Search Results (94)

Background and Aim: Anti-epidermal growth factor receptor (EGFR) therapy is commonly associated with skin toxicity, which may reflect treatment response. This study evaluated the prognostic significance of anti-EGFR-related skin toxicity in patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving palliative chemotherapy. Materials and Methods: We retrospectively analyzed 256 RAS wild-type mCRC patients treated with anti-EGFR monoclonal antibodies at Erciyes University, Kayseri, Turkey (June 2011–February 2024). Survival was estimated using the Kaplan-Meier method with log-rank comparisons. A landmark analysis at 2 months was performed to address guarantee-time bias. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Results: The median PFS was 17 months in patients with grade ≥ 2 skin toxicity versus 8 months in those with grade < 2 skin toxicity (p < 0.001). The median OS was 32 and 21 months, respectively (p < 0.001). In the landmark-adjusted multivariate analysis, grade ≥ 2 skin toxicity was an independent prognostic factor for both PFS (HR 0.52, 95% CI 0.39–0.70, p < 0.001) and OS (HR 0.50, 95% CI 0.37–0.68, p < 0.001). Additional independent factors for OS included albumin, LDH, peritoneal metastasis, age, tumor sidedness, and BMI. The objective response rates were 53.9% and 11.3% in the grade ≥ 2 and grade < 2 groups, respectively (p < 0.001). Conclusions: Grade ≥ 2 skin toxicity was significantly associated with longer PFS, OS, and a higher response rate, and was confirmed as an independent prognostic factor in multivariate analysis. These findings suggest that skin toxicity may serve as a non-invasive marker of treatment efficacy. Prospective studies with time-dependent methodologies are needed to validate these results. Full article

Colorectal cancer (CRC) shows consistent sex-related differences in incidence, anatomic distribution, molecular subtype, immune context, and clinical outcome. However, these differences are often discussed through broad parallel themes such as hormones, genetics, or the microbiome, rather than through the biological settings in which sex meaningfully modifies tumor behavior. This review argues that sex is most informative in CRC when treated as a contextual modifier whose relevance emerges only after integrating tumor sidedness, mismatch repair status, oncogenic background, immune ecology, and age at onset. The clearest signals arise from interaction-based contexts, particularly when sex is interpreted together with tumor sidedness and dMMR/MSI-H or BRAF-linked disease states. Current evidence indicates that women are enriched for proximal or right-sided, microsatellite instability-high, mismatch repair-deficient, CpG island methylator phenotype-high, and BRAF-associated CRC, whereas men more often present with distal disease and a higher overall burden. Mechanistic studies further show that sex-related differences extend beyond hormone exposure to include KRAS–STAT4–KDM5D signaling, site-specific immune-checkpoint programs, metabolic phenotypes, epigenetic biomarker variation, and microbiota–hormone crosstalk. These effects are most evident in defined clinical niches, particularly right-sided CRC, mismatch repair-deficient disease, BRAF-mutated metastatic CRC, and early-onset CRC. A sex-aware, subtype-aware, and location-aware framework therefore offers a more clinically useful interpretation of CRC heterogeneity than descriptive male-versus-female comparisons alone. Full article

Hair whorl patterns are usually used as a predictor of equine laterality, temperament and reactions to various environmental stimuli. Thus, temperament and motor laterality may be deducted in order to ease the daily work, training, handling and transportation of Thoroughbreds. We aimed to identify the number, position and orientation of hair whorl patterns to find the association between environment stimuli and the laterality, affability, trainability and anxiety of 81 individuals. We analyzed hair whorls with SPSS (Statistical Package for the Social Sciences) accompanied by a laterality paddock test and temperament questionnaire. All of our examined Thoroughbreds showed at least one circular whorl on their head. Mostly, the whorls were located on the top of the head. Compared to previous studies, the presence of linear whorls on the body was also high. We found that the counterclockwise head and clockwise whorls were associated with left and right front leg preference (p < 0.001). Full article

