tbuckley/cabot-search huggingface dataset:
Pharmacist-Led Management Model and Medication Adherence Among Patients With Chronic Heart Failure
Authors: Lingjiao Wang, Yuanyuan Zhao, Liping Han, Huan Zhang, Hejun Chen, Aixia Liu, Jing Yu, Ran Fu, Liguang Duan, Feiyue An, Zhimin Guo, Yang Lun, Chaoli Chen, Fangfang Cheng, Chaohui Song, Haixia Gao, Chunhua Zhou
Journal: JAMA Network Open (2024)

Importance Poor medication adherence is associated with high morbidity and mortality among patients with chronic heart failure (CHF), which is particularly concerning in China. Objective To assess the effect of a pharmacist-led management model incorporating a social media platform vs usual care on medication adherence in patients with CHF. Design, Setting, and Participants This prospective, multicenter randomized clinical trial was conducted from March 2021 to May 2023, with a follow-up duration of 52 weeks. The trial was conducted in the cardiology wards of 5 hospitals in China. Participants were 18 years or older, had a CHF diagnosis, and were receiving stable medication. They were randomly assigned to either the intervention group (pharmacist-led management) or the control group (usual care) in a 1:1 ratio using a computer-generated random number table with concealed allocation via opaque envelopes. Intention-to-treat data analysis was performed from June 2023 to July 2024. Intervention The intervention group received a multimodal pharmaceutical intervention, including WeChat application–based communication and education, and a standardized follow-up visit from a pharmacist every month. The control group received the standardized follow-up visit from nurses every month. Main Outcomes and Measures The primary outcome was the proportion of days covered (PDC) by heart failure medication at 52 weeks. Results Among the 445 participants analyzed, 223 were assigned to the intervention group and 222 to the control group. These patients had a mean (SD) age of 63.2 (13.3) years and included 263 males (59.1%). A total of 333 patients (74.8%) had a New York Heart Association class III or IV heart failure, indicating severe limitations in physical activity. At 52 weeks, the intervention group had a significantly higher PDC for heart failure medication (8.1%; 95% CI, 5.5%-10.7%; P &amp;amp;lt; .001) and a greater proportion of patients with PDC of 80% or greater (odds ratio, 0.34; 95% CI, 0.21-0.54; P &amp;amp;lt; .001) compared with the control group. Conclusions and Relevance This randomized clinical trial found a modest improvement in medication adherence among patients with CHF who received the pharmacist-led management intervention vs usual care. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2000040232
Health-Oriented Strategy for Clean Air and Climate Actions: Differential Health Effects of Atmospheric Components
Authors: Tao Xue, Ning Kang, Tong Zhu
Journal: Annual Review of Public Health (2024)

Health is at the forefront of clean air and climate action. However, most existing studies of health impacts were based on additive single-exposure effects, which often oversimplify the relationships between atmospheric components and health outcomes. This review examines various atmospheric components’ common sources and differential health effects, including greenhouse gases and major air pollutants such as fine particulate matter (PM 2.5 ). It emphasizes the need for a comparative assessment of health impacts across various atmospheric components. We further highlight black carbon as an illustrative example, given its higher toxicity compared with other major PM 2.5 components. By integrating the best available findings on the differential effects of particulate matter components with multiple gridded estimates of air pollution concentrations and population data, we conducted a risk assessment to quantify the health benefits of particulate matter reductions associated with China's clean air actions (2013–2020) and future climate mitigation scenarios (2020–2060). Our assessments indicate that, in regions or during periods where black carbon accounts for a higher proportion of exposure reduction relative to other PM 2.5 components, reducing per-unit concentrations of PM 2.5 can prevent more premature deaths. We propose a conceptual framework for a health-oriented strategy to enhance the effectiveness of clean air and climate initiatives.
T Cell Development and Responses in Human Immune System Mice
Authors: Mohsen Khosravi-Maharlooei, Hao Wei Li, Megan Sykes
Journal: Annual Review of Immunology (2024)

Human Immune System (HIS) mice constructed with mature human immune cells or with human hematopoietic stem cells and thymic tissue have provided an important tool for human immunological research. In this article, we first review the different types of HIS mice based on human tissues transplanted and sources of the tissues. We then focus on knowledge of human T cell development and responses obtained using HIS mouse models. These areas include the development of human T cell subsets, with a focus on $\upalpha$ $\upbeta$ conventional T cells and regulatory T cells, and human T cell responses in the settings of infection, transplantation rejection and tolerance, autoimmune disease, cancer immunotherapy, and regulatory T cell therapy. We also discuss the limitations and potential future applications of HIS mouse models.
Discovery of a non‐nucleotide stimulator of interferon genes (STING) agonist with systemic antitumor effect
Authors: Xiyuan Wang, Zhengsheng Zhan, Zhen Wang, Yan Zhang, Kaiyan Zhao, Han Li, Xiaoqian Zhou, Yuting Guo, Fengying Fan, Jian Ding, Meiyu Geng, Xuekui Yu, Wenhu Duan, Zuoquan Xie
Journal: MedComm (2024)

