bims-curels 2026-01-04 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2026–01–04
fifteen papers selected by
Cure Mito Foundation

Mitochondrial tRNA-Derived Diseases.
From care to cure: a patient engagement framework for rare disease and orphan drug research.
Approach to the Patient - Mitochondrial Diabetes: Contemporary Cases and Precision Medicine Approach.
Online education for rare genetic diseases: a systematic review.
Extracellular mitochondria: a potential player involved in exercise health benefits.
Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.
The AI doctor will see you soon: from assistants to autonomous practitioners.
Altered connectome gradient and its association with gene expression profiles in MELAS patients with stroke-like episodes.
Socioeconomic factors and post-traumatic stress disorder in Polish caregivers of children with rare genetic conditions.
Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.
Tiny genome with big impact: mitochondrial DNA in cardiovascular health.
Assessing rare disease understanding: a novel disease readiness level framework.
Exploring neurology resident experiences with a no-prep journal club to learn research study design and critical appraisal.
De-identification of clinical data: A systematic review of free text, image and tabular data approaches.
Leaning into Necessary Discomforts: Striving for Clinical Excellence While Maintaining Wellness.

Int J Mol Sci. 2025 Dec 13. pii: 12023. [Epub ahead of print]26(24):

Mitochondrial tRNA-Derived Diseases.

Antonia Petropoulou, Nikolaos Kypraios, Dimitra Rizopoulou, Adamantia Kouvela, Alexandros Maniatis, Katerina Anastasopoulou, Alexandra Anastogianni, Theodoros Korfiatis, Katerina Grafanaki, Vassiliki Stamatopoulou, Constantinos Stathopoulos.

  Mitochondrial tRNA genes are critical hotspots for pathogenic mutations and several mitochondrial diseases. They account for approximately 70-75% of disease-causing mtDNA variants despite comprising only 5-10% of the mitochondrial genome. These mutations interfere with mitochondrial translation and affect oxidative phosphorylation, resulting in remarkably heterogeneous multisystem disorders. Under this light, we systematically reviewed PubMed, Scopus, and MITOMAP databases through October 2025, indexing all clinically relevant pathogenic mt-tRNA mutations classified by affected organ systems and underlying molecular mechanisms. Approximately 500 distinct pathogenic variants were identified across all 22 mt-tRNA genes. Beyond typical syndromes like MELAS, MERRF, Leigh syndrome, and Kearns-Sayre syndrome that are linked to mt-tRNA mutations, they increasingly implicate cardiovascular diseases (cardiomyopathy, hypertension), neuromuscular disorders (myopathies, encephalopathies), sensory impairment (hearing loss, optic neuropathy), metabolic dysfunction (diabetes, polycystic ovary syndrome), renal disease, neuropsychiatric conditions, and cancer. Beyond sequence mutations, defects in post-transcriptional modification systems emerge as critical disease mechanisms affecting mt-tRNA function and stability. The mutations on tRNA genes described herein represent potential targets for emerging genome editing therapies, although several translational challenges remain. However, targeted correction of pathogenic mt-tRNA mutations holds transformative potential for precision intervention on mitochondrial diseases.

Keywords:  human diseases; mitochondrial tRNA; mt-tRNA modifications; mtDNA mutations

DOI:  https://doi.org/10.3390/ijms262412023
Ther Adv Rare Dis. 2025 Jan-Dec;6:6 26330040251404519

From care to cure: a patient engagement framework for rare disease and orphan drug research.

Nahya Awada, Anil Varughese.

