PNAS nexusPub Date : 2025-08-05eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf247
Benjamin M Winger, Frank A La Sorte, Matthew D Hack, Teresa M Pegan
{"title":"Joint evolution of the biogeography and phenology of seasonal migration.","authors":"Benjamin M Winger, Frank A La Sorte, Matthew D Hack, Teresa M Pegan","doi":"10.1093/pnasnexus/pgaf247","DOIUrl":"10.1093/pnasnexus/pgaf247","url":null,"abstract":"<p><p>In migratory species, the temporal phases of the annual cycle are linked to seasonally shifting geographic ranges. Despite intense interest in the annual cycle ecology of migratory species, a synthetic understanding of the relationship between the biogeography of the migratory annual cycle and its phenology remains elusive. Here, we investigate the spatiotemporal structure of the annual cycle in a phylogenetic comparative framework by developing a method to demarcate the pacing of annual cycle stages using eBird, a massive avian occurrence dataset, and applying it to migratory passerine birds breeding in North America. Our analyses reveal a striking negative correlation between the durations of the breeding versus nonbreeding periods, indicating that a tradeoff between the lengths of the two stationary periods is the primary axis of variation in annual cycle pacing. Our results further show that the duration of annual occupancy in the breeding versus stationary nonbreeding ranges predicts the geographic separation of these seasonal ranges, demonstrating that the ratio of time spent on stationary breeding versus nonbreeding locations evolves in tandem with a species' migration distance. In contrast, the amount of time during which species undergo seasonal migration-that is, the duration of the seasonal periods when species' geographic ranges shift latitudinally-varies relatively little across species compared with the length of the stationary periods. Our study helps untangle the complexity of seasonal distributions and schedules to reveal the integrated evolution of the biogeography of the migratory cycle, its pacing, and life history tradeoffs among species.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf247"},"PeriodicalIF":3.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-08-05eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf215
José María Fernández-Palacios, Melania Fructuoso, Juan Carlos Illera, Juan Carlos Rando, Lea de Nascimento, Enrique Fernández-Palacios, Jairo Patiño, Rüdiger Otto, Álvaro Castilla-Beltrán, Esther Martín González, Raúl Orihuela-Rivero, Josep Antoni Alcover, Robert J Whittaker
{"title":"A synthesis of terrestrial species extinctions in the Macaronesian Islands and their correspondence with human occupancy.","authors":"José María Fernández-Palacios, Melania Fructuoso, Juan Carlos Illera, Juan Carlos Rando, Lea de Nascimento, Enrique Fernández-Palacios, Jairo Patiño, Rüdiger Otto, Álvaro Castilla-Beltrán, Esther Martín González, Raúl Orihuela-Rivero, Josep Antoni Alcover, Robert J Whittaker","doi":"10.1093/pnasnexus/pgaf215","DOIUrl":"10.1093/pnasnexus/pgaf215","url":null,"abstract":"<p><p>We present the first synthesis of all known terrestrial endemic species extinctions in the biogeographical region of Macaronesia, covering all archipelagos (Azores, Madeira, Selvagens, the Canaries, and Cabo Verde) and multiple taxa (arthropods, birds, bryophytes, fungi, land molluscs, lichens, mammals, reptiles, and vascular plants). This list also includes information on the original distribution of extinct species, extinction chronologies, and likely causes of extinction, as reported by the original works' authors. Our survey identified 220 extinction records, with the highest numbers observed among land snails (111 species), arthropods (55), birds (27), and reptiles (15). The proportional impact of extinction was greatest among vertebrates: birds (50% of the original endemics lost), mammals (43%), and reptiles (28%). Very few extinctions were recorded in vascular plants or bryophytes, and none in fungi or lichens. However, these low levels of loss may partly reflect the scarcity of historical and fossil records for these taxa. Exactly half of the recorded endemic species losses (including nearly all vertebrates, as well as the arthropods and vascular plants) have extinction chronologies matching with the human occupation of the islands, providing a minimum estimate of the number of extinction events that may be directly or indirectly attributed to human activities.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf215"},"PeriodicalIF":3.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-31eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf243
Ivo Steimanis, Thomas Falk, Lara Bartels, Vishwambhar Duche, Björn Vollan
