tbuckley/cabot-search huggingface dataset:
Genomic analyses reveal the stepwise domestication and genetic mechanism of curd biogenesis in cauliflower
Authors: Rui Chen, Ke Chen, Xingwei Yao, Xiaoli Zhang, Yingxia Yang, Xiao Su, Mingjie Lyu, Qian Wang, Guan Zhang, Mengmeng Wang, Yanhao Li, Lijin Duan, Tianyu Xie, Haichao Li, Yuyao Yang, Hong Zhang, Yutong Guo, Guiying Jia, Xianhong Ge, Panagiotis F. Sarris, Tao Lin, Deling Sun
Journal: Nature Genetics (2024)

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.
Mapping and functional characterization of structural variation in 1060 pig genomes
Authors: Liu Yang, Hongwei Yin, Lijing Bai, Wenye Yao, Tan Tao, Qianyi Zhao, Yahui Gao, Jinyan Teng, Zhiting Xu, Qing Lin, Shuqi Diao, Zhangyuan Pan, Dailu Guan, Bingjie Li, Huaijun Zhou, Zhongyin Zhou, Fuping Zhao, Qishan Wang, Yuchun Pan, Zhe Zhang, Kui Li, Lingzhao Fang, George E. Liu
Journal: Genome biology (2024)

Abstract Background Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence. Results We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs ( Sus scrofa ) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV’s impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3 , whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies. Conclusions This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.
Functional variants in a TTTG microsatellite on 15q26.1 cause familial nonautoimmune thyroid abnormalities
Authors: Satoshi Narumi, Keisuke Nagasaki, Mitsuo Kiriya, Erika Uehara, Kazuhisa Akiba, Kanako Tanase-Nakao, Kazuhiro Shimura, Kiyomi Abe, Chiho Sugisawa, Tomohiro Ishii, Kenichi Miyako, Yukihiro Hasegawa, Yoshihiro Maruo, Koji Muroya, Natsuko Watanabe, Eijun Nishihara, Yuka Ito, Takahiko Kogai, Kaori Kameyama, Kazuhiko Nakabayashi, Kenichiro Hata, Maki Fukami, Hirohito Shima, Atsuo Kikuchi, Jun Takayama, Gen Tamiya, Tomonobu Hasegawa
Journal: Nature Genetics (2024)

Abstract Insufficient thyroid hormone production in newborns is referred to as congenital hypothyroidism. Multinodular goiter (MNG), characterized by an enlarged thyroid gland with multiple nodules, is usually seen in adults and is recognized as a separate disorder from congenital hypothyroidism. Here we performed a linkage analysis of a family with both nongoitrous congenital hypothyroidism and MNG and identified a signal at 15q26.1. Follow-up analyses with whole-genome sequencing and genetic screening in congenital hypothyroidism and MNG cohorts showed that changes in a noncoding TTTG microsatellite on 15q26.1 were frequently observed in congenital hypothyroidism (137 in 989) and MNG (3 in 33) compared with controls (3 in 38,722). Characterization of the noncoding variants with epigenomic data and in vitro experiments suggested that the microsatellite is located in a thyroid-specific transcriptional repressor, and its activity is disrupted by the variants. Collectively, we presented genetic evidence linking nongoitrous congenital hypothyroidism and MNG, providing unique insights into thyroid abnormalities.
Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts (Adv. Healthcare Mater. 12/2024)
Authors: Leo L. Wang, Spencer Tuohy, Karen L. Xu, Arben Nace, Ruifeng Yang, Ying Zheng, Jason A. Burdick, George Cotsarelis
Journal: Advanced Healthcare Materials (2024)
Sleep assessment using EEG-based wearables – A systematic review
Authors: C.J. de Gans, P. Burger, E.S. van den Ende, J. Hermanides, P.W.B. Nanayakkara, R.J.B.J. Gemke, F. Rutters, D.J. Stenvers
Journal: Sleep Medicine Reviews (2024)

