tbuckley/cabot-search huggingface dataset:
Analysis of Price Transparency for Oncologic Surgery Among National Cancer Institute–Designated Cancer Centers in 2020
Authors: Roy Xiao, Lauren E. Miller, Alan D. Workman, Ryan A. Bartholomew, Lucy J. Xu, Vinay K. Rathi
Journal: JAMA Surgery (2021)

In January 2019, the Centers for Medicare and Medicaid Services (CMS) began legally requiring hospitals to pub-lish chargemasters online to promote price transparency. 1Hospital chargemasters list gross charges for all items and services, which are the undiscounted prices hospitals bill patients who are uninsured, self pay, or have out-of-network insurance.
Abstract 17134: Variation Within a Left Ventricle-Specific <i>Hand1</i> Enhancer Impairs Gata Transcription Factor Binding and Disrupts Ventricular Conduction System Development
Authors: Joshua W Vincentz, Beth A Firulli, Kevin P Toolan, Dan E Arking, Nona Sotoodehnia, Juyi Wan, Peng-Sheng Chen, Corrie de Gier-de Vries, Vincent M Christoffels, Michael Rubart-von der Lohe, Anthony B Firulli
Journal: Circulation (2018)

The ventricular conduction system (VCS), composed of the His bundle, the left and right bundle branches, and the Purkinje fiber network, rapidly propagates electrical impulses through the ventricles to coordinate chamber contraction. An ECG depicts VCS-mediated ventricular depolarization as the QRS interval. Disorders of the VCS may manifest as arrhythmias, and are associated with increased risk of sudden cardiac death and overall mortality. The genetic and developmental mechanisms underlying VCS dysfunction are poorly understood. Genome-wide association studies have identified multiple single nucleotide polymorphisms (SNPs) associated with VCS arrhythmias. A majority of these SNPs occur outside of coding domains, within intergenic or intronic regions. We hypothesize that such pathogenic SNPs may impact VCS development and function by altering the expression of critical genes. Two intergenic SNPs associated with QRS prolongation occur near the bHLH cardiac transcription factor HAND1 . We have identified a left ventricle (LV) enhancer, located between these two SNPs, that is necessary and sufficient for LV cis -regulatory activity. Two evolutionarily conserved GATA transcription factor consensus-binding sites within this enhancer are bound by GATA4 and necessary for cis -regulatory activity. CRISPR-mediated deletion of this enhancer dramatically reduced Hand1 expression solely within the LV. Mice homozygous for this deleted enhancer displayed dysregulated LV gene expression, morphologically abnormal His bundles and left bundle branches, and a VCS phenotype consistent with right bundle branch block. Genome-wide association analyses of human patients with QRS prolongation revealed additional, linked SNPs, one of which overlaps with a critical GATA cis -regulatory element within the LV-specific Hand1 enhancer. This SNP disrupts GATA4 binding. Ongoing studies of mice that genetically mimic these minor SNP variants will assess reduced Hand1 expression and impaired VCS function. We conclude that a LV-specific Hand1 enhancer is necessary for VCS development and a SNP associated with QRS prolongation directly influences GATA4 binding to a critical cis -regulatory element within this enhancer.
Detection of Colorectal Neoplasms Using Linked Color Imaging: A Prospective, Randomized, Tandem Colonoscopy Trial
Authors: Issei Hasegawa, Takeshi Yamamura, Hiroto Suzuki, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Masanao Nakamura, Mitsuhiro Fujishiro
Journal: Clinical Gastroenterology and Hepatology (2021)
Abstract PO-008: Mechanistic and therapeutic links between purine biosynthesis and DNA damage in glioblastoma
Authors: Andrew J. Scott, Weihua Zhou, Kari Wilder-Romans, Anthony C. Andren, Li Zhang, Yoshie Umemura, Nathan Qi, Theodore S. Lawrence, Costas A. Lyssiotis, Daniel R Wahl
Journal: Clinical Cancer Research (2021)

