tbuckley/cabot-search huggingface dataset:
Incidence, stage and outcome of melanoma, keratinocyte and other cancers in individuals with vitiligo or alopecia: intraindividual or familial risks?
Authors: Benedicte Delcoigne, Josefin Lysell, Johan Askling
Journal: British Journal of Dermatology (2025)

Abstract Background Vitiligo and autoimmune alopecia (AA) are caused by T-cell mediated autoimmunity in genetically predisposed individuals. Studies in vitiligo have reported reduced risks for melanoma (MM), some also for keratinocyte skin cancer (KC). In AA, reduced risks for KC (and also MM) have been reported. The driving mechanisms (genetic predisposition, immunological or other effects of the disease phenotypes, or environmental) remains unclear. Whether the immune-related genetic predisposition in vitiligo and AA offers “inherent” protection against other types of cancer remains unresolved. Objectives To investigate the incidence and outcome of MM, squamous cell skin cancer (SCC) and non-cutaneous cancers in vitiligo and alopecia, vs. that in the general population, and to investigate the corresponding risks in their siblings. Methods We performed a population-based matched cohort study using data from linkage of Swedish registers. We used Cox proportional hazards regression to calculate hazard ratios (HR) contrasting patients with vitiligo or AA and the general population, and contrasting their siblings. Results Between 2006 to 2021, we included 15,030 patients with vitiligo, 18,541 with alopecia, and 17,853 and 21,821 of their siblings. Based on 17 MM events (crude incidence per 100,000, IR: 16), 23 SCC events (IR: 22) in vitiligo, and, 20 MM (IR: 15) and 24 SCC (IR: 18) in AA, the HR for MM was 0.53 (95%CI 0.32-0.86) in vitiligo and 0.53 (95%CI 0.34-0.83) in AA. Regarding SCC, HRs were 0.81 (95%CI 0.53-1.24) in vitiligo and 0.65 (95%CI 0.43-0.98) in AA. Stage at diagnosis of MM didn’t differ substantially between patients and the general population. Among siblings, HRs for MM and SCC were not statistically significantly altered (0.82 ≤ HR ≤ 1.10). In patients and their siblings, HRs for non-cutaneous solid or hematological cancers were not reduced. Conclusion In vitiligo and in AA the decreased risk of cutaneous cancers extends beyond the cell-type targeted by the autoimmune reaction. The general tendency towards somewhat reduced skin cancer risks among their siblings suggests a role for other factors than the disease phenotypes per se. Neither the vitiligo and AA phenotypes nor their immune-related genetic predispositions seem to offer any “inherent“protection against non-cutaneous malignancies.
Dendritic cell-based microrobots for enhanced systemic antigen-specific immune tolerance
Authors: Hanfeng Qin, Junbin Gao, Wenxin Xu, Yanzhen Song, Ruotian Zhang, Hong Wang, Yicheng Ye, Jia Sun, Jiamiao Jiang, Haiying Liang, Ning Zhong, Hao Tian, Xiaodong Chen, Fei Peng, Yingfeng Tu
Journal: Journal of Controlled Release (2025)
Multifunctional Tri-layer Wound Dressing containing ZnO nanoparticles and IGF-1 as an Efficient Biomaterial for Healing of Full Thickness Skin Injuries
Authors: Azin Abedi Koupai, Jaleh Varshosaz, Mohamadreza Tavakoli, Marjan Mirhaj, Saeideh Salehi, Faramarz Dobakhti
Journal: Asian Journal of Pharmaceutical Sciences (2025)
Development and Validation of the Patient-Level Chinese Diabetes Outcome Model on Long-term Complications in Type 2 Diabetes: An Application of the Hong Kong Diabetes Register
Authors: Eric S.H. Lau, Andrea O.Y. Luk, Lee-Ling Lim, Hongjiang Wu, Aimin Yang, Alice P.S. Kong, Ronald C.W. Ma, Risa Ozaki, Elaine Y.K. Chow, Chiu-Chi Tsang, Chun-Kwun O, Amy Fu, Edward W. Gregg, Philip Clarke, Wing-Yee So, Juliana N.M. Lui, Juliana C.N. Chan
Journal: Diabetes Care (2025)

