tbuckley/cabot-search huggingface dataset:
Recombinant Hypoallergenic Cat Allergy Vaccines
Authors: Daria Trifonova, Mirela Curin, Margarete Focke‐Tejkl, Zicheng Liu, Kristina Borochova, Pia Gattinger, Marianne van Hage, Hans Grönlund, Renata Kiss, Huey‐Jy Huang, Walter Keller, Ksenja Riabova, Antonina Karsonova, Michael Kundi, Inna Tulaeva, Daria Fomina, Alexander Karaulov, Rudolf Valenta
Journal: Allergy (2025)

Molecular forms of allergen-specific immunotherapy (AIT) for cat allergy are needed. Fel d 1, Fel d 4, and Fel d 7 are the most important cat allergens. IgE epitopes of Fel d 4 and Fel d 7 were mapped by blocking allergic patients' IgE binding with allergen peptide-specific antisera. Five recombinant fusion proteins (PreS-Cat 1-PreS-Cat 5) each containing hepatitis B virus (HBV)-derived PreS as an immunological carrier and non-allergenic peptides from the IgE binding sites of Fel d 1, Fel d 4, and Fel d 7 were expressed in Escherichia coli, purified, and characterized by mass spectrometry, circular dichroism (CD), and size exclusion chromatography. ImmunoCAP and basophil activation experiments demonstrated the hypoallergenic activity of PreS-Cat 1-5. The ability of PreS-Cat 1-5 to induce IgE-blocking antibodies in rabbits was compared to three licensed allergen extract-based AIT vaccines. PreS-Cat 1-5-specific IgG antibodies were tested for inhibition of allergen-specific IgE binding and specific basophil activation. T cell activation and induction of specific cytokine secretion by PreS-Cat proteins were compared with cat allergens in PBMC cultures. Recombinant hypoallergenic, biochemically and structurally defined PreS-Cat 1-5 were obtained. Two subcutaneous immunizations of rabbits with PreS-Cat 1-5 induced equal (Fel d 1) or better (Fel d 4 and Fel d 7) antibodies (PreS-Cat 5 > PreS-Cat 1 > PreS-Cat 3) blocking allergic patients' IgE binding to cat allergens than six to fifteen immunizations with allergen extract-based vaccines. PreS-Cat-specific antibodies strongly inhibited specific basophil activation. PreS-Cat 5 > PreS-Cat 1 induced significantly more IL-10 in cultured PBMCs from cat allergic patients than cat allergens. PreS-Cat 5 and PreS-Cat 1 are highly promising molecular vaccine candidates for AIT of cat allergy, combining Fel d 1-, Fel d 4-, and Fel d 7-peptides in single PreS fusion proteins.
Flow Cytometry‐Assisted Analyses of Individual Human Basophils, Mast Cells and T Cells in the Diagnosis of Immediate Drug Hypersensitivity: A Review
Authors: Jessy Elst, Christel Mertens, Michel Van Houdt, Marie‐Line M. van der Poorten, Athina L. Van Gasse, Alessandro Toscano, Michiel Beyens, Daniel Yerly, Margo M. Hagendorens, Vito Sabato, Oliver Hausmann, Didier G. Ebo
Journal: Allergy (2025)

Immediate drug hypersensitivity reactions (IDHRs) pose significant diagnostic challenges, often requiring potentially hazardous drug challenge testing (DCT). Flow cytometry-based cellular tests including the basophil activation test (BAT), the mast cell activation test (MAT) and the T cell activation test (TAT) offer promising alternatives to reduce DCT reliance. While these tests are still in development, they demonstrate potential to compete with skin tests by providing superior diagnostic performance and improved patient safety by reducing the need for DCT. Furthermore, it is encouraging that these flow cytometry-based tests are also suitable for challenging populations, such as children. Despite requiring specialised infrastructure, these tests have the potential to be cost-effective when performed in reference centres and may offer unique mechanistic insights into immediate drug hypersensitivity reactions. However, further research is needed to validate their reliability, address pharmaceutical-specific testing considerations, and potentially integrate them into clinical guidelines.
