tbuckley/cabot-search huggingface dataset:
Association of differential censoring with survival and suboptimal control arms among oncology clinical trials
Authors: Eric J Hsu, Timothy A Lin, Dor R Dabush, Zachary McCaw, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal Patel, Ramez Kouzy, Molly B El Alam, Sonal Noticewala, Yumeng Yang, Alexander D Sherry, Clifton D Fuller, Charles R Thomas, Chad Tang, Pavlos Msaouel, Prajnan Das, Bo Huang, Lu Tian, Ryan Sun, J Jack Lee, Tomer Meirson, Ethan B Ludmir
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Differential censoring, which refers to censoring imbalance between treatment arms, may bias the interpretation of survival outcomes in clinical trials. In 146 phase III oncology trials with statistically significant time-to-event surrogate primary endpoints, we evaluated the association between differential censoring in the surrogate primary endpoints, control arm adequacy, and the subsequent statistical significance of overall survival results. Twenty-four (16%) trials exhibited differential censoring that favored the control arm, whereas 15 (10%) exhibited differential censoring that favored the experimental arm. Positive overall survival was more common in control arm differential censoring trials (63%) than in trials without differential censoring (37%) or with experimental arm differential censoring (47%; odds ratio = 2.64, 95% confidence interval = 1.10 to 7.20; P = .04). Control arm differential censoring trials more frequently used suboptimal control arms at 46% compared with 20% without differential censoring and 13% with experimental arm differential censoring (odds ratio = 3.60, 95% confidence interval = 1.29 to 10.0; P = .007). The presence of control arm differential censoring in trials with surrogate primary endpoints, especially in those with overall survival conversion, may indicate an inadequate control arm and should be examined and explained.
A redox-responsive prodrug for tumor-targeted glutamine restriction
Authors: Céline Jasmin Prange, Nadia Yasmina Ben Sayed, Bing Feng, Christine Goepfert, Daniel Ortiz Trujillo, Xile Hu, Li Tang
Journal: Journal of Controlled Release (2024)

Modulating the metabolism of cancer cells, immune cells, or both is a promising strategy to potentiate cancer immunotherapy in the nutrient-competitive tumor microenvironment. Glutamine has emerged as an ideal target as cancer cells highly rely on glutamine for replenishing the tricarboxylic acid cycle in the process of aerobic glycolysis. However, non-specific glutamine restriction may induce adverse effects in unconcerned tissues and therefore glutamine inhibitors have achieved limited success in the clinic so far. Here we report the synthesis and evaluation of a redox-responsive prodrug of 6-Diazo-5-oxo-L-norleucine (redox-DON) for tumor-targeted glutamine inhibition. When applied to treat mice bearing subcutaneous CT26 mouse colon carcinoma, redox-DON exhibited equivalent antitumor efficacy but a greatly improved safety profile, particularly, in spleen and gastrointestinal tract, as compared to the state-of-the-art DON prodrug, JHU083. Furthermore, redox-DON synergized with checkpoint blockade antibodies leading to durable cures in tumor-bearing mice. Our results suggest that redox-DON is a safe and effective therapeutic for tumor-targeted glutamine inhibition showing promise for enhanced metabolic modulatory immunotherapy. The approach of reversible chemical modification may be generalized to other metabolic modulatory drugs that suffer from overt toxicity.
Antimicrobial Peptide‐ and Dentin Matrix‐Functionalized Hydrogel for Vital Pulp Therapy via Synergistic Bacteriostasis, Immunomodulation, and Dentinogenesis
Authors: Zhuo Xie, Wentao Jiang, Hui Liu, Lingling Chen, Chengkai Xuan, Zhenxing Wang, Xuetao Shi, Zhengmei Lin, Xianling Gao
Journal: Advanced Healthcare Materials (2024)

Abstract The preservation of vital pulps is crucial for maintaining the physiological functions of teeth; however, vital pulp therapy (VPT) of pulpitis teeth remains a substantial challenge due to uncontrolled infection, excessive inflammation, and limited regenerative potential. Current pulp capping agents have restricted effects in the infectious and inflammatory microenvironment. To address this, a multifunctional hydrogel (TGH/DM) with antibacterial, immunomodulatory, and mineralization‐promoting effects is designed. The antimicrobial peptide (AMP) and demineralized dentin matrix are incorporated into the hydrogel, achieving sustainable delivery of AMP and a cocktail of growth factors. In vitro results show that TGH/DM could kill endodontic microbiota, ameliorate inflammatory responses of human dental pulp stem cells (hDPSCs), and prompt odontogenic differentiation of inflammatory hDPSCs via activation of peroxisome proliferator‐activated receptor gamma. In vivo results suggest that TGH/DM is capable of inducing M2 phenotype transformation of macrophages in mice and fostering the regeneration of the dentin‐pulp complex in inflamed pulps of beagle dogs. Overall, this study first proposes the synergistic regulation of AMP and tissue‐specific extracellular matrix for the treatment of pulpitis, and the advanced hydrogel provides a facile and effective way for VPT.
Tougher Bioadhesives through Dual Stimulation Strategies
Authors: Elwin W. J. Ang, Ivan Djordjevic, Ivan Solic, Chen Yee Goh, Terry W. J. Steele
Journal: Advanced Healthcare Materials (2024)

