Insights into Metabolites Profiling and Pharmacological Investigation of Aconitum heterophyllum wall ex. Royle Stem through Experimental and Bioinformatics Techniques.

The Aconitum genus is a leading source of a wide range of structurally diverse metabolites with significant pharmacological implications. The present study investigated metabolite profiling, pharmacological investigation, anticancer potential, and molecular docking analysis of the stem part of Aconitum heterophyllum (AHS). The metabolite profiling of the AHS extract was experimentally examined using LC-MS/MS-orbitrap in both modes (ESI+/ESI-) and GC-MS in EI mode. The in vitro MTT model was used to study the anticancer potential, while the in vivo animal model was used to study the anti-inflammatory and antinociceptive activities. The MOE software was used for the molecular docking study. A total of 118 novel and previously known metabolites, among 44 metabolites (26 in ESI+ positive mode and 18 in ESI- negative mode) in the MeOH extract, while 74 metabolites (46 in ESI+ and 28 in ESI- mode) were identified in the n-hexane extract via LCMS/MS. The identified metabolites include 24 phenolic compounds, 18 alkaloids, 10 flavonoids, 24 terpenoids, 2 coumarins, 2 lignans, and 38 other fatty acids and organic compounds. The major bioactive metabolites identified were hordenine, hernagine, formononetin, chrysin, N-methylhernagine, guineesine, shogaol, kauralexin, colneleate, zerumbone, medicarpin, boldine, miraxinthin-v, and lariciresinol-4-O-glucoside. Furthermore, the GC-MS study helped in the identification of volatile and nonvolatile chemical constituents based on the mass spectrum and retention indices. The methanol extract significantly inhibited tumor progression in H9c2 and MDCK cancer cells with IC50 values of 186.39 and 199.63 µg/mL. In comparison, the positive control aconitine exhibited potent IC50 values (132.32 and 141.58 µg/mL) against H9c2 and MDCK cell lines. The anti-inflammatory (carrageenan-induced hind paw edema) and antinociceptive (acetic acid-induced writhing) effects were significantly dose-dependent, (p < 0.001) and (p < 0.05), respectively. In addition, a molecular docking study was conducted on identified ligands against the anti-inflammatory enzyme (COX-2) (PDB ID: 5JVZ) and the cancer enzyme ADAM10 (PDB ID: 6BDZ) which confirmed the anti-inflammatory and anticancer effects in an in silico model. Among all ligands, L2, L3, and L7 exhibit the most potent potential for inhibiting COX-2 inflammation with binding energies of -7.3424, -7.0427, and -8.3562 kcal/mol. Conversely, against ADAM10 cancer protein, ligands L1, L4, L6, and L7, with binding energies of -8.0650, -7.7276, -7.0454, and -7.2080 kcal/mol, demonstrated notable effectiveness. Overall, the identified metabolites revealed in this AHS research study hold promise for discovering novel possibilities in the disciplines of chemotaxonomy and pharmacology.

Clinical practice recommendations for management of Diabetes Mellitus in Arab region: An expert consensus statement from Arab Diabetes Forum (ADF).

Prevalence of diabetes in Arab region has significantly increased, resulting in a significant economic burden on healthcare systems. This surge can be attributed to obesity, rapid urbanization, changing dietary habits, and sedentary lifestyles. The Arab Diabetes Forum (ADF) has established localized recommendations to tackle the region's rising diabetes prevalence. The recommendations, which incorporate worldwide best practices, seek to enhance the quality of treatment for people with diabetes by raising knowledge and adherence among healthcare providers. The guidelines include comprehensive recommendations for screening, diagnosing, and treating type 1 and type 2 diabetes in children and adults for better overall health results.

Identification of plant based potential antifungal compounds against BMK-1 protein of Bipolaris oryzae using molecular docking approach.

