tbuckley/cabot-search huggingface dataset:
The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes
Authors: James R. Cerhan, Matthew J. Maurer, Brian K. Link, Andrew L. Feldman, Thomas M. Habermann, David L. Jaye, W. Richard Burack, Timothy J. McDonnell, Francisco Vega, Jennifer R. Chapman, Sergei Syrbu, Kiran R. Vij, Giorgio Inghirami, John P. Leonard, Leon Bernal‐Mizrachi, Umar Farooq, Thomas E. Witzig, George J. Weiner, Yucai Wang, Juan P. Alderuccio, Susan L. Slager, Melissa C. Larson, Shaun M. Riska, Brianna J. Gysbers, Julianne J. Lunde, Tanner W. Reicks, Amy A. Ayers, Colin B. O'Leary, Kathleen J. Yost, Hongfang Liu, Grzegorz S. Nowakowski, Jia Ruan, Dai Chihara, Jean L. Koff, Carla Casulo, Carrie A. Thompson, Jonathon B. Cohen, Brad S. Kahl, Loretta J. Nastoupil, Izidore S. Lossos, Jonathan W. Friedberg, Peter Martin, Christopher R. Flowers
Journal: American Journal of Hematology (2024)

Abstract To address the current and long‐term unmet health needs of the growing population of non‐Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/ ). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18–99). Participants came from 49 US states and included 538 Black/African‐Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age &lt;40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma ( N = 5883, 76.0%) and germline DNA ( N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes ( N = 1189); and collected quality of life ( N = 5281, 68.3%) and epidemiologic risk factor ( N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population‐based SEER data (2015–2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population‐based SEER rates for indolent B‐cell (follicular and marginal zone) and T‐cell lymphomas, but were 10%–15% higher than SEER rates for aggressive B‐cell subtypes (diffuse large B‐cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.
Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes
Authors: Tim ten Brink, Febriyani Damanik, Joris I. Rotmans, Lorenzo Moroni
Journal: Advanced Healthcare Materials (2024)

Abstract Biomaterials are defined as “engineered materials” and include a range of natural and synthetic products, designed for their introduction into and interaction with living tissues. Biomaterials are considered prominent tools in regenerative medicine that support the restoration of tissue defects and retain physiologic functionality. Although commonly used in the medical field, these constructs are inherently foreign toward the host and induce an immune response at the material–tissue interface, defined as the foreign body response (FBR). A strong connection between the foreign body response and tissue regeneration is suggested, in which an appropriate amount of immune response and macrophage polarization is necessary to trigger autologous tissue formation. Recent developments in this field have led to the characterization of immunomodulatory traits that optimizes bioactivity, the integration of biomaterials and determines the fate of tissue regeneration. This review addresses a variety of aspects that are involved in steering the inflammatory response, including immune cell interactions, physical characteristics, biochemical cues, and metabolomics. Harnessing the advancing knowledge of the FBR allows for the optimization of biomaterial‐based implants, aiming to prevent damage of the implant, improve natural regeneration, and provide the tools for an efficient and successful in vivo implantation.
Injectable Conductive Hydrogel with Self‐Healing, Motion Monitoring, and Bacteria Theranostics for Bioelectronic Wound Dressing
Authors: Mengyao Shan, Xin Chen, Xiaoyang Zhang, Shike Zhang, Linlin Zhang, Jinzhou Chen, Xianghong Wang, Xuying Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Wounds at joints are difficult to treat and tend to recover more slowly due to the frequent motions. When using traditional hydrogel dressings, they are easy to crack and undergo bacterial infection, difficult to match and monitor the irregular wounds. Integrating multiple functions within a hydrogel dressing to achieve intelligent wound monitoring and healing remains a significant challenge. In this research, a multifunctional hydrogel is developed based on polysaccharide biopolymer, poly(vinyl alcohol), and hydroxylated graphene through dynamic borate ester bonding and supramolecular interaction. The prepared hydrogel not only exhibits rapid self‐healing (within 60 s), injectable, conductive and motion monitoring properties, but also realizes in situ bacterial sensing and killing functions. It shows excellent bacterial sensitivity (within 15 min) and killing ability via the changes of electrical signals and photothermal therapy, avoiding the emergence of drug‐resistant bacteria. In vivo experiments prove that the hydrogel can promote wound healing effectively. In addition, it displays great electromechanical performance to achieve real‐time monitoring and prevent re‐tearing of the wound at human joints. The injectable pH‐responsive hydrogel with good biocompatibility demonstrates considerable potential as multifunctional bioelectronic dressing for the detection, treatment, management, and healing of infected joint wounds.
Disparities and social determinants of periodontal diseases
Authors: Jasim M. Albandar
Journal: Periodontology 2000 (2024)

