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Students often struggle with interpreting traditional textbook images and translating them to anatomical structures. This study aimed to compare the impact of 3D scans versus 2D images on students’ learning outcomes when learning anatomical structures on skulls from horses and pigs. Furthermore, the correlation between spatial ability and learning outcomes using 3D scans or 2D images was examined. Second-year veterinary medicine students either used 3D scans or 2D images, annotated with arrows or numbers as learning material. Students’ anatomical knowledge was tested before and after the learning session, and spatial ability was assessed using the mental rotation test. All groups improved significantly in the post-test. However, the differences between groups were not significant, suggesting that 3D scans do not necessarily lead to higher learning outcomes. The analysis of the correlation between spatial ability and learning outcomes did not prove that students with weaker spatial ability benefit from 3D scans. Students preferred 3D scans over 2D images despite similar outcomes, suggesting they are valuable for learning. However, results show that the introduction of novel learning materials likely amplified the impact of reduced learning time on the 3D group, as these materials necessitated additional time for effective comprehension and integration.

Objective: Preclinical studies have emphasized the potential connection between BRCA specific domains defects and the activity of Poly ADP-ribose polymerase inhibitors (PARPi). Nevertheless, real-world evidence regarding the impact of BRCA domain defects and mutations on PARPi efficacy are limited. The aim of his study was to evaluate the efficacy of PARPi in terms of progression free survival (PFS) according to BRCA domains defects and mutation types. Methods: A retrospective analysis was performed among 79 BRCA mutated patients, diagnosed with advanced High-grade serous ovarian carcinoma (HGSOC) who received first- and second-line platinum-based chemotherapy followed by PARPi maintenance treatment. PFS was evaluated according to BRCA1 [Really Interesting Gene (RING), DNA Binding (DBD), Serine Cluster (SCD), BRCA1 C-terminal (BRCT)] and BRCA2 [RAD-51 Domain (RAD-51 BD), DBD] specific domain defects and mutation types [missense (MS), nonsense (NS), frameshift (FS), splicing (S), or large rearrangements (LR)]. Results: After a median follow-up of 51 months, no significant difference in PFS was observed between the BRCA functional domains or mutation types in the BRCA1 and BRCA2 subgroups. Patients with BRCA2 DBD and RAD51-BD defects had the longest (39.8 months) and shortest (24.1months) median PFS, respectively (p = 0.11). Additionally, patients with BRCA1 DBD defects had the greatest benefit (median PFS = 33.8 months) while those with BRCA1 RING domain mutations experienced the worst outcome (median PFS = 30.9 months (p = 0.43). Conclusion: The efficacy of maintenance treatment with PARPi is independent by BRCA domain defects or mutation types. Patients DBD domain defects experienced numerically longer median PFS compared to those with other BRCA1/2 alterations. [ABSTRACT FROM AUTHOR]

