tbuckley/cabot-search huggingface dataset:
Unlocking the therapeutic potential of the NKG2A-HLA-E immune checkpoint pathway in T cells and NK cells for cancer immunotherapy
Authors: Yan Li, Zhu Li, Yisen Tang, Xiaomei Zhuang, Wanhua Feng, Patrick P C Boor, Sonja Buschow, Dave Sprengers, Guoying Zhou
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint blockade, which enhances the reactivity of T cells to eliminate cancer cells, has emerged as a potent strategy in cancer therapy. Besides T cells, natural killer (NK) cells also play an indispensable role in tumor surveillance and destruction. NK Group 2 family of receptor A (NKG2A), an emerging co-inhibitory immune checkpoint expressed on both NK cells and T cells, mediates inhibitory signal via interaction with its ligand human leukocyte antigen-E (HLA-E), thereby attenuating the effector and cytotoxic functions of NK cells and T cells. Developing antibodies to block NKG2A, holds promise in restoring the antitumor cytotoxicity of NK cells and T cells. In this review, we delve into the expression and functional significance of NKG2A and HLA-E, elucidating how the NKG2A-HLA-E axis contributes to tumor immune escape via signal transduction mechanisms. Furthermore, we provide an overview of clinical trials investigating NKG2A blockade, either as monotherapy or in combination with other therapeutic antibodies, highlighting the responses of the immune system and the clinical benefits for patients. We pay special attention to additional immune co-signaling molecules that serve as potential targets on both NK cells and T cells, aiming to evoke more robust immune responses against cancer. This review offers an in-depth exploration of the NKG2A-HLA-E pathway as a pivotal checkpoint in the anti-tumor responses, paving the way for new immunotherapeutic strategies to improve cancer patient outcomes.
Validation of the EuroSCAR Criteria for Acute Generalized Exanthematous Pustulosis: A Retrospective Cohort Study
Authors: Zaynah Awethe, Matthew Gallardo, Michael Goldenberg, Kelsey Nusbaum, Catherine Chung, Kristopher Fisher, Abraham M Korman, Benjamin H Kaffenberger
Journal: Journal of the American Academy of Dermatology (2024)
Characterizing Non‐Articular Pain at Early Rheumatoid Arthritis Diagnosis, Evolution over the First year of Treatment and Impact on Remission in a Prospective Real‐World Early Rheumatoid Arthritis Cohort
Authors: Charis F. Meng, Yvonne C. Lee, Orit Schieir, Marie‐France Valois, Margaret A. Butler, Gilles Boire, Glen Hazlewood, Hugues Allard‐Chamard, Carol Hitchon, Kuriya Bindee, Diane Tin, Carter Thorne, Louis Bessette, Janet Pope, Susan J. Bartlett, Vivian P. Bykerk
Journal: Arthritis & Rheumatology (2024)

