Expression Profile of Serum CircFUNDC1 and CircUHRF1 Can Differentiate Between Colorectal Cancer and Inflammatory Bowel Diseases (Ulcerative Colitis and Crohn's Disease)

ABSTRACT Background Colorectal cancer ( CRC ) is a worldwide burden. Circular RNAs are promising biomarkers for diagnosing and prognosis of CRC . Objective To investigate the possible association of sera levels of CircFUNDC1 and CircUHRF1 expression with predisposition and clinicopathological findings in CRC , ulcerative colitis ( UC ), and Crohn's disease ( CD ) in Egyptian patients. Methods The serum levels of CircFUNDC1 and CircUHRF1 were evaluated in 113 Egyptian subjects divided into four groups; CRC (31), UC (26), and CD (25) and compared to healthy controls (31) using quantitative polymerase chain reaction. Results The median values of log2 serum fold change ( FC ) of CircFUNDC1 in CRC , UC , and CD patients were 9.11, 6.58, and 6.17, respectively. It was upregulated in all case groups. CRC , UC , and CD patients had significantly higher serum CircFUNDC1 levels than controls ( p  < 0.001). However, there were no significant differences among patient groups ( CRC , UC , and CD ). The medians of log 2 of serum FC CircUHRF1 in patients with CRC , UC , and CD were −2.00, 3.33, and 3.12, respectively. The CircUHRF1 serum level was lower in the CRC group of patients, with no significant difference between the CRC group and the controls. Serum CircUHRF1 was significantly overexpressed in patients with UC and CD compared to the CRC groups or controls ( p  < 0.001). By Roc curve analysis, both genes can differentiate CRC patients from inflammatory bowel disease ( IBD ) patients or healthy controls with p  < 0.05. Conclusion Serum CircFUNDC1 is a biomarker for CRC , while CircUHRF1 is a biomarker of IBD .

Soluble C5b‐9 (sC5b‐9) in Pediatrics—A Clinical Assessment

ABSTRACT Background The soluble C5b‐9 (sC5b‐9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement‐mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted. Methods We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b‐9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [ n  = 26; median age 18.5 years (range 2–59)]. Clinical performance of the assay was assessed using plasma samples of patients who (i) developed transplant‐associated thrombotic microangiopathy [ n  = 10; median age 14 years (range 3–19)], (ii) had reduced ADAMTS13 activity [ n  = 6; median age 16 years (range 9–18)], and (iii) developed acquired Von‐Willebrand disease [ n  = 10; median age 18.5 years (range 0.5–18)]. Results The assay showed acceptable intra and inter‐precision at both low and high levels. Linearity ranged from 12.6 to 160.66 ng/mL, while accuracy and method correlation studies with a reference laboratory yielded a correlation coefficient ( R ) of 0.96. The reference range in control donors was established at ≤ 268.0 ng/mL. Clinical performance of the assay in patients' plasma revealed elevated sC5b‐9 levels suggesting complement activation in these patient cohorts compared with control levels. Conclusion The Quidel Microvue sC5b‐9 plus EIA assay demonstrated acceptable analytical performance and clinical utility for monitoring complement activation in patients. Further studies are needed to correlate sC5b‐9 levels with existing markers of complement activation.

Bypassing Blood‐Brain Barrier and Glucose Dependency of Anti‐Glioblastoma Drug Candidates Targeting Mitochondrial Respiration

ABSTRACT We attempt to address two key therapeutic obstacles affecting glioblastoma patients: low ability of anticancer drugs to penetrate the blood‐brain barrier (BBB), and temozolomide (TMZ) resistance, by targeting mitochondrial respiration of glioblastoma cells. We designed and tested over 100 new compounds based on the chemical structure of fenofibrate (FF), which in its prodrug form is cytotoxic to cancer cells by causing severe impairment of mitochondrial respiration. The compounds were designed using two key predictive tools: central nervous system–multiparameter optimization (CNS‐MPO) and BBB_SCORE. These algorithms assess how effectively compounds can penetrate the BBB. We initially selected PP1 as a lead compound by testing its BBB penetration, metabolic performance, and antitumoral efficacy. PP1 accumulated in brain tumors and triggered glioblastoma cell death. However, PP1‐induced inhibition of mitochondrial respiration was followed by an immediate glycolytic response, which attenuated PP1 toxicity in a glucose‐dependent manner. To bypass this limitation, we tested two strategies: (1) the use of PP1 in combination with glycolysis inhibitors; and (2) introduction of a new compound, PP211, which inhibited mitochondrial respiration in the absence of a concomitant increase of glycolysis. Although the combination of PP1 with glycolysis inhibitors was very effective in vitro, this drug combination demonstrated elevated toxicity in mice. PP211, instead, attenuated TMZ‐resistant tumor growth and prolonged mouse survival with only minimal general animal toxicity. In summary, we developed and tested a novel mitochondria‐targeting drug candidate, PP211, which effectively crosses the BBB, overcomes TMZ resistance, and induces tumor cell death independently of glucose levels—while exhibiting minimal systemic toxicity in preclinical models. These findings support further development of PP211 for glioblastoma therapy.