Border Region Emergency Medical Services in Migrant Emergency Care
Authors: Christine Crudo Blackburn, Mayra Rico, Lauren Knight, Brandy Sebesta, Kirk Niekamp
Journal: JAMA Network Open (2025)

Focusing on the US southern land border only through a security lens minimizes the impact of security infrastructure and migrant health needs on local emergency medical services (EMS) clinicians. To explore the perceptions and experiences regarding the impact of migration on EMS clinicians in the communities of study. This qualitative study included in-depth interviews with fire department-based EMS clinicians in 3 Arizona communities on the Mexico border from June 23 to 27, 2024. Interviews were conducted 1-on-1 while clinicians were on shift. Participants were recruited with the help of fire department leadership in each fire department. This was an exploratory study designed to identify how EMS clinicians perceive the influence of migration in the study communities. Thematic analysis was conducted using inductive, latent coding. The 67 participants were predominately male (62 [93%]), which is reflective of the EMS profession in the border region. Years of experience as EMS clinicians were fairly evenly distributed: 5 years or less (14 [21%]), 6 to 10 years (18 [27%]), 11 to 20 years (18 [27%]), and 21 or more years (17 [25%]). EMS clinicians in these communities reported serving multiple populations, often responding to complex calls, and experiencing limited downtime and mass casualty-like scenarios when there are high numbers of border crossings. Participants perceived that the local EMS system was strained, and occasionally overwhelmed, and that greater financial support from the federal government was necessary. The findings of this qualitative study of EMS clinicians suggest that migration has a complex, multidimensional influence on EMS clinicians in the border region. Deterrence-focused actions have not decreased the number of crossings but rather pushed migrants to cross in more dangerous ways, leading to more injuries and deaths. Our findings suggest that the strain placed on local EMS clinicians is unsustainable and may be exacerbated by increased deterrence-based policies. Instead, border-region EMS clinicians need increased federal funding to support their work.
Psychiatric genetics in the diverse landscape of Latin American populations
Authors: Estela M Bruxel, Diego L Rovaris, Sintia I Belangero, Gabriela Chavarría-Soley, Alfredo B Cuellar-Barboza, José J Martínez-Magaña, Sheila T Nagamatsu, Caroline M Nievergelt, Diana L Núñez-Ríos, Vanessa K Ota, Roseann E Peterson, Laura G Sloofman, Amy M Adams, Elinette Albino, Angel T Alvarado, Diego Andrade-Brito, Paola Y Arguello-Pascualli, Cibele E Bandeira, Claiton H D Bau, Cynthia M Bulik, Joseph D Buxbaum, Carolina Cappi, Nadia S Corral-Frias, Alejo Corrales, Fabiana Corsi-Zuelli, James J Crowley, Renata B Cupertino, Bruna S da Silva, Suzannah S De Almeida, Juan F De la Hoz, Diego A Forero, Gabriel R Fries, Joel Gelernter, Yeimy González-Giraldo, Eugenio H Grevet, Dorothy E Grice, Adriana Hernández-Garayua, John M Hettema, Agustín Ibáñez, Iuliana Ionita-Laza, Maria Claudia Lattig, Yago C Lima, Yi-Sian Lin, Sandra López-León, Camila M Loureiro, Verónica Martínez-Cerdeño, Gabriela A Martínez-Levy, Kyle Melin, Daniel Moreno-De-Luca, Carolina Muniz Carvalho, Ana Maria Olivares, Victor F Oliveira, Rafaella Ormond, Abraham A Palmer, Alana C Panzenhagen, Maria Rita Passos-Bueno, Qian Peng, Eduardo Pérez-Palma, Miguel L Prieto, Panos Roussos, Sandra Sanchez-Roige, Hernando Santamaría-García, Flávio M Shansis, Rachel R Sharp, Eric A Storch, Maria Eduarda A Tavares, Grace E Tietz, Bianca A Torres-Hernández, Luciana Tovo-Rodrigues, Pilar Trelles, Eva M Trujillo-ChiVacuan, Maria M Velásquez, Fernando Vera-Urbina, Georgios Voloudakis, Talia Wegman-Ostrosky, Jenny Zhen-Duan, Hang Zhou, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Paola Giusti-Rodríguez, Janitza L Montalvo-Ortiz
Journal: Nature Genetics (2025)
Three‐Dimensional Dynamic Blood‐Brain Barrier Model Incorporating Native Cell Culture Systems Based on Shape Memory Biomaterials
Authors: Wenjing Ta, Jianxiang Wang, Anqi Zheng, Ye Jia, Jin Liu, Wen Lu, Jie Zhang
Journal: Advanced Healthcare Materials (2025)

