tbuckley/cabot-search huggingface dataset:
Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials
Authors: Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S. Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B. Kunnumakkara
Journal: Military Medical Research (2024)

Abstract The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
End‐organ protective effect of serelaxin in patients hospitalized for heart failure: Results of the biomarker substudy of Relaxin in Acute Heart Failure‐2 (<scp>RELAX</scp>‐<scp>AHF</scp>‐2)
Authors: Adriaan A. Voors, Marco Metra, Douwe Postmus, Barry H. Greenberg, Gadi Cotter, Beth A. Davison, Iris E. Beldhuis, G. Michael Felker, Gerasimos Filippatos, Peter S. Pang, Piotr Ponikowski, Claudio Gimpelewicz, John R. Teerlink
Journal: European Journal of Heart Failure (2024)

Abstract Aims Serelaxin is recombinant human relaxin‐2, a hormone responsible for haemodynamic adaptations and organ protection in pregnancy. In the RELAX‐AHF trial, serelaxin demonstrated reductions in cardiac, renal and hepatic damage. In RELAX‐AHF‐2, organ damage‐related biomarkers were assessed in a biomarker substudy. Methods and results Patients enrolled within 16 h of presentation for heart failure hospitalization were randomized to 48‐h infusions of either serelaxin (30 μg/kg/day) or placebo, and plasma samples were obtained at baseline, 2, 5, and 14 days in patients participating in the biomarker substudy. Of the 6545 patients analysed in RELAX‐AHF‐2, 1020 (15.6%) patients (mean age 72 ± 12 years; 61% male) were enrolled in the biomarker substudy. Compared to placebo, serelaxin decreased percentage change from baseline in troponin T through day 14 (serelaxin +0.2% vs. placebo +40.3%; p = 0.042), as well as creatinine (−0.8% vs. +5.8%; p = 0.002), cystatin C (+3.8% vs. +8.3%; p = 0.016), and uric acid (+0.8% vs. +7.2%; p = 0.0014) at day 2. The decrease of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) from baseline to day 2 was greater in serelaxin‐treated patients (−39.8% vs. −27.6%; p = 0.002). Early changes in NT‐proBNP and troponin, but not creatinine, cystatin C and uric acid, were associated with 180‐day mortality. In this substudy population, serelaxin did not reduce 180‐day cardiovascular death (hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.49–1.25; p = 0.30), but significantly reduced worsening heart failure through day 5 (HR 0.55; 95% CI 0.33–0.93; p = 0.027). Conclusion In this substudy, serelaxin decreased plasma concentrations of cardiac, renal and hepatic injury markers. Changes of most of these markers were associated with cardiovascular mortality. In this pre‐specified biomarker subgroup, serelaxin did not reduce 180‐day cardiovascular mortality but significantly reduced worsening heart failure through day 5.
Dampened TLR2-mediated inflammatory signaling in bats
Authors: Jiaming Zeng, Xiangyi Zhang, Chen Huang, Shilin Tian, Huabin Zhao
Journal: Molecular Biology and Evolution (2024)

Abstract Bats are considered natural hosts for numerous viruses. Their ability to carry viruses that cause severe diseases or even death in other mammals without falling ill themselves has attracted widespread research attention. Toll-like receptor 2 forms heterodimers with Toll-like receptor 1 or Toll-like receptor 6 on cell membranes, recognizing specific pathogen-associated molecular patterns and playing a key role in innate immune responses. Previous studies have shown that moderate Toll-like receptor 2–mediated immune signals aid in pathogen clearance, while excessive or inappropriate Toll-like receptor 2–mediated immune signals can cause self-damage. In this study, we observed that TLR2, unlike TLR1 or TLR6, has undergone relaxed selection in bats compared with other mammals, indicating a reduced functional constraint on TLR2 specifically in bats. Indeed, our cell-based functional assays demonstrated that the ability of Toll-like receptor 2 to bind with Toll-like receptor 1 or Toll-like receptor 6 was significantly reduced in bats, leading to dampened inflammatory signaling. We identified mutations unique to bats that were responsible for this observation. Additionally, we found that mutations at residues 375 and 376 of Toll-like receptor 2 in the common ancestor of bats also resulted in reduced inflammatory response, suggesting that this reduction occurred early in bat evolution. Together, our study reveals that the Toll-like receptor 2–mediated inflammatory response has been specifically dampened in bats, which may be one of the reasons why they could harbor many viruses without falling ill.
Inhibition of Selenoprotein I promotes ferroptosis and reverses resistance to platinum chemotherapy by impairing Akt phosphorylation in ovarian cancer
Authors: Jing Li, Mimi Chen, Dingwen Huang, Ziyin Li, Yu Chen, Jinhua Huang, Yuanqun Chen, Zhili Zhou, Zhiying Yu
Journal: MedComm (2024)

