tbuckley/cabot-search huggingface dataset:
Submicroscopic malaria in pregnancy and associated adverse pregnancy events: A case-cohort study of 4,352 women on the Thailand–Myanmar border
Authors: Mary Ellen Gilder, Makoto Saito, Warat Haohankhunnatham, Clare L. Ling, Gornpan Gornsawun, Germana Bancone, Cindy S. Chu, Peter R. Christensen, Mallika Imwong, Prakaykaew Charunwatthana, Nay Win Tun, Aung Myat Min, Verena I. Carrara, Stephane Proux, Nicholas J. White, François Nosten, Rose McGready
Journal: PLoS Medicine (2025)

Malaria in pregnancy detected by microscopy is associated with maternal anaemia, reduced fetal growth, and preterm birth, but the effects of lower density (i.e., submicroscopic) malaria infections are poorly characterised. This analysis was undertaken to investigate associations between submicroscopic malaria at the first antenatal care (ANC) visit and these adverse pregnancy events on the Thailand-Myanmar border. Blood samples taken from refugee and migrant pregnant women presenting for their first ANC visit were analysed retrospectively for malaria using ultrasensitive PCR (uPCR, limit of detection 22 parasites/mL). The relationships between submicroscopic malaria and subsequent microscopically detectable malaria, anaemia, birth weight, and preterm birth were evaluated using inverse probability weighting for stratified random sampling. First ANC visit samples from 4,352 asymptomatic women (median gestational age 16.5 weeks) attending between October 1st 2012 and December 31st 2015 were analysed. The weighted proportion of women with submicroscopic malaria infection was 4.6% (95% CI 3.9-5.6), comprising 59.8% (49.5-69.4) Plasmodium vivax, 6.5% (4.0-10.5) Plasmodium falciparum, 1.8% (0.9-3.6) mixed, and 31.9% (22.2-43.5) infections which could not be speciated. Submicroscopic parasitaemia at first ANC visit was associated with subsequent microscopically detected malaria (adjusted hazard ratio [HR] 12.9, 95% CI 8.8-18.8, p < 0.001) and lower birth weight (adjusted predicted mean difference -275 g, 95% CI -510 to -40, p = 0.022). There was no association with preterm birth. Submicroscopic P. falciparum mono-infection (adjusted HR 2.8, 95% CI 1.2-6.6, p = 0.023) and coinfection with P. falciparum and P. vivax (adjusted HR 10.3, 95% CI 2.6-40.4, p = 0.001) was associated with increased risk of maternal anaemia, but submicroscopic P. vivax mono-infection was not. That uPCR was conducted for only a part of the cohort due to cost constraints is a limitation. In low transmission settings, uPCR identifies substantially more malaria infections at antenatal screening than conventional diagnostic methods. On the Thailand-Myanmar border, submicroscopic malaria at first antenatal consultation was associated with higher risks of microscopically diagnosed malaria later in pregnancy, anaemia, and reduced birth weight.
Evolution of WHO diagnostic criteria in “Classical Myeloproliferative Neoplasms” compared with the International Consensus Classification
Authors: Jürgen Thiele, Hans Michael Kvasnicka, Umberto Gianelli, Daniel A. Arber, Ayalew Tefferi, Alessandro M. Vannucchi, Tiziano Barbui, Attilio Orazi
Journal: Blood Cancer Journal (2025)
Evaluating base and retrieval augmented LLMs with document or online support for evidence based neurology
Authors: Lars Masanneck, Sven G. Meuth, Marc Pawlitzki
Journal: npj Digital Medicine (2025)

