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Background: The specific dimensions of learners that have been impacted by educational programs related to social determinants of health (SDoH) remain unknown. This study aims to elucidate how learners are affected by postgraduate education (a single 90‐min educational session) regarding tool‐guided clinical assessment of patients' social backgrounds. Methods: A pretest‐posttest design was utilized in which residents (postgraduate year (PGY) 1 or 2) and fellows in family medicine (PGY over 3) were recruited. Likert‐type questions were developed based on previous qualitative findings. Participants answered these questions before, immediately after, and 1.5 months after the educational session on tool‐guided clinical SDoH assessment. Paired‐sample t‐tests were used, and effect size was measured using Cohen's d. Results: A total of 114 residents and fellows participated. After the session, participants expressed more interest in knowing their patients' social backgrounds when considering how to address their patients and were more open to embracing a pre‐established assessment framework. Participants also considered clinical skills related to SDoH as learnable and improved their attitude toward patients. They reported that they did not perform specific interventions related to SDoH within 1.5 months after the session. Unlike previous qualitative findings, their concern about the implementation of SDoH‐related practices did not increase significantly. Conclusion: An educational session on tool‐guided SDoH assessment may have a positive impact on learners' attitudes related to addressing patients' social backgrounds without fostering concerns. [ABSTRACT FROM AUTHOR]

Background: Although nurses are expected to address the social determinants of health (SDH) in clinical settings, the perspectives of front‐line nurses on the integration of SDH into their clinical practice remain unclear. Understanding the dynamism of this integration and its outcomes can yield crucial insights into effective nursing care. This study aims to elucidate the integration and adoption of tool‐based SDH assessment nursing programs and their impacts on daily nursing care. Methods: We conducted qualitative research at a small community‐based hospital in Japan, where a tool‐based program characterized by social background interviews and documentation was implemented. Nurses at the hospital were recruited via purposive and snowball sampling. After hypothesis generation, semi‐constructed in‐depth online interviews were conducted. Each interview lasted between 30 and 50 min. The data were analyzed via thematic analysis using the framework approach. Results: A total of 16 nurses participated. Participants' incorporation of the novel SDH assessment program was bolstered by prior learning and their recognition of its practical value. Institutional support and collaborative teamwork further facilitated the adoption of this innovation. Enhanced knowledge about the social contexts of their patients contributed to increased respect, empathy, and self‐affirmation among participants, consequently enhancing the quality of nursing care. Conclusion: Through team‐based learning, reflection, and support, nurses can integrate a tool‐based SDH assessment program into their daily nursing practice. This program has the potential to empower nurses to deliver more holistic care and redefine their professional identity. Further research is warranted to assess patient‐reported outcomes. [ABSTRACT FROM AUTHOR]

The concept of social accountability in medical schools is globally accepted, but data regarding Japanese medical schools are lacking and unclear. This study aimed to elucidate the perception of social accountability of medical schools in Japan and compare this to global frameworks. A document on Japanese medical accreditation standards (Basic Medical Education: Japanese Specifications WFME Global Standards for Quality Improvement) was used for this study. We included 45 medical schools in a qualitative content analysis done via inductive category formation. The documents were also assessed using the social obligation scale. Three main categories and 15 categories were identified. The three main categories were as follows: Issues in society, Quality assurance of medical school, and Improvement of individual quality. Most categories were common to those in global frameworks, but some were characteristic of the Japanese context. The distribution of schools on the social obligation scale in six elements varied mainly 'from responsibility to responsiveness' or equal unless the elements were promoted by national policy. The social accountability of Japanese medical schools is mostly common with the global frameworks. Our findings will help the social accountability of medical schools to become better understood and developed beyond contextual borders. [ABSTRACT FROM AUTHOR]

