Advancing Research Training in Medical Education: Global Perspectives and Paradigms for Future Development.

BACKGROUND: This study delves into the dynamic field of medical education research, emphasizing the integration of research training within medical curricula. It seeks to understand the impact of such integration on the competencies of future medical professionals. OBJECTIVE: The primary aim is to systematically categorize and analyze the current trends and future directions in research training in medical education. This involves assessing the influence of research training on medical students' skills and the methodologies used in such research. METHODS: The research employs an extensive bibliographic literature review across multiple databases. It classifies studies like experiential or case studies, editorials, and original research articles. This classification is based on criteria such as geographical location, research objectives, theoretical frameworks, and methodologies. RESULTS: Findings reveal a diverse landscape in medical education research, with a significant emphasis on research training. The research showcases varying methodologies and approaches used globally, highlighting the thematic focus and geographical distribution of these studies. CONCLUSION: Research training in medical education is a globally expansive and evolving field. It underscores the importance of continuous investigation, particularly focusing on integrating research elements at curricular levels and exploring innovative educational strategies. The study also points out potential research gaps, especially in underrepresented regions, indicating directions for future research efforts.

Integrating Research and Teaching in Medical Education: Challenges, Strategies, and Implications for Healthcare.

Introduction: The integration of research and teaching in medical education offers numerous benefits, fostering critical thinking and analytical skills in students. Institutions worldwide have recognized the significance of this nexus and have implemented initiatives to link teaching with discipline-based research, promoting interdisciplinary collaboration. This article aims to explore the challenges and recommendations for integrating research and teaching in medical schools and provide recommendations to overcome these challenges. Methods: We conducted a comprehensive review of the literature to identify the common challenges faced by medical institutions in integrating research and teaching. PubMed, Scopus, Web of Science, ERIC, and Google Scholar databases were searched to assess the literature that met the study objectives with explicit inclusion and exclusion criteria. We also examined successful strategies employed by some institutions to promote research-teaching integration. Results: The challenges identified include limited resources, the need to balance research and curriculum requirements, and the importance of cultivating a research-oriented institutional culture. Successful strategies involve curriculum updates, faculty motivation, and cross-disciplinary collaboration. Implementing strategies involve vertically and horizontally integrating research methodology throughout the undergraduate curriculum and cross-integrating traditional medical courses with other disciplines. Collaboration between universities, enterprises, and schools can enhance comprehensive cooperation. Conclusion: To create a research-oriented learning environment, medical institutions should address these challenges and implement effective strategies. This approach will not only nurture research-oriented healthcare professionals but also advance medical knowledge for the benefit of patient care. By addressing these challenges and implementing appropriate strategies, medical institutions can create a research-oriented learning environment, nurturing research-oriented healthcare professionals and advancing medical knowledge to improve patient care.

Enhancing Cancer Care Amid Conflict: A Proposal for Optimizing Oncology Services During Wartime.

The landscape of cancer care within armed conflict zones is characterized by intricate challenges arising from disrupted health care systems, scarcity of resources, and population displacement. During times of war, the provision of cancer services is often disrupted, leading to significant challenges for oncologists and other health care providers. To optimize cancer services during wartime, several key priorities must be addressed. Focusing on needs assessment, treatment prioritization, drug supply chain, telemedicine, mobile clinics, cross-border collaborations, health care staff support, and continuity of care will enable health care systems to provide essential cancer services and mitigate the adverse impact of conflict on patients with cancer. This article delineates the pivotal key priorities for optimizing cancer services during wartime. It calls for collaborative action, the integration of technology, and holistic care approaches to safeguard the rights, well-being, and dignity of individuals confronting the dual challenges of cancer and conflict. By addressing these priorities, health care providers, policymakers, and stakeholders can collectively ensure that cancer services remain steadfast and compassionate even amid the turmoil of war. Thus, it may be possible to optimize cancer services during wartime, ensuring that patients with cancer continue to receive the care they need.

Utilization of ChatGPT in Medical Education: Applications and Implications for Curriculum Enhancement.