Effectively managing evidence-based information is increasingly challenging. This study tested large language models (LLMs), including document- and online-enabled retrieval-augmented generation (RAG) systems, using 13 recent neurology guidelines across 130 questions. Results showed substantial variability. RAG improved accuracy compared to base models but still produced potentially harmful answers. RAG-based systems performed worse on case-based than knowledge-based questions. Further refinement and improved regulation is needed for safe clinical integration of RAG-enhanced LLMs.
Motor protein KIF13B orchestrates hepatic metabolism to prevent metabolic dysfunction-associated fatty liver disease
Authors: Guo-Lin Miao, Wen-Xi Zhang, Yi-Tong Xu, Yi-Ran Liu, Ping-Ping Lai, Jia-Bao Guo, Gong-Lie Chen, Jing-Xuan Chen, Zi-Hao Zhou, Yan-Wei Li, Chong Zhang, Yang Ding, Lian-Xin Zhang, Yu-Fei Han, Jin-Xuan Chen, Jing-Dong Wu, Yin-Qi Zhao, Si Mei, Yang Zhao, Yuan-Wu Ma, Ling Zhang, Wei Huang, Dong-Yu Zhao, Er-Dan Dong, Yu-Hui Wang, Xun-De Xian
Journal: Military Medical Research (2025)

Kinesin family member 13B (KIF13B), a crucial motor protein, exerts multiple cellular biological functions. However, the implication of KIF13B in metabolic dysfunction-associated fatty liver disease (MAFLD) has not been explored yet. This study aimed to investigate KIF13B's role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target. We assessed KIF13B expression in MAFLD patients and rodent models. The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice, hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets. The underlying mechanisms by which Kif13b governed hepatic lipid homeostasis and MAFLD progression were explored in vitro. Finally, the Kif13b's impact on atherosclerotic development was studied in the context of MAFLD. KIF13B expression was reduced in patients and murine models with MAFLD. Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis, which is further exacerbated by different overnutrition diets. Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis (MASH) in methionine-choline-deficient diet (MCD)-fed mice. Furthermore, Kif13b deficiency accelerates atherosclerosis in the context of MAFLD. Mechanistically, Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation. Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1 (AMPKα1) to regulate the phosphorylation of AMPKα1, governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1 (Srebp1)-mediated de novo lipogenesis in the liver. This work establishes a causal relationship between KIF13B deficiency and MAFLD, emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
3D-printed perfused models of the penis for the study of penile physiology and for restoring erectile function in rabbits and pigs
Authors: Zhenxing Wang, Xuemin Liu, Tan Ye, Zhichen Zhai, Kai Wu, Yudi Kuang, Serge Ostrovidov, Dan Shao, Yingjun Wang, Kam W Leong, Xuetao Shi
Journal: Nature Biomedical Engineering (2025)
Smartwatch- and smartphone-based remote assessment of brain health and detection of mild cognitive impairment
Authors: Paul Monroe Butler, Jenny Yang, Roland Brown, Matt Hobbs, Andrew Becker, Joaquin Penalver-Andres, Philippe Syz, Sofia Muller, Gautier Cosne, Adrien Juraver, Han Hee Song, Paramita Saha-Chaudhuri, Daniel Roggen, Alf Scotland, Natalia Silveira, Gizem Demircioglu, Audrey Gabelle, Richard Hughes, Michael G. Erkkinen, Jessica B. Langbaum, Jennifer H. Lingler, Pamela Price, Yakeel T. Quiroz, Sharon J. Sha, Marty Sliwinski, Anton P. Porsteinsson, Rhoda Au, Matt T. Bianchi, Hanson Lenyoun, Hung Pham, Mithun Patel, Shibeshih Belachew
Journal: Nature Medicine (2025)
GPNMB disrupts SNARE complex assembly to maintain bacterial proliferation within macrophages
Authors: Zhenzhen Yan, Jinghong Han, Zihao Mi, Zhenzhen Wang, Yixuan Fu, Chuan Wang, Ningning Dang, Hong Liu, Furen Zhang
Journal: Cellular and Molecular Immunology (2025)

