To support carbon neutrality in civil infrastructure, bridge carbon assessment should be integrated into the early design stage, when key design options remain adjustable. However, this stage usually lacks detailed bills of quantities, material sources, transport distances, construction methods, and maintenance schedules, limiting the direct application of conventional life-cycle assessment (LCA). Published bridge carbon cases can provide reference data for early-stage assessment, but differences in system boundaries, functional units, and reporting formats hinder their direct comparison and reuse. To address this issue, this study first used a cable-stayed bridge in Ningbo, China, as a traceable LCA calculation case to establish the accounting procedure, system boundary, and reporting fields. It then combined this case with published bridge carbon cases to develop a standardized bridge carbon reporting database. The resulting database contains 39 cases across six harmonized bridge-type categories and supports similar-case retrieval and early-stage prediction modeling. Linear, polynomial, and random forest regression models were developed using the most consistently available early-stage parameters to provide initial emission estimates under limited design information. Under the fixed 70:30 data split, the random forest model achieved the best internal validation performance, with a test R² of 0.97 and a mean absolute percentage error (MAPE) of 29%. Static carbon-flow and dynamic time-weighted carbon-flow indicators are further introduced as normalized comparative indicators for interpreting stage-level contributions and temporal emission profiles. The results show that temporal weighting can alter the relative ranking and interpretation of bridge-type carbon performance. As applying these analytical modules still requires substantial expert involvement, a tool-augmented large language model (LLM) assistant was further implemented as the framework’s interaction layer to reduce this operational burden. It structures natural-language inputs, invokes predefined database and analytical tools, and explains their outputs, while engineers remain responsible for verifying the results. The proposed framework provides a traceable, human-in-the-loop approach to supporting early-stage bridge carbon assessment under incomplete design information.

Bu araştırmanın amacı, öğrencilerin matematik kaygısı ile matematik başarılarının sınıf düzeyi ve cinsiyete göre anlamlı farklılık gösterip göstermediğini belirlemek ve farklı akran türleri ile kaygı düzeylerinin öğrencilerin matematik kaygısı ve matematik başarısı üzerindeki etkilerini incelemektir. Araştırmada ilişkisel tarama modeli kullanılmıştır. Araştırmanın örneklemini, Türkiye’nin Doğu Anadolu Bölgesi’nde yer alan bir il merkezindeki Millî Eğitim Bakanlığına bağlı üç devlet okulunda öğrenim gören 5., 6. ve 7. sınıf düzeyindeki toplam 349 öğrenci oluşturmaktadır. Veriler, Matematik Kaygısı Ölçeği, Kişisel Bilgi Formu, Sosyometrik Akran İlişkileri Formu ve matematik başarı notları aracılığıyla toplanmıştır. Verilerin analizinde iki faktörlü varyans analizi (ANOVA) ve yapısal eşitlik modeli (YEM) kullanılmıştır. Bulgular, matematik başarısının yalnızca sınıf düzeyine göre anlamlı farklılık gösterdiğini, matematik kaygısında ise sınıf düzeyi ile cinsiyet etkileşiminin anlamlı olduğunu ortaya koymuştur. Yapısal eşitlik modeli sonuçları, matematik kaygısının matematik başarısını negatif yönde ve anlamlı düzeyde yordadığını göstermiştir. Ayrıca sıra arkadaşı kaygısının matematik başarısını hem doğrudan hem de matematik kaygısı aracılığıyla dolaylı olarak etkilediği; sık etkileşimde bulunulan arkadaş kaygısının ise matematik başarısını matematik kaygısı aracılığıyla dolaylı olarak etkilediği belirlenmiştir. Sıra arkadaşı, gezdiği arkadaş ve matematik kaygısı modeli, matematik başarısındaki toplam varyansın yaklaşık %22'sini açıklamaktadır. Elde edilen bulgular, akran ilişkisi türlerinin matematik başarısını matematik kaygısı aracılığıyla etkilediğini ve matematik kaygısının bu süreçte önemli bir aracı değişken olduğunu ortaya koymaktadır.