Background: The integration of artificial intelligence (AI) into medical education has sparked a paradigm shift in pedagogical approaches, reshaping the way medical knowledge is accessed, processed, and applied. Medical education is a dynamic field that demands continuous adaptation to the evolving healthcare landscape. ChatGPT, an advanced AI language model, with its natural language understanding and generation capabilities, offers a multifaceted toolset that enhances various aspects of medical education. Objective: The objective of this paper is to explore how ChatGPT, an advanced AI language model, is transforming medical education by serving as a dynamic information resource and driving curriculum reform. It aims to highlight the multifaceted uses of ChatGPT and its potential to reshape the pedagogical landscape in medical education. Methods: PubMed, Scopus, Web of Science, ERIC, and Google Scholar databases were searched to assess the literature that met the study objectives from 2019 to August 2023 with explicit inclusion and exclusion criteria. Results: The results demonstrate that ChatGPT's applications in medical education are diverse and encompass real-time curriculum adaptation, personalized learning, and collaborative learning. Its capacity to provide immediate and contextually relevant information has the potential to enhance the quality of medical education significantly. Conclusion: ChatGPT's integration into medical education represents a transformative shift in educational approaches. It offers a wide range of capabilities, from serving as a repository of medical knowledge to facilitating collaborative learning. As medical education continues to evolve, ChatGPT emerges as a powerful tool that can reshape pedagogy and drive meaningful curriculum reform to meet the needs of modern healthcare practice.ChatGPT emerges as a transformative tool that holds the potential to reshape the landscape of medical pedagogy and drive meaningful curriculum reform.

Colonic Metastasis of Primary Lung Cancer.

The colon is an uncommon secondary site for metastasis of lung adenocarcinoma. Distinguishing primary colonic carcinoma from metastatic spread of lung carcinoma can be difficult. We present a case of a patient with lung adenocarcinoma who, on abdominal computed tomography scan examination, was found to have a sigmoid tumor that was thought to represent a synchronous primary colorectal adenocarcinoma. Histological examination of endoscopic sigmoid tumor biopsies confirmed this to be metastasis from the lung adenocarcinoma. The patient subsequently developed major rectal bleeding and deteriorated significantly. This case also illustrates the poor prognosis association with colorectal metastasis of lung cancer.

The Rise of the TROP2-Targeting Agents in NSCLC: New Options on the Horizon.

BACKGROUND: Lung cancer is the most common thoracic malignancy, representing the leading cause of cancer-related deaths worldwide with a 5-year survival rate of <10%. SUMMARY: The emergence of targeted therapy and immunotherapy has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). However, for those who are not eligible for such therapy or currently have no available standard treatment options, new precision treatment approaches are needed. Human trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein that is highly expressed on several epithelial tumours including NSCLC. TROP2 is recognized as a promising molecular target for therapeutic development in various types of TROP2-expressing malignancies. As a result, several TROP2-targeted therapeutics have recently been developed for clinical use, such as anti-TROP2 antibodies and TROP2-targeted antibody-drug conjugates. Key Message: This review explores the literature data on the role of TROP2 in cancer development and the potential use of emerging TROP2 antibody-drug conjugates in NSCLC treatment.

The zinc-finger protein Red1 orchestrates MTREC submodules and binds the Mtl1 helicase arch domain.

Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome in a process requiring the RNA helicase Mtr4 and specific adaptor complexes for RNA substrate recognition. The PAXT and MTREC complexes have recently been identified as homologous exosome adaptors in human and fission yeast, respectively. The eleven-subunit MTREC comprises the zinc-finger protein Red1 and the Mtr4 homologue Mtl1. Here, we use yeast two-hybrid and pull-down assays to derive a detailed interaction map. We show that Red1 bridges MTREC submodules and serves as the central scaffold. In the crystal structure of a minimal Mtl1/Red1 complex an unstructured region adjacent to the Red1 zinc-finger domain binds to both the Mtl1 KOW domain and stalk helices. This interaction extends the canonical interface seen in Mtr4-adaptor complexes. In vivo mutational analysis shows that this interface is essential for cell survival. Our results add to Mtr4 versatility and provide mechanistic insights into the MTREC complex.

