Cut-off Criteria Research Articles

Validation of a urine- based proteomics test to predict clinically significant prostate cancer: complementing mpMRI pathway.

INTRODUCTIONː Prostate cancer (PCa) is the most frequently diagnosed cancer among men. A major clinical need is to accurately predict clinically significant PCa (csPCa). A proteomics-based 19-biomarker model (19-BM) was previously developed using capillary electrophoresis-mass spectrometry (CE-MS) and validated in 1000 patients at risk for PCa. This study aimed to validate 19-BM in a multicenter prospective cohort of 101 biopsy-naive patients using current diagnostic pathways. METHODSː Urine samples from 101 patients with PCa were analyzed using CE-MS. All patients underwent MRI using a 3-T system. The 19-BM score was estimated using support vector machine-based software (MosaCluster v1.7.0), employing a previously established cut-off criterion of -0.07. Previously developed diagnostic nomograms were calculated along with MRI. RESULTSː Independent validation of 19-BM yielded a sensitivity of 77% and a specificity of 85% (AUC:0.81). This performance surpassed those of PSA (AUC:0.56) and PSA density (AUC:0.69). For PI-RADS≤ 3 patients, 19-BM showed a sensitivity of 86% and a specificity of 88%. Integrating 19-BM with MRI resulted in significantly better accuracy (AUC:0.90) compared to individual investigations alone (AUC19BM=0.81; p=0.004 and AUCMRI:0.79; p=0.001). Examining the decision curve analysis, 19-BM with MRI surpassed other approaches for the prevailing risk interval from a 30% cut-off. CONCLUSIONSː 19-BM exhibited favorable reproducibility for the prediction of csPCa. In patients with PI-RADS≤3, 19-BM correctly classified 88% of the patients with insignificant PCa at the cost of one missed csPCa patient. Utilizing the 19-BM test could prove valuable in complementing MRI and reducing the need for unnecessary biopsies.

Population-pharmacokinetic/pharmacodynamic model of atractylodes lancea (Thunb.) DC. administration in patients with advanced-stage intrahepatic cholangiocarcinoma: a dosage prediction

BackgroundA recent phase 2A clinical study of Atractylodes lancea (Thunb.) DC. (AL) in patients with advanced-stage intrahepatic cholangiocarcinoma (iCCA) demonstrated significant reduction of the risk of tumor progression and mortality with a dose ranging from 1,000 to 2,000 mg. The present study aimed to determine the potential dosage regimen of AL for further phase 2B clinical study.MethodsPlasma-concentration time profiles of total AL bioactivity and clinical efficacy in patients with advanced-stage iCCA were obtained from Phase 2 A study. The population pharmacokinetic (pop-PK) model was developed. The pop-PK model and Monte-Carlo (MC) simulation, in conjunction with maximum concentration of AL (Cmax) as a cut-off criterion, was performed and validated with clinical data. The optimal model was used to simulate further dosage regimens and clinical efficacy of AL.ResultsThe pop-PK properties of total AL bioactivity were best described by a compartmental model with zero-order absorption (without delay) and linear clearance. None of the investigated covariates improved model accuracy.The developed pop-PK with MC simulations following once-daily dosing of 1,000 mg and 2,000 mg adequately predicted the clinical efficacy (tumor progression and mortality). The once-daily dose of 2,500 mg is recommended for further phase 2B clinical study due to its relatively high efficacy on tumor progression inhibition (73%) and mortality rate reduction (71%) without excessive number of the administered capsules (23 capsules) and low risk of toxicities (<5%).ConclusionsThe applied pop-PK model with MC simulation, along with the appropriate cut-off pharmacokinetic parameters, can be used as a potential tool for supporting dosage prediction and selection for clinical studies, and thus reducing the rate of drug development failures.Trial registrationwww.thaiclinicaltrials.org, WHO ICTRP search, TCTR20210129007, Registed 29 January 2021.