An engineered three-dimensional (3D) dynamic in vitro blood-brain barrier (BBB) model with vascular-like architecture and fluid shear forces is integrated. The model is comprised of a supply pool, fluid transport pump, flow chamber, 3D cell-scaffold, and receiving pool. The flow chamber is designed with three parallel fluid channels connected to the pump and receiving pool, thus simplifying operation and facilitating assembly with standard instruments. A disposable 3D cell-scaffold made from biocompatible shape memory material can realize configuration transformation from 2D planar structure for cell seeding to 3D tubular structure for cell culture at physiological temperature, which provides cells convenient seeding and desirable attachment. The barrier function of this model is characterized: the maximum transendothelial electrical resistance value is 523 Ω cm2 for co-cultured cell model; the apparent permeability coefficient of phenol red is in the range of 2.8-3.8 × 10-6 cm-1s; highly expressed BBB-related proteins (VE-cadherin, Occludin, Claudin-5, ZO-1 and P-gp) and the polarized transport of P-gp ligand rhodamine 123 are shown. Further, the differentiating transport characteristics of seven model drugs across BBB are presented using the integrated model. In summary, a high-fidelity 3D dynamic BBB model, suitable for researching drug trafficking across BBB and developing therapeutics for brain diseases, is constructed.
Loss of conserved long non-coding RNA MIR503HG leads to altered NOTCH pathway signalling and left ventricular non-compaction cardiomyopathy
Authors: João P Monteiro, Diptarka Saha, Ana-Mishel Spiroski, Saiba Mahesh, Peter Kaltzis, Abhijit Nadavallil, Vaibhao Janbandhu, Nicholas J Murray, Francesco Severi, Azzurra Laura De Pace, Sandra Sánchez-Esteban, Julie Rodor, Abdelaziz Beqqali, Matthew Bennett, Kevin Stewart, Adrian Thomson, Patrick W F Hadoke, Dyana Markose, John R Wilson-Kanamori, Neil C Henderson, Dónal O’Carroll, Thomas Quertermous, Richard P Harvey, Gonzalo del Monte-Nieto, Andrew H Baker
Journal: Cardiovascular Research (2025)

Abstract Aims The highly conserved long non-coding RNA (lncRNA) MIR505HG has been primarily recognized as a precursor for microRNAs (miR)-424 and miR-503. However, studies have since demonstrated that MIR503HG has distinct functions from its associated miRNAs, playing important roles in cell proliferation, invasion, apoptosis, and differentiation. While these miRNAs are known to influence cardiomyocyte differentiation, the specific role of MIR503HG in heart development remains unexplored. We seek to determine how MIR503HG deletion impacts ventricular chamber development and to identify underlying molecular mechanisms. Methods and results To study the role of the lncRNA in vivo, we generated a functional MIR503HG knockout mouse model (MIR503HG−/−) using a synthetic polyadenylation signal to terminate MIR503HG transcription without affecting miR-424/503 expression. We performed morphological analyses on embryonic and adult hearts using microCT along with cardiac functional analysis via transthoracic echocardiography. We further apply single-nuclei RNA sequencing (snRNA-seq) on adult hearts to identify potential molecular mechanisms underlying the observed phenotypes. Functional deletion of MIR503HG alone was associated with reduced compact myocardium thickness and increased trabecular myocardium in the left ventricle (LV) at embryonic day 17.5 compared to wild-type mice, indicating a LV non-compaction (LVNC) phenotype. Moreover, adult MIR503HG−/− mutant hearts showed increased trabecular complexity, impaired LV relaxation, and mitral valve regurgitation. SnRNA-seq further revealed altered expression of several genes associated with cardiomyocyte function and LVNC, including Actc1, Mib1, Mybpc3, and Myh7. Lastly, Notch1 activity was also significantly increased in mutant hearts which has been previously associated with LVNC. Conclusion MIR503HG plays a role in ventricular chamber development, and its deletion leads to an LVNC phenotype independent of the miRNA cluster within its locus, highlighting its importance in cardiac development and disease. We further suggest that abnormal Notch1 activity may underpin the LVNC phenotype presented.
