tbuckley/cabot-search huggingface dataset:
Glioblastoma Cell Lysate and Adjuvant Nanovaccines via Strategic Vaccination Completely Regress Established Murine Tumors
Authors: Songsong Zhao, Yanyi Qu, Zhiwei Sun, Shuo Zhang, Mingyu Xia, Yan Shi, Jingyi Wang, Yuan Wang, Zhiyuan Zhong, Fenghua Meng
Journal: Advanced Healthcare Materials (2025)

Abstract Tumor vaccines have shown great promise for treating various malignancies; however, glioblastoma (GBM), characterized by its immunosuppressive tumor microenvironment, high heterogeneity, and limited accessibility, has achieved only modest clinical benefits. Here, it is reported that GBM cell lysate nanovaccines boosted with TLR9 agonist CpG ODN (GlioVac) via a strategic vaccination regimen achieve complete regression of malignant murine GBM tumors. Subcutaneous administration of GlioVac promotes uptake by cervical lymph nodes and antigen presentation cells, bolstering antigen cross‐presentation and infiltration of GBM‐specific CD8 + T cells into the tumor. Notably, a regimen involving two subcutaneous and three intravenous vaccinations not only activates systemic anti‐GBM immunity but also further enhances the tumor infiltration of cytotoxic T lymphocytes, effectively reshaping the “cold” GBM tumor into a “hot” tumor. This approach led to a state of tumor‐free survival in 5 out of 7 mice bearing the established GL261 GBM model with complete protection from tumor rechallenge. In an orthotopic hRas‐GBM model induced by a lentiviral plasmid, GlioVac resulted in ≈100% complete tumor regression. These findings suggest that GlioVac provides a personalized therapeutic vaccine strategy for glioblastoma.
“BR22, a 26 kDa thyroid transcription factor-1 associated protein (TAP26), is expressed in human lung cells.” M-C.W. Yang, B. Wang, J.C. Weissler, L.R. Margraf and Y-S. Yang.<i>Eur Respir J</i>2003; 22: 28–34.
Journal: European Respiratory Journal (2025)
Engineering Antibacterial, Biocompatible, Anti‐Oxidant Titanium‐Based Implants Using Polyphenols‐Chlorhexidine Networks for Bone Regeneration
Authors: Yankai Wang, Biao Hong, Baozang Yin, Yuan Li, Liuwei Huang, Shuang Tan, Tiancheng Gao, Manfred F. Maitz, Junsheng Zhang, Shunli Zheng, Can Huang, Hua Qiu, Jialong Chen, Xiangyang Li
Journal: Advanced Healthcare Materials (2025)

Abstract Implant‐associated infections leading to osteolysis and implant loosening are an ongoing clinical challenge. Various strategies have been proposed to equip bone implants with antibacterial properties to prevent infection. However, the cytotoxicity associated with antimicrobial effects adversely impacts the osseointegration. Herein, a facile and safe strategy is proposed to endow bone implants with infection prevention, good cytocompatibility, inflammatory‐responsive antimicrobial properties, thus promoting bone healing. The coating is fabricated on the implant through both covalent and non‐covalent bonds of polyphenols with chlorhexidine (CHX). The covalent bonds guarantee long‐term stability, while non‐covalent bonds facilitate early release of CHX. Furthermore, the inclusion of polyphenols reduces the electrophilicity of CHX, inhibits reactive oxygen species generated by CHX, and minimizes interference with the mitochondrial electron transport chain, thereby reducing cellular toxicity. Consequently, the coating effectively fortified the bone implant, successfully impeding bacterial invasion within 7 days in Sprague‐Dawley rats and suppressing inflammation as well as bone resorption caused by bacteria during a 60‐day femoral implantation, thus facilitated osseointegration on the implant. The study investigated the cytotoxicity associated with mitochondrial interference induced by CHX and proposed a strategy to enhance its cellular compatibility, thereby providing a novel approach for fabricating biocompatible antibacterial bone implants.
Myeloid neoplasms after CD19-directed CAR T cells therapy in long-term B-cell lymphoma responders, a rising risk over time?
Authors: Nicolas Gazeau, David Beauvais, Rémi Tilmont, Micha Srour, Emmanuelle Ferrant, Violaine Safar, Ludovic Fouillet, Pascale Flandrin-Gresta, Nicolas Gower, Paul Chauvet, Nicolas Duployez, Benjamin Podvin, Julie Demaret, Sarah Huet, Pierre Sujobert, Hervé Ghesquières, Gandhi Damaj, Emmanuel Bachy, Franck Morschhauser, Ibrahim Yakoub-Agha, Maël Heiblig, Pierre Sesques
Journal: Leukemia (2025)

