tbuckley/cabot-search huggingface dataset:
Atomic Artificial Enzyme for Acute and Chronic Pneumonia (Adv. Healthcare Mater. 9/2025)
Authors: Wei Liu, Di Liu, Tianyi Cui, Yili Wang, Sufei Zhou, Fangzhen Tian, Ke Yang, Wei Wang, Lewei Bi, Kelong Fan, Lan Li, Hao Wang, Xiao‐Dong Zhang
Journal: Advanced Healthcare Materials (2025)
The impact of human accelerated regions on neuronal development
Authors: Jose Manuel Ruiz-Jiménez, Gabriel Santpere
Journal: Trends in Genetics (2025)

Human accelerated regions (HARs) are the fastest-evolving sequences in the human genome since the divergence from chimpanzees. Some of these regions are suspected to have contributed to the evolution of unique human brain features. Recently, Cui et al. conducted a large-scale study identifying which HARs may have influenced neuronal function.
Better Outcome Following Younger Haploidentical Donor Versus Older Matched Unrelated Donor Transplant for Fit Patients With Acute Myeloid Leukemia Transplanted in First Remission: A Study From the Global Committee and the Acute Leukemia Working Party of the <scp>EBMT</scp>
Authors: Yishan Ye, Allain Thibeault Ferhat Berland, Myriam Labopin, Jia Chen, Depei Wu, Didier Blaise, Carmen Di Grazia, Edouard Forcade, Xiao‐jun Huang, Ibrahim Yakoub‐Agha, Urpu Salmenniemi, Patrice Chevallier, Ali Bazarbachi, Arnon Nagler, Eolia Brissot, Lin Li, Yi Luo, Yanmin Zhao, Mohamad Mohty, He Huang, Fabio Ciceri, Norbert Claude Gorin
Journal: American Journal of Hematology (2025)
Gene delivery of a SUMO1-derived peptide rescues neuronal degeneration and motor deficits in an rAAV-α-synuclein-A53T mouse model of Parkinson’s disease
Authors: Zhaohui Liang, Suresh Kanna Murugappan, Yuxuan Li, Man Nga Lai, Yajing Qi, Yi Wang, Ho Yin Edwin Chan, Marianne M Lee, Michael K Chan
Journal: Molecular Therapy (2025)
Clonal Hematopoiesis and Thrombosis
Authors: Cornelia Englisch, Cihan Ay
Journal: American Journal of Hematology (2025)

ABSTRACT Clonal hematopoiesis (CH) has been the focus of many research efforts in the last years and has emerged as a risk modifier for cardiovascular disease morbidity and mortality. While substantial evidence has accumulated regarding its impact on arterial system diseases, the connection with venous thrombosis has only recently been explored. Both clinical and preclinical evidence suggest that the magnitude and mechanism underlying the association of CH with cardiovascular events vary depending on the specific mutated gene involved, indicating a causal link between CH and thrombosis development, not only in the arterial system, particularly in the context of atherosclerosis, but also in venous thrombosis. Although this growing body of knowledge has driven translational research and provided insights for improving clinical management, several questions remain unanswered. This review aims to summarize the available evidence on the link between CH and thrombosis, while highlighting the gaps that need to be addressed in future research.
Evaluation of the anti-CCR4 monoclonal antibody Mogamulizumab in advanced cutaneous T-cell lymphomas and with large cell transformation
Authors: Lou Faltot, Marie Donzel, Georgio Chidiac, Brigitte Balme, Nicolas Romain-Scelle, Marie Perier-Muzet, Stéphane Dalle
Journal: British Journal of Dermatology (2025)

We aimed to compare the response to mogamulizumab in cutaneous T-cell lymphomas between patients with tumour status and/or large cell transformation and those without, and to investigate its effectiveness, depending on the expression levels of the C-C chemokine receptor type 4 (CCR4). We found that response to mogamulizumab at 8 weeks (primary endpoint) was significantly higher in patients without tumour status and/or large cell transformation. Conversely, no significant difference was found regarding CCR4 expression levels between mogamulizumab responders and non-responders.
Validation and Derivation of MicroRNA-based Germline Signatures Predicting Radiation Toxicity in Prostate Cancer
Authors: Amar U. Kishan, Kristen McGreevy, Luca Valle, Michael Steinberg, Beth Neilsen, Maria Casado, Minsong Cao, Donatello Telesca, Joanne B. Weidhaas
Journal: Clinical Cancer Research (2025)