   Background: Rare diseases (RDs) encompass over 6000-8000 conditions, with 94% lacking available therapies. These conditions affect 400 million people globally, including three million Canadians, who face numerous challenges throughout their healthcare journey. Patient engagement (PE) is increasingly recognized as essential for improving outcomes yet remains inadequate in RD and orphan drug research particularly in Canada, where a national strategy for integrating RD patients' perspectives is lacking. To address this gap, this paper presents a Rare Disease Patient Engagement Framework (RDPEF), a structured model designed to support meaningful PE across all levels of healthcare, including research.
Objectives: To develop a RDPEF that addresses barriers to engagement, reduces stigma, and incorporates patient experience as a core element in RD and orphan drug research and decision-making.
Design: A conceptual framework development study informed by qualitative research and a targeted review of existing PE frameworks.
Methods: The RDPEF was developed using a systematic approach that combined a review of existing literature on PE frameworks with new qualitative research on the experiences of RD patients in Canada. Semi-structured interviews examined patients' healthcare journeys, focusing on disease management, access to orphan drugs, and opportunities for engagement. A thematic analysis of the existing literature and interview data identified common challenges, which guided the framework's design. The RDPEF integrates elements from various other PE models, customizes them to the specific needs of RD patients, and emphasizes engagement across the entire orphan drug lifecycle.
Results: Thematic findings from qualitative research highlighted limited to no patient involvement beyond clinical trials, significant stigma and discrimination, and the absence of structured engagement in drug review and reimbursement processes. These insights informed the development of the RDPEF, which outlines levels and forms of engagement, guiding principles (including stigma reduction), and mechanisms for integrating patient experience across healthcare, policy, and research domains.
Conclusion: The RDPEF is a timely tool for enhancing PE in orphan drug research. By addressing engagement barriers, reducing stigma, and centering patient experience, the framework offers a roadmap for patients, researchers, healthcare providers, and policymakers to create a more inclusive and responsive system for RD patients in Canada.

Keywords:  access; framework; health stigma and discrimination; orphan drugs; patient engagement; patient engagement framework; patient experience; rare diseases; research

DOI:  https://doi.org/10.1177/26330040251404519
J Clin Endocrinol Metab. 2025 Dec 31. pii: dgaf698. [Epub ahead of print]

Approach to the Patient - Mitochondrial Diabetes: Contemporary Cases and Precision Medicine Approach.

Kaylee R Oppenheimer, Nava T Himelhoch, Michael E McCullough, Tiana L Bowden, Balamurugan Kandasamy, Lisa R Letourneau-Freiberg, Rochelle N Naylor, Siri Atma W Greeley, Louis H Philipson.

  Maternally Inherited Diabetes and Deafness (MIDD) syndrome is a rare form of monogenic diabetes most often caused by the pathogenic m.3243A>G mutation in the mitochondrial tRNALeu (UUR) gene, MT-TL1. Mutations causing MIDD are also associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). This paper analyzes the data of 15 probands with mitochondrial diabetes enrolled in the University of Chicago Monogenic Diabetes Registry all of whom have confirmed pathogenic variants, primarily m.3243A>G. Three of these probands (3/15) were selected for detailed case studies and pedigree analysis. Among the total cohort, sensorineural hearing loss (80%) and muscle weakness (53%) were frequent comorbidities, and all tested individuals were negative for islet autoantibodies. Treatment regimens included insulin and sulfonylureas, with some reporting use of biguanides despite safety concerns related to mitochondrial dysfunction. Three probands noted subjective improvement with mitochondrial cocktail supplementation. Familial heteroplasmy testing revealed significant inter- and intrafamilial variability. This cohort represents one of the largest clinically characterized U.S. populations with mitochondrial diabetes and underscores the importance of urine-based heteroplasmy testing and personalized management strategies informed by mitochondrial pathophysiology.

Keywords:  Maternally Inherited Diabetes and Deafness (MIDD); Mitochondrial diabetes; and stroke-like episodes (MELAS); lactic acidosis; mitochondrial encephalomyopathy

DOI:  https://doi.org/10.1210/clinem/dgaf698
Orphanet J Rare Dis. 2025 Dec 31.

Online education for rare genetic diseases: a systematic review.

Pinar Ozmizrak, Luigi Boccuto, Tracy Brock Lowe, Stephanie Trammel, Jane DeLuca.