Abstract Periodontal diseases are highly prevalent in populations worldwide and are a major global public health problem, with major negative impacts on individuals and communities. This study investigates evidence of disparities in periodontal diseases by age groups, gender, and socioeconomic factors. There is ample evidence that these diseases disproportionally affect poorer and marginalized groups and are closely associated with certain demographics and socioeconomic status. Disparities in periodontal health are associated with social inequalities, which in turn are caused by old age, gender inequality, income and education gaps, access to health care, social class, and other factors. In health care, these factors may result in some individuals receiving better and more professional care compared to others. This study also reviews the potential causes of these disparities and the means to bridge the gap in disease prevalence. Identifying and implementing effective strategies to eliminate inequities among minorities and marginalized groups in oral health status and dental care should be prioritized in populations globally.
Cellular metabolism: A key player in cancer ferroptosis
Authors: Xianjie Jiang, Qiu Peng, Mingjing Peng, Linda Oyang, Honghan Wang, Qiang Liu, Xuemeng Xu, Nayiyuan Wu, Shiming Tan, Wenjuan Yang, Yaqian Han, Jinguan Lin, Longzheng Xia, Yanyan Tang, Xia Luo, Jie Dai, Yujuan Zhou, Qianjin Liao
Journal: Cancer Communications (2024)

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.
Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery
Authors: Violeta Raverdy, Federica Tavaglione, Estelle Chatelain, Robert Caiazzo, Chiara Saponaro, Guillaume Lassailly, Helene Verkindt, Gregory Baud, Camille Marciniak, Mikael Chetboun, Naima Oukhouya-Daoud, Viviane Gnemmi, Emmanuelle Leteurtre, Alain Duhamel, Mathurin Philippe, Guillemette Marot, Stefano Romeo, François Pattou
Journal: Metabolism (2024)

Background & aims The value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery. Methods Participants were individuals with obesity submitted to needle liver biopsy at the time of bariatric surgery, and 12 and/or 60 months after surgery. We calculated the fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), AST to platelet ratio index (APRI), Hepatic fibrosis score (HFS), Fibrosis NAFLD index (FNI), and Liver risk score (LRS) at each time point, and compared their performances for predicting significant fibrosis (F ≥ 2) and its resolution following surgery. Results At baseline, 2436 patients had liver biopsy, including 261 (10.7 %) with significant fibrosis. Overall, 672 patients had pre- and post-operative biopsies (564 at M12 and 328 at M60). The fibrosis stage decreased at M12 and M60 (p < 0.001 vs M0). Resolution of significant fibrosis occurred in 58/121 (47.9 %) at M12 and 32/50 (64 %) at M60. The mean value of all tests decreased after surgery, except for FIB-4. Performances for predicting fibrosis resolution was higher at M60 than at M12 for all tests, and maximal at M60 for FNI and LRS: area under the curve 0.843 (95%CI 0.71–0.95) and 0.92 (95%CI 0.84–1.00); positive likelihood ratio 3.75 (95 % CI 1.33–10.59) and 4.58 (95 % CI 1.65–12.70), respectively. Conclusions Results showed the value and limits of non-invasive tests for monitoring the evolution of liver fibrosis after an intervention. Following bariatric surgery, the best performances to predict the resolution of significant fibrosis were observed at M60 with tests combining liver and metabolic traits, namely FNI and LRS.
Replacing cholesterol with asiatic acid to prolong circulation and enhance anti-metastatic effects of non-PEGylated liposomes
Authors: Yicong Zhang, Yujia Wang, Hanming Zhang, Shiqi Huang, Yuai Li, Jiaying Long, Yikun Han, Qing Lin, Tao Gong, Xun Sun, Zhirong Zhang, Ling Zhang
Journal: Journal of Controlled Release (2024)
Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects
Authors: Zehao Jing, Wanqiong Yuan, Jiedong Wang, Renhua Ni, Yu Qin, Zhinan Mao, Feng Wei, Chunli Song, Yufeng Zheng, Hong Cai, Zhongjun Liu
Journal: Bioactive Materials (2024)

[This corrects the article DOI: 10.1016/j.bioactmat.2023.11.001.].
Polyethylene glycol (PEG) as a broad applicability marker for LC–MS/MS-based biodistribution analysis of nanomedicines
Authors: Astrid Hyldbakk, Terkel Hansen, Sjoerd Hak, Sven Even F. Borgos
Journal: Journal of Controlled Release (2024)

