tbuckley/cabot-search huggingface dataset:
Psychiatric Genetics in Clinical Practice: Essential Knowledge for Mental Health Professionals
Authors: Aaron D. Besterman, Mohamed A. Alnor, Mauricio Castaño, Lynn E. DeLisi, Dorothy E. Grice, Falk W. Lohoff, Christel M. Middeldorp, Daniel J. Müller, Diego Quattrone, John Nurnberger, Erika L. Nurmi, David A. Ross, Takahiro Soda, Thomas G. Schulze, Brett Trost, Elisabet Vilella, Chloe X. Yap, Gwyneth Zai, Daniel Moreno-De-Luca
Journal: American Journal of Psychiatry (2025)

The authors provide recommendations on incorporating recent advances in psychiatric genetics into clinical practice for mental health clinicians. The International Society for Psychiatric Genetics Education Committee met monthly to come to a consensus on priority topics in psychiatric genetics. Topics were then assigned to small teams of subspecialty experts to summarize the current knowledge base and create an illustrative clinical case. Topics included, familial aggregation, common and rare genetic variants, epigenetics, gene-environment interactions, pharmacogenomics, genetic counseling, and ethical and social implications. Each section was reviewed and revised by all committee members and then finalized by the Committee Chair. Key findings highlight the importance of understanding the genetic architecture of psychiatric disorders, the potential applications of genetic information in risk assessment, diagnosis, treatment selection, and patient education, as well as the ethical and social considerations surrounding the use of genetic data. The committee emphasizes the need for a nuanced approach that integrates genetic factors with environmental and experiential factors in a holistic model of care. As psychiatric genetics continues to evolve rapidly, mental health clinicians must stay informed about the latest findings and their clinical implications. Ongoing education, collaboration with genetics professionals, and effective communication strategies are crucial to harness the power of genetics while avoiding potential pitfalls such as genetic determinism and stigma. The committee recommends a balanced perspective that recognizes the complex interplay of genetic and non-genetic factors in shaping mental health outcomes.
20 Years of Aberrant Salience in Psychosis: What Have We Learned?
Authors: Philip R. Corlett, Kurt M. Fraser
Journal: American Journal of Psychiatry (2025)

Twenty years ago Shitij Kapur's "Psychosis as a state of aberrant salience" captured the attention of clinicians and cognitive and behavioral neuroscientists. It has become the de facto way of talking about delusion formation in labs and clinics. Here, evidence for this theory is critically evaluated in consideration of evolving data since its publication. A particular focus is placed on its specific predictions regarding the neural and behavioral loci of dopamine dysfunction in psychosis and finds them lacking. This examination is informed by recent advances in the understanding of the function of the dopamine system and its impacts on behavior following the explosion of new tools and probes for precise measurement and manipulation of dopaminergic circuits. Contemporary theories that have developed since Kapur-which suggest a role for dopamine in belief formation, belief updating under uncertainty, and abductive inference to the best explanation for some set of circumstances-are argued to form a more cogent theory that fits better with the work in patients with delusions and hallucinations, how they behave, and what is known about the function of their dopamine system. The original salience hypothesis has been influential as it attempted to unite neurochemical dysfunction with clinical phenomenology through computational cognitive neuroscience, which has led to the development of novel predictions that the authors highlight as future directions for the field.
Granulomatous Inflammation of Liver Mimicking Malignancy on 68Ga-FAPI PET/CT
Authors: Mine Araz, Ecenur Dursun, İrem Mesci, Can Konca, Çiğdem Soydal, Elgin Özkan, Kemal Metin Kir, Nuriye Özlem Küçük
Journal: Clinical Nuclear Medicine (2025)

