tbuckley/cabot-search huggingface dataset:
Factors associated with biological and targeted synthetic disease-modifying antirheumatic drug initiation for rheumatoid arthritis in underserved patient groups in England and Wales, UK: a national cohort study
Authors: Mark D Russell, Mark Gibson, Benjamin Zuckerman, Kanta Kumar, Shirish Dubey, Maryam A Adas, Edward Alveyn, Samir Patel, Zijing Yang, Katie Bechman, Elizabeth Price, Sarah Gallagher, Andrew P Cope, Sam Norton, James B Galloway
Journal: The Lancet Rheumatology (2024)

Quantifying health-care inequality is essential to addressing the imbalance in outcomes attributable to age, sex, race or ethnicity, and multimorbidity. In this study, we analysed differences in the initiation of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis within the universal health-care system of England and Wales, UK.
Early detection of dementia through retinal imaging and trustworthy AI
Authors: Jinkui Hao, William R. Kwapong, Ting Shen, Huazhu Fu, Yanwu Xu, Qinkang Lu, Shouyue Liu, Jiong Zhang, Yonghuai Liu, Yifan Zhao, Yalin Zheng, Alejandro F. Frangi, Shuting Zhang, Hong Qi, Yitian Zhao
Journal: npj Digital Medicine (2024)

Alzheimer's disease (AD) is a global healthcare challenge lacking a simple and affordable detection method. We propose a novel deep learning framework, Eye-AD, to detect Early-onset Alzheimer's Disease (EOAD) and Mild Cognitive Impairment (MCI) using OCTA images of retinal microvasculature and choriocapillaris. Eye-AD employs a multilevel graph representation to analyze intra- and inter-instance relationships in retinal layers. Using 5751 OCTA images from 1671 participants in a multi-center study, our model demonstrated superior performance in EOAD (internal data: AUC = 0.9355, external data: AUC = 0.9007) and MCI detection (internal data: AUC = 0.8630, external data: AUC = 0.8037). Furthermore, we explored the associations between retinal structural biomarkers in OCTA images and EOAD/MCI, and the results align well with the conclusions drawn from our deep learning interpretability analysis. Our findings provide further evidence that retinal OCTA imaging, coupled with artificial intelligence, will serve as a rapid, noninvasive, and affordable dementia detection.
Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?
Authors: Ruochen Du, Jianzhong Zhang, Rimas V Lukas, Shashwat Tripathi, Jared T Ahrendsen, Michael A Curran, Crismita Dmello, Peng Zhang, Roger Stupp, Ganesh Rao, Amy B Heimberger
Journal: Neuro-Oncology (2024)

Abstract The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, we aim to prioritize agents in this category of therapeutics for glioblastoma.
Perioperative chemoimmunotherapy induces strong immune responses and long-term survival in patients with HLA class I-deficient non-small cell lung cancer
Authors: Marta Molina-Alejandre, Francisco Perea, Virginia Calvo, Cristina Martinez-Toledo, Ernest Nadal, Belén Sierra-Rodero, Marta Casarrubios, Joaquín Casal-Rubio, Alex Martinez-Martí, Amelia Insa, Bartomeu Massuti, Santiago Viteri, Isidoro Barneto Aranda, Delvys Rodriguez-Abreu, Javier de Castro, Joaquín Mosquera Martínez, Manuel Cobo, Ignacio I Wistuba, Edwin R Parra, Javier Martín-López, Diego Megías, Rafael Muñoz-Viana, Federico Garrido, Natalia Aptsiauri, Francisco Ruiz-Cabello, Mariano Provencio, Alberto Cruz-Bermúdez
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects. Methods Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial ( NCT03081689 ). We integrated HLA tumor status with molecular data (programmed death-ligand 1 (PD-L1), TMB, TCR repertoire, TILs populations, bulk RNA-seq, and spatial transcriptomics (ST)) and clinical outcomes (pathological response and survival data) to study the activity of perioperative ChIO considering HLA class I defects. Results HLA-DEF tumors comprised 41.7% of analyzed tumors and showed a desert-like microenvironment at baseline, with lower PD-L1 levels and reduced immune infiltrate. However, perioperative ChIO induced similar complete pathological response (CPR) rates in both HLA-DEF and PRO tumors (50% and 60% respectively, p=0.670), as well as 3-year survival rates: Progression-free survival (PFS) and overall survival (OS) of 70% (95% CI 32.9% to 89.2%) for HLA-DEF, and PFS 71.4% (95% CI 40.6% to 88.2%) and OS 92.9% (95% CI 59.1% to 99.0%) for HLA-PRO (log-rank PFS p=0.909, OS p=0.137). Proof-of-concept ST analysis of a CPR HLA-DEF tumor after ChIO showed a strong immune response with tertiary lymphoid structures (TLS), CD4+T cells with HLA class II colocalization, and activated CD8+T cells. Conclusions Our findings highlight the activity of perioperative ChIO, and the potential role of TLS and T-cell immune response, in NSCLC HLA-DEF tumors.
Perspectives on non-genetic optoelectronic modulation biointerfaces for advancing healthcare
Authors: Aman Majmudar, Saehyun Kim, Pengju Li, Bozhi Tian
Journal: Med-X (2024)

