tbuckley/cabot-search huggingface dataset:
The N6-methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma
Authors: Shiyan Wang, Yong Zeng, Lin Zhu, Min Zhang, Lei Zhou, Weixiong Yang, Weishan Luo, Lina Wang, Yanming Liu, Helen Zhu, Xin Xu, Peiran Su, Xinyue Zhang, Musaddeque Ahmed, Wei Chen, Moliang Chen, Sujun Chen, Mykhaylo Slobodyanyuk, Zhongpeng Xie, Jiansheng Guan, Wen Zhang, Aafaque Ahmad Khan, Shingo Sakashita, Ni Liu, Nhu-An Pham, Paul C. Boutros, Zunfu Ke, Michael F. Moran, Zongwei Cai, Chao Cheng, Jun Yu, Ming S. Tsao, Housheng H. He
Journal: Cancer Discovery (2024)

Abstract Comprehensive N6-methyladenosine (m6A) epitranscriptomic profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 nonneoplastic lung tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptomic, proteomic, and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with nonneoplastic lung tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hypermethylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics by interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small-molecule inhibitor markedly diminished both EML4 m6A and protein abundance and efficiently suppressed lung metastases in vivo. Significance: Our study reveals a dynamic and functional epitranscriptomic landscape in LUAD, offering a valuable resource for further research in the field. We identified EML4 hypermethylation as a key driver of tumor metastasis, highlighting a novel therapeutic strategy of targeting EML4 to prevent LUAD metastasis.
Correction to: Preclinical studies of Flonoltinib Maleate, a novel JAK2/FLT3 inhibitor, in treatment of JAK2V617F-induced myeloproliferative neoplasms
Authors: Mengshi Hu, Tao Yang, Linyu Yang, Lu Niu, Jinbing Zhu, Ailin Zhao, Mingsong Shi, Xue Yuan, Minghai Tang, Jianhong Yang, Heying Pei, Zhuang Yang, Qiang Chen, Haoyu Ye, Ting Niu, Lijuan Chen
Journal: Blood Cancer Journal (2024)
Long-Term Follow-up of Levonorgestrel Intrauterine Device for Atypical Hyperplasia and Early Endometrial Cancer Reveals Relapse Characterized by Immune Exhaustion
Authors: Mikayla Borthwick. Bowen, Brenda Melendez, Qian Zhang, Richard K. Yang, Bryan M. Fellman, Barrett C. Lawson, Naomi N. Adjei, Joseph Celestino, Khalida M. Wani, Bhavana Singh, Diana L. Urbauer, Alexander J. Lazar, Karen H. Lu, Jennifer A. Wargo, Shannon N. Westin, Melinda S. Yates
Journal: Clinical Cancer Research (2024)

Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited.
Tumor-Agnostic Genomic and Clinical Analysis of <i>BRAF</i> Fusions Identifies Actionable Targets
Authors: Monica F. Chen, Soo-Ryum Yang, Jessica J. Tao, Antoine Desilets, Eli L. Diamond, Clare Wilhelm, Ezra Rosen, Yixiao Gong, Kerry Mullaney, Jean Torrisi, Robert J. Young, Romel Somwar, Helena A. Yu, Mark G. Kris, Gregory J. Riely, Maria E. Arcila, Marc Ladanyi, Mark T.A. Donoghue, Neal Rosen, Rona Yaeger, Alexander Drilon, Yonina R. Murciano-Goroff, Michael Offin
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Even though BRAF fusions are increasingly detected in standard multigene next-generation sequencing panels, few reports have explored their structure and impact on clinical course. Experimental Design: We collected data from patients with BRAF fusion–positive cancers identified through a genotyping protocol of 97,024 samples. Fusions were characterized and reviewed for oncogenic potential (in-frame status, non-BRAF partner gene, and intact BRAF kinase domain). Results: We found 241 BRAF fusion–positive tumors from 212 patients with 82 unique 5′ fusion partners spanning 52 histologies. Thirty-nine fusion partners were not previously reported, and 61 were identified once. BRAF fusion incidence was enriched in pilocytic astrocytomas, gangliogliomas, low-grade neuroepithelial tumors, and acinar cell carcinoma of the pancreas. Twenty-four patients spanning multiple histologies were treated with MAPK-directed therapies, of which 20 were evaluable for RECIST. Best response was partial response (N = 2), stable disease (N = 11), and progressive disease (N = 7). The median time on therapy was 1 month with MEK plus BRAF inhibitors [(N = 11), range 0–18 months] and 8 months for MEK inhibitors [(N = 14), range 1–26 months]. Nine patients remained on treatment for longer than 6 months [pilocytic astrocytomas (N = 6), Erdheim–Chester disease (N = 1), extraventricular neurocytoma (N = 1), and melanoma (N = 1)]. Fifteen patients had acquired BRAF fusions. Conclusions: BRAF fusions are found across histologies and represent an emerging actionable target. BRAF fusions have a diverse set of fusion partners. Durable responses to MAPK therapies were seen, particularly in pilocytic astrocytomas. Acquired BRAF fusions were identified after targeted therapy, underscoring the importance of postprogression biopsies to optimize treatment at relapse in these patients.
The Limited Value of Multivitamin Supplements
Authors: Neal D. Barnard, Hana Kahleova, Roxanne Becker
Journal: JAMA Network Open (2024)