Upon the completion of national road projects, their cost and time deviations are often reported. These deviations from the projected values are a result of complications in the time and cost management of such projects. Controlling the cost and time overrun of projects is important for successful implementation and efficient project management. However, few studies have attempted to measure the project cost and time management efficiency in civil engineering. Thus, this issue requires further investigation. In this study, large road projects that had poor cost and time management were selected. The chosen projects were configured as Decision Making Units (DMUs) in a Data Envelopment Analysis (DEA). DEA is a non-parametric modern mathematical tool for measuring relative managerial performance and determining efficient DMUs. A list containing the causes of cost and time deviations and the percentage deviation for each DMU was prepared. The cost and time management efficiency of the DMUs was calculated using DEA, and the resulting values were ordered according to importance. It is believed that this process will contribute to better cost and time management.

The successful application of extrusion-based 3D-printed geopolymer mortars largely depends on precursor chemistry, activator composition, mixture proportions, and fresh-state behavior, which is highly sensitive to time-dependent structural build-up. This review examines the relationships among mix design, geopolymerization chemistry, rheological properties, and printability requirements for 3D-printed geopolymer mortars. Particular emphasis is placed on the effects of precursor type, alkaline activator characteristics, liquid-to-solid ratio, additives, and fibers on flowability, yield stress, viscosity, extrudability, buildability, shape retention, and interlayer bonding. The review further discusses how geopolymerization kinetics influence the evolution of fresh-state properties, the printable time window, and the transition from extrusion to structural stability. In addition, early-age performance is evaluated in terms of setting behavior, green strength development, and layer-interface integrity. Current challenges, including the lack of standardized test methods, limited comparability among published studies, and the complex coupling between material design and process parameters, are also highlighted. Finally, the review identifies key research gaps and proposes future directions for developing robust, printable, and sustainable geopolymer mortar systems for additive manufacturing in construction.

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future.

9718 Background: Epidermal growth factor receptor (EGFR) is a protoncogen that is found overexpressed in colorectal carcinomas (CRC) and it correlates with a worse prognosis. The aim was to describe EGFR overexpression patterns in non-metastatic CRC and to correlate these data with follow-up. Methods: We analyzed a series of 56 CRC. Inclusion criteria were: a) resected primary adenocarcinoma; b) curative surgery; c) pT3 N0–2 M0 without progression during the first 6 months post surgery; d) minimum follow-up over 3 years. EGFR overexpression was analyzed by immunohistochemistry (IHC) using the Dako PharmaDx kit (Glostrup, Denmark). As positive control the Dako slides and a bloc cell of A431-AAM cells were used. Presence of cytoplasmic and membrane patterns (intensity 1(+), 2(+) and 3(+)) were evaluated as well as the percentage of positive cells. Statistical analysis: association between qualitative variables was analyzed by Fisher's exact test. Disease-free and overall survival distributions were estimated by the Kaplan-Meier method and were analyzed with the log rank test. All P values are from two-sided statistical tests. Results: Characteristics of the patients (pts) were as follows: mean age: 68,4 years (range: 28–91); sex: 24 male and 32 female; location: 19 right colon and 37 left colon; follow-up: 44 pts alive without disease (78,5%), 9 died of disease (16,5%) and 3 died of other causes (5%). 10 pts had metastasis in the follow-up. IHC: Forty-two cases were positive (75%) and were classified as follows: 17 with >50% of positive cells (30%), 7 with 25–50% of positive cells (13%) and 18 cases with < 25% of positive cells. Patterns of staining were cytoplasmic predominance in 27 cases (48%) and 15 with membrane predominance (27%): 4 with intensity 1(+), 9 with 2(+) and 2 with 3(+). Only those patients with tumors harboring membrane positivity 2(+) and 3(+) had more probability to present metastasis (p= 0.067). Conclusions: EGFR overexpression evaluated as a membrane pattern with 2(+) and 3(+) intensity is related with metastatic development in colon carcinoma. Suported by a grant of C.I.R. Hospital de Sabadell. Consorci Sanitari Parc Taulí. Sabadell. Spain No significant financial relationships to disclose.