68 Ga-FAPI has emerged as an alternative tracer for tumor imaging, as FAP is expressed in &gt;90% of epithelial cancers. Although promising data on this new radiotracer are increasing, false-positive results due to nonmalignant diseases with FAP uptake are also reported (for instance, chronic inflammation, arthritis, and fibrosis). In this case, we demonstrated 68 Ga-FAPI PET/CT involvement in a patient diagnosed with hepatic sarcoidosis.
Secondary Pulmonary Hypertrophic Osteoarthropathy Detected on [68Ga]Ga-FAPI-46 PET/CT
Authors: Anne-Leen Deleu, Thierry Berghmans, Patrick Flamen, Mariana Brandão
Journal: Clinical Nuclear Medicine (2025)

A 55-year-old man presented with arthralgia, digital clubbing, and pitting edema. A suspicious pulmonary mass showed high tracer uptake on both [ 18 F]FDG and [ 68 Ga]Ga-FAPI-46 PET/CT. Remarkably, FAPI PET revealed a diffuse periosteal tracer uptake of the long bones, highly suggestive for hypertrophic osteoarthropathy. The secondary and paraneoplastic nature of this condition was confirmed after a biopsy of the pulmonary mass. Hypertrophic osteoarthropathy is characterized by the clinical symptoms of arthralgia, digital clubbing, and periostosis, and is associated with malignancy in 90% of cases.
MAIT Cells Promote Cholesterol Excretion Pathways Mitigating Atherosclerosis
Authors: Hua Wang, Pukar K.C., Kaidi Zhang, Clément Materne, Marie Lhomme, Sophie Galier, Farid Ichou, Carolina Neves, Agnes Lehuen, Joel T. Haas, Joe-Elie Salem, Maryse Guerin, Philippe Lesnik
Journal: Circulation Research (2025)

BACKGROUND: Previous clinical studies have indicated reduced circulating mucosal-associated invariant T (MAIT) cells in individuals with coronary artery disease. However, the precise role and underlying mechanisms of MAIT cells in this context remain unclear. Immune homeostasis plays a pivotal role in the development of atherosclerosis. This study explores the impact of MAIT cells on atherosclerosis. METHODS: Vα19 +/− Ldlr −/− mice, characterized by a high MAIT cell frequency, and MAIT cell deficient MR1 −/− (major histocompatibility complex-related molecule 1) Ldlr −/− mice and their respective controls were used. Starting at 6 weeks of age, mice were subjected to a 1% cholesterol diet for 16 weeks. Additionally, the study analyzed circulating MAIT cell frequency and cholesterol levels in 68 patients with hypercholesterolemia. RESULTS: In Vα19 +/− Ldlr −/− mice, increased MAIT cells demonstrated a protective effect against atherosclerosis by reducing VLDL-C (very-low-density lipoprotein cholesterol) levels through heightened cholesterol excretion. This effect was accompanied by elevated jejunal ABCB1a, ABCG5, and ABCG8 expression, mediated by augmented levels of LXR transcription and activation, likely through intestinal IL-22 (interleukin-22) signaling. Conversely, cholesterol reduction mediated by intestinal cholesterol excretion was blocked by inhibition of MAIT cells. Moreover, MAIT cell-deficient MR1 −/− Ldlr −/− mice exhibited elevated total cholesterol levels and increased atherosclerotic lesions. In patients with hypercholesterolemia, circulating MAIT cell frequency displayed negative correlations with VLDL-C levels and positive correlations with HDL-C (high-density lipoprotein cholesterol) levels. CONCLUSIONS: Our findings demonstrate a new mechanism for plasma VLDL-C clearance by MAIT cell-mediated cholesterol excretion. The results provide further evidence that immunity is involved in cholesterol homeostasis. Targeting intestinal immunity to regulate cholesterol homeostasis holds promise as a new cholesterol-lowering modality to prevent atherosclerotic cardiovascular disease.
Digital clubbing, an unfamiliar feature of cryopyrin-associated periodic syndrome: a cohort study.
Authors: Jean-Benoît Monfort, Yixiang Yj Zhu, Majdouline El Moussaoui, Gilles Grateau, Angèle Soria, Léa Savey, Sophie Georgin-Lavialle
Journal: Journal of the American Academy of Dermatology (2025)
Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community
Authors: Giulia Grande, Martina Valletta, Debora Rizzuto, Xin Xia, Chengxuan Qiu, Nicola Orsini, Matilda Dale, Sarah Andersson, Claudia Fredolini, Bengt Winblad, Erika J. Laukka, Laura Fratiglioni, Davide L. Vetrano
Journal: Nature Medicine (2025)