Abstract Ovarian cancer (OV) ranks among the deadliest gynecological cancer, known for its high risk of relapse and metastasis, and a general resistance to conventional platinum‐based chemotherapy. Selenoprotein I (SELENOI) is a crucial mediator implicated in human hereditary spastic paraplegia. However, its role in human tumors remains poorly elucidated. Here, we comprehensively analyzed SELENOI expression patterns, functions, and clinical implications across various malignancies through the integration of bulk transcriptomics, cancer databases, and in vitro and in vivo experiments. Pan‐cancer analysis indicated upregulated SELENOI expression across various cancers, correlating with augmented malignancy, suppressed tumor immunity and poor prognosis. Knockdown of SELENOI caused G0/G1‐phase cell cycle arrest and diminished aggressive cancer phenotypes in OV cells. Moreover, SELENOI inhibition augments ferroptosis and reverses the cisplatin resistance in OV cells by modulating Akt phosphorylation. Conversely, overexpression of SELENOI in OV cells enhanced therapeutic sensitivity to cisplatin by upregulating Akt phosphorylation. Importantly, in vivo studies demonstrated that SELENOI inhibition suppressed ovarian tumor growth and enhanced cisplatin's anticancer effects. These findings highlight the significant role of SELENOI in OV by modulating ferroptosis and chemotherapy resistance. Targeting SELENOI represents a promising therapeutic approach to promote the efficacy of platinum‐based chemotherapy in OV, particularly in cases of resistance.
Synergistic Target‐Attacking Tumor Cells and M2 Macrophages via a Triple‐Responsive Nanoassembly for Complete Metastasis Blocking
Authors: Bei Wang, Hao Cheng, Zhongsheng Ji, Zijun Jiang, Rong Wang, Yang Ding, Jiang Ni
Journal: Advanced Healthcare Materials (2024)

Collaboration of cancerous cells and microenvironment is the root for tumor spreading, leading to difficulty in complete metastasis blockage via mono-intervention. Herein, a triple-responsive nanoassembly is designed for orienting tumor cells and migration-driving M2 tumor associated macrophages (TAMs) in microenvironment for efficient anti-metastatic therapy. Structurally, a reactive oxygen species (ROS)-responsive crosslinked short-chain polyquaternium is synthesized to bridge graphene oxide (GO) scaffold with apolipoprotein A-I crown via borate-crosslinking, electrostatic adherence, and coordinative coupling. The protein-crowning polymeric GO nanoparticles could give multimodal shielding and triple-responsive release of doxorubicin and Snail-targeted siRNA. Tailor-made apolipoprotein A-I crown fulfills nanoparticles synergistically attacking tumor cells and M2 TAMs via binding with overexpressed scavenger receptors. The findings witness the targeted accumulation and potent cytotoxicity of the hybrid nanoparticles for M2 TAMs and tumor cells; especially, elimination of M2 TAMs in tumor microenvironment holds back Snail-enhancing transforming growth factor (TGF)-β signal pathway, which collaborates with Snail silencing in tumor cells to reverse epithelial mesenchymal transition (EMT) and metastasis-promoting niche. Collectively, the synergistic targeting therapeutic platform could provide a promising solution for metastatic tumor treatment.
Multimodal data fusion AI model uncovers tumor microenvironment immunotyping heterogeneity and enhanced risk stratification of breast cancer
Authors: Yunfang Yu, Gengyi Cai, Ruichong Lin, Zehua Wang, Yongjian Chen, Yujie Tan, Zifan He, Zhuo Sun, Wenhao Ouyang, Herui Yao, Kang Zhang
Journal: MedComm (2024)

