tbuckley/cabot-search huggingface dataset:
Cholesterol homeostasis confers glioma malignancy triggered by hnRNPA2B1-dependent regulation of SREBP2 and LDLR
Authors: Juan Zhang, Bei Liu, Changwei Xu, Chenchen Ji, Anan Yin, Yifeng Liu, Yan Yao, Bowen Li, Tangdong Chen, Liangliang Shen, Yuanming Wu
Journal: Neuro-Oncology (2023)

Abstract Background Dysregulation of cholesterol metabolism is a significant characteristic of glioma, yet the underlying mechanisms are largely unknown. N6-methyladenosine (m6A) modification has been implicated in promoting tumor development and progression. The aim of this study was to determine the key m6A regulatory proteins involved in the progression of glioma, which is potentially associated with the reprogramming of cholesterol homeostasis. Methods Bioinformatics analysis was performed to determine the association of m6A modification with glioma malignancy from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Glioma stem cell (GSC) self-renewal was determined by tumor sphere formation and bioluminescence image assay. RNA sequencing and lipidomic analysis were performed for cholesterol homeostasis analysis. RNA immunoprecipitation and luciferase reporter assay were performed to determine hnRNPA2B1-dependent regulation of sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR) mRNA. The methylation status of hnRNPA2B1 promoter was determined by bioinformatic analysis and methylation-specific PCR assay. Results Among the m6A-regulatory proteins, hnRNPA2B1 was demonstrated the most important independent prognostic risk factor for glioma. hnRNPA2B1 ablation exhibited a significant tumor-suppressive effect on glioma cell proliferation, GSC self-renewal and tumorigenesis. hnRNPA2B1 triggers de novo cholesterol synthesis by inducing HMGCR through the stabilization of SREBP2 mRNA. m6A modification of SREBP2 or LDLR mRNA is required for hnRNPA2B1-mediated mRNA stability. The hypomethylation of cg21815882 site on hnRNPA2B1 promoter confers elevated expression of hnRNPA2B1 in glioma tissues. The combination of targeting hnRNPA2B1 and cholesterol metabolism exhibited remarkable antitumor effects, suggesting valuable clinical implications for glioma treatment. Conclusions hnRNPA2B1 facilitates cholesterol uptake and de novo synthesis, thereby contributing to glioma stemness and malignancy.
DNA Polymerase Diversity Reveals Multiple Incursions of Polintons During Nematode Evolution
Authors: Dae-Eun Jeong, Sameer Sundrani, Richard Nelson Hall, Mart Krupovic, Eugene V Koonin, Andrew Z Fire
Journal: Molecular Biology and Evolution (2023)

Polintons are double-stranded DNA, virus-like self-synthesizing transposons widely found in eukaryotic genomes. Recent metagenomic discoveries of Polinton-like viruses are consistent with the hypothesis that Polintons invade eukaryotic host genomes through infectious viral particles. Nematode genomes contain multiple copies of Polintons and provide an opportunity to explore the natural distribution and evolution of Polintons during this process. We performed an extensive search of Polintons across nematode genomes, identifying multiple full-length Polinton copies in several species. We provide evidence of both ancient Polinton integrations and recent mobility in strains of the same nematode species. In addition to the major nematode Polinton family, we identified a group of Polintons that are overall closely related to the major family but encode a distinct protein-primed DNA polymerase B (pPolB) that is related to homologs from a different group of Polintons present outside of the Nematoda. Phylogenetic analyses on the pPolBs support the evolutionary scenarios in which these extrinsic pPolBs that seem to derive from Polinton families present in oomycetes and molluscs replaced the canonical pPolB in subsets of Polintons found in terrestrial and marine nematodes, respectively, suggesting interphylum horizontal gene transfers. The pPolBs of the terrestrial nematode and oomycete Polintons share a unique feature, an insertion of an HNH nuclease domain, whereas the pPolBs in the marine nematode Polintons share an insertion of a VSR nuclease domain with marine mollusc pPolBs. We hypothesize that horizontal gene transfer occurs among Polintons from widely different but cohabiting hosts.
A Fast, Reproducible, High-throughput Variant Calling Workflow for Population Genomics
Authors: Cade D Mirchandani, Allison J Shultz, Gregg W C Thomas, Sara J Smith, Mara Baylis, Brian Arnold, Russ Corbett-Detig, Erik Enbody, Timothy B Sackton
Journal: Molecular Biology and Evolution (2023)