   INTRODUCTION: Rare genetic diseases are, collectively, not in fact rare. However, educational opportunities focused on rare genetic disease can be limited. The Internet has increased the availability of education related to rare genetic disease and is accessible to a diverse range of people who seek out such information, including healthcare professionals, researchers, students, patients, and the public.
PURPOSE: To assess the potential educational outreach of the Internet, this systematic literature review will appraise the landscape of what education for rare genetic disease is available online, describing its form, subject, and intended audience.
METHODS: This systematic review encompassed all results across 20 science, healthcare, and education databases published up to September 1, 2023. The search criteria were specific to online education for rare genetic diseases.
RESULTS: From 1663 total results, after applying exclusion criteria, 58 publications remained, ranging from 2002 to 2023. Although the amount of research presenting rare genetic disease education online was limited, the forms of education and its target learners were varied. Studies could have multiple target learners and healthcare professionals (68.97% of papers) and healthcare consumers (62.07% of papers) represented the most common of 5 different learners. 22 different specific conditions or categories of disease were the focus of 56.90% papers, with the remainder being general subjects like 'genetic testing' or 'rare diseases' overall. Modes of delivery were mutually exclusive per paper, with websites (29.31% of papers) and web applications/modules (24.14% of papers) being the most common of 7 different forms. The highest representation for author institutions was the USA (58.62% of papers) out of 33 countries total. The broad spread of learners, subjects, and delivery forms demonstrates the potential for online education as a vehicle for advancing the reach of rare disease education.
CONCLUSIONS: The greater accessibility afforded through online information creates an avenue for further availability of high-quality education on rare genetic diseases.

Keywords:  Genetics; Healthcare; Online education; Open educational resources; Rare disease

DOI:  https://doi.org/10.1186/s13023-025-03809-x
Biochimie. 2025 Dec 26. pii: S0300-9084(25)00316-5. [Epub ahead of print]242 97-107

Extracellular mitochondria: a potential player involved in exercise health benefits.

Mafalda Barbosa Pedrosa, Lúcio Lara Santos, Rita Ferreira, José Magalhães.

  Exercise is widely recognized as an effective nonpharmacological therapy for noncommunicable diseases, with its health benefits mediated in part by exerkines. Recently, extracellular mitochondria (ex-Mito) have been suggested as a player in mediating intercellular communication. While it is known that the health benefits of exercise involve the remodeling of mitochondria in multiple organs, the impact of exercise on circulating ex-Mito is poorly understood. Most existing studies have focused on cell-free circulating mitochondrial DNA, skeletal muscle-derived extracellular vesicles, or platelet-derived mitochondria, without focusing on other types of ex-Mito. The cellular origin of exercise-induced circulating ex-Mito and the role of each form (vesicle-enclosed, free, or as mitochondrial components) in mediating exercise's therapeutic effects are yet to be elucidated. This review aims to delve into the role of ex-Mito as potential players in exercise-related health benefits, paving the way for future research aimed at uncovering the molecular culprits of this nonpharmacological therapy, including mitochondrial transfer and transplantation.

Keywords:  Exercise training; Mitochondrial remodeling; Mitochondrial transfer; Mitochondrial transplantation; Nonpharmacological therapy

DOI:  https://doi.org/10.1016/j.biochi.2025.12.011
Neural Regen Res. 2025 Dec 30.

Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.

Jiangyu Zhao, Jing Wang, Xing Guo.

  Organoid technology, as an innovative approach, has shown great potential in disease modeling, target screening, and the development of treatment strategies. However, traditional organoids still have three major limitations in research: the absence of specific cell types, the lack of blood-brain barrier structure, and insufficient reproducibility of experimental results. In recent years, researchers have gradually overcome these limitations by introducing innovative techniques such as advanced culture methods, microfluidic systems, bioprinting, organoid transplantation, and assembloid construction. This progress has facilitated the widespread application of organoids in the study of neurodegenerative diseases. This paper aims to systematically review the technological innovations of organoids in the study of neurodegenerative diseases. By summarizing classical organoid construction strategies and their limitations, it emphasizes the value of organoids in comprehensive applications within neurodegenerative disease research. In this review, we focus on five specific neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Research in these diseases demonstrates that organoids improve experimental accessibility and reduce development cycles in disease modeling, target discovery, and therapeutic strategy formation. Using customized equipment and gene editing techniques, these organoids can be tailored to specific needs, providing pathophysiologically relevant disease models and enhancing our understanding of neurodegenerative diseases. Although organoid technology has demonstrated significant advantages in disease research, its potential for treating neurodegenerative diseases has not yet been fully explored, which may become an important direction for future research.