Abstract Agonists of the stimulator of interferon genes (STING) pathway are increasingly being recognized as a promising new approach in the treatment of cancer. Although progress in clinical trials for STING agonists in antitumor applications has been slow, there is still an urgent need for developing new potent STING agonists with versatile potential applications. Herein, we developed and identified a non‐nucleotide STING agonist called DW18343. DW18343 showed robust activation across different STING isoforms. Crystallography analysis revealed that DW18343 binds more deeply into the ligand binding domain (LBD) pocket of STING‐H232 compared to other agonists such as MSA‐2, SR‐717, or cGAMP, which likely contributes to its high potency. DW18343 triggered downstream p‐TBK1/p‐IRF3 signaling, leading to the production of multiple cytokines. Additionally, DW18343 displayed broad and long‐lasting antitumor effects in various syngeneic mouse tumor models, whether administered locally or systemically. Moreover, DW18343 induced immune memory to combat the growth of rechallenged tumors. Finally, DW18343 was shown to be an activator of both the innate and adaptive antitumor immunity in tumor tissue, potentially explaining its strong antitumor effects in vivo. In conclusion, DW18343 serves as a novel non‐nucleotide STING agonist with systemic antitumor effect through the activation of antitumor immunity.
Fluorinated chitosan mediated transepithelial delivery of sanguinarine-loaded platinum (IV) prodrug for intravesical instillation therapy of muscle-invasive bladder cancer
Authors: Xinzi Hu, Guangzhi Li, Chenfan Kong, Lisha Liu, Dashi Deng, Guizhong Xin, Jian Pan, Song Wu, Qifang Lei
Journal: Journal of Controlled Release (2024)

Cisplatin-based neoadjuvant chemotherapy is first-line strategy to inhibit progression and metastasis of muscle-invasive bladder cancer (MIBC). However, its clinical efficacy is often limited by drug resistance and severe systemic side effects, highlighting the urgent need for innovative therapeutic approaches. Despite advancements in cisplatin-based regimens, research on intravesical cisplatin delivery systems remains scarce. In this study, we developed an amphiphilic platinum(IV) prodrug micellar platform (Pt (IV)-DI-PEG) capable of efficiently encapsulating sanguinarine (San), which was further coated with fluorinated chitosan (FCS) to construct San@Pt(IV)-DI-PEG@FCS nanoparticles (SPFNPs) for intravesical instillation even targeting MIBC. The resulting SPFNPs demonstrated several advantages: the FCS coating facilitated enhanced trans-epithelial drug delivery by regulating bladder epithelial tight junction proteins, enabling efficient intravesical administration; Second, the glutathione (GSH)-responsive reduction of the Pt(IV) prodrug promoted tumor-targeted release of San and localized accumulation of Pt(II), while simultaneously depleting intracellular GSH. Furthermore, the released San induced reactive oxygen species (ROS) production, oxidative cleavage and inhibit the activation and function of poly (ADP-ribose) polymerase, collectively impairing nucleotide-excision repair and preventing the elimination of Pt-DNA adducts, resulting in persistent DNA damage, cell cycle arrest, and apoptosis in tumor cells. The synergistic effects of San and cisplatin were validated in both orthotopic mouse models and patient-derived orthotopic xenograft, demonstrating robust anti-tumor efficacy. This study underscores the potential of intravesical cisplatin formulations as a promising strategy for MIBC treatment, offering a shift from traditional systemic chemotherapy towards localized, targeted drug delivery systems.
A preclinical design approach for translation of biohybrid photosensitive nanoplatform for photodynamic therapy of breast cancer
Authors: Armin Imanparast, Amir Reza Ameri, Neda Attaran, Soheil Sharifi, Ali Tamayol, Ameneh Sazgarnia, Seyed Ali Mousavi Shaegh
Journal: Journal of Controlled Release (2024)
Smoking carcinogen induced inflammation promotes lung carcinogenesis via IRAK4 activation.
Authors: Ritesh K. Aggarwal, Simone Sidoli, Jingli Wang, Srabani Sahu, Rahul Sanawar, Varun Gupta, Srinivas Aluri, Vineeth Sukrithan, Charan T.R. Vegivinti, Phaedon D. Zavras, Divij Verma, Shanisha Gordon-Mitchell, Beamon Agarwal, Tanya Verma, Daniel T. Starczynowski, Ulrich G. Steidl, Aditi Shastri, Balazs Halmos, Lindsay M. LaFave, Haiying Cheng, Amit Verma, Yiyu Zou
Journal: Clinical Cancer Research (2024)

Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Two major carcinogens in cigarette smoke, Nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(α)pyrene (BaP) have not been tested in models that mimic inhaled exposure for prolonged periods of time.
Socioeconomic Status, Diet, and Behavioral Factors and Cardiometabolic Diseases and Mortality
Authors: Peilu Wang, Xiang Gao, Walter C. Willett, Edward L. Giovannucci
Journal: JAMA Network Open (2024)

It remains unclear how socioeconomic status (SES) is related to the association between diet and health, as well as the role of behavioral factors, in explaining socioeconomic disparities in health outcomes.
Chondrocyte-targeted bilirubin/rapamycin carrier-free nanoparticles alleviate oxidative stress and modulate autophagy for osteoarthritis therapy
Authors: Huirong Huang, Xindan Liang, Shengjie Li, Yuqi Yan, Shize Li, Chenyu Qiu, Zhanzheng Ye, Yixuan Zhu, Dingchao Shen, Yinhao Lin, Luhui Wang, Nuo Chen, Yinsha Yao, Xinyu Zhao, Fugen Wu, Xianbao Shi, Longfa Kou, Ruijie Chen, Qing Yao
Journal: Journal of Controlled Release (2024)
Impact of the tumor microenvironment on delivery of nanomedicine in tumors treated with ultrasound and microbubbles
Authors: Caroline Einen, Sofie Snipstad, Håkon F Wesche, Veronica Nordlund, Ella J Devold, Naseh Amini, Rune Hansen, Einar Sulheim, Catharina de Lange Davies
Journal: Journal of Controlled Release (2024)

The delivery of nanoparticles to tumors has been shown preclinically to be improved by microbubble-mediated ultrasound. However, the mechanisms and biological effects not fully understood. In this study, we explored the influence of the tumor microenvironment on nanoparticle uptake and microdistribution both with and without ultrasound and microbubble treatment. Three murine tumor models, KPC (pancreatic ductal adenocarcinoma), 4 T1 (triple negative mammary carcinoma) and CT26 (colon carcinoma), were characterized with respect to extracellular matrix composition, tumor stiffness and perfusion. KPC and 4 T1 tumors presented higher levels of collagen and hyaluronic acid and were stiffer compared to CT26, whereas all three tumors had similar levels of sulfated glycosaminoglycans. Furthermore, the 4 T1 tumors appeared poorly vascularized with a lower cell density compared to KPC and CT26. All three tumors presented similar nanoparticle uptake, but extravasated nanoparticles traveled significantly shorter in KPC tumors compared to 4 T1 and CT26. The effect of ultrasound and microbubble treatment on the tumor uptake and penetration of polymer nanoparticles into the extracellular matrix were evaluated using a treatment protocol previously shown to increase nanoparticle delivery to tumors. Interestingly, we found a significant increase in nanoparticle uptake in the soft CT26 tumor, but no effect of the ultrasound treatment in the stiff KPC and 4 T1 tumors, suggesting that tumor stiffness is an important parameter for treatment with ultrasound and microbubbles. Ultrasound treatment resulted in a modest but not statistically significant improvement in nanoparticle penetration through the extracellular matrix. In tumors demonstrating increased uptake of nanoparticles following ultrasound treatment, the uptake correlated positively with blood volume. These findings emphasize the importance of taking the tumor microenvironment into consideration when optimizing ultrasound parameters for delivery of nanomedicine.
In situ forming and self-crosslinkable protein hydrogels for localized cancer therapy and topical wound healing
Authors: Soomin Eom, Seong Guk Park, Yong Hoe Koo, Yeongjin Noh, Cholong Choi, Yunjung Kim, Heejin Jun, Chaenyung Cha, Jinmyoung Joo, Sebyung Kang
Journal: Journal of Controlled Release (2024)
Correction: Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study
Authors: Yan Bian, Ye Gao, Han Lin, Chang Sun, Wei Wang, Siyu Sun, Xiuling Li, Zhijie Feng, Jianlin Ren, Hezhong Chen, Chaojing Lu, Jinfang Xu, Jun Zhou, Kangkang Wan, Lei Xin, Zhaoshen Li, Luowei Wang
Journal: Journal of Hematology & Oncology (2024)
Optimal <i>in vitro</i> models as a basis for understanding and more effective treatment of infantile hemangiomas
Authors: Marko Bašković
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Optimal in vitro models as a basis for understanding and more effective treatment of infantile hemangiomas Get access Marko Bašković Marko Bašković Scientific Centre of Excellence for Reproductive and Regenerative Medicine, University of Zagreb, School of Medicine, Šalata 3, 10000 Zagreb, CroatiaChildren's Hospital Zagreb, Ulica Vjekoslava Klaića 16, 10000 Zagreb, Croatia Corresponding author: Email:[email protected] https://orcid.org/0000-0003-4218-6184 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae505, https://doi.org/10.1093/bjd/ljae505 Published: 21 December 2024 Article history Received: 17 December 2024 Accepted: 19 December 2024 Published: 21 December 2024
Bright yellow dots in children
Authors: André Luiz Vairo Donda, Rodrigo Pirmez, Antonella Tosti, Colombina Vicenzi, Daniel Fernandes Melo
Journal: British Journal of Dermatology (2024)