Abstract Therapy-related myeloid neoplasms (t-MN), including myelodysplastic neoplasms (t-MDS) and acute myeloid leukemia (t-AML), have emerged as significant late complications after CAR T cell therapy. We retrospectively analyzed 539 patients with B cell lymphoma treated with CD19 directed CAR T cell therapy across four French centers. Cumulative incidences of t-MN was estimated with relapse or death treated as competing risk. Univariate and propensity score matching (PSM) analyses were conducted to assess risk factors with age and the number of prior treatments as covariates. After a median follow-up of 25 months, the cumulative incidence of t-MN was 4.5% at 2 years. T-MN occurred predominantly as t-MDS (62%) and t-AML (38%) with high cytogenetic risk. Median overall survival after t-MN diagnosis was 4.5 months. In univariate analysis, older age ( p &lt; 0.01), higher MCV ( p &lt; 0.01), and higher ICANS grade ( p = 0.04) were associated with increased risk of t-MN. After PSM, MCV and ICANS grade remained significant risk factors. CAR T cell products with CD28 co-stimulatory domains trended towards higher t-MN risk ( p = 0.09). NGS analysis showed that 85.7% of t-MN had pre-existing mutations, most commonly TP53. This study highlights t-MN as a severe late complication of CAR T cell therapy. MCV and ICANS grade were identified as key risk factors.
ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic biomarker
Authors: Birna Thorvaldsdottir, Larry Mansouri, Lesley-Ann Sutton, Ferran Nadeu, Manja Meggendorfer, Helen Parker, Christian Brieghel, Stamatia Laidou, Riccardo Moia, Davide Rossi, Jana Kotaskova, Julio Delgado, Ana E Rodríguez-Vicente, Rocío Benito, Gian Matteo Rigolin, Silvia Bonfiglio, Lydia Scarfò, Mattias Mattsson, Zadie Davis, Panagiotis Baliakas, Inmaculada Rapado, Fatima Miras, Joaquín Martinez-Lopez, Javier de la Serna, Jesús María Hernández Rivas, María José Larráyoz, María José Calasanz, Karin E Smedby, Blanca Espinet, Anna Puiggros, Lars Bullinger, Francesc Bosch, Bárbara Tazón-Vega, Fanny Baran-Marszak, David Oscier, Florence Nguyen-Khac, Thorsten Zenz, Maria Jose Terol, Antonio Cuneo, María Hernández-Sánchez, Sarka Pospisilova, Gianluca Gaidano, Carsten U Niemann, Elias Campo, Jonathan C Strefford, Paolo Ghia, Kostas Stamatopoulos, Richard Rosenquist
Journal: Leukemia (2025)