Abstract Advancements in optoelectronic biointerfaces have revolutionized healthcare by enabling targeted stimulation and monitoring of cells, tissues, and organs. Photostimulation, a key application, offers precise control over biological processes, surpassing traditional modulation methods with increased spatial resolution and reduced invasiveness. This perspective highlights three approaches in non-genetic optoelectronic photostimulation: nanostructured phototransducers for cellular stimulation, micropatterned photoelectrode arrays for tissue stimulation, and thin-film flexible photoelectrodes for multiscale stimulation. Nanostructured phototransducers provide localized stimulation at the cellular or subcellular level, facilitating cellular therapy and regenerative medicine. Micropatterned photoelectrode arrays offer precise tissue stimulation, critical for targeted therapeutic interventions. Thin-film flexible photoelectrodes combine flexibility and biocompatibility for scalable medical applications. Beyond neuromodulation, optoelectronic biointerfaces hold promise in cardiology, oncology, wound healing, and endocrine and respiratory therapies. Future directions include integrating these devices with advanced imaging and feedback systems, developing wireless and biocompatible devices for long-term use, and creating multifunctional devices that combine photostimulation with other therapies. The integration of light and electronics through these biointerfaces paves the way for innovative, less invasive, and more accurate medical treatments, promising a transformative impact on patient care across various medical fields.
Microenvironment-responsive nanomedicines: a promising direction for tissue regeneration
Authors: Yuan Xiong, Bo-Bin Mi, Mohammad-Ali Shahbazi, Tian Xia, Jun Xiao
Journal: Military Medical Research (2024)

Abstract Severe tissue defects present formidable challenges to human health, persisting as major contributors to mortality rates. The complex pathological microenvironment, particularly the disrupted immune landscape within these defects, poses substantial hurdles to existing tissue regeneration strategies. However, the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine, providing encouraging prospects for tissue regeneration and restoration. This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration. We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration. Subsequently, we explore the design and functional properties of immunomodulatory nanosystems. Finally, we address the challenges and prospects of clinical translation in nanomedicine development, aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.
MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2
Authors: Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A Calin
Journal: Molecular Cancer (2024)
Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis
Authors: J Kenneth Baillie, Derek Angus, Katie Burnham, Thierry Calandra, Carolyn Calfee, Alex Gutteridge, Nir Hacohen, Purvesh Khatri, Raymond Langley, Avi Ma'ayan, John Marshall, David Maslove, Hallie C Prescott, Kathy Rowan, Brendon P Scicluna, Christopher Seymour, Manu Shankar-Hari, Nathan Shapiro, W Joost Wiersinga, Mervyn Singer, Adrienne G Randolph
Journal: Intensive Care Medicine (2024)
Impact of COVID-19 on outcomes with teclistamab in patients with relapsed/refractory multiple myeloma in the phase 1/2 MajesTEC-1 study
Authors: Niels W C J van de Donk, Nizar Bahlis, Luciano J Costa, María-Victoria Mateos, Ajay K Nooka, Aurore Perrot, Alfred L Garfall, Pragya Thaman, Keqin Qi, Clarissa Uhlar, Katherine Chastain, Margaret Doyle, Saad Z Usmani
Journal: Blood Cancer Journal (2024)
Collaboration in Contradiction: Self‐Adaptive Synergistic ROS Generation and Scavenge Balancing Strategies Used for the Infected Wounds Treatment
Authors: Mengtian Wang, Yangkun Liu, Shuqing Yang, Xuanbing Wang, Qindan Duan, Jiankai Liu, Xudong Tan, Linjing Long, Siyi Liu, Yawen Xiao, Zhao Li, Changhao Han, Yaoxing Yi, Yuchan Zhang, Guixue Wang, Guangchao Zang
Journal: Advanced Healthcare Materials (2024)