In this retrospective study, we performed a chart and image review of numerous pediatric patients with the confirmed diagnosis of alopecia areata. Yellow dots are one of the most common findings in adults but may appear with different characteristics in the pediatric population.
Haematohidrosis
Authors: Yashdeep Singh Pathania
Journal: British Journal of Dermatology (2024)

Sudden untimely appearance of blood over the skin without systemic or dermatological diseases may be a frightening experience both for the patient and parents. Haematohidrosis is a rare and scarcely reported entity in which patients sweat blood, usually on account of acute fear, stress or anxiety. Counselling of the patient may underscore potential underlying triggers and unravel the psychocutaneous disorder in select patients.
Unseen Spaces: Psoriasis Inversa Between the Toes
Authors: Sarah Preis, Tilo Biedermann, Alexander Zink
Journal: British Journal of Dermatology (2024)

A 6-year-old girl presented with long-standing, erythematous plaques in the interdigital spaces of her toes that were resistant to antifungal and other antimicrobial treatments. The discovery of additional lesions on fully-body examination prompted the diagnosis of inverse psoriasis, further supported by a positive family history. After topical treatment with vitamin D analogs, her lesions resolved completely within eight weeks. Interdigital psoriasis is a rare form of inverse psoriasis and should be considered in cases of resistant interdigital skin lesions, especially with a family history of psoriasis.
Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives
Authors: Yuhang Chen, Suoyi Dai, Chien-shan Cheng, Lianyu Chen
Journal: Journal of Hematology & Oncology (2024)

Lenvatinib is a multi-target tyrosine kinase inhibitor widely used in the treatment of hepatocellular carcinoma (HCC). Its primary mechanism of action involves inhibiting signal pathways such as vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR), thereby reducing tumor cell proliferation and angiogenesis and affecting the tumor's immune microenvironment. In the treatment of liver cancer, although lenvatinib monotherapy has shown good clinical effect, the problem of drug resistance is becoming more and more serious. This resistance may be caused by a variety of factors, including genetic mutations, signaling pathway remodeling, and changes in the tumor microenvironment. In order to overcome drug resistance, the combination of lenvatinib and other therapeutic strategies has gradually become a research hotspot, and it is worth noting that the combination of lenvatinib and immune checkpoint inhibitors (ICIs) has shown a good application prospect. This combination not only enhances the anti-tumor immune response but also helps improve therapeutic efficacy. However, combination therapy also faces challenges regarding safety and tolerability. Therefore, studying the mechanisms of resistance and identifying relevant biomarkers is particularly important, as it aids in early diagnosis and personalized treatment. This article reviews the mechanisms of lenvatinib in treating liver cancer, the mechanisms and efficacy of its combination with immune checkpoint inhibitors, the causes of resistance, the exploration of biomarkers, and other novel combination therapy strategies for lenvatinib. We hope to provide insights into the use and research of lenvatinib in clinical and scientific settings, offering new strategies for the treatment of liver cancer.
Glucose Abnormalities Detected by Continuous Glucose Monitoring in Very Old Adults With and Without Diabetes
Authors: Natalie R. Daya, Michael Fang, Dan Wang, Arielle Valint, B. Gwen Windham, Josef Coresh, Justin B. Echouffo-Tcheugui, Elizabeth Selvin
Journal: Diabetes Care (2024)