Abstract Carbene‐based bioadhesives have favourable attributes for tissue adhesion, including non‐specific bonding to wet and dry tissues, but suffer from relatively weak fracture strength after photocuring. Light irradiation of carbene‐precursor (diazirine) also creates inert side products that are absent under thermal activation. Herein, a dual activation method combines light irradiation at elevated temperatures for the evaluation of diazirine depletion and effects on cohesive properties. A customized photo/thermal‐rheometer evaluates viscoelastic properties, correlated to the kinetics of carbene:diazoalkane ratios via 19 F NMR). The latter exploits the sensitive ‐CF 3 functional group to determine joule‐based light/temperature kinetics on trifluoroaryl diazirine consumption. The combination of heat and photoactivation produced bioadhesives that are 3× tougher compared to control. Dual thermal/light irradiation may be a strategy to improve viscoelastic dissipation and toughness of photo‐activated adhesive resins.
Skin biomarkers predict the development of food allergy in early life
Authors: Evgeny Berdyshev, Jihyun Kim, Byung Eui Kim, Elena Goleva, Taras Lyubchenko, Irina Bronova, Anna Sofia Bronoff, Olivia Xiao, Sehun Jang, Sanghee Shin, Jeongmin Song, Jiwon Kim, Sukyung Kim, Boram Park, Kyunga Kim, Suk-Joo Choi, Soo-Young Oh, Kangmo Ahn, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2024)
Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed –1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element
Authors: Hongying Li, Jianrui Li, Jiayu Li, Hu Li, Xuekai Wang, Jing Jiang, Lei Lei, Han Sun, Mei Tang, Biao Dong, Weiqing He, Shuyi Si, Bin Hong, Yinghong Li, Danqing Song, Zonggen Peng, Yongsheng Che, Jian-Dong Jiang
Journal: Acta Pharmaceutica Sinica B (2024)

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed –1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.
Glycnsisitin A: A promising bicyclic peptide against heart failure that facilitates TFRC-mediated uptake of iron in cardiomyocytes
Authors: Jichao Zhou, Yuanyuan Liu, Xiaoli Wei, Meng Yuan, Xu Zhang, Lingfeng Qin, Bing Cui, Pingping Li, Jing Zhang, Ziming Feng, Jianshuang Jiang, Xiang Yuan, Ruibing Xu, Zhimeng Zhang, Peicheng Zhang, Xiaowei Zhang, Yanan Yang
Journal: Acta Pharmaceutica Sinica B (2024)

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A–C (1–3), with distinctive C–C and C–O–C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.
Effects of clitorienolactones from Clitoria ternatea root on calcium channel mediating hippocampal long-term potentiation in rats induced chronic cerebral hypoperfusion
Authors: Mohamad Anuar Ahad, Nelson Jeng-Yeou Chear, Muhammad Hazim Abdullah, Tan Ai Fein Ching-Ga, Ping Liao, Shunhui Wei, Vikneswaran Murugaiyah, Zurina Hassan
Journal: Ageing Research Reviews (2024)
Time and Space Dual‐Blockade Strategy for Highly Invasive Nature of Triple‐Negative Breast Cancer in Enhanced Sonodynamic Therapy Based on Fe‐MOF Nanoplatforms
Authors: Cheng Cao, Yi Lu, Xinni Pan, Yuwan Lin, Shanshan Fan, Jiaqi Niu, Shujing Lin, Haisong Tan, You Wang, Shengsheng Cui, Yanlei Liu
Journal: Advanced Healthcare Materials (2024)