Introduction: An understanding of social determinants of health (SDH) and patients' social circumstances is recommended to deliver contextualised care. However, the processes of patient care related to SDH in clinical settings have not been described in detail. Observable practice activities (OPAs) are a collection of learning objectives and activities that must be observed in daily practice and can be used to describe the precise processes for professionals to follow in specific situations (process OPA.) Methods: We used a modified Delphi technique to generate expert consensus about the process OPA for patient care related to SDH in primary care settings. To reflect the opinions of various stakeholders, the expert panel comprised clinical professionals (physicians, nurses, public health nurses, social workers, pharmacists and medical clerks), residents, medical students, researchers (medical education, health care, sociology of marginalised people), support members for marginalised people and patients. The Delphi rounds were conducted online. In Round 1, a list of potentially important steps in the processes of care was distributed to panellists. The list was modified, and one new step was added. In Round 2, all steps were acknowledged with few modifications. Results: Of 63 experts recruited, 61 participated, and all participants completed the Delphi rounds. A total of 14 observable steps were identified, which were divided into four components: communication, practice, maintenance and advocacy. The importance of ongoing patient–physician relationships and collaboration with professionals and stakeholders was emphasised for the whole process of care. Discussion: This study presents the consensus of a variety of experts on the process OPA for patient care related to SDHs. Further research is warranted to investigate how this Communication–Practice–Maintenance–Advocacy framework could affect medical education, quality of patient care, and patient outcomes. This study illustrates a means of improving curricula by showing the Communication‐Practice‐Maintenance‐Advocacy (CPMA) framework to be useful for incorporating social determinants of health into healthcare to enhance education. [ABSTRACT FROM AUTHOR]

Background and Aims: It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy. Methods: In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively. Results: Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m2) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51–4.25) and 2.56 (95% CI: 1.14–5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61–2.33). Conclusions: Obesity and heavy alcohol consumption increased the risk of HCC development after SVR. [ABSTRACT FROM AUTHOR]

The organoid culture technique has been recently applied to modeling carcinogenesis in several organs. To further explore its potential and gain novel insights into tumorigenesis, we here investigated whether pancreatic ductal adenocarcinoma (PDA) could be generated as subcutaneous tumors in immunocompromised nude mice, by genetic engineering of normal organoids. As expected, acute induction of Kras G12D in vitro occasionally led to development of tiny nodules compatible with early lesions known as pancreatic intraepithelial neoplasia (PanIN). Kras G12D -expressing cells were enriched after inoculation in the subcutis, yet proved rather declined during culture, suggesting that its advantage might depend on surrounding environments. Depletion of growth factors or concurrent Trp53 deletion resulted in its robust enrichment, invariably leading to development of PanIN or large high-grade adenocarcinoma, respectively, consistent with in vivo mouse studies for the same genotype. Progression from PanIN was also recapitulated by subsequent knockdown of common tumor suppressors, whereas the impact of Tgfbr2 deletion was only partially recapitulated, illustrating genotype-dependent requirement of the pancreatic niche for tumorigenesis. Intriguingly, analysis of tumor-derived organoids revealed that Kras G12D -expressing cells with spontaneous deletion of wild-type Kras were positively selected and exhibited an aging-related mutation signature in nude mice, mirroring the pathogenesis of human PDA, and that the sphere-forming potential and orthotopic tumorigenicity in syngenic mice were significantly augmented. These observations highlighted the relevance of the subcutis of nude mice in promoting PDA development despite its ectopic nature. Taken together, pancreatic carcinogenesis could be considerably recapitulated with organoids, which would probably serve as a novel disease model. [ABSTRACT FROM AUTHOR]