Keywords:  Alzheimer disease; Huntington's disease; Parkinson's disease; amyotrophic lateral sclerosis; bioprinting; frontotemporal dementia; microfluidics; neurodegenerative diseases; organoids; transplantation

DOI:  https://doi.org/10.4103/NRR.NRR-D-25-00924
Med Rev (2021). 2025 Dec;5(6): 511-514

The AI doctor will see you soon: from assistants to autonomous practitioners.

Tianshu Gu, Xia Meng, Yongjun Wang, Weikuan Gu.

  Artificial Intelligence (AI) is bringing an unprecedented evolution in human history. As it develops, the utilization of AI in clinical practice becomes one of the hot topics that attracts the attention of the medical field as well as the public. While we know that AI will be heavily involved in the medical system, a critical question is what we expect for the future AI medical doctor. To answer this question, it is important to understand that the developing patterns of any other discovery and industrialization do not fit the pattern of AI development, because it acts more like a human instead of simply being a machine or tool. Thus, AI doctors function like human doctors to provide patient-centered reasoning, intellectual judgment, and ethical decision-making rather than just mechanical data processing. Here we present such a likely development process, including current AI status, expected AI doctors, challenges, and future directions.

Keywords:  AI; doctor; ethics; medical robotics; personalization; population

DOI:  https://doi.org/10.1515/mr-2025-0044
AJNR Am J Neuroradiol. 2025 Dec 30. pii: ajnr.A9154. [Epub ahead of print]

Altered connectome gradient and its association with gene expression profiles in MELAS patients with stroke-like episodes.

Rong Wang, Qingyun Yu, Chong Sun, Xueling Liu, Bin Hu, Liqin Yang, Daoying Geng, Jie Lin, Yuxin Li.

BACKGROUND AND PURPOSE: Hierarchy is a fundamental principle of network organization in the human brain. Functional gradient introduces a new perspective in identifying hierarchy alterations by capturing major axes of functional connectivity (FC) in lowdimensional space. However, whether this gradient structure is disrupted in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients with stroke-like episodes (SLE) and how this disruption modulated by gene expression profiles remain unknow.
MATERIALS AND METHODS: Thirty-one MELAS patients at acute stage (MELAS-acute) and 31 healthy controls (HC) underwent restingstate functional magnetic resonance imaging (rs-fMRI) scan. Based on the whole-brain voxel-wise FC patterns, functional gradient values were generated and group-averaged gradient values were further extracted and compared from global to voxel level. Combined with the Allen Human Brain Atlas, we then assessed the spatial correlations between MELAS-related gradient alterations and gene expression profiles.
RESULTS: Relative to the HC, MELAS-acute patients exhibited global alterations in the principal gradient, including reduced gradient range and gradient variation. In addition, patients showed lower gradient values in the default mode network (DMN) but higher values in the ventral attention network (VAN) and sensorimotor network (SMN) at network and voxel level. Furthermore, we established a link between MELAS-acute related principal gradient and gene expression profiles, with two gene sets mainly enriched in mitochondrion, neuron, glutamatergic synapse, and ATPase activity.
CONCLUSIONS: These results highlight the connectome gradient alterations in MELAS patients at acute stage and its linkage with gene expression profiles, providing insight into the neurobiological basis of functional alterations during the acute SLE stage in MELAS.
ABBREVIATIONS: AHBA = Allen Human Brain Atlas; DMN = default mode network; FPN = frontoparietal network; GO = Gene ontology; HC = healthy controls; MELAS = mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MELAS-acute = MELAS patients at acute stage; MNI = Montreal Neurological Institute; SLE = stroke-like episodes; SMN = sensorimotor network; VAN = ventral attention network; VN = visual network.

DOI: https://doi.org/10.3174/ajnr.A9154
J Health Psychol. 2025 Dec 30. 13591053251386169

Socioeconomic factors and post-traumatic stress disorder in Polish caregivers of children with rare genetic conditions.

Weronika Wojtowicz, Joan Deus Yela, Albert Fornieles Deu.

