tbuckley/cabot-search huggingface dataset:
Artificial Delayed-phase Technetium-99m MIBI Scintigraphy From Early-phase Scintigraphy Improves Identification of Hyperfunctioning Parathyroid Lesions in Patients With Hyperparathyroidism
Authors: Yong-Jin Park, Se Jin Kim, Dongmin Choi, Seung Hyup Hyun
Journal: Clinical Nuclear Medicine (2025)

Purpose: The aim of this study was to generate and validate artificial delayed-phase technetium-99m methoxyisobutylisonitrile scintigraphy (aMIBI) images from early-phase technetium-99m methoxyisobutylisonitrile scintigraphy (eMIBI) images. Patients and Methods: This retrospective study included patients with hyperparathyroidism who underwent dual-phase technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy at 2 centers. The patients were divided into a training set (n = 980), an internal test set (n = 100), and an external test set (n = 253). The generation of aMIBI images from eMIBI images was performed using an unpaired image-to-image translation method. Receiver operating characteristic curves and the area under the curves (AUCs) were used to evaluate the diagnostic performance of aMIBI and eMIBI images in identifying hyperfunctioning parathyroid lesions in both the internal and external test sets. In addition, an artificial intelligence (AI)–assisted diagnostic model combining aMIBI and clinical data was evaluated. Results: The AUCs of aMIBI images were significantly higher than those of eMIBI images (internal test set: 0.944 vs 0.658, P &lt; 0.001; external test set: 0.900 vs 0.761, P &lt; 0.001). The performance of the AI-assisted diagnostic models combining aMIBI images and clinical data was significantly better than those of the aMIBI-only models in both the internal (AUC: 0.974 vs 0.944, P = 0.020) and external (AUC: 0.953 vs 0.900, P &lt; 0.001) test sets. Conclusions: The diagnostic performance of aMIBI images in identifying hyperfunctioning parathyroid lesions was significantly superior to that of eMIBI images in patients with hyperparathyroidism. Models combining aMIBI images with clinical information enhanced the diagnostic performance even further.
Association of Gene Variant Type and Location with Breast Cancer Risk in the General Population
Authors: M P Akamandisa, N J Boddicker, S Yadav, C Hu, S N Hart, C Ambrosone, H Anton-Culver, P L Auer, C Bodelon, E S Burnside, F Chen, A H Eliassen, D E Goldgar, C Haiman, J M Hodge, H Huang, E M John, R Karam, J V Lacey, S Lindstroem, E Martinez, J Na, S L Neuhausen, K M O'Brien, J E Olson, T Pal, J R Palmer, A V Patel, T Pesaran, E C Polley, M E Richardson, K Ruddy, D P Sandler, L R Teras, A Trentham-Dietz, C M Vachon, C Weinberg, S J Winham, S Yao, G Zirpoli, P Kraft, J N Weitzel, S M Domchek, F J Couch, K L Nathanson
Journal: Annals of Oncology (2025)
9MW2821, a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open label, multicenter, phase Ⅰ/Ⅱ study
Authors: J Zhang, R Liu, S Wang, Z Feng, H Yang, S Gao, X Li, X Yao, J Chen, Z Gong, Y Li, X Li, S Wang, C Hu, J Liu, M Zhang, F Yuan, B Shi, H Lou, P Zhao, F Qiu, H Guo, B Hu, D Xu, H Huang, X Zhang, M Feng, X Wang, G Li, D Liu, X Chen, P Wang
Journal: Annals of Oncology (2025)
Neurotrophic Keratopathy in Pediatric Population: an IRIS® Registry Report
Authors: Asmaa A Zidan, Joshua B Gilbert, Eric Goldberg, Connor Ross, Tobias Elze, Alice C Lorch, Joan W Miller, Leyla Yavuz Saricay, Thomas Dohlman, Reza Dana, Jia Yin
Journal: Ophthalmology (2025)
α-Synuclein Targeted Therapy with Multiple Pathological Improvement for Parkinson’s Disease by Macrocyclic Amphiphile Nanomedicine
Authors: Jian-Mei Gao, Wen-Bo Li, Yang Yi, Jia-Jia Wei, Miao-Xian Gong, Bin-Bin Pan, Xun-Cheng Su, Yu-Chen Pan, Dong-Sheng Guo, Qi-Hai Gong
Journal: Biomaterials (2025)
INNOVATIVE THERAPEUTICS FOR RENOPROTECTION: WHERE WE ARE
Authors: Monica Cortinovis, Norberto Perico, Giuseppe Remuzzi
Journal: Pharmacological Reviews (2025)

