tbuckley/cabot-search huggingface dataset:
Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection
Authors: Baoling Ying, Tamarand L. Darling, Pritesh Desai, Chieh-Yu Liang, Igor P. Dmitriev, Nadia Soudani, Traci Bricker, Elena A. Kashentseva, Houda Harastani, Saravanan Raju, Meizi Liu, Aaron G. Schmidt, David T. Curiel, Adrianus C. M. Boon, Michael S. Diamond
Journal: Nature Immunology (2024)

Abstract A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8 + T cells before XBB.1.5 challenge resulted in loss of protection against upper and lower respiratory tract infection. Thus, nasally delivered vaccines stimulate mucosal immunity against emerging SARS-CoV-2 strains, and cross-reactive memory CD8 + T cells mediate protection against lung infection by antigenically distant strains in the setting of low serum levels of cross-reactive neutralizing antibodies.
Identification of allergens from <i>Aspergillus fumigatus</i>—Potential association with lung damage in asthma
Authors: Eva‐Maria Rick, Kerry Woolnough, Matthew Richardson, William Monteiro, Michelle Craner, Michelle Bourne, David John Cousins, Ines Swoboda, Andrew John Wardlaw, Catherine Helen Pashley
Journal: Allergy (2024)

Abstract Background Component‐resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1‐ or 2‐dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained. Methods We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus . Magnetic Dynabeads coupled with anti‐human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract. Results Of the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus ‐sensitized people with asthma, 23 non‐fungal‐sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose‐bisphosphate aldolase class II (FBA2) (33%), NAD‐dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens. Conclusion In conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins.
Human Omental Mature Adipocytes used as Paclitaxel Reservoir for Cell‐Based Therapy in Ovarian Cancer
Authors: Pacome K. Andele, Stefano Palazzolo, Giuseppe Corona, Isabella Caligiuri, Urska Kamensek, Maja Cemazar, Vincenzo Canzonieri, Flavio Rizzolio
Journal: Advanced Healthcare Materials (2024)

Primary human omental adipocytes and ovarian cancer(OC) cells establish a bidirectional communication in which tumor driven lipolysis is induced in adipocytes and the resulting fatty acids are delivered to cancer cells within the tumor microenvironment. Despite meaningful improvement in the treatment of OC, its efficacy is still limited by hydrophobicity and untargeted effects related to chemotherapeutics. Herein, omental adipocytes are firstly used as a reservoir for paclitaxel, named Living Paclitaxel Bullets (LPB) and secondly benefit from the established dialogue between adipocytes and cancer cells to engineer a drug delivery process that target specifically cancer cells. These results show that mature omental adipocytes can successfully uptake paclitaxel and deliver it to OC cells in a transwell coculture based in vitro model. In addition, the efficacy of this proof-of-concept has been demonstrated in vivo and induces a significant inhibition of tumor growth on a xenograft tumor model. The use of mature adipocytes can be suitable for clinical prospection in a cell-based therapy system, due to their mature and differentiated state, to avoid risks related to uncontrolled cell de novo proliferation capacity after the delivery of the antineoplastic drug as observed with other cell types when employed as drug carriers.
Fe<sub>3</sub>O<sub>4</sub>‐Incorporated Metal‐Organic Framework for Chemo/Ferroptosis Synergistic Anti‐Tumor via the Enhanced Chemodynamic Therapy
Authors: Yuliang Xu, Sihan Wang, Jincheng Xiong, Pimiao Zheng, Huixia Zhang, Shiqi Chen, Qiang Ma, Jianzhong Shen, Tony Velkov, Chongshan Dai, Haiyang Jiang
Journal: Advanced Healthcare Materials (2024)

