threshold (0.3%–1%). The TaqMan™ qPCR SNP genotyping assay provided quicker results, making it an efficient choice for crime laboratories. However, this method had the same limitations as the SNaPshot™ assay with addtional challenges in differentiating edible hemp seed samples, and it did not provide additional CBD information. The study also highlighted the influence of two variants of one THCAS pseudogene on chemotype determination, emphasizing the necessity for precise genetic analysis for accurate categorization of cannabis varieties.

Clinical Utility and Diagnostic Accuracy of ROMA, RMI, ADNEX, HE4, and CA125 in the Prediction of Malignancy in Adnexal Masses.

We aimed to compare the clinical utility and diagnostic accuracy of the ADNEX model, ROMA score, RMI I, and RMI IV, as well as two serum markers (CA125 and HE4) in preoperative discrimination between benign and malignant adnexal masses (AMs). We conducted a retrospective study extracting all consecutive patients with AMs seen at our Institution between January 2015 and December 2020. Accuracy metrics included sensitivity (SE), specificity (SP), and area under the receiver operating characteristic curve (AUC), and their 95% confidence intervals (CI) were calculated for basic discrimination between AMs. Model performance was evaluated in terms of discrimination ability and clinical utility (net benefit, NB). A total of 581 women were included; 481 (82.8%) had a benign ovarian tumor and 100 (17.2%) had a malignant tumor. The SE and SP of CA125, HE4, ROMA score, RMI I, RMI IV, and ADNEX model were 0.60 (0.54-0.66) and 0.80 (0.76-0.83); 0.39 (0.30-0.49) and 0.96 (0.94-0.98); 0.59 (0.50-0.68) and 0.92 (0.88-0.95); 0.56 (0.46-0.65) and 0.98 (0.96-0.99); 0.54 (0.44-0.63) and 0.96 (0.94-0.98); 0.82 (0.73-0.88) and 0.91 (0.89-0.94), respectively. The overall AUC was 0.76 (0.74-0.79) for CA125, 0.81 (0.78-0.83) for HE4, 0.82 (0.80-0.85) for ROMA, 0.86 (0.84-0.88) for RMI I, 0.83 (0.81-0.86) for RMI IV, and 0.92 (0.90-0.94) for ADNEX. The NB for ADNEX was higher than other biomarkers and models across all decision thresholds between 5% and 50%. The ADNEX model showed a better discrimination ability and clinical utility when differentiating malignant from benign Ams, compared to CA125, HE4, ROMA score, RMI I, and RMI IV.

Left atrial strain demonstrates the ability to distinguish patients with pre and post-capillary pulmonary hypertension

Abstract Background The characterization of pulmonary hypertension (PH) patients into pre or postcapillary (pcPH)phenotypes poses a challenge during screening due to the ambiguity surrounding their comorbidities. This distinction is crucial as it influences treatment decisions and prognostication. Purpose Investigating Left Atrial Strain as a Discriminant Marker for Distinguishing Pre and Post-Capillary PH. Methods Out of 164 patients exhibiting both pre- and post-capillary phenotypes, 97 had optimal left atrial 2D strain. Left atrial 2D strain was performed with a GE Vivid9 ultrasound machine equipped with dedicated software, ensuring meticulous attention to image quality and region of interest thickness restricted to a maximum of 6 mm. Subsequently, the peak left atrial strain during reservoir function was quantified as part of the investigation. To determine the optimal cut-off value, ROC curve analysis was employed. Results 60 patients had pcPH while 37 had pre-capillary PH. Mean age was 65±12y. Mean pulmonary artery pressure, wedge pressure, cardiac output and pulmonary vascular resistance averaged 40,9±10,7 mm Hg, 15,7±8,7 mm Hg, 5,9±2,0 l/min and 4,7±3,1 WU, respectively. Left atrial 2D strain ranged from +2,5% to 60%, with a mean of +18,2±11,2%. From ROC cure analysis, patients with LA 2D strain > +19,1% had a precapillary phenotype with a sensitivity and a specifity of 93% and 88% respectively (Fig 1). Left atrial 2D strain demonstrates higher sensitivity compared to various parameters, such as scores from the European Society of Respiratory Disease, left ventricular end-diastolic pressure estimation from the American Society of Echocardiography, HFA-PEFF score, and H2FPEF from the AHA. Conclusion Left atrial 2D strain demonstrates superior sensitivity in distinguishing between patients with pre and post-capillary pulmonary hypertension compared to other assessment methods.FIG 1:Left atrial 2D strainFig 2:SENS of parameters and scores