Chronic kidney disease (CKD) has become highly prevalent worldwide, with major implications for public health, including increased risk of progression to kidney failure, cardiovascular events, and mortality. Up to a decade ago, renin-angiotensin system inhibitors, that is angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, were the only available pharmacological interventions to slow kidney function loss and limit the associated cardiovascular morbidity and mortality in this context. More recently, landmark trials have demonstrated the ability of novel therapeutics to significantly ameliorate kidney and cardiovascular outcomes in patients with CKD, when added on top of optimized renin-angiotensin system blockade. These include sodium-glucose cotransporter-2 inhibitors in patients with diabetic and nondiabetic kidney disease, as well as the nonsteroidal mineralcorticoid receptor antagonist finerenone and the glucagon-like peptide-1 receptor agonist semaglutide in patients with diabetic kidney disease. We herein review the evolving scenario and the latest evidence for the treatment of CKD, mainly focusing on proteinuric CKD. We started with a presentation of established and more recently approved classes of kidney protective drugs, followed by a discussion of therapeutic interventions under clinical investigation to slow CKD progression. Finally, we underscore the added value of personalized and multidrug interventions, which are becoming increasingly more feasible with the availability of a growing number of kidney protective agents, and are likely to stand as the most powerful tools to safely slow, or even prevent, the progression of proteinuric CKD. SIGNIFICANCE STATEMENT: Chronic kidney disease (CKD) is highly prevalent globally, and is associated with substantial morbidity and mortality. This review provides a comprehensive overview of the currently approved and emerging therapeutic options for the treatment of proteinuric CKD. As novel kidney protective agents have recently become available, the outcomes of patients with CKD could hopefully improve over the few decades ahead.
Spectrum of γ-Secretase dysfunction as a unifying predictor of ADAD age at onset across PSEN1, PSEN2 and APP causal genes
Authors: Sara Gutiérrez Fernández, Cristina Gan Oria, Dieter Petit, Wim Annaert, John M Ringman, Nick C Fox, Natalie S Ryan, Lucía Chávez-Gutiérrez
Journal: Molecular Neurodegeneration (2025)

Abstract Background Autosomal Dominant Alzheimer's Disease (ADAD), caused by mutations in Presenilins ( PSEN1/2 ) and Amyloid Precursor Protein ( APP ) genes, typically manifests with early onset (&lt; 65 years). Age at symptom onset (AAO) is relatively consistent among carriers of the same PSEN1 mutation, but more variable for PSEN2 and APP variants, with these mutations associated with later AAOs than PSEN1 . Understanding this clinical variability is crucial for understanding disease mechanisms, developing predictive models and tailored interventions in ADAD, with potential implications for sporadic AD. Methods We performed biochemical assessment of γ-secretase dysfunction on 28 PSEN2 and 19 APP mutations, including disease-associated, unclear and benign variants. This analysis has been valuable in the assessment of PSEN1 variant pathogenicity, disease onset and progression. Results Our analysis reveals linear correlations between the molecular composition of Aβ profiles and AAO for both PSEN2 (R 2 = 0.52) and APP (R 2 = 0.69) mutations. The integration of PSEN1, PSEN2 and APP correlation data shows parallel but shifted lines, suggesting a common pathogenic mechanism with gene-specific shifts in onset. We found overall “delays” in AAOs of 27 years for PSEN2 and 8 years for APP variants, compared to PSEN1. Notably, extremely inactivating PSEN1 variants delayed onset, suggesting that reduced contribution to brain APP processing underlies the later onset of PSEN2 variants. Conclusion This study supports a unified model of ADAD pathogenesis wherein γ-secretase dysfunction and the resulting shifts in Aβ profiles are central to disease onset across all causal genes. While similar shifts in Aβ occur across causal genes, their impact on AAO varies in the function of their contribution to APP processing in the brain. This biochemical analysis establishes quantitative relationships that enable predictive AAO modelling with implications for clinical practice and genetic research. Our findings also support the development of therapeutic strategies modulating γ-secretase across different genetic ADAD forms and potentially more broadly in AD.
EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update
Authors: Linda Rüegg, Andrea Pluma, Sabrina Hamroun, Irene Cecchi, Luis Fernando Perez-Garcia, Philip O Anderson, Laura Andreoli, Sara Badreh Wirström, Vladimira Boyadhzieva, Christina Chambers, Nathalie Costedoat-Chalumeau, Radboud J E M Dolhain, Rebecca Fischer-Betz, Ian Giles, Carina Gøtestam-Skorpen, Maria Hoeltzenbein, Francesca Marchiori, Karoline Mayer-Pickel, Anna Molto, Catherine Nelson-Piercy, Ole Haagen Nielsen, Angela Tincani, Marianne Wallenius, Astrid Zbinden, Yvette Meissner, Axel Finckh, Frauke Förger
Journal: Annals of the Rheumatic Diseases (2025)

