tbuckley/cabot-search huggingface dataset:
Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer
Authors: Shin-Chih Lin, Ya-Chuan Tsai, Ying-Lan Chen, Hui-Kuan Lin, Yun-Chen Huang, Yi-Syuan Lin, Yu-Sheng Cheng, Hsing-Yi Chen, Chia-Jung Li, Tsung-Yen Lin, Shih-Chieh Lin
Journal: Drug Resistance Updates (2024)

The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive. Drug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function. NUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3'UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells. The un-methylation of NUDT21-mediated 3'UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance.
Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety
Authors: Jinyi Wang, Tingting Zhou
Journal: Medicinal Research Reviews (2024)

Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.
Fluorescence and Photoacoustic (FL/PA) Dual-Modal Probe: Responsive to Reactive Oxygen Species (ROS) for Atherosclerotic Plaque Imaging
Authors: Qianqian Yu, Yi Duan, Nian Liu, Zhirong Zhu, Ying Sun, Haojian Yang, Yiqi Shi, Xiangyu Li, Wei-Hong Zhu, Lixin Wang, Qi Wang
Journal: Biomaterials (2024)
Indirect influence on the BDNF/TrkB receptor signaling pathway via GPCRs, an emerging strategy in the treatment of neurodegenerative disorders
Authors: Mirjana Antonijevic, Patrick Dallemagne, Christophe Rochais
Journal: Medicinal Research Reviews (2024)

Abstract Neuronal survival depends on neurotrophins and their receptors. There are two types of neurotrophin receptors: a nonenzymatic, trans‐membrane protein of the tumor necrosis factor receptor (TNFR) family–p75 receptor and the tyrosine kinase receptors (TrkR) A, B, and C. Activation of the TrkBR by brain‐derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT‐4/5) promotes neuronal survival, differentiation, and synaptic function. It is shown that in the pathogenesis of several neurodegenerative conditions (Alzheimer's disease, Parkinson's disease, Huntington's disease) the BDNF/TrkBR signaling pathway is impaired. Since it is known that GPCRs and TrkR are regulating several cell functions by interacting with each other and generating a cross‐communication in this review we have focused on the interaction between different GPCRs and their ligands on BDNF/TrkBR signaling pathway.
The recent advance and prospect of poly(ADP‐ribose) polymerase inhibitors for the treatment of cancer
Authors: Yi‐Ru Bai, Wei‐Guang Yang, Rui Jia, Ju‐Shan Sun, Dan‐Dan Shen, Hong‐Min Liu, Shuo Yuan
Journal: Medicinal Research Reviews (2024)

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.
Role of NEK2 in tumorigenesis and tumor progression
Authors: Jiliang Xia, Hongyan Zhao, Jacob L Edmondson, Brian Koss, Fenghuang Zhan
Journal: Trends in Molecular Medicine (2024)

Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase found in the nucleus and cytoplasm throughout the cell cycle. NEK2 is overexpressed in many cancers and is a biomarker of poor prognosis. Factors contributing to NEK2 elevation in cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, and the circular RNA (circRNA)/long noncoding RNA (lncRNA)-miRNA axis. NEK2 overexpression produces chromosomal instability and aneuploidy, thereby enhancing cancer progression and suppressing antitumor immunity, which highlights the prominence of NEK2 in tumorigenesis and tumor progression. Small-molecule inhibitors targeting NEK2 have demonstrated promising therapeutic potential in vitro and in vivo across various cancer types. This review outlines the regulatory mechanisms of NEK2 expression, emphasizes its functional roles in cancer initiation and progression, and highlights the anticancer properties of NEK2 inhibitors.
A scoping review of large language model based approaches for information extraction from radiology reports
Authors: Daniel Reichenpfader, Henning Müller, Kerstin Denecke
Journal: npj Digital Medicine (2024)