Erikka Loftfield, PhD, MPH; Caitlin P. O'Connell, MPH; Christian C. Abnet, PhD, MPH; Barry I. Graubard, PhD; Linda M. Liao, PhD; Laura E. Beane Freeman, PhD; Jonathan N. Hofmann, PhD; Neal D. Freedman, PhD, MPH; Rashmi Sinha, PhD
Suicide and Self-Harm—Toward the Full Picture From the Full Population
Authors: Morten Hesse, Julie Elizabeth Brummer
Journal: JAMA Network Open (2024)

Philippe Mortier, PhD; Susana Conde, PhD; Itxaso Alayo, MSc; Franco Amigo, MPH; Laura Ballester, PhD; Roser Cirici Amell, PhD; Daniel Guinart, PhD; Salvatore Fabrizio Contaldo, PhD; Montserrat Ferrer, PhD; Angela Leis, PhD; Miguel Angel Mayer, PhD; Ana Portillo-Van Diest, MPH; Beatriz Puértolas-Gracia, MPH; Juan Manuel Ramírez-Anguita, PhD; Carlos Peña-Salazar, PhD; Ferran Sanz, PhD; Ronald C. Kessler, PhD; Diego Palao, PhD; Víctor Pérez Sola, PhD; Lars Mehlum, PhD; Ping Qin, PhD; Gemma Vilagut, PhD; Jordi Alonso, PhD
Recurrence Rate of Melanoma In Situ Excised With a 5-mm Excisional Margin
Authors: John A. Zitelli
Journal: JAMA Dermatology (2024)

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Treatment of Pyoderma Gangrenosum With Vilobelimab
Authors: Sonia Himed, Hoda Tawfik, Benjamin H. Kaffenberger
Journal: JAMA Dermatology (2024)

This case report describes a man in his 20s with psoriasis who was receiving stable treatment with adalimumab for 3 years and was diagnosed with pyoderma gangrenosum and was referred for a 6-month history of multiple inflammatory ulcers on the right dorsal foot and ankle.
Playing Russian Roulette: Parent and Adolescent Perspectives on Tumor Surveillance for Adolescents with Cancer Predisposition Syndromes
Authors: Rachel Elias, Alise Blake, Lori Dean, Jessica S. Flynn, Leila Sachner, Lynn Harrison, Rose McGee, Kim E. Nichols, Katianne M. Howard Sharp
Journal: Clinical Cancer Research (2024)

Cancer predisposition syndrome (CPS) surveillance allows for the early detection and treatment of neoplasms; however, the psychosocial impact of tumor surveillance is poorly understood for cancer-affected adolescents with CPS and their parents. To gain further insight, we qualitatively characterized the affective and cognitive experience of adolescents undergoing tumor surveillance.
Association of Gaseous Ambient Air Pollution and Dementia-Related Neuroimaging Markers in the ARIC Cohort, Comparing Exposure Estimation Methods and Confounding by Study Site
Authors: Katie M. Lynch, Erin E. Bennett, Qi Ying, Eun Sug Park, Xiaohui Xu, Richard L. Smith, James D. Stewart, Duanping Liao, Joel D. Kaufman, Eric A. Whitsel, Melinda C. Power
Journal: Environmental Health Perspectives (2024)