To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety. According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.
The application of organoids in investigating immune evasion in the microenvironment of gastric cancer and screening novel drug candidates
Authors: Liuyue Kan, Ying Yu, Yaxue Wang, Lei Shi, Tingyuan Fan, Hui Chen, Chuanli Ren
Journal: Molecular Cancer (2025)

Gastric cancer (GC) is a prevalent digestive system tumor, the fifth most diagnosed cancer worldwide, and a leading cause of cancer deaths. GC is distinguished by its pronounced heterogeneity and a dynamically evolving tumor microenvironment (TME). The lack of accurate disease models complicates the understanding of its mechanisms and impedes the discovery of novel drugs. A growing body of evidence suggests that GC organoids, developed using organoid culture technology, preserve the genetic, phenotypic, and behavioral characteristics. GC organoids hold significant potential for predicting treatment responses in individual patients. This review provides a comprehensive overview of the current clinical treatment strategies for GC, as well as the history, construction and clinical applications of organoids. The focus is on the role of organoids in simulating the TME to explore mechanisms of immune evasion and intratumoral microbiota in GC, as well as their applications in guiding clinical drug therapy and facilitating novel drug screening. Furthermore, we summarize the limitations of GC organoid models and underscore the need for continued technological advancements to benefit both basic and translational oncological research.
A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers
Authors: Jialing Cheng, Zhiyang Chen, Demin Lin, Yanfang Yang, Yanjing Bai, Lingshuang Wang, Jie Li, Yuchen Wang, Hongliang Wang, Youbai Chen, Jun Ye, Yuling Liu
Journal: Acta Pharmaceutica Sinica B (2025)
Navigating health financing cliffs: a new era in global health
Authors: Kumanan Rasanathan, Maylene M Beltran, Alberta A Biritwum-Nyarko, Mark S Blecher, Mark Dybul, Hajime Inoue, Kelechi Ohiri, Walaiporn Patcharanarumol, Yogan Pillay, K Srinath Reddy, Minghui Ren, Zubin Cyrus Shroff, Bright Simons, Susan Sparkes, Kalipso Chalkidou
Journal: The Lancet (2025)
Immunogenicity and safety of different immunisation schedules of the VLA15 Lyme borreliosis vaccine candidate in adults, adolescents, and children: a randomised, observer-blind, placebo-controlled, phase 2 trial
Authors: Laura Wagner, Michaela Obersriebnig, Vera Kadlecek, Romana Hochreiter, Santhosh Kumar Ghadge, Julian Larcher-Senn, Lisa Hegele, Jason D Maguire, Ulla Derhaschnig, Juan Carlos Jaramillo, Susanne Eder-Lingelbach, Nicole Bézay
Journal: The Lancet Infectious Diseases (2025)
Harmonizing nature’s timescales in ecosystem models
Authors: Vivienne P Groner, Jacob Cook, C David L Orme, Priyanga Amarasekare, Edward Comyn-Platt, Taran Rallings, Jaideep Joshi, Robert M Ewers
Journal: Trends in Ecology & Evolution (2025)

