Med最新文献

{"title":"Adoptive MAIT cell therapy for liver cancer enhanced by multimodal modulation of immune receptors and checkpoints.","authors":"Yan-Ruide Li, Xinyuan Shen, Yichen Zhu, Yuning Chen, Jie Huang, Shelby Yeh, Thomas Yuen, Coral L Clune, Paulina Dominguez-Vela, Shreya Gumate, Vatche G Agopian, Lili Yang","doi":"10.1016/j.medj.2026.101272","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101272","url":null,"abstract":"<p><strong>Background: </strong>Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that recognize riboflavin-derived metabolites presented by the monomorphic major histocompatibility complex (MHC)-class I-related molecule MR1. MAIT cells are highly enriched in the human liver and are increasingly implicated in liver cancer immunity, yet their antitumor potential and therapeutic applicability remain incompletely defined.</p><p><strong>Methods: </strong>Here, we profiled MAIT cells derived from peripheral blood of healthy donors and patients with hepatocellular carcinoma, revealing disease-associated phenotypic alterations marked by immune checkpoint dysregulation. To address current therapeutic limitations, we developed a robust ex vivo expansion platform capable of generating MAIT cells with high yield, purity, and potent cytotoxic function. Using multiple human liver cancer subcutaneous and orthotopic xenograft mouse models, we demonstrate that adoptively transferred MAIT cells mediate effective tumor targeting and killing in vivo.</p><p><strong>Findings: </strong>Mechanistically, MAIT cell antitumor activity is driven by both T cell receptor (TCR)-dependent recognition and natural killer receptor (NKR)-mediated cytotoxicity and is further enhanced by antigen stimulation; cytokine receptor signaling, particularly via interleukin (IL)-15; and immune checkpoint modulation involving programmed cell death protein 1 (PD-1) and T cell immunoglobulin and ITIM domain (TIGIT). In addition, MAIT cells demonstrated a favorable safety profile, with no evidence of liver toxicity observed in xenograft mouse models.</p><p><strong>Conclusions: </strong>Together, these findings establish MAIT cells as functional antitumor effectors in liver cancer and provide a mechanistic and translational framework for adoptive MAIT cell therapy enhanced by multimodal modulation of immune receptors and checkpoints.</p><p><strong>Funding: </strong>Major funding was provided by the California Institute for Regenerative Medicine (CIRM).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101272"},"PeriodicalIF":13.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human oral and airway viral genome catalog from metagenomes enables virome characterization informing respiratory health.","authors":"Xiaohui Zou, Yawen Ni, Qing Zhang, Kang Chang, Shenghui Li, Yue Zhang, Hailong Yu, Chun Wang, Xiaoxuan Yao, Shibin Chen, Xiaolu Nie, Jiankang Zhao, Binghuai Lu, Yanqin Li, Ning Gan, Zhong Wang, Qiulong Yan, Bin Cao","doi":"10.1016/j.medj.2026.101269","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101269","url":null,"abstract":"<p><strong>Background: </strong>Viral communities of the upper aerodigestive tract represent an important component of the human microbial ecosystem but remain poorly characterized due to the limited availability of habitat-specific reference resources.</p><p><strong>Methods: </strong>We integrated 19,997 public and 2,673 newly sequenced oral and airway metagenomes to establish the Oral and Airway Viral Genome Catalogue (OAVGC). Viral genomes were reconstructed and characterized through taxonomic assignment, prokaryotic host prediction, functional annotation, and assessment of putative antibacterial activity. Our prospective longitudinal aging cohort, alongside 5 in-house datasets and publicly cohorts, were analyzed to investigate associations between airway virome profiles and respiratory health.</p><p><strong>Findings: </strong>The OAVGC comprised 141,459 high-quality viral genomes (completeness ≥90%) clustered into 68,708 viral operational taxonomic units (vOTUs). Approximately half of these viruses and families are previously undescribed, with independent cross-cohort detection and PCR assays providing additional support for their occurrence. Across multiple respiratory infection cohorts, the virome exhibited convergent diversity reductions and compositional signatures. In the prospective cohort, the baseline airway virome was correlated with host lung function and geriatric health scores. Virome-based machine learning classifiers demonstrated potential for predicting the future occurrence of upper respiratory tract infections up to 12 months in advance, outperforming bacteriome-based models in our prediction analyses.