Xenophagy plays a crucial role in restraining the growth of intracellular bacteria in macrophages. However, the machinery governing autophagosome‒lysosome fusion during bacterial infection remains incompletely understood. Here, we utilize leprosy, an ideal model for exploring the interactions between host defense mechanisms and bacterial infection. We highlight the glycoprotein nonmetastatic melanoma protein B (GPNMB), which is highly expressed in macrophages from lepromatous leprosy (L-Lep) patients and interferes with xenophagy during bacterial infection. Upon infection, GPNMB interacts with autophagosomal-localized STX17, leading to a reduced N-glycosylation level at N296 of GPNMB. This modification promotes the degradation of SNAP29, thus preventing the assembly of the STX17-SNAP29-VAMP8 SNARE complex. Consequently, the fusion of autophagosomes with lysosomes is disrupted, resulting in inhibited cellular autophagic flux. In addition to Mycobacterium leprae, GPNMB deficiency impairs the proliferation of various intracellular bacteria in human macrophages, suggesting a universal role of GPNMB in intracellular bacterial infection. Furthermore, compared with their counterparts, Gpnmbfl/fl Lyz2-Cre mice presented decreased Mycobacterium marinum amplification. Overall, our study reveals a previously unrecognized role of GPNMB in host antibacterial defense and provides insights into its regulatory mechanism in SNARE complex assembly.
NR4A1 Acts as a Novel Regulator of Platelet Activation and Thrombus Formation
Authors: Wenhua Liu, Gaoxiang Li, Jianfeng Shi, Yu Gao, Peiliang Fang, Yichao Zhao, Fangyuan Zhong, Xiao Guo, Yuyan Lyu, Xingwen Da, Zhaoyan Li, Jingjing Fa, Liuhua Hu, Ancai Yuan, Lei Chen, Junling Liu, Alex F. Chen, Bin Sheng, Yong Ji, Xiyuan Lu, Jun Pu
Journal: Circulation Research (2025)

BACKGROUND: Mounting evidence indicates that nuclear receptors play a critical regulatory role in platelet pathophysiology and thrombotic disorders. Although NR4A (the nuclear receptor subfamily 4 group A) plays an important role in cardiovascular pathophysiology, the expression profile and biological function of NR4A member 1 (NR4A1) in platelets have never been reported. METHODS: We evaluated the functions and the underlying mechanisms of NR4A1 in platelet activation and thrombus formation using platelet-specific NR4A1-deficient mice and NR4A1-specific agonists. Using a hyperlipidemic mouse model and platelets from patients with hypercholesterolemia, we explored the influence of hypercholesterolemia on NR4A1 expression and the effects of NR4A1-specific agonists on platelet hyperreactivity induced by hypercholesterolemia. RESULTS: NR4A1 was expressed in both human and mouse platelets. Platelet-specific NR4A1 deletion accelerated FeCl 3 -induced carotid arterial occlusive thrombus formation, enhanced collagen/epinephrine-induced pulmonary thromboembolism, and exacerbated microvascular microthrombi obstruction and infarct expansion in an acute myocardial infarction model. NR4A1-deficient platelets exhibited enhanced agonist-induced aggregation responses, integrin α IIb β 3 activation, dense granule release, α-granule release, platelet spreading, and clot retraction. Consistently, pharmacological activation of NR4A1 by specific agonists decreased platelet activation in both mouse and human platelets. Mechanistically, CAP1 (adenylyl cyclase-associated protein 1) was identified as the direct downstream interacting protein of NR4A1. NR4A1 deletion decreased cAMP levels and phosphorylation of VASP (vasodilator-stimulated phosphoprotein), while NR4A1-specific agonists increased cAMP levels and phosphorylation of VASP in platelets. Importantly, NR4A1 expression in platelets was upregulated in the setting of hypercholesterolemia, which was derived from its upregulation in megakaryocytes in a reactive oxygen species-dependent manner. Platelets from hypercholesterolemic patients and mice exhibited hyperreactivity. However, NR4A1-specific agonists significantly inhibited the activation of hypercholesterolemic platelets to the levels of healthy control platelets. CONCLUSIONS: We provide the first evidence that nuclear receptor NR4A1 negatively regulates platelet activation and thrombus formation. NR4A1 may serve as a novel therapeutic target for managing thrombosis-based cardiovascular diseases, especially with hypercholesterolemia.
Neuronal somatic mutations are increased in multiple sclerosis lesions
Authors: Allan Motyer, Stacey Jackson, Bicheng Yang, Ivon Harliwong, Wei Tian, Wing In Avis Shiu, Yunchang Shao, Bo Wang, Catriona McLean, Michael Barnett, Trevor J Kilpatrick, Stephen Leslie, Justin P Rubio
Journal: Nature Neuroscience (2025)
Advancing clinical genomics with Middle Eastern and South Asian pangenomes
Authors: Nasna Nassir, Mohamed A. Almarri, Hosneara Akter, Hamda Hassan Khansaheb, K. M. Furkan Uddin, Ahmad Abou Tayoun, Stefan S. Du Plessis, Marc Haber, Alawi Alsheikh-Ali, Mohammed Uddin
Journal: Nature Medicine (2025)
The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes
Authors: Alex Tokolyi, Elodie Persyn, Artika P. Nath, Katie L. Burnham, Jonathan Marten, Thomas Vanderstichele, Manuel Tardaguila, David Stacey, Ben Farr, Vivek Iyer, Xilin Jiang, Samuel A. Lambert, Guillaume Noell, Michael A. Quail, Diana Rajan, Scott C. Ritchie, Benjamin B. Sun, Scott A. J. Thurston, Yu Xu, Christopher D. Whelan, Heiko Runz, Slavé Petrovski, Daniel J. Gaffney, David J. Roberts, Emanuele Di Angelantonio, James E. Peters, Nicole Soranzo, John Danesh, Adam S. Butterworth, Michael Inouye, Emma E. Davenport, Dirk S. Paul
Journal: Nature Genetics (2025)
Comment on ‘Incidence of non-infectious uveitis among patients with hidradenitis suppurativa’
Authors: Alan Y Hsu, Chun-Ju Lin, Ning-Yi Hsia, Chun-Ting Lai, Yi-Yu Tsai
Journal: British Journal of Dermatology (2025)