Modeling complex, nonlinear ecosystem processes across different timescales presents a significant challenge. We identify two key issues: selecting a representative timestep that captures interconnected processes across various timescales, and simulating these processes in an appropriate sequence. By synthesizing existing ecosystem frameworks, we find shared compromises between biological realism and computational performance. For the representative timestep, these include 'selective elimination of timescales', 'biting the bullet', 'each in their own time', and 'capture the unseen'. For processing order, we identify hierarchical, logical, iterative, and random approaches. Similar challenges exist in other disciplines, and we show how transferring methods from multiple fields, along with smarter computing, can improve timescale integration. Overcoming these challenges requires innovative transdisciplinary solutions, and we outline directions for future research.
Antigen Uptake in the Gut: An Underappreciated Piece to the Puzzle?
Authors: Devesha H. Kulkarni, Rodney D. Newberry
Journal: Annual Review of Immunology (2025)

The mammalian gut is a vast, diverse, and dynamic single-layer epithelial surface exposed to trillions of microbes, microbial products, and the diet. Underlying this epithelium lies the largest collection of immune cells in the body; these cells encounter luminal substances to generate antigen-specific immune responses characterized by tolerance at homeostasis and inflammation during enteric infections. How the outcomes of antigen-specific tolerance and inflammation are appropriately balanced is a central question in mucosal immunology. Furthermore, how substances large enough to generate antigen-specific responses cross the epithelium and encounter the immune system in homeostasis and during inflammation remains largely unexplored. Here we discuss the challenges presented to the gut immune system, the identified pathways by which luminal substances cross the epithelium, and insights suggesting that the pathways used by substances to cross the epithelium affect the ensuing immune response.
Genetic Regulation of Cell Death: Insights from Autoinflammatory Diseases
Authors: Hirotsugu Oda, Alessandro Annibaldi, Daniel L. Kastner, Ivona Aksentijevich
Journal: Annual Review of Immunology (2025)

Metazoans have evolved innate antimicrobial defenses that promote cellular survival and proliferation. Countering the inevitable molecular mechanisms by which microbes sabotage these pathways, multicellular organisms rely on an alternative, perhaps more ancient, strategy that is the immune equivalent of suicide bombing: Infection triggers cell death programs that summon localized or even systemic inflammation. The study of human genetics has now unveiled a level of complexity that refutes the naive view that cell death is merely a blunt instrument or an evolutionary afterthought. To the contrary, findings from patients with rare diseases teach us that cell death–induced inflammation is a sophisticated, tightly choreographed process. We herein review the emerging body of evidence describing a group of illnesses—inborn errors of cell death, which define many of the molecular building blocks and regulatory elements controlling cell death–induced inflammation in humans—and provide a possible road map to countering this process across the spectrum of rare and common illnesses.
Cellular and Molecular Mechanisms of Innate Memory Responses
Authors: Musa M. Mhlanga, Stephanie Fanucchi, Mumin Ozturk, Maziar Divangahi
Journal: Annual Review of Immunology (2025)

There has been an increasing effort to understand the memory responses of a complex interplay among innate, adaptive, and structural cells in peripheral organs and bone marrow. Trained immunity is coined as the de facto memory of innate immune cells and their progenitors. These cells acquire epigenetic modifications and shift their metabolism to equip an imprinted signature to a persistent fast-responsive functional state. Recent studies highlight the contribution of noncoding RNAs and modulation of chromatin structures in establishing this epigenetic readiness for potential immune perturbations. In this review, we discuss recent studies that highlight trained immunity–mediated memory responses emerging intrinsically in innate immune cells and as a complex interplay with other cells at the organ level. Lastly, we survey epigenetic contributors to trained immunity phenotypes—specifically, a recently discovered regulatory circuit coordinating the regulation of a key driver of trained immunity.
Bidirectional Communication Between the Innate and Adaptive Immune Systems
Authors: Kathrynne A. Warrick, Charles N. Vallez, Hannah E. Meibers, Chandrashekhar Pasare
Journal: Annual Review of Immunology (2025)