Abstract Purpose: While radiation therapy (RT) is one of the primary treatment modalities used in the treatment of cancer, patients often experience toxicity during or after treatment. RT-induced genitourinary (GU) toxicity is a significant survivorship challenge for patients with prostate cancer (PCa), but identifying those at risk has been challenging. Herein, we attempt (i) to validate a previously identified biomarker of late RT-induced GU toxicity, PROSTOX, consisting primarily of microRNA-based germline biomarkers (mirSNPs), and (ii) to investigate the possibility of temporally and genetically defining other forms of RT-associated GU toxicity. Experimental Design: We included 148 patients enrolled in MIRAGE (NCT 04384770), a trial comparing MRI versus CT-guided prostate stereotactic body radiotherapy (SBRT). Linear regression was used to evaluate the association between PROSTOX score and late GU grade toxicity. Machine learning approaches were used to develop predictive models for acute and chronic GU toxicity and the accuracy of all models was assessed using area under the curve (AUC) metrics. A comparative gene ontology (GO) analysis was performed. Results: PROSTOX accurately predicts late GU toxicity, achieving an AUC of 0.76, and demonstrates strong correlation with GU toxicity grade (p-1.2E-9). mirSNP-based signatures can distinguish acute and chronic RT toxicity (AUCs of 0.770 and 0.763). Finally, GO analysis identifies unique pathways involved in each form of GU toxicity: acute, chronic and late. Conclusions: These findings provide strong evidence for the continued application of mirSNPs to predict toxicity to RT, and to act as a path for the continued personalization of RT with improved patient outcomes.
Author Correction: Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry
Authors: Poornima Bhat-Nakshatri, Hongyu Gao, Aditi S Khatpe, Adedeji K Adebayo, Patrick C McGuire, Cihat Erdogan, Duojiao Chen, Guanglong Jiang, Felicia New, Rana German, Lydia Emmert, George Sandusky, Anna Maria Storniolo, Yunlong Liu, Harikrishna Nakshatri
Journal: Nature Medicine (2025)
Use of a Robot-Assisted Thrombectomy System in Acute Ischemic Stroke
Authors: Ming Yang, Haoquan Sun, Lei Li, Qi Wu, Xingkai Yang, Shen Qu, Feng Gao
Journal: JAMA Neurology (2025)

This observational study examines the feasibility and safety of a new preloaded robot-assisted thrombectomy system specifically designed for mechanical thrombectomy.
Mortality Among Veterans With Opioid Use Disorder After Medical Hospitalization
Authors: Michael A. Incze, Sophia Huebler, Jacob D. Baylis, Andrea Stofko, A. Taylor Kelley, Ingrid A. Binswanger, Adam J. Gordon
Journal: JAMA Internal Medicine (2025)

This cohort study estimates the risk of opioid-related and all-cause mortality during prespecified time periods after hospital discharge among US veterans with opioid use disorder.
Change in Default Prescription Length and Statin Prescribing Behavior
Authors: Mili Mehta, Alexander C. Fanaroff, Corinne M. Rhodes, Aria Xiong, Christopher K. Snider, E. Madeline Grenader, Michael O. Harhay, Nune Mehrabyan, Maryanne K. Peifer, Kevin G. M. Volpp, M. Kit Delgado
Journal: JAMA Internal Medicine (2025)