The REarranged during Transfection (RET) receptor tyrosine kinase plays a crucial role in the development of various anatomical structures during embryogenesis and it is involved in many physiological cellular processes. This protein is also associated with the initiation of various cancer types, such as thyroid cancer, non-small cell lung cancer, and multiple endocrine neoplasms. In breast cancer, and especially in the estrogen receptor-positive (ER+) subtype, the activity of RET is of notable importance. Indeed, RET seems to be involved in tumor progression, resistance to therapies, and cellular proliferation. Nevertheless, the ways RET alterations could impact the prognosis of breast cancer and its response to treatment remain only partially elucidated. Several inhibitors of RET kinase have been developed thus far, with various degrees of selectivity toward RET inhibition. These molecules showed notable efficacy in the treatment of RET-driven tumors, including some breast cancer cases. Despite these encouraging results, further investigation is needed to fully understand the potential role RET inhibition in breast cancer. This review aims to recapitulate the existing evidence about the role of RET oncogene in breast cancer, from its pathogenic and potentially prognostic role, to the clinical applications of RET inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: 3D models are increasingly popular in veterinary teaching. However, students struggle with transferring 2D textbook images to 3D anatomical structures. Therefore, this study aimed to compare the learning outcome of 3D scans and 2D images of horse and pig skulls. Furthermore, the relationship between spatial ability and learning outcome was analyzed when using the different learning materials. Second-year veterinary medicine students participated in a practical anatomy course using 3D scans or 2D images as learning material and performed a test to determine their spatial ability. Independently of the learning material, all groups displayed high learning outcomes with no significant differences between the groups. In addition, it could not be stated that 3D scans support students with lower spatial ability. Nevertheless, students preferred 3D scans, finding them more motivating, although they did not necessarily improve learning outcomes. Students often struggle with interpreting traditional textbook images and translating them to anatomical structures. This study aimed to compare the impact of 3D scans versus 2D images on students' learning outcomes when learning anatomical structures on skulls from horses and pigs. Furthermore, the correlation between spatial ability and learning outcomes using 3D scans or 2D images was examined. Second-year veterinary medicine students either used 3D scans or 2D images, annotated with arrows or numbers as learning material. Students' anatomical knowledge was tested before and after the learning session, and spatial ability was assessed using the mental rotation test. All groups improved significantly in the post-test. However, the differences between groups were not significant, suggesting that 3D scans do not necessarily lead to higher learning outcomes. The analysis of the correlation between spatial ability and learning outcomes did not prove that students with weaker spatial ability benefit from 3D scans. Students preferred 3D scans over 2D images despite similar outcomes, suggesting they are valuable for learning. However, results show that the introduction of novel learning materials likely amplified the impact of reduced learning time on the 3D group, as these materials necessitated additional time for effective comprehension and integration. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is an angio‐proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS‐CoV‐2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non‐latent viral infections. We report a case series of KS characterized by tumor progression after SARS‐CoV‐2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS‐CoV‐2," "HHV‐8," "Kaposi's sarcoma," "IL‐6," and "COVID‐19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID‐19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS‐CoV‐2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS‐CoV‐2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS. [ABSTRACT FROM AUTHOR]

Thymic epithelial tumors are rare malignancies with an incidence of 1.7 cases per million people per year. They pose significant management challenges due to their association with autoimmune disorders. In this case report, we present the 21-year history of a patient diagnosed with advanced B2/B3 thymoma and Good's syndrome. The patient achieved a complete and durable response after receiving only two cycles of the immune checkpoint inhibitor Nivolumab. However, this positive outcome was accompanied by the development of severe immune-related myocarditis complicated by reactivation of cytomegalovirus. Moreover, the patient developed a highly uncommon subdiaphragmatic pararectal dissemination of the thymic tumor, which is a condition rarely described in the literature. Despite the success in achieving complete and durable response with immune checkpoint inhibitors, the emergence of immune-related adverse events highlights the potential challenges associated with these treatments, emphasizing the need for careful monitoring and a comprehensive understanding of the intricate interplay between cancer, immune system dysregulations and immunotherapy. [ABSTRACT FROM AUTHOR]

Thymic epithelial tumors (TET) patients are at high risk of autoimmune and hypoimmune complications. Limited evidence is available on the potential risk of immune-related and inflammatory reactions induced by SARS-Cov-2 vaccine in this patient population. In order to identify subjects at higher risk for vaccine complications, we prospectively evaluated a panel of serum biomarkers related to inflammation (TNF-α, IL-1β, −6, −10, −12, and −17A, IFN-α, β and γ, MPO, MMP-9), and vascular damage (E- and P-selectin, VEGF-A, P-ANCA and MCP-1) in 44 TET patients and in 30 healthy controls along the whole SARS-Cov-2 vaccine cycle. About 50 % of subjects (either TET and controls) showed an increase of serum biochemical markers of inflammation and endothelial damage with a large heterogeneity of values. Such increase appeared early, after the first dose in control subjects and later, after the second dose in TET patients (in which we observed mainly an increase of inflammatory biomarkers). The values normalized after about 3 months and did not increase after the third, booster dose. No autoimmune or vascular complications were observed in the study subjects and no difference was observed in terms of vaccine response among subjects showing serum biomarkers increase and those who experienced no changes. Our data highlight the relevance of Sars-Cov-2 vaccine in TET patients, as it resulted safe and prevented severe COVID-19. However, further studies are awaited to explore the mechanisms and the potential consequences of the observed increase of serum inflammatory and vascular damage biomarkers. [ABSTRACT FROM AUTHOR]

