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IntroductionUnderstanding the mutational landscape of colon cancer (CC) is crucial for targeted therapy development. Microsatellite instability (MSI-H), rat sarcoma (RAS), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations (MT) are pivotal markers. Further investigation into clinicopathological features of RAS and BRAF MT in microsatellite stable (MSS) and MSI-H tumors is warranted.MethodsA retrospective analysis of 4883 localized CC patients (pts.) was conducted. Molecular profiling assessed MSI, KRAS, NRAS, and BRAF MT. Correlation with clinicopathological data employed ANOVA and Chi-square tests. Disease-free survival (DFS) and overall survival (OS) were analyzed adjusting for age, gender, sidedness, UICC stage, Charlson Comorbidity Index (CCI). A Cox model incorporated all variables as covariates.ResultsThis analysis included 4883 pts. (2302 female/2572 male, 3865 (79.2%) MSS, 1018 (20.8%) MSI-H). MSS pts. had more All-Wild Type (WT), KRAS MT, and NRAS MT tumors vs. MSI-H pts. (42.1% vs. 21.1%; 39.8% vs. 15.4%; 3.6% vs. 0.7%; p

Ultra-thin films of low damping ferromagnetic insulators with perpendicular magnetic anisotropy have been identified as critical to advancing spin-based electronics by significantly reducing the threshold for current-induced magnetization switching while enabling new types of hybrid structures or devices. Here, we have developed a new class of ultra-thin spinel structure Li0.5Al1.0Fe1.5O4 (LAFO) films on MgGa2O4 (MGO) substrates with: 1) perpendicular magnetic anisotropy; 2) low magnetic damping and 3) the absence of degraded or magnetic dead layers. These films have been integrated with epitaxial Pt spin source layers to demonstrate record low magnetization switching currents and high spin-orbit torque efficiencies. These LAFO films on MGO thus combine all of the desirable properties of ferromagnetic insulators with perpendicular magnetic anisotropy, opening new possibilities for spin based electronics.

Objective: This expert opinion paper proposes a design for a state-of-the-art magnetic resonance image (MRI) acquisition protocol for knee osteoarthritis clinical trials in early and advanced disease. Semi-quantitative and quantitative imaging endpoints are supported, partly amendable to automated analysis. Several (peri-) articular tissues and pathologies are covered, including synovitis. Method: A PubMed literature search was conducted, with focus on the past 5 years. Further, osteoarthritis imaging experts provided input. Specific MRI sequences, orientations, spatial resolutions and parameter settings were identified to align with study goals. We strived for implementation on standard clinical scanner hardware, with a net acquisition time ≤30 ​min. Results: Short- and long-term longitudinal MRIs should be obtained at ≥1.5T, if possible without hardware changes during the study. We suggest a series of gradient- and spin-echo-sequences, supporting MOAKS, quantitative analysis of cartilage morphology and T2, and non-contrast-enhanced depiction of synovitis. These sequences should be properly aligned and positioned using localizer images. One of the sequences may be repeated in each participant (re-test), optimally at baseline and follow-up, to estimate within-study precision. All images should be checked for quality and protocol-adherence as soon as possible after acquisition. Alternative approaches are suggested that expand on the structural endpoints presented. Conclusions: We aim to bridge the gap between technical MRI acquisition guides and the wealth of imaging literature, proposing a balance between image acquisition efficiency (time), safety, and technical/methodological diversity. This approach may entertain scientific innovation on tissue structure and composition assessment in clinical trials on disease modification of knee osteoarthritis.

