Use of SGLT2 Inhibitors vs GLP-1 RAs and Anemia in Patients With Diabetes and CKD.

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown. Objective: To evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3. Design, Setting, and Participants: This retrospective cohort study used target trial emulation of an expanded CREDENCE and DAPA-CKD study framework. The study was conducted among adults with T2D and CKD initiating SGLT2 inhibitors or GLP-1 RAs between January 1, 2016, and December 31, 2021, with follow-up until December 31, 2022. The study was conducted at the Chang Gung Medical Foundation, the largest multi-institutional hospital system in Taiwan. Exposures: Initiation of SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures: The primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level <12-13 g/dL or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes) or anemia treatment initiation. Changes in hematological parameters, including hemoglobin level, hematocrit level, and red blood cell count, were evaluated during the follow-up period for as long as 3 years. Results: The cohort included a total of 13 799 patients with T2D and CKD, initiating SGLT2 inhibitors (12 331 patients; mean [SD] age, 62.4 [12.3] years; 7548 [61.2%] male) or GLP-1 RAs (1468 patients; mean [SD] age, 61.5 [13.3] years; 900 [61.3%] male). After the median follow-up period of 2.5 years, patients receiving SGLT2 inhibitors had lower incidence of composite anemia outcomes (hazard ratio [HR], 0.81; 95% CI, 0.73-0.90) compared with those receiving GLP-1 RAs. SGLT2 inhibitors were associated with a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71-0.87) but not with a lower rate of anemia treatment initiation (HR, 0.99; 95% CI, 0.83-1.19). Changes in hematological parameters for SGLT2 inhibitors and GLP-1 RAs throughout the 3-year follow-up period supported the primary analyses. Conclusions and Relevance: In this multi-institutional cohort study with target trial emulation, SGLT2 inhibitors were associated with a decreased risk of composite anemia outcomes, especially anemia event occurrences. SGLT2 inhibitors may be considered as an adjunct therapy to reduce anemia incidence in patients with T2D and CKD.

Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127.

Increasing use of covalent and noncovalent inhibitors of Bruton's tyrosine kinase (BTK) has elucidated a series of acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance mutations in BTK with distinct enzymatic activities, including some that impair BTK enzymatic activity while imparting novel protein-protein interactions that sustain B cell receptor (BCR) signaling. Furthermore, we describe a clinical-stage BTK and IKZF1/3 degrader, NX-2127, that can bind and proteasomally degrade each mutant BTK proteoform, resulting in potent blockade of BCR signaling. Treatment of chronic lymphocytic leukemia with NX-2127 achieves >80% degradation of BTK in patients and demonstrates proof-of-concept therapeutic benefit. These data reveal an oncogenic scaffold function of mutant BTK that confers resistance across clinically approved BTK inhibitors but is overcome by BTK degradation in patients.

ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms.

Solid tumors are dense three-dimensional (3D) multicellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune-suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contribution of ILT2 and ILT4 to immune inhibition in the context of solid tumor tissue has not been fully explored. We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that although ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. In a 3D spheroid tumor model, dual ILT2/ILT4 blockade was required for the optimal activation of myeloid cells, including the secretion of CXCL9 and CCL5, upregulation of CD86 on dendritic cells, and downregulation of CD163 on macrophages. Humanized mouse tumor models showed increased immune activation and cytolytic T-cell activity with combined ILT2 and ILT4 blockade, including evidence of the generation of immune niches, which have been shown to correlate with clinical response to immune-checkpoint blockade. In a human tumor explant histoculture system, dual ILT2/ILT4 blockade increased CXCL9 secretion, downregulated CD163 expression, and increased the expression of M1 macrophage, IFNγ, and cytolytic T-cell gene signatures. Thus, we have revealed distinct contributions of ILT2 and ILT4 to myeloid cell biology and provide proof-of-concept data supporting the combined blockade of ILT2 and ILT4 to therapeutically induce optimal myeloid cell reprogramming in the tumor microenvironment.

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

Association between recently raised anticholinergic burden and risk of acute cardiovascular events: nationwide case-case-time-control study.

