UNASSIGNED: T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves\' disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation.
UNASSIGNED: Through gene landscape analysis, a protein-protein interaction network of 40 Tex-related genes was constructed. mRNA expression levels were compared between GD patients and healthy control (HCs). Unsupervised clustering categorized GD cases into subtypes, revealing distinctions in gene expression, immune cell infiltration, and immune responses. Weighted gene co-expression network analysis and differential gene expression profiling identified potential therapeutic targets. RT-qPCR validation of candidate gene expression was performed using blood samples from 112 GD patients. Correlations between Tex-related gene expression and clinical indicators were analyzed.
UNASSIGNED: Extensive Tex-related gene interactions were observed, with six genes displaying aberrant expression in GD patients. This was associated with atypical immune cell infiltration and regulation. Cluster analysis delineated two GD subtypes, revealing notable variations in gene expression and immune responses. Screening efforts identified diverse drug candidates for GD treatment. The Tex-related gene CBL was identified for further validation and showed reduced mRNA expression in GD patients, especially in cases of relapse. CBL mRNA expression was significantly lower in patients with moderate-to-severe thyroid enlargement than in those without such enlargement. Additionally, CBL mRNA expression was negatively correlated with the disease-specific indicator thyrotropin receptor antibodies.
UNASSIGNED: Tex-related genes modulate GD pathogenesis, and their grouping aids subtype differentiation and exploration of therapeutic targets. CBL represents a potential marker for GD recurrence.

UNASSIGNED: Self-learning is a learning process in which students harvest the enterprise, to express their learning goals, choose assets for learning, practice learning strategies, and assess the outcomes achieved. Many forms of self-learning were introduced in integrative medical curricula such as Team-based learning (TBL) and Problem-based learning (PBL). This study aims to evaluate self-learning in the otolaryngology module and determine the type of self-learning that students prefer and which of these types has a stronger impact on achieving the educational objectives of the module.
UNASSIGNED: A cross-sectional study was done on the 270 students of studied the otolaryngology module in three consecutive years representing the whole class of the fifth-year medical students along three consecutive years. A Likert scale questionnaire was distributed to measure the students\' satisfaction with the current teaching and learning.
UNASSIGNED: The obtained results revealed higher students \'satisfaction with TBL than other modalities supported by high achievement in TBL-related questions. In addition, there is a significant difference between TBL and PBL (p = .00044). No significant differences were obtained either between TBL and CBL (p = .16570) or between TBL and Seminar presentation (p = .16570). In addition, no significant correlations were obtained between PBL and CBL (p = .34677), between PBL and seminar presentation (p = .46496), and between CBL and seminar (p = .99967).
UNASSIGNED: The results showed that the highest students\' satisfaction was towards TBL compared to other educational methods. These results encourage clinical educators to insert and implement TBL in most of the integrative curriculum modules, especially that of the clinical years.

The CBL (Casitas B-lineage lymphoma) family, as a class of ubiquitin ligases, can regulate signal transduction and activate receptor tyrosine kinases through various tyrosine kinase-dependent pathways. There are three members of the family: c-CBL, CBL-b, and CBL-c. Numerous studies have demonstrated the important role of CBL in various cellular pathways, particularly those involved in the occurrence and progression of cancer, hematopoietic development, and regulation of T cell receptors. Therefore, the purpose of this review is to comprehensively summarize the function and regulatory role of CBL family proteins in different human tumors, as well as the progress of drug research targeting CBL family, so as to provide a broader clinical measurement strategy for the treatment of tumors.