To characterize the prevalence of continuous glucose monitoring (CGM)-defined glucose abnormalities in a large, community-based population of very old adults (>75 years). A cross-sectional analysis of 1,150 older adults with and without diabetes who attended the Atherosclerosis Risk in Communities Study (2021-2022). Diabetes was based on a self-reported diagnosis of diabetes by a health care provider, use of diabetes medication, or a hemoglobin A1c (HbA1c) ≥6.5%. Prediabetes was defined as an HbA1c of 5.7% to <6.5% and normoglycemia as an HbA1c of <5.7%. We analyzed CGM metrics, including mean glucose, measures of hyperglycemia, and the coefficient of variation, by diabetes status. Of the 1,150 participants (mean age 83 years, 59% women, 26% who are Black), 35.1% had normoglycemia, 34.5% had prediabetes, and 30.4% had diabetes. The summary 24-h ambulatory glucose profile for participants with prediabetes was very similar to those with normoglycemia. No participants with normoglycemia or prediabetes had a CGM mean glucose >140 mg/dL, while 32.7% of participants with diabetes had a CGM mean glucose >140 mg/dL. In very old adults with normal or prediabetes HbA1c, hyperglycemia detected by CGM was rare. This suggests that HbA1c adequately captures the burden of hyperglycemia for most people in this population.
Combined pyrotinib and fulvestrant for hormone receptor‐positive and HER2‐positive metastatic breast cancer: A multicenter, single‐arm, phase II trial
Authors: Jianli Zhao, Yunfang Yu, Wei Ren, Linxiaoxiao Ding, Yongjian Chen, Peng Yuan, Jian Yue, Yaping Yang, Guorong Zou, Tao Chen, Jie Chai, Li Zhang, Wenjing Wu, Yinduo Zeng, Xiujuan Gui, Yangyang Cai, Simin Luo, Zhongyu Yuan, Kang Zhang, Herui Yao, Ying Wang
Journal: MedComm (2024)

Abstract This multicenter, single‐arm, phase II clinical trial (NCT04034589) evaluated the efficacy and safety of pyrotinib combined with fulvestrant in patients with HR‐positive/HER2‐positive metastatic breast cancer who had experienced trastuzumab treatment failure. A total of 46 patients were enrolled, receiving pyrotinib orally once daily and fulvestrant intramuscularly on days 1 and 15 of cycle 1, followed by monthly doses on day 1. The primary endpoint was progression‐free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. The median PFS was 18.2 months (95% CI, 11.9–31.1) overall, 19.5 months (95% CI, 10.6–NA) for those receiving the combination as first‐line therapy, and 18.4 months (95% CI, 16.7–NA) for patients with brain metastases. Median OS was not reached, with a 3‐year OS rate of 75.2% (95% CI, 62.8–90.2%). The ORR was 32.5%, and the DCR was 97.5%. Responses were observed in patients with low tumor mutation burden and ZNF217 mutation. Importantly, no grade 4 or higher treatment‐related adverse events or deaths were reported, indicating a favorable safety profile. In conclusion, the combination of pyrotinib and fulvestrant demonstrated promising antitumor activity and acceptable safety in HR‐positive/HER2‐positive metastatic breast cancer patients.
Metastatic brain tumors: from development to cutting‐edge treatment
Authors: Guilong Tanzhu, Liu Chen, Jiaoyang Ning, Wenxiang Xue, Ce Wang, Gang Xiao, Jie Yang, Rongrong Zhou
Journal: MedComm (2024)

Abstract Metastatic brain tumors, also called brain metastasis (BM), represent a challenging complication of advanced tumors. Tumors that commonly metastasize to the brain include lung cancer and breast cancer. In recent years, the prognosis for BM patients has improved, and significant advancements have been made in both clinical and preclinical research. This review focuses on BM originating from lung cancer and breast cancer. We briefly overview the history and epidemiology of BM, as well as the current diagnostic and treatment paradigms. Additionally, we summarize multiomics evidence on the mechanisms of tumor occurrence and development in the era of artificial intelligence and discuss the role of the tumor microenvironment. Preclinically, we introduce the establishment of BM models, detailed molecular mechanisms, and cutting‐edge treatment methods. BM is primarily treated with a comprehensive approach, including local treatments such as surgery and radiotherapy. For lung cancer, targeted therapy and immunotherapy have shown efficacy, while in breast cancer, monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates are effective in BM. Multiomics approaches assist in clinical diagnosis and treatment, revealing the complex mechanisms of BM. Moreover, preclinical agents often need to cross the blood–brain barrier to achieve high intracranial concentrations, including small‐molecule inhibitors, nanoparticles, and peptide drugs. Addressing BM is imperative.