OBJECTIVE: To evaluate the association between recently raised anticholinergic burden and risk of acute cardiovascular events in older adults. DESIGN: Case-case-time-control study (ie, incorporating a case crossover design and a control crossover design consisting of future cases). SETTING: Taiwan's National Health Insurance Research Database. PARTICIPANTS: 317 446 adults aged ≥65 who were admitted to hospital because of an incident acute cardiovascular event between 2011 and 2018. Acute cardiovascular events included myocardial infarction, strokes, arrhythmias, conduction disorders, and cardiovascular death. MAIN OUTCOME MEASURES: The anticholinergic burden was measured for each participant by adding up the anticholinergic scores for individual drugs using the Anticholinergic Cognitive Burden Scale. Scores were classified into three levels (0 points, 1-2 points, and ≥3 points). For each participant, anticholinergic burden levels during hazard periods (day -1 to -30 before the cardiovascular event) were compared with randomly selected 30 day reference periods (ie, periods between days -61 and -180). Conditional logistic regression determined odds ratios with 95% confidence intervals to evaluate the association between acute cardiovascular events and recently raised anticholinergic burden. RESULTS: The crossover analyses included 248 579 current cases. Participants' average age on the index date was 78.4 years (standard deviation 0.01), and 53.4% were men. The most frequently prescribed drugs with anticholinergic activity were antihistamines (68.9%), gastrointestinal antispasmodics (40.9%), and diuretics (33.8%). Among patients with varying levels of anticholinergic burden in different periods, more patients carried higher levels of anticholinergic burden during hazard periods than during reference periods. For example, 17 603 current cases had 1-2 points of anticholinergic burden in the hazard period with 0 points in the reference period, while 8507 current cases had 0 points in the hazard period and 1-2 points in the reference period. In the comparison of 1-2 points versus 0 points of anticholinergic burden, the odds ratio was 1.86 (95% confidence interval 1.83 to 1.90) in the case crossover analysis and 1.35 (1.33 to 1.38) in the control crossover analysis, which yielded a case-case-time-control odds ratio of 1.38 (1.34 to 1.42). Similar results were found in the comparison of ≥3 versus 0 points (2.03, 1.98 to 2.09) and ≥3 versus 1-2 points (1.48, 1.44 to 1.52). The findings remained consistent throughout a series of sensitivity analyses (eg, cut-off points for anticholinergic burden categories were redefined and different scales were used to measure anticholinergic burden). CONCLUSIONS: An association was found between recently raised anticholinergic burden and increased risk of acute cardiovascular events. Furthermore, a greater increase in anticholinergic burden was associated with a higher risk of acute cardiovascular events.

Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study.

Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers.

SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.

Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells. Mechanistically, SMYD3 binds to and regulates the transcription of UHRF1, encoding for a reader of H3K9me3, which binds to H3K9me3-enriched promoters of key immune-related genes, recruits DNMT1, and silences their expression. SMYD3 further maintains the repression of immune-related genes through intragenic deposition of H4K20me3. In vivo, Smyd3 depletion induces influx of CD8+ T cells and increases sensitivity to anti-programmed death 1 (PD-1) therapy. SMYD3 overexpression is associated with decreased CD8 T cell infiltration and poor response to neoadjuvant pembrolizumab. These data support combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in HPV-negative HNSCC.

Machine learning applications on neonatal sepsis treatment: a scoping review.

INTRODUCTION: Neonatal sepsis is a major cause of health loss and mortality worldwide. Without proper treatment, neonatal sepsis can quickly develop into multisystem organ failure. However, the signs of neonatal sepsis are non-specific, and treatment is labour-intensive and expensive. Moreover, antimicrobial resistance is a significant threat globally, and it has been reported that over 70% of neonatal bloodstream infections are resistant to first-line antibiotic treatment. Machine learning is a potential tool to aid clinicians in diagnosing infections and in determining the most appropriate empiric antibiotic treatment, as has been demonstrated for adult populations. This review aimed to present the application of machine learning on neonatal sepsis treatment. METHODS: PubMed, Embase, and Scopus were searched for studies published in English focusing on neonatal sepsis, antibiotics, and machine learning. RESULTS: There were 18 studies included in this scoping review. Three studies focused on using machine learning in antibiotic treatment for bloodstream infections, one focused on predicting in-hospital mortality associated with neonatal sepsis, and the remaining studies focused on developing machine learning prediction models to diagnose possible sepsis cases. Gestational age, C-reactive protein levels, and white blood cell count were important predictors to diagnose neonatal sepsis. Age, weight, and days from hospital admission to blood sample taken were important to predict antibiotic-resistant infections. The best-performing machine learning models were random forest and neural networks. CONCLUSION: Despite the threat antimicrobial resistance poses, there was a lack of studies focusing on the use of machine learning for aiding empirical antibiotic treatment for neonatal sepsis.

