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Recent trials provide evidence that HER2 is a potential new target for patients with colorectal cancer. While HER2-positive tumors do not show a very encouraging response to anti-HER2-positive agents like trastuzumab alone, promising results have been observed when combined with other synergistically acting tyrosine kinase inhibitors (TKIs). Our meta-analysis was conducted following the Cochrane Handbook and written following the PRISMA guidelines. The protocol was registered on PROSPERO with the registration number CRD42022338935. After a comprehensive search for relevant articles, 14 CTs were identified and uploaded to Rayyan, and six trials were ultimately selected for inclusion. The meta-analysis revealed that a median of three prior lines of therapy was used before enrolling in the six trials comprising 238 patients with HER2-positive metastatic colorectal cancer (mCRC). The pooled objective response rate (ORR) and disease control rate (DCR) were 31.33% (95% confidence interval [CI] 24.27-38.39) and 74.37% (95% CI 64.57-84.17), respectively. The pooled weighted progression-free survival (PFS) was 6.2 months. The pooled ORR and DCR meta-analysis indicate a significant response to HER2-targeted therapy in this patient in HER2-positive mCRC. Additionally, a pooled PFS of 6.2 months suggests that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes in this population.

It has been recently reported that immune activity of some animal peptides/proteins has been found in some plants. In this study, the presence of immune reactivity of alarin, asprosin, paraoxonase, elabela, glucagon, and nesfatin-1 like molecules was investigated in two plant species related to Kastamonu Taşköprü garlic (an endemic cultivar of the Allium sativum L.) and Tunceli garlic (Allium tuncelianum).

As there are limited studies examining relationships between argumentation-based teaching approach and critical thinking and argumentation skills in social studies, the aim of this study was to examine the effects of argumentation-based teaching approach on students' critical thinking disposition and argumentation skills, and the relationship between students' argumentation skills and critical thinking disposition. We used a quasi-experimental design with pretest-posttest equivalent control groups. The participants of this study were 94 seventh grade students from three different classrooms in a middle school in Erzurum district of Turkey. We utilized University of Florida Engagement, Maturity and Innovativeness Critical Thinking Disposition Instrument (UF/EMICTDI) to identify students' critical thinking disposition and argumentation activities to document students' argumentation skills. We used one-way ANOVA and multiple comparisons Tukey tests to analyze the data obtained via the UF/EMICTDI, correlation and regression analysis to investigate the relationships between students' argumentation skills and critical thinking disposition. Argumentation Evaluation Rubric was used in order to evaluate the arguments that the students formed. Results showed that there was no statistically significant difference between students' pretest critical thinking disposition scores in the experimental and control groups but there was a statistically significant difference between students' post-test critical thinking disposition scores. Additionally, we observed that students' argumentation skills enhanced throughout the study, there was a statistically significant positive relationship between students' argumentation skills and critical thinking disposition, and argumentation skills variable was the predictor of critical thinking disposition. We recommend future research studies to examine the effects of the argumentation-based science learning approach on different higher-order thinking skills. Additionally, in social studies classes, similar activities employed in this study on "Population in Our Country" unit can be used in teaching different topics/units in order to improve students' argumentation skills.

The aim of this study is to investigate the effects of using multiple writing-to-learn activities on the critical thinking skills and dispositions of prospective teachers. For this purpose, the current study employed an embedded mixed-methods design and was carried out with 34 prospective Social Studies teachers who are studying at a public university. Research data were collected with the California Critical Thinking Disposition Inventory, as well as using the Holistic Critical Thinking Scoring Rubric, and also, semi-structured interview forms. In the research process, a variety of writing activities such as letters, diaries, columns and news articles were used for learning purposes. The quantitative data obtained in the research were analyzed descriptively and predictively, while the qualitative data were subjected to content analysis. The results of the study revealed that the writing-to learn activities led the prospective Social Studies teachers to do research, use evidence, get to know different ideas, and evaluate what they learned in a holistic way. Such a situation made a significant difference on the critical thinking skills and critical thinking dispositions of the prospective Social Studies teachers. Given such a result, it is recommended to draw upon writing-to-learn activities in order to develop different courses, subjects and higher-order thinking skills.