Metal-organic framework (MOF)-based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, an enhanced chemodynamic anti-tumor therapy strategy by promoting the Fenton reaction by using core-shell zeolitic imidazolate framework-8 (ZIF-8)@Fe
Coagulant Protein‐Free Blood Coagulation Using Catechol‐Conjugated Adhesive Chitosan/Gelatin Double Layer
Authors: Soomi Kim, Keumyeon Kim, Mi‐Young Koh, Minjae Do, Moon Sue Lee, Ji Hyun Ryu, Haeshin Lee
Journal: Advanced Healthcare Materials (2024)

Since the discovery of polyphenolic underwater adhesion in marine mussels, researchers strive to emulate this natural phenomenon in the development of adhesive hemostatic materials. In this study, bio-inspired hemostatic materials that lead to pseudo-active blood coagulation, utilizing traditionally passive polymer matrices of chitosan and gelatin are developed. The two-layer configuration, consisting of a thin, blood-clotting catechol-conjugated chitosan (CHI-C) layer and a thick, barrier-functioning gelatin (Geln) ad-layer, maximizes hemostatic capability and usability. The unique combination of coagulant protein-free condition with CHI-C showcases not only coagulopathy-independent blood clotting properties (efficacy) but also exceptional clinical potential, meeting all necessary biocompatibility evaluation (safety) without inclusion of conventional coagulation triggering proteins such as thrombin or fibrinogen. As a result, the CHI-C/Geln is approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea) as a class II medical device. Hemostatic efficacy observed in multiple animal models further demonstrates the superiority of CHI-C/Geln sponges in achieving quick hemostasis compared to standard treatments. This study not only enriches the growing body of research on mussel-inspired materials but also emphasizes the potential of biomimicry in developing advanced medical materials, contributing a promising avenue toward development of readily accessible and affordable hemostatic materials.
Natural Polymer‐Polyphenol Bioadhesive Coacervate with Stable Wet Adhesion, Antibacterial Activity, and On‐Demand Detachment
Authors: Margarida M. A. Sacramento, Mariana B. Oliveira, José R.B. Gomes, João Borges, Benjamin R. Freedman, David J. Mooney, João M. M. Rodrigues, João F. Mano
Journal: Advanced Healthcare Materials (2024)

Medical adhesives are emerging as an important clinical tool as adjuvants for sutures and staples in wound closure and healing and in the achievement of hemostasis. However, clinical adhesives combining cytocompatibility, as well as strong and stable adhesion in physiological conditions, are still in demand. Herein, a mussel-inspired strategy is explored to produce adhesive coacervates using tannic acid (TA) and methacrylate pullulan (PUL-MA). TA|PUL-MA coacervates mainly comprise van der Waals forces and hydrophobic interactions. The methacrylic groups in the PUL backbone increase the number of interactions in the adhesives matrix, resulting in enhanced cohesion and adhesion strength (72.7 Jm
Data science opportunities of large language models for neuroscience and biomedicine
Authors: Danilo Bzdok, Andrew Thieme, Oleksiy Levkovskyy, Paul Wren, Thomas Ray, Siva Reddy
Journal: Neuron (2024)

Large language models (LLMs) are a new asset class in the machine-learning landscape. Here we offer a primer on defining properties of these modeling techniques. We then reflect on new modes of investigation in which LLMs can be used to reframe classic neuroscience questions to deliver fresh answers. We reason that LLMs have the potential to (1) enrich neuroscience datasets by adding valuable meta-information, such as advanced text sentiment, (2) summarize vast information sources to overcome divides between siloed neuroscience communities, (3) enable previously unthinkable fusion of disparate information sources relevant to the brain, (4) help deconvolve which cognitive concepts most usefully grasp phenomena in the brain, and much more.
Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021
Authors: Mairead Skally, Kathleen Bennett, Hilary Humphreys, Fidelma Fitzpatrick
Journal: Eurosurveillance (2024)