Abstract Breast cancer is the leading cancer among women, with a significant number experiencing recurrence and metastasis, thereby reducing survival rates. This study focuses on the role of long noncoding RNAs (lncRNAs) in breast cancer immunotherapy response. We conducted an analysis involving 1027 patients from Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University, and The Cancer Genome Atlas, utilizing RNA sequencing and pathology whole‐slide images. We employed unsupervised clustering to identify distinct lncRNA expression patterns and developed an AI‐based pathology model using convolutional neural networks to predict immune–metabolic subtypes. Additionally, we created a multimodal model integrating lncRNA data, immune‐cell scores, clinical information, and pathology images for prognostic prediction. Our findings revealed four unique immune–metabolic subtypes, and the AI model demonstrated high predictive accuracy, highlighting the significant impact of lncRNAs on antitumor immunity and metabolic states within the tumor microenvironment. The AI‐based pathology model, DeepClinMed‐IM, exhibited high accuracy in predicting these subtypes. Additionally, the multimodal model, DeepClinMed‐PGM, integrating pathology images, lncRNA data, immune‐cell scores, and clinical information, showed superior prognostic performance. In conclusion, these AI models provide a robust foundation for precise prognostication and the identification of potential candidates for immunotherapy, advancing breast cancer research and treatment strategies.
Multiscale Thermal Analysis of Gold Nanostars in 3D Tumor Spheroids: Integrating Cellular‐Level Photothermal Effects and Nanothermometry via X‐Ray Spectroscopy
Authors: Rosalía López‐Méndez, Anastasiia Dubrova, Javier Reguera, Rául Magro, Fátima Esteban‐Betegón, Ana Parente, Miguel Ángel García, Julio Camarero, Emiliano Fonda, Claire Wilhelm, Álvaro Muñoz‐Noval, Ana Espinosa
Journal: Advanced Healthcare Materials (2024)

Abstract In the pursuit of enhancing cancer treatment efficacy while minimizing side effects, near‐infrared (NIR) photothermal therapy (PTT) has emerged as a promising approach. By using photothermally active nanomaterials, PTT enables localized hyperthermia, effectively eliminating cancer cells with minimal invasiveness and toxicity. Among these nanomaterials, gold nanostars (AuNS) stand out due to their tunable plasmon resonance and efficient light absorption. This study addresses the challenge of measuring nanoscale temperatures during AuNS‐mediated PTT by employing X‐ray absorption spectroscopy (XAS) within 3D tumor spheroids. It also aims to investigate the heat generated at the nanoscale and the resultant biological damage observed at a larger scale, utilizing confocal microscopy to establish connections between AuNS heat generation, tissue damage, and their impacts on cellular structure. These nanoscale and microscale thermal effects have been compared with macroscopic values obtained from infrared thermography, as part of a multiscale thermal analysis. The findings underscore the efficacy of AuNS in enhancing PTT and provide insights into the spatial distribution of thermal effects within tumor tissues. This research advances the understanding of localized hyperthermia in cancer therapy and underscores the potential of AuNS‐based PTT for clinical applications.
Nanofiber‐based Multifunctional Microspheres for Rapid Hemostasis and Microorganism Removal of Water
Authors: Qing Li, Lingjun Ye, Yanqiu Leng, Kun Yu, Enling Hu, Fei Lu, Ruiqi Xie, Sha Jiang, Hang Gao, Rong Bao, Fangyin Dai, Guangqian Lan
Journal: Advanced Healthcare Materials (2024)

Abstract Constructing hemostats capable of effectively controlling severe hemorrhage from irregular wounds presents significant challenges and imperatives. In this study, a novel approach is introduced using nanofibrous chitin microspheres (NCM) that are compressed to 60% strain (NCM‐60%) to amplify their water‐initiated expansion performance. This unique capacity allows NCM‐60% to efficiently conform to and fill irregular bleeding cavities, even those of varying depths and curvatures, thereby promoting rapid blood coagulation at deep hemorrhage sites. NCM‐60% exhibits effective control of severe femoral artery and “J”‐shaped liver hemorrhages in 151 ± 6 s and 68 ± 15 s, respectively, revealing its exceptional hemostatic efficacy. Furthermore, NCM‐60% exhibited promising capabilities in removing microbes from water, achieving removal rates of over 96% of bacteria. Blood compatibility assessments and cytotoxicity tests further confirmed the favorable biocompatibility of NCM‐60%. Importantly, NCM‐60% is found to biodegrade and be absorbed in vivo within 12 weeks. This study represents the first instance of leveraging chitin nanofiber‐based biomaterials to design water‐initiated expansion micro‐hemostat, and integrate hemostatic functions with waterborne microorganism removal, thereby expanding the potential applications of micro‐nanostructural materials in emergency first‐aid scenarios.
Specific gFET‐Based Aptasensors for Monitoring of Microbiome Quality: Quantification of the Enteric Health‐Relevant Bacterium <i>Roseburia Intestinalis</i>
Authors: Yiting Zhang, Hu Xing, Runliu Li, Jakob Andersson, Anil Bozdogan, Robert Strassl, Bastian Draphoen, Mika Lindén, Marius Henkel, Uwe Knippschild, Roger Hasler, Christoph Kleber, Wolfgang Knoll, Ann‐Kathrin Kissmann, Frank Rosenau
Journal: Advanced Healthcare Materials (2024)