Background: Although the BRAF gene mutation in colorectal cancer has a prognostic value and a therapeutic interest, very few studies address the prevalence of this mutation in the Middle East, and hardly any among the Lebanese population. Moreover, we studied the correlation between this mutation and other clinical and pathological variables. Methods: In this descriptive, retrospective, single-center study, BRAF mutational status was reviewed in colorectal tumor samples collected from 2015 to 2021 of Lebanese patients with confirmed metastatic colorectal cancer. The genetic analysis was done in two different molecular laboratories. Clinical characteristics were selected from the computerized medical records of included patients. Statistical calculations were performed with SPSS (version 21.0) statistical software. Results: The study included 190 patients. BRAF mutation was detected in 10 patients (5.3%). A positive correlation was observed between the presence of a BRAF mutation and the right-sidedness of the tumor (p = 0.001) as well as with the presence of microsatellite instability (p = 0.004). However, we could not establish a relationship between BRAF mutation and other characteristics such as age (p = 0.682), gender (p = 0.392), the degree of histologic differentiation (p = 0.594), and the presence of peritoneal metastases (p = 0.707). Conclusions: The BRAF mutation was found in 5.3% of colorectal cancers in Lebanon. A positive correlation was suggested with the colon sidedness and the microsatellite instability. However, it was still insufficient to establish statistically significant associations between other variables and the BRAF mutation. Full article

Background/Objectives: Venous thromboembolism (VTE) is a common and clinically significant complication in patients with metastatic colorectal cancer (mCRC). Tumor sidedness and molecular alterations such as RAS and BRAF mutations are established prognostic factors in mCRC; however, their role in VTE risk stratification remains unclear. This study aimed to evaluate the association between primary tumor sidedness, KRAS/NRAS/BRAF mutational status, and VTE occurrence in patients with mCRC treated in the outpatient setting. Methods: This multicenter ambispective observational study included 224 patients with mCRC treated with first-line chemotherapy with or without targeted therapy. All patients had known KRAS/NRAS/BRAF statuses. The primary endpoint was the association between tumor sidedness and VTE risk. Secondary endpoints included associations between oncogenic mutations and VTE, subgroup analyses according to tumor localization and mutational status, and overall survival (OS). Multivariate logistic regression was used to identify independent predictors of VTE. Results: After a median follow-up of 21 months, VTE occurred in 23.3% of patients. The incidence of VTE was significantly higher in right-sided colorectal cancer (RCRC) compared with left-sided colorectal cancer (LCRC) (41.0% vs. 17.6%, p < 0.001). Although KRAS/NRAS and BRAF mutations were more frequent in RCRC, mutational status was not independently associated with VTE. In multivariate analysis, right-sided tumor location remained a strong predictor of VTE (OR 5.2; 95% CI 1.9–14.1; p = 0.001), along with anti-EGFR therapy. The Khorana score classified most patients as low risk and did not reliably identify those who developed VTE. VTE occurrence was not significantly associated with OS, whereas right-sided tumor location was associated with inferior survival. Conclusions: Right-sided tumor location is an independent predictor of VTE in patients with mCRC and confers a high absolute thrombotic risk not captured by the Khorana score. Incorporating tumor sidedness into VTE risk assessment may improve identification of patients who could benefit from primary thromboprophylaxis. Full article

Background: Metastasectomy is a cornerstone of multimodal management in metastatic colorectal cancer (mCRC), yet contemporary real-world data focusing specifically on RAS wild-type (RAS-WT) disease remain limited. We aimed to evaluate survival outcomes and prognostic factors associated with metastasectomy in patients with RAS-WT mCRC using a large national multicentre registry. Methods: This retrospective cohort study utilized data from the ONKO-KOLON Türkiye registry. A total of 1079 patients with pathologically confirmed KRAS/NRAS wild-type mCRC were identified and categorized according to receipt of metastasectomy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and compared with log-rank tests across multiple clinically relevant time origins, including metastatic diagnosis, initial colorectal cancer diagnosis, and time of metastasectomy. Prognostic factors within the metastasectomy cohort were assessed using univariate Cox proportional hazards models. Serum CEA and CA19-9 were analyzed after log₁₀ transformation. Results: Among 1079 patients, 185 (17.1%) underwent metastasectomy. Patients receiving metastasectomy demonstrated significantly longer OS compared with those managed non-surgically when survival was calculated from the time of metastatic diagnosis (hazard ratio [HR] for death 0.36, 95% CI 0.27–0.47; p < 0.001), as well as improved PFS (HR for progression or death 0.39, 95% CI 0.30–0.52; p < 0.001). The survival advantage remained consistent when OS was measured from the time of initial colorectal cancer diagnosis (HR 0.37, 95% CI 0.25–0.50; p < 0.001). Median OS following metastasectomy was 43 months (95% CI 31.4–45.6). In univariate analyses within the metastasectomy cohort, higher baseline CA19-9 levels were significantly associated with inferior OS when analyzed both as a continuous variable (per log₁₀ increase; HR 1.81, 95% CI 1.20–2.75; p = 0.005) and as a categorical variable (above vs. below threshold; HR 0.37, 95% CI 0.16–0.86; p = 0.021). Other clinicopathologic factors, including age, CEA, tumor sidedness, grade, MSI status, and metastatic burden, were not significantly associated with survival. Conclusions: In this large, real-world national cohort of RAS-WT mCRC, metastasectomy was strongly associated with prolonged survival across multiple clinically relevant time frames. Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC. Full article