Objective Our objective was to characterize nonarticular pain (NAP) at early rheumatoid arthritis (RA) diagnosis, the evolution over the first year of treatment, associations with active RA inflammation, and the impact on remission. Methods This real‐world, longitudinal multicenter cohort study observed participants with active early RA (symptoms &lt;1 year and Clinical Disease Activity Index [CDAI] &gt;2.8) enrolled between January 2017 and January 2022 who completed a body pain diagram over 1 year. Participants were grouped by prespecified definitions of NAP: (1) none, (2) regional, or (3) widespread. Rheumatologists performed joint counts. Descriptive statistics summarized the frequency and evolution of NAP patterns over 1 year. Chi‐square tests compared the proportions of tender and/or swollen joints by the presence of pain in each NAP section. Multiadjusted generalized estimating equations regression models estimated associations of NAP patterns with remission outcomes. Results Participants (N = 392) were 70% female, with a mean ± SD age of 56 ± 14 years and mean ± SD symptoms duration of 5.1 ± 2.7 months. More than half reported NAP at baseline, with most (73%) presenting with regional NAP. Common patterns of regional NAP were axial (40%) and pain in upper quadrants (17%). A total of 43% of those with regional NAP persisted or worsened over 1 year, whereas 73% of those with widespread NAP resolved or improved. Joint inflammation was more frequently reported in areas with NAP versus areas without NAP. Regional and widespread NAP were associated with lower odds of reaching CDAI remission (adjusted odds ratio 0.42, 95% confidence interval 0.26–0.70 and adjusted odds ratio 0.30, 95% confidence interval 0.12–0.74), respectively. Conclusion Regional NAP is common and persistent in early RA and impacts remission. RA activity may contribute to NAP. More attention to NAP in RA care is warranted. image
Targeting long non‐coding <scp>RNA H19</scp> in Subchondral Bone Osteocytes Alleviates Cartilage Degradation in Osteoarthritis
Authors: Rongliang Wang, Babak Mehrjou, Dorsa Dehghan‐Banian, Belle Yu Hsuan Wang, Qiangqiang Li, Shuai Deng, Chuanhai Liu, Zhe Zhang, Yanlun Zhu, Haixing Wang, Dan Li, Xiaomin Lu, Jack Chun Yiu Cheng, Michael Tim Yun Ong, Hon Fai Chan, Gang Li, Paul K. Chu, Wayne Yuk Wai Lee
Journal: Arthritis & Rheumatology (2024)

Introduction Emerging evidence suggests long non‐coding RNA (lncRNA) H19 is associated with osteoarthritis (OA) pathology. However, how H19 contributes to OA has not been reported. This study aims to investigate the biological function of H19 in OA subchondral bone remodeling and OA progression. Methods Clinical joint samples and OA animal models induced by medial meniscus destabilization (DMM) surgery were used to verify the causal relationship between osteocyte H19 and OA subchondral bone and cartilage changes. MLO‐Y4 osteocyte cells subjected to fluid shear stress were used to verify the mechanism underlying H19‐mediated mechano‐response. Finally, the antisense oligonucleotide (ASO) against H19 was delivered to mice knee joints by magnetic metal‐organic framework (MMOF) nanoparticles in order to develop a site‐specific delivery method for targeting osteocyte H19 for OA treatment. Results Both clinical OA subchondral bone and wildtype mice with DMM‐induced OA exhibit aberrant higher subchondral bone mass with more H19 expressing osteocytes. On the contrary, osteocyte‐specific deletion of H19 mice is less vulnerable to DMM‐induced OA phenotype. In MLO‐Y4 cells, H19‐mediated osteocyte mechano‐response through PI3K/AKT/GSK3 signals activation by EZH2‐induced H3K27me3 regulation on PP2A inhibition. Targeted inhibition of H19 (using ASO‐loaded MMOF) substantially alleviates subchondral bone remodeling and OA phenotype. Discussion In summary, our results provide new evidence that the elevated H19 expression in osteocytes may contribute to aberrant subchondral bone remodeling and OA progression. H19 appears to be required for the osteocyte response to mechanical stimulation, and targeting H19 represents a new promising approach for OA treatment. image
Corrigendum to ‘Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy’ [Biomaterials 314 (2025) 122871]
Authors: Haimei Li, Zichen Wang, Yulin Hu, Guangqin He, Liang Huang, Yi Liu, Zhong Lin Wang, Peng Jiang
Journal: Biomaterials (2024)
Bioprinting of Aptamer‐Based Programmable Bioinks to Modulate Multiscale Microvascular Morphogenesis in 4D
Authors: Deepti Rana, Vincent R. Rangel, Prasanna Padmanaban, Vasileios D. Trikalitis, Ajoy Kandar, Hae‐Won Kim, Jeroen Rouwkema
Journal: Advanced Healthcare Materials (2024)