This quality improvement study examines the association of changing the default supply for statin prescriptions to 90 days with clinician prescribing behavior.
Invasive Group A Streptococcal Infections in 10 US States
Authors: Christopher J. Gregory, Jennifer Onukwube Okaro, Arthur Reingold, Shua Chai, Rachel Herlihy, Susan Petit, Monica M. Farley, Lee H. Harrison, Kathy Como-Sabetti, Ruth Lynfield, Paula Snippes Vagnone, Daniel Sosin, Bridget J. Anderson, Kari Burzlaff, Tasha Martin, Ann Thomas, William Schaffner, H. Keipp Talbot, Bernard Beall, Sopio Chochua, Yunmi Chung, Soyoun Park, Chris Van Beneden, Yuan Li, Stephanie J. Schrag
Journal: JAMA (2025)

Importance Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity, mortality, and economic burden. Objective To update trends in invasive GAS disease incidence rates in 10 US states between 2013 and 2022. Design, Setting, and Participants Clinical, demographic, and laboratory data for invasive GAS cases were collected as part of population-based surveillance in the Active Bacterial Core surveillance network covering 34.9 million persons across 10 US states. A case was defined as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis or streptococcal toxic shock syndrome between January 1, 2013, and December 31, 2022. Demographic and clinical data were collected from medical record review. From 2013 to 2014, available isolates were emm typed and antimicrobial susceptibilities determined using conventional methods; from 2015 onward, whole-genome sequencing was used. Main Outcomes and Measures Incidence rates by sex, age, race, and selected risk factors; clinical syndromes, outcomes, and underlying patient conditions; and isolate characteristics, including antimicrobial susceptibility. Results Surveillance in 10 US states identified 21 312 cases of invasive GAS from 2013 through 2022, including 1981 deaths. The majority of cases (57.5%) were in males. Among case-patients, 1272 (6.0%) were aged 0 to 17 years, 13 565 (63.7%) were aged 18 to 64 years, and 6474 (30.4%) were 65 years or older; 5.5% were American Indian or Alaska Native, 14.3% were Black, and 67.1% were White. Incidence rose from 3.6 per 100 000 persons in 2013 to 8.2 per 100 000 persons in 2022 ( P &amp;amp;lt; .001 for trend). Incidence was highest among persons 65 years or older; however, the relative increase over time was greatest among adults aged 18 to 64 years (3.2 to 8.7 per 100 000 persons). Incidence was higher among American Indian or Alaska Native persons than in other racial and ethnic groups. People experiencing homelessness, people who inject drugs, and residents of long-term care facilities had substantially elevated GAS incidence rates. Among tested isolates, those nonsusceptible to macrolides and clindamycin increased from 12.7% in 2013 to 33.1% in 2022. Conclusions Invasive GAS infections increased substantially in 10 US states during a surveillance period from 2013 to 2022. Accelerated efforts to prevent and control GAS are needed, especially among groups at highest risk of infection.
Comparing durvalumab, olaparib, and cediranib monotherapy, combination therapy, or chemotherapy in patients with platinum-resistant ovarian cancer with prior bevacizumab: the phase II NRG-GY023 trial
Authors: Jung-Min Lee, Austin Miller, Peter G. Rose, Mariam AlHilli, Christina Washington, Veena S. John, Chirag A. Shah, Koji Matsuo, Jean Siedel, David S. Miller, Elizabeth E. Hopp, Andrea O'Shea, John K. Chan, Leslie S. Bradford, Christopher B. Morse, Christa I. Nagel, Kerry J. Rodabaugh, Elise C. Kohn, Kathleen N. Moore, Joyce F. Liu
Journal: Clinical Cancer Research (2025)