Abstract Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), the prognostic significance of somatic ATM mutations remains uncertain. We evaluated the effects of ATM aberrations (del(11q) and/or ATM mutations) on time-to-first-treatment (TTFT) in 3631 untreated patients with CLL, in the context of IGHV gene mutational status and mutations in nine CLL-related genes. ATM mutations were present in 246 cases (6.8%), frequently co-occurring with del(11q) (112/246 cases, 45.5%). ATM -mutated patients displayed a different spectrum of genetic abnormalities when comparing IGHV-mutated (M-CLL) and unmutated (U-CLL) cases: M-CLL was enriched for SF3B1 and NFKBIE mutations, whereas U-CLL showed mutual exclusivity with trisomy 12 and TP53 mutations. Isolated ATM mutations were rare, affecting 1.2% of Binet A patients and &lt;1% of M-CLL cases. While univariable analysis revealed shorter TTFT for Binet A patients with any ATM aberration compared to ATM -wildtype, multivariable analysis identified only del(11q), trisomy 12, SF3B1 , and EGR2 mutations as independent prognosticators of shorter TTFT among Binet A patients and within M-CLL and U-CLL subgroups. These findings highlight del(11q), and not ATM mutations, as a key biomarker of increased risk of early progression and need for therapy, particularly in otherwise indolent M-CLL, providing insights into risk-stratification and therapeutic decision-making.
Prenatally derived macrophages support choroidal health and decline in age-related macular degeneration
Authors: Seth D. Fortmann, Blake F. Frey, Robert F. Rosencrans, Yvonne Adu-Rutledge, Edgar Ready V, Kameron V. Kilchrist, Robert S. Welner, Michael E. Boulton, Daniel R. Saban, Maria B. Grant
Journal: The Journal of Experimental Medicine (2025)

Hallmark findings in age-related macular degeneration (AMD) include the accumulation of extracellular lipid and vasodegeneration of the choriocapillaris. Choroidal inflammation has long been associated with AMD, but little is known about the immune landscape of the human choroid. Using 3D multiplex immunofluorescence, single-cell RNA sequencing, and flow cytometry, we unravel the cellular composition and spatial organization of the human choroid and the immune cells within it. We identify two populations of choroidal macrophages with distinct FOLR2 expression that account for the majority of myeloid cells. FOLR2+ macrophages predominate in the nondiseased eye, express lipid-handling machinery, uptake lipoprotein particles, and contain high amounts of lipid. In AMD, FOLR2+ macrophages are decreased in number and exhibit dysfunctional lipoprotein metabolism. In mice, FOLR2+ macrophages are negative for the postnatal fate-reporter Ms4a3, and their depletion causes an accelerated AMD-like phenotype. Our results show that prenatally derived resident macrophages decline in AMD and are implicated in multiple hallmark functions known to be compromised in the disease.
Phosphatidic acid phosphatase LPIN1 in phospholipid metabolism and stemness in hematopoiesis and AML
Authors: Karin Huber, Swati Garg, Lena Schlautmann, Rui Wang, Lixiazi He, Richard Huth, Alireza Pouya, Christian Rohde, Maike Janssen, Christian Lüchtenborg, Christian Arnold, Pilar M. Luque‐Navarro, Judith B. Zaugg, Simon Raffel, Carsten Müller‐Tidow, Irmela Jeremias, Luisa C. López‐Cara, Britta Brügger, Caroline Pabst
Journal: HemaSphere (2025)

Abstract Targeting metabolism represents a promising approach to eradicate leukemic stem cells (LSCs) that are considered critical drivers of relapse in acute myeloid leukemia (AML). In this study, we demonstrate that the phosphatidic acid phosphatase LPIN1, which regulates the synthesis of diacylglycerol, the key substrate for triacylglycerol, and phospholipid production, is crucial for the function of healthy and leukemic hematopoietic stem and progenitor cells (HSPC and LSC). LPIN1 mRNA was highly expressed in the CD34+ compartment of primary human AML samples. LPIN1 suppression inhibited the proliferation of primary leukemic cells and normal HSPCs in vitro and in xenotransplantation assays. Lipidomics analyses revealed a reduction of phosphatidylcholine (PC) and phosphatidylethanolamine and an upregulation of sphingomyelin upon LPIN1 depletion. Distinct phospholipid composition was associated with genetic AML groups, and targeting PC production by choline kinase inhibitors showed strong anti‐leukemic activity. In summary, our data establish a regulatory role of LPIN1 in HSPC and LSC function and provide novel insights into the role of glycerophospholipid homeostasis in stemness and differentiation.
The demographic history of populations and genomic imprinting have shaped the transposon patterns in <i>Arabidopsis lyrata</i>
Authors: Nélida Padilla-García, Audrey Le Veve, Vojtěch Čermák, Ömer İltaş, Adrián Contreras-Garrido, Sylvain Legrand, Jean-Marc Aury, Robert Horvath, Clément Lafon Placette
Journal: Molecular Biology and Evolution (2025)