The Stability of Linguistic Skills of Arabic-Speaking Children Between Kindergarten and First Grade.

This study aimed to evaluate the stability of phonological awareness (PA) and language achievements between kindergarten and first grade among Arabic-speaking children. A total of 1,158 children were assessed in PA and language skills in both grades and were classified based on distinct and integrated achievements on PA and language following percentiles' cutoff criteria. The classification of distinct achievements constituted high, intermediate, low, and very low achievement-based groups for each domain. The classification of the integrated achievements on both domains constituted four groups: intermediate-high PA and language, very low PA, very low language, and doubly low (very low PA and language). Descriptive statistics and McNemar's tests were used to examine the stability of these groups. The analyses showed a significant improvement in achievements on most tasks. The distinct classification for PA and language indicated that many more kindergarteners in the extreme distribution with high and very low achievement levels maintained this profile in first grade compared to those with intermediate achievements. For PA, 55.7% of kindergarteners with high, 30% with intermediate, 30.4% with low, and 45.5% with very low achievements maintained their achievements in first grade. For language, 52.5% of kindergarteners with high, 34.5% with intermediate, 38.8% with low, and 59.8% with very low achievements maintained their language achievements. The integrated classification indicated a higher achievement stability rate for kindergarteners with intermediate-high PA and language (91.3%) and for doubly low achievers (84.7%) compared to very low PA (24.1%) or very low language (31.8%) achievers. The study indicated a higher variability in the distribution of the intermediate achievements compared to the high and very low achievements, which were more stable across grade. The results emphasize the need for dynamic linguistic assessments and early intervention for children with very low achievements in PA and language who show a poor prognosis.

Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis.

Breast cancer (BC) is the most prevalent cancer among women globally. Metastasis is the leading cause of mortality in most cancers. Early BC detection before metastasis can enhance survival rates. Understanding BC metastasis mechanisms could aid in developing metastasis-specific treatments. The role of long non-coding RNAs (lncRNA) in cancer progression is recognized, yet the importance of specific lncRNAs in BC, despite potential alterations, remains inadequately explored. We utilized bioinformatics tools to identify novel lncRNAs dysregulated in metastasis. To achieve this objective, the gene expression profile of GSE102484, encompassing metastatic and non-metastatic BC tissue samples, was analyzed using the limma package in R with cut-off criteria set at an adjusted p-value < 0.005 and |fold change (FC)| ≥ 0.5. We used WGCNA analysis to find co-expression genes for lncRNAs. Then, we identified hub genes and performed pathway enrichment to better understand the results. Considering the defined criteria, eight novels of dysregulated lncRNAs and top 10 miRNAs were identified. Dysregulated lncRNAs are found in yellow, green, brown, purple, and turquoise co-expression modules from WGCNA analysis. Enrichment analysis of these co-expressed modules revealed relevant pathways to metastasis, such as epithelial-to-mesenchymal transition and integrin cell-surface interactions, as well as regulation of HIF1-alpha. In addition, SDPR, TGFB1I1, ILF3, KIF4A, and COL5A1 were identified as hub genes. Based on DElncRNA-miRNADEmRNA connections and co-expression, we ultimately constructed lncRNA-associated ceRNA axes. The current study may identify novel lncRNAs implicated in BC metastasis; still, additional research is required to determine the potential functions of these lncRNAs in BC metastasis.