Rice brown spot is an important disease of rice worldwide that inflicts substantial yield losses. The antimicrobial potential of methanol, acetone and dimethyl sulfoxide (DMSO) extracts of different medicinal plants, viz., Syzygium aromaticum, Saussurea costus, Acorus calamus, Bergenia ciliate, Geranium pratense, Mentha longifolia, Inula racemosa, Podophyllum hexandrum, Heracleum candicans and Picrorhiza kurroa, against the brown spot pathogen Bipolaris oryzae in vitro was evaluated via mycelial growth inhibition and spore germination inhibition assays. Among the plant extracts tested, 100% mycelial inhibition was observed for the methanol extract of Syzygium aromaticum at all three concentrations (2000 ppm, 3000 ppm and 4000 ppm), followed by the methanol extract of Inula racemosa (90.33%) at 4000 ppm. A maximum conidial germination inhibition of 83.54% was exhibited by the Heracleum candicans leaf extract. Phytochemical profiling of Syzygium aromaticum and Inula racemosa through liquid chromatography and mass spectrometry (HR-LCMS) revealed the presence of several compounds, such as eugenol, ursolic acid, quercetin, chlorogenic acid, and noscapine. A molecular docking approach was used to identify key inhibitory molecules against B. oryzae. Among the compounds detected in S. aromaticum and Inula racemosa, ursolic acid and noscapine were found to have the greatest binding affinity for the Big Mitogen Activated Protein Kinase (BMK-1) enzyme present in B. oryzae. In conclusion, S. aromaticum and Inula racemosa are potent compounds that could serve as lead compounds for drug discovery in the future.

Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells.

BACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu. METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors. RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2. CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.

BrMYB116 transcription factor enhances Cd stress tolerance by activating FIT3 in yeast and Chinese cabbage.

Cd (cadmium) is a highly toxic heavy metal pollutant often present in soil and detrimentally impacting the production and quality of horticultural crops. Cd affects various physiological and biochemical processes in plants, including chlorophyll synthesis, photosynthesis, mineral uptake and accumulation, and hormonal imbalance, leading to cell death. The MYB family of transcription factors plays a significant role in plant response to environmental influences. However, the role of MYB116 in abiotic stress tolerance remains unclear. In this study, we reported that Chinese cabbage transcription factor BrMYB116 enhanced Cd stress tolerance in yeast. The expression level of BrMYB116 was increased by Cd stress in Chinese cabbage. Additionally, yeast cells overexpressing BrMYB116 showed improved Cd stress tolerance and reduced Cd accumulation. Moreover, we found that BrMYB116 interacted with facilitator of iron transport (FIT3) to enhance Cd stress tolerance. ChIP-qPCR results showed that ScFIT3 was activated through specific binding to its promoter. Additionally, the overexpression of ScFIT3 induced Cd stress tolerance and reduced Cd accumulation in yeast and Chinese cabbage. These results suggest new avenues for plant genomic modification to mitigate Cd toxicity and enhance the safety of vegetable production.

Frameworks for procurement, integration, monitoring, and evaluation of artificial intelligence tools in clinical settings: A systematic review.

Research on the applications of artificial intelligence (AI) tools in medicine has increased exponentially over the last few years but its implementation in clinical practice has not seen a commensurate increase with a lack of consensus on implementing and maintaining such tools. This systematic review aims to summarize frameworks focusing on procuring, implementing, monitoring, and evaluating AI tools in clinical practice. A comprehensive literature search, following PRSIMA guidelines was performed on MEDLINE, Wiley Cochrane, Scopus, and EBSCO databases, to identify and include articles recommending practices, frameworks or guidelines for AI procurement, integration, monitoring, and evaluation. From the included articles, data regarding study aim, use of a framework, rationale of the framework, details regarding AI implementation involving procurement, integration, monitoring, and evaluation were extracted. The extracted details were then mapped on to the Donabedian Plan, Do, Study, Act cycle domains. The search yielded 17,537 unique articles, out of which 47 were evaluated for inclusion based on their full texts and 25 articles were included in the review. Common themes extracted included transparency, feasibility of operation within existing workflows, integrating into existing workflows, validation of the tool using predefined performance indicators and improving the algorithm and/or adjusting the tool to improve performance. Among the four domains (Plan, Do, Study, Act) the most common domain was Plan (84%, n = 21), followed by Study (60%, n = 15), Do (52%, n = 13), & Act (24%, n = 6). Among 172 authors, only 1 (0.6%) was from a low-income country (LIC) and 2 (1.2%) were from lower-middle-income countries (LMICs). Healthcare professionals cite the implementation of AI tools within clinical settings as challenging owing to low levels of evidence focusing on integration in the Do and Act domains. The current healthcare AI landscape calls for increased data sharing and knowledge translation to facilitate common goals and reap maximum clinical benefit.