This letter is a comment on the previous publication, ‘Incidence of non-infectious uveitis among patients with hidradenitis suppurativa’ by Ayodele et al.
Cross-Species Insights from Single-Nucleus Sequencing Highlight Aging-Related Hippocampal Features in Tree Shrew
Authors: Liu-Lin Xiong, Rui-Ze Niu, Li Chen, Li-Ren Huangfu, Jing Li, Lu-Lu Xue, Yi-Fei Sun, Li-Mei Wang, Yong-Ping Li, Jia Liu, Ting-Hua Wang
Journal: Molecular Biology and Evolution (2025)

The tree shrew brain has garnered considerable attention due to its remarkable similarities to human brain. However, the cellular composition and genetic signatures of tree shrew hippocampus across postnatal life remain poorly characterized. Here, we establish the first single-nucleus transcriptomic atlas of tree shrew hippocampus spanning postnatal life, detailing the dynamics and diversity of the neurogenic lineage, oligodendrocytes, microglia, and endothelial cells. Notably, cross-species transcriptomic comparison among humans, macaques, tree shrews, and mice reveals that the tree shrew transcriptome resembles that of macaques, making it a promising model for simulating human neurological diseases. More interestingly, we identified a unique class of tree shrew-specific neural stem cells and established SOX6, ADAMTS19, and MAP2 as their markers. Furthermore, aberrant gene expression and cellular dysfunction in the tree shrew hippocampus are linked to neuroinflammation and cognitive impairment during tree shrew aging. Our study provides extensive resources on cell composition and transcriptomic profiles, serving as a foundation for future research on neurodevelopmental and neurological disorders in tree shrews.
Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations
Authors: Frédéric Millot, Mirella Ampatzidou, Nirmalya Roy Moulik, Sanjay Tewari, Alaa Elhaddad, Mahmoud Hammad, Herbert Pichler, Thomas Lion, Athanasios Tragiannidis, Haruko Shima, Wenbin An, Wenyu Yang, Axel Karow, Roula Farah, Maaike Luesink, Michael Dworzak, Stephanie Sembill, Barbara De Moerloose, Petr Sedlacek, Kirk R Schultz, Krzysztof Kalwak, Birgitta Versluys, Uma Athale, Nobuko Hijiya, Markus Metzler, Meinolf Suttorp
Journal: Leukemia (2025)
Using aptamers for targeted delivery of RNA therapies
Authors: Julia Driscoll, Piyush Gondaliya, Dylan A Zinn, Rupesh Jain, Irene K Yan, Haidong Dong, Tushar Patel
Journal: Molecular Therapy (2025)