Unravelling key genes associated with ovine Brucellosis by differential gene expression analysis: A holistic bioinformatics study

Ovine Brucellosis, caused by Brucella ovis bacteria, is a pathognomonic reproductive infectious disease of sheep that causes epididymitis in rams (male sheep) and placental inflammation in ewes (female sheep) leading to reduced fertility. The specific molecular process that causes alterations in genome of sheep during brucellosis is not yet fully understood. This study aimed to identify key host genes associated with the pathogenesis of ovine brucellosis caused by B. ovis. The GSE35614 dataset containing six healthy and six Brucella ovis infected sample of rams in the chronic phase 2 was obtained from the NCBI GEO database to examine and detect any differences in gene expression (DEGs). Functional and pathway enrichment analyse of the DEGs were performed along with the construction of protein-protein interaction network. Next, functional modules and hub genes were clustered and identified respectively, using the MCODE plugin. As a result, a total of 316 differentially expresses genes were filtered according to the provided cut-off criteria. The enriched DEGs were related to extracellular matrix interaction, cell adhesion mediated by integrin, angiogenesis, and inflammatory response. Furthermore, the hub gene analysis resulted in five hub genes namely, FN1, FBN1, CDH1, CD44, and SPP1, were up-regulated during the infection which could lead to reproductive disorders in sheep. In conclusion, the DEGs, functional and pathways terms, along with hub genes identified in the current study can provide prospective targets for the early diagnosis and treatment of brucellosis and provide insight into the molecular mechanism underlying the alterations that occur during brucellosis in sheep.

Thioclava arctica sp. nov. and Zhongshania arctica sp. nov., isolated from the surface sediment of the Arctic Ocean and reclassification of Marortus luteolus Yu et al. 2019 as a later heterotypic synonym of Zhongshania marina On et al. 2019.

Two Gram-stain-negative bacterial strains, 15-R06ZXC-3T and R06B22T, were isolated from the surface sediment of the Arctic Ocean. Phylogenetic analyses based on the 16S rRNA gene and genome sequences indicated that strain 15-R06ZXC-3T belongs to the genus Thioclava, while strain R06B22T belongs to the genus Zhongshania. Strain 15-R06ZXC-3T showed the closest relationship to Thioclava indica DT23-4T. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain 15-R06ZXC-3T and all of the type strains of the genus Thioclava ranged from 20.8 to 30.4% and 79.1 to 85.7%, respectively. Strain R06B22T was most closely related to Zhongshania marina DSW25-10T. The dDDH and ANI values between strain R06B22T and all of the type strains of the genus Zhongshania ranged from 18.6 to 20.4% and 77.5 to 79.4%, respectively. These dDDH and ANI values were all below the standard cutoff criteria for the delineation of bacterial species, indicating that the two strains may represent novel species within their respective genera. Furthermore, their phenotypic and chemotaxonomic characteristics also differentiated them from closely related species. Based on the polyphasic analyses, strains 15-R06ZXC-3T and R06B22T separately represent novel species of the genera Thioclava and Zhongshania, for which the names Thioclava arctica sp. nov. (type strain 15-R06ZXC-3T = MCCC 1A07434T= KCTC 8342T) and Zhongshania arctica sp. nov. (type strain R06B22T = MCCC 1A08273T= KCTC 8343T) are proposed. Additionally, phylogenomic analyses showed that the strain Marortus luteolus ZX-21T was clustered with the strain Z. marina DSW25-10T and all other type strains of the genus Zhongshania. Furthermore, the ANI and dDDH values between strains ZX-21T and DSW25-10T were 97.6% and 78.8±2.5%, respectively, strongly indicating that they represented a single species. Therefore, it is proposed that M. luteolus Yu et al. 2019 be recognized as a later heterotypic synonym of Z. marina On et al. 2019.

Psychometric Properties of the Serbian Version of the Arm, Shoulder, and Hand Disability Self-Assessment Questionnaire: Criterion Validity, Construct Validity, and Internal Consistency.

