医学最新文献

{"title":"PI3Kγ inhibition drives M1 macrophage differentiation and synergizes with PD-L1 blockade to improve survival in poorly immunogenic head and neck squamous cell carcinoma.","authors":"Pete P Jordanides, Sushmitha Jagadeesha, Puja Upadhaya, Nathan M Ryan, Kelvin Anderson, Felipe F Lamenza, Suvekshya Shrestha, Arham Siddiqui, Anna R Bopp, Sherefuddin H Pracha, Peyton Roth, Reegan Kehres, Xiaokui Mo, Steve Oghumu","doi":"10.1080/15384047.2025.2600701","DOIUrl":"10.1080/15384047.2025.2600701","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally with high mortality rates, highlighting the urgent need for novel therapeutic strategies. We investigated the efficacy of combining phosphoinositide 3-kinase gamma (PI3Kγ) inhibition with programmed death-ligand 1 (PD-L1) blockade in a poorly immunogenic HNSCC model.</p><p><strong>Materials and methods: </strong>Mouse bone marrow-derived macrophages (BMDMs) were differentiated and polarized in the presence or absence of the PI3Kγ inhibitor IPI-549 or culture supernatants from MOC2 cells treated with or without IPI-549. MOC2 cells were orthotopically injected into C57BL/6 mice, and treated with anti-PD-L1, IPI-549, combined anti-PD-L1 and IPI-549 or vehicle control. Tumor burden, survival, and immunological responses were evaluated.</p><p><strong>Results and conclusion: </strong>Dual inhibition of PI3Kγ (using IPI-549) and PD-L1 demonstrated nearly significant reduction in primary tumor burden and significantly increased survival compared to single or control treatments. PI3Kγ inhibition promoted macrophage differentiation toward an antitumoral M1 phenotype. In the bone marrow, dual therapy significantly increased MHC-II expression across various myeloid cell subsets and effectively normalized myelopoiesis. Notably, combination therapy increased CD8+ T-cell infiltration into tumors while decreasing T-cell exhaustion marker (LAG-3, CTLA-4, and TIM-3) and protumoral cytokine (IL-4). Combined PI3Kγ and PD-L1 inhibition offers a promising strategy for treating poorly immunogenic HNSCC by simultaneously targeting multiple immunosuppressive mechanisms. These findings provide a strong rationale for combining PI3Kγ and PD-L1 inhibitors as a therapeutic strategy for poorly immunogenic HNSCC, potentially improving clinical outcomes for patients.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2600701"},"PeriodicalIF":4.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the classroom: a qualitative study of voluntary home visits to older adults as a tool for empathy and professional growth in medical students.","authors":"Adi Finkelstein, Naama Constantini, Netanel Gelkop, Tamar Guttman, Anya Krichevsky, Naama Mittelman, Gavriel Parker Sahala, Nir Weigert, Mici Phillips, Ohad Avny, Tali Sahar","doi":"10.1080/10872981.2025.2605378","DOIUrl":"10.1080/10872981.2025.2605378","url":null,"abstract":"<p><p>Global populations are rapidly aging, posing significant challenges. Yet, ageism among clinicians and medical students persists, undermining empathy and care quality. Traditional short-term educational efforts have limited effect; sustained, relationship-based programs hold promise but remain understudied. To address this, we implemented a year-long service-learning project, where first-year medical students visit elderly individuals at their homes to engage in light physical activities and discuss life challenges. This qualitative study examines the project's impact on first, second, and third-year medical students.From August to October 2020, we recruited, via convenience sampling, first-year medical students of three consecutive cohorts (<i>n</i> = 313) that completed ten home visits with older adults; of these sixty (19%) students participated in focus groups/interviews and 128 (41%) submitted reflective assignments. Data was manually analyzed using Braun and Clarke's six-phase reflexive thematic approach until saturation. We adhered to the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist.Three major themes and seven sub-themes emerged. First, building trusting patient-physician relationships, characterized by empathy, trust, and effective communication, alongside a balance between physician responsibility and patient autonomy. Second, embracing uncertainty and holistic care, which involved navigating medical ambiguity and integrating psychosocial dimensions into clinical reasoning. Third, reflecting on vulnerability, aging, and mortality, encompassing the emotional impact of disability and decline; reframing aging positively; and processing experiences of death and loss. Participants described profound shifts in their perspectives on aging, care relationships, and their professional identities; changes that persisted throughout their pre-clinical training. To conclude, early and sustained engagement with older adults in their home environment through a structured service-learning project enhanced medical students' professional development, empathy, and attitudes toward aging. Incorporating similar programs into medical education curricula may provide substantial pedagogical benefits. Future research should assess long-term impacts on career choices and care quality.</p>","PeriodicalId":47656,"journal":{"name":"Medical Education Online","volume":"31 1","pages":"2605378"},"PeriodicalIF":3.