Polyethylene glycol (PEG) conjugation (PEGylation) is a well-established strategy to improve the pharmacokinetic and biocompatibility properties of a wide variety of nanomedicines and therapeutic peptides and proteins. This broad use makes PEG an attractive 'allround' candidate marker for the biodistribution of such PEGylated compounds. This paper presents the development of a novel strategy for PEG quantification in biological matrices. The methodology is based on sample hydrolysis which both decomposes the sample matrix and degrades PEGylated analytes to specific molecular fragments more suitable for detection by LC–MS/MS. Method versatility was demonstrated by applying it to a wide variety of PEGylated compounds, including polymeric poly(ethylbutyl cyanoacrylate) (PEBCA) nanoparticles, lipidic nanoparticles (Doxil®, LipImage 815™ and lipid nanoparticles for nucleic acid delivery) and the antibody Cimzia®. Method applicability was assessed by analyzing plasma and tissue samples from a comprehensive drug biodistribution study in rats, of both PEBCA and LipImage 815™ nanoparticles. The results demonstrated the method's utility for biodistribution studies on PEG. Importantly, by using the method described herein in tandem with quantification of nanoparticle payloads, we showed that this approach can provide detailed understanding of various critical aspects of the in vivo behavior of PEGylated nanomedicines, such as drug release and particle stability. Together, the presented results demonstrate the novel method as a robust, versatile and generic approach for biodistribution analysis of PEGylated therapeutics.
Streptococcus salivarius K12 Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors: A Randomized Controlled Trial
Authors: Xingchen Peng, Zixia Li, Yiyan Pei, Shuhao Zheng, Jinchi Liu, Jingjing Wang, Ruidan Li, Xin Xu
Journal: Journal of Clinical Oncology (2024)

PURPOSE Oral mucositis (OM) is a common debilitating toxicity associated with radiotherapy (RT) for malignant head and neck tumors. This prospective, randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy and safety of Streptococcus salivarius K12 (SsK12) in reducing the incidence, duration, and severity of severe OM (SOM). METHODS A total of 160 patients with malignant head and neck tumors undergoing definitive or postoperative adjuvant RT were randomly assigned (1:1) to receive SsK12 probiotic (n = 80) or placebo (n = 80) at West China Hospital, Sichuan University, Chengdu, China. Patients were instructed to suck SsK12 or placebo lozenges thrice daily from the initiation to the end of RT. OM was evaluated twice a week during RT and once a week thereafter for up to 8 weeks. The primary end point was the incidence of SOM. Adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. RESULTS Baseline patient characteristics were similar in the SsK12 and placebo groups. The incidence of SOM was significantly lower in the SsK12 group as compared with the placebo group (36.6% v 54.2%; P = .0351). The duration (median, 0.0 days v 7.0 days; mean, 8.9 days v 18.3 days; P = .0084) and time to develop SOM (median, not estimable v 42.0 days; hazard ratio, 0.55 [95% CI, 0.34 to 0.89]; log-rank test: P = .0123) were also improved in the case of the SsK12 group. Adverse events were similar between the groups, and mild or moderate gastrointestinal reactions (flatulence or dyspepsia) associated with the lozenges were observed in two patients in the SsK12 group. High-throughput sequencing results indicated that SsK12 inhibited opportunistic pathogens and enriched oral commensals during RT. CONCLUSION In this prospective, randomized clinical trial, SsK12 probiotic significantly reduced the incidence, onset, and duration of SOM with a good safety profile.
Nanoparticles targeting the intestinal Fc receptor enhance intestinal cellular trafficking of semaglutide
Authors: Soraia Pinto, Mahya Hosseini, Stephen T. Buckley, Wen Yin, Javad Garousi, Torbjörn Gräslund, Sven van Ijzendoorn, Hélder A. Santos, Bruno Sarmento
Journal: Journal of Controlled Release (2024)