Dynamic growth factor presentation influences how individual endothelial cells assemble into complex vascular networks. Here, programmable bioinks are developed that facilitate dynamic vascular endothelial growth factor (VEGF) presentation to guide vascular morphogenesis within 3D-bioprinted constructs. Aptamer's high affinity is leveraged for rapid VEGF sequestration in spatially confined regions and utilized aptamer-complementary sequence (CS) hybridization to tune VEGF release kinetics temporally, days after bioprinting. It is shown that spatial resolution of programmable bioink, combined with CS-triggered VEGF release, significantly influences the alignment, organization, and morphogenesis of microvascular networks in bioprinted constructs. The presence of aptamer-tethered VEGF and the generation of instantaneous VEGF gradients upon CS-triggering restricted hierarchical network formation to the printed aptamer regions at all spatial resolutions. Network properties improved as the spatial resolution decreased, with low-resolution designs yielding the highest network properties. Specifically, CS-treated low-resolution designs exhibited significant vascular network remodeling, with an increase in vessel density(1.35-fold), branching density(1.54-fold), and average vessel length(2.19-fold) compared to non-treated samples. The results suggest that CS acts as an external trigger capable of inducing time-controlled changes in network organization and alignment on-demand within spatially localized regions of a bioprinted construct. It is envisioned that these programmable bioinks will open new opportunities for bioengineering functional, hierarchically self-organized vascular networks within engineered tissues.
Functional Assessment of a Bioprinted Immuno‐Mimetic Peyer's Patch Recapitulating Gut‐Associated Lymphoid Tissue
Authors: Jongho Park, Gihyun Lee, Je‐Kyun Park
Journal: Advanced Healthcare Materials (2024)

Gut immune models have attracted much interest in better understanding the microbiome in the human gastrointestinal tract. The gut-associated lymphoid tissue (GALT) has complex structures that interact with microorganisms, including the intestinal monolayer as a physiological barrier and the Peyer's patch (PP) involved in the immune system. Although essential for studying GALT and microbiome interactions, current research often uses simplified models that only recapitulate some components. In this study, GALT is recapitulated to consider the morphology and function of lymphocyte-containing PP beneath the intestinal monolayer and to analyze microbiome interaction. Using the bioprinting technique, a dome-shaped structure array for the PP is fabricated, and epithelial cells are cocultured to form the intestinal monolayer. The developed GALT model shows stable cell differentiation on the hydrogel while exhibiting durability against lipopolysaccharides. It also exhibits increased responsiveness to Escherichia coli, as indicated by elevated nitric oxide levels. In addition, the model underscores the critical role of GALT in maintaining bacterial coexistence and in facilitating immune defense against foreign antigens through the secretion of immunoglobulin A by lymphocyte spheroids. The proposed GALT model is expected to provide significant insights into studying the gut-immune system complexity and microbiome.
K<sub>2</sub>FeO<sub>4</sub>‐Enhanced Photodynamic Therapy of Breast Cancer via In Situ Synthesis of Fe<sub>2</sub>O<sub>3</sub> and O<sub>2</sub>
Authors: Yi Sun, Xin Peng, Yudong Guan, Tong Su, Zezun Xie, Ziying Wu, Yongxuan Long, Huihui Zhu, Jie Shao, Xiaoli Mai, Xuzhi Shi, Tingting Wu, Zhaogang Teng, Bing Zhang, Kun Chen, Xiaoyan Xin
Journal: Advanced Healthcare Materials (2024)

Photodynamic Therapy (PDT) offers a promising minimally invasive treatment for breast cancer, but its efficacy is limited by the hostile tumor microenvironment (TME), including hypoxia and high glutathione (GSH) levels. Although various strategies to improve oxygen concentration or reduce reactive oxygen species (ROS) resistance for enhanced PDT have been explored, they typically require intricate design and complex synthesis of multifunctional nanocarriers. Thus, this study introduces a facile K
Fluorocarbon‐Functionalized Polymerization‐Induced Self‐Assembly Nanoparticles Alleviate Hypoxia to Enhance Sonodynamic Cancer Therapy
Authors: Zhikang Xu, Xuanxuan Zhang, Qianyun Shan, Wei Zhu, Shangxu Jiang, Rumei Li, Xiaojin Wu, Meng Huo, Bin Ying, Chen Chen, Xiaoting Chen, Kai Zhang, Weiyu Chen, Jian Chen
Journal: Advanced Healthcare Materials (2024)