UnlabelledThe transcription factor AP-1 is downstream of growth factor (GF) receptors (GFRs) and stress-related kinases, both of which are implicated in breast cancer endocrine resistance. Previously, we have suggested that acquired endocrine resistance is associated with increased activity of AP-1 in an in vivo model. In this report, we provide direct evidence for the role of AP-1 in endocrine resistance. First, significant overlap was found between genes modulated in tamoxifen resistance and a gene signature associated with GF-induced estrogen receptor (ER) cistrome. Interestingly, these overlapping genes were enriched for key signaling components of GFRs and stress-related kinases and had AP-1 motifs in their promoters/enhancers. Second, to determine a more definitive role of AP-1 in endocrine resistance, AP-1 was inhibited using an inducible dominant-negative (DN) cJun expressed in MCF7 breast cancer cells in vitro and in vivo AP-1 blockade enhanced the antiproliferative effect of endocrine treatments in vitro, accelerated xenograft tumor response to tamoxifen and estrogen deprivation in vivo, promoted complete regression of tumors, and delayed the onset of tamoxifen resistance. Induction of DN-cJun after the development of tamoxifen resistance resulted in dramatic tumor shrinkage, accompanied by reduced proliferation and increased apoptosis. These data suggest that AP-1 is a key determinant of endocrine resistance by mediating a global shift in the ER transcriptional program.ImplicationsAP-1 represents a viable therapeutic target to overcome endocrine resistance. Mol Cancer Res; 14(5); 470-81. ©2016 AACR.

IntroductionIn vitro assays of angiogenesis face immense problems considering their reproducibility based on the inhomogeneous characters of endothelial cells (ECs). It is necessary to detect influencing factors, which affect the angiogenic potency of ECs.ObjectiveThis study aimed to analyse expression profiles of vimentin (VIM), triosephosphate isomerase (TPI) and adenosylmethionine synthetase isoform type-2 (MAT2A) during the whole angiogenic cascade in vitro. Furthermore, the impact of knocking down vimentin (VIM) on angiogenesis in vitro was evaluated, while monitoring TPI and MAT2A expression.MethodsA long-term cultivation and angiogenic stimulation of human dermal microvascular ECs was performed. Cells were characterized via VEGFR-1 and VEGFR-2 expression and a shRNA-mediated knockdown of VIM was performed. The process of angiogenesis in vitro was quantified via morphological staging and mRNA-and protein-levels of all proteins were analysed.ResultsWhile native cells ran through the angiogenic cascade chronologically, knockdown cells only entered beginning stages of angiogenesis and died eventually. Cell cultures showing a higher VEGFR-1 expression survived exclusively and displayed an upregulation of MAT2A and TPI expression. Native cells highly expressed VIM in early stages, MAT2A mainly in the beginning and TPI during the course of angiogenesis in vitro.ConclusionVIM knockdown led to a deceleration of angiogenesis in vitro and knockdown cells displayed expressional changes in TPI and MAT2A. Cell populations with a higher number of stalk cells emerged as being more stable against manipulations and native expression profiles provided an indication of VIM and MAT2A being relevant predominantly in beginning stages and TPI during the whole angiogenic cascade in vitro.

At the start of the COVID-pandemic in March 2020, the Institutes of Veterinary Anatomy of the five German educational institutions were confronted with the challenge of digitalising all lectures for the second and fourth semesters of veterinary students. After an online kick-off event and a preliminary status quo meeting, available digital teaching material was exchanged for students to stream from learning platforms. Lectures were either synchronized or made available as audio recordings and connotated slides on the learning platforms. Fortunately, digital microscopic slides had already been in use, which made it easy for students to access them. Dissection exercises mostly consisted of self-study, using instructive videos and interactive exercises. In the second half of the semester, four of the educational institutions were able to offer a restricted number of in-person gross anatomy classes under reinforced conditions. Success monitoring took place online through different formats, and partially on a voluntary basis, via the learning platforms. Although the past two semesters had to almost exclusively take place online due to the unprecedented circumstances, and joint efforts of the five veterinary institutions, there is a general consensus that the practical education in anatomy, histology and embryology is essential to veterinary students. In fact, it is the only way they can obtain the necessary skills to successfully complete the rest of their degree.