tbuckley/cabot-search huggingface dataset:
NK cells restrain cytotoxic CD8 <sup>+</sup> T cells in the submandibular gland via PD-1–PD-L1
Authors: Samantha M. Borys, Shanelle P. Reilly, Ian Magill, David Zemmour, Laurent Brossay
Journal: Science Immunology (2024)

The increasing use of anti–programmed cell death 1 (PD-1) immune checkpoint blockade has led to the emergence of immune-related adverse events (irAEs), including dysfunction of the submandibular gland (SMG). In this study, we investigated the immunoregulatory mechanism contributing to the susceptibility of the SMG to irAEs. We found that the SMGs of PD-1–deficient mice and anti–programmed cell death ligand 1 (PD-L1)–treated mice harbor an expanded population of CD8 + T cells. We demonstrate that natural killer (NK) cells expressing PD-L1 tightly regulate CD8 + T cells in the SMG. When this immunoregulation is disrupted, CD8 + T cells clonally expand and acquire a unique transcriptional profile consistent with T cell receptor (TCR) activation. These clonally expanded cells phenotypically overlapped with cytotoxic GzmK + CD8 + T autoimmune cells identified in patients with primary Sjögren’s syndrome. Understanding how NK cells modulate CD8 + T cell activity in the SMG opens new avenues for preventing irAEs in patients undergoing checkpoint blockade therapies.
A Unified Probabilistic Approach to Traffic Conflict Detection
Authors: Yiru Jiao, Simeon C. Calvert, Sander van Cranenburgh, Hans van Lint
Journal: Analytic Methods in Accident Research (2024)

Traffic conflict detection is essential for proactive road safety by identifying potential collisions before they occur.Existing methods rely on surrogate safety measures tailored to specific interactions (e.g., car-following, side-swiping, or path-crossing) and require varying thresholds in different traffic conditions.This variation leads to inconsistencies and limited adaptability of conflict detection in evolving traffic environments, particularly as the integration of autonomous driving systems adds complexity.Consequently, there is an increasing need for consistent detection of traffic conflicts across interaction contexts.To address this need, we propose a unified probabilistic approach in this study.The proposed approach establishes a unified framework of traffic conflict detection, where traffic conflicts are formulated as context-dependent extreme events of road user interactions.The detection of conflicts is then decomposed into a series of statistical learning tasks: representing interaction contexts, inferring proximity distributions, and assessing extreme collision risk.The unified formulation accommodates diverse hypotheses of traffic conflicts and the learning tasks enable data-driven analysis of factors such as motion states of road users, environment conditions, and participant characteristics.Jointly, this approach supports consistent and comprehensive evaluation of the collision risk emerging in road user interactions.We demonstrate the proposed approach by experiments using real-world trajectory data.A unified metric for indicating conflicts is first trained with lane-change interactions on German highways, and then compared with existing metrics using near-crash events from the U.S. 100-Car Naturalistic Driving Study.Our results show that the unified metric provides effective collision warnings, generalises across distinct datasets and traffic environments, covers a broad range of conflict types, and captures a long-tailed distribution of conflict intensity.In summary, this study provides an explainable and generalisable approach that enables traffic conflict detection across varying interaction contexts.The findings highlight its potential to enhance the safety assessment of traffic infrastructures and policies, improve collision warning systems for autonomous driving, and deepen the understanding of road user behaviour in safety-critical interactions.
Modulating active targeting nanoparticle design according to tumor progressions
Authors: Huifang Nie, Rong Huang, Guangwei Jiang, Wenshuai Li, Lan Yang, Meng Zhang, Min Qian, Wei Guo, Tao Ye, Rongqin Huang
Journal: Acta Pharmaceutica Sinica B (2024)

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α v β 3 because of the multivalent interactions between larger active nanoparticles and integrin α v β 3. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.
NIR-II-activated whole-cell vaccine with ultra-efficient semiconducting diradical oligomers for breast carcinoma growth and metastasis inhibition
Authors: Yijian Gao, Yachao Zhang, Yujie Ma, Xiliang Li, Yu Wang, Huan Chen, Yingpeng Wan, Zhongming Huang, Weimin Liu, Pengfei Wang, Lidai Wang, Chun-Sing Lee, Shengliang Li
Journal: Acta Pharmaceutica Sinica B (2024)