Cell-free DNA Fragmentomics Assay to Discriminate the Malignancy of Breast Nodules and Evaluate Treatment Response
Authors: Jiaqi Liu, Yalun Li, Wanxiangfu Tang, Tianyi Qian, Lijun Dai, Ziqi Jia, Heng Cao, Chenghao Li, Yuchen Liu, Yansong Huang, Jiang Wu, Dongxu Ma, Guangdong Qiao, Hua Bao, Shuang Chang, Dongqin Zhu, Shanshan Yang, Xuxiaochen Wu, Xue Wu, Hengyi Xu, Hongyan Chen, Yang Shao, Xiang Wang, Zhihua Liu, Jianzhong Su
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract The fragmentomics-based cell­free DNA (cfDNA) assays have recently illustrated prominent abilities to identify various cancers from non-conditional healthy controls, while their accuracy for identifying early-stage cancers from benign lesions with inconclusive imaging results remains uncertain. Especially for breast cancer, current imaging-based screening methods suffer from high false positive rates for women with breast nodules, leading to unnecessary biopsies, which add to discomfort and healthcare burden. Here, we enrolled 613 female participants in this multi-center study and demonstrated that cfDNA fragmentomics (cfFrag) is a robust non-invasive biomarker for breast cancer using whole-genome sequencing. Among the multimodal cfFrag profiles, the fragment size ratio (FSR), fragment size distribution (FSD), and copy number variation (CNV) show more distinguishing ability than Griffin, motif breakpoint (MBP), and neomer. The cfFrag model using the optimal three fragmentomics features discriminated early-stage breast cancers from benign nodules, even at a low sequencing depth (3×). Notably, it demonstrated a specificity of 94.1% in asymptomatic healthy women at a 90% sensitivity for breast cancers. Moreover, we comprehensively showcased the clinical utilities of the cfFrag model in predicting patient responses to neoadjuvant chemotherapy (NAC) and in combining with multimodal features, including radiological results and cfDNA methylation features [with area under the curve (AUC) values of 0.93–0.94 and 0.96, respectively].