Background/Objectives: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a widely employed self-report tool for assessing upper extremity function. The aim of this study was to assess the psychometric properties of the Serbian version of the DASH by determining its criterion and construct validity, as well as internal consistency. Methods: This cross-sectional study was conducted among patients with hand and wrist disabilities at the Institute for Orthopedics "Banjica", Serbia. The psychometric properties of the Serbian version of the DASH were analyzed through an examination of its factorial structure and internal consistency. The DASH consists of 30 items, 24 of which assess function, 21 of which focus on physical function and three on social/role function. The remaining six items evaluate symptoms related to pain, tingling/numbness, weakness, and stiffness. Results: A total of 297 patients were included in the study. The mean age was 47.4 ± 16.8 years, with 50.5% males. Three models were assessed to determine the reliability and validity of the questionnaire across different domains. Model 1 examined a single-factor structure. In Model 2, the items were divided into two domains: Physical Function and Psychosocial/Symptoms. In Model 3, items were subdivided into three domains: Physical Function, Symptoms, and Psychosocial. All models demonstrated an excellent internal consistency with a Cronbach's alpha > 0.9 for most domains. The values for the fit indices Tucker-Lewis index (TLI) and Comparative-Fit Index (CFI) were above their cut-off criteria of 0.9, while the Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square Residual (SRMR) were below the suggested value of 0.06, indicating an excellent level of models fit. Standardized factor loadings were statistically significant (p < 0.05). Conclusions: The present study provided the evidence for the appropriate metric properties of the Serbian version of the DASH. Results support both the unidimensional and multidimensional structures of the DASH.

A-062 Determination Neonatal 17-Hydroxyprogesterone Cutoff Levels for Congenital Adrenal Hyperplasia in Korea: 3 years' experience

Abstract Background Newborn screening for congenital adrenal hyperplasia (CAH) is a crucial practice with significant global adoption. While it offers substantial benefits, it also presents challenges due to high false positive rates, which can lead to mental strain for families and unnecessary hospital visits. Our research delved into the impact of birth weight (BW), gestational age (GA), and GA combined with sampling time on 17-hydroxyprogesterone (17-OHP) concentration. Specifically, we aimed to establish appropriate 17-OHP cutoff values for preterm, low birth weight weight (LBW), and sick newborns. Methods A total of 2,429 newborns born between October 2020 and January 2024 were screened for CAH. Samples were collected from neonates on a filter paper with a heel prick method. The 17-OHP concentration was measured by AutoDELFIA Neonatal 17-hydroxyprogesterone kit (PerkinElmer, Turku, Finland). This assay is a solid phase, time-resolved fluoroimmunoassay based on the competitive reaction between europium labeled 17-OHP and sample 17-OHP for a limited amount of binding sites on 17-OHP specific polyclonal antibodies. The 99.5 percentile was applied to the cutoff of 17-OHP for CAH. Results 17-OHP concentrations in newborns with lower BW and GA were significantly higher than those in normal BW and term newborns. 17-OHP concentration showed a statistically significant negative correlation with BW (r = -0.512, p &amp;lt; 0.001) and GA (r = -0.578, p &amp;lt; 0.001). Not only the full-term subgroup, but also preterm subgroups had a same tendency of 17-OHP concentration decrease with increasing sampling time. Application of newly establishing 99.5 percentile cutoff criteria significantly reduced recall rates to 1.02%, 0.81%, and 1.45% according to each criterion of BW, GA, and GA with sampling time, respectively. Conclusions This research introduces novel 17-OHP cutoff values for preterm, low birth weight (LBW), and sick newborns in the context of congenital adrenal hyperplasia (CAH). We analyzed the distribution of these cutoff values, considering factors such as birth weight, gestational age, and the timing of sample collection. Notably, applying the newly established cutoff criteria led to a significant reduction in false positive rates. Our laboratory’s data can serve as a valuable reference for other institutions aiming to set appropriate cutoffs, thereby minimizing unnecessary follow-up tests and enhancing the efficiency of CAH screening. As we continue to accumulate additional data, further reserch in this field remains promising.