The increasing availability of genomic resequencing data sets and high-quality reference genomes across the tree of life present exciting opportunities for comparative population genomic studies. However, substantial challenges prevent the simple reuse of data across different studies and species, arising from variability in variant calling pipelines, data quality, and the need for computationally intensive reanalysis. Here, we present snpArcher, a flexible and highly efficient workflow designed for the analysis of genomic resequencing data in nonmodel organisms. snpArcher provides a standardized variant calling pipeline and includes modules for variant quality control, data visualization, variant filtering, and other downstream analyses. Implemented in Snakemake, snpArcher is user-friendly, reproducible, and designed to be compatible with high-performance computing clusters and cloud environments. To demonstrate the flexibility of this pipeline, we applied snpArcher to 26 public resequencing data sets from nonmammalian vertebrates. These variant data sets are hosted publicly to enable future comparative population genomic analyses. With its extensibility and the availability of public data sets, snpArcher will contribute to a broader understanding of genetic variation across species by facilitating the rapid use and reuse of large genomic data sets.
Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma
Authors: Yanfei Sun, Guangjing Mu, Xuehai Zhang, Yibo Wu, Shuai Wang, Xu Wang, Zhiwei Xue, Chuanwei Wang, Jilong Liu, Wenbo Li, Lin Zhang, Yunyun Guo, Feihu Zhao, Xuemeng Liu, Zhiyi Xue, Yan Zhang, Shilei Ni, Jian Wang, Xingang Li, Mingzhi Han, Bin Huang
Journal: Neuro-Oncology (2023)

Abstract Background Altered branched-chain amino acid (BCAA) metabolism modulates epigenetic modification, such as H3K27ac in cancer, thus providing a link between metabolic reprogramming and epigenetic change, which are prominent hallmarks of glioblastoma multiforme (GBM). Here, we identified mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), an enzyme involved in leucine degradation, promoting GBM progression and glioma stem cell (GSC) maintenance. Methods In silico analysis was performed to identify specific molecules involved in multiple processes. Glioblastoma multiforme cells were infected with knockdown/overexpression lentiviral constructs of HMGCL to assess malignant performance in vitro and in an orthotopic xenograft model. RNA sequencing was used to identify potential downstream molecular targets. Results HMGCL, as a gene, increased in GBM and was associated with poor survival in patients. Knockdown of HMGCL suppressed proliferation and invasion in vitro and in vivo. Acetyl-CoA was decreased with HMGCL knockdown, which led to reduced NFAT1 nuclear accumulation and H3K27ac level. RNA sequencing-based transcriptomic profiling revealed FOXM1 as a candidate downstream target, and HMGCL-mediated H3K27ac modification in the FOXM1 promoter induced transcription of the gene. Loss of FOXM1 protein with HMGCL knockdown led to decreased nuclear translocation and thus activity of β-catenin, a known oncogene. Finally, JIB-04, a small molecule confirmed to bind to HMGCL, suppressed GBM tumorigenesis in vitro and in vivo. Conclusions Changes in acetyl-CoA levels induced by HMGCL altered H3K27ac modification, which triggers transcription of FOXM1 and β-catenin nuclear translocation. Targeting HMGCL by JIB-04 inhibited tumor growth, indicating that mediators of BCAA metabolism may serve as molecular targets for effective GBM treatment.
Mapping and Functional Dissection of the Rumpless Trait in Piao Chicken Identifies a Causal Loss of Function Mutation in the Novel Gene <i>Rum</i>
Authors: Ying Guo, Jing Tian, Chi Song, Wei Han, Chunhong Zhu, Huifang Li, Shuangjie Zhang, Kuanwei Chen, Ning Li, Örjan Carlborg, Xiaoxiang Hu
Journal: Molecular Biology and Evolution (2023)