Statin effects on the incidence of major non-cardiovascular disease events among a global cohort of people with HIV: a randomised controlled trial
Authors: Marissa R Diggs, Triin Umbleja, Sara McCallum, Markella V Zanni, Sarah M Chu, Kathleen V Fitch, Gerald S Bloomfield, Judith S Currier, Esteban Martinez, Philip E Castle, Aya Awwad, Mamta K Jain, Roger Bedimo, Bronwyn Hendricks, Jose Narrea, Vincente Estrada, Jorge Pinto, Judith A Aberg, Carlos D Malvestutto, Carl J Fichtenbaum, Michael T Lu, Heather J Ribaudo, Pamela S Douglas, Steven K Grinspoon
Journal: The Lancet HIV (2025)
Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation
Authors: Federico Lussana, Chiara F Magnani, Stefania Galimberti, Giuseppe Gritti, Giuseppe Gaipa, Daniela Belotti, Benedetta Cabiati, Sara Napolitano, Silvia Ferrari, Alex Moretti, Chiara Buracchi, Gian Maria Borleri, Benedetta Rambaldi, Giuliana Rizzuto, Anna Grassi, Muriel Paganessi, Cristian Meli, Sarah Tettamanti, Giulia Risca, Giulia Pais, Giulio Spinozzi, Fabrizio Benedicenti, Giovanni Cazzaniga, Chiara Capelli, Elisa Gotti, Martino Introna, Josée Golay, Eugenio Montini, Adriana Balduzzi, Maria Grazia Valsecchi, Giuseppe Dastoli, Alessandro Rambaldi, Andrea Biondi
Journal: Blood Cancer Journal (2025)
Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice
Authors: Joie Lin, Julia A Callender, Joshua E Mayfield, Daniel B McClatchy, Daniel Ojeda-Juárez, Mahsa Pourhamzeh, Katrin Soldau, Timothy D Kurt, Garrett A Danque, Helen K Khuu, Josephina E Ronson, Donald P Pizzo, Yixing Du, Maxwell A Gruber, Alejandro M Sevillano, Jin Wang, Christina D Orrú, Joy Chen, Gail Funk, Patricia Aguilar-Calvo, Brent D Aulston, Subhojit Roy, Jong M Rho, Jack D Bui, Alexandra C Newton, Stuart A Lipton, Byron Caughey, Gentry N Patrick, Kim Doré, John R Yates Iii, Christina J Sigurdson
Journal: Journal of Clinical Investigation (2025)

Neuronal hyperexcitability precedes synapse loss in certain neurodegenerative diseases, yet the synaptic membrane interactions and downstream signaling events remain unclear. The disordered amino terminus of the prion protein (PrPC) has been implicated in aberrant signaling in prion and Alzheimer's disease. To disrupt neuronal interactions and signaling linked to the amino terminus, here we CRISPR-engineered a knock-in mouse expressing mutant PrPC (G92N), generating an N-linked glycosylation site between two functional motifs. Mice developed seizures and necrosis of hippocampal pyramidal neurons, similar to prion-infected mice and consistent with excitotoxicity. Phosphoproteomics revealed phosphorylated glutamate receptors and calcium-sensitive kinases, including protein kinase C (PKC). Additionally, 92N-PrPC-expressing neurons show persistent calcium influx as well as dendritic beading, which was rescued by an NMDA receptor antagonist. Finally, survival of Prnp92N mice was prolonged by blocking active NMDA receptor channels. We propose dysregulated PrPC - NMDA receptor - induced signaling can trigger excitatory - inhibitory imbalance, spongiform degeneration, and neurotoxicity, and that calcium dysregulation is central to PrPC-linked neurodegeneration.