Correction: Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome.

[This corrects the article DOI: 10.1371/journal.pone.0183272.].

Does Curriculum Analysis in Clinical Residency Training Need to be Different?

OBJECTIVES: Curriculum analysis is an essential process in exploring the validity of assumptions behind the curriculum and judging its perspectives, goals, and objectives. This study analysed the curriculum of the Internal Medicine Residency Programme at the Sudan Medical Specialisation Board, exploring the programme's strengths, weaknesses, and areas for improvement. MATERIALS AND METHODS: A qualitative descriptive analysis method using Harden Ten Questions framework was used, implemented through document analysis. Thematic analysis was used to categorise the findings following the Harden Ten Questions framework. RESULTS: The analysis of this curriculum using Harden Ten Questions framework revealed that it is built on needs assessment, with clear objectives and contents, good organisation of the contents and a precise management process. However, there is a need to improve the areas related to training strategies, training methods, assessment methods and the learning environment. CONCLUSIONS: This study showed that the curriculum is built to meet the needs of the Sudanese community. The contents fit for internal medicine clinical residency and the methods of training are likely to foster long-life learning. The curriculum needs some improvement particularly in the following areas such as clinical teaching, trainee assessments, and learning environments. Harden Ten Questions framework for curricula was practical to some degree in analysing the postgraduate curriculum. However, some suggestions have been made regarding the original framework to make it more adaptable to curriculum analysis at postgraduate level. The systematic analysis is transferable to the analysis of other undergraduate or postgraduate medical curricula in Sudan.

YvcI from Bacillus subtilis has in vitro RNA pyrophosphohydrolase activity.

RNA degradation is one of several ways for organisms to regulate gene expression. In bacteria, the removal of two terminal phosphate moieties as orthophosphate (Bacillus subtilis) or pyrophosphate (Escherichia coli) triggers ribonucleolytic decay of primary transcripts by 5'-monophosphate-dependent ribonucleases. In the soil-dwelling firmicute species B. subtilis, the RNA pyrophosphohydrolase BsRppH, a member of the Nudix family, triggers RNA turnover by converting primary transcripts to 5'-monophospate RNA. In addition to BsRppH, a source of redundant activity in B. subtilis has been proposed. Here, using recombinant protein expression and in vitro enzyme assays, we provide evidence for several additional RNA pyrophosphohydrolases, among them MutT, NudF, YmaB, and YvcI in B. subtilis We found that in vitro, YvcI converts RNA 5'-di- and triphosphates into monophosphates in the presence of manganese at neutral to slightly acidic pH. It preferred G-initiating RNAs and required at least one unpaired nucleotide at the 5'-end of its substrates, with the 5'-terminal nucleotide determining whether primarily ortho- or pyrophosphate is released. Exchanges of catalytically important glutamate residues in the Nudix motif impaired or abolished the enzymatic activity of YvcI. In summary, the results of our extensive in vitro biochemical characterization raise the possibility that YvcI is an additional RNA pyrophosphohydrolase in B. subtilis.

An essential thioredoxin-type protein of Trypanosoma brucei acts as redox-regulated mitochondrial chaperone.