Abstract Rumpless chickens exhibit an abnormality in their tail development. The genetics and biology of this trait has been studied for decades to illustrate a broad variation in both the types of inheritance and the severity in the developmental defects of the tail. In this study, we created a backcross pedigree by intercrossing Piao (rumpless) with Xianju (normal) to investigate the genetic mechanisms and molecular basis of the rumpless trait in Piao chicken. Through genome-wide association and linkage analyses, the candidate region was fine-mapped to 798.5 kb (chromosome 2: 86.9 to 87.7 Mb). Whole-genome sequencing analyses identified a single variant, a 4.2 kb deletion, which was completely associated with the rumpless phenotype. Explorations of the expression data identified a novel causative gene, Rum, that produced a long, intronless transcript across the deletion. The expression of Rum is embryo-specific, and it regulates the expression of MSGN1, a key factor in regulating T-box transcription factors required for mesoderm formation and differentiation. These results provide genetic and molecular experimental evidence for a novel mechanism regulating tail development in chicken and report the likely causal mutation for the tail abnormity in the Piao chicken. The novel regulatory gene, Rum, will, due to its role in fundamental embryo development, be of interest for further explorations of a potential role in tail and skeletal development also in other vertebrates.
The Effect of Anxiety on Intraoperative and Postoperative Pain in Patients Undergoing Dermatologic Surgery: Learn to Manage
Authors: Giulio Gualdi, Alessia Loda, Andrea Andreassi, Carlo Francesco Tomasini, Cesare Ariasi, Chiara Giorgini, Cristina Ciuluvica Neagu, Ernesto De Piano, Francesca Saracino, Giulio Gualdi, Martina Volontè, Paolo Amerio, Piergiacomo Calzavara-Pinton, Pietro Rubegni, Stefano Bighetti
Journal: International Journal of Surgery (2023)

Background: Dermatological surgery has a primary role in dermatologists' daily practice and is usually performed under local anesthesia. This approach required particular attention in patient management before, after, and especially during the surgical procedures. Many people experience anxiety and negative emotions when approaching surgery, and how they feel before surgery affects outcomes after surgery. Objective: The main goals of the present research were to measure and describe anxiety and pain in dermatologic surgery patients and to investigate the anxiety prediction power in predicting surgical pain. Anxiety has been considered at two different moments: before the surgery (preoperative anxiety) and immediately after (postoperative anxiety). Intraoperative as well as postoperative pain have been assessed. The relationships between these two main variables and other factors, including demographics, skin disease history, and vital signs, have been analyzed. Results: The first data concerns the number of patients who experienced preoperative clinical anxiety, which is equal to 150 (29.4%) and has been reduced to 74 (14.5%) regarding postoperative anxiety. Preoperative anxiety, but not postoperative anxiety, significantly contributes to pain prediction. Occupation and previous tumor surgery resulted the main factors associated with preoperative anxiety in intraoperative pain prediction. Diastolic blood pressure, patient occupation, and previous tumor surgery were associated with preoperative anxiety in predicting postoperative pain. Conclusion: Detecting anxiety pre and post-surgery in patients and knowing its relation with pain may allow corrective or palliative measures since anti-inflammatory medication may increase the risk of postoperative bleeding and complications. Patients with features linked to pain perception variation require increased attention to pain management.
Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease
Authors: Talha Munir, David A. Cairns, Adrian Bloor, David Allsup, Kate Cwynarski, Andrew Pettitt, Shankara Paneesha, Christopher P. Fox, Toby A. Eyre, Francesco Forconi, Nagah Elmusharaf, Ben Kennedy, John Gribben, Nicholas Pemberton, Oonagh Sheehy, Gavin Preston, Anna Schuh, Renata Walewska, Lelia Duley, Dena Howard, Anna Hockaday, Sharon Jackson, Natasha Greatorex, Sean Girvan, Sue Bell, Julia M. Brown, Nichola Webster, Surita Dalal, Ruth de Tute, Andrew Rawstron, Piers E.M. Patten, Peter Hillmen
Journal: New England Journal of Medicine (2023)

The combination of ibrutinib and venetoclax has been shown to improve outcomes in patients with chronic lymphocytic leukemia (CLL) as compared with chemoimmunotherapy. Whether ibrutinib-venetoclax and personalization of treatment duration according to measurable residual disease (MRD) is more effective than fludarabine-cyclophosphamide-rituximab (FCR) is unclear.
Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study
Authors: Michael Wang, Tanya Siddiqi, Leo I. Gordon, Manali Kamdar, Matthew Lunning, Alexandre V. Hirayama, Jeremy S. Abramson, Jon Arnason, Nilanjan Ghosh, Amitkumar Mehta, Charalambos Andreadis, Scott R. Solomon, Ana Kostic, Christine Dehner, Ricardo Espinola, Lily Peng, Ken Ogasawara, Amy Chattin, Laurie Eliason, M. Lia Palomba
Journal: Journal of Clinical Oncology (2023)