Post-discharge use of antipsychotics in patients with hospital-acquired delirium and associated risk of mortality - A population-based nested case-control study.

OBJECTIVE: To evaluate post-discharge use of antipsychotics in patients with incident hospital-acquired delirium and the associated risk of mortality. METHODS: We conducted a nested case-control study for patients newly diagnosed with hospital-acquired delirium and subsequently discharged from hospital using Taiwan's National Health Insurance Database (NHID) from 2011 to 2018. RESULTS: The use of antipsychotics after discharge did not increase the risk of mortality (adjusted OR: 1·03; 95% CI: 0·98-1·09). CONCLUSIONS: The findings suggested that using antipsychotics after discharge in patients with hospital-acquired delirium may not increase the risk of mortality.

Gender differences in the intention to withhold life-sustaining treatments involving severe dementia for self and on behalf of parent or spouse.

BACKGROUND: Few studies have explored gender differences in the attitudes toward advanced care planning and the intention to withhold life-sustaining treatments (LSTs) involving severe dementia in Asian countries. We examined gender differences in the attitude toward the Patient Autonomy Act (PAA) in Taiwan and how the gender differences in these attitudes affect the intention to withhold LSTs for severe dementia. We also investigated self-other differences in the intention to withhold LSTs between genders. METHODS: Between March and October 2019, a structured questionnaire was distributed to hospitalized patients' family members through face-to-face contact in an academic medical center. Exploratory factor analysis and independent and paired-sample t-tests were used to describe gender differences. Mediation analyses controlled for age, marital status, and education level were conducted to examine whether the attitude toward the PAA mediates the gender effect on the intention to withhold LSTs for severe dementia. RESULTS: Eighty respondents filled out the questionnaire. Exploratory factor analysis of the attitude toward the PAA revealed three key domains: regarding the PAA as (1) promoting a sense of abandonment, (2) supporting patient autonomy, and (3) contributing to the collective good. Relative to the men, the women had lower average scores for promoting a sense of abandonment (7.48 vs. 8.94, p = 0.030), higher scores for supporting patient autonomy (8.74 vs. 7.94, p = 0.006), and higher scores for contributing to the collective good (8.64 vs. 7.47, p = 0.001). Compared with the women, the men were less likely to withhold LSTs for severe dementia (15.84 vs. 18.88, p = 0.01). Mediation analysis revealed that the attitude toward the PAA fully mediated the gender differences in the intention to withhold LSTs for severe dementia. Both men and women were more likely to withhold LSTs for themselves than for their parents. Compared with the women, the men were more likely to withhold resuscitation for themselves than for their parents (p = 0.05). Women were more likely to agree to enteral tube feeding and a tracheotomy for their husbands than for themselves; men made consistent decisions for themselves and their wives in those LST scenarios. CONCLUSION: Gender influences the attitude toward advanced care planning and consequently affects the intention to withhold LSTs, indicating that there may be a difference in how men and women perceive EOL decision-making for severe dementia in Taiwan. Further studies are warranted.

Medical students' affective reactions to workplace experiences: qualitative investigation in a Chinese cultural context.