Evidence linking gaseous air pollution to late-life brain health is mixed.
Combination Targeted Therapy with Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers
Authors: Jena D. French, Bryan R. Haugen, Francis P. Worden, Daniel W. Bowles, Andrew G. Gianoukakis, Bhavana Konda, Ramona Dadu, Eric J. Sherman, Shaylene McCue, Nathan R. Foster, Yuri E. Nikiforov, Ticiana D.J. Farias, Paul J. Norman, Lori J. Wirth
Journal: Clinical Cancer Research (2024)

Lenvatinib, a potent multikinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer; however, most patients experience disease progression, warranting further therapy. We evaluated the efficacy and safety of lenvatinib plus pembrolizumab in these patients.
Preventing Surgical Site Infections in the Era of Escalating Antibiotic Resistance and Antibiotic Stewardship
Authors: Dustin R. Long, Adam Cifu, Stephen J. Salipante, Robert G. Sawyer, Kaylie Machutta, John C. Alverdy
Journal: JAMA Surgery (2024)

According to the Centers for Disease Control and Prevention and governing bodies within the American College of Surgeons, the administration of antibiotics as prophylaxis against infection prior to a planned elective procedure is, with rare exception, routinely recommended. The goal of "getting to zero" infections remains a high priority for policymakers, practitioners, and certainly for patients.
Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin
Authors: Tianze Yu, Xiaoqiang Xu, Yang Liu, Xiaokai Wang, Shi Wu, Zhuoqiong Qiu, Xiaochun Liu, Xiaoyu Pan, Chaoying Gu, Shangshang Wang, Lixin Dong, Wei Li, Xu Yao
Journal: Cell Host & Microbe (2024)
Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial
Authors: Jiejie Li, Xia Meng, Fu-Dong Shi, Jing Jing, Hong-Qiu Gu, Aoming Jin, Yong Jiang, Hao Li, S Claiborne Johnston, Graeme J Hankey, J Donald Easton, Liguo Chang, Penglai Shi, Lihua Wang, Xianbo Zhuang, Haitao Li, Yingzhuo Zang, Jianling Zhang, Zengqiang Sun, Dongqi Liu, Ying Li, Hongqin Yang, Jinguo Zhao, Weiran Yu, Anxin Wang, Yuesong Pan, Jinxi Lin, Xuewei Xie, Wei-Na Jin, Shuya Li, Siying Niu, Yilong Wang, Xingquan Zhao, Zixiao Li, Liping Liu, Huaguang Zheng, Yongjun Wang
Journal: BMJ (2024)

Abstract Objectives To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). Design Multicentre, double blind, randomised, placebo controlled trial. Setting 244 hospitals in China between 11 August 2022 and 13 April 2023. Participants 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. Interventions Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. Main outcome measures The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. Results 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). Conclusions The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. Trial registration ClinicalTrials.gov, NCT05439356 .
Firearm Policy in the Hospital Setting—Recognizing Health Care as a “Sensitive Place”
Authors: Joshua B. Romero, Daniel G. Aaron, Richard S. Saver, Joseph Blocher
Journal: JAMA (2024)