OBJECTIVE: Dental materials science is one of the fundamental disciplines in stomatology, encompassing clinical areas such as orthodontics, prosthodontics, and endodontics. Due to its extensive knowledge base, strong professional nature, and wide scope, teaching dental materials science presents a challenge. This study aimed to enhance the application of dental materials science in oral teaching by comparing the effectiveness of different teaching methods.
METHODS: This research project was evaluated by the Xi\'an Jiaotong University Committee on Human Subjects Research and approved as exempt research. A total of 56 clinical stomatology students from the first year and second year cohorts at the Stomatology Hospital of Xi\'an Jiaotong University were selected for the study. The first year cohort served as the nonteaching reform class, while the second year cohort formed the teaching reform class. The impact of the teaching reform was assessed through a questionnaire survey and final examination results.
RESULTS: The questionnaire survey of students in the teaching reform class indicated a significant improvement in their interest in professional courses and overall satisfaction with the teaching. Additionally, the final examination results revealed a significantly greater rate of excellence among students in the teaching reform class than among those in the nonteaching reform class, with no students failing.
CONCLUSIONS: The use of diverse teaching modes can enhance the quality and effectiveness of dental materials science instruction, offering a new approach for improving teaching in this discipline.

Calcium ions function as key messengers in the context of intracellular signal transduction. The ability of plants to respond to biotic and abiotic stressors is highly dependent on the calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK) signaling network. Here, a comprehensive effort was made to identify all members of the soybean CBL gene family, leading to the identification of 15 total genes distributed randomly across nine chromosomes, including 13 segmental duplicates. All the GmCBL gene subfamilies presented with similar gene structures and conserved motifs. Analyses of the expression of these genes in different tissues revealed that the majority of these GmCBLs were predominantly expressed in the roots. Significant GmCBL expression and activity increases were also observed in response to a range of stress-related treatments, including salt stress, alkaline stress, osmotic stress, or exposure to salicylic acid, brassinosteroids, or abscisic acid. Striking increases in GmCBL1 expression were observed in response to alkaline and salt stress. Subsequent analyses revealed that GmCBL1 was capable of enhancing soybean salt and alkali tolerance through the regulation of redox reactions. These results offer new insight into the complex mechanisms through which the soybean CBL gene family regulates the responses of these plants to environmental stressors, highlighting promising targets for efforts aimed at enhancing soybean stress tolerance.

We conducted a phase 1 study evaluating 3 dose levels of quizartinib (30 mg, 40 mg or 60 mg) in combination with azacitidine for HMA-naïve or relapsed/refractory MDS or MDS/MPN with FLT3 or CBL mutations. Overall, 12 patients (HMA naïve: n=9, HMA failure: n=3) were enrolled; 7 (58 %) patients had FLT3 mutations and 5 (42 %) had CBL mutations. The maximum tolerated dose was not reached. Most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (n=5, 42 %), anemia (n=4, 33 %), lung infection (n=2, 17 %), skin infection (n=2, 17 %), hyponatremia (n=2, 17 %) and sepsis (n=2, 17 %). The overall response rate was 83 % with median relapse-free and overall survivals of 15.1 months (95 % CI 0.0-38.4 months) and 17.5 months (95 % CI NC-NC), respectively. FLT3 mutation clearance was observed in 57 % (n=4) patients. These data suggest quizartinib is safe and shows encouraging activity in FLT3-mutated MDS and MDS/MPN. This study is registered at Clinicaltrials.gov as NCT04493138.

Small group-based instructional approaches such as case-based learning (CBL) and team-based learning (TBL) are widely used in medical education to promote collaboration and team learning. During the pandemic, many medical schools shifted from face-to-face instruction to online settings. While CBL/TBL are intended to foster collaborative skills, it is unclear how its use evolves in an online setting and whether the online setting impacts students\' perceptions and behaviors in collaboration. This study examined how the change from in-person to online CBL/TBL impacted students\' collaboration. We used a mixed-methods sequential design, first collecting and analyzing retrospective cohort quantitative data with the Class of 2023 through peer evaluation surveys followed by six focus groups. Students\' assessment of their peers was generally positive. Nonparametric testing showed significant differences for two questions with less positive perceptions in the virtual setting compared to when students had in-person CBL/TBL. The focus group results identified several themes related to collaboration and learning communities. In the virtual setting, students not only lost collaboration opportunities with their group members in CBL/TBL, but also learning opportunities and social connections with other groups and the community as a whole. Virtual learning environments may have presented challenges for collaborative learning and the establishment of a sense of community.