IntroductionMinimally invasive mitral valve repair/replacement has emerged as a widely accepted surgical approach for managing mitral valve disorders. Continuous technological progress has contributed to the refinement of this procedure, leading to improved safety, decreased surgical trauma, and faster recovery times. Despite these advancements, there remains a scarcity of data concerning minimally invasive complex mitral valve repair surgeries when combined with additional procedures.MethodsBetween November 2008 and December 2022, 153 patients underwent an operation using a minimally invasive technique. All patients underwent mitral valve surgery for severe mitral valve insufficiency/stenosis in combination with at least one additional procedure for tricuspid valve repair (n = 52, 34%), patent foramen ovale or atrial septal defect closure (n = 34, 22.2%), left atrial appendage occlusion (n = 25, 16.3%), or electrophysiological procedure (n = 101, 66.0%). Two concomitant procedures were conducted in 98 patients (64.1%), three concomitant procedures in 49 patients (32%), and four concomitant procedures in 6 patients (3.9%).ResultsSurgical success was achieved in 99.3% of the patients (n = 152), one patient required a revision of the mitral valve repair on the first postoperative day due to systolic anterior motion phenomenon. Mitral valve repair was performed in 136 patients (88.9%), while 15 patients (9.8%) received a mitral valve replacement as per a preoperative decision due to severe mitral valve stenosis, and two patients (1.3%) underwent other mitral valve procedures. Therapeutic success in treating atrial fibrillation was achieved in 86 patients (85.1%) of the 101 who received an additional maze-procedure. The 30-day mortality rate was 0.7%, with one patient succumbing to respiratory failure. Neurological complications occurred in 7 patients (4.6%). Freedom from reoperation was calculated as 98% at 5-year follow-up and 96.5% at 10-year follow-up.ConclusionMinimally invasive mitral valve surgery, even when performed alongside concomitant procedures, stands out as a reproducible and safe technique with outstanding outcomes. It is imperative to advance towards the next frontier in minimally invasive surgery, encouraging experienced surgeons to undertake more complex procedures using minimally invasive approaches. These results help envision extending the boundaries of minimally invasive surgery by performing complex mitral valve procedures and associated interventions entirely through endoscopic means in suitable patients.

ABSTRACT: The state of Santa Catarina is the largest national producer of onions. The consumption of onion (Allium cepa) by domestic animals can cause hemolytic anemia and hyperhemoglobinemia of Heinz bodies in erythrocytes. The epidemiological data and the pathological clinical picture were obtained during a visit to the property where the disease occurred. A herd of 54 beef cattle from a property in the municipality of Bom Retiro/SC, was placed in an onion crop, which had not been completely harvested because it was outside the desired standard for trade. The animals remained in this field for eight days. At the end of this period, all of them presented apathy, anorexia, brown urine and mucous membranes and an onion odor on expiration. The macroscopic changes observed were pale mucous membranes, blood with decreased viscosity and increased clotting time, liver with an evident lobular pattern and remains of onion in the rumen. The carcass gave off a strong onion odor. By histological analysis, there was central lobular coagulation necrosis in bridging in the liver. In the kidneys, there were intracytoplasmic hyaline droplets in tubular epithelial cells and a deposit of eosinophilic material in the lumen of the tubules. For the diagnosis of onion poisoning, epidemiological data associated with clinical signs, such as pale mucous membranes with evidence of hemoglobin pigmentation (brown mucosa) and hemoglobinuria, should be taken into account. This article seems to be the first report of onion poisoning in cattle in Brazil.

Abstract Background The DNA damage response (DDR) is a physiological network preventing malignant transformation, e.g. by halting cell cycle progression upon DNA damage detection and promoting DNA repair. Glioblastoma are incurable primary tumors of the nervous system and DDR dysregulation contributes to acquired treatment resistance. Therefore, DDR targeting is a promising therapeutic anti-glioma strategy. Here, we investigated Ataxia telangiectasia and Rad3 related (ATR) inhibition (ATRi) and functionally-instructed combination therapies involving ATRi in experimental glioma. Methods We used acute cytotoxicity to identify treatment efficacy as well as RNAseq and DigiWest protein profiling to characterize ATRi-induced modulations within the molecular network in glioma cells. Genome-wide CRISPR/Cas9 functional genomic screens and subsequent validation with functionally-instructed compounds and selected shRNA-based silencing were employed to discover and investigate molecular targets modifying response to ATRi in glioma cell lines in vitro, in primary cultures ex vivo and in zebrafish and murine models in vivo. Results ATRi monotherapy displays anti-glioma efficacy in vitro and ex vivo and modulates the molecular network. We discovered molecular targets by genome-wide CRISPR/Cas9 loss-of-function and activation screens that enhance therapeutic ATRi effects. We validated selected druggable targets by a customized drug library and functional assays in vitro, ex vivo and in vivo. Conclusion In conclusion, our study leads to the identification of novel combination therapies involving ATRi that could inform future preclinical studies and early phase clinical trials.

Abstract Ultra-thin films of low damping ferromagnetic insulators with perpendicular magnetic anisotropy have been identified as critical to advancing spin-based electronics by significantly reducing the threshold for current-induced magnetization switching while enabling new types of hybrid structures or devices. Here, we have developed a new class of ultra-thin spinel structure Li0.5Al1.0Fe1.5O4 (LAFO) films on MgGa2O4 (MGO) substrates with: 1) perpendicular magnetic anisotropy; 2) low magnetic damping and 3) the absence of degraded or magnetic dead layers. These films have been integrated with epitaxial Pt spin source layers to demonstrate record low magnetization switching currents and high spin-orbit torque efficiencies. These LAFO films on MGO thus combine all of the desirable properties of ferromagnetic insulators with perpendicular magnetic anisotropy, opening new possibilities for spin based electronics.