Background Community-associated Clostridioides difficile infections (CA-CDI) have increased worldwide. Patients with CDI-related symptoms occurring &lt; 48 hours after hospitalisation and no inpatient stay 12 weeks prior are classified as CA-CDI, regardless of hospital day attendances 3 months before CDI onset. Healthcare-associated (HA) CDIs include those with symptom onset ≥ 48 hours post hospitalisation. Aim To consider an incubation period more reflective of CDI, and changing healthcare utilisation, we measured how varying surveillance specifications to categorise patients according to their CDI origin resulted in changes in patients’ distribution among CDI origin categories. Methods New CDI cases between 2012–2021 from our hospital were reviewed. For patients with CA-CDI, hospital day attendances in the 3 months prior were recorded. CA-CDI patients with hospital day attendances and recently discharged CDI patients (RD-CDI; CDI onset 4–12 weeks after discharge) were combined into a new ‘healthcare-exposure’ category (HE-CDI). Time from hospitalisation to disease onset was varied and the midpoint between optimal and balanced cut-offs was used instead of 48 hours to categorise HA-CDI. Results Of 1,047 patients, 801 (76%) were HA-CDI, 205 (20%) CA-CDI and 41 (4%) were RD-CDI. Of the CA-CDI cohort, 45 (22%) met recent HE-CDI criteria and, when reassigned, reduced CA-CDI to 15%. Sensitivity analysis indicated a day 4 cut-off for assigning HA-CDI. Applying this led to 46 HA-CDI reassigned as CA-CDI. Applying both HE and day 4 criteria led to 72% HA-CDI, 20% CA-CDI, and 8% HE-CDI (previously RD-CDI). Conclusion CDI surveillance specifications reflecting healthcare exposure and an incubation period more characteristic of C. difficile may improve targeted CDI prevention interventions.
Encephalitis in HIV-negative immunodeficient patients: a prospective multicentre study, France, 2016 to 2019
Authors: Sophie Landré, Florence Ader, Olivier Epaulard, Pierre Tattevin, Jean Paul Stahl, Alexandra Mailles
Journal: Eurosurveillance (2024)

Background Data on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes. Aim We aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients. Methods Patients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson’s chi-squared test and Student’s t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome. Results ID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70–6.85). Conclusions Varicella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.
Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024
Authors: Mónica López-Lacort, Cintia Muñoz-Quiles, Ainara Mira-Iglesias, F Xavier López-Labrador, Beatriz Mengual-Chuliá, Carlos Fernández-García, Mario Carballido-Fernández, Ana Pineda-Caplliure, Juan Mollar-Maseres, Maruan Shalabi Benavent, Francisco Sanz-Herrero, Matilde Zornoza-Moreno, Jaime Jesús Pérez-Martín, Santiago Alfayate-Miguelez, Rocío Pérez Crespo, Encarnación Bastida Sánchez, Ana Isabel Menasalvas-Ruiz, Mª Cinta Téllez-González, Samuel Esquiva Soto, Carlos Del Toro Saravia, Iván Sanz-Muñoz, José María Eiros, Vanesa Matías Del Pozo, Marina Toquero-Asensi, Eliseo Pastor-Villalba, José Antonio Lluch-Rodrigo, Javier Díez-Domingo, Alejandro Orrico-Sánchez
Journal: Eurosurveillance (2024)

The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023–Jan 2024), where a universal immunisation programme began late September (coverage range: 79–99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.
Detection of Crimean–Congo haemorrhagic fever virus in Hyalomma marginatum ticks, southern France, May 2022 and April 2023
Authors: Célia Bernard, Charlotte Joly Kukla, Ignace Rakotoarivony, Maxime Duhayon, Frédéric Stachurski, Karine Huber, Carla Giupponi, Iyonna Zortman, Philippe Holzmuller, Thomas Pollet, Mélanie Jeanneau, Alice Mercey, Nathalie Vachiery, Thierry Lefrançois, Claire Garros, Vincent Michaud, Loic Comtet, Léa Despois, Philippe Pourquier, Caroline Picard, Alexandra Journeaux, Damien Thomas, Sabine Godard, Elodie Moissonnier, Stéphane Mely, Manon Sega, Delphine Pannetier, Sylvain Baize, Laurence Vial
Journal: Eurosurveillance (2024)