Importance Hospitals are hot zones of the US gun injury epidemic. To shelter these facilities from the dangers of gun violence, state legislatures have enacted laws to reduce the carrying of firearms on hospital premises. However, these efforts currently face serious Second Amendment challenges in federal courts. The ongoing legal battles, which have wide-ranging implications for patient and clinician safety as well as public health generally, are setting the stage for a Supreme Court case that may decide the fate of firearm regulations in US hospitals. A permissible pathway for advancing sensible gun regulation in hospitals is urgently needed. Observations Since the Supreme Court established a new constitutional test for firearm laws in New York State Rifle &amp;amp;amp; Pistol Association v Bruen (2022), states now face unprecedentedly high barriers to enacting health-protecting legislation regarding firearms. Post- Bruen , the Supreme Court requires that laws be consistent with “this Nation’s historical tradition of firearms regulation.” This means that states hoping to enact laws barring public carry of firearms in hospitals must demonstrate that hospitals are a “sensitive place” as a historical matter (ie, analogous to a location where firearms were traditionally restricted). By reasoning from analogy, it is clear several historical comparators exist for regulating firearms in hospitals. Although the hospital (as understood today) did not exist in the 1700s, it is sufficiently analogous to asylums and schools, to name a few examples. These settings all share a common denominator with the modern-day hospital: serving vulnerable populations or individuals who may be at heightened risk of misusing firearms. Conclusions and Relevance The Supreme Court’s interpretation of the Second Amendment right to bear arms is threatening democratically enacted laws seeking to shelter hospitals from firearm violence. However, it is clear that hospitals and other health care settings are a sensitive place with compelling historical analogies. Policymakers’ strategic deployment of the sensitive places designation, along with its rightful judicial recognition in the hospital setting, are critical to upholding laws that protect health care facilities, patients, and professionals from firearm violence—a conclusion consistent with the US Constitution, history, medical ethics, and common sense.
Comparing Phylogeographies to Reveal Incompatible Geographical Histories within Genomes
Authors: Benjamin Singer, Antonello Di Nardo, Jotun Hein, Luca Ferretti
Journal: Molecular Biology and Evolution (2024)

Modern phylogeography aims at reconstructing the geographic movement of organisms based on their genomic sequences and spatial information. Phylogeographic approaches are often applied to pathogen sequences and therefore tend to neglect the possibility of recombination, which decouples the evolutionary and geographic histories of different parts of the genome. Genomic regions of recombining or reassorting pathogens often originate and evolve at different times and locations, which characterize their unique spatial histories. Measuring the extent of these differences requires new methods to compare geographic information on phylogenetic trees reconstructed from different parts of the genome. Here we develop for the first time a set of measures of phylogeographic incompatibility, aimed at detecting differences between geographical histories in terms of distances between phylogeographies. We study the effect of varying demography and recombination on phylogeographic incompatibilities using coalescent simulations. We further apply these measures to the evolutionary history of human and livestock pathogens, either reassorting or recombining, such as the Victoria and Yamagata lineages of influenza B and the O/Ind-2001 foot-and-mouth disease virus strain. Our results reveal diverse geographical paths of migration that characterize the origins and evolutionary histories of different viral genes and genomic segments. These incompatibility measures can be applied to any phylogeography, and more generally to any phylogeny where each tip has been assigned either a continuous or discrete "trait" independent of the sequence. We illustrate this flexibility with an analysis of the interplay between the phylogeography and phylolinguistics of Uralic-speaking human populations, hinting at patrilinear language transmission.
An Injectable Living Hydrogel with Embedded Probiotics as a Novel Strategy for Combating Multifaceted Pathogen Wound Infections
Authors: Siyuan Tao, Sixuan Zhang, Kongchang Wei, Katharina Maniura‐Weber, Zhihao Li, Qun Ren
Journal: Advanced Healthcare Materials (2024)

Abstract Wound infections pose a significant challenge in healthcare, and traditional antibiotic treatments often result in the development of resistant pathogens. Addressing this gap, ProGel is introduced, a living hydrogel created by entrapping probiotic Lactobacillus plantarum as a therapeutic component within a gelatin matrix. With a double‐syringe system, ProGel can be easily mixed and applied, conforming swiftly to any wound shape and forming hydrogel in situ. It also demonstrates robust mechanical and self‐healing properties owing to the Schiff‐base bonds. ProGel sustains more than 80% viability of the entrapped L. plantarum while restricting their escape from the hydrogel. After a week of storage, more than 70% viability of the entrapped L. plantarum is preserved. Importantly, ProGel exhibits broad‐spectrum antimicrobial efficacy against pathogens commonly associated with wound infections, i.e., Pseudomonas aeruginosa (7Log reduction), Staphylococcus aureus (3‐7Log reduction), and Candida albicans (40–70% reduction). Moreover, its cytocompatibility is affirmed through coculture with human dermal fibroblasts. The effectiveness of ProGel is further highlighted in more clinically relevant tests on human skin wound models infected with P. aeruginosa and S. aureus , where it successfully prevents the biofilm formation of these pathogens. This study showcases an injectable living hydrogel system for the management of complex wound infections.
Immune evasion impacts the landscape of driver genes during cancer evolution
Authors: Lucie Gourmet, Andrea Sottoriva, Simon Walker-Samuel, Maria Secrier, Luis Zapata
Journal: Genome biology (2024)