Background: Peritoneal metastasis (PM) from colorectal cancer (CRC) carries a poor prognosis. The Peritoneal Cancer Index (PCI) is among the principal prognostic stratification tools, yet the prognostic value of the anatomical distribution of disease beyond total PCI is underexplored. This pilot study evaluated whether quadrant-specific involvement adds prognostic information in patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), with a focused analysis of oligometastatic disease (PCI ≤ 6). Methods: A single-institution cohort of 48 CRC-PM patients treated with CRS + HIPEC was analyzed. Primary endpoints were OS, DFS, and PRFS, with a focused evaluation of the oligometastatic subset (PCI ≤ 6). Comparative statistics used Student’s two-sample t test for continuous variables and chi-square or two-sided Fisher’s exact tests for categorical variables. Survival was estimated by Kaplan–Meier with log-rank tests, and prognostic factors were evaluated using Cox regression. Results: Median follow-up was 177 months (IQR 87–224). Outcomes favored PCI ≤ 6: 5-year OS and DFS were 54% and 37.5% versus 6.6% and 0% for PCI > 6, and median OS 64 vs. 29 months (log-rank p = 0.007), median DFS 30 vs. 7 months (p = 0.0002), and median PRFS 26 vs. 8 months (p = 0.0002). In the PCI ≤ 6 subset (n = 27), quadrant 3 (left upper quadrant) was associated with higher recurrence risk and shorter DFS, remaining independently prognostic for DFS (p = 0.005) and PRFS (p = 0.005). For PRFS, quadrants 7 and 8 also showed associations on univariable analysis; Q7 remained independent (p = 0.047), whereas Q8 was borderline (p = 0.077). A histology-related signal at Q8 (p = 0.011) was exploratory due to very small mucinous and signet-ring strata. Sidedness and synchronicity yielded no significant differences in quadrant involvement within PCI ≤ 6. No quadrant effects were observed in PCI > 6. Conclusions: PCI remains the dominant prognostic determinant after CRS + HIPEC, yet in oligometastatic disease, the anatomical distribution adds complementary prognostic information, particularly involvement of Q3 and Q7. These findings are hypothesis-generating and warrant validation in larger, preferably multicenter cohorts with standardized quadrant mapping. If confirmed, quadrant-directed operative planning, including consideration of prophylactic resection in selected high-risk regions, could be prospectively evaluated. Full article

Heterotaxy syndrome is characterized by a tendency for bilaterally symmetric arrangement (isomerism) of inner organs. It is frequently associated with complex congenital heart defects (CHDs). In “heterotaxic” hearts, the tendency for isomerism is confined to the atria. The ventricular segment always shows asymmetric arrangements (D-hand or L-hand topology). This study aimed to determine the statistical distribution of ventricular topology among patients with CHDs associated with heterotaxy and to identify possible associations between ventricular topology and cardiovascular disorders and survival. It is a retrospective cross-sectional study on 192 patients treated at a single center between 2000 and 2023. Our cohort had 115 patients of left atrial isomerism (LAI) and 77 of right atrial isomerism (RAI). The whole cohort (n = 192) showed a bias towards ventricular D-hand topology (67%), which was statistically significant in LAI (74%). In contrast, RAI showed an almost equal distribution (57% D-hand, 43% L-hand). No significant associations were found between ventricular topology and major CHDs or mortality. Significant associations were observed between ventricular topology and cardiac apex position, direction of p-wave axis, and aortic arch sidedness. We conclude that, in the setting of heterotaxy, especially RAI, ventricular topology and aortic arch sidedness both behave as binary anatomical variables showing a tendency for randomized occurrence. This tendency for statistically symmetric distribution is interpreted as reflecting the syndrome-specific tendency for bilateral symmetry. Full article