The magnetic states of antiferromagnetic insulating thin films are a promising medium for information storage, but characterization of these states has proven to be challenging. One approach is via magnetotransport measurements in an adjacent heavy metal layer. To this end, we synthesized and characterized a series of Cr2O3 films and bilayers on Al2O3 substrates with three different orientations: m-plane, a-plane, and c-plane. X-ray diffraction results demonstrated orientation control of the Cr2O3 thin film, with m-plane films displaying a higher degree of mosaic spread than the a- and c-plane films. Reciprocal space maps showed that the films are mostly relaxed, although there was a small and different degree of strain in each orientation. The m-plane films were under 2% compressive strain, the a-plane film was under 0.5% compressive strain, and the c-plane film was completely relaxed to bulk values. To probe the magnetic state of the films, we measured the angular dependent magnetoresistance of Cr2O3/Pt bilayers for each orientation. We found a nontrivial temperature dependence of the sign of the magnetoresistance, pointing to the complex interplay between the exchange and anisotropy energies that vary with orientation. We propose that strain and mosaic spread may contribute to a difference in magnetic anisotropies among the samples and the resulting temperature dependence of the magnetoresistance. This work demonstrates the importance of considering the competition between antiferromagnetic exchange and magnetic anisotropy when storing information in the spin state of an antiferromagnetic insulator.

The heterogenization of molecular catalysts within a porous solid acting as macroligand can advantageously open access to enhanced stability and productivity, and thus to more sustainable catalytic process. Herein, a porous organic polymer (POP) made through metal‐free polymerization using bipyridine repeating units is reported. This N‐rich POP is an efficient macroligand for the heterogenization of molecular rhodium complexes. The intrinsic catalytic activity of the heterogenized catalyst is slightly higher than that of its homogeneous molecular counterpart for formic acid production as a unique carbon‐containing product. The heterogenization of the rhodium catalysts enables recycling for a total productivity of up to 8.3 g of formic acid per gram of catalyst after 7 reuses using visible light as the sole energy source.

Objective: Endothelin receptor B (ETB) together with ETA mediates cellular effects of endothelin 1 (ET-1), an autocrine and endocrine peptide produced by the endothelium and other cells. It regulates vascular tone and controls kidney function. Metabolic syndrome is due to high caloric intake and is characterized by insulin resistance, dyslipidemia, and white adipose tissue (WAT) accumulation. ETA/ETB antagonism has been demonstrated to favorably influence insulin resistance. Our study explored the role of ETB in metabolic syndrome. Methods: Wild type (etb+/+) and rescued ETB-deficient (etb−/−) mice were fed a high-fat diet, and energy, glucose, and insulin metabolism were analyzed, and hormones and lipids measured in serum and tissues. Cell culture experiments were performed in HepG2 cells. Results: Compared to etb+/+ mice, etb−/− mice exhibited better glucose tolerance and insulin sensitivity, less WAT accumulation, lower serum triglycerides, and higher energy expenditure. Protection from metabolic syndrome was paralleled by higher hepatic production of fibroblast growth factor 21 (FGF21) and higher serum levels of free thyroxine (fT4), stimulators of energy expenditure. Conclusions: ETB deficiency confers protection from metabolic syndrome by counteracting glucose intolerance, dyslipidemia, and WAT accumulation due to enhanced energy expenditure, effects at least in part dependent on enhanced production of thyroid hormone/FGF21. ETB antagonism may therefore be a novel therapeutic approach in metabolic syndrome.

Abstract Objectives This report provides information about the public release of the 2018–2019 Maize G X E project of the Genomes to Fields (G2F) Initiative datasets. G2F is an umbrella initiative that evaluates maize hybrids and inbred lines across multiple environments and makes available phenotypic, genotypic, environmental, and metadata information. The initiative understands the necessity to characterize and deploy public sources of genetic diversity to face the challenges for more sustainable agriculture in the context of variable environmental conditions. Data description Datasets include phenotypic, climatic, and soil measurements, metadata information, and inbred genotypic information for each combination of location and year. Collaborators in the G2F initiative collected data for each location and year; members of the group responsible for coordination and data processing combined all the collected information and removed obvious erroneous data. The collaborators received the data before the DOI release to verify and declare that the data generated in their own locations was accurate. ReadMe and description files are available for each dataset. Previous years of evaluation are already publicly available, with common hybrids present to connect across all locations and years evaluated since this project’s inception.

