tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial
Authors: Xiongjing Jiang, Felix Mahfoud, Wei Li, Hui Dong, Jing Yu, Shuhua Yu, Xiaoping Chen, Peijian Wang, Zhiqiang Li, Lucas Lauder, Zhifang Wang, Zheng Ji, Yifei Dong, Bing Han, Zhiming Zhu, Yulin Chen, Jianzhong Xu, Xingsheng Zhao, Weidong Fan, Wen Xie, Brad Hubbard, Xi Hu, Kazuomi Kario, Runlin Gao
Journal: Circulation (2024)

BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is a sham-controlled trial investigating the safety and efficacy of RDN in China. METHODS: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; Shanghai Angiocare Medical Technology, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. RESULTS: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (−13.0±12.1 mm Hg) compared with the sham control group (−3.0±13.0 mm Hg; baseline-adjusted between-group difference, −9.4 mm Hg [95% CI, −12.8 to −5.9]; P &lt;0.001). Compared with sham, 24-hour diastolic BP was lowered by −5.0 mm Hg ([95% CI, −7.5 to −2.4]; P &lt;0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by −6.4 mm Hg ([95% CI, −10.5 to −2.3]; P =0.003) and −5.1 mm Hg ([95% CI, −8.2 to −2.0]; P =0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. CONCLUSIONS: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02901704.
ARID1A-Deficient Tumors Acquire Immunogenic Neoantigens during the Development of Resistance to Targeted Therapy
Authors: Masahiro Okada, Satoru Yamasaki, Hiroshi Nakazato, Yuhya Hirahara, Takuya Ishibashi, Masami Kawamura, Kanako Shimizu, Shin-ichiro Fujii
Journal: Cancer Research (2024)