To report the primary analysis results from the mantle cell lymphoma (MCL) cohort of the phase I seamless design TRANSCEND NHL 001 (ClinicalTrials.gov identifier: NCT02631044) study.
Patient Navigation for Timely, Guideline-Adherent Adjuvant Therapy for Head and Neck Cancer: A National Landscape Analysis
Authors: Evan M. Graboyes, Michelle Chappell, Kelsey A. Duckett, Katherine Sterba, Chanita Hughes Halbert, Elizabeth G. Hill, Bhishamjit Chera, Jessica McCay, Sidharth V. Puram, Salma Ramadan, Vlad C. Sandulache, Russel Kahmke, Brian Nussenbaum, Anthony J. Alberg, Electra D. Paskett, Elizabeth Calhoun
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Aligned with the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers, in November 2021 the Commission on Cancer approved initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery for head and neck cancer (HNC) as its first and only HNC quality metric. Unfortunately, &gt;50% of patients do not commence PORT within 6 weeks, and delays disproportionately burden racial and ethnic minority groups. Although patient navigation (PN) is a potential strategy to improve the delivery of timely, equitable, guideline-adherent PORT, the national landscape of PN for this aspect of care is unknown. Materials and Methods: From September through November 2022, we conducted a survey of health care organizations that participate in the American Cancer Society National Navigation Roundtable to understand the scope of PN for delivering timely, guideline-adherent PORT for patients with HNC. Results: Of the 94 institutions that completed the survey, 89.4% (n=84) reported that at least part of their practice was dedicated to navigating patients with HNC. Sixty-eight percent of the institutions who reported navigating patients with HNC along the continuum (56/83) reported helping them begin PORT. One-third of HNC navigators (32.5%; 27/83) reported tracking the metric for time-to-PORT at their facility. When estimating the timeframe in which the NCCN and Commission on Cancer guidelines recommend commencing PORT, 44.0% (37/84) of HNC navigators correctly stated ≤6 weeks; 71.4% (60/84) reported that they did not know the frequency of delays starting PORT among patients with HNC nationally, and 63.1% (53/84) did not know the frequency of delays at their institution. Conclusions: In this national landscape survey, we identified that PN is already widely used in clinical practice to help patients with HNC start timely, guideline-adherent PORT. To enhance and scale PN within this area and improve the quality and equity of HNC care delivery, organizations could focus on providing better education and support for their navigators as well as specialization in HNC.
Letter to Santa
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2023)