The rational utilization of ROS is key to treating infected wounds. Exogenous ROS can destroy bacterial structures, quickly kill bacteria, and inhibit secondary infections. However, excess ROS at the wound will cause a secondary inflammatory response. Acute infections exacerbate this damage by increasing endogenous ROS, complicating the maintenance of ROS homeostasis. Therefore, regulating the balance of ROS production and scavenging in wounds has emerged as a promising strategy for wound treatment. Conventional ROS balancing platforms are mostly based on the " all for one" strategy of functional superposition and lack self-adaptability and integration. To subvert this conventional strategy, this study proposes a "one for all" self-adaptive integrated photodynamic therapy (PDT)-antioxidant model to actively regulate the ROS balance. A gelatin-hyaluronic acid hydrogel embedded with Se-modified cerium dioxide nanoparticles (Gel-HA-Se@CeO2 NPs) is designed for treating infected wounds. The Se@CeO2 NPs serve both as nanoenzymes and photosensitizers(PS). As nanoenzymes, they exhibit catalase and superoxide dismutase activities, converting hydrogen peroxide and superoxide anions into oxygen. As a PS, it synergizes with oxygen under NIR irradiation to rapidly produce singlet oxygen. Additionally, Se modification enhances the PDT effects by disrupting bacterial antioxidant systems. In vitro and in vivo experiments revealed that the ROS balance platform polarizes M1-type macrophages to M2-type macrophages, altering the wound microenvironment from proinflammatory to prohealing. RNA sequencing revealed that this hydrogel accelerated the reconstruction of the vascular network of the wound by activating the PI3K/AKT pathway and increasing VEGF secretion.This strategy is believed to be beneficial not only for infected wounds but also for treating other conditions that involve the regulation of reactive oxygen species, such as tumors and bacterial infections.
NFAT5 governs cellular plasticity-driven resistance to KRAS-targeted therapy in pancreatic cancer
Authors: Daiyong Deng, Habeebunnisa Begum, Tong Liu, Jiangyan Zhang, Qiang Zhang, Ting-yu Chu, Hong Li, Alexander Lemenze, Mainul Hoque, Patricia Soteropoulos, Pingping Hou
Journal: The Journal of Experimental Medicine (2024)

Resistance to KRAS therapy in pancreatic ductal adenocarcinoma (PDAC) involves cellular plasticity, particularly the epithelial-to-mesenchymal transition (EMT), which poses challenges for effective targeting. Chronic pancreatitis, a known risk factor for PDAC, elevates TGFβ levels in the tumor microenvironment (TME), promoting resistance to KRAS therapy. Mechanistically, TGFβ induces the formation of a novel protein complex composed of SMAD3, SMAD4, and the nuclear factor NFAT5, triggering EMT and resistance by activating key mediators such as S100A4. Inhibiting NFAT5 attenuates pancreatitis-induced resistance to KRAS inhibition and extends mouse survival. Additionally, TGFβ stimulates PDAC cells to secrete CCL2, recruiting macrophages that contribute to KRAS bypass through paracrine S100A4. Our findings elucidate the role of TGFβ signaling in EMT-associated KRAS therapy resistance and identify NFAT5 as a druggable target. Targeting NFAT5 could disrupt this regulatory network, offering a potential avenue for preventing resistance in PDAC.
EGFR-directed antibodies promote HER2 ADC internalization and efficacy
Authors: Avantika Gupta, Flavia Michelini, Hong Shao, Celine Yeh, Joshua Z Drago, Dazhi Liu, Eric Rosiek, Yevgeniy Romin, Negin Ghafourian, Sheeno Thyparambil, Sandra Misale, Wungki Park, Elisa de Stanchina, Yelena Y Janjigian, Rona Yaeger, Bob T Li, Sarat Chandarlapaty
Journal: Cell Reports Medicine (2024)

Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor receptor 2 (HER2)-targeting antibody drug conjugate that has remarkable activity in HER2-positive cancers. However, the degree of benefit of T-DXd is not uniform among solid tumors even with high levels of HER2. Despite high HER2 expression, the HER2/T-DXd complex may not always undergo internalization and payload release dependent on the receptor's conformation and context. We hypothesize that epidermal growth factor receptor (EGFR), a dimerization partner of HER2, can modulate HER2 trafficking through endocytic pathways and affect T-DXd uptake. We demonstrate that elevated EGFR expression levels can promote EGFR/HER2 heterodimer formation and suppress T-DXd internalization and efficacy. Knockdown of EGFR expression or pharmacologic stimulation of EGFR endocytosis with EGFR monoclonal antibodies restores T-DXd trafficking and antitumor activity in EGFR-overexpressing cancers in vivo. Our results reveal EGFR overexpression to be a potential mechanism of resistance to T-DXd, which can be overcome by combination therapy strategies targeting EGFR.
Three vs 6 Cycles of Chemotherapy for High-Risk Retinoblastoma
Authors: Huijing Ye, Kang Xue, Ping Zhang, Rongxin Chen, Xiaowen Zhai, Li Ling, Wei Xiao, Lijuan Tang, Hongsheng Wang, Yuxiang Mao, Siming Ai, Yingwen Bi, Qing Liu, Yusha Zou, Jiang Qian, Huasheng Yang
Journal: JAMA (2024)

Importance Adjuvant therapy is an important and effective treatment for retinoblastoma. However, there is a lack of head-to-head clinical trials comparing 3 vs 6 cycles of CEV chemotherapy (carboplatin, etoposide, and vincristine) for enucleated unilateral retinoblastoma with high-risk pathological features. Objective To assess whether 3 cycles of CEV chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features. Design, Setting, and Participants This double-center, randomized, open-label, noninferiority trial was conducted at 2 premier eye centers in China and included 187 patients who had undergone enucleation for unilateral retinoblastoma with high-risk pathological features (massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration) between August 2013 and March 2024. The final date of follow-up was March 21, 2024. Interventions Patients were randomly assigned to receive either 3 (n = 94) or 6 (n = 93) cycles of CEV chemotherapy regimen after enucleation. Main Outcomes and Measures The primary end point was disease-free survival, with a noninferiority margin of 12%. Secondary end points encompassed overall survival, safety, economic burden, and the quality of life of children. Results All 187 patients (median [IQR] age, 25.0 [20.0-37.0] months; 83 [44.4%] female) completed the trial. Median (IQR) follow-up was 79.0 (65.5-102.5) months. Five-year disease-free survival was 90.4% for the 3-cycle group vs 89.2% for the 6-cycle group (difference, 1.2% [95% CI, −7.5% to 9.8%]), which met the noninferiority criterion ( P = .003 for noninferiority). The 6-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the 3-cycle group. Conclusions and Relevance Among patients with unilateral pathologic high-risk retinoblastoma, 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy. Trial Registration ClinicalTrials.gov Identifier: NCT01906814
Clinic Characteristics and Antibiotic Prescribing for Acute Respiratory Infections in Japan
Authors: Ryuhei Aoyama, Yusuke Tsugawa, Masahiro Ishikane, Kei Kitajima, Daichi Sato, Atsushi Miyawaki
Journal: JAMA Network Open (2024)

This cross-sectional study examined clinic characteristics associated with antibiotic prescribing for acute respiratory infections in primary care in Japan.
Levels of Satisfaction and Regret With Gender-Affirming Medical Care in Adolescence
Authors: Kristina R. Olson, G. F. Raber, Natalie M. Gallagher
Journal: JAMA Pediatrics (2024)