Roseburia intestinalis, enriched in the gut, is closely associated with obesity, intestinal inflammation, and other diseases. A novel detection method for R. intestinalis to replace the commonly used 16S rRNA sequencing technique is aim to developed, thus enabling real-time and low-cost monitoring of gut microbiota. The optimal solution is to utilize rGO-FET (reduced graphene oxide field-effect transistor) functionalized with aptamers. Due to the high sensitivity of graphene sensors to electronic changes in the system, it is anticipated to achieve detection sensitivity that traditional fluorescence detection techniques cannot attain. The previous work reported a nucleic acid aptamer library, Ri 7_2, capable of quantitatively tracking R. intestinalis in complex systems. However, due to the complexity of the aptamer library itself, large-scale industrial synthesis is challenging, significantly limiting its further commercial application potential. Therefore, in this study, through Next-Generation Sequencing analysis, four representative single aptamers from the aptamer library is strategically selected, named A-Rose 1, A-Rose 2, A-Rose 3, and A-Rose 4, and confirmed their excellent performance similar to the aptamer library Ri 7_2. Furthermore, aptamer-modified rGO-FET demonstrated universality in detecting R. intestinalis in a series of biochemical analyses, providing a novel and powerful diagnostic tool for the clinical diagnosis of R. intestinalis.
Re: ‘Potent in-vitro activity of sulbactam-durlobactam against NDM-producing Escherichia coli including cefiderocol and aztreonam-avibactam-resistant isolates’ by Poirel et al.
Authors: Balaji Veeraraghavan, Kamini Walia, Adrian Egli
Journal: Clinical Microbiology and Infection (2024)
Corrigendum to “PB@PDA@Ag nanosystem for synergistically eradicating MRSA and accelerating diabetic wound healing assisted with laser irradiation” [Biomaterials 243 (2020) 119936]
Authors: Chunyi Tong, Xianghua Zhong, Yuejun Yang, Xu Liu, Guowei Zhong, Chang Xiao, Bin Liu, Wei Wang, Xiaoping Yang
Journal: Biomaterials (2024)
The Risk of Developing Second Primary Malignancies in Cutaneous Melanoma Survivors
Authors: Thomas Z Rohan, Jenna Mandel, Lauren Banner, Rachel Zachian, Henry Yang, Emily Lee, Megan O'Donnell-Cappelli, Safiyyah Bhatti, TingTing Zhan, Jason B Lee, Neda Nikbakht
Journal: Journal of the American Academy of Dermatology (2024)
A Multisynergistic Strategy for Bone Tumor Treatment: Orchestrating Oxidative Stress and Autophagic Flux Inhibition by Environmental‐Response Nanoparticle
Authors: Xiaochen Chen, Pengfei Tian, Wenwen Chai, Liyan Zhang, Muyan Qin, Mengke Fan, Na Liang, Jua Kim, Yansong Wang, Weijia William Lu, Deping Wang, Xu Cui, Haobo Pan
Journal: Advanced Healthcare Materials (2024)