</p><p><strong>Conclusions: </strong>The OAVGC provides an unprecedented genomic and functional resource for investigating the ecological and clinical associations of the oral-airway virome, revealing its potential impact on respiratory health and capacity to predict future infections.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (82341113) and National Key R&D Program of China (2022YFA1304303).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101269"},"PeriodicalIF":13.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma to rhabdomyosarcoma plasticity in the setting of immunotherapy.","authors":"Andrew D Knight, Emily J Robitschek, Jia-Ren Lin, Tyler Aprati, Giuseppe Tarantino, Jaijia Chen, Dennie T Frederick, Alvin Shi, Ana B Larque, Benchun Miao, Rumya S Raghavan, Tatyana Sharova, John H Shin, Peter Sorger, Manolis Kellis, Keith T Flaherty, Nir Hacohen, Genevieve M Boland, Ivan Chebib, David Liu, Ryan J Sullivan, Arnav Mehta","doi":"10.1016/j.medj.2026.101266","DOIUrl":"10.1016/j.medj.2026.101266","url":null,"abstract":"<p><strong>Background: </strong>Acquired resistance to immune checkpoint inhibitors (ICIs) remains a significant challenge in the treatment of metastatic melanoma. Phenotypic plasticity, such as dedifferentiation and transdifferentiation, is an increasingly recognized mechanism of treatment resistance.</p><p><strong>Methods: </strong>We present a case of a 70-year-old man with metastatic melanoma who experienced progression through sequential treatments including pembrolizumab in combination with the HDAC inhibitor entinostat and ipilimumab. During treatment, a histologically distinct pleomorphic rhabdomyosarcoma (RMS) emerged at metastatic sites. Longitudinally acquired tumor samples representing both phenotypes were analyzed using whole-exome sequencing (WES), RNA sequencing (RNA-seq), and high-plex tissue imaging (spatial proteomics).</p><p><strong>Findings: </strong>WES revealed driver mutations (e.g., NRAS and NF1) and loss of heterozygosity (LOH) shared between phenotypes indicating a common ancestral clone. Phylogenetic analysis demonstrated an early divergence of the phenotypes, with each later acquiring unique mutations. RNA-seq showed mutually exclusive expression of lineage-specific markers as well as epithelial-mesenchymal transition and myogenic gene set enrichment in the RMS samples. High-plex imaging identified distinct tumor microenvironments, with RMS lesions enriched in CD163⁺ macrophages.</p><p><strong>Conclusions: </strong>This case provides molecular evidence of phenotypic plasticity occurring under the selective pressure of immune checkpoint inhibitor therapy.</p><p><strong>Funding: </strong>This study was supported by the National Institutes of Health (K12CA087723 and K08CA234458), the Doris Duke Charitable Foundation, and Adelson Medical Research Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101266"},"PeriodicalIF":13.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection.","authors":"Siqi Yong, Jiaying Zhang, He Tian, Zehua Wang, Shaohua Zhang, Robin Barry Chan, Yingjuan Zhou, Guibin Wang, Lianchun Liang, Zhifeng Song, Jingwen Han, Gaofeng Ma, Sin Man Lam, Yingmei Feng, Guanghou Shui","doi":"10.1016/j.medj.2026.101264","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101264","url":null,"abstract":"<p><strong>Background: </strong>Monkeypox virus (MPXV) infects diverse human cell types, and human immunodeficiency virus (HIV) co-infection is common. The immunometabolic consequences of MPXV infection, and how it may be altered by HIV, remain poorly defined.</p><p><strong>Methods: </strong>We performed quantitative plasma lipidomics and precise metabolomics in a discovery cohort (n = 81) comprising MPXV-monoinfected (MPLWOH), MPXV-HIV-coinfected (MPLWH), and HIV-monoinfected (PLWH) patients and healthy controls, integrating exosome proteomics, cytokine profiling, and transcriptomics of exosome-treated HepG2 and A549 cells for functional interpretation. An independent validation cohort (n = 65) was used to assess cross-cohort reproducibility.