Triple-negative breast cancer (TNBC), due to its high malignant degree and strong invasion ability, leads to poor prognosis and easy recurrence, so effectively curbing the invasion of TNBC is the key to obtaining the ideal therapeutic effect. Herein, a therapeutic strategy is developed that curbs high invasions of TNBC by inhibiting cell physiological activity and disrupting tumor cell structural function to achieve the time and space dual-blockade. The time blockade is caused by the breakthrough of the tumor-reducing blockade based on the ferroptosis process and the oxidation-toxic free radicals generated by enhanced sonodynamic therapy (SDT). Meanwhile, alkyl radicals from 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) and
Dual‐ROS Sensitive Moieties Conjugate Inhibits Curcumin Oxidative Degradation for Colitis Precise Therapy
Authors: Dunsheng Liang, Xiaofan Shen, Lu Han, Hao Ren, Tao Zang, Lulu Tan, Zhaoxiang Lu, Xiaoping Liao, Berwin Singh Swami Vetha, Yahong Liu, Chaoqun Zhang, Jian Sun
Journal: Advanced Healthcare Materials (2024)

Abstract Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti‐oxidation and anti‐inflammatory potential. However, curcumin exhibits low solubility (&lt;1 µg mL −1 ), poor tissue‐targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide‐oxalate‐curcumin) nanoparticle (SeOC‐NP) with dual‐reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one‐step synthetic strategy. The results confirmed that dual‐ROS sensitive chemical moieties endowed SeOC‐NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high‐efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4‐fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC‐NP significantly enhanced the antioxidant activity and anti‐inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro‐inflammatory cytokines. In mouse colitis models, orally administered SeOC‐NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS‐responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.
Ichthyosis: multinational European study on patient characteristics, involved body sites and impact on quality of life
Authors: May El Hachem, Rita De Marco, José María Soria de Francisco, Anne Audouze, Mandy Aldwin-Easton, Charbel Skayem, Charles Taieb, Markéta Saint Aroman, Hélène Ghienne, Catherine Baissac, Juliette Mazereeuw, Christine Bodemer
Journal: British Journal of Dermatology (2024)

We present the first large multinational study of ichthyosis to better understand the disease characteristics, the body sites involved and the effect of the disease on the quality of life of patients.
Glucose Metabolism of Hippocampal Subfields in Medial Temporal Lobe Epilepsy
Authors: Tse-Hao Lee, Yen-Cheng Shih, Yi-Jiun Lu, Chien-Chen Chou, Cheng-Chia Lee, Hsiang-Yu Yu, Syu-Jyun Peng
Journal: Clinical Nuclear Medicine (2024)

Purpose Reduced glucose metabolism in the hippocampus is commonly observed in cases of medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). Glucose metabolism among the various hippocampal subfields has not been thoroughly investigated. Patients and Methods This study examined 29 patients (18 females; 15–58 years) diagnosed with HS who underwent surgery for drug-resistant epilepsy. FreeSurfer 7.1.1 was used in the processing of MRI data and 18 F-FDG PET scans to derive volumetric data and the FDG SUVr in the whole hippocampus and hippocampal subfields, including the CA1, CA2-4, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), and subiculum. Asymmetries in the volume and SUVr between the 2 sides from the subfields of the hippocampus were defined in terms of an asymmetry index. Comparisons of the asymmetry index among these regions were performed. The correlations between asymmetry index values and postoperative outcomes and presurgical neuropsychological test results were also evaluated. Result The CA1, CA2-4, subiculum, GC-ML-DG, and whole hippocampus presented reductions in volume and hypometabolism ipsilateral to MTLE. Asymmetries in volume and SUVr were significantly less pronounced in the CA1 and subiculum than in the CA2-4 or GC-ML-DG. Postoperative seizure outcomes were not correlated with the asymmetry index for volume or SUVr in any hippocampal subfield. In cases of left MTLE, scores of immediate logical memory and delayed logical memory were positively correlated with the asymmetry index for SUVr in the following subfields: CA1 ( R = 0.829, P = 0.021; R = 0.770, P = 0.043), CA2-4 ( R = 0.825, P = 0.022; R = 0.894, P = 0.007), subiculum ( R = 0.882, P = 0.009; R = 0.853, P = 0.015), GC-ML-DG ( R = 0.850, P = 0.015; R = 0.796, P = 0.032), and whole hippocampus ( R = 0.841, P = 0.018; R = 0.822, P = 0.023). In cases of right MTLE, the scores for delayed face memory were positively correlated with the asymmetry index for SUVr in the subiculum ( R = 0.935, P = 0.006). Conclusions In cases of HS, changes in glucose metabolism levels varied among the hippocampal subfields. Asymmetries in glucose metabolism among the CA-1, CA2-4, subiculum, and GC-ML-DG subregions were correlated with scores for verbal memory among patients with left MTLE. Asymmetric glucose metabolism in the subiculum was also correlated with visual memory scores among patients with right MTLE.
Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis
Authors: Evangelia Beslika, Adelino Leite-Moreira, Leon J De Windt, Paula A da Costa Martins
Journal: Cardiovascular Research (2024)