Sonodynamic therapy (SDT) is an ultrasound-based, noninvasive cancer treatment that targets tumor cells by triggering reactive oxygen species production. However, the limited accumulation of sonosensitizers and the insufficient supply of O
Real-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis
Authors: Sophie Nagle, Yann Nguyen, Mary-Jane Guerry, Thomas Quemeneur, Dimitri Titeca-Beauport, Thomas Crépin, Rafik Mesbah, Idris Boudhabhay, Grégory Pugnet, Céline Lebas, Antoine Néel, Alexandre Karras, Eric Hachulla, Juliette Woessner, Vincent Pestre, Raphaël Borie, Stephane Vinzio, Jean-Baptiste Gouin, Sara Melboucy-Belkhir, Roderau Outh, Benjamin Subran, Mathieu Gerfaud-Valentin, Sebastien Humbert, Philippe Kerschen, Yurdagul Uzunhan, Tiphaine Goulenok, Maxime Beydon, Nathalie Costedoat-Chalumeau, Xavier Puechal, Benjamin Terrier
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background</h3> The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC. <h3>Methods</h3> We conducted a retrospective, multicentre study comparing PEXIVAS redGC with standGC in patients with AAV. The primary composite outcome was the occurrence of death, ESKD, AAV progression before remission or relapse within the 12 months following induction. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Factors associated with the occurrence of the primary outcome were estimated. <h3>Results</h3> A total of 234 patients were included. The primary composite outcome occurred in 42/126 (33%) patients with redGC versus 20/108 (19%) with standGC. In unweighted multivariable analysis and in weighted analysis, redGC was independently associated with the primary outcome but not with death or ESKD. Among redGC-treated patients, those with serum creatinine&gt;300 µmol/L were more likely to achieve the primary outcome. RTX-treated patients who received redGC were more likely to experience death or ESKD and to achieve the primary outcome. <h3>Conclusion</h3> In this study of patients with AAV primarily treated with RTX, redGC was associated with an increased risk of the primary outcome consisting of death, ESKD, AAV progression before remission or relapse.
Highly pathogenic avian influenza (HPAI) H5 virus exposure in domestic cats and rural stray cats, the Netherlands, October 2020 to June 2023
Authors: Mirjam B H M Duijvestijn, Nancy N M P Schuurman, Johannes C M Vernooij, Michelle A J M van Leeuwen, Judith M A van den Brand, Jaap A Wagenaar, Frank J M van Kuppeveld, Herman F Egberink, Cornelis A M de Haan, Josanne H Verhagen
Journal: Eurosurveillance (2024)