Cancers arising from the biliary tract are refractory to conventional therapies, requiring the development of novel therapeutics. However, only a limited number of genetically engineered mouse models have been created, partly because of time-consuming work required. Besides, liver-specific gene manipulation mostly resulted in concurrent development of hepatocellular carcinoma, another type of liver cancer, and gallbladder-restricted gene targeting is still not feasible. Consequently, establishment of cancer type–specific disease modeling remains a technical challenge. To address this issue, we took an alternative cell-based approach to quickly induce tumorigenesis ex vivo. Specifically, murine primary organoids from liver and gallbladder were transduced with lentiviral vectors to reconstitute genetic alterations common in biliary tract cancers, followed by inoculation in immunodeficient mice. Although any single genetic alteration did not induce tumors, mutant Kras and repression of major tumor suppressors cooperated for tumor development within 2 months. Induced lesions varied among normal, dysplastic and papillary lesions to adenocarcinoma, recapitulating multistep tumorigenesis even in a heterotopic situation. We further demonstrated that two putative oncogenes in intrahepatic cholangiocellular carcinoma, mutant Pik3ca and FGFR2-AHCYL1 fusion, were rather modest drivers for liver-derived organoids, probably requiring additional mutations or hepatic niche to robustly induce full-blown tumors. Thus, we showed that cancer cells could be readily generated from primary cells in the biliary tract, at least in cases where genetic factors play dominant roles. Collectively, this study will likely contribute to gaining mechanistic insights into biliary carcinogenesis and providing valuable resources for drug discovery. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion Although primary care professionals often encounter difficulties when attending to patients in complex and challenging social situations (CCSS), little is known about how professionals cultivate an optimistic approach to caring for patients in CCSS. This study aims to recruit professionals who exhibit a passion for seeing patients in CCSS, to gain insights into their positive attitude.We conducted a qualitative study in Japan of 30 primary care professionals: 15 physicians and 15 non‐physician professionals (nurses, medical social workers and medical clerks). We performed online in‐depth interviews and employed a thematic analysis utilising the framework approach to identify how the participants felt a passion for seeing patients in CCSS.Two themes emerged about the passion: (i) the joy derived from interacting with patients and (ii) the joy derived from professional growth or development. Participants expressed curiosity about their patients, found happiness in the journey with them and established irreplaceable relationships. Concurrently, participants noted professional growth as expert generalists, and their team developed collaboration and competency through accumulating experience and learning. These two domains of joy were intricately interconnected. In addition, several factors related to developing, maintaining and spreading the positive attitude were identified.This study described the positive attitude of primary care professionals towards engaging with patients in CCSS. Despite the inherent challenges, these professionals demonstrated vibrancy and pleasure in their interactions with patients and their professional development. Workplace culture including team‐based support and continuous learning is important in fostering and maintaining such an attitude. [ABSTRACT FROM AUTHOR]

Background: Several organisations have called for primary care professionals to address social determinants of health (SDoH) in clinical settings. For primary care physicians to fulfill their community health responsibilities, the implications of the SDoH recommendations need to be clarified., Aim: To describe primary care physicians' views about being asked to address SDoH in clinical settings, from both positive and negative perspectives., Design & Setting: A qualitative study in Japan. Twenty-one physicians were purposively recruited., Method: 'Love and breakup letter' methodology was used to collect qualitative data that contained both positive and negative feelings. Participants wrote love and breakup letters about being asked to address SDoH in a clinical setting, then undertook an in-depth online interview. Data were analysed via thematic analysis using the framework approach., Results: The following themes were identified: (i) primary care physicians take pride in being expected to address SDoH; (ii) primary care physicians rely on the recommendations as a partner, even in difficult situations; (iii) primary care physicians consider the recommendations to be bothersome, with unreasonable demands and challenges, especially when supportive surroundings are lacking; and (iv) primary care physicians reconstruct the recommendations on the basis of their experience., Conclusion: Primary care physicians felt both sympathy and antipathy towards recommendations asking them to address SDoH in their clinical practice. The recommendations were not followed literally, instead contributing to physicians' clinical mindlines. Professional organisations that plan to develop and publish recommendations about SDoH should consider how their recommendations might be perceived by their target audience., (Copyright © 2023, The Authors.)

Ferric nitrilotriacetate induces oxidative renal tubular damage via Fenton-reaction, which subsequently leads to renal cell carcinoma (RCC) in rodents. Here, we used gene expression microarray and array-based comparative genomic hybridization analyses to find target oncogenes in this model. At the common chromosomal region of amplification (4q22) in rat RCCs, we found ptprz1, a tyrosine phosphatase (also known as protein tyrosine phosphatase zeta or receptor tyrosine phosphatase beta) highly expressed in the RCCs. Analyses revealed genomic amplification up to eightfold. Despite scarcity in the control kidney, the amounts of PTPRZ1 were increased in the kidney after 3 weeks of oxidative stress, and mRNA levels were increased 16 approximately 552-fold in the RCCs. Network analysis of the expression revealed the involvement of the beta-catenin pathway in the RCCs. In the RCCs, dephosphorylated beta-catenin was translocated to nuclei, resulting in the expression of its target genes cyclin D1, c-myc, c-jun, fra-1, and CD44. Furthermore, knockdown of ptprz1 with small interfering RNA (siRNA), in FRCC-001 and FRCC-562 cell lines established from the induced RCCs, decreased the amounts of nuclear beta-catenin and suppressed cellular proliferation concomitant with a decrease in the expression of target genes. These results demonstrate that chronic oxidative stress can induce genomic amplification of ptprz1, activating beta-catenin pathways without the involvement of Wnt signaling for carcinogenesis. Thus, iron-mediated persistent oxidative stress confers an environment for gene amplification.