Crimean–Congo haemorrhagic fever (CCHF), a potentially severe zoonotic viral disease causing fever and haemorrhagic manifestations in humans. As the Crimean–Congo haemorrhagic fever virus (CCHFV) has been detected in ticks in Spain and antibodies against the virus in ruminant sera in Corsica, it was necessary to know more about the situation in France. In 2022–2023, CCHFV was detected in 155 ticks collected from horses and cattle in southern France.
p63 controls metabolic activation of hepatic stellate cells and fibrosis via an HER2-ACC1 pathway
Authors: Marcos F. Fondevila, Eva Novoa, Maria J. Gonzalez-Rellan, Uxia Fernandez, Violeta Heras, Begoña Porteiro, Tamara Parracho, Valentina Dorta, Cristina Riobello, Natalia da Silva Lima, Samuel Seoane, Maria Garcia-Vence, Maria P. Chantada-Vazquez, Susana B. Bravo, Ana Senra, Magdalena Leiva, Miguel Marcos, Guadalupe Sabio, Roman Perez-Fernandez, Carlos Dieguez, Vincent Prevot, Markus Schwaninger, Ashwin Woodhoo, Maria L. Martinez-Chantar, Robert Schwabe, Francisco J. Cubero, Marta Varela-Rey, Javier Crespo, Paula Iruzubieta, Ruben Nogueiras
Journal: Cell Reports Medicine (2024)

The p63 protein has pleiotropic functions and, in the liver, participates in the progression of nonalcoholic fatty liver disease (NAFLD). However, its functions in hepatic stellate cells (HSCs) have not yet been explored. TAp63 is induced in HSCs from animal models and patients with liver fibrosis and its levels positively correlate with NAFLD activity score and fibrosis stage. In mice, genetic depletion of TAp63 in HSCs reduces the diet-induced liver fibrosis. In vitro silencing of p63 blunts TGF-β1-induced HSCs activation by reducing mitochondrial respiration and glycolysis, as well as decreasing acetyl CoA carboxylase 1 (ACC1). Ectopic expression of TAp63 induces the activation of HSCs and increases the expression and activity of ACC1 by promoting the transcriptional activity of HER2. Genetic inhibition of both HER2 and ACC1 blunt TAp63-induced activation of HSCs. Thus, TAp63 induces HSC activation by stimulating the HER2-ACC1 axis and participates in the development of liver fibrosis.
Fast and Stable Antibacterial Coating of Photosensitive Aggregation‐Induced Emission Luminogens for Disinfection on Medical Devices
Authors: Mian Chen, Ruihua Dong, Jiayi Song, Jie Qi, Jiangjiang Zhang, Zheng Zhao, Wentian Zhang, Ying Li, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2024)