4089 Background: Overexpression of HER2 is an important biomarker in gastroesophageal junction (GEJ) and gastric cancer (GC) and a predictive factor for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit in overall survival of adding trastuzumab to chemotherapy inHER2-positive advanced GEJ/GC patients, following validated scoring criteria by a central laboratory. This study examines the incidence of HER2 positivity (local laboratories) in GEJ/GC according to EMA Herceptin label. Methods: HER-EAGLE was an epidemiological, non–interventional, international study assessing HER2 status by IHC/ISH in tumor samples from any stage GEJ/GC patients. Neutral buffered 10% formalin embedded tissues (surgical excision specimens or minimum 6-8 biopsies) analyzed via validated Ventana and Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+. Overall and subgroup estimates calculated with 95%CI. Data from the Spanish cohort are presented. Results: The Spanish cohort of HER-EAGLE included 1,954 participants (63.7% males) from 33 hospitals (Dec2010 to Aug2011), with 469 biopsies (24.0%) and 1,479 excisions (75.7%). Samples were 13.7% GEJ and 86.3% GC, and the adenocarcinomas were 1,137 intestinal (58.2%), 510 diffused (26.1%), 163 mixed (8.3%; Laureen classification), and 144 not available (7.3%). Median time from sampling to HER2 analysis of 5.1 years (range from days to 12 years). Total of 210 cases tested IHC 3+ (10.7%), 215 IHC 2+ (11.0%), 308 IHC 1+ (15.8%), and 1,221 IHC 0 (62.5%). Overall, HER2 positivity (IHC 3+ or IHC2+/ISH+) was 14.1% (95%CI 12.61 – 15.75). HER2 positivity by histological type was higher in intestinal adenocarcinomas (19.5%) compared to diffused (4.5%) or in mixed (9.2%). Conclusions: HER-EAGLE confirmed the feasibility of community based HER2 testing in GC as the first study with a high number of samples analyzed by local laboratories. The incidence of HER2-positivity (EMA label definition) was similar to the ToGA screening population, and it was again higher in adenocarcinomas of intestinal type (19.5%).

AIMS: To compare the immunohistochemical expression of prognostic markers p27(Kip1), p45(Skp2) and Ki67 in Merkel cell carcinoma (primary neuroendocrine carcinoma of the skin, MCC), small cell neuroendocrine carcinoma of lung and urinary bladder (SNC), and cutaneous squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry was performed using antibodies directed against p27(Kip1), p45(Skp2) and Ki67 on 72 tumour cases: 24 MCC, 25 SCC, and 23 SNC (15 from the lung and eight from the urinary bladder). Percentages of positive cells were determined for each marker and statistically analysed. Expression profiles on MCC and SCC were significantly different for all three markers. MCC and SNC exhibited significant similarities in their p27(Kip1) and p45(Skp2) expression profiles. In contrast, MCC and SNC differed significantly in their Ki67 proliferation indices, which were much higher in SNC. Additionally, MCC cases showed an association between increased proliferation indices and the appearance of local recurrence(s) and/or metastases. CONCLUSION: The immunohistochemical profile of MCC differs from that of SCC, in spite of their common oncogenesis and the supposed metaplastic origin of MCC, and resembles that of SNC, except for Ki67 levels, which were higher in the latter (characterized by greater biological aggressiveness). High levels of Ki67 also appear to be a prognostic factor in MCC.

Fibrous benign proliferations of the testis and paratesticular tissues are an uncommon and heterogeneous group of lesions that can mimic true neoplasms. Among them, those considered to be reactive proliferations have been included in the category of fibrous pseudotumors and are often associated with trauma, hydrocele, or infection. We report 2 cases of nodular and diffuse fibrous proliferation. This condition is part of the spectrum of reactive benign fibrous lesions and has previously been described in the testicular tunics and paratesticular region only. One of our 2 cases had the peculiarity of being located in the penile shaft, whereas the other involved the tunica vaginalis. To the best of our knowledge, this is the first report of a diffuse and nodular fibrous tumor involving the penis.

Idiopathic pylephlebitis and primary sclerosing peritonitis are two highly unusual entities. To our knowledge, the association of the two diseases has not been described previously. We report a 42-year-old patient with a protein S deficiency who presented with fever and chills, in whom idiopathic pylephlebitis was diagnosed. A year later, the patient was readmitted because of recurrent vomiting and weight loss. An exploratory laparotomy yielded diagnosis of sclerosing peritonitis, which resolved after surgery. The short time interval between the processes suggests that they were related to each other, and also to the protein S deficiency.

Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinically observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. We have used the catalytic subunit of human telomerase hTERT and large T to immortalize primary UV-unexposed keratinocytes. Then, mutant HRAS G12V has been introduced to transform these immortal keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics. We observed three major tissue architectures: solid, sarcomatoid and cystic growth types, which were primarily composed of pleomorphic and basaloid cells but in some cases displayed focal apocrine differentiation. We demonstrate that the cells generated represent different stages of skin cancerogenesis and as such can be used to identify novel tumor-promoting alterations such as the overexpression of the PADI2 oncogene in solid-type SCC. Importantly, the cultured cells maintain the characteristics from the xenograft they were derived from while being amenable to manipulation and analysis. The availability of cell lines representing different clinical manifestations opens a new tool to study the stochastic and deterministic factors that cause case-to-case heterogeneity despite departing from the same set of oncogenes and the same genetic background.