Effective bidirectional communication between the innate and adaptive immune systems is crucial for tissue homeostasis and protective immunity against infections. The innate immune system is responsible for the early sensing of and initial response to threats, including microbial ligands, toxins, and tissue damage. Pathogen-related information, detected primarily by the innate immune system via dendritic cells, is relayed to adaptive immune cells, leading to the priming and differentiation of naive T cells into effector and memory lineages. Memory T cells that persist long after pathogen clearance are integral for durable protective immunity. In addition to rapidly responding to reinfections, memory T cells also directly instruct the interacting myeloid cells to induce innate inflammation, which resembles microbial inflammation. As such, memory T cells act as newly emerging activators of the innate immune system and function independently of direct microbial recognition. While T cell–mediated activation of the innate immune system likely evolved as a protective mechanism to combat reinfections by virulent pathogens, the detrimental outcomes of this mechanism manifest in the forms of autoimmunity and other T cell–driven pathologies. Here, we review the complexities and layers of regulation at the interface between the innate and adaptive immune systems to highlight the implications of adaptive instruction of innate immunity in health and disease.
Human Immune Responses to Epstein-Barr Virus Highlighted by Immunodeficiencies
Authors: Sylvain Latour
Journal: Annual Review of Immunology (2025)

Inborn errors of immunity (IEIs) represent unique in natura models that uncover key components of immunity in humans, in particular those that predispose to infections. Epstein-Barr virus (EBV) is one of the most common opportunistic infectious agents in humans and is responsible for several diseases, including infectious mononucleosis, nonmalignant and malignant lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, and smooth muscle and epithelial tumors. For most individuals, EBV infection persists for life without pathological consequences. IEIs that do not predispose to EBV infection suggest that innate and humoral responses are not necessary or redundant for the immune response to EBV. IEIs associated with high susceptibility to EBV infection provide unequivocal genetic proof of the central role of CD8 + T cell responses in immunity to EBV. They also highlight the distinct steps and pathways required for, on the one hand, the effector cytotoxic functions of CD8 + T cells and, on the other hand, the expansion and maturation of cytotoxic CD8 + T cells.
Protein Synthesis and Metabolism in T Cells
Authors: Linda V. Sinclair, Doreen A. Cantrell
Journal: Annual Review of Immunology (2025)

T lymphocytes are essential for immune responses to pathogens and tumors. Their ability to rapidly clonally expand and differentiate to effector cells following infection, and then to curb effector function following infection clearance, is fundamental for adaptive immunity. Proteome remodeling in response to immune activation is a fundamental mechanism that allows T cells to swiftly reprogram for acquisition of effector function and is possible only because antigen receptor– and cytokine-driven signal transduction pathways can trigger massive increases in protein synthesis. Equally, the ability to repress protein synthesis supports a return to quiescence once pathogens are cleared to avoid autoimmunity and to generate memory T cell populations. This review discusses what is known about T cell proteomes and the regulatory mechanisms that control protein synthesis in T cells. The focus is on how this fundamental process is dynamically controlled to ensure immune homeostasis.
Barrier Integrity and Immunity: Exploring the Cutaneous Front Line in Health and Disease
Authors: Keitaro Fukuda, Yoshihiro Ito, Masayuki Amagai
Journal: Annual Review of Immunology (2025)

Immune responses are influenced by not only immune cells but also the tissue microenvironment where these cells reside. Recent advancements in understanding the underlying molecular mechanisms and structures of the epidermal tight junctions (TJs) and stratum corneum (SC) have significantly enhanced our knowledge of skin barrier functions. TJs, located in the granular layer of the epidermis, are crucial boundary elements in the differentiation process, particularly in the transition from living cells to dead cells. The SC forms from dead keratinocytes via corneoptosis and features three distinct pH zones critical for barrier function and homeostasis. Additionally, the SC–skin microbiota interactions are crucial for modulating immune responses and protecting against pathogens. In this review, we explore how these components contribute both to healthy and disease states. By targeting the skin barrier in therapeutic strategies, we can enhance its integrity, modulate immune responses, and ultimately improve outcomes for patients with inflammatory skin conditions.