{"title":"The role of women in learning games and water management outcomes.","authors":"Ivo Steimanis, Thomas Falk, Lara Bartels, Vishwambhar Duche, Björn Vollan","doi":"10.1093/pnasnexus/pgaf243","DOIUrl":"10.1093/pnasnexus/pgaf243","url":null,"abstract":"<p><p>Economic games have emerged as promising tools for fostering sustainable resource management, yet their gender dynamics remain underexplored. We examine how women's participation relates to the effectiveness of game-based learning in 56 Indian communities facing water management challenges. These structured experiential learning environments allow participants to develop system understanding, problem-solving capacities, and collective action through active engagement. Our results suggest that greater female involvement is associated with improved water management outcomes 2 years after the intervention. Notably, the presence of female leaders correlated with broader participation among women, which in turn was linked to the development of more effective management rules. These findings indicate that gender-balanced participation may enhance the success of such interventions. Incorporating women in game-based learning has the potential to support long-term improvements in resource management, highlighting the importance of inclusive approaches.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf243"},"PeriodicalIF":3.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-29eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf242
Lev Ostrer, Taylor A Crooks, Michael D Howe, Sang Vo, Ziyi Jia, Pooja Hegde, Nathan Schacht, Courtney C Aldrich, Anthony D Baughn
{"title":"Mechanism of the dual action self-potentiating antitubercular drug morphazinamide.","authors":"Lev Ostrer, Taylor A Crooks, Michael D Howe, Sang Vo, Ziyi Jia, Pooja Hegde, Nathan Schacht, Courtney C Aldrich, Anthony D Baughn","doi":"10.1093/pnasnexus/pgaf242","DOIUrl":"10.1093/pnasnexus/pgaf242","url":null,"abstract":"<p><p>Pyrazinamide (PZA) is a cornerstone of first-line antitubercular drug therapy and is unique in its ability to kill nongrowing populations of <i>Mycobacterium tuberculosis</i> through disruption of coenzyme A (CoA) metabolism. Unlike other drugs, PZA action is conditional and requires potentiation by host-relevant environmental stressors, such as low pH and nutrient limitation. Despite its pivotal role in tuberculosis therapy, the durability of this crucial drug is challenged by the emergent spread of drug resistance. To advance drug discovery efforts, we characterized the activity of a more potent PZA analog, morphazinamide (MZA). Here, we demonstrate that like PZA, MZA acts in part through impairment of CoA metabolism. Unexpectedly, we find that, in contrast to PZA, MZA does not require potentiation and maintains bactericidal activity against PZA-resistant strains due to an additional mechanism involving aldehyde release. Further, we find that the principal mechanism for resistance to the aldehyde component is through promoter mutations that increase expression of the mycothiol oxidoreductase MscR. Our findings reveal a dual-action synergistic mechanism of MZA that results in a faster kill rate and a higher barrier to resistance. These observations provide new insights for the discovery of improved therapeutic approaches for addressing the growing problem of drug-resistant tuberculosis.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf242"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk of bias and low reproducibility in meta-analytic evidence from fast-tracked publications during the coronavirus disease 2019 pandemic.","authors":"Xuerong Liu, Wei Li, Qianyu Zhang, Jingyu Lei, Xiaodi Han, Yaozhi Wang, Chang Shen, Yu Zhan, Yanyan Li, Liping Shi, Jidong Ren, Jingxuan Zhang, Xiaolin Zhang, Yan Wu, Haiping Liao, Lei Xia, Jia Luan, Yue Li, Tatum Madeleine Cummins, Zhengzhi Feng, Chunji Huang, Zhiyi Chen","doi":"10.1093/pnasnexus/pgaf238","DOIUrl":"10.1093/pnasnexus/pgaf238","url":null,"abstract":"<p><p>The fast-tracked publication of coronavirus disease 2019 (COVID-19)-related meta-analytic evidence has undeniably facilitated rapid public health policymaking; however, concerns are mounting that this publication policy may compromise research quality and scientific integrity. To investigate this, we conducted a meta-research study systematically evaluating risk of bias (ROB), transparency, and reproducibility in pandemic-era meta-analyses synthesizing COVID-19-derived mental health problem epidemics. From 98 identified studies-including data from 18.6 million individuals across 94 countries-we observed significant ROBs in publication, with one new meta-analysis published approximately every 5 days at peak output. Despite apparent sample diversity, nearly half of participants were from China, and only 8.9% originated from less economically developed countries. Of these meta-analyses, a substantial proportion (70.6%) showed discrepancies between Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided reporting and actual research conducts, while 57.1% exhibited high