tbuckley/cabot-search huggingface dataset:
Cause-specific mortality in 13,099 patients with metabolic dysfunction-associated steatotic liver disease in Sweden
Authors: Gabriel Issa, Ying Shang, Rickard Strandberg, Hannes Hagström, Axel Wester
Journal: Journal of Hepatology (2025)

Data on cause-specific mortality in metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. We aimed to determine the rate and risk of death from different causes in patients with MASLD compared to the general population in Sweden. In this population-based cohort study, we identified individuals with an ICD-10 code for MASLD in inpatient or specialized outpatient care using Swedish healthcare registers 2002-2020 (n=13,099) and matched them with up to 10 controls (median 9) from the general population for age, sex, municipality, and calendar year (n=118,884). We used Cox regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for eleven different primary causes of death. 15-year cumulative incidences of death were calculated while accounting for competing risks. In total, 1,628 (12.4%) deaths occurred in patients with MASLD and 9,119 (7.7%) in controls during a median follow-up of 4.7 (interquartile range [IQR] 2.0-9.2) and 5.8 years (IQR 2.7-10.5), respectively. MASLD was associated with higher all-cause mortality (HR=1.85, 95%CI=1.74-1.96) and higher rates of all specific causes of death except mental health disorder. The strongest associations were observed for non-hepatocellular carcinoma (HCC) liver-related (HR=26.9, 95%CI=19.4-37.3) and HCC-related mortality (HR=35.0, 95%CI=17.0-72.1). However, the highest estimated 15-year cumulative incidence of death in patients with MASLD was for non-HCC cancer (7.3%) and cardiovascular disease (7.2%). MASLD was strongly associated with liver- and HCC-related mortality, but the absolute risks of death were highest for non-HCC cancer and cardiovascular disease. Mortality was increased for nearly all causes in patients with MASLD, suggesting that earlier multidisciplinary care is needed to reduce excess mortality. Previous studies on mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were either small, restricted to liver-related mortality, relying on liver biopsy to identify patients and thus inducing selection bias, or mainly using data from old cohorts. In a nationwide cohort study of all patients diagnosed with MASLD in inpatient or specialized outpatient care in Sweden between 2002 and 2020, we found a nearly doubled all-cause mortality rate and higher mortality than the general population from a wide range of causes, indicating that earlier multidisciplinary care may be needed to reduce premature mortality in patients with MASLD. The absolute risk estimates of death in our study may be useful for clinicians and policymakers to inform patients about their prognosis and potentially implement clinical or public health strategies to reduce premature mortality.
Integrating multimodal data to understand cortical circuit architecture and function
Authors: Anton Arkhipov, Nuno da Costa, Saskia de Vries, Trygve Bakken, Corbett Bennett, Amy Bernard, Jim Berg, Michael Buice, Forrest Collman, Tanya Daigle, Marina Garrett, Nathan Gouwens, Peter A. Groblewski, Julie Harris, Michael Hawrylycz, Rebecca Hodge, Tim Jarsky, Brian Kalmbach, Jerome Lecoq, Brian Lee, Ed Lein, Boaz Levi, Stefan Mihalas, Lydia Ng, Shawn Olsen, Clay Reid, Joshua H. Siegle, Staci Sorensen, Bosiljka Tasic, Carol Thompson, Jonathan T. Ting, Cindy van Velthoven, Shenqin Yao, Zizhen Yao, Christof Koch, Hongkui Zeng
Journal: Nature Neuroscience (2025)
CAR T or NK cells targeting mismatched HLA-DR molecules in acute myeloid leukemia after allogeneic hematopoietic stem cell transplant