Radiological imaging is a globally prevalent diagnostic method, yet the free text contained in radiology reports is not frequently used for secondary purposes. Natural Language Processing can provide structured data retrieved from these reports. This paper provides a summary of the current state of research on Large Language Model (LLM) based approaches for information extraction (IE) from radiology reports. We conduct a scoping review that follows the PRISMA-ScR guideline. Queries of five databases were conducted on August 1st 2023. Among the 34 studies that met inclusion criteria, only pre-transformer and encoder-based models are described. External validation shows a general performance decrease, although LLMs might improve generalizability of IE approaches. Reports related to CT and MRI examinations, as well as thoracic reports, prevail. Most common challenges reported are missing validation on external data and augmentation of the described methods. Different reporting granularities affect the comparability and transparency of approaches.
Biomimetic multi-channel nerve conduits with micro/nanostructures for rapid nerve repair
Authors: Xinqing Wang, Shuo Chen, Xiaolei Chen, Juan Wu, Zhenhua Huang, Jing Wang, Fangping Chen, Changsheng Liu
Journal: Bioactive Materials (2024)

Peripheral nervous system (PNS) injuries often lead to significant sensory and motor impairments. Traditional artificial nerve conduits, lacking anisotropic structures, have been associated with prolonged repair time and failures in nerve regeneration. This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries (PNI). A 3D oriented fibers scaffold featuring distinct radial (RFs) and longitudinal (LFs) fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques. This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures. The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance, effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold. In a rat model with a 10 mm nerve defect, the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks. These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.
Novel Nano Drug‐Loaded Hydrogel Coatings for the Prevention and Treatment of CAUTI
Authors: Jibin Wu, Jianling Yan, Sijia Xu, Xuan Zou, Yinghua Xu, Xiaobao Jin, Xuemei Lu, Shuiqing Gui
Journal: Advanced Healthcare Materials (2024)

Abstract Catheter‐associated urinary tract infection (CAUTI) is a prevalent type of hospital‐acquired infection, affecting approximately 15% to 25% of patients with urinary catheters. Long‐term use of the catheter can lead to colonization of microorganisms and biofilm formation, and may develop into bacterial CAUTI. However, the frequent replacement of catheters in clinical settings can result in tissue damage, inflammation, ulceration, and additional complications, causing discomfort and pain for patients. In light of these challenges, a novel nanodrug‐supported hydrogel coating called NP‐AM/FK@OMV‐P/H has been developed in this study. Through in vitro experiments, it is confirmed that OMV nano‐loaded liquid gel coating has an effective reaction against E.coli HAase and releases antibacterial drugs. This coating has also demonstrated strong inhibition of E.coli and has shown the ability to inhibit the formation of bacterial biofilm. These findings highlight the potential of the OMV nanoparticle gel coating in preventing and treating bacterial infections. Notably, NP‐AM/FK@OMV‐P/H has exhibited greater efficacy against multidrug‐resistant E.coli associated with UTIs compared to coatings containing single antimicrobial peptides or antibiotics. Additionally, it has demonstrated good biosecurity. In conclusion, the NP‐AM/FK@OMV‐P/H coating holds great potential in providing benefits to patients with CAUTI.
Tofacitinib Citrate Coordination‐Based Dual‐Responsive/Scavenge Nanoplatform Toward Regulate Colonic Inflammatory Microenvironment for Relieving Colitis
Authors: Jiafeng Zou, Kun Jiang, You Chen, Ying Ma, Chuanhe Xia, Wenxing Ding, Min Yao, Yiting Lin, Yanzuo Chen, Yuzheng Zhao, Feng Gao
Journal: Advanced Healthcare Materials (2024)