</p><p><strong>Findings: </strong>MPXV infection induced broad lipid remodeling, with elevations in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and reductions in phosphatidylcholine (PC), lysophospholipids, cholesteryl ester (CE), and exosomal lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). These lipid alterations were correlated with tissue injury markers and inflammatory cytokines. The MPLWH group exhibited more severe metabolic disruption, including marked sulfatide (SL) depletion, lower cholesterol and high-density lipoprotein cholesterol (HDL-c), and extensive rewiring of lipid-cytokine associations. SL depletion in MPLWH correlated with abundances of COPI-mediated retrograde trafficking proteins in exosomes. Transcriptomic profiling of exosome-treated cells provided functional validation: MPLWOH exosomes induced lipid metabolism and repair-associated epithelial programs, while MPLWH exosomes drove phospholipid remodeling and acute inflammatory and mucosal barrier-stress responses.</p><p><strong>Conclusions: </strong>MPXV infection reprograms host lipid metabolism and exosome composition, with HIV co-infection amplifying inflammatory, metabolic, and trafficking disruptions. These convergent multi-omics signatures link systemic lipid dysregulation to exosome-mediated immunomodulation and identify potential targets for host-directed interventions.</p><p><strong>Funding: </strong>This study was funded by the Major Project of Guangzhou National Laboratory.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101264"},"PeriodicalIF":13.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bimodal large language model reduces misalignment in patient education: A double-blinded randomized trial.","authors":"Peixing Wan, Zigeng Huang, Haoquan Huang, Guihan Liang, Mingyan Guo, Sulin Xu, Xinti Sun, Wenjun Tang, Dajun Pei, Jing Chen, Yulan Nie, Shaofen Deng, Yizhi Zhou, Hongru Duan, Rong Zhang, Xiaoying Xu, Erfu Hai, Minghui Cao, Erping Long","doi":"10.1016/j.medj.2026.101263","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101263","url":null,"abstract":"<p><strong>Background: </strong>Effective patient education requires accurate communication aligned with patients' emotional and semantical needs. Text-based large language models (LLMs) lack access to non-verbal cues, which may contribute to misaligned responses.</p><p><strong>Methods: </strong>We evaluated emotional and semantic misalignment in a text-based LLM using 64,200 utterances from 16,583 patient education cases across six departments and three centers. Dolphin was developed integrating text and audio cues and evaluated through emotion recognition, semantic consistency assessment, branch-level ablations, and a double-blinded randomized trial against a matched text-based LLM comparator (Chinese Clinical Trial Registry: (ChiCTR2500095933).</p><p><strong>Findings: </strong>The text-based LLM showed emotional misalignment in 36.7% of responses and semantic misalignment in 28.3% of cases, with higher misalignment under greater burden. Dolphin outperformed the text-based LLM in emotion recognition accuracy (0.886 vs. 0.713) and semantic consistency (84.9% vs. 82.1%; both adjusted p < 0.001). Ablations supported contribution of audio branches. Dolphin received higher expert ratings than the text-based LLM and human educators (all p < 0.001). In 555 patients, Dolphin was associated with greater patient satisfaction (98.6% vs. 93.8%), suggestion acceptance (76.1% vs. 58.9%; p < 0.001), proactive disclosure (44.6% vs. 26.5%; p < 0.001), and fewer 7-day unplanned recontact (12.9% vs. 22.9%; p = 0.002). No unsafe recommendations or safety events were identified.</p><p><strong>Conclusions: </strong>Compared with text-based LLM, Dolphin improved emotional-semantic alignment and patient-education outcomes, supporting bimodal alignment as a strategy for reducing misalignment-driven communication failures.</p><p><strong>Funding: </strong>National Natural Science Foundation of China, State Key Laboratory Special Fund, and Chinese Academy of Medical Sciences Innovation Fund.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101263"},"PeriodicalIF":13.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concomitant lipid-lowering and anticoagulation therapy for recurrent venous thromboembolism prevention: A Bayesian meta-analysis.","authors":"Harsini Raaja Sulochana, Yufan Yang, Laura Bindila, Ioannis T Farmakis, Stavros V Konstantinides, Luca Valerio, Philipp S Wild, Vincent Ten Cate","doi":"10.1016/j.medj.2026.101262","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101262","url":null,"abstract":"<p><strong>Background: </strong>It is unclear whether combined anticoagulation (AC) plus lipid-lowering therapies (LLTs) enhance AC efficacy for venous thromboprophylaxis while maintaining an acceptable safety profile.