Abstract Glioblastoma (GBM) is the most common and aggressive adult brain cancer. Radiation therapy (RT) is a critical treatment modality, and development of RT resistance is the predominant cause of recurrence and mortality in GBM patients. Using cell line models as well as patient-derived xenografts and neurospheres in orthotopic brain tumor models, we have identified increased rates and dependence upon de novo purine biosynthesis as a hallmark of GBM RT resistance. More recently, we have discovered that radiation treatment acutely stimulates flux through de novo purine synthesis in cell line and neurosphere models of GBM. This RT-induced increase in de novo purine synthesis is dependent on signaling through the DNA damage response and thus appears to be an adaptive mechanism to supply purines to repair radiation-induced DNA damage. To determine whether this regulatory mechanism also exists in vivo, we have used advanced metabolomic and metabolic tracing techniques with 13C-labeled glucose and 15N-labeled glutamine in mice bearing RT-resistant GBM patient-derived orthotopic brain tumors. We found that that orthotopic GBM PDXs had elevated activity of de novo purine synthesis that increased further after RT, while normal cortex had little activity even after RT. These observations have therapeutic relevance, as targeting this metabolic pathway with the FDA-approved purine biosynthesis inhibitor mycophenolate mofetil (MMF) overcomes GBM radiation resistance in mouse models in vivo. The lack of de novo purine synthesis in normal cortex suggests that targeting this pathway may be tumor specific. Collectively our data suggest that de novo synthesis of purines mediates RT resistance in GBM and that treatment of brain tumors with MMF in combination with RT may be a promising therapeutic strategy in patients. Citation Format: Andrew J. Scott, Weihua Zhou, Kari Wilder-Romans, Anthony C. Andren, Li Zhang, Yoshie Umemura, Nathan Qi, Theodore S. Lawrence, Costas A. Lyssiotis, Daniel R Wahl. Mechanistic and therapeutic links between purine biosynthesis and DNA damage in glioblastoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-008.
Health equity in focus: introducing the Association of Black Gastroenterologists and Hepatologists
Authors: Darrell M Gray, Adjoa Anyane-Yeboa, Rachel B Issaka, Sophie Balzora, Darrell M Gray, Adjoa Anyane-Yeboa, Rachel B Issaka, Sophie Balzora, Valérie Antoine-Gustave, Rotonya M Carr, Alexandra Guillaume, Ugo Iroku, Folasade P May, Renee Williams, Pascale M White
Journal: The Lancet. Gastroenterology & hepatology (2021)
The Uncomfortable Look
Authors: Jude Dumfeh
Journal: Annals of Internal Medicine (2021)

On Being a DoctorApril 2021The Uncomfortable LookJude Dumfeh, MDJude Dumfeh, MDGottlieb Memorial Hospital, Melrose Park, IllinoisSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-4687 Audio Reading - “The Uncomfortable Look” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “The Uncomfortable Look” by Jude Dumfeh, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail He was a young man in police custody, admitted to the ICU with diabetic ketoacidosis. As I reviewed the medical record, I was struck by the fact that he had been in college about a year ago. I walked into his room and met a Black man in his 20s, shackled to the bed with handcuffs, with a police officer present. He was mild mannered and didn't fit the stereotype of someone in custody. I could not help but wonder how he went from being a college student to a prisoner in about a year. I asked the officer to ... Author, Article, and Disclosure InformationAffiliations: Gottlieb Memorial Hospital, Melrose Park, IllinoisCorresponding Author: Jude Dumfeh, MD, Gottlieb Memorial Hospital, 701 West North Avenue, Melrose Park, IL 60160; e-mail, jude.[email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Uncomfortable Look” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “The Uncomfortable Look” by Jude Dumfeh, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics April 2021Volume 174, Issue 4Page: 562 ePublished: 20 April 2021 Issue Published: April 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Bioactive Decellularized Extracellular Matrix Derived from 3D Stem Cell Spheroids under Macromolecular Crowding Serves as a Scaffold for Tissue Engineering
Authors: Cheng‐En Chiang, Yi‐Qiao Fang, Chao‐Ting Ho, Marisa Assunção, Sheng‐Ju Lin, Yu‐Chieh Wang, Anna Blocki, Chieh‐Cheng Huang
Journal: Advanced Healthcare Materials (2021)