Abstract Ulcerative colitis is an inflammation of the colon characterized by immune dysregulation and intestinal inflammation. Developing safe oral nanomedicines that suppress intestinal inflammation, while modulating colonic inflammatory microenvironment by scavenging reactive oxygen species (ROS) and hydrogen sulfide (H 2 S) is crucial for the effective treatment of colitis. Here, the tofacitinib citrate and copper coordination‐based nanoparticle (TF‐Cu nanoparticle, T‐C) to dual‐scavenge ROS and H 2 S by coordination competition is synthesized. Moreover, the coordination of T‐C using computer simulation is explored. To enhance the acid stability and inflammatory targeting of T‐C, it is encapsulated with hyaluronic acid‐modified chitosan, along with a calcium pectinate coating (T‐C@HP). Owing to the dual pH/pectinase‐responsive characteristics of T‐C@HP, the nanoplatform can target inflamed colonic lesions, inhibiting phosphorylated Janus kinase 1. Furthermore, T‐C@HP scavenges ROS and H 2 S, as well as increases NADPH levels, which is investigated by combining biosensor (HyPer7 and iNap1/c) and chemical probes. T‐C@HP also alleviates colitis by regulating the colonic inflammatory microenvironment through multiple processes, including the modulation of apoptosis, macrophage polarization, tight junction, mucus layer, and intestinal flora. Complemented by satisfactory anti‐inflammatory and biosafety results, this nanoplatform represents a promising, effective, and safe treatment option for colitis patients.
Aspirin hypersensitivity diagnostic index (<scp>AHDI</scp>): In vitro test for diagnosing of N‐<scp>ERD</scp> based on urinary 15‐oxo‐<scp>ETE</scp> and <scp>LTE<sub>4</sub></scp> excretion
Authors: Lucyna Mastalerz, Gabriela Trąd, Piotr Szatkowski, Adam Ćmiel, Anna Gielicz, Radosław Kacorzyk, Hanna Plutecka, Joanna Szaleniec, Agnieszka Gawlewicz‐Mroczka, Bogdan Jakieła, Marek Sanak
Journal: Allergy (2024)

15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E4 (LTE4) and assessed their diagnostic value to identify patients with N-ERD. The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE4 excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested. Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE4-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%. We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.
From dread to disorder: A meta-analysis of the impact of death anxiety on mental illness symptoms
Authors: Rachel E. Menzies, Keegan McMullen, Grazia D. Riotto, Sabina Iliescu, Benjamin Petrovic, Monique Remfrey
Journal: Clinical Psychology Review (2024)

Growing research suggests that death anxiety may be transdiagnostic, playing a key role in the development and symptomology of psychopathology. This meta-analysis examined the relationship between death anxiety and mental illness symptoms. In total, 104 papers were included, representing cross-sectional data from 99 studies (n
Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion
Authors: Lin Xu, Jie Fang, Jiezhou Pan, Hexu Qi, Yun Yin, Yunxiang He, Xueqi Gan, Yifei Li, Yu Li, Junling Guo
Journal: Bioactive Materials (2024)

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn
Antibodies to PfEMP1 and Variant Surface Antigens: Protection after Controlled Human Malaria Infection in Semi-immune Kenyan Adults
Authors: Ann W Kinyua, Louise Turner, Hannah W Kimingi, Kennedy Mwai, Kioko Mwikali, Cheryl Andisi, B Kim Lee Sim, Philip Bejon, Melissa C Kapulu, Samson M Kinyanjui, Thomas Lavstsen, Abdirahman I Abdi
Journal: Journal of Infection (2024)

Acquisition of antibodies to Plasmodium falciparum variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from PfEMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.
Antihelical erythema/papules as a potential risk factor for acute and subacute interstitial pneumonia in MDA5+ dermatomyositis: A retrospective cohort study
Authors: Szeman Cheung, Jiaqi Ye, Shile Chen, Mingyu Ye, Qian Zhao, Jie Zheng, Hua Cao
Journal: Journal of the American Academy of Dermatology (2024)
Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders
Authors: Yumei Qin, Yun Zhu, Lu Lu, Haoshuang Wu, Jinpeng Hu, Fan Wang, Bo Zhang, Jian Wang, Xia Yang, Rifang Luo, Juan Chen, Qing Jiang, Li Yang, Yunbing Wang, Xingdong Zhang
Journal: Biomaterials (2024)
Pre-packaged cold-chain ready-to-eat food as a source of sporadic listeriosis in Beijing, China
Authors: Yanlin Niu, Chao Wang, Yuzhu Liu, Penghang Zhang, Yangbo Wu, Mingying Li, Jingjing Zhao, Xiaoyuan Zhang, Xiaochen Ma
Journal: Journal of Infection (2024)