OBJECTIVE Patient-level simulation models, mainly developed in Western populations, capture complex interactions between risk factors and complications to predict the long-term effectiveness and cost-effectiveness of novel treatments and identify high-risk subgroups for personalized care. However, incidence of outcomes varies significantly by ethnicity and region. We used high-quality, patient-level register data to develop the Chinese Diabetes Outcomes Model (CDOM) for predicting incident and recurrent events in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS The CDOM was developed using the prospective Hong Kong Diabetes Register (HKDR) cohort (n = 21,453; median follow-up duration, 7.9 years; 166,433 patient-years). It was externally validated with a retrospective territory-wide cohort of Chinese patients with T2D attending Hong Kong publicly funded diabetes centers and community clinics (n = 176,120; follow-up duration, 7.2 years; 953,523 patient-years). RESULTS The CDOM predicted first and recurrent events with satisfactory performance during internal (C-statistic = 0.740–0.941) and external (C-statistic = 0.758–0.932) validation after calibration. The respective C-statistic values for cancer were 0.664 and 0.661. Subgroup analysis showed consistent performance during internal (C-statistic = 0.632–0.953) and external (C-statistic = 0.598–0.953) validation after calibration. CONCLUSIONS The CDOM, developed using comprehensive register data with long-term follow-up, is a robust tool for predicting long-term outcomes in Chinese patients with T2D. The model enables the identification of patient subgroups to augment study design and develop tailored novel treatment strategies, inform policy, and guide practice to improve cost-effectiveness of diabetes care.
Mechanical Confinement Triggers Spreading and Migration of Immobile Cells by Deforming Nucleus
Authors: Ran Rao, Haoxiang Yang, Kailong Qiu, Min Xu, Hao Liu, Jinghao Shen, Weihao Wang, Runjie Nie, Huan Chen, Hongyuan Jiang
Journal: Biomaterials (2025)
Using Ecological Momentary Assessment to Redefine Postdialysis Fatigue in Patients with Kidney Failure
Authors: Cramer J. Kallem, Alaa A. Alghwiri, Jonathan Yabes, Sarah Erickson, Zhuoheng Han, Maria-Eleni Roumelioti, Jennifer L. Steel, Mark Unruh, Manisha Jhamb
Journal: Journal of the American Society of Nephrology (2025)

Background: Patients with kidney failure have a high symptom burden and many report an acute exacerbation of symptoms immediately following in-center hemodialysis (HD). Very few studies have used ecological momentary assessment (EMA) to examine post-HD patient-centered outcomes. Methods: Participants in the Technology Assisted Collaborative Care (TĀCcare) trial completed an automated telephone-administered Daytime Insomnia Symptom Scale (DISS) at 4 time points daily for 7 consecutive days. The DISS yields 4 symptom domain scores: Positive Mood, Negative Mood, Alert Cognition, and Sleepiness/Fatigue. Post-HD symptom domains and item-level scores were compared to similar time points on non-HD days using linear mixed models analyses. Mixed models were also used to explore the association of post-dialysis symptom burden with demographic, psychosocial, hemodialysis treatment, and disease-specific characteristics. All analyses were adjusted for age, race, sex, and Charlson Comorbidity Index Results: 156 HD patients with available EMA data were evaluated [mean age=58±14 years, 55% men, 51% White]. In the post-HD period, patients reported significantly lower Positive Mood [mean difference (MD)= -0.22, 95% CI (-0.29, -0.14)] and Alert Cognition [MD= -0.13, 95% CI (-0.18, -0.08)] and higher Negative Mood [MD=0.12, 95% CI (0.05, 0.19)] and Sleepiness/Fatigue [MD=0.51, 95% CI (0.42, 0.61)] compared to non-HD days. The mean post-dialysis symptom exacerbation total score was 0.70 ± 1.21, representing an increase of 6% of the maximum scale range. In the post-dialysis period, relative to non-dialysis days, the mean decrease in Positive Mood and Alert Cognition scores equaled 4% and 2% of the maximum scale range respectively; the mean increase in Negative Mood and Sleepiness/Fatigue scores equaled 2% and 9% of the maximum scale range respectively. Conclusions: Patients with kidney failure reported worsening of both fatigue and mood symptoms post- HD.