Most known thioredoxin-type proteins (Trx) participate in redox pathways, using two highly conserved cysteine residues to catalyze thiol-disulfide exchange reactions. Here we demonstrate that the so far unexplored Trx2 from African trypanosomes (Trypanosoma brucei) lacks protein disulfide reductase activity but functions as an effective temperature-activated and redox-regulated chaperone. Immunofluorescence microscopy and fractionated cell lysis revealed that Trx2 is located in the mitochondrion of the parasite. RNA-interference and gene knock-out approaches showed that depletion of Trx2 impairs growth of both mammalian bloodstream and insect stage procyclic parasites. Procyclic cells lacking Trx2 stop proliferation under standard culture conditions at 27°C and are unable to survive prolonged exposure to 37°C, indicating that Trx2 plays a vital role that becomes augmented under heat stress. Moreover, we found that Trx2 contributes to the in vivo infectivity of T. brucei. Remarkably, a Trx2 version, in which all five cysteines were replaced by serine residues, complements for the wildtype protein in conditional knock-out cells and confers parasite infectivity in the mouse model. Characterization of the recombinant protein revealed that Trx2 can coordinate an iron sulfur cluster and is highly sensitive towards spontaneous oxidation. Moreover, we discovered that both wildtype and mutant Trx2 protect other proteins against thermal aggregation and preserve their ability to refold upon return to non-stress conditions. Activation of the chaperone function of Trx2 appears to be triggered by temperature-mediated structural changes and inhibited by oxidative disulfide bond formation. Our studies indicate that Trx2 acts as a novel chaperone in the unique single mitochondrion of T. brucei and reveal a new perspective regarding the physiological function of thioredoxin-type proteins in trypanosomes.

Crystal structures of Rea1-MIDAS bound to its ribosome assembly factor ligands resembling integrin-ligand-type complexes.

The Rea1 AAA+-ATPase dislodges assembly factors from pre-60S ribosomes upon ATP hydrolysis, thereby driving ribosome biogenesis. Here, we present crystal structures of Rea1-MIDAS, the conserved domain at the tip of the flexible Rea1 tail, alone and in complex with its substrate ligands, the UBL domains of Rsa4 or Ytm1. These complexes have structural similarity to integrin α-subunit domains when bound to extracellular matrix ligands, which for integrin biology is a key determinant for force-bearing cell-cell adhesion. However, the presence of additional motifs equips Rea1-MIDAS for its tasks in ribosome maturation. One loop insert cofunctions as an NLS and to activate the mechanochemical Rea1 cycle, whereas an additional ß-hairpin provides an anchor to hold the ligand UBL domains in place. Our data show the versatility of the MIDAS fold for mechanical force transmission in processes as varied as integrin-mediated cell adhesion and mechanochemical removal of assembly factors from pre-ribosomes.

Unusual Sites of High-Grade Neuroendocrine Carcinomas: A Case Series and Review of the Literature.

BACKGROUND Neuroendocrine tumors (NETs) encompass a diverse group of varying clinicopathological entities arising from cells of the endocrine and nervous systems. The presentation of these unique tumors can range from occult disease discovered incidentally to hyperactive, metastatic secretory tumors. NETs most commonly originate in the gastrointestinal and respiratory tract, although they may occur at any site in the body due to the wide distribution of neuroendocrine cells. Their classification system is complex and continues to evolve, and the current system uses histological grade in defining these subtypes. Neuroendocrine carcinomas (NECs), or high-grade, poorly-differentiated NETs, are the most aggressive subtype. Surgical resection remains the primary treatment modality and may be curative, thus early diagnosis is paramount. Management of advanced NETs remains both a diagnostic and therapeutic challenge; however, advances in our understanding of these unique neoplasms as well as an evolving classification system has led to the development of adjunctive therapeutic approaches aimed to minimize morbidity and improve patient outcomes. CASE REPORT We present 6 cases of unusual sites of high-grade neuroendocrine carcinomas involving the cervix, gallbladder, oesophagus, ovary, prostate, and urinary bladder. CONCLUSIONS Our case series highlights the heterogenous and aggressive nature of this subtype of NETs as well as their diagnostic and therapeutic difficulties. We also review the evolution of the NET classification system and its impact on the management of these malignancies.

DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation.