BackgroundHighly pathogenic avian influenza (HPAI) H5Nx and human H1N1pdm2009 influenza viruses can infect cats. Infections in cats may result in viral adaptations or recombinant viruses, which may facilitate zoonotic transfer.AimWe aimed to investigate the presence of HPAI H5 clade 2.3.4.4 and H1 influenza viruses and antibodies to these viruses in domestic and rural stray cats in the Netherlands and factors associated with exposure.MethodsSera from stray and domestic cats, sampled 2020-2023, were analysed by ELISA and confirmed by hemagglutination inhibition assay (HAI) and pharyngeal swabs and lung tissue for influenza A virus by RT-qPCR.ResultsIn 701 stray cats, 83 (11.8%; 95% confidence interval (CI): 9.5-14.5) sera were positive for HPAI H5 and 65 findings were confirmed. In HAI, two sera were positive for both HPAI H5 and H1. In 871 domestic cats, four (0.46%; 95% CI: 0.13-1.2) sera were HPAI H5 positive and none were confirmed but 40 (4.6%; 95% CI: 3.3-6.2) sera were seropositive for H1 and 26 were confirmed. Stray cats living in nature reserves (odds ratio (OR) = 5.4; 95% CI: 1.5-20.1) and older cats (OR = 3.8; 95% CI: 2.7-7.1) were more likely to be HPAI H5 seropositive. No influenza A virus was detected in 230 cats.ConclusionThe higher HPAI H5 seroprevalence in stray cats compared with domestic cats suggests more frequent viral exposure, most likely due to foraging on wild birds. In contrast, exposure to H1 was more common in domestic cats compared with stray cats.
Effectiveness of the autumn 2023 COVID-19 vaccine dose in hospital-based healthcare workers: results of the VEBIS healthcare worker vaccine effectiveness cohort study, seven European countries, season 2023/24
Authors: Camelia Savulescu, Albert Prats-Uribe, Kim Brolin, Anneli Uusküla, Colm Bergin, Catherine Fleming, Rita Murri, Viesturs Zvirbulis, Dace Zavadska, Vania Gaio, Corneliu P Popescu, Raluca Hrisca, Maria Cisneros, Miriam Latorre-Millán, Liis Lohur, Jonathan McGrath, Lauren Ferguson, Katleen De Gaetano Donati, Ilze Abolina, Dagne Gravele, Ausenda Machado, Simin-Aysel Florescu, Mihaela Lazar, Pilar Subirats, Laura Clusa Cuesta, Jacklyn Sui, Claire Kenny, Rosaria Santangelo, Dainis Krievins, Elza Anna Barzdina, Camila Valadas Henriques, Alma Gabriela Kosa, Saftica-Mariana Pohrib, Carmen Muñoz-Almagro, Ana Milagro, Sabrina Bacci, Anthony Nardone
Journal: Eurosurveillance (2024)

COVID-19 vaccination recommendations include healthcare workers (HCWs). We measured COVID-19 vaccine effectiveness (CVE) of the autumn 2023 dose against laboratory-confirmed SARS-CoV-2 infection in a prospective cohort study of 1,305 HCWs from 13 European hospitals. Overall CVE was 22% (95% CI: −17 to 48), 49% (95% CI: −8 to 76) before and −11% (95% CI: −84 to 34) after the start of BA.2.86/JN.1 predominant circulation. Autumn 2023 COVID-19 vaccination led to a moderate-to-low reduction in SARS-CoV-2 infection incidence in HCWs. Monitoring of CVE is crucial for COVID-19 prevention.
Enhanced echovirus 11 genomic surveillance in neonatal infections in Spain following a European alert reveals new recombinant forms linked to severe cases, 2019 to 2023
Authors: Maria Dolores Fernandez-Garcia, Nerea Garcia-Ibañez, Juan Camacho, Almudena Gutierrez, Laura Sánchez García, Cristina Calvo, Antonio Moreno-Docón, Ana Isabel Menasalvas, Antonio Medina, Mercedes Perez-Ruiz, Maria Carmen Nieto Toboso, Carmen Muñoz-Almagro, Cristian Launes, Carla Berengua, María Cabrerizo
Journal: Eurosurveillance (2024)

Background In 2023, a European alert was issued regarding an increase in severe enterovirus (EV) neonatal infections associated with echovirus 11 (E11) new lineage 1. Aim To analyse E11-positive cases between 2019 and 2023 to investigate whether the new lineage 1 circulated in Spain causing severe neonatal infections. Methods EV-positive samples from hospitalised cases are sent for typing to the National Reference Enterovirus Laboratory. Available samples from 2022–23 were subjected to metagenomic next-generation sequencing. Results Of 1,288 samples genotyped, 103 were E11-positive (98 patients: 6 adults, 33 neonates, 89 children under 6 years; male to female ratio 1.9). E11 detection rate was similar before and after detection of the new lineage 1 in Spain in June 2022 (9.7% in 2019 vs 10.6% in 2023). The proportion of E11-infected ICU-admitted neonates in 2019–2022 (2/7) vs 2022–2023 (5/12) did not significantly differ (p = 0.65). In severe neonatal infections, 4/7 E11 strains were not linked to the new lineage 1. The three novel E11 recombinant genomes were associated with severe (n = 2) and non-severe (n = 1) cases from 2022–2023 and clustered outside the new lineage 1. Coinfecting pathogenic viruses were present in four of 10 E11-positive samples. Conclusion The emergence of the new lineage 1 is not linked with an increase in incidence or severity of neonatal E11 infections in Spain. The detection of two novel E11 recombinants associated with severe disease warrants enhancing genomic and clinical surveillance.
A cluster of Mayaro virus infections in a film team returning from Suriname, February 2024
Authors: Hans Martin Orth, Stefanie Pfau, Martin Gabriel, Stephan Günther, Dennis Tappe, Daniel Hornuss, Irmela Müller-Stöver, Martha Charlotte Holtfreter, Tom Luedde, Jonas Schmidt-Chanasit, Torsten Feldt
Journal: Eurosurveillance (2024)