The complex configuration of the internal flow field in aero-engines leads to limitations on sensor installation positions, and how to accurately identify the disturbances of the installation influence parameters under this constraint has long been a significant challenge. To address this issue, this study proposes an optimization algorithm to identify the optimal sensor layout. This is achieved by employing mutually distinct integer encoding, which ensures the uniqueness of each sensor position and prevents duplication. More importantly, an objective evaluation system incorporating tracking error, sensor comprehensiveness, and spatial coverage is integrated into the fitness function design, thereby overcoming the one-sidedness and limitations of single-indicator evaluation. Building upon this foundation, a sensor optimization scheme is proposed for identifying installation influence parameters. This scheme integrates the rapid search capability of the Tabu Bee Colony Random Variation Dimension Algorithm with the global optimization capability of an Improved Genetic Random Variation Dimension Algorithm, resulting in a Tabu Bee Colony–Improved Genetic Random Variation Dimension Optimization Algorithm (TBC-IG-RVDOA). For each installation influence parameter, different perturbation conditions were established, and the selected optimal sensor combination was then validated using the Extended Kalman Filter (EKF). Experimental studies show that, under all perturbation scenarios, the TBC-IG-RVDOA demonstrates strong convergence, high computational efficiency, and fitness function values consistently exceeding 0.92, thereby accurately capturing the changes in each installation influence parameter. Full article

Background: Tumor sidedness in colon cancer has been linked to biological and clinical differences, but its impact on survival and prognostic factors remains unclear. This study aimed to find the predictors of overall survival (OS) in patients with right-sided colon cancer (RCC) and left-sided colon cancer (LCC) undergoing surgical treatment. Methods: A retrospective single-center study was conducted on 247 patients with colon cancer, including 117 with RCC and 130 with LCC. Clinical, surgical, and pathological variables were analyzed. Cox regression and ROC curve analyses were used to identify independent predictors of OS in the overall cohort and tumor-side subgroups. Results: RCC patients were older (69 vs. 68 years, p = 0.03), had lower hemoglobin levels (11.7 vs. 12.95 g/dL, p < 0.01), and more often presented with anemia (34.18% vs. 11.48%, p < 0.001). LCC patients more frequently underwent emergency surgery (13.74% vs. 5.69%, p = 0.03). Mucinous adenocarcinomas were more frequent in RCC (12.82% vs. 5.38%, p = 0.03), whereas distant metastases (15.38% vs. 6.84%, p = 0.03) and liver metastases (14.61% vs. 6.84%, p = 0.04) were more common in LCC. The one-year overall survival was similar between LCC and RCC before (88.09% vs. 91.52%, p = 0.15) and after propensity score matching (89.32% vs. 91.87%, p = 0.60) In multivariate Cox regression, independent predictors of lower OS included advanced AJCC stage (HR = 34.54, p < 0.001) in RCC, while, in LCC, AJCC stage (HR = 31.14, p = 0.001 and stoma (HR = 5.86, p = 0.01) were significant. Tumor location itself was not associated with OS (p = 0.18). Conclusions: Prognostic factors in colon cancer vary with tumor location. Side-specific risk stratification may improve outcome prediction and guide personalized management. Full article

Background/Objectives: MicroRNAs (miRNAs) regulate gene expression and are proposed as biomarkers in colorectal cancer (CRC). This study evaluated miR-185-5p, miR-141-5p, and miR-21-5p expression in CRC tissues; their association with tumor location, histopathology, and clinical outcomes; and the suitability of miR-16-5p and miR-151a-3p as housekeeping controls. Previous reports suggest tumor-suppressive roles for miR-185 and miR-141 and an oncogenic function for miR-21, though findings remain inconsistent. Methods: Paired tumor and adjacent normal tissues from 70 CRC patients were analyzed. RNA was extracted from FFPE samples, and miRNA expression quantified by RT-qPCR. Relative expression values were normalized to miR-151a-3p. Tumor–normal differences, localization effects, and associations with clinicopathological and outcome variables were assessed using repeated-measures ANOVA and non-parametric tests. Results: miR-185-5p and miR-141-5p were significantly reduced in tumors compared with normal mucosa while miR-21-5p was upregulated. miR-16-5p showed higher expression in normal tissue, indicating its instability and unsuitability as a housekeeping control. A modest but significant localization effect was observed for miR-185, while other miRNAs were minimally influenced by location. Baseline asymmetry between non-tumor samples, observed for miR-185-5p, further indicated sidedness effects. None of the miRNAs were associated with stage, histological type, grade, invasion, immune infiltration, progression, or five-year survival. Conclusions: miR-185-5p, miR-141-5p, and miR-21-5p show robust tumor–normal differences, supporting their diagnostic potential, while miR-16-5p is unsuitable as a housekeeper. Modest but significant localization effect was observed for miR-185 in right-sided tumors. None showed prognostic value in stage I–III CRC. Larger, location-stratified studies are warranted. Full article