It's me, Margaret.Yep, I am still here at JNCCN, though not for too much longer.In fact, this will be my last letter, since my term as Editor-in-Chief ends next year.I hope that doesn't make you feel bad, as I'm sure you look forward to hearing from me each year.But it's OK; efforts to choose my successor are underway, and I'm sure the new Editor-in-Chief will be in touch.As for me, I will still be working at UCSF and will be counting on your generous support for so many things we need there!How are you and Mrs. Claus doing?Did you both remember to get your flu and updated COVID vaccines?I do worry about you.You are an older adult, and a tad overweight, so you need to look out for yourself and be extra careful.It wouldn't be a bad idea to wear a mask in crowded places, but I know it's hard to stuff that big beard into a regular N95.Maybe the elves can make a special one for you.Speaking of the elves, I hope you are giving due consideration to diversity, equity, and inclusion (DEI) whenever you are hiring.When I see pictures of your workshop, I don't see many lady elves, and I can't remember seeing a single elf of color.I'll send you a link to our DEI training module; it will definitely open your eyes and heart to elves with different backgrounds.This brings me to my wish list for this year.I asked for world peace last year, and that didn't happen.I am not saying it's your fault, but it does lower my expectations for this year.Just sayin'.My focus this year is on women in medicine, especially in oncology.A crisis is looming, and it would be great if you could help.
What Constitutes Quality of Life? Perspectives of Adolescents and Young Adults With Advanced Cancer
Authors: Jane Hinkle, Lori Wiener, Andrea Altschuler, Katharine E. Brock, Mallory Casperson, Chun R. Chao, Lauren Fisher, Lawrence H. Kushi, Joshua R. Lakin, Anna Lefebvre, Corey M. Schwartz, Dov M. Shalman, Catherine B. Wall, Jennifer W. Mack
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Adolescents and young adults (AYAs) with advanced cancer identify maintaining a good quality of life (QoL) as a central goal of end-of-life care. QoL is a dynamic and subjective overarching concept that refers to an individual’s relative satisfaction with their own life. Despite its importance to AYAs with advanced cancer, a patient-centered definition of QoL is lacking in this population. Patients and Methods: This qualitative secondary analysis of semistructured interviews was conducted across 3 institutions and 1 online support community among AYA patients with advanced cancer, family caregivers, and health care providers who cared for living or recently deceased AYAs. Interviewees were asked about priorities in receipt of care. Interviews were transcribed using NVivo software for primary analysis, and previously coded excerpts were screened for references to QoL. Relevant excerpts were sorted into organizing domains. Results: Participants included 23 AYA patients, 28 family caregivers, and 29 health care providers (including physicians, nurses, nurse practitioners, social workers, and psychologists). Four domains of QoL were identified: psychosocial and physical well-being, dignity, normalcy, and personal and family relationships. Within each domain there was agreement across AYAs, caregivers, and health care providers, with nuanced perspectives provided by AYAs of different ages. Personal and family relationships was the most frequently referenced domain of QoL among all participants. A common feature of each domain was that adaptation to current circumstances impacted perspectives on QoL. Patients valued active participation in the development of a care plan that supported these domains. Conclusions: AYAs with advanced cancer, their caregivers, and health care providers agree on several broad domains of QoL in this population. To provide high-quality, patient-centered care, care plans should integrate these domains to enable AYAs to maximize their QoL throughout their advanced cancer care.
Review of Dermatology, Second Edition
Authors: Stephanie Munie
Journal: Journal of the American Academy of Dermatology (2023)

Review of Dermatology (Alikhan and Hocker, 2024) offers a thorough overview of a wide range of topics in a practical, well-organized, and straightforward manner. Its simple bulleted structure, with key points highlighted along the way, allows for an easy-to-read and easy-to-reference tool for busy physicians. High-yield topics in dermatopathology, general and pediatric dermatology, cosmetics, and dermatologic surgery are presented succinctly with appropriate attention to detail, encompassing a spectrum of rare to frequently-encountered conditions.
Words Matter: Unintended Side Effects of “Financial Toxicity”
Authors: Eric C. Blackstone, Barbara J. Daly
Journal: Journal of the National Comprehensive Cancer Network (2023)

igh out-of-pocket costs of treatment in the United States are a major driver of health disparities.The financial burdens associated with medical care are frequently referred to in the literature as "financial toxicity."This term was popularized after articles by Zafar and Abernethy in 2013 highlighted the growing out-of-pocket costs borne by patients with cancer. 1,2They describe financial toxicity as consisting of both "objective financial burden" and the subjective distress resulting from that burden.The authors attribute increasing costs to 4 factors: "an aging populace, more patients with access to treatment, innovation, and overutilization."Since 2013, the concept of financial toxicity has gained significant popularity in the oncology literature and has been adopted in other specialties, such as neurology. 3The reasons for this are understandable.Clinicians are familiar with the notion of unintended and sometimes serious noxious side effects of treatments.Chemotherapeutic agents powerful enough to slow or eradicate cancerous cells often are just as powerful in damaging healthy tissue.Thus, explanation of potential toxicity is routinely included in discussions with patients about recommended treatment."Financial toxicity" is a useful idiom that encourages clinicians to screen for, identify, and attempt to manage treatment-induced financial problems just as they do for other treatment-related toxicities.However, this choice of language may obscure rather than illuminate causes of the problem and our responsibility to work toward solutions.
Granzyme K– and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease
Authors: Risako Koga, Takashi Maehara, Ryuichi Aoyagi, Ryusuke Munemura, Yuka Murakami, Atsushi Doi, Michihito Kono, Hidetaka Yamamoto, Hiroaki Niiro, Tamotsu Kiyoshima, Mika Tanabe, Toshiaki Nakano, Yuta Matsukuma, Mitsuhiro Kawano, John H. Stone, Shiv Pillai, Seiji Nakamura, Shintaro Kawano
Journal: Journal of Allergy and Clinical Immunology (2023)