A multicenter prospective clinical trial reveals cell free DNA methylation markers for early esophageal cancer
Authors: Ruixiang Zhang, Yongzhan Nie, Xiaobing Chen, Tao Jiang, Jinhai Wang, Yuhui Peng, Guangpeng Zhou, Yong Li, Lina Zhao, Beibei Chen, Yunfeng Ni, Yan Cheng, Yiwei Xu, Zhenyu Zhu, Xianchun Gao, Zhen Wu, Tianbao Li, Jie Zhao, Cantong Liu, Gang Zhao, Jiakuan Chen, Jing Zhao, Gang Ji, Xiaoliang Han, Jie He, Yin Li
Journal: Journal of Clinical Investigation (2025)

BACKGROUND. Current methods for detecting esophageal cancer (EC) are generally invasive or exhibit limited sensitivity and specificity, especially for the identification of early-stage tumors.
Gallbladder cancer and dysplasia in cholecystectomy specimens: A large study in high-incidence regions of South America
Authors: Felix Boekstegers, Carol Barahona Ponce, Erik Morales, Cesar Muñoz-Castro, Cristian Lindner, Ivan Schneider Lira, Belarmino Manques, Alicia Colombo Flores, Catalina Valenzuela, Jaime Castillo, Gonzalo de Toro, Mauricio Almau, Cristina Inklemona, Carolina Ituarte, Gerardo F Arroyo, Loreto Spencer, Hector Losada, Juan Carlos Araya, Bruno Nervi, Claudio Mengoa Quintanilla, Paola Montenegro, Ana Lineth Garcia, Sidney Rojas Orellana, Alejandro Ortega, Francisco Rothhammer, Justo Lorenzo Bermejo
Journal: Clinical Gastroenterology and Hepatology (2025)
Multiplexed epigenetic memory editing using CRISPRoff sensitizes glioblastoma to chemotherapy
Authors: Katie Lin, Christopher Zou, Akane Hubbard, Sasha Sengelmann, Laine Goudy, I-Ching Wang, Rohit Sharma, Joanna Pak, Kyla Foster, Tomoko Ozawa, John F de Groot, Joanna Phillips, Harish N Vasudevan, David R Raleigh, Alexander Marson, Niren Murthy, Luke A Gilbert, Mitchel S Berger, S John Liu
Journal: Neuro-Oncology (2025)

Abstract Background Glioblastoma (GBM) carries a poor prognosis, and new therapeutic strategies are necessary to improve outcomes for patients with this disease. Alkylating chemotherapies including temozolomide (TMZ) and lomustine (CCNU) are critical for treating GBM, but resistance mechanisms, including hypomethylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter, undermine treatment. CRISPRoff is a programmable epigenetic memory editor that can induce stable and heritable gene silencing after transient delivery, and we hypothesize that CRISPRoff could potentiate the activity of TMZ and CCNU through long term suppression of target genes. Methods We transiently delivered CRISPRoff mRNA along with sgRNAs against target genes using both electroporation and lipid nanoparticles (LNPs) into established GBM cell lines, patient-derived primary GBM cultures, and orthotopic GBM xenografts. Gene repression, specificity, and stability was measured by RT-qPCR, Western blot, bisulfite sequencing, and RNA-sequencing. Sensitivity to chemotherapies was measured by cell viability dose response, microscopy, and bioluminescence imaging. Genome-wide mapping of CCNU sensitizers was performed using CRISPRi screens. Results CRISPRoff induced complete suppression of MGMT and sensitization to TMZ that were stable for over 8 months of continuous cell propagation. GBM orthotopic tumors treated with CRISPRoff against MGMT demonstrated sensitivity to TMZ in vivo, and CRISPRoff delivery resulted in chemosensitivity in patient-derived primary GBM. Genome-wide CRISPRi screens identified combinatorial genetic vulnerabilities (BRIP1, FANCE) that were targetable by multiplexed CRISPRoff to achieve sensitization to CCNU. Conclusion Transient delivery of a site-specific epigenetic memory can induce stable, complete, and multiplexed suppression of target genes for therapeutic application in GBM.
Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatin in patients with HER2-negative BC and HRD –long-term survival of the GeparOLA study
Authors: Peter A. Fasching, Sabine Schmatloch, Jan Hauke, Julia Rey, Christian Jackisch, Peter Klare, Theresa Link, Claus Hanusch, Jens Huober, Andrea Stefek, Johannes Holtschmidt, Andreas Schneeweiss, Christoph Uleer, Wolfgang D. Schmitt, Gabriele Doering, Kerstin Rhiem, Carsten Denkert, Rita K. Schmutzler, Christine Solbach, Eric Hahnen, Andreas Hartkopf, Michael Untch, Vesna Bjelic-Radisic, Valentina Nekljudova, Jens-Uwe Blohmer, Sibylle Loibl
Journal: Clinical Cancer Research (2025)

Abstract Backgound: The GeparOLA study evaluated paclitaxel(P) plus olaparib(O) in neoadjuvant chemotherapy (NACT) for patients with HER2-negative early breast cancer (eBC) with homologous recombination deficiency (HRD). HRD was defined by high HRD-score or germline(g)/tumor(t) BRCA1/2 mutations (g/tBRCA1/2mut). Here, we report long-term outcome data. Patients and Methods: GeparOLA (NCT02789332) was a randomized, multicenter, prospective, open-label, phase II trial. Patients with HER2-negative eBC, HRD, indication for chemotherapy (cT2-cT4a-d or cT1c and cN+ or cT1c and pNSLN+ or cT1c and triple-negative[TN]BC or cT1c and Ki-67&amp;gt;20%), were randomly assigned to P+O or P+carboplatin(Cb), both followed by epirubicin+cyclophosphamide(EC). Long-term efficacy endpoints were secondary endpoints and included invasive disease-free survival(iDFS), distant disease-free survival(DDFS) and overall survival(OS). Results: Between 09/2016 and 07/2018, 107 patients were randomized and 106 (PO N=69;PCb N=37) started treatment. The median age was 47.0 years; 35.8% had cT1 tumors; 31.4% were cN+; 86.8% had G3 tumors; 89.6% had Ki-67&amp;gt;20% and 72.6% were TN. After median follow-up of 49.8 months, 18(15 PO; 3 PCb) iDFS events and 7(6 PO; 1 PCb) deaths were reported. The 4-year iDFS (76.0%PO vs 88.5%PCb, HR=2.86 [95%CI 0.83-9.90],log-rank p=0.081), DDFS (81.2%PO vs 93.4%PCb, HR=3.03 [95%CI 0.67-13.67],log-rank p=0.129) and OS (89.2%PO vs 96.9%PCb, HR=3.27 [95%CI 0.39-27.20],log-rank p=0.244) tended to be inferior with O. Patients without g/tBRCA1/2mut benefited from Cb [7/30 patients had iDFS/DDFS events in PO vs 0/16 in PCb]. Conclusion: For HER2-negative eBC with HRD, olaparib showed a tendency for inferior outcomes compared to carboplatin, particularly in patients without g/tBRCA1/2mut. In patients with g/tBRCA1/2mut olaparib may replace carboplatin.