Aggregation-induced emission luminogens (AIEgens) are promising photosensitizers that have exhibited excellent antibacterial ability with abundant reactive oxygen species (ROS) generation. TTCPy-PF6 and TTCPy-Br are deposited on the surface of diverse solid substrates through plasma-assistant electrostatic self-assembly. The AIEgens-covered coating can effectively eliminate different pathogenic Gram-positive (G+) bacteria and even their multidrug-resistant (MDR) mutants with negligible side effects such as cytotoxicity, hemolysis, and inflammation. Moreover, the AIEgen-coated surface can maintain high stability for long-time antibacterial usage, which is dependent on the ROS-mediated disruption of the attached bacteria. The AIEgen-based coatings with broad surface applicability have many advantages in high antibacterial ability, great biocompatibility, and low possibility of antibiotic pollution. The robust antibacterial ability and excellent biological safety of the AIEgen-based coatings would be helpful for the disinfection of medical devices.
Multiomic molecular characterization of the response to combination immunotherapy in MSS/pMMR metastatic colorectal cancer
Authors: Shogo Takei, Yosuke Tanaka, Yi-Tzu Lin, Shohei Koyama, Shota Fukuoka, Hiroki Hara, Yoshiaki Nakamura, Yasutoshi Kuboki, Daisuke Kotani, Takashi Kojima, Hideaki Bando, Saori Mishima, Toshihide Ueno, Shinya Kojima, Masashi Wakabayashi, Naoya Sakamoto, Motohiro Kojima, Takeshi Kuwata, Takayuki Yoshino, Hiroyoshi Nishikawa, Hiroyuki Mano, Itaru Endo, Kohei Shitara, Akihito Kawazoe
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Immune checkpoint inhibitor (ICI) combinations represent an emerging treatment strategies in cancer. However, their efficacy in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer (CRC) is variable. Here, a multiomic characterization was performed to identify predictive biomarkers associated with patient response to ICI combinations in MSS/pMMR CRC for the further development of ICI combinations. Methods Whole-exome sequencing, RNA sequencing, and multiplex fluorescence immunohistochemistry of tumors from patients with MSS/pMMR CRC, who received regorafenib plus nivolumab (REGONIVO) or TAS-116 plus nivolumab (TASNIVO) in clinical trials were conducted. Twenty-two and 23 patients without prior ICI from the REGONIVO and TASNIVO trials were included in this study. A biomarker analysis was performed using samples from each of these studies. Results The epithelial-mesenchymal transition pathway and genes related to cancer-associated fibroblasts were upregulated in the REGONIVO responder group, and the G2M checkpoint pathway was upregulated in the TASNIVO responder group. The MYC pathway was upregulated in the REGONIVO non-responder group. Consensus molecular subtype 4 was significantly associated with response (p=0.035) and longer progression-free survival (p=0.006) in the REGONIVO trial. CD8 + T cells, regulatory T cells, and M2 macrophages density was significantly higher in the REGONIVO trial responders than in non-responders. Mutations in the POLE gene and patient response were significantly associated in the TASNIVO trial; however, the frequencies of other mutations or tumor mutational burden were not significantly different between responders and non-responders in either trial. Conclusions We identified molecular features associated with the response to the REGONIVO and TASNIVO, particularly those related to tumor microenvironmental factors. These findings are likely to contribute to the development of biomarkers to predict treatment efficacy for MSS/pMMR CRC and future immunotherapy combinations for treatment.
Federated machine learning in healthcare: A systematic review on clinical applications and technical architecture
Authors: Zhen Ling Teo, Liyuan Jin, Nan Liu, Siqi Li, Di Miao, Xiaoman Zhang, Wei Yan Ng, Ting Fang Tan, Deborah Meixuan Lee, Kai Jie Chua, John Heng, Yong Liu, Rick Siow Mong Goh, Daniel Shu Wei Ting
Journal: Cell Reports Medicine (2024)

Federated learning (FL) is a distributed machine learning framework that is gaining traction in view of increasing health data privacy protection needs. By conducting a systematic review of FL applications in healthcare, we identify relevant articles in scientific, engineering, and medical journals in English up to August 31st, 2023. Out of a total of 22,693 articles under review, 612 articles are included in the final analysis. The majority of articles are proof-of-concepts studies, and only 5.2% are studies with real-life application of FL. Radiology and internal medicine are the most common specialties involved in FL. FL is robust to a variety of machine learning models and data types, with neural networks and medical imaging being the most common, respectively. We highlight the need to address the barriers to clinical translation and to assess its real-world impact in this new digital data-driven healthcare scene.
Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease
Authors: Lilian von Werdt, Tina M. Binz, Ruth Tuura O’Gorman, Alenka Schmid, Nadja Naef, Valentin Rousson, Oliver Kretschmar, Rabia Liamlahi, Bea Latal, Melanie Ehrler
Journal: JAMA Network Open (2024)

Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population.