We have investigated magnesium aluminum ferrite thin films with a range of iron concentrations and identified the optimal iron content to obtain high crystalline quality thin films with the low magnetic damping required for spin current-based applications. Epitaxial MgAl 2-x FexO4 films with 0.8 < x < 2.0 were grown by pulsed laser deposition on single crystal MgAl2O4 substrates and were characterized structurally and magnetically. We find that the x = 1.5 composition minimizes the room-temperature magnetic damping with a typical Gilbert damping parameter of α eff = 1.8 × 10-3. This minimized damping is governed by a competition between the more robust magnetic ordering with increased iron content, x, and the more defective structure due to larger film-substrate lattice mismatch with increased iron content. The temperature-dependent magnetization curves indicate that Tc is suppressed below room temperature for iron content x ≤ 1.2 and eventually suppressed entirely for x = 0.8. X-ray magnetic circular dichroism results indicate that for all x the magnetic moment is dominated by Fe 3 + cations distributed in a 60:40 ratio on the octahedral and tetrahedral sites, with minimal contribution from Fe 2 + cations. Films with x = 1.4-1.6 exhibit very strong ferromagnetic resonance and low Gilbert damping with α eff = (1.8-6) × 10-3, making them ideal candidates for microwave and spintronic applications.

Abstract Patients with severe asymptomatic primary mitral regurgitation (MR) can be safely managed with an active surveillance strategy. Left atrial (LA) size is affected by MR severity, left ventricular function and is also associated with the risk of atrial fibrillation and may be an integrative parameter for risk stratification. The present study sought to determine the predictive value of LA size in a large series of asymptomatic patients with severe MR. 280 consecutive patients (88 female, median age 58 years) with severe primary MR and no guideline-based indications for surgery were included in a follow-up program until criteria for mitral surgery were reached. Event-free survival was determined and potential predictors of outcome were assessed. Survival free of any indication for surgery was 78% at 2 years, 52% at 6 years, 35% at 10 years and 19% at 15 years, respectively. Left atrial (LA) diameter was the strongest independent echocardiographic predictor of event-free survival with incremental predictive value for the thresholds of 50, 60 and 70 mm, respectively. In a multivariable analysis that encompassed age at baseline, previous history of atrial fibrillation, left ventricular end systolic diameter), LA diameter, sPAP > 50 mmHg and year of inclusion, LA diameter was the strongest independent echocardiographic predictor of event-free survival (adjusted HR = 1.039, p

Abstract Background Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions. Methods We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS. Results After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62–0.79) in the left lung vs 0.14 (IQR 0.14–0.16; p

Abstract Background The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period. Methods MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition. Results Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee). Conclusions A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. Trial Registration Clinicaltrials.gov identification: NCT03883568.

High-quality epitaxial ferrites, such as low-damping MgAl-ferrite (MAFO), are promising nanoscale building blocks for all-oxide heterostructures driven by pure spin current. However, the impact of oxide interfaces on spin dynamics in such heterostructures remains an open question. Here, we investigate the spin dynamics and chemical and magnetic depth profiles of 15-nm-thick MAFO coherently interfaced with an isostructural 1-8-nm-thick overlayer of paramagnetic CoCr2O4 (CCO) as an all-oxide model system. Compared to MAFO without an overlayer, effective Gilbert damping in MAFO/CCO is enhanced by a factor of >3, irrespective of the CCO overlayer thickness. We attribute this damping enhancement to spin scattering at the approximately 1-nm-thick chemically disordered layer at the MAFO-CCO interface, rather than spin pumping or proximity-induced magnetism. Our results indicate that damping in ferrite-based heterostructures is strongly influenced by interfacial chemical disorder, even if the thickness of the disordered layer is a small fraction of the ferrite thickness.

Electron microscopy has been instrumental in our understanding of complex biological systems. Although electron microscopy reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An electron-microscopy-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we synthesize small lanthanide-doped nanoparticles and measure the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nanolabels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colours, so the imaging of biomolecules in a multicolour electron microscopy modality may be possible.