A Systemic Review and Meta-analysis of Laparoscopic Surgery Versus Open Surgery for Gallbladder Cancer.

Introduction: Laparoscopy in gallbladder cancer (GBC) has a possible role in staging, radical cure, and palliation in gallbladder cancer. However, a few studies have advocated the use of laparoscopic approach and concluded the safety of this approach. This present study was undertaken to determine the safety and feasibility between open and laparoscopic cholecystectomy in patients with the non-metastatic GBC. Materials and Methods: A systematic database search was performed in MEDLINE, Embase, and Google Scholar for relevant articles. As a result, a list of such studies, clinical trials, published in English up to May 2021, was obtained,14 studies were included and statistical analysis was conducted using RevMan software 5.3 (The Nordic Cochrane Centre). Results: The 5-year survival rate was reported in 13 out of 14 studies (1388 patients), and all compared laparoscopic and open approach. There was no significant heterogeneity in between the studies (chi-square, 10.66; df, 12; I2, 0%). There was significant higher overall survival in open group (389/850 vs 194/538 or 1.45, 95% CI (1.12-1.88), P value, 0.005). There was no significant difference in recurrence rate, operative time, blood loss, lymph node yield, and postoperative complication in between open and laparoscopic groups. Conclusions: Our present study demonstrates that overall survival is significantly increased with open approach when compared with laparoscopic approach. There is no difference in recurrence rate, operative time, blood loss, lymph node yield, and postoperative complications between the open and laparoscopic cholecystectomy groups.

New reports of pathogen spectrum associated with bulb rot and their interactions during the development of rot in tulip.

Bulb rot, a highly damaging disease of tulip plants, has hindered their profitable cultivation worldwide. This rot occurs in both field and storage conditions posing significant challenges. While this disease has been attributed to a range of pathogens, previous investigations have solely examined it within the framework of a single-pathogen disease model. Our study took a different approach and identified four pathogens associated with the disease: Fusarium solani, Penicillium chrysogenum, Botrytis tulipae, and Aspergillus niger. The primary objective of our research was to examine the impact of co-infections on the overall virulence dynamics of these pathogens. Through co-inoculation experiments on potato dextrose agar, we delineated three primary interaction patterns: antibiosis, deadlock, and merging. In vitro trials involving individual pathogen inoculations on tulip bulbs revealed that B. tulipae,was the most virulent and induced complete bulb decay. Nonetheless, when these pathogens were simultaneously introduced in various combinations, outcomes ranged from partial bulb decay to elongated rotting periods. This indicated a notable degree of antagonistic behaviour among the pathogens. While synergistic interactions were evident in a few combinations, antagonism overwhelmingly prevailed. The complex interplay of these pathogens during co-infection led to a noticeable change in the overall severity of the disease. This underscores the significance of pathogen-pathogen interactions in the realm of plant pathology, opening new insights for understanding and managing tulip bulb rot.

Transcriptome Analysis of Intermittent Light Induced Early Bolting in Flowering Chinese Cabbage.