Mayaro virus is endemic to the tropical Americas, where the incidence is currently increasing. Like other viruses of the Semliki Forest virus serocomplex, such as Alphavirus chikungunya , symptomatic infections are typically characterised by an acute febrile disease followed by long-lasting arthralgia. Cases in travellers are rarely reported but may be underdiagnosed. We report on four people who diagnosed with Mayaro fever after working in remote areas of Suriname as members of a film team.
Integrating indicator-based and event-based surveillance data for risk mapping of West Nile virus, Europe, 2006 to 2021
Authors: Kyla Serres, Diana Erazo, Garance Despréaux, María F Vincenti-González, Wim Van Bortel, Elena Arsevska, Simon Dellicour
Journal: Eurosurveillance (2024)

Background West Nile virus (WNV) has an enzootic cycle between birds and mosquitoes, humans being incidental dead-end hosts. Circulation of WNV is an increasing public health threat in Europe. While detection of WNV is notifiable in humans and animals in the European Union, surveillance based on human case numbers presents some limitations, including reporting delays. Aim We aimed to perform risk mapping of WNV circulation leading to human infections in Europe by integrating two types of surveillance systems: indicator-based and event-based surveillance. Methods For indicator-based surveillance, we used data on human case numbers reported to the European Centre for Disease Prevention and Control (ECDC), and for event-based data, we retrieved information from news articles collected through an automated biosurveillance platform. In addition to these data sources, we also used environmental data to train ecological niche models to map the risk of local WNV circulation leading to human infections. Results The ecological niche models based on both types of surveillance data highlighted new areas potentially at risk of WNV infection in humans, particularly in Spain, Italy, France and Greece. Conclusion Although event-based surveillance data do not constitute confirmed occurrence records, integrating both indicator-based and event-based surveillance data proved useful. These results underscore the potential for a more proactive and comprehensive strategy in managing the threat of WNV in Europe by combining indicator- and event-based and environmental data for effective surveillance and public health response.
Predicting deterioration in dengue using a low cost wearable for continuous clinical monitoring
Authors: Damien Keng Ming, John Daniels, Ho Quang Chanh, Stefan Karolcik, Bernard Hernandez, Vasileios Manginas, Van Hao Nguyen, Quang Huy Nguyen, Tu Qui Phan, Thi Hue Tai Luong, Huynh Trung Trieu, Alison Helen Holmes, Vinh Tho Phan, Pantelis Georgiou, Sophie Yacoub
Journal: npj Digital Medicine (2024)

Close vital signs monitoring is crucial for the clinical management of patients with dengue. We investigated performance of a non-invasive wearable utilising photoplethysmography (PPG), to provide real-time risk prediction in hospitalised individuals. We performed a prospective observational clinical study in Vietnam between January 2020 and October 2022: 153 patients were included in analyses, providing 1353 h of PPG data. Using a multi-modal transformer approach, 10-min PPG waveform segments and basic clinical data (age, sex, clinical features on admission) were used as features to continuously forecast clinical state 2 h ahead. Prediction of low-risk states (17,939/80,843; 22.1%), defined by NEWS2 and mSOFA < 6, was associated with an area under the precision-recall curve of 0.67 and an area under the receiver operator curve of 0.83. Implementation of such interventions could provide cost-effective triage and clinical care in dengue, offering opportunities for safe ambulatory patient management.