tbuckley/cabot-search huggingface dataset:
Meiotic nuclear divisions 1 (MND1) fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma
Authors: Quanli Zhang, Run Shi, Yongkang Bai, Lijuan Meng, Jingwen Hu, Hongyu Zhu, Tongyan Liu, Xiaomeng De, Siwei Wang, Jie Wang, Lin Xu, Guoren Zhou, Rong Yin
Journal: Cancer Communications (2021)

Abstract Background Considering the increase in the proportion of lung adenocarcinoma (LUAD) cases among all lung cancers and its considerable contribution to cancer‐related deaths worldwide, we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD. Methods The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) data were combined, and a promising risk biomarker called meiotic nuclear divisions 1 (MND1) was selectively acquired. Cell viability assays and subcutaneous xenograft models were used to validate the oncogenic role of MND1 in LUAD cell proliferation and tumor growth. A series of assays, including mass spectrometry, co‐immunoprecipitation (Co‐IP), and chromatin immunoprecipitation (ChIP), were performed to explore the underlying mechanism. Results MND1 up‐regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis. In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle. The results of the Co‐IP, ChIP and dual‐luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel‐like factor 6 (KLF6), and thereby protecting E2F transcription factor 1 (E2F1) from KLF6‐induced transcriptional repression. Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner. Conclusions MND1, KLF6, and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD. MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.
Disposable E-Cigarette Use among U.S. Youth — An Emerging Public Health Challenge
Authors: Teresa W. Wang, Andrea S. Gentzke, Linda J. Neff, Emily V. Glidden, Ahmed Jamal, Eunice Park-Lee, Chunfeng Ren, Karen A. Cullen, Brian A. King, Karen A. Hacker
Journal: New England Journal of Medicine (2021)

Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).In this international platform trial, the control group used in the analysis was not restricted to patients who had undergone concurrent randomization, and both trial agents were reported to improve survival. 5This trial led some treatment guideline committees to recommend the use of these agents (www .cas .mhra .gov .uk/ ViewandAcknowledgment/ ViewAttachment .aspx?Attachment_id=103745).One cannot say with certainty that the statistical modeling was not successful in eliminating bias, especially in a complex and hard to understand platform trial such as REMAP-CAP.The added value from this trial relative to the other randomized trials with straightforward, comparable controls can be questioned.
Schedule-dependent activity of Temozolomide in melanoma xenograft models
Authors: Lianzhu Liang, Suining Lee, Bohdan Yaremko, Ming Liu
Journal: Cancer Research (2005)

1372  Schedule-dependent activity of Temozolomide in melanoma xenograft models Temozolomide (TMZ) is an alkylating agent approved for use in recurrent anaplastic astrocytoma. In the current studies, we evaluated the efficacy of TMZ against a panel of human melanoma models. The antitumor activity of TMZ was compared to that of DTIC in melanoma xenografts. DTIC requires metabolic activation in the liver while TMZ is spontaneously converted to its active form in solution at physiological pH. Using both cultured cells and tumor xenografts, we also evaluated the effects of scheduling on the antitumor activity of TMZ. Different schedules were evaluated using the same total dose of TMZ administered as constant daily dosing, single pulse, or intermittent pulse. In colony formation assays, melanoma cells (LOX, A2058) were treated for either 8 days or 4 days total. In 8 day experiments, cells were given TMZ for either 8 consecutive days, 2 consecutive days, or 2 separate days. Drug treatment given on 2 separate days showed superior inhibition of colony formation compared to the other schedules (p
Correction: complex landscape of alternative splicing in myeloid neoplasms
Authors: Courtney E. Hershberger, Devlin C. Moyer, Vera Adema, Cassandra M. Kerr, Wencke Walter, Stephan Hutter, Manja Meggendorfer, Constance Baer, Wolfgang Kern, Niroshan Nadarajah, Sven Twardziok, Mikkael A. Sekeres, Claudia Haferlach, Torsten Haferlach, Jaroslaw P. Maciejewski, Richard A. Padgett
Journal: Leukemia (2021)
CLO21-017: Hospitalization and Supportive Care Measure (SCM) Utilization in Patients With Germline BRCA1/2 Mutated (gBRCA1/2mut) HER2- Advanced Breast Cancer (ABC) in EMBRACA: Results From an Extended Follow-up Post-hoc Analysis
Authors: Sara Hurvitz, Alexander Niyazov, Ying Chen, Hope S. Rugo
Journal: Journal of the National Comprehensive Cancer Network (2021)

"CLO21-017: Hospitalization and Supportive Care Measure (SCM) Utilization in Patients With Germline BRCA1/2 Mutated (gBRCA1/2mut) HER2- Advanced Breast Cancer (ABC) in EMBRACA: Results From an Extended Follow-up Post-hoc Analysis" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Liquid Metal‐Based Soft Electronics for Wearable Healthcare
Authors: Young‐Geun Park, Ga‐Yeon Lee, Jiuk Jang, Su Min Yun, Enji Kim, Jang‐Ung Park
Journal: Advanced Healthcare Materials (2021)