The succession of molecular events leading to eukaryotic translation reinitiation-whereby ribosomes terminate translation of a short open reading frame (ORF), resume scanning, and then translate a second ORF on the same mRNA-is not well understood. Density-regulated reinitiation and release factor (DENR) and multiple copies in T-cell lymphoma-1 (MCTS1) are implicated in promoting translation reinitiation both in vitro in translation extracts and in vivo. We present here the crystal structure of MCTS1 bound to a fragment of DENR. Based on this structure, we identify and experimentally validate that DENR residues Glu42, Tyr43, and Tyr46 are important for MCTS1 binding and that MCTS1 residue Phe104 is important for tRNA binding. Mutation of these residues reveals that DENR-MCTS1 dimerization and tRNA binding are both necessary for DENR and MCTS1 to promote translation reinitiation in human cells. These findings thereby link individual residues of DENR and MCTS1 to specific molecular functions of the complex. Since DENR-MCTS1 can bind tRNA in the absence of the ribosome, this suggests the DENR-MCTS1 complex could recruit tRNA to the ribosome during reinitiation analogously to the eukaryotic initiation factor 2 (eIF2) complex in cap-dependent translation.

Students' perception of the learning environment and its relation to their study year and performance in Sudan.

OBJECTIVES: To evaluate students' perceptions of the learning environment and to assess any differences in perception related to students' performance and their year of study. METHODS: A descriptive cross-sectional study was performed of 638 students from the second, sixth and tenth semesters at the Faculty of Medicine at Gezira University, Sudan. This study employed the Arabic-translated Dundee Ready Education Environment Measure. The main predictor variables were the study year and academic performance. Descriptive statistics and one-way analysis of variance with a post hoc Tukey-Kramer multiple comparisons test were used for data analysis. RESULTS: The overall score for this study was 122/200 (SD=16.6), indicating a positive perception of the learning environment. The overall mean score was 109.94/200 (SD=21.2) for Semester 2 students, 122.9/200 (SD=20.29) for Semester 6 students, and 116.53 (SD=20.12) for Semester 10 students, reflecting a significant difference in students' perceptions in different years of study (F (2,2422) = 3.21, p=0.04). There was also a significant difference between the mean overall scores with respect to academic performance. High-achieving students' mean DREEM score was 126 (SD=24.4); while low-achieving students' mean DREEM score was 102 (SD=26.25) (F(2,2453) = 3.53, p=0.029). CONCLUSIONS: High achievers' perceptions of the learning environment are significantly better than those of low achievers. A significant difference was observed between students in different years of study. The differences in students' academic performance should be further investigated, targeting specific domains. A large-scale study is required to differentiate between the weakness and the strength of each academic level.

Visualizing the Assembly Pathway of Nucleolar Pre-60S Ribosomes.

Eukaryotic 60S ribosomal subunits are comprised of three rRNAs and ∼50 ribosomal proteins. The initial steps of their formation take place in the nucleolus, but, owing to a lack of structural information, this process is poorly understood. Using cryo-EM, we solved structures of early 60S biogenesis intermediates at 3.3 Å to 4.5 Å resolution, thereby providing insights into their sequential folding and assembly pathway. Besides revealing distinct immature rRNA conformations, we map 25 assembly factors in six different assembly states. Notably, the Nsa1-Rrp1-Rpf1-Mak16 module stabilizes the solvent side of the 60S subunit, and the Erb1-Ytm1-Nop7 complex organizes and connects through Erb1's meandering N-terminal extension, eight assembly factors, three ribosomal proteins, and three 25S rRNA domains. Our structural snapshots reveal the order of integration and compaction of the six major 60S domains within early nucleolar 60S particles developing stepwise from the solvent side around the exit tunnel to the central protuberance.

Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome.

In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. Here we report the crystal structure of a complex between Imp4 and a short helical element of Mpp10 to a resolution of 1.88 Å. Furthermore, we extend the interaction network of Mpp10 and characterize two novel interactions. Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome.

Structural basis for 5'-ETS recognition by Utp4 at the early stages of ribosome biogenesis.