Authors: Shunya Ikeda, Kana Hasegawa, Yosuke Kogue, Takao Arimori, Ryuhei Kawamoto, Tansri Wibowo, Moto Yaga, Yuri Inada, Hirofumi Uehara, Miwa Matsubara, Mana Tachikawa, Makiko Suga, Shuhei Kida, Kumi Shibata, Kazuhito Tsutsumi, Kentaro Fukushima, Jiro Fujita, Tomoaki Ueda, Shinsuke Kusakabe, Akihisa Hino, Michiko Ichii, Asao Hirose, Hirohisa Nakamae, Masayuki Hino, Takafumi Nakao, Megumu Inoue, Kyoko Yoshihara, Satoshi Yoshihara, Shuji Ueda, Tetsuro Tachi, Hideki Kuroda, Koki Murakami, Noriyuki Kijima, Haruhiko Kishima, Eri Igashira, Mari Murakami, Tsuyoshi Takiuchi, Tadashi Kimura, Takashi Hiroshima, Toru Kimura, Yasushi Shintani, Chihaya Imai, Kosuke Yusa, Ryota Mori, Takayuki Ogino, Hidetoshi Eguchi, Kiyoshi Takeda, Yusuke Oji, Atsushi Kumanogoh, Junichi Takagi, Naoki Hosen
Journal: Nature Cancer (2025)
Neural ensembles that encode nocifensive mechanical and heat pain in mouse spinal cord
Authors: Ming-Dong Zhang, Jussi Kupari, Jie Su, Kajsa A. Magnusson, Yizhou Hu, Laura Calvo-Enrique, Dmitry Usoskin, Gioele W. Albisetti, Mikaela M. Ceder, Katharina Henriksson, Andrew D. Leavitt, Hanns Ulrich Zeilhofer, Tomas Hökfelt, Malin C. Lagerström, Patrik Ernfors
Journal: Nature Neuroscience (2025)

Acute pain is an unpleasant experience caused by noxious stimuli. How the spinal neural circuits attribute differences in quality of noxious information remains unknown. By means of genetic capturing, activity manipulation and single-cell RNA sequencing, we identified distinct neural ensembles in the adult mouse spinal cord encoding mechanical and heat pain. Reactivation or silencing of these ensembles potentiated or stopped, respectively, paw shaking, lifting and licking within but not across the stimuli modalities. Within ensembles, polymodal Gal+ inhibitory neurons with monosynaptic contacts to A-fiber sensory neurons gated pain transmission independent of modality. Peripheral nerve injury led to inferred microglia-driven inflammation and an ensemble transition with decreased recruitment of Gal+ inhibitory neurons and increased excitatory drive. Forced activation of Gal+ neurons reversed hypersensitivity associated with neuropathy. Our results reveal the existence of a spinal representation that forms the neural basis of the discriminative and defensive qualities of acute pain, and these neurons are under the control of a shared feed-forward inhibition.
Phase of firing does not reflect temporal order in sequence memory of humans and recurrent neural networks
Authors: Stefanie Liebe, Johannes Niediek, Matthijs Pals, Thomas P. Reber, Jennifer Faber, Jan Boström, Christian E. Elger, Jakob H. Macke, Florian Mormann
Journal: Nature Neuroscience (2025)

Abstract The temporal order of a sequence of events has been thought to be reflected in the ordered firing of neurons at different phases of theta oscillations. Here we assess this by measuring single neuron activity (1,420 neurons) and local field potentials (921 channels) in the medial temporal lobe of 16 patients with epilepsy performing a working-memory task for temporal order. During memory maintenance, we observe theta oscillations, preferential firing of single neurons to theta phase and a close relationship between phase of firing and item position. However, the firing order did not match item order. Training recurrent neural networks to perform an analogous task, we also show the generation of theta oscillations, theta phase-dependent firing related to item position and, again, no match between firing and item order. Rather, our results suggest a mechanistic link between phase order, stimulus timing and oscillation frequency. In both biological and artificial neural networks, we provide evidence supporting the role of phase of firing in working-memory processing.