Abstract Purifying selection is expected to prevent the accumulation of transposable elements within their host, especially when located in and around genes and if affected by epigenetic silencing. However, positive selection may favour the spread of TEs causing genomic imprinting under parental conflict, as genomic imprinting allows parent-specific influence over resource accumulation to the progeny. Concomitantly, the number and frequency of TE insertions in natural populations are conditioned by demographic events. In this study, we aimed to test how demography and selective forces interact to affect the accumulation of TEs around genes, depending on their epigenetic silencing and with a particular focus on imprinted genes. To this aim, we compared the frequency and distribution of TEs in A. lyrata from Europe and North America. Generally, we found that TE insertions showed a lower frequency when they were inserted in or near genes, especially TEs targeted by epigenetic silencing, suggesting purifying selection at work. We also found that many TEs were lost or got fixed in North American populations during the colonization and the postglacial range expansion from refugia of the species in North America, as well as during the transition to selfing, suggesting a potential “TE load’. Finally, we found that silenced TEs increased in frequency and even tended to reach fixation when they were linked to imprinted genes. We conclude that in A. lyrata, genomic imprinting has spread in natural populations through demographic events and positive selection acting on silenced TEs, potentially under a parental conflict scenario.
Premeal Whey Protein Lowers Postprandial Blood Glucose in Women With Gestational Diabetes Mellitus: A Randomized, Crossover Clinical Trial
Authors: Stine Smedegaard, Ulla Kampmann, Per G. Ovesen, Louise B. Suder, Janni H. Knudsen, Gregers Wegener, Lise H. Brunsgaard, Nikolaj Rittig
Journal: Diabetes Care (2025)

OBJECTIVE To examine how whey protein served as a premeal affects postprandial glucose excursions in women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS A placebo-controlled, single-blinded, crossover, randomized trial including women with and without GDM (20–36 weeks’ gestation) was performed. Participants were studied in the laboratory and at home. In the laboratory, women were randomized to consume 20 g of whey or placebo 30 min before undergoing, 7–14 days later, a 75-g oral glucose tolerance test (OGTT). Blood was sampled consecutively 3 hours following the OGTT. The primary end point was the incremental area under the curve (iAUC) for glucose. At home, participants wore continuous glucose monitors and, on subsequent days, randomly consumed 0, 10, 15, 20, and 30 g of whey 30 min before breakfast. RESULTS Twelve women with GDM and 12 pregnant women with normal glucose tolerance (NGT) to part in the trials. Intake of premeal whey resulted in lowered peak glucose by −1.0 mmol/L (95% CI −1.6 to −0.4) in women with GDM and −0.7 mmol/L (95% CI −1.3 to −0.1) in women without GDM compared with placebo. Insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1 levels increased rapidly after whey consumption in both groups. At home, a premeal of 30 g of whey dose-dependently reduced incremental glucose peaks with a maximum of −2.0 mmol/L (95% CI −2.5 to −1.5) in women with GDM compared with placebo. CONCLUSIONS Premeal whey consumption acutely lowers postprandial blood glucose in women with GDM and those with NGT, with 15–30 g lowering the glucose iAUC of women with GDM. These findings emphasize the need for long-term studies to assess the impact of whey premeals in pregnancies affected by GDM.
Alterations in Semen Quality and Immune‐Related Factors in Men with Infertility who Recovered from COVID‐19
Authors: Ying Zhang, Feiyin Zhu, Zhe Zhang, Jing Wang, Tianyi Liao, Yu Xi, Defeng Liu, Haitao Zhang, Haocheng Lin, Jiaming Mao, Wenhao Tang, Lianming Zhao, Peng Yuan, Liying Yan, Qiang Liu, Kai Hong, Jie Qiao
Journal: MedComm (2025)