Abstract Neoantigen-based immunotherapy is an attractive potential treatment for previously intractable tumors. To effectively broaden the application of this approach, stringent biomarkers are crucial to identify responsive patients. ARID1A, a frequently mutated subunit of SWI/SNF chromatin remodeling complex, has been reported to determine tumor immunogenicity in some cohorts; however, mutations and deletions of ARID1A are not always linked to clinical responses to immunotherapy. In this study, we investigated immunotherapeutic responses based on ARID1A status in targeted therapy-resistant cancers. Mouse and human BRAFV600E melanomas with or without ARID1A expression were transformed into resistant to vemurafenib, an FDA-approved specific BRAFV600E inhibitor. Anti-PD-1 antibody treatment enhanced antitumor immune responses in vemurafenib-resistant ARID1A-deficient tumors but not in ARID1A-intact tumors or vemurafenib-sensitive ARID1A-deficient tumors. Neoantigens derived from accumulated somatic mutations during vemurafenib resistance were highly expressed in ARID1A-deficient tumors and promoted tumor immunogenicity. Furthermore, the newly generated neoantigens could be utilized as immunotherapeutic targets by vaccines. Finally, targeted therapy resistance–specific neoantigen in experimental human melanoma cells lacking ARID1A were validated to elicit T-cell receptor responses. Collectively, the classification of ARID1A-mutated tumors based on vemurafenib resistance as an additional indicator of immunotherapy response will enable a more accurate prediction to guide cancer treatment. Furthermore, the neoantigens that emerge with therapy resistance can be promising therapeutic targets for refractory tumors. Significance: Chemotherapy resistance promotes the acquisition of immunogenic neoantigens in ARID1A-deficient tumors that confer sensitivity to immune checkpoint blockade and can be utilized for developing antitumor vaccines, providing strategies to improve immunotherapy efficacy.
Extracellular vesicles for delivering therapeutic agents in ischemia/reperfusion injury
Authors: Weihang Zhou, Xinchi Jiang, Jianqing Gao
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Ischemia/reperfusion (I/R) injury is marked by the restriction and subsequent restoration of blood supply to an organ. This process can exacerbate the initial tissue damage, leading to further disorders, disability, and even death. Extracellular vesicles (EVs) are crucial in cell communication by releasing cargo that regulates the physiological state of recipient cells. The development of EVs presents a novel avenue for delivering therapeutic agents in I/R therapy. The therapeutic potential of EVs derived from stem cells, endothelial cells, and plasma in I/R injury has been actively investigated. Therefore, this review aims to provide an overview of the pathological process of I/R injury and the biophysical properties of EVs. We noted that EVs serve as nontoxic, flexible, and multifunctional carriers for delivering therapeutic agents capable of intervening in I/R injury progression. The therapeutic efficacy of EVs can be enhanced through various engineering strategies. Improving the tropism of EVs
Reprogramming Tumor Microenvironment with Precise Photothermal Therapy by Calreticulin Nanobody-Engineered Probiotics
Authors: Liuhai Zheng, Huifang Wang, Xiaoru Zhong, Lin Jia, Guangwei Shi, Chongzhi Bai, Runwei Yang, Zhenhui Huang, Yuke Jiang, Jinxi Wei, Zhiyu Dong, Jiexuan Li, Ying Long, Lingyun Dai, Zhijie Li, Chunbo Chen, Jigang Wang
Journal: Biomaterials (2024)
3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair
Authors: Tao Zhang, Shihao Sheng, Weihuang Cai, Huijian Yang, Jiameng Li, Luyu Niu, Wanzhuo Chen, Xiuyuan Zhang, Qirong Zhou, Chuang Gao, Zuhao Li, Yuanwei Zhang, Guangchao Wang, Hao Shen, Hao Zhang, Yan Hu, Zhifeng Yin, Xiao Chen, Yuanyuan Liu, Jin Cui, Jiacan Su
Journal: Bioactive Materials (2024)
CSF and blood glial fibrillary acidic protein for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis
Authors: Yutong Zou, Yifei Wang, Xiaoli Ma, Danni Mu, Jian Zhong, Chaochao Ma, Chenhui Mao, Songlin Yu, Jing Gao, Ling Qiu
Journal: Ageing Research Reviews (2024)
Shear-thinning Hydrogel for Allograft Cell Transplantation and Externally Controlled Transgene Expression
Authors: Mariah G Bezold, Bryan R Dollinger, Carlisle R DeJulius, Megan C Keech, Andrew R Hanna, Anna R Kittel, Fang Yu, Mukesh K Gupta, Richard D'Arcy, Jonathan M Brunger, Craig L Duvall
Journal: Biomaterials (2024)
Regulatory considerations for developing remote measurement technologies for Alzheimer’s disease research
Authors: Gül Erdemli, Margarita Grammatikopoulou, Bertil Wagner, Srinivasan Vairavan, Jelena Curcic, Dag Aarsland, Gayle Wittenberg, Spiros Nikolopoulos, Marijn Muurling, Holger Froehlich, Casper de Boer, Niraj M Shanbhag, Vera J M Nies, Neva Coello, Dianne Gove, Ana Diaz, Suzanne Foy, Wim Dartee, Anna-Katharine Brem
Journal: npj Digital Medicine (2024)
Monascus pigment-protected bone marrow-derived stem cells for heart failure treatment
Authors: Tian Yue, Wentai Zhang, Haifeng Pei, Dunzhu Danzeng, Jian He, Jiali Yang, Yong Luo, Zhen Zhang, Shiqiang Xiong, Xiangbo Yang, Qisen Ji, Zhilu Yang, Jun Hou
Journal: Bioactive Materials (2024)
Non-invasive multimodal CT deep learning biomarker to predict pathological complete response of non-small cell lung cancer following neoadjuvant immunochemotherapy: a multicenter study
Authors: Guanchao Ye, Guangyao Wu, Yu Qi, Kuo Li, Mingliang Wang, Chunyang Zhang, Feng Li, Leonard Wee, Andre Dekker, Chu Han, Zaiyi Liu, Yongde Liao, Zhenwei Shi
Journal: Journal for ImmunoTherapy of Cancer (2024)