Abstract Purpose: We assessed the efficacy of anti-PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared to the standard-of-care chemotherapy (SOC) in platinum-resistant epithelial ovarian cancer (PROC) patients, with prior bevacizumab. Patients and Methods: NRG-GY023 was the first, randomized 4-arm superiority phase II trial enrolling high-grade serous/endometrioid or clear cell PROC patients with prior bevacizumab exposure. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin), DOC, durvalumab+cediranib (DC), or olaparib+cediranib (OC). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. The design had 80% power to detect a hazard ratio (HR) of 0.5 using a one-sided, ⍺=0.1 level test for each comparison to the SOC with a pre-planned interim analysis. Experimental arms with HR estimate (vs SOC)&amp;gt;0.87 could be discontinued. Results: 153 patients were enrolled between 4/28/2021, and 2/1/2023. Accrual was permanently closed on 2/1/2023, due to futility. With a data cut-off of 9/9/2024, the median PFS was 3.4, 2.9, 2.5 and 2.8 months, and median OS was 7.5, 8.3, 5.7 and 10.2 months for SOC, DOC, DC and OC, respectively. ORR was 4.3%(95%CI:0.00-0.19), 15.9%(95%CI:0.07-0.29), 11.9%(95%CI:0.05-0.24) and 9.1%(95%CI:0.03-0.20) for SOC, DOC, DC, OC. Compared to SOC, the PFS HR estimates for DOC, DC, OC were 1.003(95%CI:0.56-1.80), 1.108(95%CI:0.63-1.96), and 1.021(95%CI:0.57-1.82). for SOC, DOC, DC, OC, respectively. No new safety signals were observed. Conclusion: In PROC patients with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.
Single-cell transcriptomic landscape deciphers intratumoral heterogeneity and subtypes of acral and mucosal melanoma
Authors: Yunyan Li, Ziyang Cui, Xiaole Song, Yeqing Chen, Cang Li, Junfeng Shi, Wenkang Qian, Guoxin Ren, Jiang Zhou, Chunpu Li, Xiaoqing Ma, Yifan Chen, Dongdong Jia, Yongli Zhang, Zhilin Zhang, Ronghao Zhang, Zhaotian Zhang, Yong Chen, Zhixiang Xu, Wantao Chen, Xiao Miao, Hongmeng Yu, Jianxin Chen, Kai Wang, Colin R. Goding, Zhi Wei, Tao Li, Rutao Cui
Journal: Clinical Cancer Research (2025)

Abstract Purpose: To identify the specific intratumoral and microenvironmental heterogeneity of acral (AM) and mucosal melanoma (MM), we aimed to delineate their distinct cellular compositions, evolutionary trajectories, and subtype-specific therapeutic strategies. Experimental Design: Single-cell transcriptomic and genomic landscapes were analyzed across 42 melanoma samples (28 AM, 11 MM, and 3 non-acral cutaneous melanoma [CM]), supplemented by in vitro and in vivo validation. Tumor and stromal cells were profiled using scRNA-seq, whole-exome sequencing, and functional assays, including transwell migration, co-culture systems, and xenograft models. Results: Tumor cells exhibited divergent evolutionary routes, with MM dominated by MGP⁺/PCOLCE⁺ subpopulations showing high epithelial-to-mesenchymal transition (EMT) potential. MM displayed elevated neutrophil infiltration and CXCL3⁺ tumor-associated macrophages, while AM was enriched with PI16⁺ cancer-associated fibroblasts (CAFs) promoting tumor proliferation. Molecular classification revealed MM subtypes: an antigen-presenting subtype linked to favorable outcomes and a proliferative subtype associated with recurrence. TIGIT⁺ Treg cells were enriched in AM, suggesting targeted inhibition potential. Genomic analysis connected BRAF/NRAS mutations to ALDOA⁺ stem-like tumor cells and identified PTGDS as a therapeutic target in triple-WT melanomas. Conclusions: Our study provides a comprehensive comparison of AM and MM, uncovering subtype-specific stromal-immune interactions and molecular programs. The findings highlight actionable targets (e.g., TIGIT in AM, CXCL3⁺ macrophages in MM) and propose a framework for precision therapies, biomarker-driven trials, and risk stratification to improve outcomes in these aggressive melanomas.
Comorbidity in Midlife and Cancer Outcomes
Authors: Jessica A. Lavery, Paul C. Boutros, Chaya S. Moskowitz, Lee W. Jones
Journal: JAMA Network Open (2025)