  This study examined post-traumatic stress disorder (PTSD) severity in caregivers of children with rare genetic conditions, focusing on the role of socioeconomic variables: education, family income, marital status, residence, and religious practice. One hundred parents were recruited: 50 of children with rare diseases and 50 of healthy children. The rare disease group was recruited via a patient association and Facebook groups; the control group through parenting forums and social media. A purposive and convenience sampling strategy was applied. All participants completed the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition DSM-5 (PCL-5) and a sociodemographic questionnaire. Data were analyzed using independent samples t-tests and two-way ANOVAs. No significant difference in overall PTSD severity emerged between groups. However, caregivers with higher education showed greater PTSD severity when caring for a child with a rare disease. Other socioeconomic factors were not significant. Tailored mental health support is recommended.

Keywords:  caregivers; post-traumatic stress disorder; rare diseases; socioeconomic factors

DOI:  https://doi.org/10.1177/13591053251386169
Pharmaceuticals (Basel). 2025 Dec 17. pii: 1900. [Epub ahead of print]18(12):

Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.

Noga Gershoni Emek, Andrew M Tan, Michal Geva, Andrea Fekete, Carmen Abate, Michael R Hayden.

  Pridopidine is a highly selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). The S1R is a ubiquitous chaperone protein enriched in the central nervous system and regulates multiple pathways critical for neuronal cell function and survival, including cellular stress responses, mitochondrial function, calcium signaling, protein folding, and autophagy. S1R has a crucial role in the ER mitochondria-associated membrane (MAM), whose dysfunction is implicated in several neurodegenerative diseases. By activating the S1R, pridopidine corrects multiple cellular pathways necessary to the cell's ability to respond to stress, which are disrupted in neurodegenerative diseases. Pridopidine restores MAM integrity; rescues Ca2+ homeostasis and autophagy; mitigates ER stress, mitochondrial dysfunction, and oxidative damage; and enhances brain-derived neurotrophic factor (BDNF) axonal transport and secretion, synaptic plasticity, and dendritic spine density. Pridopidine demonstrates neuroprotective effects in in vivo models of neurodegenerative diseases (NDDs). Importantly, pridopidine demonstrates the biphasic dose response characteristic of S1R agonists. In clinical trials in HD and ALS, pridopidine has shown benefits across multiple endpoints. Pridopidine's mechanism of action, modulating core cellular survival pathways, positions it as a promising candidate for disease modification for different nervous system disorders. Its broad therapeutic potential includes neurodevelopmental disorders, and rare diseases including Wolfram syndrome, Rett syndrome, and Vanishing White Matter Disease. Here, we review the experimental data demonstrating pridopidine's S1R-mediated neuroprotective effects. These findings underscore the therapeutic relevance of S1R activation and support further investigation of pridopidine for the treatment of different neurodegenerative diseases including ALS and HD.

Keywords:  S1R agonist; Sigma-1 receptor; neurodegenerative disease; neuroprotection; pridopidine

DOI:  https://doi.org/10.3390/ph18121900
J Genet Genomics. 2025 Dec 30. pii: S1673-8527(25)00351-0. [Epub ahead of print]

Tiny genome with big impact: mitochondrial DNA in cardiovascular health.

Yafang Yang, Jiaoyu Li, Lu Qian, Yuyan Xiong, Yi Yu.

  Cardiovascular diseases remain the leading cause of mortality worldwide. Mitochondrion, a key cellular organelle, harbors its own mitochondrial DNA (mtDNA) fundamental to cellular energy production through oxidative phosphorylation (OXPHOS). Beyond its canonical bioenergetic function, mtDNA integrity, copy number, and genetic variation play critical roles in maintaining cardiovascular function. This review provides a comprehensive overview of the multifaceted contributions of mtDNA to cardiovascular health and disease. We summarize the structural features and core biological functions of mtDNA, as well as the regulatory mechanisms governing its replication, biogenesis, and turnover. Particular emphasis is focused on mtDNA abnormalities, including point mutations, large-scale deletions, copy number alterations, and epigenetic modifications, and how these disturbances drive key pathogenic processes such as oxidative stress, chronic inflammation, apoptosis, and cellular senescence within the cardiovascular system. Furthermore, we highlight accumulating evidence linking mtDNA dysregulation to major cardiovascular disorders, including heart failure, atherosclerosis, and hypertension. Finally, we discuss the emerging diagnostic potential of circulating cell-free mtDNA and related mtDNA-derived metrics as non-invasive biomarkers, and outline therapeutic strategies aimed at preserving mtDNA integrity, modulating mtDNA content, or applying gene-based interventions to mitigate cardiovascular pathology.