Eukaryotic ribosome biogenesis begins with the co-transcriptional assembly of the 90S pre-ribosome. The 'U three protein' (UTP) complexes and snoRNP particles arrange around the nascent pre-ribosomal RNA chaperoning its folding and further maturation. The earliest event in this hierarchical process is the binding of the UTP-A complex to the 5'-end of the pre-ribosomal RNA (5'-ETS). This oligomeric complex predominantly consists of ß-propeller and α-solenoidal proteins. Here we present the structure of the Utp4 subunit from the thermophilic fungus Chaetomium thermophilum at 2.15 Å resolution and analyze its function by UV RNA-crosslinking (CRAC) and in context of a recent cryo-EM structure of the 90S pre-ribosome. Utp4 consists of two orthogonal and highly basic ß-propellers that perfectly fit the EM-data. The Utp4 structure highlights an unusual Velcro-closure of its C-terminal ß-propeller as relevant for protein integrity and potentially Utp8 recognition in the context of the pre-ribosome. We provide a first model of the 5'-ETS RNA from the internally hidden 5'-end up to the region that hybridizes to the 3'-hinge sequence of U3 snoRNA and validate a specific Utp4/5'-ETS interaction by CRAC analysis.

Analyzing the Curriculum of the Faculty of Medicine, University of Gezira using Harden's 10 questions framework.

INTRODUCTION: Despite the importance of curriculum analysis for internal refinement of a programme, the approach for such a step in under-described in the literature. This article describes the analysis of the medical curriculum at the Faculty of Medicine, University of Gezira (FMUG). This analysis is crucial in the era of innovative medical education since introducing new curricula and curricular changes has become a common occurrence in medical education worldwide. METHODS: The curriculum analysis was qualitatively approached using descriptive analysis and adopting Harden's 10 Questions of curriculum development framework approach. Answering Harden's questions reflects the fundamental curricular components and how the different aspects of a curriculum framework fit together. The key features highlighted in the curriculum-related material and literature have been presented. RESULTS: The analysis of the curriculum of FMUG reveals a curriculum with interactive components. Clear structured objectives and goals reflect the faculty's vision. The approach for needs assessment is based on a scientific ground, and the curriculum integrated contents have been set to meet national and international requirements. Adopting SPICES strategies helps FMUG and students achieve the objectives of the curriculum. Multiple motivated instructional methods are adopted, fostering coping with the programme objectives and outcomes. A wide range of assessment methods has been adopted to assess the learning outcomes of the curriculum correctly, reliably, and in alignment with the intended outcomes. The prevailing conducive educational environment of FMUG is favourable for its operation and profoundly influences the outcome of the programme. And there is a well-defined policy for curriculum management, monitoring and evaluation. CONCLUSION: Harden's 10 questions are satisfactorily addressed by the multi-disciplinary and well-developed FMUG curriculum. The current curriculum supports the well-written faculty missions and educational objectives. It presents a structured, conceptual framework that supports the validity of the assumption behind the curriculum. The curriculum enhances intellectual and academic pursuits and supports social accountability.

Interaction network of the ribosome assembly machinery from a eukaryotic thermophile.

Ribosome biogenesis in eukaryotic cells is a highly dynamic and complex process innately linked to cell proliferation. The assembly of ribosomes is driven by a myriad of biogenesis factors that shape pre-ribosomal particles by processing and folding the ribosomal RNA and incorporating ribosomal proteins. Biochemical approaches allowed the isolation and characterization of pre-ribosomal particles from Saccharomyces cerevisiae, which lead to a spatiotemporal map of biogenesis intermediates along the path from the nucleolus to the cytoplasm. Here, we cloned almost the entire set (∼180) of ribosome biogenesis factors from the thermophilic fungus Chaetomium thermophilum in order to perform an in-depth analysis of their protein-protein interaction network as well as exploring the suitability of these thermostable proteins for structural studies. First, we performed a systematic screen, testing about 80 factors for crystallization and structure determination. Next, we performed a yeast 2-hybrid analysis and tested about 32,000 binary combinations, which identified more than 1000 protein-protein contacts between the thermophilic ribosome assembly factors. To exemplary verify several of these interactions, we performed biochemical reconstitution with the focus on the interaction network between 90S pre-ribosome factors forming the ctUTP-A and ctUTP-B modules, and the Brix-domain containing assembly factors of the pre-60S subunit. Our work provides a rich resource for biochemical reconstitution and structural analyses of the conserved ribosome assembly machinery from a eukaryotic thermophile.