The landscape of N6-methyladenosine in localized primary prostate cancer
Authors: Xin Xu, Helen Zhu, Rupert Hugh-White, Julie Livingstone, Stefan Eng, Nicole Zeltser, Yujuan Wang, Kinga Pajdzik, Sujun Chen, Kathleen E. Houlahan, Wenqin Luo, Shun Liu, Xi Xu, Minzhi Sheng, Wang Yuan Guo, Jaron Arbet, Yuxi Song, Miranda Wang, Yong Zeng, Shiyan Wang, Guanghui Zhu, Tingxiao Gao, Wei Chen, Xinpei Ci, Wenjie Xu, Kexin Xu, Michele Orain, Valerie Picard, Helene Hovington, Alain Bergeron, Louis Lacombe, Bernard Têtu, Yves Fradet, Mathieu Lupien, Gong-Hong Wei, Marianne Koritzinsky, Robert G. Bristow, Neil E. Fleshner, Xue Wu, Yang Shao, Chuan He, Alejandro Berlin, Theodorus van der Kwast, Hon Leong, Paul C. Boutros, Housheng Hansen He
Journal: Nature Genetics (2025)

N6-methyladenosine (m6A), the most abundant internal RNA modification in humans, regulates most aspects of RNA processing. Prostate cancer is characterized by widespread transcriptomic dysregulation; therefore, we characterized the m6A landscape of 162 localized prostate tumors with matched DNA, RNA and protein profiling. m6A abundance varied dramatically across tumors, with global patterns emerging via complex germline–somatic cooperative regulation. Individual germline polymorphisms regulated m6A abundance, cooperating with somatic mutation of cancer driver genes and m6A regulators. The resulting complex patterns were associated with prognostic clinical features and established the biomarker potential of global and locus-specific m6A patterns. Tumor hypoxia dysregulates m6A profiles, bridging prior genomic and proteomic observations. Specific m6A sites, such as those in VCAN, drive disease aggression, associating with poor outcomes, tumor growth and metastasis. m6A dysregulation is thus associated with key events in the natural history of prostate cancer: germline risk, microenvironmental dysregulation, somatic mutation and metastasis. Transcriptome-wide m6A RNA methylation profile in 162 primary prostate tumors identifies m6A association with prognostic clinical features and disease aggression.
Osteopontin attenuates the foreign-body response to silicone implants
Authors: Michelle F Griffin, Jennifer B Parker, Ruth Tevlin, Norah E Liang, Caleb Valencia, Annah Morgan, Maxwell Kuhnert, Mauricio Downer, Emily L Meany, Jason L Guo, Dominic Henn, Renato S Navarro, Kerry Shefren, Dung Nguyen, Geoffrey C Gurtner, Sarah C Heilshorn, Charles K F Chan, Michael Januszyk, Eric A Appel, Arash Momeni, Derrick C Wan, Michael T Longaker
Journal: Nature Biomedical Engineering (2025)
Neoadjuvant BMS-813160, nivolumab, gemcitabine and nab-paclitaxel for patients with pancreatic cancer
Authors: Patrick M. Grierson, Crystal Wolf, Rama Suresh, Andrea Wang-Gillam, Benjamin R. Tan, Lee Ratner, Peter Oppelt, Olivia Aranha, Ashley Frith, Katrina S. Pedersen, Jennifer Spann, Nicholas Boice, Amberly Brown, John M. Baer, Emily G. Butka, Faiz Ahmad, Yifei Xu, Jingxia Liu, David G. DeNardo, Kian-Huat Lim
Journal: Clinical Cancer Research (2025)