BACKGROUND: Compassion fatigue, unprofessional behavior, and burnout are prompting educators to examine medical students' affective reactions to workplace experiences. Attributes of both students and learning environments are influenced by their socio-cultural backgrounds. To prevent 'educational cultural hegemony', opinion leaders have advocated research in under-represented cultural contexts, of which Asia is a prime example. This study aimed to broaden the discourse of medical education by answering the question: how do students react affectively to workplace experiences in a Chinese cultural context? METHODS: In 2014, the authors recruited five female and seven male Taiwanese clerkship students to make 1-2 audio-diary recordings per week for 12 weeks describing affective experiences, to which they had consciously reacted. The authors analyzed transcripts of these recordings thematically in the original Mandarin and prepared a thick description of their findings, including illustrative extracts. An English-speaking education researcher helped them translate this into English, constantly comparing the interpretation with the original, untranslated data. RESULTS: (Mis) matches between their visions of future professional life and clerkship experiences influenced participants' affective reactions, thoughts, and behaviors. Participants managed these reactions by drawing on a range of personal and social resources, which influenced the valence, strength, and nature of their reactions. This complex set of interrelationships was influenced by culturally determined values and norms, of which this report provides a thick description. CONCLUSION: To avoid educational cultural hegemony, educators need to understand professional behavior in terms of complex interactions between culturally-specific attributes of individual students and learning environments. TRIAL REGISTRATION: The ethics committee of the National Taiwan University (NTU) Hospital gave research ethics approval ( 20130864RINB ).

Identifying Key Genetic Regions for Cell Sheet Morphogenesis on Chromosome 2L Using a Drosophila Deficiency Screen in Dorsal Closure.

Cell sheet morphogenesis is essential for metazoan development and homeostasis of animal form - it contributes to developmental milestones including gastrulation, neural tube closure, heart and palate formation and to tissue maintenance during wound healing. Dorsal closure, a well-characterized stage in Drosophila embryogenesis and a model for cell sheet morphogenesis, is a remarkably robust process during which coordination of conserved gene expression patterns and signaling cascades regulate the cellular shape changes and movements. New 'dorsal closure genes' continue to be discovered due to advances in imaging and genetics. Here, we extend our previous study of the right arm of the 2nd chromosome to the left arm of the 2nd chromosome using the Bloomington deficiency kit's set of large deletions, which collectively remove 98.9% of the genes on the left arm of chromosome two (2L) to identify 'dorsal closure deficiencies'. We successfully screened 87.2% of the genes and identified diverse dorsal closure defects in embryos homozygous for 49 deficiencies, 27 of which delete no known dorsal closure gene. These homozygous deficiencies cause defects in cell shape, canthus formation and tissue dynamics. Within these deficiencies, we have identified pimples, odd-skipped, paired, and sloppy-paired 1 as dorsal closure genes on 2L that affect lateral epidermal cells. We will continue to identify novel 'dorsal closure genes' with further analysis. These forward genetic screens are expected to identify new processes and pathways that contribute to closure and links between pathways and structures already known to coordinate various aspects of closure.

Impact of major illnesses and geographic regions on do-not-resuscitate rate and its potential cost savings in Taiwan.

BACKGROUND/PURPOSE: Do-not-resuscitate (DNR) is a legal order that demonstrates a patient's will to avoid further suffering from advanced treatment at the end of life. The concept of palliative care is increasingly accepted, but the impacts of different major illnesses, geographic regions, and health expenses on DNR rates remain unclear. METHODS: This study utilized the two-million National Health Insurance (NHI) Research Database to examine the percentage of DNR rates among all deaths in hospitals from 2001 to 2011. DNR in the study was defined as no resuscitation before death in hospitals. Death records were extracted from the database and correlated with healthcare information. Descriptive statistics were compiled to examine the relationships between DNR rates and variables including major illnesses, geographic regions, and NHI spending. RESULTS: A total of 126,390 death records were extracted from the database for analysis. Among cancer-related deaths, pancreatic cancer patients had the highest DNR rate (86.99%) and esophageal cancer patients had the lowest DNR rate (71.62%). The higher DNR rate among cancer-only patients (79.53%) decreased with concomitant dialysis (66.07%) or ventilator use (57.85%). The lower DNR rates in patients with either chronic dialysis (51.27%) or ventilator use (59.10%) increased when patients experienced these two conditions concomitantly (61.31%). Although DNR rates have consistently increased over time across all regions of Taiwan, a persistent disparity was noted between the East and the South (76.89% vs. 70.78% in 2011, p < 0.01). After adjusting for potential confounders, DNR patients had significantly lower NHI spending one year prior to death ($67,553), compared with non-DNR patients. CONCLUSION: Our study found that DNR rates varied across cancer types and decreased in cancer patients with concomitant chronic dialysis or ventilator use. Disparities in DNR rates were evident across geographic regions in Taiwan. A wider adoption of the DNR policy may achieve substantial savings in health expenses and improve patients' quality of life.