Polysomnography (PSG) is the reference standard of sleep measurement, but is burdensome for the participant and labor intensive. Affordable electroencephalography (EEG)-based wearables are easy to use and are gaining popularity, yet selecting the most suitable device is a challenge for clinicians and researchers. In this systematic review, we aim to provide a comprehensive overview of available EEG-based wearables to measure human sleep. For each wearable, an overview will be provided regarding validated population and reported measurement properties. A systematic search was conducted in the databases OVID MEDLINE, Embase.com and CINAHL. A machine learning algorithm (ASReview) was utilized to screen titles and abstracts for eligibility. In total, 60 papers were selected, covering 34 unique EEG-based wearables. Feasibility studies indicated good tolerance, high compliance, and success rates. The 42 included validation studies were conducted across diverse populations and showed consistently high accuracy in sleep staging detection. Therefore, the recent advancements in EEG-based wearables show great promise as alternative for PSG and for at-home sleep monitoring. Users should consider factors like user-friendliness, comfort, and costs, as these devices vary in features and pricing, impacting their suitability for individual needs.
A Functional RNA-Origami as Direct Thrombin Inhibitor with Fast-acting and Specific Single-Molecule Reversal Agents in vivo model
Authors: Abhichart Krissanaprasit, Emily Mihalko, Katherine Meinhold, Aryssa Simpson, Jennifer Sollinger, Sanika Pandit, Daniel M Dupont, Jørgen Kjems, Ashley C Brown, Thomas H LaBean
Journal: Molecular Therapy (2024)
TAI-GAN: A Temporally and Anatomically Informed Generative Adversarial Network for early-to-late frame conversion in dynamic cardiac PET inter-frame motion correction
Authors: Xueqi Guo, Luyao Shi, Xiongchao Chen, Qiong Liu, Bo Zhou, Huidong Xie, Yi-Hwa Liu, Richard Palyo, Edward J. Miller, Albert J. Sinusas, Lawrence Staib, Bruce Spottiswoode, Chi Liu, Nicha C. Dvornek
Journal: Medical Image Analysis (2024)
Biomaterials‐Based Technologies in Skeletal Muscle Tissue Engineering
Authors: Wei Luo, Hanli Zhang, Renwen Wan, Yuxi Cai, Yinuo Liu, Yang Wu, Yimeng Yang, Jiani Chen, Deju Zhang, Zhiwen Luo, Xiliang Shang
Journal: Advanced Healthcare Materials (2024)

For many clinically prevalent severe injuries, the inherent regenerative capacity of skeletal muscle remains inadequate. Skeletal muscle tissue engineering (SMTE) seeks to meet this clinical demand. With continuous progress in biomedicine and related technologies including micro/nanotechnology and 3D printing, numerous studies have uncovered various intrinsic mechanisms regulating skeletal muscle regeneration and developed tailored biomaterial systems based on these understandings. Here, the skeletal muscle structure and regeneration process are discussed and the diverse biomaterial systems derived from various technologies are explored in detail. Biomaterials serve not merely as local niches for cell growth, but also as scaffolds endowed with structural or physicochemical properties that provide tissue regenerative cues such as topographical, electrical, and mechanical signals. They can also act as delivery systems for stem cells and bioactive molecules that have been shown as key participants in endogenous repair cascades. To achieve bench-to-bedside translation, the typical effect enabled by biomaterial systems and the potential underlying molecular mechanisms are also summarized. Insights into the roles of biomaterials in SMTE from cellular and molecular perspectives are provided. Finally, perspectives on the advancement of SMTE are provided, for which gene therapy, exosomes, and hybrid biomaterials may hold promise to make important contributions.
circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)
Authors: Yi-fang Tang, Zheng-hua Liu, Lei-yi Zhang, Sheng-hao Shi, Shun Xu, Jin-An Ma, Chun-Hong Hu, Fang-wen Zou
Journal: Molecular Cancer (2024)

Abstract Background Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. Methods Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. Results The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. Conclusions Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance. Graphical Abstract
Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study
Authors: Seogsong Jeong, Yun Hwan Oh, Joseph C Ahn, Seulggie Choi, Sun Jae Park, Hye Jun Kim, Gyeongsil Lee, Joung Sik Son, Heejoon Jang, Dong Hyeon Lee, Meng Sha, Lei Chen, Won Kim, Sang Min Park
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort.Methods: Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression.Results: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68–3.21; P&lt;0.001), incident (aHR, 1.85; 95% CI, 1.63–2.10; P&lt;0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18–1.50; P&lt;0.001) had an increased risk of HCC compared to persistent non-MASLD.Conclusions: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.
Reply to the Letter Regarding “Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study”
Authors: Masatoshi Kudo, Kaoru Tsuchiya, Tatsuya Yamashita, Hironori Koga, Yuki Nakagawa, Masafumi Ikeda
Journal: Liver Cancer (2024)
Targeting lysosomal quality control as a therapeutic strategy against aging and diseases
Authors: Yuchen He, Yishu Fan, Xenab Ahmadpoor, Yumin Wang, Zhong Alan Li, Weihong Zhu, Hang Lin
Journal: Medicinal Research Reviews (2024)

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.
Effectiveness of autumn 2023 COVID-19 vaccination and residual protection of prior doses against hospitalisation in England, estimated using a test-negative case-control study
Authors: Freja C.M. Kirsebom, Julia Stowe, Jamie Lopez Bernal, Alex Allen, Nick Andrews
Journal: Journal of Infection (2024)

The last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent BA.4-5 or monovalent XBB.1.5 boosters were given. During the study period, the JN.1 variant became dominant in England.
Correlation of antigen expression with epigenetic modifications after rAAV delivery of a human factor IX variant in mice and rhesus macaques
Authors: Katja Pekrun, Calvin J. Stephens, Adriana Gonzalez-Sandoval, Aranyak Goswami, Feijie Zhang, Alice F. Tarantal, Grant Blouse, Mark A. Kay
Journal: Molecular Therapy (2024)
Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice
Authors: Nicholas You Zhi Cheang, Kai Sen Tan, Peck Szee Tan, Kiren Purushotorma, Wee Chee Yap, Kirsteen McInnes Tullett, Benson Yen Leong Chua, Aileen Ying-Yan Yeoh, Caris Qi Hui Tan, Xinlei Qian, Huixin Chen, Douglas Jie Wen Tay, Irina Caminschi, Yee Joo Tan, Paul Anthony Macary, Chee Wah Tan, Mireille Hanna Lahoud, Sylvie Alonso
Journal: Molecular Therapy (2024)
Engineered IgM and IgG cleaving enzymes for mitigating antibody neutralization and complement activation in AAV gene transfer
Authors: Timothy J Smith, Zachary C Elmore, Robert M Fusco, Joshua A Hull, Alan Rosales, Michele Martinez, Alice F Tarantal, Aravind Asokan
Journal: Molecular Therapy (2024)