Cryptorchidism is a common congenital disorder in male horses characterized by the failure of one or both testes to descend into the scrotum. This developmental anomaly has important clinical, surgical, and economic implications, particularly in breeding animals. This retrospective study investigates the prevalence and laterality of cryptorchidism in a large equine population presented to two veterinary referral hospitals—Colorado State University Veterinary Teaching Hospital (CSU VTH, 1984–2014) and Oakridge Equine Hospital (OEH, 2008–2023). Medical records were reviewed to identify affected horses, and data on breed, age, and laterality of retained testes were collected. Anatomical location of retention (inguinal vs. abdominal) was excluded due to inconsistent documentation across the study period. A total of 777 horses met the inclusion criteria, with Quarter Horses comprising the majority of clinical cases. Quarter Horses exhibited a strong predisposition for left-sided testicular retention, whereas Thoroughbreds and Arabians more commonly presented with right-sided retention. These breed-specific trends in laterality suggest possible developmental factors influencing testicular descent. Understanding these patterns can aid in clinical diagnosis, improve surgical planning, and contribute to evidence-based breeding recommendations aimed at reducing the incidence of cryptorchidism in equine populations. Full article

Laterality or sidedness in the horse is commonly addressed as part of the horse’s training. An international online survey regarding horse and rider sidedness and asymmetry was conducted, with 2304 useable responses. Confidence intervals (95%) were used to evaluate if some response options were chosen more frequently. Discounting answers of ‘not sure’ or ‘not applicable’, the right fore hoof was more often perceived to be more upright (22%) than the left (15%), and the left shoulder was more prominent (24%) more often than the right (17%), whilst most respondents reported no difference. Both lunging and bending was perceived to be most difficult to the right (48% and 52%) than to the left (33% and 42%), and more horses fell in on the right circle (lunging 40%, riding 38%) than on the left (31% and 33%). Horses commonly tracked their hindquarters to the left in walk, trot and left canter. Correspondence analysis showed that responses indicating horse side bias and relative symmetry, respectively, were associated across several questions, suggesting consistent individual patterns. While the mechanisms underpinning sidedness remain unclear, this study provides insights into horse owners’ perceptions of laterality and related matters. Full article

To enhance the refinement of urban traffic demand management, this study explores the impact of introducing incentive and penalty mechanisms in the urban road travel reservation strategy (TRS) on both heterogeneous users and the road network. The existing research on TRS has primarily focused on static evaluations, which have limitations in terms of the one-sidedness of travel service methods and the homogeneity of users’ travel choices. Moreover, these studies overlook the multidimensional decision-making of travelers and the synergistic effects of urban multimodal transportation systems. To overcome these limitations, this paper introduces incentives and penalties for users and develops an agent-based multi-objective optimization model. The model optimizes travel incentive schemes to maximize social benefits, considering the interests of both system managers and travelers. Additionally, an agent-based dynamic traffic simulation model is constructed, incorporating individual travel decisions, real-time traffic conditions, and the balance of road supply and demand. The findings indicate that the introduction of incentive and penalty mechanisms increased the transportation system’s revenue by 17.26% and reduced travel costs by 2.67%. TRS implementation significantly improved traffic performance and reduced congestion across the road network. Specifically, the average speed, road saturation, and network traffic volume increased by 6.7%, 9.3%, and 3.7%, respectively. Moreover, the proportion of users participating in reservation travel increased by 48.5%, with travelers more willing to adjust their travel times. Heterogeneous travelers with different time valuations showed distinct responses to the TRS. In conclusion, TRS offers significant potential in promoting sustainable urban transportation, providing both theoretical insights and practical implications for urban planners and policymakers. Full article

Most accidents during the construction of nuclear power plants are caused by human unsafe behavior. How to scientifically determine the risk management priority of human unsafe behaviors is the basis for effectively preventing accidents in under-construction nuclear power plants. Although employees are adopted for control in under-construction nuclear power plants, the records of unsafe behaviors are mostly recorded by inspectors, and the records of behaviors may have missing values. To overcome the above problems, this paper applies machine learning algorithms to construct an employee behavioral risk assessment model. Firstly, by analyzing the influencing factors of unsafe behaviors, the assessment indexes are proposed, then the Random Forest algorithm is used to obtain the characteristic importance of the proposed indexes and exclude those with smaller characteristic importance. Finally, the harmony search (HS) algorithm is used to optimize the back propagation (BP) neural network to construct an assessment model and compare with the BP evaluation model. The results show that the HS-BP model is more accurate and efficient. The results show that the method can comprehensively and effectively analyze workers‘ unsafe behaviors, and the BP neural network is optimized to construct the assessment model using the Harmonic Search algorithm, which is more accurate than the original model. The use of the machine learning method to assess workers’ behaviors can objectively output the risk level and overcome the one-sidedness and subjectivity of the traditional expert evaluation method. Full article