The purpose of this study was to investigate the effects of the argumentation-based science learning approach on students' academic achievements and examine student views about use of this approach in social studies. We used a mixed methods research design to document changes as a result of an argumentation-based science learning approach implementation. The participants were 94 seventh grade students from three different classrooms of a middle school in Erzurum, Turkey. We developed the Population in our Country Academic Achievement Test to collect quantitative data before and after the implementation, and used a semi-structured interview form to collect quantitative data after the implementation. Using descriptive, one-way ANOVA, and multiple comparison Tukey test statistical data analysis methods, we analyzed the quantitative data. Then, we used content analysis method to analyze the qualitative data. Results of the quantitative data analysis showed that there was no statistically significant difference between academic achievements mean scores of the students in the experimental and control groups in the pre-test. However, after the implementation, there were statistically significant differences between groups indicating that academic achievement mean scores of students in the experimental group was statistically higher than those students in the control groups in the post-test. Results of the qualitative data analysis indicated the argumentation-based science learning approach activities helped students understand subjects better, facilitated their learning, provided permanent learning opportunities, increased their interest and attitudes towards the course, and enhanced their success in social studies. These results suggested that implementing the argumentation-based science learning approach in social studies was effective in enhancing students' academic achievement and resulted in developing positive views of students about the approach.

KRAS mutations are common driver oncogenes associated with the development of several solid tumors. KRAS oncogene has been considered a highly challenging target for drug development because of structural features, including the lack of deep groove on its catalytic unit. However, by leveraging cysteine residues, covalent KRAS inhibitors irreversibly trap KRAS G12C mutants in their inactive GDP-bound state. These agents have resulted in significant clinical responses among patients with KRAS G12C-mutant solid tumors, including patients with colorectal cancer (CRC). Other allele-specific inhibitors of KRAS oncogene and panKRAS and panRAS inhibitors are also currently being investigated in clinical trials. This review article overviews recent clinical progress on KRAS G12C targeting for the management of patients with KRAS G12C-mutant CRC and provides an update on other RAS targeting approaches. We also discuss the unique biological features of RAS-mutant CRC, which require the combination of KRAS inhibitors and anti-epidermal growth factor receptor therapy, and elaborate on resistance mechanisms and novel therapeutic avenues that may define future treatment paradigms of patients with RAS-mutant CRC. KRAS oncogene is now actionable: A review of the literature and future therapeutic opportunities. [ABSTRACT FROM AUTHOR]

COVID-19 is the most devastating pandemic situation we have experienced in our age, affecting all systems. Although it affects all systems, it shows its most important effect through thrombophilia. Therefore, the possible cause of sudden death due to COVID-19 may be embolism caused by thrombophilia. D-dimer amounts increase due to COVID-19. The thrombosis is associated with sudden death in COVID-19 disease in populations. Since individuals with thrombophilia will be more prone to death due to COVID-19, it may be appropriate to administer low doses of Clexane (Enoxaparin sodium) or low-weight heparin for prophylactic purposes in order to consider these individuals at high risk and to prevent deaths. Moreover, in order not to risk the lives of healthcare professionals with thrombophilia, it would be appropriate to keep them away from individuals with COVID-19 disease and to employ them in different healthcare services according to their fields of expertise. It should also not be forgotten that different symptoms related to COVID-19 appear day by day, these different symptoms probably show that the virus has undergone mutations in order to survive, but no matter what, its effect on thrombophilia has not been eliminated yet. This compilation aims to present the reasons and causes of death due to COVID-19, possible treatment options, and thrombophilia panel tests and new parameters that may have a place in the meticulous interpretation of these tests and possible etiopathology in the light of current information. Therefore, presenting this information in a rational manner and keeping the parameters of the thrombophilia panel under strict control predict that the deaths due to the virus will be partially reduced.

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed “screening and diagnostic” algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alphalipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/ predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN. [ABSTRACT FROM AUTHOR]

Background: Apelin (APLN), elabela (ELA), and nitric oxide (NO) have effects on physiological and behavioural properties in biological systems. This study was designed to determine APLN, ELA and NO levels in schizophrenia patients and assess whether these molecules are of diagnostic value. Methods: A total of 33 schizophrenic patients and 32 ageand sex-adjusted healthy participants were included in the study. ELA, APLN and NO levels were measured using ELISA methods. Results: Although the ELA and NO levels of the patients were lower than the control group, APLN levels were higher (p = 0.039, p = 0.019, p = 0.048, respectively). There was a significant negative correlation between APLN levels and triglyceride (TG) and body mass index (BMI) levels (r = -0.426, p = < 0.001 and r = -0.330, p = 0.007, respectively). Respectively, the areas under the receiver-operating characteristic (ROC) curves of the ELA/APLN, ELA/NO and APLN/NO ratios were 0.628, 0.590 and 0.709, 95% confident intervals (CI): 0.491-0.764, 0.450-0.730 and 0.579-0.840. Conclusions: Decreased levels of ELA and NO and increased APLN levels in schizophrenia suggest that these molecules may be involved in its etiopathology. The APLN/NO ratio also seems to show promise in the diagnosis of the disease and may be used in future.