Systemic dosing of adeno-associated viral (AAV) vectors poses potential risk of adverse side effects including complement activation triggered by anti-capsid immunity. Due to the multifactorial nature of toxicities observed in this setting, a wide spectrum of immune modulatory regimens are being investigated in the clinic. Here, we discover an IgM cleaving enzyme (IceM) that degrades human IgM, a key trigger in the anti-AAV immune cascade. We then engineer a fusion enzyme (IceMG) with dual proteolytic activity against human IgM and IgG. IceMG cleaves B cell surface antigen receptors and inactivates phospholipase gamma signaling in vitro. Importantly, IceMG is more effective at inhibiting complement activation compared with an IgG cleaving enzyme alone. Upon IV dosing, IceMG rapidly and reversibly clears circulating IgM and IgG in macaques. Antisera from these animals treated with IceMG shows decreased ability to neutralize AAV and activate complement. Consistently, pre-conditioning with IceMG restores AAV transduction in mice passively immunized with human antisera. Thus, IgM cleaving enzymes show promise in simultaneously addressing multiple aspects of anti-AAV immunity mediated by B cells, circulating antibodies and complement. These studies have implications for improving safety of AAV gene therapies and possibly broader applications including organ transplantation and autoimmune diseases.
Unlocking the future: Machine learning sheds light on prognostication for early-stage hepatocellular carcinoma: Editorial on “Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma”
Authors: Junlong Dai, Jimmy Che-To Lai, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip
Journal: Clinical and Molecular Hepatology (2024)
Atezolizumab and bevacizumab for hepatocellular carcinoma: How to approach salvage therapy for non-responders?: Editorial on “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study”
Authors: Naoshi Nishida
Journal: Clinical and Molecular Hepatology (2024)

Running head: Salvage therapy for non-responders to ICI in HCC Abbreviations; atezolizumab and bevacizumab combination therapy (Atezo/Bev), hepatocellular carcinoma (HCC), progression-free survival (PFS), post-progression survival (PPS), overall survival (OS), durvalumab and tremelimumab combination therapy (Durva/Treme), tyrosine kinase inhibitors (TKIs), objective response rate (ORR), propensity score (PS), disease control rate (DCR), immune checkpoint inhibitors (ICIs), activating transcription factor 3 (ATF3), C-C chemokine ligand (CCL), fibroblast growth factor receptor 4 (FGFR4), relative dose intensity (RDI), adverse events (AEs), vascular endothelial growth factor receptor 2 (VEGFR2), α-fetoprotein (AFP), tumor immune microenvironment (TIME), artificial intelligence (AI)
An Immune‐Regulating Polysaccharide Hybrid Hydrogel with Mild Photothermal Effect and Anti‐Inflammatory for Accelerating Infected Wound Healing
Authors: ShengZhe Zhou, Xueliang Zhang, Wei Ni, Yu He, Ming Li, Caixia Wang, Yubing Bai, Hao Zhang, Min Yao
Journal: Advanced Healthcare Materials (2024)

Abstract Bacterial infections and excessive inflammation present substantial challenges for clinical wound healing. Hydrogels with mild photothermal (PTT) effects have emerged as promising agents owing to their dual actions: positive effects on cells and negative effects on bacteria. Here, an injectable self‐healing hydrogel of oxidized konjac glucomannan/arginine‐modified chitosan (OKGM/CS‐Arg, OC) integrated with protocatechualdehyde‐@Fe (PF) nanoparticles capable of effectively absorbing near‐infrared radiation is synthesized successfully. The OC/PF hydrogels exhibit excellent mechanical properties, biocompatibility, and antioxidant activity. Moreover, in synergy with PTT, OC/PF demonstrates potent antibacterial effects while concurrently stimulating cell migration and new blood vessel formation. In methicillin‐resistant Staphylococcus aureus ‐infected full‐thickness mouse wounds, the OC/PF hydrogel displays remarkable antibacterial and anti‐inflammatory activities, and accelerates wound healing by regulating the wound immune microenvironment and promoting M2 macrophage polarization. Consequently, the OC/PF hydrogel represents a novel therapeutic approach for treating multidrug‐resistant bacterial infections and offers a technologically advanced solution for managing infectious wounds in clinical settings.
Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer
Authors: Moumita Kundu, Ramesh Butti, Venketesh K. Panda, Diksha Malhotra, Sumit Das, Tandrima Mitra, Prachi Kapse, Suresh W. Gosavi, Gopal C. Kundu
Journal: Molecular Cancer (2024)

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.