Publisher Correction: Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes.

The original version of this Article contained an error in the spelling of the author Woochul Song, which was incorrectly given as Woochul C. Song. This has been corrected in both the PDF and HTML versions of the Article.

Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes.

Synthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar[5]arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m-2 h-1 bar-1 compared with 4-7 L m-2 h-1 bar-1) over similarly rated commercial membranes.

The outcomes and controversies of transplant tourism-Lessons of an 11-year retrospective cohort study from Taiwan.

BACKGROUND: Transplant tourism has increased rapidly in the past two decades, accounting for about 10% of world organ transplants. However it is ethically controversial and discouraged by professional guidelines. We conducted this study to investigate the outcomes and trends of overseas kidney and liver transplantation in Taiwan to provide a sound basis for ethical reflection. METHODS AND FINDINGS: The Taiwanese National Health Insurance Research Database was used to identify 2381 domestic and 2518 overseas kidney transplant (KT) recipients from 1998 to 2009 and 1758 domestic and 540 overseas liver transplantation (LT) recipients from 1999 to 2009. Cox proportional hazards models were used to assess the risks of mortality and graft failure. The numbers of overseas transplantation increased after 2000, reached a peak in 2005 and decreased after 2007. Compared to their domestic counterparts, the overseas KT recipients were older, male predominant, with shorter pre-op dialysis period and more comorbidities. Similarly, the overseas LT recipients were older, male predominant and had more hepatocellular carcinoma cases. The 1-, 5-, and 10-year patient survival rates were 96.9%, 91.7% and 83.0% respectively for domestic KT and 95.8%, 87.8% and 73.1% for overseas KT (p<0.001). The 1-, 5-, and 10-year patient survival rates were 89.2%, 79.5%, 75.2% for domestic LT and 79.8%, 54.7%, 49.9% for overseas LT (p<0.001). CONCLUSION: The poorer outcomes of the overseas groups may be due to more older patients, more comorbidities (KT), or more hepatocellular carcinoma recurrences (LT). After domestic reform and international ethical challenges, the numbers of organ tourism decreased but the practice still persisted surreptitiously. Compulsory registration policies for overseas transplantation with international conventions to sanction organ trafficking and transplant tourism should be considered to stop these controversial practices.

Emotional Learning and Identity Development in Medicine: A Cross-Cultural Qualitative Study Comparing Taiwanese and Dutch Medical Undergraduates.

PURPOSE: Current knowledge about the interplay between emotions and professional identity formation is limited and largely based on research in Western settings. This study aimed to broaden understandings of professional identity formation cross-culturally. METHOD: In fall 2014, the authors purposively sampled 22 clinical students from Taiwan and the Netherlands and asked them to keep audio diaries, narrating emotional experiences during clerkships using three prompts: What happened? What did you feel/think/do? How does this interplay with your development as a doctor? Dutch audio diaries were supplemented with follow-up interviews. The authors analyzed participants' narratives using a critical discourse analysis informed by Figured Worlds theory and Bakhtin's concept of dialogism, according to which people's spoken words create identities in imagined future worlds. RESULTS: Participants talked vividly, but differently, about their experiences. Dutch participants' emotions related to individual achievement and competence. Taiwanese participants' rich, emotional language reflected on becoming both a good person and a good doctor. These discourses constructed doctors' and patients' autonomy in culturally specific ways. The Dutch construct centered on "hands-on" participation, which developed the identity of a technically skilled doctor, but did not address patients' self-determination. The Taiwanese construct located physicians' autonomy within moral values more than practical proficiency, and gave patients agency to influence doctor-patient relationships. CONCLUSIONS: Participants' cultural constructs of physician and patient autonomy led them to construct different professional identities within different imagined worlds. The contrasting discourses show how medical students learn about different meanings of becoming doctors in culturally specific contexts.