The association between hunger-coping economic tradeoffs and food insecurity among female recipients of charitable food assistance

Food insecurity is an indicator of well-being in the United States. A high proportion of recipients of charitable food assistance (CFA) are women and are often in charge of specific household managerial responsibilities (e.g., childcare, transportation). Consequently, they frequently face choices between paying for food and paying for other basic need(s). This study aims to examine which hunger-coping economic tradeoffs place females with at least one dependent child in the house and females without a dependent child in the house at risk for experiencing food insecurity. Data was collected at 10 Houston-area and 10-Atlanta-area food pantries in 2022 (N=883). Using USDA cutoff criteria, households were considered food insecure based on ≥3 affirmative responses to the 18-item Food Security Scale Module. Hunger-coping economic tradeoff experiences were based on affirmative responses to whether anyone in the household ever had to choose between food and six basic needs (i.e. childcare, medicine/medical care, utilities, rent/mortgage, transportation, education). Covariate-adjusted logistic regression models were conducted to understand the relationship between six hunger-coping economic tradeoffs and food insecurity for the entire analytic sample and stratified by whether the female participant had a child in house. Standard errors in all regression models were corrected to account for multiple observations within a pantry. Adults, on average, were 55 years old (58% food insecure; 47% Hispanic; 42% black). Four hunger-coping economic tradeoffs were related to experiencing food insecurity. Economic tradeoffs between food and a) medicine/medical care and b) transportation elevated the likelihood of food insecurity, regardless of child status. Tradeoffs between food and childcare increased the risk for experiencing food insecurity among females with a dependent child. Deciding to pay between food and utilities was related to food insecurity experiences among females without a dependent child. Increases in Supplemental Nutrition Assistance Program (SNAP) benefits and eligibility along with programs to enhance resources related to medical care, transportation, childcare and utilities could help reduce food insecurity, especially among CFA recipients.

Mploying Virial Coefficients for Optimal Solutions in Variational Calculations

In this study, virial coefficients for one and two-electron hydrogen and helium-like quantum dot structures confined in an infinite potential well were calculated. The virial coefficients were determined based on the dot radius using the Quantum Genetic Algorithm (QGA) method. Calculations were performed using Fernandez's expression; however, due to calculation errors in confined systems, this equivalent expression was found unsuitable as a direct stopping criterion. Instead, virial coefficients were calculated using the ⟨T⟩/⟨V⟩ relationship, and the results were plotted. The fitting function obtained for the virial coefficients is proposed as an effective cutoff criterion for electronic structure calculations of quantum dot systems.

Airspaces-derived exosomes contain disease-relevant protein signatures in a mouse model of cystic fibrosis (CF)-like mucoinflammatory lung disease.

Exosomes, membrane-bound extracellular vesicles, ranging from approximately 30-200nm in diameter, are released by almost all cell types and play critical roles in intercellular communication. In response to the prevailing stress, the exosome-bound protein signatures vary in abundance and composition. To identify the bronchoalveolar lavage fluid (BALF) exosome-bound proteins associated with mucoinflammatory lung disease and to gain insights into their functional implications, we compared BALF exosomes-derived proteins from adult Scnn1b transgenic (Scnn1b-Tg+) and wild type (WT) mice. A total of 3,144 and 3,119 proteins were identified in BALF exosomes from Scnn1b-Tg+ and WT mice, respectively. Using cutoff criteria (Log2 fold-change > 1 and adjusted p-value < 0.05), the comparison of identified proteins revealed 127 and 30 proteins that were significantly upregulated and downregulated, respectively, in Scnn1b-Tg+ versus WT mice. In addition, 52 and 27 proteins were exclusively enriched in Scnn1b-Tg+ and WT mice, respectively. The identified exosome-bound proteins from the homeostatic airspaces of WT mice were mostly relevant to the normal physiological processes. The protein signatures enriched in the BALF exosomes of Scnn1b-Tg+ mice were relevant to macrophage activation and mucoinflammatory processes. Ingenuity pathway analyses revealed that the enriched proteins in Scnn1b-Tg+ mice contributed to the inflammatory responses and antimicrobial defense pathways. Selective proteins including, RETNLA/FIZZ1, LGALS3/Galectin-3, S100A8/MRP8, and CHIL3/YM1 were immunolocalized to specific cell types. The comparative analysis between enriched BALF exosome proteins and previously identified differentially upregulated genes in Scnn1b-Tg+ versus WT mice suggested that the compartment-/cell-specific upregulation in gene expression dictates the enrichment of their respective proteins in the lung airspaces. Taken together, this study demonstrates that the BALF exosome-bound protein signatures reflect disease-relevant disturbances. Our findings suggest that the exosomes carry disease-relevant protein signatures that can be used as a diagnostic as well as predictive biomarkers for mucoinflammatory lung disease.