Importance Comorbidities in midlife are common but how these conditions are associated with cancer outcomes is poorly understood. Objective To investigate the association between different comorbidities and risk of incident cancer and cancer mortality. Design, Setting, and Participants This cohort study is a secondary analysis of the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial conducted at 10 PLCO screening centers across the US. Participants included adults aged 55 to 74 years without a history of cancer enrolled between 1993 and 2001. Statistical analysis was performed from June 2023 to December 2024. Exposures Self-reported history of 12 comorbid conditions classified into 5 distinct classifications guided by World Health Organization categorization. Main Outcome and Measures Outcomes included risk of all cancers combined, risk of 19 individual cancer types, and cancer mortality. Multivariable Cox proportional hazards models were used to estimate the association between comorbidity classifications and cancer outcomes. Results Among 128 999 participants included in the analysis, 330 (0.3%) were American Indian, 5414 (4.2%) were Asian or Pacific Islander, 6704 (5.2%) were non-Hispanic Black, and 114 073 (88.4%) were non-Hispanic White; 64 171 (49.7%) were male; and the median (IQR) age was 62 (58-66) years. After a median (IQR) follow-up of 20 (19-22) years, the risk of any incident cancer was significantly higher for individuals with a history of respiratory (hazard ratio [HR], 1.07 [95% CI, 1.02-1.12]) and cardiovascular conditions (HR, 1.02 [95% CI, 1.00-1.05]). History of each comorbid condition evaluated was significantly associated with incidence of at least 1 cancer type. The strongest association was between history of liver conditions and risk of liver cancer (HR, 5.57 [95% CI, 4.03-7.71]), whereas metabolic conditions (obesity or type 2 diabetes) were significantly associated with higher risk of 9 cancer types and lower risk of 4 cancer types. Respiratory (HR, 1.19 [95% CI, 1.11-1.28]), cardiovascular (HR, 1.08 [95% CI, 1.04-1.13]), and metabolic (HR, 1.09 [95% CI, 1.05-1.14]) conditions were positively associated with a higher hazard of cancer death. Conclusions and Relevance In this cohort study of 128 999 adults without a history of cancer, comorbidities in midlife were associated with the overall risk of cancer and more strongly associated with risk of multiple individual cancer types, with the direction of association differing across cancer types. These results may inform clinical management of patients at risk for cancer.
Virtual Lung Screening Trial (VLST): An In Silico Study Inspired by the National Lung Screening Trial for Lung Cancer Detection
Authors: Fakrul Islam Tushar, Liesbeth Vancoillie, Cindy McCabe, Amareswararao Kavuri, Lavsen Dahal, Brian Harrawood, Milo Fryling, Mojtaba Zarei, Saman Sotoudeh-Paima, Fong Chi Ho, Dhrubajyoti Ghosh, Michael R Harowicz, Tina D Tailor, Sheng Luo, W Paul Segars, Ehsan Abadi, Kyle J Lafata, Joseph Y Lo, Ehsan Samei
Journal: Medical Image Analysis (2025)
Pre-fertilization-origin preservation of brown fat-mediated energy expenditure in humans
Authors: Takeshi Yoneshiro, Mami Matsushita, Sayuri Fuse-Hamaoka, Miyuki Kuroiwa, Yuko Kurosawa, Yosuke Yamada, Makoto Arai, Yuchen Wei, Makoto Iida, Kenichi Kuma, Toshimitsu Kameya, Tomoya Harada, Yoshihiro Matsumura, Tsuyoshi Osawa, Yoshiko Aoki, Hisashi Nakamura, Takafumi Hamaoka, Juro Sakai, Masayuki Saito
Journal: Nature Metabolism (2025)
Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
Authors: Louise A Huuki-Myers, Kelsey D Montgomery, Sang Ho Kwon, Sophia Cinquemani, Nicholas J Eagles, Daianna Gonzalez-Padilla, Sean K Maden, Joel E Kleinman, Thomas M Hyde, Stephanie C Hicks, Kristen R Maynard, Leonardo Collado-Torres
Journal: Genome biology (2025)
Mg<sup>2+</sup>‐Loaded Black Phosphorus Nanosheet Protects against Cerebral Ischemic Injury through Anti‐Oxidative and Anti‐Inflammatory Effects
Authors: Min Wang, Xinyi Xia, Yaoyao Li, Kai Zhang, Xu Cheng, Xuehua Wen, Lijun Zhao, Xiaopeng Guo, Fahuan Song, Aiping Cheng
Journal: Advanced Healthcare Materials (2025)