Targeting tumor-associated macrophages through C-C chemokine receptor type 2 (CCRs) in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy and restores T cell immunity in preclinical models. We conducted a phase I/II single institution study (NCT03496662) combining chemotherapy gemcitabine and nab-paclitaxel (GnP), CCR2/5 inhibitor BMS-813160 and nivolumab for four 28-day cycles for patients with borderline resectable (BR) or locally advanced (LA) PDAC. The recommended phase 2 dose (RP2D) of BMS-813160 was established in the 3+3 design. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included resection rate, median progression-free survival (mPFS) and overall survival (mOS). 8 patients were treated with GnP alone (control arm) and 31 patients (29 response evaluable) were treated at RP2D. No grade 3/4 toxicities attributed to nivolumab or BMS-813160 were identified. After 4 cycles of study treatment (N=26), ORR was 35.7% and 16.7% among BR- and LA-PDAC patients respectively, compared to 0% of control patients. 78.6% BR- and 16.7% of LA-PDAC patients who completed study treatment underwent surgical resection. For intent-to-treat analyses, BR-PDAC patients had a mPFS and mOS of 14.6 and 20.4 months respectively; and for LA-PDAC patients, were 14.7 and 17 months, respectively. Biomarker analyses showed decreased intratumoral monocytes, macrophages, enhanced T cell proliferation and effector gene expression. Neoadjuvant BMS-813160/nivolumab/GnP was well tolerated and appears to achieve comparable ORR and resectability to historical data, however with prolonged PFS and OS in LA-PDAC patients, warranting a larger phase II study with a more efficacious CCR2-targeted therapeutic.
Soft Pneumatic Device Designed to Mimic the Periosteal Environment for Regulating the Fate of Mesenchymal Stem Cells
Authors: Gwang‐Bum Im, Jae Gyeong Lee, Hosub Lim, Jae‐Won Lee, Hyun Su Park, Yongju Kim, Nauman Asad, Hak‐Rin Kim, Jeong Jae Wie, Suk Ho Bhang
Journal: Advanced Healthcare Materials (2025)

Abstract Replicating the complex mechanical forces of muscle movement and fluid flow in in vitro cell culture systems is crucial for understanding cell differentiation and development. However, previous research focused on cell differentiation on static micro/nanotextures without a force field or flat 2‐dimensional substrates under a continuous in‐plane mechanical force. In this study, cell differentiation is reported using a spatial geometric platform that can periodically modulate complex mechanical forces through a custom‐made soft pneumatic device (SPD) to mimic the interfaces between periosteum and interstitial fluid. To elucidate fluidic dynamics and cell fates relevant to bone physiology, the platform exhibited distinct functional responses based on mechanical force levels: low mechanotransduction induced mesenchymal stem/progenitor cells differentiation into osteoprogenitor cells (≈1.5‐fold increase in osteo‐differentiation), while high mechanotransduction resulted in structural disruptions resembling cell detachment without protein degradation (≈2‐fold increase in effective cell detachment). Numerical simulations of SPD elucidated the principal mechanical components for programmable cell differentiation and detachment by deconvoluting the in‐plane and out‐of‐plane mechanical forces of the SPD complex mode. This study offers comprehensive and novel insights into the correlation between mechanical forces and cell differentiation, recovery, and injury in organisms.