Objectives Although neoadjuvant immunochemotherapy has been widely applied in non-small cell lung cancer (NSCLC), predicting treatment response remains a challenge. We used pretreatment multimodal CT to explore deep learning-based immunochemotherapy response image biomarkers. Methods This study retrospectively obtained non-contrast enhanced and contrast enhancedbubu CT scans of patients with NSCLC who underwent surgery after receiving neoadjuvant immunochemotherapy at multiple centers between August 2019 and February 2023. Deep learning features were extracted from both non-contrast enhanced and contrast enhanced CT scans to construct the predictive models (LUNAI-uCT model and LUNAI-eCT model), respectively. After the feature fusion of these two types of features, a fused model (LUNAI-fCT model) was constructed. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. SHapley Additive exPlanations analysis was used to quantify the impact of CT imaging features on model prediction. To gain insights into how our model makes predictions, we employed Gradient-weighted Class Activation Mapping to generate saliency heatmaps. Results The training and validation datasets included 113 patients from Center A at the 8:2 ratio, and the test dataset included 112 patients (Center B n=73, Center C n=20, Center D n=19). In the test dataset, the LUNAI-uCT, LUNAI-eCT, and LUNAI-fCT models achieved AUCs of 0.762 (95% CI 0.654 to 0.791), 0.797 (95% CI 0.724 to 0.844), and 0.866 (95% CI 0.821 to 0.883), respectively. Conclusions By extracting deep learning features from contrast enhanced and non-contrast enhanced CT, we constructed the LUNAI-fCT model as an imaging biomarker, which can non-invasively predict pathological complete response in neoadjuvant immunochemotherapy for NSCLC.
Opportunities for Microphysiological Systems in Toxicity Testing of New Drug Modalities
Authors: Tengku Ibrahim Maulana, Nienke R. Wevers, Theodora Kristoforus, Morgan Chandler, Henriette L. Lanz, Jos Joore, Paul Vulto, Remi Villenave, Stefan Kustermann, Peter Loskill, Kristin M. Bircsak
Journal: The Annual Review of Pharmacology and Toxicology (2024)

New drug modalities offer life-saving benefits for patients through access to previously undruggable targets. Yet these modalities pose a challenge for the pharmaceutical industry, as side effects are complex, unpredictable, and often uniquely human. With animal studies having limited predictive value due to translatability challenges, the pharmaceutical industry seeks out new approach methodologies. Microphysiological systems (MPS) offer important features that enable complex toxicological processes to be modeled in vitro such as ( a ) an adjustable complexity of cellular components, including immune components; ( b ) a modifiable tissue architecture; ( c ) integration and monitoring of dynamic mechanisms; and ( d ) a multiorgan connection. Here we review MPS studies in the context of four clinical adverse events triggered by new drug modalities: peripheral neuropathy, thrombocytopenia, immune-mediated hepatotoxicity, and cytokine release syndrome. We conclude that while the use of MPS for testing new drug modality–induced toxicities is still in its infancy, we see strong potential going forward.
Targeting IL-33 reprograms the tumor microenvironment and potentiates antitumor response to anti-PD-L1 immunotherapy
Authors: Yanyang Nan, Yu Bai, Xiaozhi Hu, Kaicheng Zhou, Tao Wu, An Zhu, Mengyang Li, Zihan Dou, Zhonglian Cao, Xumeng Zhang, Shuwen Xu, Yuanzhen Zhang, Jun Lin, Xian Zeng, Jiajun Fan, Xuyao Zhang, Xuebin Wang, Dianwen Ju
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The main challenge against patients with cancer to derive benefits from immune checkpoint inhibitors targeting PD-1/PD-L1 appears to be the immunosuppressive tumor microenvironment (TME), in which IL-33/ST2 signal fulfills critical functions. However, whether IL-33 limits the therapeutic efficacy of anti-PD-L1 remains uncertain. Methods Molecular mechanisms of IL-33/ST2 signal on anti-PD-L1 treatment lewis lung carcinoma tumor model were assessed by RNA-seq, ELISA, WB and immunofluorescence (IF). A sST2-Fc fusion protein was constructed for targeting IL-33 and combined with anti-PD-L1 antibody for immunotherapy in colon and lung tumor models. On this basis, bifunctional fusion proteins were generated for PD-L1-targeted blocking of IL-33 in tumors. The underlying mechanisms of dual targeting of IL-33 and PD-L1 revealed by RNA-seq, scRNA-seq, FACS, IF and WB. Results After anti-PD-L1 administration, tumor-infiltrating ST2 + regulatory T cells (Tregs) were elevated. Blocking IL-33/ST2 signal with sST2-Fc fusion protein potentiated antitumor efficacy of PD-L1 antibody by enhancing T cell responses in tumor models. Bifunctional fusion protein anti-PD-L1-sST2 exhibited enhanced antitumor efficacy compared with combination therapy, not only inhibited tumor progression and extended the survival, but also provided long-term protective antitumor immunity. Mechanistically, the superior antitumor activity of targeting IL-33 and PD-L1 originated from reducing immunosuppressive factors, such as Tregs and exhausted CD8 + T cells while increasing tumor-infiltrating cytotoxic T lymphocyte cells. Conclusions In this study, we demonstrated that IL-33/ST2 was involved in the immunosuppression mechanism of PD-L1 antibody therapy, and blockade by sST2-Fc or anti-PD-L1-sST2 could remodel the inflammatory TME and induce potent antitumor effect, highlighting the potential therapeutic strategies for the tumor treatment by simultaneously targeting IL-33 and PD-L1.
Somatic Mosaicism in Brain Disorders
Authors: Rachel R. Corrigan, Lauren M. Mashburn-Warren, Hyojung Yoon, Tracy A. Bedrosian
Journal: Annual Review of Pathology Mechanisms of Disease (2024)