Abstract Scaffolds for tissue engineering aim to mimic the native extracellular matrix (ECM) that provides physical support and biochemical signals to modulate multiple cell behaviors. However, the majority of currently used biomaterials are oversimplified and therefore fail to provide a niche required for the stimulation of tissue regeneration. In the present study, 3D decellularized ECM (dECM) scaffolds derived from mesenchymal stem cell (MSC) spheroids and with intricate matrix composition are developed. Specifically, application of macromolecular crowding (MMC) to MSC spheroid cultures facilitate ECM assembly in a 3D configuration, resulting in the accumulation of ECM and associated bioactive components. Decellularized 3D dECM constructs produced under MMC are able to adequately preserve the microarchitecture of structural ECM components and are characterized by higher retention of growth factors. This results in a stronger proangiogenic bioactivity as compared to constructs produced under uncrowded conditions. These dECM scaffolds can be homogenously populated by endothelial cells, which direct the macroassembly of the structures into larger cell‐carrying constructs. Application of empty scaffolds enhances intrinsic revascularization in vivo, indicating that the 3D dECM scaffolds represent optimal proangiogenic bioactive blocks for the construction of larger engineered tissue constructs.
Multiple immune-related toxicities in cancer patients treated with anti-programmed cell death protein 1 immunotherapies: a new surrogate marker for clinical trials?
Authors: A. Laparra, M. Kfoury, S. Champiat, F.X. Danlos, P. Martin-Romano, A. Simonaggio, C. Baldini, P. Vuagnat, C. Mateus, A.L. Voisin, L. Albiges, B. Besse, C. Even, C. Robert, S. Laghouati, C. Massard, A. Marabelle, O. Lambotte, J.M. Michot
Journal: Annals of Oncology (2021)
Abstract PO-025: Radiation-induced and FACS-sorted senescent tdTOMp16+ cells upregulate profibrotic genes in C57BL/6 stromal target cells
Authors: Amitava Mukherjee, Michael Epperly, Donna Shields, Wen Hou, Renee Fisher, Diala Hamade, Joel S. Greenberger
Journal: Clinical Cancer Research (2021)