Phase 1 trial of selinexor in pediatric recurrent/refractory solid and CNS tumors (ADVL1414): A Children's Oncology Group Phase 1 Consortium Trial
Authors: Adam L. Green, Charles G. Minard, Xiaowei Liu, Stephanie L. Safgren, Kerice Pinkney, Lauren Harris, Gabrielle Link, John DeSisto, Stephan Voss, Marvin D. Nelson, Joel M. Reid, Elizabeth Fox, Brenda J. Weigel, Julia Glade Bender
Journal: Clinical Cancer Research (2025)

Abstract Background: Selinexor is a first-in-class, central nervous system (CNS)-penetrant, oral inhibitor of exportin 1 (XPO1), the main nuclear exporter of many key tumor suppressors. We report a phase 1 trial of selinexor in children and adolescents with recurrent CNS and solid tumors (NCT02323880). Methods: A rolling-six design was used to evaluate the maximum tolerated dose (MTD) and first dose pharmacokinetics (PK) of selinexor administered once (QW, 35-45 mg/m2) or twice (BIW, 20-35 mg/m2) weekly during a 28-day cycle (Part A). Ten additional patients with high-grade glioma (HGG) were treated at the QW MTD (Part B). Results: In Part A, 49 patients were enrolled. Continuous BIW dosing was limited by extended hematologic toxicity. The MTD on a BIW schedule for three weeks on/one-week off (BIW 3/1) was 20 mg/m2/dose. Dose-limiting toxicities (DLTs) on this schedule included fatigue, acute reversible neurologic changes, neutropenia, thrombocytopenia, and AST/ALT increase. On a continuous QW schedule, the MTD was 35 mg/m2/dose, DLTs included seizure and thrombocytopenia. In Part B (HGG expansion), there were no additional DLTs observed. Non-dose-limiting toxicity included lymphopenia, leukopenia, neutropenia, thrombocytopenia, anorexia, fatigue, hypophosphatemia, nausea, and vomiting. There were no objective responses. The median number of cycles received was 1 (range 1-9); Eight of 59 patients (13.5%) received 5-9 cycles, five of whom had HGG. Conclusions: Selinexor-related toxicities were primarily hematologic and neurologic requiring dose or dose-frequency reduction. The MTD and recommended initial phase 2 dose of selinexor in children and adolescents with recurrent solid and CNS tumors is 35 mg/m2/dose QW.
An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma
Authors: Annegret Holm, Matthew S. Graus, Jill Wylie-Sears, Jerry Wei Heng Tan, Maya Alvarez-Harmon, Luke Borgelt, Sana Nasim, Long Chung, Ashish Jain, Mingwei Sun, Liang Sun, Pascal Brouillard, Ramrada Lekwuttikarn, Yanfei Qi, Joyce Teng, Miikka Vikkula, Harry Kozakewich, John B. Mulliken, Mathias Francois, Joyce Bischoff
Journal: Journal of Clinical Investigation (2025)

Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis, and regression. Propranolol, the mainstay treatment, inhibits IH vessel formation via a β-adrenergic receptor independent off-target effect of its R(+) enantiomer on the endothelial SRY box transcription factor 18 (SOX18). Transcriptomic profiling of patient-derived hemangioma stem cells (HemSC) uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss and gain of function of SOX18 confirmed it is both necessary and sufficient for R(+) propranolol suppression of the MVP, including regulation of sterol regulatory element binding protein 2 (SREBP2) and the rate-limiting enzyme HMG-CoA reductase (HMGCR). AThe biological relevance of the endothelial SOX18-MVP axis in IH patient tissue was demonstrated by nuclear co-localization of SOX18 and SREBP2. Functional validation in a preclinical IH xenograft model revealed that statins – competitive inhibitors of HMGCR – efficiently suppress IH vessel formation. We propose an novel endothelial SOX18-MVP-axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH. The pleiotropic effects of R(+) propranolol and statins along the SOX18-MVP axis to disable an endothelial-specific program may have therapeutic implications for other vascular disease entities involving pathological vasculogenesis and angiogenesis.