BACKGROUND: Lysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified.
RESULTS: We report the case of a 64-year-old female who was diagnosed with acute monoblastic leukemia (M5a) and who acquired the rare KMT2A::CBL fusion. The patient received multiple cycles of therapy but did not achieve remission and eventually succumbed to severe infection and disease progression. Additionally, we characterized the predicted KMT2A-CBL protein structure in this case to reveal the underlying leukemogenic mechanisms and summarized reported cases of hematological malignancies with KMT2A::CBL fusion to investigate the correlation of gene rearrangements with clinical outcomes.
CONCLUSIONS: This report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.

Casitas B-lineage lymphoma (CBL) encodes an adaptor protein with E3-ligase activity negatively controlling intracellular signaling downstream of receptor tyrosine kinases. Somatic CBL mutations play a driver role in a variety of cancers, particularly myeloid malignancies, whereas germline defects in the same gene underlie a RASopathy having clinical overlap with Noonan syndrome (NS) and predisposing to juvenile myelomonocytic leukemia and vasculitis. Other features of the disorder include cardiac defects, postnatal growth delay, cryptorchidism, facial dysmorphisms, and predisposition to develop autoimmune disorders. Here we report a novel CBL variant (c.1202G>T; p.Cys401Phe) occurring de novo in a subject with café-au-lait macules, feeding difficulties, mild dysmorphic features, psychomotor delay, autism spectrum disorder, thrombocytopenia, hepatosplenomegaly, and recurrent hypertransaminasemia. The identified variant affects an evolutionarily conserved residue located in the RING finger domain, a known mutational hot spot of both germline and somatic mutations. Functional studies documented enhanced EGF-induced ERK phosphorylation in transiently transfected COS1 cells. The present findings further support the association of pathogenic CBL variants with immunological and hematological manifestations in the context of a presentation with only minor findings reminiscent of NS or a clinically related RASopathy.

BACKGROUND: Depending on the subject area and the \'case\' used, many methods can be used to describe case-based learning (CBL). The majority of health professional education is patient-centered. As a result, clinical presentations and diseases are combined with social and clinical sciences, and student learning is linked to real-world applications. The purpose of this study was to evaluate how medical students at the Faculty of Medicine, National Ribat University, felt about the implementation of CBL.
METHODS: This descriptive cross-sectional study was conducted on 171 final-year medical students (100 females and 71 males). Students were voluntarily invited to complete a self-administered questionnaire consisting of 15 closed-ended questions with 5-point Likert scale responses, covering data on perception, awareness, and barriers to CBL.
RESULTS: The CBL satisfaction rate among medical students was 92.4%. The mean value of the medical student\'s perception was 3.7 out of 5. Regarding perceptions of CBL, 65.5% of students agreed with the positive impact of CBL on their academic performance. \"8.2%\" (14/171) of students strongly concur that CBL improved teamwork, while \"31.6%\" (54/171) strongly disagree. \"36.3%\" of students strongly believe that CBL improved their ability to use clinical reasoning. Regarding CBL barriers, 53% of medical students considered a group of twenty participants per session to be a barrier. (69%) of students refused to consider physical presence as a barrier. \"76.6%\" of the students agreed that the moderator\'s approach and style can have a big influence on the CBL session\'s outcome.
CONCLUSIONS: Overall, students had positive perceptions of CBL. Academic performance, clinical reasoning, teamwork, and information retention and retrieval were all improved by incorporating CBL into training modules. Students agreed that the group size of 20 students per session was a barrier, despite their moderate to excellent knowledge of CBL. Preparation for CBL is both time-consuming and tiring. Despite this, students agree that CBL has a positive impact on the learning process.