Abstract Acute Radiation Syndrome and the multiorgan failure from delayed effects of acute radiation exposure present challenging consequences of radiation terrorism or a radiological accident. Recent research suggests that radiation-induced cellular senescence plays an important role in radiation-induced pulmonary fibrosis (RIPF), and that clearance of senescent cells (SCs) could be an effective therapeutic strategy. However, the identification and targeted removal of only senescent cells using drugs have been difficult. Here we have established a bone-marrow stromal cell line from a tdTOMp16+ mouse. We show that 5 Gy irradiation induces ~9% cellular senescence in tdTOMp16+ stromal line after 10 days and can be isolated as a pure population of red tdTOMp16+ cells by FACS sorting. To confirm that these irradiated and then sorted red cells are senescent, we cultured them as single cells in 96-well plates and followed for four weeks. None of the 960 irradiated red cells we plated divided after 2 weeks, 137 of these cells remained intact and assumed large and flat cellular morphology. In contrast, 50 of 800 cells that were irradiated but didn’t turn red, divided, as did 104 of 560 nonirradiated control cells (0 Gy) divided. There was significant upregulation of senescent cell markers including SA-ß-gal, p16, and p21 in the irradiated and sorted red cells when compared to irradiated nonred cells. Sorted irradiated red, non-irradiated, or irradiated non-red cells were placed on the top well of transwells. There was a significant induction of fibrotic genes Ctgf, Tgf- ß, collagen 1a, and collagen 3 in C57/B6 stromal target cells in the bottom layer by irradiated red cells, but not the other cell populations irradiated non-red. Thus, radiation-induced biomarkers of fibrosis are induced by senescent cells. Citation Format: Amitava Mukherjee, Michael Epperly, Donna Shields, Wen Hou, Renee Fisher, Diala Hamade, Joel S. Greenberger. Radiation-induced and FACS-sorted senescent tdTOMp16+ cells upregulate profibrotic genes in C57BL/6 stromal target cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-025.
Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Authors: Michael W Knitz, Thomas E Bickett, Laurel B Darragh, Ayman J Oweida, Shilpa Bhatia, Benjamin Van Court, Shiv Bhuvane, Miles Piper, Jacob Gadwa, Adam C Mueller, Diemmy Nguyen, Varuna Nangia, Douglas G Osborne, Xiyuan Bai, Sarah E Ferrara, Mary-Keara Boss, Andrew Goodspeed, Matthew A Burchill, Beth A Jirón Tamburini, Edward D Chan, Curtis R Pickering, Eric T Clambey, Sana D Karam
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Numerous trials combining radiation therapy (RT) and immunotherapy in head and neck squamous cell carcinoma (HNSCC) are failing. Using preclinical immune cold models of HNSCC resistant to RT-immune checkpoint inhibitors, we investigate therapeutic approaches of overcoming such resistance by examining the differential microenvironmental response to RT. Methods We subjected two HPV-negative orthotopic mouse models of HNSCC to combination RT, regulatory T cells (Treg) depletion, and/or CD137 agonism. Tumor growth was measured and intratumorous and lymph node immune populations were compared among treatment groups. Human gene sets, genetically engineered mouse models DEREG and BATF3–/– , flow and time-of-flight cytometry, RNA-Seq, Treg adoptive transfer studies, and in vitro experiments were used to further evaluate the role of dendritic cells (DCs) and Tregs in these treatments. Results In MOC2 orthotopic tumors, we find no therapeutic benefit to targeting classically defined immunosuppressive myeloids, which increase with RT. In these radioresistant tumors, supplementing combination RT and Treg depletion with anti-CD137 agonism stimulates CD103 + DC activation in tumor-draining lymph nodes as characterized by increases in CD80 + and CCR7 + DCs, resulting in a CD8 T cell-dependent response. Simultaneously, Tregs are reprogrammed to an effector phenotype demonstrated by increases in interferonγ + , tumor necrosis factorα + , PI3K + , pAKT + and Eomes + populations as well as decreases in CTLA4 + and NRP-1 + populations. Tumor eradication is observed when RT is increased to an 8 Gy x 5 hypofractionated regimen and combined with anti-CD25+ anti-CD137 treatment. In a human gene set from oral squamous cell carcinoma tumors, high Treg number is associated with earlier recurrence. Conclusions Regulating Treg functionality and DC activation status within the lymph node is critical for generating a T cell effector response in these highly radioresistant tumors. These findings underscore the plasticity of Tregs and represent a new therapeutic opportunity for reprogramming the tumor microenvironment in HNSCCs resistant to conventional radioimmunotherapy approaches.
調節性T細胞移動はグルコキナーゼ仲介される解糖に依存している【Powered by NICT】
Authors: Kishore Madhav, C P Cheung Kenneth, Fu Hongmei, Bonacina Fabrizia, Wang Guosu, Coe David, J Ward Eleanor, Colamatteo Alessandra, Jangani Maryam, Baragetti Andrea, Matarese Giuseppe, M Smith David, Haas Robert, Mauro Claudio, C Wraith David, Okkenhaug Klaus, L Catapano Alberico, De Rosa Veronica, D Norata Giuseppe, M Marelli-Berg Federica
Journal: Immunity (2017)
Non-Myeloablative Transplant in Severe Sickle Cell Disease Is Safe & Effective. Single Center Experience from Saudi Arabia
Authors: Mohsen Al-Zahrani, Ahmed Alaskar, Moussab Damlaj, Khadega Abuelgasim, Giamal Gmati, Hind Abdin Salama, Samer Ghazi, Osama Ali, Bader Alahmari, Ayman Hejazi
Journal: Blood (2017)
Corrugated Indurated Short Cords on the Neck of a Teenage Girl
Authors: An-kang Gu, Jing Li, Li-Tao Zhang
Journal: JAMA Dermatology (2021)

A teenage girl presents with corrugated, elevated, and indurated short cords in the front of the neck surrounded by sclerotic skin. No other similar lesions are found on the body. What is your diagnosis?
In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers
Authors: Menglong Chen, Hui Shi, Shixue Gou, Xiaomin Wang, Lei Li, Qin Jin, Han Wu, Huili Zhang, Yaqin Li, Liang Wang, Huan Li, Jinfu Lin, Wenjing Guo, Zhiwu Jiang, Xiaoyu Yang, Anding Xu, Yuling Zhu, Cheng Zhang, Liangxue Lai, Xiaoping Li
Journal: Genome Medicine (2021)

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.
Covid-19: Government race review “misused evidence,” says Marmot
Authors: Gareth Iacobucci
Journal: BMJ (2021)

A review commissioned by the government that dismissed the notion that structural racism may have contributed to poor health outcomes among ethnic minority groups during the covid-19 pandemic was guilty of a “misuse of evidence,” a world expert on health inequalities has said.