Abstract Ischemic stroke is a severe neurological disease, with high morbidity and mortality worldwide. To date, the treatment of ischemic stroke is limited, and its consequent ischemia‐reperfusion injury is an important reason for this result. Excessive reactive oxygen species (ROS) and inflammatory storm followed by ischemia‐reperfusion alter the microenvironment of cerebral ischemic penumbra, leading to the devastating damage to the brain. Herein, we design a black phosphorus nanosheets (BPNSs) loaded with magnesium ions (Mg 2+ ) and polydopamine (PBP@Mg) to tackle the above problems. BPNSs of PBP@Mg effectively scavenge excessive ROS in neurocytes. Mg 2+ plays an anti‐inflammatory role in ischemic penumbra. Furthermore, polydopamine improves the stability of BPNSs. PBP@Mg is subsequently injected into the lateral ventricle of a rat model of ischemic stroke, resulting in an improvement of the ischemic microenvironment and a reduction in ischemic volume. BPNSs of PBP@Mg counteract against the excessive generation of ROS and the neuronal apoptosis in ischemic penumbra. Meanwhile, PBP@Mg dramatically suppresses inflammation by promoting the transformation of microglia from M1 to M2 in ischemic penumbra. PBP@Mg group exhibit a significantly better performance in neurofunctional behavior compared to ischemic group. Taken together, this study provides a novel therapeutic approach for cerebral ischemia‐reperfusion injury via anti‐oxidative and anti‐inflammatory effects.
GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias
Authors: Huilin Tang, William T. Donahoo, Steven T. DeKosky, Yao An Lee, Pareeta Kotecha, Mikael Svensson, Jiang Bian, Jingchuan Guo
Journal: JAMA Neurology (2025)

Importance The association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) and risk of Alzheimer disease and related dementias (ADRD) remains to be confirmed. Objective To assess the risk of ADRD associated with GLP-1RAs and SGLT2is in people with type 2 diabetes (T2D). Design, Setting, and Participants This target trial emulation study used electronic health record data from OneFlorida+ Clinical Research Consortium from January 2014 to June 2023. Patients were 50 years or older with T2D and no prior diagnosis of ADRD or antidementia treatment. Among the 396 963 eligible patients with T2D, 33 858 were included in the GLP-1RA vs other glucose-lowering drug (GLD) cohort, 34 185 in the SGLT2i vs other GLD cohort, and 24 117 in the GLP-1RA vs SGLT2i cohort. Exposures Initiation of treatment with a GLP-1RA, SGLT2i, or other second-line GLD. Main Outcomes and Measures ADRD was identified using clinical diagnosis codes. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazard regression models with inverse probability of treatment weighting (IPTW) to adjust for potential confounders. Results This study included 33 858 patients in the GLP-1RA vs other GLD cohort (mean age, 65 years; 53.1% female), 34 185 patients in the SGLT2i vs other GLD cohort (mean age, 65.8 years; 49.3% female), and 24 117 patients in the GLP-1RA vs SGLT2i cohort (mean age, 63.8 years; 51.7% female). In IPTW-weighted cohorts, the incidence rate of ADRD was lower in GLP-1RA initiators compared with other GLD initiators (rate difference [RD], −2.26 per 1000 person-years [95% CI, −2.88 to −1.64]), yielding an HR of 0.67 (95% CI, 0.47-0.96). SGLT2i initiators had a lower incidence than other GLD initiators (RD, −3.05 per 1000 person-years [95% CI, −3.68 to −2.42]), yielding an HR of 0.57 (95% CI, 0.43-0.75). There was no difference between GLP-1RAs and SGLT2is, with an RD of −0.09 per 1000 person-years (95% CI, −0.80 to 0.63) and an HR of 0.97 (95% CI, 0.72-1.32). Conclusion and Relevance In people with T2D, both GLP-1RAs and SGLT2is were statistically significantly associated with decreased risk of ADRD compared with other GLDs, and no difference was observed between both drugs.