Abstract Evidence regarding the clinical validity of blood biomarkers of Alzheimer’s disease (AD) in the general population is limited. We estimated the hazard and predictive performance of six AD blood biomarkers for incident all-cause and AD dementia—the ratio of amyloid-β 42 to amyloid-β 40 and levels of tau phosphorylated at T217 (p-tau217), tau phosphorylated at T181 (p-tau181), total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)—in a cohort of 2,148 dementia-free older adults from Sweden, who were followed for up to 16 years. In multi-adjusted Cox regression models, elevated baseline levels of p-tau181, p-tau217, NfL, and GFAP were associated with a significantly increased hazard for all-cause and AD dementia, displaying a non-linear dose–response relationship. Elevated concentrations of p-tau181, p-tau217, NfL, and GFAP demonstrated strong predictive performance (area under the curve ranging from 70.9% to 82.6%) for 10-year all-cause and AD dementia, with negative predictive values exceeding 90% but low positive predictive values (PPVs). Combining p-tau217 with NfL or GFAP further improved prediction, with PPVs reaching 43%. Our findings suggest that these biomarkers have the potential to rule out impending dementia in community settings, but they might need to be combined with other biological or clinical markers to be used as screening tools.
The Chinese gut virus catalogue reveals gut virome diversity and disease-related viral signatures
Authors: Qiulong Yan, Liansha Huang, Shenghui Li, Yue Zhang, Ruochun Guo, Pan Zhang, Zhixin Lei, Qingbo Lv, Fang Chen, Zhiming Li, Jinxin Meng, Jing Li, Guangyang Wang, Changming Chen, Hayan Ullah, Lin Cheng, Shao Fan, Wei You, Yan Zhang, Jie Ma, Shanshan Sha, Wen Sun
Journal: Genome Medicine (2025)

The gut viral community has been increasingly recognized for its role in human physiology and health; however, our understanding of its genetic makeup, functional potential, and disease associations remains incomplete. In this study, we collected 11,286 bulk or viral metagenomes from fecal samples across large-scale Chinese populations to establish a Chinese Gut Virus Catalogue (cnGVC) using a de novo virus identification approach. We then examined the diversity and compositional patterns of the gut virome in relation to common diseases by analyzing 6311 bulk metagenomes representing 28 disease or unhealthy states. The cnGVC contains 93,462 nonredundant viral genomes, with over 70% of these being novel viruses not included in existing gut viral databases. This resource enabled us to characterize the functional diversity and specificity of the gut virome. Using cnGVC, we profiled the gut virome in large-scale populations, assessed sex- and age-related variations, and identified 4238 universal viral signatures of diseases. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.698) and high-risk patients from controls (AUC = 0.761), and its predictive ability was also validated in external cohorts. Our resources and findings significantly expand the current understanding of the human gut virome and provide a comprehensive view of the associations between gut viruses and common diseases. This will pave the way for novel strategies in the treatment and prevention of these diseases.
Advantages of updated WHO mutation catalog combined with existing whole-genome sequencing-based approaches for Mycobacterium tuberculosis resistance prediction
Authors: Yiwang Chen, Xuecong Zhang, Jialei Liang, Qi Jiang, Mijiti Peierdun, Peng Xu, Howard E. Takiff, Qian Gao
Journal: Genome Medicine (2025)