CRAFTING A FOUCAULDIAN GENEALOGY METHOD FOR ANALYZING CURRICULUM-AS-DISCOURSE IN SOUTH AFRICA

Introduction/Frame: (Contextualization/Justification) Viewing curriculum as discourse can enable educators to identify how historical markers of discrimination are repeated. Historical markers are archaeologically embedded in the various dimensions of a curriculum and find expression in preferred ways of thinking, speaking, doing, and being. Such historical hypernorms are often maintained by practical rationalities, or technologies of power that reify their taken-for-granted legitimacy as ‘truth regimes’. Research Question/Objectives: This phase of the study aimed to critically explore and disclose how the (socio/politico-historically constructed) rules of knowledge-formation in a contemporary occupational therapy curriculum-as-discourse, are reproduced and maintained as truths at a university that historically supported apartheid in South Africa. Methodology: A Foucauldian Discourse Analysis (FDA) approach was used to systematically craft a genealogy analysis method from foundational Foucauldian theory. Adjacent, a lens of the ‘dimensions of the curriculum’ was employed: i.e., the formal, the informal, the hidden, and the negated curriculum. Various data sources were categorized accordingly, e.g., overarching policy documents; social events; timetables and prescribed texts; physical teaching spaces; espoused values, and underlying assumptions modelled during assessment in teaching and learning spaces. Results: Following the four rules of knowledge-formation that ensued from an archaeology analysis, the contemporary reification of the historical markers was problematised through various technologies of power and self, as well modes of reasoning. Examples are pervasive white demographics of both students and faculty reifying cognitive monopoly and mono-cultural epistemologies; the rationalization of highly ritualized (over)assessment of students suppressing adult-to-adult transactionalism in andragogy practices; the reproduction of mono-cultural epistemologies in clinical training operating in the hidden curriculum. Final considerations: Consciously dismantling the rationalising strategies for the continuation of discriminatory patterns of inclusion and exclusion in a curriculum, can open a space for critical dialogue, disruption, and reconfiguration of a curriculum-as-discourse towards social justice, and epistemic freedom in (higher) education.

Deciphering autism heterogeneity: a molecular stratification approach in four mouse models

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication, as well as restrained or stereotyped behaviors. The inherent heterogeneity within the autism spectrum poses challenges for developing effective pharmacological treatments targeting core features. Successful clinical trials require the identification of robust markers to enable patient stratification. In this study, we identified molecular markers within the oxytocin and immediate early gene families across five interconnected brain structures of the social circuit. We used wild-type and four heterogeneous mouse models, each exhibiting unique autism-like behaviors modeling the autism spectrum. While dysregulations in the oxytocin family were model-specific, immediate early genes displayed widespread alterations, reflecting global changes across the four models. Through integrative analysis, we identified Egr1, Foxp1, Homer1a, Oxt, and Oxtr as five robust and discriminant molecular markers that allowed the successful stratification of the four models. Importantly, our stratification demonstrated predictive values when challenged with a fifth mouse model or identifying subgroups of mice potentially responsive to oxytocin treatment. Beyond providing insights into oxytocin and immediate early gene mRNA dynamics, this proof-of-concept study represents a significant step toward the potential stratification of individuals with ASD. This work has implications for the success of clinical trials and the development of personalized medicine in autism.

The Prognostic Value of Interleukin 4 and Interleukin 6 in H-pylori Peptic Ulcer Disease

Abstract Background Helicobacter pylori is a Gram-negative bacteria that colonizes the gastrointestinal mucosa and causes chronic inflammation and leads to different diseases such as peptic ulcer, bile reflux, gastritis, autoimmunity, or allergic response etc. This also develops into gastric cancer. Aim of the Work The present study aims to evaluate the prognostic value of interleukin 4, interleukin 6 in hpylori infected patients before and after treatment Patients and Methods This cohort study was conducted in Ain Shams University Hospital inpatient ward and Gastroenterology outpatient clinic for 6 month between August 2023 to February 2024 in Ain Shams University Hospital. This study was performed on 45 Egyptian patients with peptic ulcer due to H-pylori. Results There was significant difference between before and after treatment as regards HB, WBCs, Albumin and CRP (P < 0.05). There was significant difference between before and after treatment as regards IL-6 and IL-4 (P < 0.05). There was significant positive correlation between IL-6, CRP and WBCs (p < 0.05). Also, there was significant positive correlation between IL-4, CRP and WBCs (p < 0.05). The diagnostic accuracy of IL-4 as a discriminatory marker between before and after treatment among H-pylori infected patients was assessed using ROC curve which revealed a sensitivity 91.7% and specificity of 66.7% at cutoff value >50.7 pg/ml, with an acceptable discriminative accuracy of 80%. While the diagnostic accuracy of IL-6 as a discriminatory marker between before and after treatment among H-pylori infected patients was assessed using ROC curve which revealed a sensitivity 98.11% and specificity of 90.1% at cutoff value >40.8 pg/ml, with an acceptable discriminative accuracy of 87%. Conclusion In this study we concluded that there is an increased production of IL-6 and IL-4 among H- pylori infected patients that may be an important mediator of the inflammatory response. Serum IL-6 and IL- 4 is significantly lower after treatment of H. Pylori infected patients. Still, we caution that studies with larger groups of patients and properly matched control groups, are needed to confirm these findings.

Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies

BackgroundPhenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney function decline. Here, we measured urinary (u)DKK3 levels in 195 pediatric renal ciliopathy patients to assess its potential as a discriminative and prediction marker. MethodsUDKK3 concentration was measured in 357 spot urine samples from 247 individuals including 52 healthy age-matched controls. Disease entities comprised nephronophthisis (NPH) (n=37), autosomal recessive polycystic kidney disease (ARPKD) (n=61), Bardet Biedl syndrome (BBS) (n=57) and hepatocyte nuclear factor 1 beta (HNF1B)-nephropathy (n=40). Results were correlated with chronic kidney disease (CKD) stage and annual estimated glomerular filtration rate (eGFR) decline. ResultsMedian uDKK3/creatinine ratios in all disease entities were significantly higher compared with healthy controls (11pg/mg uDKK3/crea, p<0.001): NPH 1.219pg/mg, HNF1B 731pg/mg, BBS 541pg/mg and ARPKD 437pg/mg. A significant correlation of CKD stage with uDKK3 levels was observed for all disease entities (p<0.0001) with no other clinical parameter having a relevant impact. In our cohort, uDKK3 values >4.700 pg/mg were associated with a significantly greater annual eGFR loss independently of diagnosis and eGFR (p=0.0029). While we observed a trend towards lower uDKK3 levels in glomerulopathies compared to renal ciliopathies, there was no discriminative difference between individual ciliopathy entities (p=0.2637). ConclusionIn renal ciliopathies uDKK3 is a marker to assess disease severity and estimate short-term kidney function decline.

Optimization of serum samples derivatization process by I-Optimal Split-plot design of experiments for GC–MS metabolomics of inflammatory neuropathies

The derivatization process is critical in gas chromatography coupled to mass spectrometry-based untargeted metabolomics. This process aims to increase common non-volatile compounds’ vapor pressure and thermal stability by two sequential steps: methoximation and silylation. Up to now, there are no standardized conditions for performing these reactions. In this study, we simultaneously optimized these procedures using an I-Optimal Split-plot design in serum samples of healthy individuals. The resultant two-factor interaction model performed well with R2 > 0.90 and R2-adjusted > 0.70 in the statistical analysis. The results revealed interactions between methoximation and silylation conditions. The optimized conditions were applied for the GC–MS untargeted metabolomics analysis of serum samples of patients with inflammatory neuropathies and healthy controls. The orthogonal partial least square discriminant analysis with satisfactory cross-validation results (R2 = 0.744, Q2 = 0.557) determined 32 metabolites with VIP score > 1. Short- and long-chain organic acids, fatty acids, and carbohydrates were annotated as potential discriminative molecular markers.

Predictive Analysis of Breast Cancer from Full-Field Digital Mammography Images using Residual Network

Breast cancer has been a significant contributor to cancer-related mortality, but advancements in early detection through regular mammography and improvements in treatment modalities have contributed to declining mortality rates in several regions. This study presents a novel approach to cancer diagnosis utilizing Full-Field Digital Mammography images through predictive analysis methods. By using predictive analytic techniques and mammography images, this study offers a novel way to cancer detection. The research involves the application of deep learning techniques to extract valuable insights from cancer images captured by mammography devices. The CBIS-DDSM (Curated Breast Imaging Subset of Digital Database for Screening Mammography) dataset including images from patients with varying types and stages of cancer, is collected and pre-processed to ensure uniformity and quality. Relevant features, including color, texture, and shape characteristics, are extracted, and a rigorous feature selection process is employed to identify discriminative markers. The Residual Network (ResNet) model is selected and trained on the dataset, with a focus on classification accuracy and robust predictive performance. Validation metrics, such as accuracy, IoU (Intersection over Union) score, dice score, and ROC (Receiver Operating Characteristic) curve are employed to evaluate the model’s efficiency. After analysis, the proposed method had the best degree of mass lesion detection accuracy, at 99.24%. This research contributes to the advancement of non-invasive and efficient diagnostic tools, potentially enhancing early detection and intervention in cancer patients. The proposed method not only demonstrates promising results in terms of diagnostic accuracy but also emphasizes interpretability, seamless integration into clinical workflows, and adherence to ethical standards.

Genetics of 21-OH Deficiency and Genotype-Phenotype Correlation: Experience of the Hellenic National Referral Center.