Importance There is a need to improve the evidence base for gender-affirming medical care provided to adolescents, including the experiences of those who have received this care. Objective To examine rates of satisfaction, regret, and continuity of care in adolescents who received puberty blockers and/or gender-affirming hormones as part of gender-affirming medical care. Design, Setting, and Participants This survey study used the 2023 online survey wave of an ongoing longitudinal study, the Trans Youth Project, among a community-based sample of transgender youth and their parents initially recruited throughout the US and Canada between 2013 and 2017. The satisfaction and regret data include responses from a youth or their parent representing 87% of the youth aged 12 years or older in the cohort who have received gender-affirming medical care (235 of 269 youths). Of these, 220 completed the 2023 survey (main sample); information about continuity of care was available for all youth. Data analysis was performed from April to August 2024. Exposure Satisfaction, regret, and continuity of care following puberty blockers or suppression and/or gender-affirming hormones. Main Outcomes and Measures Self- or parent-reported satisfaction or regret with gender-affirming care and continuation of care. Results Among the 220 youths in the main sample (mean [SD] age, 16.07 [2.40] years; 30 [14%] multiracial, non-Hispanic; 18 [8%] White, Hispanic; 155 [70%] White, non-Hispanic; 17 [8%] other race and ethnicity, including Asian, Black [Hispanic and non-Hispanic], Hispanic with unknown race, multiracial Hispanic, or Native American; gender at last interaction: 68 [31%] boys, 132 [60%] girls, 20 [9%] gender diverse, eg, nonbinary) and their parents, very high levels of satisfaction and low levels of regret with puberty blockers and gender-affirming hormones as well as high levels of continuation of care were reported. Of these 220 respondents in the main sample, 9 were regretful of having received blockers (n = 8) and/or hormones (n = 3; 2 of these individuals reported regret with both), of whom 4 have stopped all gender-affirming medical care and 1 has continued to receive blockers but plans to stop. The 4 others have continued care, suggesting that regret is not synonymous with stopping care. Conclusions and Relevance The findings suggest that youth accessing puberty blockers and hormones as part of gender-affirming care tend to be satisfied with and not regretful of that care several years later. While regret was rare, these experiences need to be better understood.
Cannabis-Derived Product Types, Flavors, and Compound Types From an E-Commerce Website
Authors: Matthew C. Nali, Joshua S. Yang, Zhuoran Li, Meng Zhen Larsen, Tim K. Mackey
Journal: JAMA Network Open (2024)

Importance Cannabis-derived products (CDPs) are widely available and diverse. A classification of product and flavor types is necessary to establish a foundation for comparative research, although research aiming to classify cannabis in its variety of products, flavors, and cannabinoid compounds based on public online e-commerce data is lacking. Objective To analyze data from a large cannabis e-commerce marketplace to identify and characterize cannabis product types, flavors, and compound types. Design, Setting, and Participants This qualitative study was conducted in 2 phases: (1) data mining of the cannabis e-commerce website Weedmaps for product listings in the US between September 1 and November 30, 2023 and (2) grouping CDPs into product, flavor, and cannabinoid compound categories. Exposures Cannabis product listings. Main Outcomes and Measures Product listings and descriptions were extracted from the platform. Coding was performed for specific product characteristics, routes of administration (ROAs), and characterization of flavors. Results A total of 573 854 unique US CDP sales listings from the platform were collected; after removing 72 842 nonconsumable items, 501 012 were analyzed. Product ROAs included multisystem (205 637 [41.04%]), respiratory (185 296 [36.98%]), digestive (98 941 [19.75%]), epidermal (9487 [1.89%]), and oral (1651 [0.33%]). Nearly half (210 575 [42.03%]) of all product listings included at least 1 flavor, with 247 762 instances of flavors. The 3 most common flavors were lemon (22 106 [8.92%]), cake (19 463 [7.86%]), and strawberry (13 961 [5.63%]). The most common cannabinoid compound type was Δ 9 -tetrahydrocannabinol (54 699 [63.30%]). Conclusions and Relevance This qualitative study categorized more than half a million CDPs for product and flavor types. Results are needed for comparative studies on product and market availability and can help in assessing concerns about appealing characteristics. The results can also inform future market surveillance efforts aimed at identifying new and emerging products as cannabis policy continues to move toward greater legalization.