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.
Drug delivery systems based on mesoporous silica nanoparticles for the management of hepatic diseases
Authors: Boyan Liu, Wenshi Liu, Miao Xu, Tongyi Zhao, Bingxin Zhou, Ruilin Zhou, Ze Zhu, Xuchun Chen, Zhiye Bao, Keke Wang, Heran Li
Journal: Acta Pharmaceutica Sinica B (2024)

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.
snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses
Authors: Will Macnair, Daniela Calini, Eneritz Agirre, Julien Bryois, Sarah Jäkel, Rebecca Sherrard Smith, Petra Kukanja, Nadine Stokar-Regenscheit, Virginie Ott, Lynette C Foo, Ludovic Collin, Sven Schippling, Eduard Urich, Erik Nutma, Manuel Marzin, Federico Ansaloni, Sandra Amor, Roberta Magliozzi, Elyas Heidari, Mark D Robinson, Charles Ffrench-Constant, Gonçalo Castelo-Branco, Anna Williams, Dheeraj Malhotra
Journal: Neuron (2024)
Gabapentin is an Efficacy Treatment for Facial Flushing and Erythema of Erythematotelangiectatic Rosacea: A Randomized Clinical noninferiority Trial
Authors: Jinyu Wei, Mei Wan, Qiquan Chen, Jian Fu, Ling Yang, Rongrong Ni, Lan Ge, Yanjun Dan, Xiao Chen, Minmin Kong, Ling Li, Shuguang Chen, Shichao Yang, Lian Zhang, Aiai Xia, Li Tang, Yanqi Zhang, Mingwang Zhang, Zhiqiang Song, Jian Li
Journal: Journal of the American Academy of Dermatology (2024)
Age against the machine—susceptibility of large language models to cognitive impairment: cross sectional analysis
Authors: Roy Dayan, Benjamin Uliel, Gal Koplewitz
Journal: BMJ (2024)

Abstract Objective To evaluate the cognitive abilities of the leading large language models and identify their susceptibility to cognitive impairment, using the Montreal Cognitive Assessment (MoCA) and additional tests. Design Cross sectional analysis. Setting Online interaction with large language models via text based prompts. Participants Publicly available large language models, or “chatbots”: ChatGPT versions 4 and 4o (developed by OpenAI), Claude 3.5 “Sonnet” (developed by Anthropic), and Gemini versions 1 and 1.5 (developed by Alphabet). Assessments The MoCA test (version 8.1) was administered to the leading large language models with instructions identical to those given to human patients. Scoring followed official guidelines and was evaluated by a practising neurologist. Additional assessments included the Navon figure, cookie theft picture, Poppelreuter figure, and Stroop test. Main outcome measures MoCA scores, performance in visuospatial/executive tasks, and Stroop test results. Results ChatGPT 4o achieved the highest score on the MoCA test (26/30), followed by ChatGPT 4 and Claude (25/30), with Gemini 1.0 scoring lowest (16/30). All large language models showed poor performance in visuospatial/executive tasks. Gemini models failed at the delayed recall task. Only ChatGPT 4o succeeded in the incongruent stage of the Stroop test. Conclusions With the exception of ChatGPT 4o, almost all large language models subjected to the MoCA test showed signs of mild cognitive impairment. Moreover, as in humans, age is a key determinant of cognitive decline: “older” chatbots, like older patients, tend to perform worse on the MoCA test. These findings challenge the assumption that artificial intelligence will soon replace human doctors, as the cognitive impairment evident in leading chatbots may affect their reliability in medical diagnostics and undermine patients’ confidence.
Understanding the Effectiveness of Water, Sanitation, and Hygiene Interventions: A Counterfactual Simulation Approach to Generalizing the Outcomes of Intervention Trials
Authors: Andrew F. Brouwer, Mondal H. Zahid, Marisa C. Eisenberg, Benjamin F. Arnold, Sania Ashraf, Jade Benjamin-Chung, John M. Colford, Ayse Ercumen, Stephen P. Luby, Amy J. Pickering, Mahbubur Rahman, Alicia N.M. Kraay, Joseph N.S. Eisenberg, Matthew C. Freeman
Journal: Environmental Health Perspectives (2024)

While water, sanitation, and hygiene (WASH) interventions can reduce diarrheal disease, many large-scale trials have not found the expected health gains for young children in low-resource settings. Evidence-based guidance is needed to improve interventions and remove barriers to diarrheal disease reduction.
FDA Approval Summary: Nadofaragene firadenovec-vncg for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer
Authors: Laronna Colbert, Yuxia Jia, Anurag Sharma, Jiang Hu, Zhenzhen Xu, Daniel L. Suzman, Asha Das, Peter Bross, Paul G. Kluetz, Lola A. Fashoyin-Aje
Journal: Clinical Cancer Research (2024)