Population Pharmacokinetics and Exposure–Response Relationships of Etrolizumab in Patients with Moderately‐to‐Severely Active Crohn's Disease

Abstract This study aimed to characterize the pharmacokinetics (PK) of etrolizumab, an IgG1‐humanized monoclonal anti‐β7 integrin antibody, and assess its exposure–response (ER) relationship for key clinical outcomes in patients with moderately‐to‐severely active Crohn's disease. ER analyses were based on data from Phase 3 BERGAMOT trial, which evaluated etrolizumab at 105 or 210 mg during induction phase and 105 mg during maintenance phase. Population pharmacokinetic analysis was performed to characterize etrolizumab PK and identify influential covariates. ER analyses were conducted at end of induction and maintenance for clinical remission, endoscopic improvement, and endoscopic remission. ER modeling was performed using logistic regression, and full covariate model was used to examine the impact of baseline covariates on clinical outcomes. Pharmacokinetics of etrolizumab was best characterized using a two‐compartment model with first‐order absorption, demonstrating a time‐dependent decrease in clearance. Typical maximum reduction of clearance was 22.0% (95% CI: 20.5%‐23.5%) with onset half‐life of 3.45 (95% CI: 2.84‐4.04) weeks. Baseline body weight, albumin, and C‐reactive protein were the most impactful covariates for etrolizumab exposure. Based on population PK results, trough concentration at Week 4 of induction was selected as exposure metric. Etrolizumab exposure–response slope was significant ( P < .05) for clinical remission, endoscopic improvement, and endoscopic remission final models in maintenance phase, but none of final ER models of induction phase. For all induction ER endpoints, tumor necrosis factor (TNF)‐naive patients had significantly higher probability of a favorable outcome at end of induction compared to TNF‐experienced patients. In summary, exposure–response was more evident at end of maintenance than at end of induction.

Catalytic synthesis of 2‐furyl methanol from leaves of Acacia auriculiformis using zinc chloride: a pathway to green chemical synthesis

Abstract BACKGROUND The catalytic conversion of biomass‐derived feedstocks into valuable chemicals is a key focus in sustainable chemistry. This study explores the zinc chloride ( ZnCl 2 )‐catalyzed synthesis of 2‐furyl methanol from Acacia auriculiformis leaves. The influence of reaction parameters, including catalyst concentration, temperature, and time, on product yield was systematically investigated. RESULTS Gas chromatographic–mass spectrometric results confirmed the formation of 2‐furyl methanol, with a maximum yield of 9.35%, equivalent to 458.04 mg g −1 of feed, obtained at 40 °C using 1.0% ZnCl 2 catalyst. The reaction pathway involves ZnCl 2 ‐assisted thermal hydrolysis, dehydration, and mild hydrogenation of hemicellulose‐derived pentose sugars. Comparative catalyst studies (using BaCl 2 , NaOH , ZnO , CaO , and MgO ) revealed that ZnCl 2 exhibited superior selectivity and efficiency in the conversion process. CONCLUSION Zinc chloride proved to be an effective catalyst for the selective synthesis of 2‐furyl methanol from lignocellulosic biomass. This study highlights the potential of ZnCl 2 for biomass valorization, offering a green and sustainable route to bio‐based chemical production and contributing valuable insights for future industrial applications. © 2025 Society of Chemical Industry (SCI).

Can cavum septum pellucidum width and length measurements also be reliable indicators of corpus callosum measurements in normal fetuses?

Abstract Objective To examine the association between cavum septum pellucidum (CSP) and corpus callosum (CC) length and width measurements in mid‐trimester sonographic screening in normal fetuses. Methods This prospective cohort study examined 152 pregnant women who underwent mid‐trimester sonographic fetal anomaly screening. CSP and CC lengths and their anterior, middle, and posterior width measurements were examined sonographically. The association between length and width measurements of both structures, gestational week and CSP ratio (length/width) were evaluated. Results The mean CSP length was 7.96 ± 1.09 mm, and the mean middle width was 3.43 ± 0.82 mm. The mean CC length was 20 ± 3.76 mm, and the mean middle width was 3.43 ± 0.82 mm. There was a positive correlation between CSP and CC lengths ( r  = 0.691, p  < 0.001). There was also a significant correlation between CSP and CC anterior, middle and posterior widths (anterior ( r  = 0.366, p  < 0.001), middle ( r  = 0.305, p  < 0.001), and posterior ( r  = 0.233, p  = 0.004)). All CSP and CC measurements were correlated with gestational age, biparietal diameter (BPD), and head circumference (HC) ( p  < 0.001, for all). The CSP ratio was not related to CC dimensions ( p  > 0.05, for all) and also decreased with the increase in BPD and HC dimensions ( r  = −0.186, p  = 0.022, and r  = −0.174, p  = 0.032; respectively). Conclusion In normal fetuses, the length and width of the CC and CSP structures developed in relation to each other, as well as to the gestational week, BPD, and HC dimensions. In addition, while the CSP ratio was not found to be associated with CC dimensions, it decreased due to the increase in BPD and HC sizes.