Taking Complete Finite Prefixes To High Level, Symbolically*

Unfoldings are a well known partial-order semantics of P/T Petri nets that can be applied to various model checking or verification problems. For high-level Petri nets, the so-called symbolic unfolding generalizes this notion. A complete finite prefix of a P/T Petri net’s unfolding contains all information to verify, e.g., reachability of markings. We unite these two concepts and define complete finite prefixes of the symbolic unfolding of high-level Petri nets. For a class of safe high-level Petri nets, we generalize the well-known algorithm by Esparza et al. for constructing small such prefixes. We evaluate this extended algorithm through a prototype implementation on four novel benchmark families. Additionally, we identify a more general class of nets with infinitely many reachable markings, for which an approach with an adapted cut-off criterion extends the complete prefix methodology, in the sense that the original algorithm cannot be applied to the P/T net represented by a high-level net.

Clinical Predictors of Mood Disorders and Prevalence of Neuropsychiatric Symptoms in Patients with Systemic Lupus Erythematosus.

Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery-Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders.

Classification of hallux valgus deformity-is there a standard?

Hallux valgus deformity severity is one determent for the surgical procedure for hallux valgus (HV) correction. HV deformities are usually classified into mild/moderate/severe. The aim was to investigate the cut-off criteria used to classify HV deformity. The study was based on a previous living systematic review. Four common databases were searched for the last decade. All review-steps were conducted by two reviewers. Data assessed were the individual cut-off values used to classify HV deformity into mild/moderate/severe, and the referenced classification systems. 46 studies were included. 21/18 studies grade deformity based on the intermetatarsal angle (IMA)/ hallux valgus angle (HVA) with great heterogeneity throughout the different cut-off values. The most referenced classification systems were the Coughlin and Mann's and the Robinson classification. The currently used classification systems are heterogenic, and no standard could be defined. The community should define a uniform classification system. Level I, systematic review of randomized controlled trials and prospective comparative studies.

Clinician-Prioritized Measures to Use in a Remote Concussion Assessment: Delphi Study.

There is little guidance available, and no uniform assessment battery is used in either in-person or remote evaluations of people who are experiencing persistent physical symptoms post concussion. Selecting the most appropriate measures for both in-person and remote physical assessments is challenging because of the lack of expert consensus and guidance. This study used expert consensus processes to identify clinical measures currently used to assess 5 physical domains affected by concussion (neurological examination, cervical spine, vestibular, oculomotor, or effort) and determine the feasibility of applying the identified measures virtually. The Delphi approach was used. In the first round, experienced clinicians were surveyed regarding using measures in concussion assessment. In the second round, clinicians reviewed information regarding the psychometric properties of all measures identified in the first round by at least 15% (9/58) of participants. In the second round, experts rank-ordered the measures from most relevant to least relevant based on their clinical experience and documented psychometric properties. A working group of 4 expert clinicians then determined the feasibility of virtually administering the final set of measures. In total, 59 clinicians completed survey round 1 listing all measures they used to assess the physical domains affected by a concussion. The frequency counts of the 146 different measures identified were determined. Further, 33 clinicians completed the second-round survey and rank-ordered 22 measures that met the 15% cutoff criterion retained from round 1. Measures ranked first were coordination, range of motion, vestibular ocular motor screening, and smooth pursuits. These measures were feasible to administer virtually by the working group members; however, modifications for remote administration were recommended, such as adjusting the measurement method. Clinicians ranked assessment of coordination (finger-to-nose test and rapid alternating movement test), cervical spine range of motion, vestibular ocular motor screening, and smooth pursuits as the most relevant measures under their respective domains. Based on expert opinion, these clinical measures are considered feasible to administer for concussion physical examinations in the remote context, with modifications; however, the psychometric properties have yet to be explored. RR2-10.2196/40446.