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, Cochrane CENTRAL library, and Web of Science, including randomized controlled trials (RCTs) and observational studies published until May 2026. The associations of LLT+AC vs. AC monotherapy with efficacy outcomes (i.e., recurrent venous thromboembolism [rVTE] and post-thrombotic syndrome [PTS] risk), safety outcomes (i.e., major bleeding), and other outcomes were analyzed. A Bayesian random-effects meta-analysis was used to aggregate study estimates (95% credible interval [CrI]) and calculate the posterior probability of benefit (relative risk [RR] < 1).</p><p><strong>Findings: </strong>The search yielded 28 (17 observational studies and 11 RCTs) studies eligible for meta-analysis. The pooled effect size of LLT+AC vs. AC alone for rVTE was RR = 0.73 [95% CrI: 0.58; 1.05, P(RR < 1) = 0.97]. In addition, there was a 17% lower risk observed for PTS [RR = 0.83, 95% CrI: 0.40; 1.59, P(RR < 1) = 0.74]. Major bleeding risk was 15% lower [RR = 0.85, 95% CrI: 0.76; 0.96, P(RR < 1) = 0.99]. Combined LLT+AC reduced D-dimer [log SMD = -0.15; 95% CrI: -0.43; 0.13, P(SMD < 0) = 0.88] and C-reactive protein levels [log SMD = -0.86; 95% CrI: -1.48; -0.08; P(SMD < 0) = 0.98] relative to AC monotherapy.</p><p><strong>Conclusions: </strong>The available evidence suggests potential benefit of LLT+AC combination therapy over AC monotherapy, with respect to both safety and efficacy, though further evidence from RCTs is necessary to generate conclusive evidence.</p><p><strong>Funding: </strong>DIASyM research core (BMBF 031L0219).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101262"},"PeriodicalIF":13.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-driven therapeutic antisense oligonucleotide for processing-deficient progeroid laminopathies.","authors":"Lin Lv, Chang Liu, Lidan Hu, Lefan Cai, Jinzhao Liang, Hanying Jia, Ningyuan You, Haoluo Xi, Yanhong Feng, Jingjing Wang, Zhekai Li, Qiuyang Yu, Gang Wang, Jin Zhang, Hongguang Xia, Xudong Fu, Leslie B Gordon, Jianhua Mao, Zhihong Liu, Ning Shen","doi":"10.1016/j.medj.2026.101193","DOIUrl":"10.1016/j.medj.2026.101193","url":null,"abstract":"<p><strong>Background: </strong>Progeroid laminopathies (PLs), including Hutchinson-Gilford progeria syndrome (HGPS), are rare premature aging disorders in which cardiovascular complications drive early mortality. Antisense oligonucleotides (ASOs) represent a promising therapeutic strategy, yet optimal design principles and their impact on cardiovascular pathology remain insufficiently defined.</p><p><strong>Methods: </strong>We developed an AI-driven pipeline to design ASOs targeting the 3'UTR of LMNA transcripts to suppress processing-deficient pathogenic lamin A isoforms. Lead candidates were evaluated in patient-derived induced pluripotent stem cell-derived cardiomyocytes (PL-iCMs), 3D cardiac organoids, and LMNA transgenic mouse models. Efficacy, toxicity, and systemic transcriptional responses were assessed using molecular, histological, and serum biochemical analyses.</p><p><strong>Findings: </strong>The optimized ASO, LM2556, selectively reduced progerin and farnesylated pre-lamin A expression while preserving lamin C. LM2556 mitigated cellular senescence and improved structural and functional phenotypes in PL-iCMs and cardiac organoids. In vivo, LM2556 decreased pathogenic lamin A isoforms across multiple tissues without evidence of hepatotoxicity or nephrotoxicity. Long-term administration ameliorated progeroid features, improved cardiovascular pathology, extended median lifespan by 82.86%, and enhanced overall healthspan in LMNA transgenic mice.</p><p><strong>Conclusions: </strong>These findings establish an AI-based framework for therapeutic ASO design and provide proof-of-concept evidence that targeting the 3'UTR of LMNA transcripts can effectively suppress pathogenic lamin A isoforms and ameliorate systemic progeroid phenotypes.</p><p><strong>Funding: </strong>This work was funded by the National Natural Science Foundation of China (82450116 and 82502251).