Keywords:  Mitochondrial DNA; cardiovascular diseases; diagnosis and therapy; inflammation; mitochondrial dysfunction; oxidative stress

DOI:  https://doi.org/10.1016/j.jgg.2025.12.009
Orphanet J Rare Dis. 2025 Dec 29. 20(1): 628

Assessing rare disease understanding: a novel disease readiness level framework.

Kazuki Kitahara, Shingo Kano.

   BACKGROUND: Drug development for rare diseases has hurdles against setting high priority because of the size of the market. Although many countries have incentive policies for the development of orphan drugs (drugs used against rare diseases), evaluation methods for determining the rare diseases warranting resource support have not yet been established. To promote research and development (R&D) of rare diseases and drug development, methods measuring the level of understanding of rare diseases and its comparison with that of other diseases are warranted. This study proposes a grading system for measuring simultaneously the level of understanding of rare diseases and progress in product development.
METHODS: Using the Technology Readiness Levels (TRL) framework developed by the National Aeronautics and Space Administration, we proposed a Disease Readiness Level (DRL) to assess the understanding of rare diseases by comparing the characteristics of existing TRL derivatives in the medical field, adding a clinical guideline in the middle stage and extending the assessment period to earlier stages than product development. Case studies with the developed framework were conducted for four rare diseases.
RESULTS: The DRL comprehensively described the four selected rare diseases, muscular dystrophy, progressive fibrodysplasia ossificans, Tangier disease, and idiopathic peripheral pulmonary artery stenosis from their disease origin in the pre-product development phase to the launch of therapeutic strategies over a longer period than previous TRL derivatives.
CONCLUSIONS: This study developed a comprehensive framework for rare diseases that focuses on the disease rather than the product for assessment and covers information spanning disease discovery to drug development. The results of case studies using the framework suggest that DRL can analyze both the level of understanding of rare diseases and the progress of the product research and development (R&D), and can be used as a potential indicator for the allocation of R&D resources.

Keywords:  Clinical guideline; Disease readiness levels; Disease understanding; Rare diseases; Regulatory readiness levels; Research and development; Research progress; Technology readiness levels

DOI:  https://doi.org/10.1186/s13023-025-04135-y
BMC Med Educ. 2025 Dec 29. 25(1): 1732

Exploring neurology resident experiences with a no-prep journal club to learn research study design and critical appraisal.

Katherine A Fu, Sally Elting, Joy M Chan, Roy E Strowd.

   BACKGROUND: Critical appraisal of research is an important skill in practicing evidence-based medicine. Traditional journal clubs often involve pre-session preparation, which can be challenging for resident physicians with competing professional commitments. To address these challenges, the UCLA neurology residency program implemented a "no-prep" journal club format, eliminating prerequisite preparation and emphasizing active, collaborative learning. This study uses a qualitative approach within a constructivist paradigm to explore neurology residents' experiences and the influence of this format on learning critical appraisal.
METHODS: We conducted four monthly no-prep journal clubs during the 2023-2024 academic year. A qualitative study design was used, and data were collected via one-on-one semi-structured interviews with neurology residents. Interview transcripts were descriptively coded, categorized, and analyzed to identify themes using inductive thematic analysis.
RESULTS: Nine neurology residents were interviewed, and five themes were identified. Participants felt that the no-prep journal club format established a psychologically safe learning environment, as it removed participation hesitancy due to inadequate preparation. This format helped learners identify their knowledge gaps, situating them in their zones of proximal development. The presence of the resident and faculty facilitators offered scaffolding for residents to navigate beyond this zone toward independent study design. Regarding behavior change, residents mentioned the format promoted active critique when reading research and the application of this information to patient care. Bookending the session with a clinical case promoted engagement by grounding the format in clinical relevance.
CONCLUSIONS: This no-prep journal club format reflected core elements of constructivist theory. Residents' prompt identification of knowledge gaps illustrated Vygotsky's zone of proximal development, while facilitator support provided the scaffolding necessary to advance their learning. Traditional and flipped classroom style journal club formats are challenged by the necessary prerequisite preparation. In contrast, the no-prep journal club illustrates how learning efficiency in critical appraisal can be improved even in the absence of preparatory work.