In flowering Chinese cabbage, early booting is one of the most important characteristics that is linked with quality and production. Through fixed light intensity (280 µmol·m-2·s-1) and fixed intermittent lighting in flowering Chinese cabbage, there was early bolting, bud emergence, and flowering. Moreover, the aboveground fresh weight, blade area, dry weight of blade, and quantification of the leaves in flowering Chinese cabbage were significantly reduced, while the thickness of tillers, tillers height, dry weight of tillers, and tillers weight were significantly increased. The chlorophyll contents and soil-plant analysis and development (SPAD) value decreased in the early stage and increased in the later stage. The nitrate content decreased, while the photosynthetic rate, vitamin C content, soluble sugar content, soluble protein content, phenolic content, and flavonoid content increased, and mineral elements also accumulated. In order to explore the mechanism of intermittent light promoting the early bolting and flowering of '49d' flowering Chinese cabbage, this study analyzed the transcriptional regulation from a global perspective using RNA sequencing. A total of 17,086 differentially expressed genes (DEGs) were obtained and 396 DEGs were selected that were closely related to early bolting. These DEGs were mainly involved in pollen wall assembly and plant circadian rhythm pathways, light action (34 DEGs), hormone biosynthesis and regulation (26 DEGs), development (21 DEGs), and carbohydrate synthesis and transport (6 DEGs). Three hub genes with the highest connectivity were identified through weighted gene co-expression network analysis (WGCNA): BrRVE, BrLHY, and BrRVE1. It is speculated that they may be involved in the intermittent light regulation of early bolting in flowering Chinese cabbage. In conclusion, intermittent light can be used as a useful tool to regulate plant growth structure, increase planting density, enhance photosynthesis, increase mineral accumulation, accelerate growth, and shorten the breeding cycle.

Zero-valent iron (nZVI) nanoparticles mediate SlERF1 expression to enhance cadmium stress tolerance in tomato.

Cadmium (Cd) pollution threatens plant physiological and biochemical activities and crop production. Significant progress has been made in characterizing how nanoparticles affect Cd stress tolerance; however, the molecular mechanism of nZVI nanoparticles in Cd stress remains largely uncharacterized. Plants treated with nZVI and exposed to Cd had increased antioxidant capacity and reduced Cd accumulation in plant tissues. The nZVI treatment differentially affected the expression of genes involved in plant environmental responses, including those associated with the ERF transcription factor. SlEFR1 was upregulated by Cd stress in nZVI-treated plants when compared with the control and the predicted protein-protein interactions suggested SlERF1 interacts with proteins associated with plant hormone signaling pathway and related to stress. Yeast overexpressing SlEFR1 grew faster after Cd exposure and significantly had higher Cd stress tolerance when compared with empty vector controls. These results suggest that nZVI induces Cd stress tolerance by activating SlERF1 expression to improve plant growth and nutrient accumulation. Our study reveals the molecular mechanism of Cd stress tolerance for improved plant growth and will support new research on overcoming Cd stress and improving vegetable crop production.

Determinants of Overweight Among Type Two Diabetes Mellitus Patients Attending Public Hospitals At Awusi Resu Zone of Afar Region: Unmatched Case-Control Study.

Background: Diabetes is a major cause of morbidity and mortality; affecting More than 415 million people. Objective: The primary aim of this study was to assess the determinants of being overweight among Type 2 Diabetic patients attending diabetic clinics of public Hospitals in the Awusi resu zone of Afar region, Northeast Ethiopia. Methods: A hospital-based unmatched case-control study design was conducted from May 5 to June 5/2021 by systematic random sampling 286 study participants were involved in the study (96 cases and 190 controls); Logistic regression analysis was performed to identify the best model of factors leading to overweight. The odds ratio and 95% confidence interval were used as a measure of association. Results: Those who have attended college and above have an AOR; of 10.30 CI: (4.16-25.50) ten times higher odds of being overweight when compared to those unable/able to read. Only those who have a family history of diabetes AOR: 3.10 CI (1.04-9.30) have three folds of being overweight when compared to their counterparts. Of those who use insulin for controlling blood glucose (AOR: 0.14 CI (0.03-0.74) 96% at less likely to be overweight compared to those who use exercise. Conclusion and Recommendation: In this study, educational level, Family History, and type of blood glucose controlling mechanism were important predictors of overweight on T2DM. Moreover the diabetes patients were recommended to use insulin for controlling blood glucose.