Overt and covert genetic causes of pediatric acute lymphoblastic leukemia
Authors: Ulrik Stoltze, Stefanie V. Junk, Anna Byrjalsen, Hélène Cavé, Giovanni Cazzaniga, Sarah Elitzur, Eva Fronkova, Lisa Lyngsie Hjalgrim, Roland P. Kuiper, Louise Lundgren, Melina Mescher, Theis Mikkelsen, Agata Pastorczak, Marion Strullu, Jan Trka, Karin Wadt, Shai Izraeli, Arndt Borkhardt, Kjeld Schmiegelow
Journal: Leukemia (2025)
Correction: Krüppel-like factor 3 inhibition by mutated lncRNA <i>Reg1cp</i> results in human high bone mass syndrome
Authors: Mi Yang, Qi Guo, Hui Peng, Yu-Zhong Xiao, Ye Xiao, Yan Huang, Chang-Jun Li, Tian Su, Yun-Lin Zhang, Min-Xiang Lei, Hui-Ling Chen, Tie-Jian Jiang, Xiang-Hang Luo
Journal: The Journal of Experimental Medicine (2025)
Colorectal Tumors in Diverse Patient Populations Feature a Spectrum of Somatic Mutational Profiles
Authors: Marco Matejcic, Jamie K. Teer, Hannah J. Hoehn, Diana B. Diaz, Kritika Shankar, Jun Gong, Nathalie T. Nguyen, Nicole C. Loroña, Domenico Coppola, Clifton G. Fulmer, Ozlen Saglam, Kun Jiang, W. Douglas Cress, Teresita Muñoz-Antonia, Idhaliz Flores, Edna R. Gordián, José A. Oliveras Torres, Seth I. Felder, Julian Sanchez, Jason B. Fleming, Erin M. Siegel, Jennifer A. Freedman, Julie Dutil, Mariana C. Stern, Brooke L. Fridley, Jane C. Figueiredo, Stephanie L. Schmit
Journal: Cancer Research (2025)

Abstract Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic/genomic studies. Leveraging the Latino Colorectal Cancer Consortium (LC3) and other existing datasets, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer to map somatic mutational features by ethnicity and genetic similarity. Global proportions of African, Asian, European, and Native American genetic ancestries were estimated using ADMIXTURE. Associations between these proportions and somatic mutational features were examined using logistic regression. APC, TP53, and KRAS were the top three mutated genes across all participants and in the subset of Latino individuals in LC3. In analyses examining recurrently mutated genes, tumors from patients of Latino ethnicity had fewer KRAS and PIK3CA mutations compared to tumors from non-Latino patients. Genetic ancestry overall was associated with CDC27 mutation status, and African genetic ancestry was associated with SMAD2 mutation status. In exome-wide analyses, African genetic ancestry was significantly associated with higher odds of mutation in KNCN and TMEM184B. Native American genetic ancestry was associated with a lower frequency of microsatellite instability-high (MSI-H) tumors. The SBS11 mutational signature was associated with Native American genetic ancestry as well as Latino ethnicity. In an independent replication dataset, MSK-IMPACT, estimates of association were largely consistent in direction, but non-significant. A meta-analysis of LC3 and MSK-IMPACT showed that African genetic ancestry was significantly associated with KRAS mutation status and MSI status. This work facilitates precision medicine initiatives by providing insights into the contribution of genetic ancestry to molecular features of colorectal tumors.
The Use of CT Densitometry for the Assessment of Emphysema in Clinical Trials: A Position Paper from the Fleischner Society
Authors: Raúl San José Estépar, R. Graham Barr, Sean B Fain, Philippe A Grenier, Eric A. Hoffman, Stephen M Humphries, Miranda Kirby, Nancy Obuchowski, Christopher J Ryerson, Joon Beom Seo, Ruth Tal-Singer, Samuel Y Ash, Alexander A Bankier, James Crapo, MeiLan Han, Liz Kellermeyer, Jonathan Goldin, Cynthia H. McCollough, John D Newell Jr., Bruce E Miller, Lars H Nordenmark, Martine Remy-Jardin, Mathias Prokop, Yoshiharu Ohno, Edwin K Silverman, Charlie Strange, George R Washko, David A. Lynch
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Emphysema's significant morbidity and mortality underscore the need for reliable outcome metrics in clinical trials. However, commonly accepted COPD outcome measures do not adequately capture emphysema severity or progression. Computed tomography (CT) metrics have been validated as accurate indicators of pathological emphysema and predictors of COPD progression, exacerbations, and mortality. This Position Paper reviews the evidence supporting CT densitometry as a biomarker for emphysema, establishes implementation standards, and highlights areas for future research. A systematic literature review addressed three key questions: whether CT densitometry can be used as a diagnostic biomarker of emphysema, whether CT densitometry can be used as prognostic biomarker, and whether longitudinal change in densitometry can be used as a disease progression monitoring biomarker. Emphysema metrics, such as the percentage of low attenuation areas (LAA-950), are validated, highly reproducible diagnostic and prognostic biomarkers. Volume-adjusted lung density is recommended for disease monitoring. Both metrics demonstrate a scan-rescan intra-class correlation coefficient of 0.99 with proper technique. The paper also discusses relevant CT physics, techniques, and sources of variation, including technical factors, physiological changes, and software analysis. Key recommendations for clinical trials include using standardized CT techniques, proper subject selection, and longitudinal evaluation with volume-adjusted lung density.