Using a sporadic case of listeriosis suspected to have been caused by consuming a pre-packaged cold-chain ready-to-eat (RTE) food in Beijing, China in 2021 as an exemplar, this study demonstrated the importance of thoroughly investigating the source of listeriosis up to the production point for mitigating infection risk during routine monitoring of Listeria in food facilities and national surveillance program using whole-genome sequencing (WGS).
Comparative Effects of GLP-1 Receptor Agonists and Metformin on Glaucoma Risk in Type 2 Diabetes Patients
Authors: Jawad Muayad, Asad Loya, Zain S. Hussain, Muhammad Z. Chauhan, Amer F. Alsoudi, Ticiana De Francesco, Iqbal Ike K. Ahmed
Journal: Ophthalmology (2024)
Efficacy and safety of low-dose Interleukin-2 in the treatment of moderate to severe bullous pemphigoid: a single center perspective-controlled trial
Authors: Ruzeng Xue, Guomin Li, Yao Zhou, Bocheng Wang, Yingping Xu, Peizhen Zhao, Lijun Teng, Jinjin Zheng, Hongfang Liu, Suyun Ji, Dirk M. Elston, Yunsheng Liang
Journal: Journal of the American Academy of Dermatology (2024)
Keratinocyte Carcinomas in Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study
Authors: Christina Boull, Yan Chen, Cindy Im, Alan Geller, Yadav Sapkota, James E. Bates, Rebecca Howell, Michael A. Arnold, Miriam Conces, Louis S. Constine, Leslie Robison, Yutaka Yasui, Gregory T. Armstrong, Joseph P. Neglia, Lucie M. Turcotte
Journal: Journal of the American Academy of Dermatology (2024)
Somatic Molecular Heterogeneity in Bilateral Macronodular Adrenocortical Disease (BMAD) Differs Among the Pathological Subgroups
Authors: Florian Violon, Lucas Bouys, Patricia Vaduva, Albain Chansavang, Louis Vaquier, Franck Letourneur, Brigitte Izac, Gaëtan Giannone, Daniel De Murat, Martin Gaillard, Annabel Berthon, Bruno Ragazzon, Eric Pasmant, Mathilde Sibony, Jérôme Bertherat
Journal: Endocrine Pathology (2024)
Evolving Spectrum of Adenosine Deaminase Deficiency: Assessing Genotype Pathogenicity Based on Expressed ADA Activity of 46 Variants
Authors: Ines Santisteban, Francisco X. Arredondo-Vega, Pawan Bali, Busra Dalgic, Hyun Ho Lee, Minsoo Kim, Jake Hermanson, Teresa K. Tarrant, Michael S. Hershfield
Journal: Journal of Allergy and Clinical Immunology (2024)

BackgroundDeficiency of adenosine deaminase (ADA or ADA1) has broad clinical and genetic heterogeneity. Screening techniques can identify asymptomatic infants whose phenotype and prognosis are indeterminate, and who may carry ADA variants of unknown significance.ObjectiveWe systematically assessed the pathogenic potential of rare ADA missense variants to better define the relationship of genotype to red blood cell (RBC) total deoxyadenosine nucleotide (dAXP) content and to phenotype.MethodsWe expressed 46 ADA missense variants in the ADA-deficient SØ3834 strain of Escherichia coli and defined genotype categories (GCs) ranked I to IV by increasing expressed ADA activity. We assessed relationships among GC rank, RBC dAXP, and phenotype in 58 reference patients with 50 different genotypes. We used our GC ranking system to benchmark AlphaMissense for predicting variant pathogenicity, and we used a minigene assay to identify exonic splicing variants in ADA exon 9.ResultsThe 46 missense variants expressed ∼0.001% to ∼70% of wild-type ADA activity (40% had <0.05% of wild-type ADA activity and 50% expressed >1%). RBC dAXP ranged from undetectable to >75% of total adenine nucleotides and correlated well with phenotype. Both RBC dAXP and clinical severity were inversely related to total ADA activity expressed by both inherited variants. Our GC scoring system performed better than AlphaMissense in assessing variant pathogenicity, particularly for less deleterious variants.ConclusionFor ADA deficiency, pathogenicity is a continuum and conditional, depending on the total ADA activity contributed by both inherited variants as indicated by GC rank. However, in patients with indeterminate phenotype identified by screening, RBC dAXP measured at diagnosis may have greater prognostic value than GC rank.