The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.

Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

The American Thyroid Association risk stratification and long-term outcomes of differentiated thyroid cancer: a 20-year follow-up of patients in Saudi Arabia.

Background: Studies have reported differing factors associated with poor outcomes in patients with differentiated thyroid cancer (DTC). We aimed to describe our 20 years of experience in the management of thyroid cancer (TC) and identify predictors of treatment outcomes. Methods: We conducted a retrospective review of medical records of patients with TC seen in the Thyroid Center at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia, between the years 2000 and 2020. Demographic and clinical data including pathological characteristics were collected. The American Thyroid Association (ATA) risk stratification was determined for all patients at the postoperative period as well as the response to therapy at the final follow-up visit. Results: A total of 674 patients (mean age: 47.21 years) with TC, 571 (84.7%) of which were women, were included. There were 404 (60.0%) patients with ATA low risk, 127 (18.8%) with intermediate risk, and 143 (21.2%) with high-risk histology. Overall, 461 patients (68.4%) had an excellent response to treatment, 65 (9.6%) had an indeterminate response, 83 (12.3%) had a biochemical incomplete response, and 65 (9.6%) had a structural incomplete response. Patients who had an excellent response were mostly ATA low risk (n = 318 of 431, 68.1%), whereas 40 of 65 patients (61.5%) of those with ATA high-risk histology had a structural incomplete response to treatment. There were significantly more women who had an excellent response compared with men. Obesity, lymphovascular invasion, and size of the tumor were significant predictors of worse outcomes to therapy. Conclusion: Tumor size, lymphovascular invasion, and obesity are strong predictors of a worse response to therapy among patients with TC. Patients with obesity should be carefully followed up regardless of their risk stratification in light of the recent compelling evidence associating obesity with thyroid cancer and its higher risk of a worse disease outcome. ATA risk stratification is well correlated with patient long-term outcomes.

Detection of early prognostic biomarkers for metastasis of Ewing's sarcoma in pediatric patients.

AIMS: Ewing's Sarcoma is an extremely aggressive tumor in children. The disease is associated with highly metastatic rate, especially at the time of diagnosis, contributing to a lower survival rate and poor prognosis. The study aimed to identify predictive biomarkers for metastatic Ewing's sarcoma through in-depth analysis of the plasma proteome profile of pediatric Ewing's sarcoma patients. MAIN METHODS: Plasma samples from Ewing's sarcoma patients and control individuals were profiled using both shotgun and dimethyl-labeled proteomics analysis. Subsequently, Ewing's sarcoma patients were further stratified according to their metastatic state and chemotherapy response. Western blot was used for validation. Univariate and multivariate analyses were performed to determine proteome metastasis predictors. Receiver operating characteristic (ROC) analysis was done to assess the diagnostic significance of the potential plasma Ewing's sarcoma biomarkers. KEY FINDINGS: Our results revealed a set of proteins significantly associated with the metastatic Ewing's sarcoma disease profile. These proteins include ceruloplasmin and several immunoglobulins. Additionally, our study disclosed significant differentially expressed proteins in pediatric Ewing's sarcoma, including CD5 antigen-like, clusterin, and dermcidin. Stable isotope dimethyl labeling and western blot further confirmed our results, strengthening the impact of such proteins in disease development. Furthermore, an unbiased ROC curve evaluated and confirmed the predictive power of these biomarker candidates. SIGNIFICANCE: This study presented potential empirical predictive circulating biomarkers for determining the disease status of pediatric Ewing's sarcoma, which is vital for early prediction.

parazitCUB: An R package to streamline the process of investigating the adaptations of parasites' codon usage bias.