Michael Marmot, director of the Institute of Health Equity at University College London, said that the Commission on Race and Ethnic Disparities,1 chaired by Tony Sewell, failed to acknowledge that racism could account for the “adverse distribution of socioeconomic characteristics” that cause health inequalities when it selectively quoted his evidence.

But although the report has been roundly condemned for concluding that there was “no evidence of systemic or institutional racism” in the UK,2 Marmot said the reaction to it had given him some hope. “Because of their …
Association of heated tobacco product use with tobacco use cessation in a Japanese workplace: a prospective study
Authors: Makiko Kanai, Osamu Kanai, Takahiro Tabuchi, Tadashi Mio
Journal: Thorax (2021)

We investigated how use of heated tobacco products (HTPs) affects tobacco cessation in a Japanese workplace. We offered cessation programmes for 158 tobacco users from November 2018 to April 2019 and surveyed the quitting rate in August 2019. Successful quitting was defined as stopping use of all kinds of nicotine-containing tobacco products. A Poisson regression analysis adjusted with inverse probability weighting showed that HTP users (either exclusive HTP users or dual users) were less likely than exclusive cigarette users to quit tobacco (risk ratio, 0.77; 95% CIs 0.61 to 0.97, p=0.024). The use of HTPs should not be recommended to assist in smoking cessation. Trial registration UMIN000034719.
Abstract 15543: Association Between Body Mass Index and Prognosis of Patients Hospitalized With Heart Failure
Authors: yuta seko, Takao Kato, Takeshi Morimoto, Hidenori Yaku, YASUTAKA INUZUKA, Yodo Tamaki, Neiko Ozasa, Masayuki Shiba, Erika Yamamoto, Yusuke Yoshikawa, Yugo Yamashita, Takeshi Kitai, Ryoji Taniguchi, Moritake Iguchi, kazuya nagao, Takafumi Kawai, Akihiro Komasa, Ryusuke Nishikawa, Yuichi Kawase, Takashi Morinaga, Mamoru Toyofuku, Yutaka Furukawa, Kenji Ando, Kazushige Kadota, Yukihito Sato, Koichiro Kuwahara, Takeshi Kimura
Journal: Circulation (2020)

Background: The prognostic implications of very low body mass index (BMI) values remain unclear in patients with acute decompensated heart failure (ADHF). This study aimed to investigate the prognostic impact of BMI classification based on the World Health Organization criteria in patients with ADHF. Methods and Results: Using data from 4056 consecutive patients with ADHF hospitalized in 19 participating hospitals in Japan between October 2014 and March 2016, we analyzed 3509 patients with available BMI data at discharge. The patients were divided into five groups; (1) Severely underweight: BMI&lt;16 kg/m 2 , (2) Underweight: BMI≥16 kg/m 2 and &lt;18.5 kg/m 2 , (3) Normal weight: BMI≥18.5 kg/m 2 and &lt;25 kg/m 2 , (4) Overweight: BMI≥25 kg/m 2 and &lt;30 kg/m 2 (5) Obese: BMI≥30 kg/m 2 . The primary outcome measure was all-cause death. The median follow-up duration was 471 days, with 96.4% follow up at 1-year. The cumulative 1-year incidence of all-cause death was higher in underweight groups, and lower in overweight groups (Severely underweight: 36.3%, Underweight: 23.9%, Normal weight: 14.4%, Overweight: 7.9%, and Obese: 9.0%, P&lt;0.001). After adjusting confounders, the excess mortality risk remained significant in the severely underweight group (HR, 2.38; 95%CI, 1.88-3.02; P&lt;0.001), and in the underweight group (HR, 1.33; 95%CI, 1.10-1.62; P=0.003) relative to the normal weight group, while the lower mortality risk was no longer significant in the overweight group (HR, 0.76; 95%CI, 0.57-1.01; P=0.06), and in the obese group (HR, 0.89; 95%CI, 0.53-1.50; P=0.66). Conclusions: Lower BMI, not obesity, was associated with a higher risk for all-cause death after discharge in patients with ADHF.