Liver resection versus radiofrequency ablation for solitary small hepatocellular carcinoma measuring≤3cm: a systematic review and meta-analysis
Authors: Ming Yang, Guangjun Li, Kunlin Chen, Youwei Wu, Ting Sun, Wentao Wang
Journal: International Journal of Surgery (2025)

Background: Controversy remains regarding liver resection (LR) and radiofrequency ablation (RFA) for patients with single hepatocellular carcinomas (HCCs) measuring 3 cm or less. The purpose of our study was to compare the prognosis between LR and RFA in patients with solitary HCCs ≤3 cm. Methods: The meta-analysis followed the PRISMA guidelines and the Cochrane Handbook. All RCTs and cohort studies that compared LR versus RFA in patients with solitary HCCs≤3 cm were comprehensively searched in the PubMed, Cochrane Library, Embase, and Web of Science databases up to 30 January 2024. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). Results: A total of 6356 patients with solitary HCCs≤3 cm and 5829 patients with solitary HCCs≤2 cm from 39 included studies were analyzed (LR = 5759, RFA = 6426). The present meta-analysis of two RCTs showed no statistically significant difference in OS between LR and RFA. However, the meta-analysis of cohort studies revealed that, compared with RFA, LR conferred a superior OS advantage (HR = 0.80, 95% CI: 0.68–0.93, P = 0.005). There was a significant improvement in the DFS rate with LR over RFA (HR = 0.63, 95% CI: 0.49–0.81) and in the RFS rate (HR = 0.65, 95% CI: 0.55–0.76). Compared with RFA, LR resulted in better OS (HR = 0.73, 95% CI: 0.54–0.97), DFS (HR = 0.74, 95% CI: 0.67–0.82) and RFS (HR = 0.71, 95% CI: 0.57–0.90) in patients with a solitary HCC lesion ≤2 cm. Conclusions: Evidence from cohort studies suggested that in patients with a solitary HCC lesion ≤ 3 cm, LR is preferable to RFA. Additional RCTs are needed to confirm the validity of this evidence.
Late Adverse Events After Chimeric Antigen Receptor T-Cell Therapy for Patients With Aggressive B-Cell Non-Hodgkin Lymphoma
Authors: Lina Camacho-Arteaga, Gloria Iacoboni, Mi Kwon, Rebeca Bailén, Rafael Hernani, Ana Benzaquén, Lucía López-Corral, Estefania Pérez-López, Lina María Leguízamo-Martínez, Maria Calvo-Orteu, Manuel Guerreiro, Aitana Balaguer-Rosello, Carla Alonso-Martínez, Xavier Vidal, Pere Barba, Antònia Agustí
Journal: JAMA Network Open (2025)

Importance Acute adverse events (AEs) after chimeric antigen receptor (CAR) T-cell infusion are well documented, but less information is available regarding the long-term toxic effects. Objective To assess the occurrence of late AEs for adult patients with large B-cell lymphoma (LBCL) treated with commercially available CD19-targeted CAR T cells. Design, Setting, and Participants A prospective, observational, clinical practice cohort study was conducted from September 1, 2018, to December 31, 2022, among 172 adult patients in 6 Spanish hospitals who received CD19-targeted CAR T-cell therapy for relapsed or refractory LBCL and survived at least 3 months after infusion, without subsequent antilymphoma therapy. Exposure Treatment with tisagenlecleucel or axicabtagene ciloleucel. Main Outcomes and Measures Data on any late AEs occurring in this patient population were collected until the patients received new antilymphoma therapy, were lost to follow-up, died, or reached 24 months after infusion, whichever occurred first. Data collection for each patient started at the third month after infusion and included new-onset AEs, as well as persistent AEs that started earlier but were still ongoing at that time point. Results The study enrolled 172 patients (mean [SD] age, 58.5 [13.7] years; 101 men [58.7%]), of whom 135 (78.5%) experienced at least 1 late AE of any grade. Infections were the late AEs with the highest incidence (5.6 per 100 person-months [95% CI, 4.5-7.0 per 100 person-months]), followed by neutropenia (3.6 per 100 person-months [95% CI, 2.9-4.5 per 100 person-months]) and thrombocytopenia (2.2 per 100 person-months [95% CI, 1.7-3.0 per 100 person-months]). The incidence of infectious episodes remained stable during the whole study period, while cytopenias decreased beyond 6 months after infusion. All cases of nonrelapse-related mortality were due to infections (COVID-19 pneumonia in 3 patients and sepsis or bacterial pneumonia in 4 patients). Twenty-three patients (13.4%) experienced 27 dermatologic AEs, all mild, with most of them (88.9% [24 of 27]) starting beyond 3 months after infusion. Fifteen neurologic AEs were reported in 15 patients (8.7%), and 10 patients (5.8%) developed 13 cardiovascular AEs. Five secondary neoplasms were reported in 4 patients (2.3%), with no cases of T-cell malignant neoplasms. Conclusions and Relevance This cohort study suggests that CAR T-cell therapy has a favorable safety profile. However, continuous follow-up of patients is needed, as serious AEs can occur years after infusion.