Abstract Tumor therapy has advanced significantly in recent years, but tumor cells can still evade and survive the treatment through various mechanisms. Notably, tumor cells use autophagy to sustain viability by removing impaired mitochondria and clearing excess reactive oxygen species (ROS). In this study, the aim is to amplify intracellular oxidative stress by inhibiting mitochondrial autophagic flux. Multisynergistic environmental‐response nanoparticles (ERNs) are engineered by integrating gold nanoparticles and copper peroxide with borosilicate bioactive glass. The controlled release of copper and inhibition of autophagy flux triggered an overabundance and accumulation of oxidative stress within the tumor cells. This stress triggered immunogenic tumor cell death, believed to initiate a systemic immune response. The tumor microenvironment (TME) transitioned back to a normal physiological state as tumor cells are ablated. ERNs responded to the microenvironment changes by depositing hydroxyapatite on the surface and spontaneously enhancing bone regeneration. This innovative formulation facilitates the functional transition of ERNs from “anti‐tumor therapy” to “biomineralization” that kills cancers and induces new bone formation. Overall, it is shown that the ERNs effectively eradicate cancers by utilizing chemodynamic therapy, starvation therapy, and immunotherapy.
Management of acute decompensated valvular heart disease
Authors: Enzo Lüsebrink, Hugo Lanz, Antonia Kellnar, Nicole Karam, Samir Kapadia, Raj Makkar, William T. Abraham, Azeem Latib, Martin Leon, Anna Sannino, Mony Shuvy, Mayra Guerrero, Neil Fam, Javed Butler, Marianna Adamo, Volker Rudolph, Gilbert H.L. Tang, Thomas J. Stocker, Karl‐Philipp Rommel, Philipp Lurz, Holger Thiele, Steffen Massberg, Fabien Praz, Bernard Prendergast, Jörg Hausleiter
Journal: European Journal of Heart Failure (2024)
In‐Ear Electronics with Mechanical Adaptability for Physiological Sensing
Authors: Shuyun Zhuo, Zihuan Wu, Chris Williams, Chithiravel Sundaresan, Shideh Kabiri Ameri
Journal: Advanced Healthcare Materials (2024)

Abstract Significant developments have been made in the field of wearable healthcare by utilizing soft materials for the construction of electronic sensors. However, the lack of adaptability to complex topologies, such as ear canal, results in inadequate sensing performance. Here, we report an in‐ear physiological sensor with mechanical adaptability, which softens upon contact with the ear canal's skin, thus reducing the sensor‐skin mechanical mismatch and interface impedance. An efficient strategy of mechanical adjustment and switching is exploited to increase the softness of the device, leading to a significant decrease in Young's modulus from 30.5 MPa of thermoplastic polyurethane (TPU) to 0.86 MPa of TPU/Ecoflex foam (TEF).The mechanical adaptability at body temperature endows the in‐ear device improved device‐canal contact area and interface stability. As a result, the TEF‐based in‐ear device demonstrates reliable sensing, low motion artifact, and high comfort in electroencephalography (EEG) and core body temperature sensing. High quality EEG signals of alpha, beta, delta, and gamma are measured during different activities. Moreover, the TEF‐based in‐ear device exhibits high reusability for over 4 months, which makes it suitable for long‐term healthcare monitoring.
Five-factor personality traits and functional somatic disorder: A systematic review and meta-analysis
Authors: Thomas Tandrup Lamm, Victoria Von Schrottenberg, Anneline Rauch, Bo Bach, Heidi Frølund Pedersen, Mette Trøllund Rask, Eva Ørnbøl, Kaare Bro Wellnitz, Lisbeth Frostholm
Journal: Clinical Psychology Review (2024)

Functional Somatic Disorders (FSD) is an umbrella term for various conditions characterized by persistent and troublesome physical symptoms, that are not better explained by other psychiatric or somatic conditions. Personality traits may play a crucial role in FSD, but the link is not fully understood. This study presents a systematic review and meta-analysis examines the relationship between the Five-Factor Model (FFM) of personality traits and FSD.
Cellular senescence as a key contributor to secondary neurodegeneration in traumatic brain injury and stroke
Authors: Zhihai Huang, Peisheng Xu, David C. Hess, Quanguang Zhang
Journal: Translational Neurodegeneration (2024)

Abstract Traumatic brain injury (TBI) and stroke pose major health challenges, impacting millions of individuals globally. Once considered solely acute events, these neurological conditions are now recognized as enduring pathological processes with long-term consequences, including an increased susceptibility to neurodegeneration. However, effective strategies to counteract their devastating consequences are still lacking. Cellular senescence, marked by irreversible cell-cycle arrest, is emerging as a crucial factor in various neurodegenerative diseases. Recent research further reveals that cellular senescence may be a potential driver for secondary neurodegeneration following brain injury. Herein, we synthesize emerging evidence that TBI and stroke drive the accumulation of senescent cells in the brain. The rationale for targeting senescent cells as a therapeutic approach to combat neurodegeneration following TBI/stroke is outlined. From a translational perspective, we emphasize current knowledge and future directions of senolytic therapy for these neurological conditions.