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation.","authors":"Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen","doi":"10.1080/10717544.2025.2610532","DOIUrl":"10.1080/10717544.2025.2610532","url":null,"abstract":"<p><p>The recurrence following the discontinuation of medication is a formidable challenge in managing psoriasis. Changes in the microbiome accompany the onset of psoriasis relapse, highlighting a potential therapeutic modality. To evaluate the superiority of the topical administration of aptamer-functionalized curcumin mesoporous silica (Apt-GA+Cur@μmS) plus blue light (BL) in restoring dysbiosis and intervening in recurrence in a murine model, a psoriasis relapse murine model with double imiquimod induction was established. With a BL-responsive shell, Apt-GA+Cur@μmS released curcumin (Cur) to assist BL to improve the preventative and therapeutic effects in the psoriasis relapse murine model, as evidenced by the psoriasis area and severity index, histology, splenic index, and dorsal IL-17A level. We also observed a negative correlation between splenic nitric oxide (NO) levels and the splenic index, indicating a possible mechanism by which Apt-GA+Cur@μmS&BL may function in the treatment of splenomegaly. Treatment with Apt-GA+Cur@μmS&BL exhibited a higher alpha diversity than the model group, with levels similar to those of healthy mice, indicating that this combination could adjust the composition of the dorsal microbiome to a healthier state. A reduction in the combined relative abundance of <i>Staphylococcus</i>, <i>Streptococcus,</i> and <i>Corynebacterium</i> as well as restoration of dysbiosis was also verified through 16S rDNA gene sequencing <i>in vivo</i>. Collectively, BL and Apt-GA+Cur@μmS cotherapy alleviates psoriasiform lesions in a double imiquimod-induced murine model by inhibiting IL-17A and increasing splenic NO. Additionally, this cotherapy restores the eubiosis of the dorsal lesions. Thus, it is a promising and innovative therapeutic modality for psoriasis inflammation alleviation and recurrence intervention.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2610532"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological insights regarding the prognostic value of lncRNA PGM5P4-AS1 in breast cancer.","authors":"Rashad Ismayilov, Arzu Oguz","doi":"10.1080/15384047.2026.2614802","DOIUrl":"10.1080/15384047.2026.2614802","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2614802"},"PeriodicalIF":4.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drawbacks in dopaminergic neurotransmission: compromising sexual performance.","authors":"Anastasia Armeni, Rossella E Nappi, Peter Chedraui","doi":"10.1080/09513590.2026.2662695","DOIUrl":"https://doi.org/10.1080/09513590.2026.2662695","url":null,"abstract":"","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"42 1","pages":"2662695"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction statement: effects of the position of fibroids on fertility.","authors":"","doi":"10.1080/09513590.2026.2661492","DOIUrl":"https://doi.org/10.1080/09513590.2026.2661492","url":null,"abstract":"","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"42 1","pages":"2661492"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA prime and peptide boost immunization elicits robust neoantigen-specific CD8 ⁺ T cell responses and therapeutic protection in mouse tumor models.","authors":"Pablo Morgado-Cáceres, Francisca Hofmann-Vega, Diego Figueroa, Juan Saavedra-Almarza, Felipe Gálvez-Cancino, Ximena Díaz, Evelyn Menares, Eduardo Roa, Sofia Hidalgo, Manuel Varas-Godoy, Vincenzo Borgna, Alvaro Lladser","doi":"10.1080/2162402X.2025.2606497","DOIUrl":"10.1080/2162402X.2025.2606497","url":null,"abstract":"<p><p>Therapeutic immunization against tumor neoantigens has the potential to induce potent and highly selective CD8⁺ T-cell-mediated antitumor immunity. Consequently, immunization strategies that generate robust neoantigen-specific T-cell responses are needed. Here, we tested homologous and heterologous DNA- and peptide-based immunization strategies using a neoantigen model. We observed that priming with DNA followed by peptide boost immunization elicited the strongest CD8⁺ T-cell responses, which exhibited effector and memory precursor phenotypes and led to the formation of circulating and skin-resident memory T cells. In prophylactic settings, this immunization regimen delayed the growth of B16F10 melanoma and rejected EL4 lymphoma cells expressing a self-antigen. In a therapeutic setting, a DNA prime-peptide boost eliminated EL4 tumors expressing the neo-epitope model in most mice. Consistently, DNA prime-peptide boost targeting two bona fide neoepitopes of MC38 tumor model elicited neoepitope-specific CD8⁺ T-cell responses and a marked therapeutic effect, which may be enhanced by combining with anti-PD-1 antibody. These results highlight the potential of DNA prime-peptide boost as a promising strategy for therapeutic neoantigen immunization that elicits strong CD8⁺ T-cell responses and potent antitumor effects.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2606497"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between oxidative balance score and benign prostatic hyperplasia: an analysis based on the NHANES from 2003 to 2008.","authors":"Feihong Xie, Zongke Yang","doi":"10.1080/13685538.2025.2611694","DOIUrl":"10.1080/13685538.2025.2611694","url":null,"abstract":"<p><strong>Purpose: </strong>The pathophysiology of benign prostatic hyperplasia (BPH), a prevalent condition among aging males, remains unclear. Given emerging evidence implicating oxidative stress (OS) in prostatic pathogenesis, this study investigated the association between the comprehensive Oxidative Balance Score (OBS) and BPH prevalence.