The WHO recently released a second edition of the mutation catalog for predicting drug resistance in Mycobacterium tuberculosis (MTB). This study evaluated its effectiveness compared to existing whole-genome sequencing (WGS)-based prediction methods and proposes a novel approach for its optimization. We tested the accuracy of five tools—the WHO catalog, TB Profiler, SAM-TB, GenTB, and MD-CNN—for predicting drug susceptibility on a global dataset of 36,385 MTB isolates with high-quality phenotypic drug susceptibility testing (DST) and WGS data. By integrating the genotypic DST predictions of these five tools in an ensemble machine learning framework, we developed an improved computational model for MTB drug susceptibility prediction. We then validated the ensemble model on 860 MTB isolates with phenotypic and WGS data collected in Shenzhen, China (2013–2019) and Valencia, Spain (2014–2016). Among the five genotypic DST tools for predicting susceptibility to ten drugs, MD-CNN exhibited the highest overall performance (AUC 92.1%; 95% CI 89.8–94.4%). The WHO catalog demonstrated the highest specificity of 97.3% (95% CI 95.8–98.4%), while TB Profiler had the best sensitivity at 79.5% (95% CI 71.8–86.2%). The ensemble machine learning model (AUC 93.4%; 95% CI 91.4–95.4%) outperformed all of the five individual tools, with a specificity of 95.4% (95% CI 93.0–97.6%) and a sensitivity of 84.1% (95% CI 78.8–88.8%), principally due to considerable improvements in second-line drug resistance predictions (AUC 91.8%; 95% CI 89.6–94.0%). The second edition of the WHO MTB mutation catalog does not, by itself, perform better than existing tools for predicting MTB drug resistance. An integrative approach combining the WHO catalog with other genotypic DST methods significantly enhances prediction accuracy.
A global call to action for disability inclusion in health research
Authors: Anna M. Anderson, Rachelle A. Martin, Willyanne DeCormier Plosky, Lieketseng Ned, Bonnielin K. Swenor, Jodie Bailie, Kaaren Mathias, Jasjot K. Maggo, Mildred A. Omino, Amy M. Russell, Anna M. M. Lawson, Anna E. Brown, Barbara E. Bierer, Sameed Shariq, Mrisho Mwifadhi, Katherine H. O. Deane, Sharad Philip, Victoria Shepherd, Nicola E. Walsh, Gretl A. McHugh
Journal: Nature Medicine (2025)
An SSTR2–somatostatin chemotactic axis drives T cell progenitor homing to the intestines
Authors: Borja Ocón, Kevin F. Brulois, Husein Hadeiba, Mohammed Gaafarelkhalifa, Aiman Ayesha, Yuhan Bi, Menglan Xiang, Jacob Gulman, Maryam Kooshesh, Junliang Pan, Eugene C. Butcher
Journal: Nature Immunology (2025)
Socio-economic status is a social construct with heritable components and genetic consequences
Authors: Abdel Abdellaoui, Hilary C. Martin, Martin Kolk, Adam Rutherford, Michael Muthukrishna, Felix C. Tropf, Melinda C. Mills, Brendan P. Zietsch, Karin J. H. Verweij, Peter M. Visscher
Journal: Nature Human Behaviour (2025)
Projectome-based characterization of hypothalamic peptidergic neurons in male mice
Authors: Zhuolei Jiao, Taosha Gao, Xiaofei Wang, Ao Wang, Yawen Ma, Li Feng, Le Gao, Lingfeng Gou, Wen Zhang, Nasim Biglari, Emma E. Boxer, Lukas Steuernagel, Xiaojing Ding, Zixian Yu, Mingjuan Li, Mengtong Gao, Mingkun Hao, Hua Zhou, Xuanzi Cao, Shuaishuai Li, Tao Jiang, Jiamei Qi, Xueyan Jia, Zhao Feng, Biyu Ren, Yu Chen, Xiaoxue Shi, Dan Wang, Xinran Wang, Luyao Han, Yikai Liang, Liuqin Qian, Chenxi Jin, Jiawen Huang, Wei Deng, Congcong Wang, E Li, Yue Hu, Zi Tao, Humingzhu Li, Xiang Yu, Min Xu, Hung-Chun Chang, Yifeng Zhang, Huatai Xu, Jun Yan, Anan Li, Qingming Luo, Ron Stoop, Scott M. Sternson, Jens C. Brüning, David J. Anderson, Mu-ming Poo, Yidi Sun, Shengjing Xu, Hui Gong, Yan-Gang Sun, Xiaohong Xu
Journal: Nature Neuroscience (2025)
Estimates of the Mutation Rate per Year Can Explain Why the Molecular Clock Depends on Generation Time
Authors: Loveday Lewin, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2025)