Research efforts over the past decade have defined the genetic landscape of somatic variation in the brain. Neurons accumulate somatic mutations from development through aging with potentially profound functional consequences. Recent studies have revealed the contribution of somatic mosaicism to various brain disorders including focal epilepsy, neuropsychiatric disease, and neurodegeneration. One notable finding is that the effect of somatic mosaicism on clinical outcomes can vary depending on contextual factors, such as the developmental origin of a variant or the number and type of cells affected. In this review, we highlight current knowledge regarding the role of somatic mosaicism in brain disorders and how biological context can mediate phenotypes. First, we identify the origins of brain somatic variation throughout the lifespan of an individual. Second, we explore recent discoveries that suggest somatic mosaicism contributes to various brain disorders. Finally, we discuss neuropathological associations of brain mosaicism in different biological contexts and potential clinical utility.
A Response to the Letter to the Editor: The Role of Personalization and Standardization in Stereotactic Body Radiation Therapy
Authors: Antonin Levy, Sonja Adebahr, Coen Hurkmans, Catherine Fortpied, Cécile Le Pechoux, Corinne Faivre-Finn, Ursula Nestle
Journal: Journal of Thoracic Oncology (2024)
Amphiphilic cytokine traps remodel marrow adipose tissue for hematopoietic microenvironment amelioration
Authors: Shunshu Deng, Shuang Zhang, Tong Shen, Xuanlin Wang, Zehua Gao, Wenchao Zhang, Kai Dai, Jing Wang, Changsheng Liu
Journal: Bioactive Materials (2024)
A Response to the Letter to the Editor: Comment on “Clinical Utility of Circulating Tumor DNA in Patients With Advanced KRAS(G12C)-Mutated NSCLC Treated With Sotorasib”
Authors: Sophie M Ernst, Jan H von der Thüsen, Hendrikus J Dubbink, Anne-Marie C Dingemans
Journal: Journal of Thoracic Oncology (2024)
Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial
Authors: Qinhua Fan, Chongming Wu, Yawei Du, Boyang Wang, Yanming Xie, Zeling Zhang, Wenquan Su, Zizhuo Wang, Changchang Xu, Xueke Li, Ying Ding, Xinjiang An, Jing Chen, Yunying Xiao, Rong Yu, Nan Li, Juan Wang, Yiqun Teng, Hongfen Lv, Nian Yang, Yuling Wen, Xiaoli Huang, Wei Pan, Yufeng Liu, Xueqin Xi, Qianye Zhao, Changshan Liu, Jian Xu, Haitao Zhang, Lie Zhuo, Qiangquan Rong, Yu Xia, Qin Shen, Shao Li, Junhong Wang, Shengxian Wu
Journal: Acta Pharmaceutica Sinica B (2024)

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.
A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus
Authors: Lai Wang, Haoyuan Yin, Jiao Jiang, Qilin Li, Changxing Gao, Wenrui Li, Bo Zhang, Yue Xin, Hongyang Li, Ming Zhao, Qianjin Lu
Journal: Acta Pharmaceutica Sinica B (2024)