Keywords:  Critical appraisal; Evidence-based medicine; Graduate medical education; Journal club; Qualitative methods; Research study design

DOI:  https://doi.org/10.1186/s12909-025-08275-4
Int J Med Inform. 2025 Dec 19. pii: S1386-5056(25)00442-3. [Epub ahead of print]208 106225

De-identification of clinical data: A systematic review of free text, image and tabular data approaches.

Pedro Faustini, Annabelle McIver, Ryan Sullivan, Mark Dras.

   BACKGROUND: The digitisation of healthcare has generated vast amounts of data in various formats, including free-text notes, tabular records and medical images. This data is critical for research and innovation, but often contains sensitive information that must be de-identified to ensure patient privacy and regulatory compliance. Natural Language Processing (NLP) enables automated de-identification of sensitive information to safely share medical datasets.
OBJECTIVE: This study aims to systematically review the literature on NLP-based de-identification techniques applied to free-text medical reports, tabular data, and burned-in text within medical images over the past decade. It seeks to identify state-of-the-art methods, analyse how de-identification tasks are assessed, and find existing gaps for future research.
METHODS: We systematically searched five important databases (PubMed, Web of Science, DBLP, ACM and IEEE) for articles published from January 2015 to December 2024 (10 years) about de-identification of medical data in free text, tabular data and burned-in pixels in images. We filtered the articles based on their titles and abstracts against inclusion and exclusion criteria, followed by a quality filter.
RESULTS: From a set of 734 papers, 83 articles were deemed relevant. Most studies de-identify free text, with a few working with tabular data and a much scarcer number dealing with text embedded in the pixels of the images.
CONCLUSIONS: De-identification techniques have evolved, with increased use of Language Models and a decline in recurrence-based neural networks. Off-the-shelf tools often require customisation for optimal performance. Most studies de-identify English content, supported by the prevalence of English datasets. Key challenges include the phenomenon of code-mixing (i.e., more than one language used in the same sentence) and the scarcity of available datasets for reproducibility.

Keywords:  Clinical data; De-identification; Systematic review

DOI:  https://doi.org/10.1016/j.ijmedinf.2025.106225
ATS Sch. 2025 Dec;6(4): 420-431

Leaning into Necessary Discomforts: Striving for Clinical Excellence While Maintaining Wellness.

Hitesh H Patel, Erica Lin.

  Medical education is redefining clinical excellence in the face of high learner (medical student and house staff) burnout rates, exposing a dichotomy between clinical rigor and well-being. Endurance-based traditions that once equated long hours with competence persist, yet contemporary evidence shows that effective learning environments, grounded in psychological safety and timely bidirectional feedback, improve both performance and well-being. Through the lens of early career clinician educators, we trace the origins of hardship-driven training, review data linking burnout to impaired clinical performance, and describe how competency-based medical education, anchored in entrustable professional activities and qualitative milestones, shifts success metrics from hours logged to skills demonstrated. We explore generational shifts that intensify the need for transparent discussions of expectations between learners and educators. We advocate for a culture in which mistakes are viewed as learning opportunities rather than failures. Finally, we argue that educational reforms must undergo rigorous, longitudinal evaluation before widespread implementation to ensure that they enhance competence, reduce burnout, and maximize patient safety. Clarifying which stressors cultivate mastery and which merely exhaust will allow us to produce physicians who learn more effectively, care for patients more safely, and remain in the profession longer. By cocreating psychologically safe, data-driven training models that retain "necessary discomforts" while eliminating "unnecessary harms," medical education can reconcile its dual obligations to clinical excellence and learner well-being.

Keywords:  burnout; clinical excellence; wellness

DOI:  https://doi.org/10.34197/ats-scholar.2025-0033PS