</p><p><strong>Materials and methods: </strong>The National Health and Nutrition Examination Survey (NHANES) database was selected to determine BPH using a self-report questionnaire, and multivariate logistic regression was performed to explore the correlation between OBS and BPH. Smoothed curve fitting, threshold effect analysis, and stratified analysis were performed.</p><p><strong>Results: </strong>The present study, which ultimately included 621 participants, showed that after adjusting for potential confounders, an increase in OBS was associated with a slightly increased risk of developing BPH compared with the lowest tertile (T1) (OR = 1.07, 95% CI: 1.02,1.13, <i>P</i> = 0.015; OR = 1.09, 95% CI: 1.01, 1.17, <i>P</i> = 0.029). Smoothed curve fitting showed that when OBS was >21, the risk of developing BPH was associated with a 27% increase in the risk (OR = 1.27, 95% CI: 1.13, 1.43).</p><p><strong>Conclusion: </strong>This study reveals a significant non-linear association between OBS and BPH: when OBS > 21, higher OBS scores are associated with an increased risk of BPH.</p>","PeriodicalId":55542,"journal":{"name":"Aging Male","volume":"29 1","pages":"2611694"},"PeriodicalIF":3.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of bipolar disorder with concomitant pregnancy-induced hypertension and associated pharmacotherapies in the United States, Canada and Saudi Arabia over a five-year period (2019-2023).","authors":"Kelly Mover, Nicole Shirvani, Walter Wills, Suzanne Lababidi, Terrika Jones, Bryna Peplinski","doi":"10.1080/0167482X.2025.2609622","DOIUrl":"10.1080/0167482X.2025.2609622","url":null,"abstract":"<p><strong>Background: </strong>Rates of hypertensive disorders affecting pregnancy are increasing, and bipolar disorder is more common in pregnancy than previously thought.</p><p><strong>Objective: </strong>The authors investigated differences in the incidence of hypertensive disorders of pregnancy between those with and without bipolar disorder (BPD) and between those receiving and not receiving pharmacotherapy for BPD. Differences in the incidence of hypertensive disorders of pregnancy in those with BPD between those on prophylactic aspirin (ASA) and not, were also examined.</p><p><strong>Methods: </strong>EPIC COSMOS was used to examine records from 2019 to 2023.</p><p><strong>Results: </strong>The authors found a meaningful difference in proportions between those with and without BPD when observing development of hypertensive disorders of pregnancy across years. Slightly increased odds of hypertensive disorders were found among those reporting BPD pharmacotherapy compared to those not. Slightly increased odds of hypertensive disorders occurred in those with BPD reporting ASA.</p><p><strong>Conclusions: </strong>The increased odds among those reporting BPD pharmacotherapy could be due to sequelae of disease, medication used, or comorbidities. These findings further corroborate prior evidence of the increasing prevalence of both maternal health complications and mental health disorders int eh United States.</p>","PeriodicalId":50072,"journal":{"name":"Journal of Psychosomatic Obstetrics & Gynecology","volume":"47 1","pages":"2609622"},"PeriodicalIF":2.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring medical Artificial Intelligence Readiness among Korean medical students: a cross-sectional study.","authors":"Jihyun Si","doi":"10.1080/10872981.2026.2696610","DOIUrl":"https://doi.org/10.1080/10872981.2026.2696610","url":null,"abstract":"<p><strong>Introduction: </strong>Artificial intelligence (AI) is rapidly transforming healthcare systems and clinical practice, increasing the need to prepare future physicians to work effectively with AI technologies in clinical contexts. Despite growing interest in integrating AI into medical education, empirical evidence regarding medical students' readiness to use AI remains limited. This study aimed to assess medical AI readiness among Korean medical students and explore factors associated with their readiness.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted among medical students enrolled in a six-year medical program at a university in Korea. A total of 204 students participated in the study. Medical AI readiness was measured using the Medical Artificial Intelligence Readiness Scale for Medical Students (MAIRS-MS), which assesses four domains: cognition, ability, vision, and ethics. Descriptive statistics, independent t-tests, and Pearson's correlation analyses were performed using SPSS version 27.</p><p><strong>Results: </strong>The overall mean score of medical AI readiness was 4.19 on a 7-point Likert scale, indicating a moderate level of medical AI readiness. Among the subscales, ethics showed the highest mean score (4.69), followed by vision (4.44), ability (4.18), and cognition (3.92). The frequency of AI use was significantly associated with medical AI readiness, whereas the daily duration of AI use was not. No significant gender differences were observed. When students were divided into the low (pre-medical years 1-2) and high (medical years 1-4) groups, the high group showed significantly higher scores only in the ability subscale.</p><p><strong>Conclusions: </strong>The findings suggest that medical students are not yet sufficiently prepared to utilize AI technologies in clinical practice, particularly in terms of knowledge and practical competencies related to AI. These results highlight the need for structured and longitudinal AI education in medical curricula to better prepare future physicians for AI-integrated healthcare environments.</p>","PeriodicalId":47656,"journal":{"name":"Medical Education Online","volume":"31 1","pages":"2696610"},"PeriodicalIF":4.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}