Tripterygium wilfordii Hook F (TWHF) is a traditional Chinese medicine widely used in the treatment of systemic lupus erythematosus (SLE), with triptolide (TP) as its main active ingredient. However, its side effects also induced by TP, especially hepatotoxicity and reproductive toxicity, largely limit its application in a subset of patients. Monoclonal antibodies (mAbs) developed for the treatment of SLE that deplete B cells by targeting B cell-expressing antigens, such as CD19, have failed in clinical trials, partly due to their poor efficacy in consuming B cells. Here, we report the development of a rationally designed antibody‒drug conjugate (ADC), CD19 mAb-TP conjugate, to alleviate the side effects of TWHF and simultaneously improve the therapeutic efficacy of CD19 mAb. The CD19 mAb-TP conjugate, which was named ADC-TP, selectively depleted B cell subsets both in vitro and in vivo and effectively alleviated disease symptoms in mouse lupus models with enhanced therapeutic efficacy than CD19 mAb and fewer side effects than TP. Our present study proposes a CD19 mAb‒TP conjugate strategy to mitigate the toxicity of TWHF while also enhancing the therapeutical efficacy of CD19 mAbs for the treatment of SLE, providing a feasible method for improving the current agents used for treating SLE.
High throughput and rapid isolation of extracellular vesicles and exosomes with purity using size exclusion liquid chromatography
Authors: Kshipra S Kapoor, Kristen Harris, Kent A Arian, Lihua Ma, Beatriz Schueng Zancanela, Kaira A Church, Kathleen M McAndrews, Raghu Kalluri
Journal: Bioactive Materials (2024)
Pollution of Soil by Pharmaceuticals: Implications for Metazoan and Environmental Health
Authors: Chubin Zhang, Leon P. Barron, Stephen R. Stürzenbaum
Journal: The Annual Review of Pharmacology and Toxicology (2024)

The use of pharmaceuticals has grown substantially and their consequential release via wastewaters poses a potential threat to aquatic and terrestrial environments. While transportation prediction models for aquatic environments are well established, they cannot be universally extrapolated to terrestrial systems. Pharmaceuticals and their metabolites are, for example, readily detected in the excreta of terrestrial organisms (including humans). Furthermore, the trophic transfer of pharmaceuticals to and from food webs is often overlooked, which in turn highlights a public health concern and emphasizes the pressing need to elucidate how today's potpourri of pharmaceuticals affect the terrestrial system, their biophysical behaviors, and their interactions with soil metazoans. This review explores the existing knowledge base of pharmaceutical exposure sources, mobility, persistence, (bio)availability, (bio)accumulation, (bio)magnification, and trophic transfer of pharmaceuticals through the soil and terrestrial food chains.
Reused Protein Segments Linked to Functional Dynamics
Authors: Yiğit Kutlu, Gabriel Axel, Rachel Kolodny, Nir Ben-Tal, Turkan Haliloglu
Journal: Molecular Biology and Evolution (2024)

Protein space is characterized by extensive recurrence, or "reuse," of parts, suggesting that new proteins and domains can evolve by mixing-and-matching of existing segments. From an evolutionary perspective, for a given combination to persist, the protein segments should presumably not only match geometrically but also dynamically communicate with each other to allow concerted motions that are key to function. Evidence from protein space supports the premise that domains indeed combine in this manner; we explore whether a similar phenomenon can be observed at the sub-domain level. To this end, we use Gaussian Network Models (GNMs) to calculate the so-called soft modes, or low-frequency modes of motion for a dataset of 150 protein domains. Modes of motion can be used to decompose a domain into segments of consecutive amino acids that we call "dynamic elements", each of which belongs to one of two parts that move in opposite senses. We find that, in many cases, the dynamic elements, detected based on GNM analysis, correspond to established "themes": Sub-domain-level segments that have been shown to recur in protein space, and which were detected in previous research using sequence similarity alone (i.e. completely independently of the GNM analysis). This statistically significant correlation hints at the importance of dynamics in evolution. Overall, the results are consistent with an evolutionary scenario where proteins have emerged from themes that need to match each other both geometrically and dynamically, e.g. to facilitate allosteric regulation.
Mycosis Fungoides – an unwelcome guest in my life
Authors: Cristina Grechin, Li Jie Helena Yoo, Stephanie Lynn Ryan, Síona Ní Raghallaigh
Journal: British Journal of Dermatology (2024)

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma. Despite its relatively good prognosis, with high survival rates, the literature illustrates that MF may cause a significant deterioration in the patient’s quality of life due to uncertainty regarding disease progression. Our patient’s perspective highlights the significant impact of MF has had on his quality of life. We hope that this report serves as a reminder to dermatologists and other healthcare professionals that it is important to consider the psychological impact that can be associated with a diagnosis of MF. Living with and managing MF successfully, is a challenge for both, patient and physician.