On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months. The major efficacy outcome measures were complete response (CR) at any time and duration of response (DoR). Fifty subjects experienced CR 3 months after initial treatment (CR=51%; 95% CI: 40.7; 61.3%), of whom 46% remained in response for ≥12 months. The median DoR was 9.7 months (range: 3 to 52+). Common adverse reactions included instillation site discharge, fatigue, bladder spasm, micturition urgency, hematuria, chills, pyrexia, and dysuria. The approval of nadofaragene firadenovec provides a new therapy option for patients with BCG-unresponsive NMIBC with CIS who are ineligible for cystectomy.
Childhood Exposure to Interparental Physical Violence and Adult Cardiovascular Disease
Authors: Cancan Cui, Lin Liu, Haibin Li, Yitian Qi, Jiayin Song, Ning Han, Zhijia Wang, Xinyun Shang, Chen Sheng, Lois Balmer, Zhiyuan Wu
Journal: JAMA Network Open (2024)

Importance Childhood adverse experiences have been linked with long-term risk of cardiovascular disease (CVD), yet the transgenerational associations between interparental behaviors and CVD remain poorly understood. Objectives To explore the association between exposure to childhood interparental physical violence and the subsequent risk of CVD and to examine whether the association is modified by adult depressive symptoms. Design, Setting, and Participants This population-based cohort study included data from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing study recruiting individuals aged 45 years or older, dated between June 1, 2011, and December 31, 2020, with a follow-up duration of 9 years. The data were analyzed from October 1, 2023, to May 10, 2024. Exposures An early life exposure questionnaire with information on the frequency of witnessing interparental physical violence was administered. Depressive symptoms were assessed via the validated 10-item Center for Epidemiologic Studies Depression Scale. Main Outcomes and Measures The outcome measures included self-reported physician-diagnosed heart disease (defined as myocardial infarction, angina, coronary heart disease, heart failure, or other heart problems) and stroke. Multivariate Cox proportional hazards regression models using attained age as the time scale were conducted. Results Of 10 424 participants, the mean (SD) age was 58.1 (9.0) years, 5332 (51.2%) were female, and 872 (8.4%) reported exposure to interparental physical violence. Exposure to childhood interparental physical violence was associated with increased risks of adult-onset CVD (hazard ratio [HR], 1.36; 95% CI, 1.20-1.55), heart disease (HR, 1.36; 95% CI, 1.17-1.57), and stroke (HR, 1.28; 95% CI, 1.03-1.61). Participants exposed to childhood interparental physical violence had a greater prevalence of depressive symptoms (2371 of 9335 participants [25.4%]), which mediated 11.0% of the association between childhood interparental physical violence and CVD (HR, 1.26; 95% CI, 1.09-1.45). Conclusions and Relevance In this cohort study, childhood exposure to interparental physical violence was associated with a higher risk of adult-onset CVD, which was partially mediated by adult depressive symptoms. The findings emphasize the need for comprehensive strategies and policy efforts that address the social determinants of interparental violence and provide household education opportunities.
Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation
Authors: Benjamin M Jacobs, Christiane Gasperi, Sudhakar Reddy Kalluri, Raghda Al-Najjar, Mollie O McKeon, Jonathan Else, Albert Pukaj, Friederike Held, Stephen Sawcer, Maria Ban, Bernhard Hemmer
Journal: Cell Reports Medicine (2024)
Optimal timing of anti-PD-1 antibody combined with chemotherapy administration in patients with NSCLC