methodological ROBs due to insufficient data sources and lack of sensitivity analysis. Alarmingly, none achieved full computational reproducibility, and fewer than one-fifth were fully replicable. Furthermore, neither publication in high-impact journals, citation performance, nor fast-track publication mode correlated with lower ROBs that we identified above. To address these limitations, we re-estimated global COVID-19-derived mental health epidemics using their individual participant data after minimizing identified ROBs. Our recalibrated meta-analytic findings provide more reliable benchmarks for understanding the pandemic's mental health impact. This study demonstrated that rigorous methodology and scientific integrity must remain central priorities-even under urgent, crisis-driven conditions-establishing a foundation for transparent, reproducible, and unbiased global mental health surveillance during public health emergencies.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf238"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-29eCollection Date: 2025-07-01DOI: 10.1093/pnasnexus/pgaf194
Hany Farid
{"title":"Mitigating the harms of manipulated media: Confronting deepfakes and digital deception.","authors":"Hany Farid","doi":"10.1093/pnasnexus/pgaf194","DOIUrl":"10.1093/pnasnexus/pgaf194","url":null,"abstract":"<p><p>The ability to distort the visual record is not new. Airbrushed images attempted to alter the historical archives in the early 1900s. Today, digitally manipulated cheapfakes and deepfakes supercharge the spread of lies and conspiracies. While not fundamentally new, today's enhanced ability to easily create, distribute, and amplify manipulated media has heightened the risks. Reasonable and proportional interventions can and should be adopted that would allow for the creative uses of these powerful new technologies while mitigating the risk they pose to individuals, societies, and democracies.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf194"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-29eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf241
Zijun Wang, Lik-Wei Wong, Sreedharan Sajikumar
{"title":"Differential expression of long-term depression, and synaptic tagging and capture in mouse hippocampal area CA2 synapses.","authors":"Zijun Wang, Lik-Wei Wong, Sreedharan Sajikumar","doi":"10.1093/pnasnexus/pgaf241","DOIUrl":"10.1093/pnasnexus/pgaf241","url":null,"abstract":"<p><p>CA2 hippocampal neurons have received renewed interest due to their unique functions and plasticity properties that differ between synapses within the same neuronal population. However, detailed studies on long-term depression (LTD) in CA2 pyramidal neurons are lacking. In this study, LTD was induced and characterized at both Schaffer collateral-CA2 (SC-CA2) and entorhinal cortex-CA2 (EC-CA2) synapses in young, male mice. This LTD was found to be dependent on N-methyl-D-aspartate receptors, protein synthesis, and p75 neurotrophin receptors. However, weaker stimulations could only induce early LTD in EC-CA2 but not SC-CA2 synapses, consistent with its \"plasticity-resistant\" nature. CA2 LTD is capable of undergoing heterosynaptic synaptic tagging and capture (STC), although the machinery involved differs between SC-CA2 and EC-CA2 synapses. SC-CA2, but not EC-CA2, requires precursor brain-derived neurotrophic factor activity to maintain LTD. Subsequently, quantitative shotgun proteomics analysis yields complexin-2 as a strong candidate plasticity-related product involved in LTD in the CA2. These results reveal interesting differences in STC machinery between synaptic populations of a common set of neurons, enhancing our understanding of hippocampal circuitry involving the CA2. Interesting implications regarding the heterogeneous biochemical makeup of CA2 pyramidal neurons and fundamental STC theory that arise as a consequent of our results are also discussed further.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf241"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-29eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf235
Julian A Arts, Sofia Fallo, Melanie S Florencio, Jos G A Smits, Dulce Lima Cunha, Janou A Y Roubroeks, Mor M Dickman, Vanessa L S LaPointe, Rosemary Yu, Huiqing Zhou