Prediction of Coronary Artery Abnormalities Using Computed Tomography Angiography and Transthoracic Echocardiography Before Arterial Switch Operation İn Neonates With Dextro‐Transposition of the Great Arteries

ABSTRACT Background The aim of this study was to evaluate and compare the diagnostic accuracy of transthoracic echocardiography (TTE) and cardiac computed tomography angiography (CTA) in identifying coronary artery anatomy in neonates diagnosed with dextro‐Transposition of the Great Arteries (d‐TGA) before undergoing an arterial switch operation (ASO). Methods The retrospective cohort of newborns diagnosed with d‐TGA who underwent arterial switch surgery between January 2023 and September 2024 was analyzed. Preoperative coronary artery anatomy was assessed using TTE and CTA. The findings from these imaging modalities were compared with intraoperative coronary artery findings, considered the gold standard. The results were evaluated statistically. Results A total of 40 cases (22 males) were included in the study. The median operative age was 5 days (IQR: 3–7 days), and the median weight was 3.1 kg (IQR: 2.9–3.4 kg). The sensitivity and specificity of CTA were determined as 93% and 100%, respectively, while TTE demonstrated a sensitivity of 57% and a specificity of 92%. Coronary anomalies were identified in 23% of patients using TTE and in 38% using CTA. The positive predictive value (PPV) and negative predictive value (NPV) of TTE were calculated as 89% and 66%, respectively, with an overall accuracy of 74%. For CTA, the PPV and NPV were 100% and 94%, respectively, with an overall accuracy of 96%. The area under the curve (AUC) was 1.0 for CTA and 0.91 for TTE. Chi‐square analysis revealed significant differences, with χ 2  = 5.36 ( p  < 0.05) for TTE and χ 2  = 23.51 ( p  < 0.001) for CTA. Conclusion Cardiac CTA may be a more reliable diagnostic tool than TTE for preoperative evaluation of coronary artery anatomy in newborns with d‐TGA. The combined use of TTE and CTA may be recommended to maximize the accuracy of coronary artery assessment and improve surgical outcomes in this high‐risk population.

Efficacy of Cerebroplacental Doppler Ratio in Predicting Adverse Fetal Outcomes in Cases of Fetal Growth Restriction Multicenter Study

ABSTRACT Introduction Fetal growth restriction (FGR) is a significant cause of perinatal morbidity and mortality. Differentiating FGR from small‐for‐gestational‐age fetuses is critical for risk assessment. This study investigates the cerebroplacental ratio (CPR) as a noninvasive predictor of adverse fetal outcomes, particularly neonatal intensive care unit (NICU) admissions, intrauterine fetal death (IUFD), and birth weight variability. Methods This prospective, multicentre study included 60 pregnant women (gestational age 28–34 weeks) divided into normal and abnormal CPR groups. Doppler ultrasonography assessed umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices. Statistical analysis included receiver operating characteristic (ROC) curves for CPR, UA, and MCA indices to predict adverse outcomes. Results Abnormal CPR correlated with increased NICU admissions (46.7%), IUFD (10%), and lower birth weight (mean: 2138 g). Elevated UA PI and reduced MCA PI were observed in the abnormal CPR group. Sensitivity and specificity analyses identified CPR (cutoff: 1.1) as a modestly accurate predictor of adverse outcomes. Discussion CPR effectively stratifies risk in high‐risk pregnancies but requires further validation. Abnormal Doppler findings highlight placental insufficiency and compromised cerebral perfusion. These findings could refine FGR management strategies.

Evaluation of dental students and alumni's confidence level in orthodontic diagnosis and treatment‐planning: A qualitative study

Abstract Background Orthodontic education, besides some other factors, influences the confidence level of recently graduated dentists to diagnose subjects seeking orthodontic treatment and provide treatment plans. This study aims to explore the factors that influence the confidence level of undergraduate dental students to diagnose subjects seeking orthodontic treatment and provide treatment plans after graduation. Methods A qualitative study was undertaken using focus groups and interviews. Purposive sampling was used, focus groups and face to face semi‐structured interviews were adopted as the method of data collection. Three focus groups were evaluated including fifth‐year undergraduate, postgraduate orthodontic students, and recently graduated general dentists. In addition, eleven interviews were performed with the fifth‐year undergraduate students. Data collection ceased upon reaching data saturation, with thematic analysis employed for qualitative data analysis. Results Six themes and two sub‐themes were extracted from the data. More focus on the theory was highly noticed, and most of the participants exhibited a low level of self confidence in extrapolating orthodontic diagnosis and establishing treatment plans after graduation. In addition, they believed that practical teaching sessions mostly deal with wire bending and demanded to expand the clinical orthodontic knowledge to be able to indicate the right diagnosis and initiate proper treatment plans. Conclusions Clinical and practical training alongside theoretical foundation represent key factors in orthodontic education required to obtain confidence in orthodontic practice among dental undergraduate students and alumni. The findings help in enhancing undergraduate programs via providing a clinically oriented orthodontic education from student perceptions.

Aligning dental curriculum to support an entrustable professional activities framework: Structure, instruction, assessment, and infrastructure