Abstract Background Carcinogenesis is driven by interactions between genetic mutations and the local tumor microenvironment. Recent research has identified hundreds of cancer driver genes; however, these studies often include a mixture of different molecular subtypes and ecological niches and ignore the impact of the immune system. Results In this study, we compare the landscape of driver genes in tumors that escaped the immune system (escape +) versus those that did not (escape −). We analyze 9896 primary tumors from The Cancer Genome Atlas using the ratio of non-synonymous to synonymous mutations (dN/dS) and find 85 driver genes, including 27 and 16 novel genes, in escape − and escape + tumors, respectively. The dN/dS of driver genes in immune escaped tumors is significantly lower and closer to neutrality than in non-escaped tumors, suggesting selection buffering in driver genes fueled by immune escape. Additionally, we find that immune evasion leads to more mutated sites, a diverse array of mutational signatures and is linked to tumor prognosis. Conclusions Our findings highlight the need for improved patient stratification to identify new therapeutic targets for cancer treatment.
Wearable sensor-based quantitative gait analysis in Parkinson’s disease patients with different motor subtypes
Authors: Weishan Zhang, Yun Ling, Zhonglue Chen, Kang Ren, Shengdi Chen, Pei Huang, Yuyan Tan
Journal: npj Digital Medicine (2024)

Abstract Gait impairments are among the most common and disabling symptoms of Parkinson’s disease and worsen as the disease progresses. Early detection and diagnosis of subtype-specific gait deficits, as well as progression monitoring, can help to implement effective and preventive personalized treatment for PD patients. Yet, the gait features have not been fully studied in PD and its motor subtypes. To characterize comprehensive and objective gait alterations and to identify the potential gait biomarkers for early diagnosis, subtype differentiation, and disease severity monitoring. We analyzed gait parameters related to upper/lower limbs, trunk and lumbar, and postural transitions from 24 tremor-dominant (TD) and 20 postural instability gait difficulty (PIGD) dominant PD patients who were in early stage and 39 matched healthy controls (HC) during the Timed Up and Go test using wearable sensors. Results show: (1) Both TD and PIGD groups showed restricted backswing range in bilateral lower extremities and more affected side (MAS) arm, reduced trunk and lumbar rotation range in the coronal plane, and low turning efficiency. The receiver operating characteristic (ROC) analysis revealed these objective gait features had high discriminative value in distinguishing both PD subtypes from the HC with the area under the curve (AUC) values of 0.7~0.9 ( p &lt; 0.01). (2) Subtle but measurable gait differences existed between TD and PIGD patients before the onset of clinically apparent gait impairment. (3) Specific gait parameters were significantly associated with disease severity in TD and PIGD subtypes. Objective gait biomarkers based on wearable sensors may facilitate timely and personalized gait treatments in PD subtypes through early diagnosis, subtype differentiation, and disease severity monitoring.
Correction to “A Core–Shell Nanoplatform for Synergistic Enhanced Sonodynamic Therapy of Hypoxic Tumor via Cascaded Strategy”
Authors: Lei Wang, Mengya Niu, Cuixia Zheng, Hongjuan Zhao, Xiuxiu Niu, Li Li, Yujie Hu, Yingjie Zhang, Jinjin Shi, Zhenzhong Zhang
Journal: Advanced Healthcare Materials (2024)
A novel controlled metabolic accelerator for the treatment of obesity‐related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a <scp>HuMAIN</scp> trial
Authors: Dalane W. Kitzman, Gregory D. Lewis, Ambarish Pandey, Barry A. Borlaug, Andrew J. Sauer, Sheldon E. Litwin, Kavita Sharma, Diane K. Jorkasky, Shaharyar Khan, Sanjiv J. Shah
Journal: European Journal of Heart Failure (2024)