ABSTRACT The emergence of coronavirus disease 2019 (COVID‐19) has triggered research into its impact on male reproductive health. However, studies exploring the effects of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on semen quality in infertile men remain limited. Herein, we enrolled 781 male infertile patients who recovered from COVID‐19 and analyzed their semen and blood samples collected at different time points. We found that SARS‐CoV‐2 RNA was undetectable in semen samples. Compared with pre‐COVID‐19 status, total sperm count, sperm concentration, vitality, motility, and percentage of sperm cells with normal morphology decreased significantly in the first month post‐COVID‐19. However, these alterations were reversed in the third month. Furthermore, seminal plasma samples exhibited reduced proinflammatory cytokine levels and notable changes in amino acid, nucleic acid, and carbohydrate metabolism by the third month compared with those in the first month. By contrast, no significant alterations in reproductive hormone levels were found. Vitality, progressive motility, and total motility negatively correlated with body temperature when it was above 38°C. In conclusion, semen quality initially decreases post‐COVID‐19 but reverses after approximately 3 months, with a decline related to inflammatory and fever. These findings may provide guidance to infertile male patients who need assisted reproductive technology.
Tobacco-Related Clinical Services and Tobacco-Free Policies in Behavioral Health Treatment Facilities — United States, 2023
Authors: Brenna VanFrank, Emilia Pasalic, Briana Oliver, Kevin Caron, Karuna Nerurkar, Kristy Marynak, Ahmed Jamal, Krishna Palipudi, Margaret Mahoney, Anna Schecter, Chanel Recasner, Elizabeth Hazelwood, Naomi Tomoyasu
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Evidence-based cessation treatments and tobacco-free policies support and increase smoking cessation, which has positive physical health impacts and is associated with positive behavioral health outcomes. Implementation of these strategies in substance use and mental health treatment facilities (behavioral health treatment facilities) could help decrease tobacco use among persons with behavioral health conditions. Data from the 2023 National Substance Use and Mental Health Services Survey were analyzed to ascertain the number and percentage of behavioral health treatment facilities that offered tobacco-related clinical services and had tobacco-free policies. In 2023, tobacco cessation counseling was the most commonly offered cessation service in facilities treating mental health conditions (53.1%) and substance use disorders (69.9%). Fewer than one half of facilities offered nicotine replacement therapy (35.0% of mental health and 40.2% of substance use facilities) or non-nicotine cessation medication (33.6% of mental health and 35.3% of substance use facilities). Policies prohibiting both smoking and vaping were reported by 53.9% of mental health and 33.9% of substance use facilities. Among facilities with a tobacco-free policy, 64.4% of mental health and 81.8% of substance use facilities offered at least one cessation service. Opportunities remain to improve cessation supports in behavioral health treatment facilities, including tobacco-free policies and integrated tobacco cessation treatment services. These strategies could help decrease tobacco-related disease and improve behavioral health outcomes.
<i>Notes from the Field:</i> Assessment of Awareness, Use, and Access Barriers to Cooling Centers in Maricopa County, Arizona — August 1–September 15, 2023
Authors: Aaron Gettel, Meaghan Batchelor, Jessica Bell, Heather L. Walker, Kathryn G. Burr, June Vutrano, Angela Moreth, Jessica R. White, Rebecca Sunenshine, Ariella P. Dale, Jackie Ward, Nicole M. Jarrett
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Leveraging Longitudinal Patient-Reported Outcomes Trajectories to Predict Survival in Non-Small-Cell Lung Cancer
Authors: Jiawei Zhou, Benyam Muluneh, Zhaoyang Wang, Huaxiu Yao, Jim H. Hughes
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Despite their potential, patient-reported outcomes (PRO) are often underutilized in clinical decision-making, especially when improvements in PRO do not align with clinical outcomes. This misalignment may result from insufficient analytical methods that overlook the temporal dynamics and substantial variability of PRO data. To address these gaps, we developed a novel approach to investigate the prognostic value of longitudinal PRO dynamics in non-small-cell lung cancer (NSCLC) using Lung Cancer Symptom Scale (LCSS) data. Methods: Longitudinal patient-reported LCSS data from 481 NSCLC participants in the placebo arm of a Phase III trial were analyzed. A population modeling approach was applied to describe PRO progression trajectories while accounting for substantial variability in the data. Associations between PRO model parameters and survival outcomes were assessed using Cox proportional hazards models. Model-informed PRO parameters were used to predict survival via machine learning. Results: A PRO progression model described LCSS dynamics and predicted a median time to symptom progression of 229 days (95% confidence interval [CI]: 15-583). Faster PRO progression rates were significantly associated with poorer survival (Hazard ratio [HR] 1.13, 95% CI: 1.076-1.18), while greater improved PRO effects by placebo/prior treatment correlated with improved survival (HR 0.93, 95% CI: 0.883-0.99). A machine learning model using PRO parameters achieved an AUC-ROC of 0.78, demonstrating their potential to predict overall survival. Conclusions: This study demonstrates that longitudinal PRO data can provide prognostic insights into survival in NSCLC. The findings support the use of PRO dynamics to improve clinical decision-making and optimize patient-centered treatment strategies.
Vaccination against influenza viruses annually: Renewing or narrowing the protective shield?
Authors: Hanover C. Matz, Ali H. Ellebedy
Journal: The Journal of Experimental Medicine (2025)