{"title":"Prediction of cell states and key transcription factors of the human cornea through integrated single-cell omics analyses.","authors":"Julian A Arts, Sofia Fallo, Melanie S Florencio, Jos G A Smits, Dulce Lima Cunha, Janou A Y Roubroeks, Mor M Dickman, Vanessa L S LaPointe, Rosemary Yu, Huiqing Zhou","doi":"10.1093/pnasnexus/pgaf235","DOIUrl":"10.1093/pnasnexus/pgaf235","url":null,"abstract":"<p><p>The cornea, a transparent tissue composed of multiple layers, allows light to enter the eye. Several single-cell RNA-seq (scRNA-seq) analyses have been performed to explore the cell states and to understand the cellular composition of the human cornea. However, inconsistences in cell state annotations between these studies complicate the application of these findings in corneal studies. To address this, we integrated scRNA-seq data from four published studies and created a human corneal cell state meta-atlas. This meta-atlas was subsequently evaluated in two applications. First, we developed a machine learning pipeline cPredictor, using the human corneal cell state meta-atlas as input, to annotate corneal cell states. We demonstrated the accuracy of cPredictor and its ability to identify novel marker genes and rare cell states in the human cornea. Furthermore, cPredictor revealed the differences of the cell states between pluripotent stem cell-derived corneal organoids and the human cornea. Second, we integrated the scRNA-seq-based cell state meta-atlas with chromatin accessibility data, conducting motif-focused and gene regulatory network analyses. These approaches identified distinct transcription factors (TFs) driving cell states of the human cornea. The novel marker genes and TFs were validated by immunohistochemistry. Overall, this study offers a reliable and accessible reference for profiling corneal cell states, which facilitates future research in cornea development, disease, and regeneration.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf235"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-28eCollection Date: 2025-09-01DOI: 10.1093/pnasnexus/pgaf236
Nicholas T Thomas, Camille R Brightwell, Allison M Owen, Alexander R Keeble, Sabin Khadgi, Yuan Wen, Christopher S Fry, Kevin A Murach
{"title":"Satellite cells choreograph an immune cell-fibrogenic cell circuit during mechanical loading in geriatric skeletal muscle.","authors":"Nicholas T Thomas, Camille R Brightwell, Allison M Owen, Alexander R Keeble, Sabin Khadgi, Yuan Wen, Christopher S Fry, Kevin A Murach","doi":"10.1093/pnasnexus/pgaf236","DOIUrl":"10.1093/pnasnexus/pgaf236","url":null,"abstract":"<p><p>Muscle stem cells, or satellite cells (SCs), decline in number throughout the lifespan and may become senescent in very old age. Whether and how remaining SCs contribute to muscle adaptation in the oldest-old is unclear. Using acute mechanical overload in geriatric SC replete and depleted mice (28-month-old) combined with single-cell RNA-sequencing, we show: (i) subsets of geriatric SCs display signs of senescence as well as normal fate progression during overload, (ii) SCs express markers that may contribute to the regulation of innervation, (iii) the presence of SCs during overload enhances global intercellular communication and increases mRNA levels of the cell surface receptor <i>Cd74</i> in immune cells, (iv) macrophage migration inhibitory factor (<i>Mif</i>), the primary ligand for CD74, is enriched in fibrogenic cells and is more pronounced in the absence of SCs-perhaps to normalize dysregulated fibrotic signaling and migration in macrophages, and (v) SCs influence cell fate dynamics to promote the canonical macrophage response to hypertrophic loading. Our findings expose the behavior of SCs in response to mechanical loading in the oldest-old in vivo and reveal a SC-macrophage-fibrogenic cell circuit in geriatric muscle that could support an early proadaptive inflammatory environment.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 9","pages":"pgaf236"},"PeriodicalIF":3.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-25eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf234
Jinhua Sheng, Yu Xin, Qiao Zhang, Luyun Wang, Binbing Wang
{"title":"An imaging genetics network model for clinical score assessment in Alzheimer's disease.","authors":"Jinhua Sheng, Yu Xin, Qiao Zhang, Luyun Wang, Binbing Wang","doi":"10.1093/pnasnexus/pgaf234","DOIUrl":"10.1093/pnasnexus/pgaf234","url":null,"abstract":"<p><p>Imaging genomics has recently emerged as a prominent focus in Alzheimer's disease (AD) research, showing great potential in predicting and diagnosing. In this paper, we propose a dual-stream imaging genetics network (DS-IGN) approach to AD clinical score assessment. DS-IGN is composed of two branches: one processes longitudinal data (neuroimaging) and the other handles static data (gene information). The imaging branch leverages hypergraphs to capture high-order relationships, constructing hypergraphs for samples and image features and performing weighted fusion. The genetic branch introduces an attention mechanism to adaptively adjust the weights of different genetic loci, which is particularly effective when multiple genes interact. By integrating both imaging and genetic features, DS-IGN effectively predicts patients' clinical scores in advance, providing early warnings of cognitive decline and supporting timely interventions to slow disease progression.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf234"},"PeriodicalIF":3.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}