Abstract Rates of molecular evolution are known to vary across species, often deviating from the classical expectation of a strict molecular clock. In many cases, the rate of molecular evolution has been found to correlate to generation time, an effect that could be explained if species with shorter generation times have higher mutation rates per year. We investigate this hypothesis using direct estimates of the mutation rate for 133 eukaryotic species from diverse taxonomic groups. Using a phylogenetic comparative approach, we find a strong negative correlation between mutation rate per year and generation time, consistent across all phylogenetic groups. Our results provide a simple explanation for why generation time plays a pivotal role in driving rates of molecular evolution across eukaryotes.
Road to extinction? Past and present population structure and genomic diversity in the koala
Authors: Binia De Cahsan, Marcela Sandoval Velasco, Michael V Westbury, David A Duchêne, Mikkel H Strander Sinding, Hernán E Morales, Daniela C Kalthoff, Ian Barnes, Selina Brace, Roberto Portela Miguez, Alfred L Roca, Alex D Greenwood, Rebecca N Johnson, Matthew J Lott, M Thomas P Gilbert
Journal: Molecular Biology and Evolution (2025)

Koalas are arboreal herbivorous marsupials, endemic to Australia. During the late 1800s and early 1900s, the number of koalas declined dramatically due to hunting for their furs. In addition, anthropogenic activities have further decimated their available habitat, and decreased population numbers. Here, we utilise 37 historic and 25 modern genomes sampled from across their historic and present geographic range, to gain insights into how their population structure and genetic diversity have changed across time; assess the genetic consequences of the period of intense hunting, and the current genetic status of this iconic Australian species. Our analyses reveal how genome-wide heterozygosity has decreased through time and unveil previously uncharacterised mitochondrial haplotypes and nuclear genotypes in the historic dataset, which are absent from today's koala populations.
The expansion and diversification of epigenetic regulatory networks underpins major transitions in the evolution of land plants
Authors: Romy Petroll, Ranjith K Papareddy, Rafal Krela, Alice Laigle, Quentin Riviere, Kateřina Bišová, Iva Mozgová, Michael Borg
Journal: Molecular Biology and Evolution (2025)

Epigenetic silencing is essential for regulating gene expression and cellular diversity in eukaryotes. While DNA and H3K9 methylation silence transposable elements (TEs), H3K27me3 marks deposited by the Polycomb repressive complex 2 (PRC2) silence varying proportions of TEs and genes across different lineages. Despite the major development role epigenetic silencing plays in multicellular eukaryotes, little is known about how epigenetic regulatory networks were shaped over evolutionary time. Here, we analyse epigenomes from diverse species across the green lineage to infer the chronological epigenetic recruitment of genes during land plant evolution. We first reveal the nature of plant heterochromatin in the unicellular chlorophyte microalga Chlorella sorokiniana and identify several genes marked with H3K27me3, highlighting the deep origin of PRC2-regulated genes in the green lineage. By incorporating genomic phylostratigraphy, we show how genes of differing evolutionary age occupy distinct epigenetic states in plants. While young genes tend to be silenced by H3K9 methylation, genes that emerged in land plants are preferentially marked with H3K27me3, some of which form part of a common network of PRC2-repressed genes across distantly-related species. Finally, we analyse the potential recruitment of PRC2 to plant H3K27me3 domains and identify conserved DNA-binding sites of ancient transcription factor (TF) families known to interact with PRC2. Our findings shed light on the conservation and potential origin of epigenetic regulatory networks in the green lineage, while also providing insight into the evolutionary dynamics and molecular triggers that underlie the adaptation and elaboration of epigenetic regulation, laying the groundwork for its future consideration in other eukaryotic lineages.
Multianalyte Nanopore Detection of Alzheimer's Biomarkers: A Label‐Free Platform with Improved Sensitivity and Range
Authors: Qianshan Liu, Yulin Ouyang, Yunjiao Wang, Shuo Zhou, Yang Zhan, Liang Wang
Journal: Advanced Healthcare Materials (2025)