RNA based treatments that can silence, introduce or restore gene expression to target human diseases are emerging as a new class of therapeutics. Despite their potential for use in broad applications, their clinical translation has been hampered by a need for delivery to specific cells and tissues. Cell targeting based on the use of aptamers provides an approach for improving their delivery to the desired sites of action. Aptamers are nucleic acid oligonucleotides with structural conformations that provide a robust capacity for the recognition of cell surface molecules that can be used for directed targeting. Aptamers can be directly conjugated to therapeutic RNA molecules, in the form of aptamer-oligonucleotide chimeras, or incorporated into nanoparticles used as vehicles for the delivery of these therapeutics. Herein, we discuss the use of aptamers for cell-directed RNA therapies, provide an overview of different types of aptamer-targeting RNA therapeutics and review examples of their therapeutic applications. Challenges associated with manufacturing and scaling up production, and key considerations for their clinical implementation are also outlined.
Clinical Applications of Oligonucleotides for Cancer Therapy
Authors: Vittorio DeFranciscis, Giovanni Amabile, Marcin Kortylewski
Journal: Molecular Therapy (2025)

Oligonucleotide therapeutics (ONTs) represent a rapidly evolving modality for cancer treatment, capitalizing on their ability to modulate gene expression with high specificity. With more than 20 nucleic acid-based therapies that gained regulatory approval, advances in chemical modifications, sequence optimization, and novel delivery systems have propelled ONTs from research tools to clinical realities. ONTs, including siRNAs, antisense oligonucleotides (ASOs), saRNA, miRNA, aptamers, and decoys, offer promising solutions for targeting previously "undruggable" molecules, such as transcription factors, and enhancing cancer immunotherapy by overcoming tumor immune evasion. The promise of ONT application in cancer treatment is exemplified by the recent FDA approval of the first oligonucleotide-based treatment to myeloproliferative disease. At the same time, there are challenges in delivering ONTs to specific tissues, mitigating off-target effects, and improving cellular uptake and endosomal release. This review provides a comprehensive overview of ONTs in clinical trials, emerging delivery strategies, and innovative therapeutic approaches, emphasizing the role of ONTs in immunotherapy and addressing hurdles that hinder their clinical translation. By examining advances and remaining challenges, we highlight opportunities for ONTs to revolutionize oncology and enhance patient outcomes.
Human alveolar echinococcosis – global, regional and national annual incidence and prevalence rates
Authors: Britta Lundström-Stadelmann, Ali Rostami, Caroline F Frey, Paul R Torgerson, Seyed Mohammad Riahi, Kimia Bagheri, Marc Kaethner, Anja Lachenmayer, Guido Beldi, Robin B Gasser, Andrew Hemphill
Journal: Clinical Microbiology and Infection (2025)
Deep mutational learning for the selection of therapeutic antibodies resistant to the evolution of Omicron variants of SARS-CoV-2
Authors: Lester Frei, Beichen Gao, Jiami Han, Joseph M. Taft, Edward B. Irvine, Cédric R. Weber, Rachita K. Kumar, Benedikt N. Eisinger, Andrey Ignatov, Zhouya Yang, Sai T. Reddy
Journal: Nature Biomedical Engineering (2025)