Abstract Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis (AS). AS is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. At a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, known as cardiomyocyte hypertrophy, while their proliferation capacity is attenuated upon the first developmental stages. Cardiomyocytes, in order to cope with the increased workload (overload), suffer alterations in their morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity, and cell death mechanisms. Moreover, modifications in the cardiomyocyte niche, involving inflammation, immune infiltration, fibrosis, and angiogenesis, contribute to the subsequent events of a pathologic hypertrophic response. Considering the emerging need for a better understanding of the condition and treatment improvement, as the only available treatment option of AS consists of surgical interventions at a late stage of the disease, when the cardiac muscle state is irreversible, large animal models have been developed to mimic the human condition, to the greatest extend. Smaller animal models lack physiological, cellular and molecular mechanisms that sufficiently resemblance humans and in vitro techniques yet fail to provide adequate complexity. Animals, such as the ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries), and porcine (pig, Sus scrofa), have contributed to research by elucidating implicated cellular and molecular mechanisms of the condition. Essential discoveries of each model are reported and discussed briefly in this review. Results of large animal experimentation could further be interpreted aiming at prevention of the disease progress or, alternatively, at regression of the implicated pathologic mechanisms to a physiologic state. This review summarizes the important aspects of the pathophysiology of LV hypertrophy and the applied surgical large animal models that currently better mimic the condition.
Pulmonary Damage Biomarkers for Risk of Rheumatoid Arthritis–Associated Interstitial Lung Disease: Enabling Early Detection and Risk Stratification
Authors: Pierre‐Antoine Juge, Paul F. Dellaripa, Jeffrey A. Sparks
Journal: Arthritis & Rheumatology (2024)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Assessing racial, ethnic, and nativity disparities in US cancer mortality using a new integrated platform
Authors: Mandi Yu, Lihua Liu, James (Todd) Gibson, Dave Campbell, Qinran Liu, Steve Scoppa, Eric J Feuer, Paulo S Pinheiro
Journal: JNCI Journal of the National Cancer Institute (2024)

Foreign-born populations in the United States have markedly increased, yet cancer trends remain unexplored. Survey-based Population-Adjusted Rate Calculator (SPARC) is a new tool for evaluating nativity differences in cancer mortality.
Review of global epidemiology data for alopecia areata highlights gaps and a call for action
Authors: Cathryn Sibbald, Leslie Castelo-Soccio
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Review of global epidemiology data for alopecia areata highlights gaps and a call for action Get access Cathryn Sibbald, Cathryn Sibbald Writing - original draft, Writing - review & editing Division of Dermatology, Department of Paediatrics, SickKids Hospital, Toronto, ON, CanadaDivision of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada Correspondence: Cathryn Sibbald. Email: cathryn.sibbald@sickkids.ca https://orcid.org/0000-0001-9288-1121 Search for other works by this author on: Oxford Academic Google Scholar Leslie Castelo-Soccio Leslie Castelo-Soccio Writing - review & editing National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA https://orcid.org/0000-0003-3289-446X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae088, https://doi.org/10.1093/bjd/ljae088 Published: 01 March 2024 Article history Received: 21 February 2024 Accepted: 23 February 2024 Published: 01 March 2024 Corrected and typeset: 15 March 2024
Cancer Radiosensitization Nanoagent to Activate cGAS‐STING Pathway for Molecular Imaging Guided Synergistic Radio/Chemo/Immunotherapy
Authors: Zede Wu, Qiuyu Li, Kai Zhu, Shuting Zheng, Honglei Hu, Meirong Hou, Li Qi, Siwen Chen, Yikai Xu, Bingxia Zhao, Chenggong Yan
Journal: Advanced Healthcare Materials (2024)

Abstract Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation‐induced DNA damage can activate the cyclic‐GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS‐STING pathway. Herein, this work integrates hafnium oxide (HfO 2 ) nanoparticles (radiosensitizer) and 7‐Ethyl‐10‐hydroxycamptothecin (SN38, chemotherapy drug, STING agonist) into a polydopamine (PDA)‐coated core‐shell nanoplatform (HfO 2 @PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy. The co‐delivery of HfO 2 /SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS‐STING pathway, which then triggers dendritic cells maturation and CD8 + T cells recruitment. Consequently, the growth of both primary and abscopal tumors in tumor‐bearing mice is efficiently inhibited. Moreover, the HfO 2 @PDA/Fe/SN38 complexes exhibit favorable magnetic resonance imaging (MRI)/photoacoustic (PA) bimodal molecular imaging properties. In summary, these developed multifunctional complexes have the potential to intensify immune activation to realize simultaneous cancer Radio/Chemo/Immunotherapy for clinical translation.