Blood-Based Proteomic Profiling Identifies OSMR as a Novel Biomarker of AML Outcomes
Authors: Patrick K Reville, Bofei Wang, Jennifer Marvin-Peek, Bin Yuan, Yu-An Kuo, Araceli Isabella Garza, Jessica L Root, Wei Qiao, Andrea Arruda, Ivo Veletic, Yiwei Liu, Nicholas J Short, Courtney D. DiNardo, Tapan M. Kadia, Naval G. Daver, Philip L Lorenzi, Koji Sasaki, Steven M Kornblau, Mark D Minden, Farhad Ravandi, Hagop M Kantarjian, Hussein A. Abbas
Journal: Blood (2025)
Clinical implementation of AI-based screening for risk for opioid use disorder in hospitalized adults
Authors: Majid Afshar, Felice Resnik, Cara Joyce, Madeline Oguss, Dmitriy Dligach, Elizabeth S Burnside, Anne Gravel Sullivan, Matthew M Churpek, Brian W Patterson, Elizabeth Salisbury-Afshar, Frank J Liao, Cherodeep Goswami, Randy Brown, Marlon P Mundt
Journal: Nature Medicine (2025)
Prevention and interception trials in inflammatory bowel disease: an international taskforce assessment on clinical trial design
Authors: Sailish Honap, Nelly Agrinier, Joana Torres, Kenneth Croitoru, Sun-Ho Lee, Williams Turpin, Ryan C Ungaro, Manasi Agrawal, Inga Peter, Dan Turner, Iris Dotan, Ailsa L Hart, Patrick Netter, Geert D'Haens, David T Rubin, Siew C Ng, Richard Gearry, Vipul Jairath, Ashwin N Ananthakrishnan, Silvio Danese, Jean-Frederic Colombel, Laurent Peyrin-Biroulet
Journal: The Lancet. Gastroenterology & hepatology (2025)
Genomic prediction with kinship-based multiple kernel learning produces hypothesis on the underlying inheritance mechanisms of phenotypic traits
Authors: Daniele Raimondi, Nora Verplaetse, Antoine Passemiers, Deborah Sarah Jans, Isabelle Cleynen, Yves Moreau
Journal: Genome biology (2025)

Genomic prediction encompasses the techniques used in agricultural technology to predict the genetic merit of individuals towards valuable phenotypic traits. It is related to Genome Interpretation in humans, which models the individual risk of developing disease traits. Genomic prediction is dominated by linear mixed models, such as the Genomic Best Linear Unbiased Prediction (GBLUP), which computes kinship matrices from SNP array data, while Genome Interpretation applications to clinical genetics rely mainly on Polygenic Risk Scores. In this article, we exploit the positive semidefinite characteristics of the kinship matrices that are conventionally used in GBLUP to propose a novel Genomic Multiple Kernel Learning method (GMKL), in which the multiple kinship matrices corresponding to Additive, Dominant, and Epistatic Inheritance Mechanisms are used as kernels in support vector machines, and we apply it to both worlds. We benchmark GMKL on simulated cattle phenotypes, showing that it outperforms the classical GBLUP predictors for genomic prediction. Moreover, we show that GMKL ranks the kinship kernels representing different inheritance mechanisms according to their compatibility with the observed data, allowing it to produce hypotheses on the normally unknown inheritance mechanisms generating the target phenotypes. We then apply GMKL to the prediction of two inflammatory bowel disease cohorts with more than 6500 samples in total, consistently obtaining results suggesting that epistasis might have a relevant, although underestimated role in inflammatory bowel disease (IBD). We show that GMKL performs similarly to GBLUP, but it can formulate biological hypotheses about inheritance mechanisms, such as suggesting that epistasis influences IBD.
Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes
Authors: Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J Erin Wiedmeier-Nutor, Linda B Baughn, S Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar
Journal: Blood Cancer Journal (2025)

Venetoclax (Ven), a BCL-2 inhibitor, has demonstrated efficacy in patients with relapsed/refractory multiple myeloma (RRMM) harboring a t(11;14) and/or elevated BCL-2 expression. However, data from clinical trial remain inconclusive. This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic sites between Jan 2015 and Dec 2023. The median age was 62 years, with a median of 3 prior lines of therapy. Among the cohort, 82% had t(11;14), and elevated BCL-2 expression was identified in 17 of 18 non-t(11;14) patients tested. Ven combinations included Ven-Dex (VenD; 48.3%), Proteasome Inhibitor-Ven (30.2%), and Daratumumab-Ven (19%) with other combinations making up the rest. The overall response rate was 57%; 64% for t(11;14) patients and 26% for non-t(11;14) patients. Median progression-free survival (PFS) was 9.4 months overall; 11.8 months for t(11;14) patients and 2.9 months for those without (p < 0.001). Among t(11;14) patients, the presence of del(17p) or 1q gain/amplification significantly reduced PFS to 7.7 months. Venetoclax-based regimens remain an important option for t(11;14) patients, but efficacy is limited in patients without a t(11;14). The presence of secondary high-risk cytogenetics imparts an inferior PFS.