Due to matrix interference, detection methods for protein biomarkers in body fluids are limited. Commonly used methods often require antibody modification or fluorescent labeling. Furthermore, subtle differences in protein sequences make it more challenging to detect and differentiate multiple biomarkers. This study introduces a novel nanopore-based method for simultaneous, label-free detection of key Alzheimer's disease (AD) biomarkers in biological samples. The technique enables distinguishable and ultrasensitive detection of amyloid-beta peptides (Aβ42,Aβ40) amyloid precursor protein (APP669-711), and tubulin associated unit (Tau) proteins in cerebrospinal fluid and serum. The method successfully identifies AD biomarkers by directly detecting Aβ42 in cerebrospinal fluid and can detect age-dependent changes in Aβ levels in AD mice models, demonstrating reliability comparable to established enzyme linked immunosorbent assay (ELISA) assays and brain plaque-staining confocal imaging. Notably, this method achieves significant advancements in detecting 2.1 pm Aβ42 and 1.5 pm APP(669-711), as well as 627 fm Aβ40 in serum. This improvement in nanopore technology addresses the challenges of detecting Aβ and Tau alterations in complex biological samples and differentiating between similar protein sequences. The study marks a significant advancement in the analysis of pathogenic proteins in physiological samples, also offering a powerful tool for AD research and diagnostics.
Müller Glial‐Derived Small Extracellular Vesicles Mitigate RGC Degeneration by Suppressing Microglial Activation via Cx3cl1‐Cx3cr1 Signaling
Authors: Hai‐Dong Qian, Xiang‐Yuan Song, Guan‐Wen He, Xue‐Ni Peng, Ying Chen, Pan Huang, Jing Zhang, Xiao‐Yan Lin, Qiao Gao, Sen‐Miao Zhu, Tong Li, Zai‐Long Chi
Journal: Advanced Healthcare Materials (2025)

Retinal ganglion cell (RGC) degeneration leads to irreversible blindness. Müller glia (MG) play pivotal roles in retinal homeostasis and disease through paracrine signaling. Small extracellular vesicles (sEVs) are bioactive nanomaterials derived from all types of live cells and are recognized as a potential strategy for neuroprotective therapy. The aim of this study is to investigate the potential roles of MG-derived sEVs (MG-sEVs) in a mouse model of optic nerve injury (ONC). It is found that MG-sEVs treatment effectively mitigates RGC degeneration and suppresses microglial activation, thereby improves visual function in ONC mice. Retinal transcriptomic analysis reveals a strong correlation between C-x3-c motif chemokine ligand 1 (Cx3cl1)-mediated glial activation and inflammation. Subsequently, it is confirmed that the expression levels of Cx3cl1 and proinflammatory cytokines are significantly decreased in retinas treated with MG-sEVs. The components analysis of MG-sEVs cargo identifies that miR-125b-5p and miR-16-5p target Cx3cl1 gene to regulate its expression. It is also observed that Cx3cl1 colocalizes on the microglia of transgenic C-x3-c motif chemokine receptor 1 (Cx3Cr1)-GFP mice. In conclusion, MG-sEVs mitigate RGC degeneration by suppressing microglial activation via Cx3cl1-Cx3cr1 signaling. This research provides additional opportunities for the treatment of RGC degeneration.