Analysis of Human Papillomavirus-Associated Cervical Cancer Differentially Expressed Genes and Identification of Prognostic Factors using Integrated Bioinformatics Approaches.

Human papillomavirus (HPV)-induced cervical cancer progresses through a series of steps. Despite our limited understanding of the mechanisms driving this progression, identifying the key genes involved could significantly improve early detection and treatment. Two gene expression profiles of GSE9750 and GSE6791, which included cervical cancer HPV-positive and -negative samples, were evaluated using the R limma package with established cut-off criteria of P value < 0.05 and | fold change| ≥ 1. KEGG pathway enrichment was performed to identify potential pathways. Weighted gene co-expression network analysis (WGCNA) was used to discover co-expressed gene modules and trait-module connections. Considering the defined criteria, 115 differentially expressed genes (DEGs) were identified. The DEG's KEGG pathway enrichment analysis revealed enrichment in highly relevant pathways to the HPV infection, including cell cycle, viral carcinogenesis, autophagy-animal, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and microRNAs in cancer. WGCNA results in 13 co-expression modules, and the magenta module is identified with significant relations to HPV, cervical cancer stage, and metastasis traits. The survival analysis identified BEX1 and CDC45 as potential prognostic factors in HPV-associated cervical cancer. The innovation of our work lies in identifying essential genes associated with the multi-step process of cervical carcinogenesis. In fact, the current study has the potential to give a distinct viewpoint on the molecular pathways linked to cervical cancer. Considering the potential importance of the hub genes, we recommend conducting in-depth wet lab research to determine their impact on the biological mechanisms of cervical cancer.

P052 OPTIMAL ADRENAL VEIN SAMPLING LATERALIZATION CRITERIA FOR DIAGNOSIS OF UNILATERAL PRIMARY ALDOSTERONISM USING ALDOSTERONE CONCENTRATION MEASURED BY LC-MS/MS POST-ACTH STIMULATION

Background: Primary aldosteronism (PA) is characterized by excessive, autonomous secretion of aldosterone from one or both adrenal glands. Identification of unilateral disease and surgical resection can lead to cure, and is dependent on accurate criteria for lateralization of excess aldosterone during adrenal vein (AV) sampling (AVS). Current evidence for AVS lateralization cut-offs using plasma aldosterone concentration (PAC) measured by LC-MS/MS and post-surgical outcomes is limited. Aim: To determine optimal cut-off criteria to define lateralization of PA on AVS based on PAC measured by LC-MS/MS post-ACTH stimulation and post-surgical outcomes data. Methods: This study involved 60 subjects with PA who had PAC measured by LC-MS/MS post ACTH-stimulation during bilaterally-cannulated AVS, underwent unilateral adrenalectomy between July 2015-July 2021 and were followed up for ≥6 months. AVS lateralization parameters (lateralization index [LI; dominant PAC/cortisol(AV) ÷ non-dominant PAC/cortisol(AV)], contralateral suppression index [CSI; non-dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)], lateralization ratio [LR; dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)] and post-surgical outcome data were examined. Complete biochemical remission (CR) of PA post-surgery was defined using PASO International Consensus Criteria. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for LI, CSI and LR based on cases who achieved CR of PA post-surgery (n=55) vs those who did not (n=5). Results: Optimal cut-off LI during ACTH-stimulated AVS to identify unilateral PA cases who achieved CR post-surgery was 5.1 (AUC=0.92, P&lt;0.001; 92.7% sensitivity, 80.0% specificity) while the optimal cut-off for CSI was 0.6 (AUC=0.887, P&lt;0.001; 82.1% sensitivity, 100.0% specificity), and for LR was 3.3 (AUC=0.695, P=0.202; 80.0% sensitivity, 80.0% specificity). Cases with LR of 2.0-3.3 also achieved CR post-surgery if it was associated with CSI &lt;0.6. Conclusion: LI of &gt;5.1 provides high sensitivity and CSI &lt;0.6 high specificity for identification of surgically curable unilateral PA during ACTH-stimulated AVS when PAC is analyzed by LC-MS/MS.