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101193"},"PeriodicalIF":13.3,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-reactive zonation of mesenchymal-like phenotypes in human glioblastoma.","authors":"Alejandro Mossi Albiach, Jokubas Janusauskas, Jesper Kjaer Jacobsen, Ivana Kapustová, Razieh Karamzadeh, Egle Kvedaraite, Lijuan Hu, Marina C M Franck, Maria Ramal García, David Fernández-García, Camiel Mannens, Simone Codeluppi, Johannes B Munting, Lars E Borm, Alia Shamikh, Peter Lönnerberg, Kimberly Siletti, Oscar Persson, Sten Linnarsson","doi":"10.1016/j.medj.2026.101228","DOIUrl":"10.1016/j.medj.2026.101228","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the deadliest brain cancer, characterized by large cellular diversity. Both neurodevelopment-like and mesenchymal-like cell states have been described, with the latter being strongly implicated in malignancy and disease progression. However, the spatial organization of these mesenchymal-like cell states has not been systematically described outside the tumor bulk.</p><p><strong>Methods: </strong>We performed deep single-cell RNA sequencing of rare glioblastoma cases where tissue could be sampled from tumor core to macroscopically normal cortex and 888-plex enhanced electric single-molecule fluorescence in situ hybridization (EEL-FISH) spatial transcriptomics on a large cohort of standard resections. We also established four glioblastoma organoid lines to test in vitro inducibility of mesenchymal-like cell states under hypoxia and blood plasma exposure.</p><p><strong>Findings: </strong>We discovered that previously defined mesenchymal-like tumor cell states were shared across both malignant and non-malignant cell types and spatially confined to the tumor bulk. Peripheral regions were instead dominated by neurodevelopment-like tumor states and endogenous microglia. In patient-derived organoids and non-malignant astrocytes, the mesenchymal transcriptional state could be reversibly induced in vitro by hypoxia and human plasma, indicative of a wound response. Multiplex single-molecule spatial transcriptomics revealed that the activation of mesenchymal-like states was associated with hypoxia and organized by distance to perivascular niches.</p><p><strong>Conclusions: </strong>Our findings clarify the cellular landscape and biology of glioblastoma, wherein the mesenchymal state arises at least partly as a reactive tissue state shared by all cells in the tumor bulk.</p><p><strong>Funding: </strong>This work was supported by Region Stockholm, Erling-Persson Family Foundation (Atlas of Childhood Disease), Hjärnfonden (FO2023-0309), Swedish Research Council (2022-01248), and Torsten Söderberg Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101228"},"PeriodicalIF":13.3,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming HER2-Positive gastroesophageal cancer immune contexture with bispecific therapy: HERIZON-GEA-01.","authors":"Raghav Sundar, Samuel J Klempner","doi":"10.1016/j.medj.2026.101260","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101260","url":null,"abstract":"<p><p>The HERIZON-GEA-01 trial in patients with advanced HER2-positive gastroesophageal adenocarcinoma demonstrated improved outcomes with the addition of the HER2xHER2-bispecific antibody zanidatamab to chemotherapy. The addition of tislelizumab, an anti-PD-1 antibody to chemotherapy and zanidatamab suggests additional survival improvements. HER2-targeting strategies leveraging spatially restricted target degradation and immune modulation are reframing HER2 approaches in HER2-positive gastroesophageal cancer.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 8","pages":"101260"},"PeriodicalIF":13.3,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LSD therapy: A few hundred meters from where it began.","authors":"Felix Müller, Anna M Becker, Christopher Böhlke, Matthias E Liechti, Undine E Lang","doi":"10.1016/j.medj.2026.101233","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101233","url":null,"abstract":"<p><p>In Basel, only a few hundred meters from where LSD was first synthesized, we tested LSD-assisted therapy for major depression in a randomized trial comparing two high doses with two low doses, each paired with supportive psychotherapy. This Backstory reflects on treating patients, long dosing days, and what remains uncertain.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 8","pages":"101233"},"PeriodicalIF":13.3,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}