Semaglutide is the first oral glucagon-like peptide-1 (GLP-1) analog commercially available for the treatment of type 2 diabetes. In this work, semaglutide was incorporated into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) to improve its delivery across the intestinal barrier. The nanocarriers were surface-decorated with either a peptide or an affibody that target the human neonatal Fc receptor (hFcRn), located on the luminal cell surface of the enterocytes. Both ligands were successfully conjugated with the PLGA-PEG via maleimide-thiol chemistry and thereafter, the functionalized polymers were used to produce semaglutide-loaded NPs. Monodisperse NPs with an average size of 170 nm, neutral surface charge and 3% of semaglutide loading were obtained. Both FcRn-targeted NPs exhibited improved interaction and association with Caco-2 cells (cells that endogenously express the hFcRn), compared to non-targeted NPs. Additionally, the uptake of FcRn-targeted NPs was also observed to occur in human intestinal organoids (HIOs) expressing hFcRn through microinjection into the lumen of HIOs, resulting in potential increase of semaglutide permeability for both ligand-functionalized nanocarriers. Herein, our study demonstrates valuable data and insights that the FcRn-targeted NPs has the capacity to promote intestinal absorption of therapeutic peptides.
Systemic delivery of mutant huntingtin lowering antisense oligonucleotides to the brain using apolipoprotein A-I nanodisks for Huntington disease
Authors: Nicholas S. Caron, Amirah E.-E. Aly, Hailey Findlay Black, Dale D.O. Martin, Mandi E. Schmidt, Seunghyun Ko, Christine Anderson, Emily M. Harvey, Lorenzo L. Casal, Lisa M. Anderson, Seyed M.R. Rahavi, Gregor S.D. Reid, Michael N. Oda, Danica Stanimirovic, Abedelnasser Abulrob, Jodi L. McBride, Blair R. Leavitt, Michael R. Hayden
Journal: Journal of Controlled Release (2024)

Efficient delivery of therapeutics to the central nervous system (CNS) remains a major challenge for the treatment of neurological diseases. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion mutation in the HTT gene which codes for a toxic mutant huntingtin (mHTT) protein. Pharmacological reduction of mHTT in the CNS using antisense oligonucleotides (ASO) ameliorates HD-like phenotypes in rodent models of HD, with such therapies being investigated in clinical trials for HD. In this study, we report the optimization of apolipoprotein A-I nanodisks (apoA-I NDs) as vehicles for delivery of a HTT-targeted ASO (HTT ASO) to the brain and peripheral organs for HD. We demonstrate that apoA-I wild type (WT) and the apoA-I K133C mutant incubated with a synthetic lipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, can self-assemble into monodisperse discoidal particles with diameters <20 nm that transmigrate across an in vitro blood-brain barrier model of HD. We demonstrate that apoA-I NDs are well tolerated in vivo, and that apoA-I K133C NDs show enhanced distribution to the CNS and peripheral organs compared to apoA-I WT NDs following systemic administration. ApoA-I K133C conjugated with HTT ASO forms NDs (HTT ASO NDs) that induce significant mHTT lowering in the liver, skeletal muscle and heart as well as in the brain when delivered intravenously in the BACHD mouse model of HD. Furthermore, HTT ASO NDs increase the magnitude of mHTT lowering in the striatum and cortex compared to HTT ASO alone following intracerebroventricular administration. These findings demonstrate the potential utility of apoA-I NDs as biocompatible vehicles for enhancing delivery of mutant HTT lowering ASOs to the CNS and peripheral organs for HD.
Branched pegylated linker-auristatin to control hydrophobicity for the production of homogeneous minibody-drug conjugate against HER2-positive breast cancer
Authors: Emmanuel Douez, Emilie Allard-Vannier, Imène Ait Mohamed Amar, Louis Jolivet, Fanny Boursin, Aurélie Maisonial-Besset, Tiffany Witkowski, Jean-Michel Chezal, Cyril Colas, Stéphanie Letast, Etienne Auvert, Caroline Denevault-Sabourin, Nicolas Aubrey, Nicolas Joubert
Journal: Journal of Controlled Release (2024)
Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy
Authors: Peishan Li, Ying Xie, Jinling Wang, Chunjie Bao, Jialun Duan, Yixuan Liu, Qian Luo, Jiarui Xu, Yuxin Ren, Min Jiang, Jianwei Li, Haitao Guo, Huihui Zhao, Guiling Wang, Yanqin Liang, Wanliang Lu
Journal: Bioactive Materials (2024)

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8
Passive immunotherapy for Alzheimer's disease
Authors: Xiaoyi Guo, Li Yan, Denghong Zhang, Yingjun Zhao
Journal: Ageing Research Reviews (2024)

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by cognitive impairment with few therapeutic options. Despite many failures in developing AD treatment during the past 20 years, significant advances have been achieved in passive immunotherapy of AD very recently. Here, we review characteristics, clinical trial data, and mechanisms of action for monoclonal antibodies (mAbs) targeting key players in AD pathogenesis, including amyloid-β (Aβ), tau and neuroinflammation modulators. We emphasized the efficacy of lecanemab and donanemab on cognition and amyloid clearance in AD patients in phase III clinical trials and discussed factors that may contribute to the efficacy and side effects of anti-Aβ mAbs. In addition, we provided important information on mAbs targeting tau or inflammatory regulators in clinical trials, and indicated that mAbs against the mid-region of tau or pathogenic tau have therapeutic potential for AD. In conclusion, passive immunotherapy targeting key players in AD pathogenesis offers a promising strategy for effective AD treatment.