Authors: Yachang Huo, Dan Wang, Shuangning Yang, Yujie Xu, Guohui Qin, Chenhui Zhao, Qingyang Lei, Qitai Zhao, Yaqing Liu, Kaiyuan Guo, Songyun Ouyang, Ting Sun, Hongmin Wang, Feifei Fan, Na Han, Hong Liu, Hongjie Chen, Lijun Miao, Li Liu, Yuqing Duan, Wei Lv, Lihua Liu, Zhixin Zhang, Shundong Cang, Liping Wang, Yi Zhang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Anti-programmed cell death 1 (PD-1) antibody combined with chemotherapy simultaneously is regarded as the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) by current clinical guidelines. Different immune statuses induced by chemotherapy considerably affect the synergistic effects of the chemo-anti-PD-1 combination. Therefore, it is necessary to determine the optimal timing of combination treatment administration. Methods The dynamic immune status induced by chemotherapy was observed in paired peripheral blood samples of patients with NSCLC using flow cytometry and RNA sequencing. Ex vivo studies and metastatic lung carcinoma mouse models were used to evaluate immune activity and explore the optimal combination timing. A multicenter prospective clinical study of 170 patients with advanced NSCLC was performed to assess clinical responses, and systemic immunity was assessed using omics approaches. Results PD-1 expression on CD8 + T cells was downregulated on day 1 (D1) and D2, but recovered on D3 after chemotherapy administration, which is regulated by the calcium influx-P65 signaling pathway. Programmed cell death 1 ligand 1 expression in myeloid-derived suppressor cells was markedly reduced on D3. RNA sequencing analysis showed that T-cell function began to gradually recover on D3 rather than on D1. In addition, ex vivo and in vivo studies have shown that anti-PD-1 treatment on D3 after chemotherapy may enhance the antitumor response and considerably inhibit tumor growth. Finally, in clinical practice, a 3-day-delay sequential combination enhanced the objective response rate (ORR, 68%) and disease control rate (DCR, 98%) compared with the simultaneous combination (ORR=37%; DCR=81%), and prolonged progression-free survival to a greater extent than the simultaneous combination. The new T-cell receptor clones were effectively expanded, and CD8 + T-cell activity was similarly recovered. Conclusions A 3-day-delay sequential combination might increase antitumor responses and clinical benefits compared with the simultaneous combination.
Deep profiling deconstructs features associated with memory CD8+ T cell tissue residence
Authors: Milcah C Scott, Zoë Steier, Mark J Pierson, J Michael Stolley, Stephen D O'Flanagan, Andrew G Soerens, Sathi P Wijeyesinghe, Lalit K Beura, Gayathri Dileepan, Brandon J Burbach, Marco Künzli, Clare F Quarnstrom, Olivia C Ghirardelli Smith, Eyob Weyu, Sara E Hamilton, Vaiva Vezys, Alex K Shalek, David Masopust
Journal: Immunity (2024)
Neoadjuvant chemotherapy by liposomal doxorubicin boosts immune protection of tumor membrane antigens-based nanovaccine
Authors: Yang Chen, Hao Qin, Nan Li, Yaohua Wei, Yixuan Lin, Ronghui Deng, Hao Ding, Yuanyuan Lv, Tianyu Ma, Rong Li, Changhao Xiong, Guyu Zheng, Hanqing Chen, Jian Shi, Yuliang Zhao, Ruifang Zhao, Guangjun Nie
Journal: Cell Reports Medicine (2024)
Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors
Authors: Marjolein M G Kes, Francisco Morales-Rodriguez, Esther A Zaal, Terezinha de Souza, Natalie Proost, Marieke van de Ven, Marry M van den Heuvel-Eibrink, Jeroen W A Jansen, Celia R Berkers, Jarno Drost
Journal: Cell Reports Medicine (2024)
Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma
Authors: Tanjina Kader, Jia-Ren Lin, Clemens B. Hug, Shannon Coy, Yu-An Chen, Ino de Bruijn, Natalie Shih, Euihye Jung, Roxanne J. Pelletier, Mariana Lopez Leon, Gabriel Mingo, Dalia K. Omran, Jong Suk Lee, Clarence Yapp, Baby A. Satravada, Ritika Kundra, Yilin Xu, Sabrina Chan, Juliann B. Tefft, Jeremy L. Muhlich, Sarah H. Kim, Stefan M. Gysler, Judith Agudo, James R. Heath, Nikolaus Schultz, Charles W. Drescher, Peter K. Sorger, Ronny Drapkin, Sandro Santagata
Journal: Cancer Discovery (2024)

Abstract High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC-class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer.
Gender-affirming healthcare for incarcerated transgender and gender diverse people: an international scoping review
Authors: Chloe Fuller, Lin Tong, Martha Paynter
Journal: International Journal of Transgender Health (2024)

Background Transgender and gender diverse (TGD) people face unique challenges and have distinct needs while incarcerated. Gender-affirming healthcare improves mental health outcomes and supports gender transition. While in recent years, correctional institutions have begun to recognize and address the gender-affirming healthcare needs of TGD people, there is a lack of understanding and awareness of TGD people's experiences when accessing gender-affirming healthcare while incarcerated.