The diagnostic potential of urine in paediatric patients undergoing initial treatment for tuberculous meningitis

Tuberculous meningitis (TBM)—the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture—an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified—1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol—which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Prioritising Appointments by Telephone Interview: Duration from Symptom Onset to Appointment Request Predicts Likelihood of Inflammatory Rheumatic Disease.

Background: This study aims to determine the rate of inflammatory rheumatic diseases (IRDs) in a cohort of initial referrals and the efficacy of prioritising appointments to the early arthritis clinic (EAC) based on symptom duration. Methods: In the present study, we used algorithm-based telephone triage to assign routine care appointments according to the time between symptom onset and request for an appointment (cut-off criterion: 6 months). This retrospective, monocentric analysis evaluated the effectiveness of our triage in identifying patients with IRDs as a function of the assigned appointment category (elective, EAC, or emergency appointment). Results: A total of 1407 patients were included in the study (34.7% male; 65.3% female). Of the 1407 patients evaluated, 361 (25.7%) presented with IRD. There were significant differences in the frequency of inflammatory diagnoses between appointment categories (p < 0.001): elective 13.8%, EAC 32.9%, and emergency 45.9%. The sample without the emergency category included a total of 1222 patients. The classification into "inflammatory" or "non-inflammatory" in this subsample was as follows: Sensitivity was 37.7%, and specificity was 92.6%. The positive predictive value (PPV) was 59.8%, and the negative predictive value (NPV) was 83.6%. Overall, 80.2% of patients were correctly assigned using the appointment category and C-reactive protein (CRP). Conclusions: The algorithm-based triage system presented here, which focuses on the time between symptom onset and request for an appointment, allows for the prioritisation of appointments in favour of patients with IRDs and thus earlier initiation of therapy.

Yet anOther Dose Algorithm (YODA) for independent computations of dose and dose changes due to anatomical changes

Objective. To assess the viability of a physics-based, deterministic and adjoint-capable algorithm for performing treatment planning system independent dose calculations and for computing dosimetric differences caused by anatomical changes. Approach. A semi-numerical approach is employed to solve two partial differential equations for the proton phase-space density which determines the deposited dose. Lateral hetereogeneities are accounted for by an optimized (Gaussian) beam splitting scheme. Adjoint theory is applied to approximate the change in the deposited dose caused by a new underlying patient anatomy. Main results. The dose engine’s accuracy was benchmarked through three-dimensional gamma index comparisons against Monte Carlo simulations done in TOPAS. For a lung test case, the worst passing rate with (1 mm, 1%, 10% dose cut-off) criteria is 94.55%. The effect of delivering treatment plans on repeat CTs was also tested. For non-robustly optimized plans the adjoint component was accurate to 5.7% while for a robustly optimized plan it was accurate to 4.8%. Significance. Yet anOther Dose Algorithm is capable of accurate dose computations in both single and multi spot irradiations when compared to TOPAS. Moreover, it is able to compute dosimetric differences due to anatomical changes with small to moderate errors thereby facilitating its use for patient-specific quality assurance in online adaptive proton therapy.