21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to CYP21A2 gene pathogenic variants. Τhe aim of this study was the identification of CYP21A2 variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by using the existing hormonal assessment and genotypes of the 500 subjects tested, to identify a biomarker that could differentiate between the heterozygotes and the cases with no pathogenic variants identified. Five hundred subjects with clinical suspicion of 21-OHD underwent CYP21A2 gene sequencing and Multiplex Ligation Dependent Probe Amplification (MLPA). Genetic diagnosis was achieved in 27.4% of the subjects tested, most of which presented with the non-classic form (NC) of 21-OHD. Heterozygotes accounted for 42.6% of cases, whereas no pathogenic variants were identified in 27% of cases. De novo aberrations, duplications, and five novel variants were also identified. Statistical analysis revealed that the difference between the basal and 60' post-ACTH stimulation 17-hydroxyprogesterone concentrations (Δ17-OHP60-0) could be a potential biomarker (p < 0.05) distinguishing the heterozygotes from the cases with no pathogenic variants identified, although no clear cut-off value could be set. Further analysis revealed overlapping clinical manifestations among all the subjects tested. The presented phenotypic traits of the subjects tested and the inability to identify a discriminative biochemical marker highlight the importance of comprehensive CYP21A2 genotyping to ascertain the correct genetic diagnosis and proper genetic counselling.

A comprehensive in silico analysis and experimental validation of miRNAs capable of discriminating between lung adenocarcinoma and squamous cell carcinoma.

Accurate differentiation between lung adenocarcinoma (AC) and lung squamous cell carcinoma (SCC) is crucial owing to their distinct therapeutic approaches. MicroRNAs (miRNAs) exhibit variable expression across subtypes, making them promising biomarkers for discrimination. This study aimed to identify miRNAs with robust discriminatory potential between AC and SCC and elucidate their clinical significance. MiRNA expression profiles for AC and SCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and supervised machine learning methods (Support Vector Machine, Decision trees and Naïve Bayes) were employed. Clinical significance was assessed through receiver operating characteristic (ROC) curve analysis, survival analysis, and correlation with clinicopathological features. Validation was conducted using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, signaling pathway and gene ontology enrichment analyses were conducted to unveil biological functions. Five miRNAs (miR-205-3p, miR-205-5p, miR-944, miR-375 and miR-326) emerged as potential discriminative markers. The combination of miR-944 and miR-326 yielded an impressive area under the curve of 0.985. RT-qPCR validation confirmed their biomarker potential. miR-326 and miR-375 were identified as prognostic factors in AC, while miR-326 and miR-944 correlated significantly with survival outcomes in SCC. Additionally, exploration of signaling pathways implicated their involvement in key pathways including PI3K-Akt, MAPK, FoxO, and Ras. This study enhances our understanding of miRNAs as discriminative markers between AC and SCC, shedding light on their role as prognostic indicators and their association with clinicopathological characteristics. Moreover, it highlights their potential involvement in signaling pathways crucial in non-small cell lung cancer pathogenesis.

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma.

It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

Behind the Protein Battle Lines in the 1970s: Nutritional Turmoil in the Postwar World.

This study examines the development of international debates about the perception of nutrients, particularly protein, with a focus on the "Protein Debate" of the late 20th century. The nutritional obsession with protein has been ongoing since the early 19th century, when scientific nutrition was established, and has been at the center of debates surrounding food, agriculture, healthcare, and the environment, changing in shape and form over time. In addition to being a nutrient necessary for optimal physical and mental performance, protein has been a marker of poverty and discrimination at the international level and explains differences in individual living standards. Kwashiorkor, also known as protein calorie disorder, medicalized the problem of poverty in the Third World or underdeveloped countries. By the 1970s, the nutritional discussion of protein had undergone a radical transformation, with implications for the entire development discourse, including poverty and human rights. This study of the historical discourse on protein deficiency goes beyond the scientific focus on nutritional status, food, and dietary health to identify the social, economic, and cultural implications of nutrition.

Characterization and discrimination of donkey milk lipids and volatiles across lactation stages

The lipid and flavor in milk are key factors that affect its quality, which profiles during donkey lactation are not yet clear. In this study, the lipids and volatile compounds (VOCs) in donkey milk from stages of lactation were analyzed by using LC-MS and GC-IMS. A total of 1774 lipids were identified in donkey milk, spanning over 6 major categories and attributed to 30 subclasses. The 233 differentially expressed lipids were identified between donkey colostrum and mature milk, which participate in 20 metabolic pathways, including glycerophospholipid, linoleic acid, and sphingolipid. Additionally, 35 VOCs in donkey milk were identified, including 28.57% aldehydes, 28.57% ketones, 25.71% esters, and 8.57% alcohols. Of these VOCs, 15 were determined to be characteristic flavors in donkey milk, mainly including methyl 2-methylbutanoate, 2-pentanone, and butyl acetate. 11 significantly different VOCs were found between the groups. Acetone, 2-heptanone, and ethyl acetate-m were considered potential discriminatory markers.