Recently, the copper efflux transporters ATP7B and ATP7A have been implicated in the transport of and resistance to platinum drugs in breast and ovarian cancers. Because of the extensive use of oxaliplatin in colorectal cancer (CRC), we examined the expression of both transporters in tumors from CRC patients treated with oxaliplatin/5FU and sought to determine whether their expression can predict clinical outcome in these patients. ATP7B and ATP7A levels were determined by quantitative real-time PCR in 50 primary tumors of previously untreated patients with advanced colorectal adenocarcinoma who were subsequently treated with oxaliplatin/5FU. Additionally, ATP7B protein expression was assessed by immunohistochemical staining using a tissue microarray. Patients with the lowest mRNA expression levels of ATP7B had a significantly longer time to progression (TTP) (p = 0.0009) than patients with the highest levels (12.14 months vs. 6.43 months) who also had an increased risk of progression (HR = 3.56; 95% CI, 1.6-7.9; p = 0.002). Furthermore, patients with low levels of both protein and mRNA of ATP7B derived the maximum benefit from oxaliplatin/5FU with the longest TTP as compared with patients with high levels of ATP7B protein and mRNA (14.64 months vs. 4.63 months, respectively, p = 0.01) and showed a nonsignificant trend toward a lower response rate (37.5% and 75%, respectively). In conclusion, ATP7B mRNA and protein expression in colorectal tumors is associated with clinical outcome to oxaliplatin/5FU. Prospective studies are required to evaluate the role of this marker in tailoring chemotherapy.

Introduction Cdk5 has been related to cancer progression and metastasis and to response to DNA damage in cancer. In colorectal cancer (CRC), our previous results showed that Cdk5 was overexpressed in CRC tumours as compared to normal tissues. CDK5 gene knockdown was associated with decreased migration and invasion of colon cancer cells but has no effect on cell proliferation; this effect was not not observed in cell lines with BRAF or KRAS mutations. In cell lines with acquired resistance to oxaliplatin (OXA) CDK5 knockdown overcame this resistance. The aim of this work was to study the involvement of Cdk5 on migration and invasion according to KRAS status and to investigate the prognostic and predictive value of Cdk5 in representative patients cohorts. Material and methods SW48 (KRAS WT) and the isogenic SW48 KI G12V (KRAS mutant) cell lines were used (Horizon Discovery Ltd). CDK5 gene was silenced with specific siRNA (Ambion, 5 nM) to study its role in migration and invasion using Boyden chamber assays (HTS transwell, Corning). Comparisons between different experimental conditions were carried out using the T test. For clinical studies, we used 342 tumour samples from CRC patients (Non-treated stage II-III frozen n=135; stage IV FFPE=207). Stage IV tumours corresponded to patients treated with schedules containing irinotecan (n=139) or OXA (n=68) without antitarget drugs. Cdk5 expression was analysed by qPCR (Taqman assay) or by immunohistochemistry. Log rank (LR) and cox regression (CR) tests were used to study differences in disease-free (DFS) overall survival (OS) or time to progression (TTP); Chi-square or Fisher’s tests were used to study differences in response rates (ORR). Results and discussions CDK5 gene silencing was associated with decreased cell migration only in SW48 G12V cells (p=0.035). High Cdk5 mRNA levels was a bad prognostic factor in stage II (DFS CR HR=4.15; p=0.022; OS CR HR=8.25, p=0.048) and III (DFS LR 24 months vs. not reached; p=0.048). In stage II, Cdk5 prognostic value was associated with KRAS mutant status (CR p=0.045). In stage IV CRC, Cdk5 positive IHC staining was associated with worse TTP (LR 8 vs. 18 months, p=0.043; CR HR=2.17) and ORR (53% vs. 87%, p=0.029) only in OXA-treated patients. Conclusion These data confirm previous results establishing Cdk5 as a tumor-promoting factor in CRC, especially in a KRAS-mutated environment. Cdk5 immunostaining predicts outcome of stage IV CRC patients treated with OXA. Extensive data will be presented during the EACR meeting.