Dietary whey protein protects against Crohn’s disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome
Authors: Runping Su, Weijie Wen, Yufeng Jin, Zhirui Cao, Zhiyang Feng, Jie Chen, Yu Lu, Guicheng Zhou, Chao Dong, Shanshan Gao, Xue Li, Hu Zhang, Kang Chao, Ping Lan, Xiaojian Wu, Anna Philips, Kun Li, Xiang Gao, Fen Zhang, Tao Zuo
Journal: Gut (2025)

Background The gut microbiome and diet are important factors in the pathogenesis and management of Crohn’s disease (CD). However, the role of the gut phageome under dietary influences is unknown. Objective We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection. Design We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo. Results On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila , which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation. Conclusion Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.
Endothelial-like cancer-associated fibroblasts facilitate pancreatic cancer metastasis via vasculogenic mimicry and paracrine signalling
Authors: Xugang Sun, Wenrun Cai, Haorui Li, Chuntao Gao, Xi Ma, Yu Guo, Danqi Fu, Di Xiao, Zhaoyu Zhang, Yifei Wang, Shengyu Yang, Yukuan Feng, Tiansuo Zhao, Jihui Hao
Journal: Gut (2025)

Background Cancer-associated fibroblasts (CAFs) are highly heterogeneous in the progression of pancreatic ductal adenocarcinoma (PDAC) and vasculogenic mimicry (VM) refers to a phenomenon in which cancer cells adopt endothelial-like characteristics. Objective To identify a novel protumoural CAF subtype undertaking VM. Design We used single-cell RNA sequencing and mIHC to identify FAPα + CD144 + endothelial-like CAFs (endoCAFs) and combined prospective and retrospective analyses to assess its clinical outcomes. Tube formation, proliferation and invasion assay were conducted on cell lines, organoids, the orthotopic tumour model and LSL-Kras G12D/+ , LSL-Trp53 R172H/+ and Pdx1-Cre (KPC) mouse model. Mechanically, we performed cytokine array assays, RNA-sequencing, IP-mass spectrometry, ChIP and luciferase analyses. Importantly, an siRNA delivery nanosystem was developed to precisely target FAPα + CD144 + endoCAFs in vivo. Results FAPα + CD144 + endoCAFs were present in the tumour microenvironment of PDAC, and patients with a higher CD144 + CAFs proportion displayed poor prognosis of PDAC. FAPα + CD144 + endoCAFs not only acquired a VM phenotype to provide metastatic conduits but also promoted the proliferation and invasion of tumour cells in situ through paracrine signalling, thereby actively facilitating the metastasis of tumour cells. The CD144-β-catenin-STAT3 signalling axis was activated, and CD144 and downstream secreted cytokines were transcriptionally upregulated to maintain the dual roles of endoCAFs. A CAF-targeting siRNA delivery nanosystem, via loading FAPα and siCD144, was administered to precisely target FAPα + CD144 + endoCAFs, which substantially inhibited their protumoural roles in vivo. Conclusion FAPα + CD144 + endoCAFs can promote metastasis of PDAC via undertaking VM and paracrine through activation of the CD144-β-catenin-STAT3 signalling axis. CAF-targeting siRNA delivery nanosystem can inhibit tumour progression by precisely targeting FAPα + CD144 + endoCAFs.