Most antibodies for treating COVID-19 rely on binding the receptor-binding domain (RBD) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). However, Omicron and its sub-lineages, as well as other heavily mutated variants, have rendered many neutralizing antibodies ineffective. Here we show that antibodies with enhanced resistance to the evolution of SARS-CoV-2 can be identified via deep mutational learning. We constructed a library of full-length RBDs of Omicron BA.1 with high mutational distance and screened it for binding to the angiotensin-converting-enzyme-2 receptor and to neutralizing antibodies. After deep-sequencing the library, we used the data to train ensemble deep-learning models for the prediction of the binding and escape of a panel of eight therapeutic antibody candidates targeting a diverse range of RBD epitopes. By using in silico evolution to assess antibody breadth via the prediction of the binding and escape of the antibodies to millions of Omicron sequences, we found combinations of two antibodies with enhanced and complementary resistance to viral evolution. Deep learning may enable the development of therapeutic antibodies that remain effective against future SARS-CoV-2 variants.
A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity
Authors: Lu Sun, Xiaoyan Li, Feixiang Xu, Yuwen Chen, Xushuo Li, Zhicheng Yang, Ying Yang, Ke Wang, Tianyi Ren, Zihao Lin, Hua Wang, Xiangdong Wang, Yan Lu, Zhenju Song, Zhou-Li Cheng, Duojiao Wu
Journal: Nature Immunology (2025)

Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNAs. ac4C-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion. Conditional deletion of Nat10 in mouse T cells causes severe cell cycle arrest and limitation of cell expansion due to MYC deficiency, ultimately exacerbating infection in an acute lymphocytic choriomeningitis virus model. Additionally, T cells from older individuals with lower NAT10 levels show proliferative defects, which may partially account for impaired antiviral responses in older individuals. This study reveals a mechanism governing T cell expansion, signal-dependent mRNA degradation induction and the potential in vivo biological significance of ac4C modification in T cell-mediated immune responses.
Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial
Authors: Ramez N Eskander, Michael W Sill, Lindsey Beffa, Richard G Moore, Joanie M Hope, Fernanda B Musa, Robert S Mannel, Mark S Shahin, Guilherme H Cantuaria, Eugenia Girda, Elizabeth Lokich, Juraj Kavecansky, Charles A Leath, Lilian T Gien, Emily M Hinchcliff, Shashikant B Lele, Lisa M Landrum, Floor Backes, Roisin E O'Cearbhaill, Tareq Al Baghdadi, Emily K Hill, Premal H Thaker, Veena S John, Stephen Welch, Amanda N Fader, Matthew A Powell, Carol Aghajanian
Journal: Nature Medicine (2025)
A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system
Authors: Justin H. Wilde, Yu-Yo Sun, Spenser R. Simpson, Ethan R. Hill, Zhongxiao Fu, Emily J. Bian, Melissa M. Kinkaid, Paulina Villanueva, Aden F. Weybright, William R. Terrell, Zoraiz Qureshi, Shashika S. Perera, Heather S. Sheppard, James R. Stone, Bijoy K. Kundu, Chia-Yi Kuan, Kiel D. Neumann
Journal: Nature Biomedical Engineering (2025)

Reactive oxygen and nitrogen species (RONS) contribute to the pathogenesis of neurodegeneration, but the inability to detect RONS in vivo in the central nervous system has confounded the interpretation of results of clinical trials of antioxidants. Here we report the synthesis and characterization of a positron emission tomography (PET) probe, [18F]fluoroedaravone ([18F]FEDV), for the in vivo quantification of oxidative stress. Derived from the antioxidant edaravone, the probe can diffuse through the blood-brain barrier and is stable in human plasma. In mice, PET imaging with [18F]FEDV allowed for the detection of RONS after intrastriatal injection of sodium nitroprusside, in the middle cerebral artery after stroke by photothrombosis, and in brains with tauopathy. When using dynamic PET imaging coupled with parametric mapping, the sensitivity of [18F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [18F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.