Abstract Atomic layer deposition in solution (sALD) is just emerging as a technology for the preparation of thin films. Unlike ALD from the gas phase, it allows for mild reaction conditions in a solvent phase and at room temperature, thus decreasing the energy requirements of the process and widening the range of accessible precursor molecules. In this work, the deposition of thin films of titania on silica is investigated using titanium(IV) isopropoxide (TTIP) and water as precursors, which are alternatingly brought into contact with the support in a home‐built plug flow reactor. The mechanism of covalent grafting of the precursor to the surface, subsequent hydrolysis, and reaction to a layer of titania are investigated in detail using magic angle spinning (MAS) solid‐state nuclear magnetic resonance (NMR) spectroscopy. TTIP preferentially reacts with Q2 groups of condensed silica. 2D solid‐state NMR spectra allow to clearly show the successful grafting of this compound to the support by the appearance of a characteristic signal at −107 ppm, which is tentatively attributed to silicon nuclei in a SiOTi bond, and to reveal the presence of titanol groups on the emerging TiO2 film.

Phenomic and genomic approaches are required to evaluate the progress of breeding strategies. Here, the authors analyse 65 years of genetic progress in maize, showing that breeders have selected traits with stable effects on yield whereas not for adaptive traits key for climate change adaptation.

Abstract We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro‐oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein–Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI‐high (MSI‐H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p

Introduction: Understanding the mutational landscape of colon cancer (CC) is crucial for targeted therapy development. Microsatellite instability (MSI-H), rat sarcoma (RAS), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations (MT) are pivotal markers. Further investigation into clinicopathological features of RAS and BRAF MT in microsatellite stable (MSS) and MSI-H tumors is warranted. Methods: A retrospective analysis of 4883 localized CC patients (pts.) was conducted. Molecular profiling assessed MSI, KRAS, NRAS, and BRAF MT. Correlation with clinicopathological data employed ANOVA and Chi-square tests. Disease-free survival (DFS) and overall survival (OS) were analyzed adjusting for age, gender, sidedness, UICC stage, Charlson Comorbidity Index (CCI). A Cox model incorporated all variables as covariates. Results: This analysis included 4883 pts. (2302 female/2572 male, 3865 (79.2%) MSS, 1018 (20.8%) MSI-H). MSS pts. had more All-Wild Type (WT), KRAS MT, and NRAS MT tumors vs. MSI-H pts. (42.1% vs. 21.1%; 39.8% vs. 15.4%; 3.6% vs. 0.7%; p<0.001 for each). BRAF MT tumors (95.5% BRAF V600E MT) were more prevalent in MSI-H individuals (62.8% vs. 8.1%, p<0.001). KRAS and BRAF MT tumors were more frequently right-sided, while BRAF MT tumors were associated with female gender, advanced disease stage, lymph node positivity, and poorer differentiation in the MSS subset (p<0.001). Common KRAS mutations included p.G12D (30.44%) and p.G12V (21.3%) in MSS and p.G13D (28.9%) and p.G12D (22.37%) in MSI-H. NRAS MT tumors were dominated by codon 61 mutations (51.7%). Survival analysis revealed worst prognosis in BRAF MT MSS tumors (DFS: HR 1.74 (95% CI 1.15-2.62, p=0.009; OS: HR 1.61 (95% CI 0.99-2.6), p=0.055). The 3-years DFS and 5-years OS rates were lowest in this subset (61.6% and 57.7% respectively). Discussion: These findings highlight the complex interplay between molecular subtypes, clinicopathological features, and survival outcomes in early CC. Further research is needed to elucidate underlying mechanisms and develop personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Critical thinking (CT) is an essential set of skills and dispositions for professionals. While viewed as an important part of professional education, approaches to teaching and assessing critical thinking have been siloed within disciplines and there are limited data on whether student perceptions of learning align with faculty perceptions of teaching. Materials and methods: The authors used a convergent mixed methods approach in required core courses in schools of education, government, and medicine at one university in the Northeast United States. Faculty surveys and student focus groups (FG) addressed definitions, strategies, and barriers to teaching CT. Results and conclusions: Sixty-four (51.6%) faculty completed the survey, and 34 students participated in FGs. Among faculty, 54.0% (34/63) reported explicitly teaching CT; but students suggested teaching CT was predominantly implicit. Faculty-reported strategies differed among schools. Faculty defined CT in process terms such as 'analyzing'; students defined CT in terms of viewpoints and biases. Our results reveal a lack of explicit, shared CT mental models between faculty and students and across professional schools. Explicit teaching of CT may help develop a shared language and lead to better understanding and application of the skills and dispositions necessary to succeed in professional life. [ABSTRACT FROM AUTHOR]