Examining the intricate association between parasites and their hosts, particularly at the codon level, assumes paramount importance in comprehending evolutionary processes and forecasting the characteristics of novel parasites. While diverse metrics and statistical analyses are available to explore codon usage bias (CUB), there presently exists no dedicated tool for examining the co-adaptation of codon usage between parasites and hosts. Therefore, we introduce the parazitCUB R package to address this challenge in a scalable and efficient manner, as it is capable of handling extensive datasets and simultaneously analyzing of multiple parasites with optimized performance. parazitCUB enables the elucidation of parasite-host interactions and the evolutionary patterns of parasites through the implementation of various indices, cluster analysis, multivariate analysis, and data visualization techniques. The tool can be accessed at the following location: https://github.com/AliYoussef96/parazitCUB.

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes.

Osteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.

Correlation between physician- and patient-directed disease assessments in ulcerative colitis patients from Saudi Arabia and Kuwait: Data from ICONIC.

Background: The aim of the observational, prospective study was to validate a novel, nonverbal assessment tool for perceived disease burden-Pictorial Representation of Illness and Self-Measure (PRISM)-in ulcerative colitis (UC) against established patient health questionnaires. The cumulative burden of patients recently diagnosed (<3 years) with UC was also evaluated. Methods: "ICONIC" - Understanding the impact of ulcerative colitis and its associated disease burden on patients - was a noninterventional, multicountry, multicenter study performed in a 2-year follow-up format in adult patients with recently diagnosed UC in 33 countries, regardless of disease severity or treatment. Data collection consisted of five visits, scheduled at approximately 6-month intervals. For the current analysis, patient data from Saudi Arabia and Kuwait were evaluated. The collected data comprised demographics, disease-related data, UC treatment, and healthcare resources, as well as physician- and patient-assessed quality-of-life and disease burden questionnaires. Correlations between selected questionnaire scores were performed using Spearman's rho. Results: Disease severity at baseline and throughout the study was slightly less favorable in this country analysis compared with the global study cohort. Disease burden was assessed by PRISM and improved within 24 months. Conclusions: The detected moderate correlation between PRISM and other assessment methods supports the validity of PRISM. Differences in perceptions of UC-related burden between physician and patient may reflect to some degree insufficient patient-physician communication.

Prognostic Value of Tumor Markers in Gastric Cancer: A Tertiary Cancer Centre Experience.

OBJECTIVES: Gastric cancer is a heterogeneous malignancy in terms of stage-wise prognosis. This study aimed at finding any prognostic significance of preoperative carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 in resectable gastric cancer. METHODS: A total of 57 patients at Kidwai Memorial Institute of Oncology, Bengaluru, India from January 2022 to March 2023 were included in this observational prospective study. Included patients had a resectable tumor at clinical staging. Patients were divided into two categories (raised and non-raised) based on serum tumor marker (CEA and CA 19-9) levels. Their relationship with clinicopathological features was studied. The association was studied using chi-square test, and p-value <0.05 was considered significant. RESULTS: The mean age of the study group was 55.47 years with male predominance (63.2%, n=36). Raised CEA and CA 19-9 were seen in 15.8% (n=9) and 10.5% (n=6) patients, respectively, while both markers were raised in 5.3% (n=3). Raised CEA was found significantly associated with grade 3 adenocarcinoma stomach (OR 7.825, 95%CI: 1.374-44.562; p= 0.020) and intraoperative finding of inoperability due to occult intra-abdominal disease (p<0.05). CA 19-9 (pre- and post-operative levels) had no statistically significant association (p>0.05) with the grade of adenocarcinoma. CONCLUSION: This study indicates a benefit in estimating CEA for the prediction of prognosis in gastric cancer. CEA levels have been found to predict chances of finding occult intra-abdominal metastasis in gastric cancer.