Annual vaccines are recommended for the seasonal influenza virus. While yearly updates to the vaccine are necessary due to the constant evolution of influenza viruses, some studies have suggested repeat vaccination may result in a reduction in vaccine effectiveness in subsequent years. This review examines the available evidence that repeated annual influenza virus vaccination may have effects on future vaccine responses, and it synthesizes the available data with studies that may indicate potential immunological mechanisms underlying these effects. The goal is to examine the available literature to determine whether these mechanisms can be subverted to improve seasonal influenza virus vaccine efficacy.
Mechanomedicine for Addressing Skeletal Muscle Insulin Resistance
Authors: Lu Wang, Le Chang, Yufei Ma, Yuanbo Jia, Bin Gao, Wei Cui, Feng Xu
Journal: Endocrine Reviews (2025)

Abstract Skeletal muscle insulin resistance (IR) is a critical deficiency in IR pathophysiology that significantly affects overall metabolic health. Skeletal muscle is mechanically sensitive since its structure and function are significantly influenced by factors, such as mechanical stretching and tissue stiffness. These mechanical stimuli can cause adaptive changes that enhance muscle performance and resilience. In this review, we discuss the current state of skeletal muscle IR research from the perspective of mechanomedicine. We also systematically and comprehensively present the evolution of mechanomedicine in addressing skeletal muscle IR by various disciplines, including biomechanics, mechanobiology, mechanodiagnosis, and mechanotherapy. The goal of the review is to provide significant theoretical insights and practical methods for elucidating the pathogenesis of IR and to advance diagnostic and therapeutic approaches informed by mechanomedicine.
Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts
Authors: Jia-Nan Cheng, Zheng Jin, Chunxia Su, Tao Jiang, Xiaobin Zheng, Jinming Guo, Xingyi Li, Han Chu, Jia Jia, Qin Zhou, Xiaofang Ding, Yiwen Zhang, Shouxia Xu, Fancong Dong, Qiao Zhang, Xinxin Yang, Tao Yang, Xiaoming Cheng, Haoran Zha, Degao Chen, Yisong Y Wan, Xindong Liu, Lilin Ye, Haidong Tang, Alistair L J Symonds, Qi-Jing Li, Qingzhu Jia, Bo Zhu
Journal: Cancer Cell (2025)