Wearable healthcare devices have garnered substantial interest for the realization of personal health management by monitoring the physiological parameters of individuals. Attaining the integrity between the devices and the biological interfaces is one of the greatest challenges to achieving high-quality body information in dynamic conditions. Liquid metals, which exist in the liquid phase at room temperatures, are advanced intensively as conductors for deformable devices because of their excellent stretchability and self-healing ability. The unique surface chemistry of liquid metals allows the development of various sensors and devices in wearable form. Also, the biocompatibility of liquid metals, which is verified through numerous biomedical applications, holds immense potential in uses on the surface and inside of a living body. Here, the recent progress of liquid metal-based wearable electronic devices for healthcare with respect to the featured properties and the processing technologies is discussed. Representative examples of applications such as biosensors, neural interfaces, and a soft interconnection for devices are reviewed. The current challenges and prospects for further development are also discussed, and the future directions of advances in the latest research are explored.
An Open Dialogue on Health Disparities and Structural Racism: Response to Open Peer Commentaries
Authors: Maya Sabatello, Mary Jackson Scroggins, Greta Goto, Alicia Santiago, Alma McCormick, Kimberly Jacoby Morris, Christina R. Daulton, Carla L. Easter, Gwen Darien
Journal: The American Journal of Bioethics (2021)

This article refers to:Structural Racism in the COVID-19 Pandemic: Moving ForwardThe Role of Race in Pandemic Vaccine AllocationWhat's True in Truth and Reconciliation? Why Epistemic Justice is of Paramount Importance in Addressing Structural Racism in HealthcareThe Invisibility of Asian Americans in COVID-19 Data, Reporting, and ReliefEquitable Access to Research Benefits: Considerations for COVID-19 Vaccine Development and Clinical Trial CrossoverThe Birth of Injustice: COVID-19 Hospital Infection Control Policy on Latinx Birth ExperienceReifying Racism in the COVID-19 Pandemic ResponseStructural Racism in the COVID-19 Pandemic: Don’t Forget about the Children!Addressing COVID-19 Health Disparities & LatinidadTruth and Reconciliation of Racial and Ethnic Health Disparities: A Case Study of COVID-19Latinos and Structural Racism
FGF19/SOCE/NFATc2 signaling circuit facilitates the self-renewal of liver cancer stem cells
Authors: Jingchun Wang, Huakan Zhao, Lu Zheng, Yu Zhou, Lei Wu, Yanquan Xu, Xiao Zhang, Guifang Yan, Halei Sheng, Rong Xin, Lu Jiang, Juan Lei, Jiangang Zhang, Yu Chen, Jin Peng, Qian Chen, Shuai Yang, Kun Yu, Dingshan Li, Qichao Xie, Yongsheng Li
Journal: Theranostics (2021)

Background & Aims: Liver cancer stem cells (LCSCs) mediate therapeutic resistance and correlate with poor outcomes in patients with hepatocellular carcinoma (HCC). Fibroblast growth factor (FGF)-19 is a crucial oncogenic driver gene in HCC and correlates with poor prognosis. However, whether FGF19 signaling regulates the self-renewal of LCSCs is unknown. Methods: LCSCs were enriched by serum-free suspension. Self-renewal of LCSCs were characterized by sphere formation assay, clonogenicity assay, sorafenib resistance assay and tumorigenic potential assays. Ca2+ image was employed to determine the intracellular concentration of Ca2+. Gain- and loss-of function studies were applied to explore the role of FGF19 signaling in the self-renewal of LCSCs. Results: FGF19 was up-regulated in LCSCs, and positively correlated with certain self-renewal related genes in HCC. Silencing FGF19 suppressed self-renewal of LCSCs, whereas overexpressing FGF19 facilitated CSCs-like properties via activation of FGF receptor (FGFR)-4 in none-LCSCs. Mechanistically, FGF19/FGFR4 signaling stimulated store-operated Ca2+ entry (SOCE) through both the PLCγ and ERK1/2 pathways. Subsequently, SOCE-calcineurin signaling promoted the activation and translocation of nuclear factors of activated T cells (NFAT)-c2, which transcriptionally activated the expression of stemness-related genes (e.g., NANOG, OCT4 and SOX2), as well as FGF19. Furthermore, blockade of FGF19/FGFR4-NFATc2 signaling observably suppressed the self-renewal of LCSCs. Conclusions: FGF19/FGFR4 axis promotes the self-renewal of LCSCs via activating SOCE/NFATc2 pathway; in turn, NFATc2 transcriptionally activates FGF19 expression. Targeting this signaling circuit represents a potential strategy for improving the therapeutic efficacy of HCC.
Human–chimpanzee fused cells reveal cis-regulatory divergence underlying skeletal evolution
Authors: David Gokhman, Rachel M. Agoglia, Maia Kinnebrew, Wei Gordon, Danqiong Sun, Vivek K. Bajpai, Sahin Naqvi, Coral Chen, Anthony Chan, Chider Chen, Dmitri A. Petrov, Nadav Ahituv, Honghao Zhang, Yuji Mishina, Joanna Wysocka, Rajat Rohatgi, Hunter B. Fraser
Journal: Nature Genetics (2021)
Factors Contributing to Missing COVID-19 Cases During Contact Tracing
Authors: Shannan N. Rich, Veronica L. Richards, Emily M. Klann
Journal: JAMA Internal Medicine (2021)

Darpun D. Sachdev, MD; Hannah K. Brosnan, MPH; Michael J. A. Reid, MD, MPH; Michelle Kirian, MPH; Stephanie E. Cohen, MD, MPH; Trang Q. Nguyen, PhD, MPH; Susan Scheer, PhD, MPH
Chromosome-scale genome assembly provides insights into rye biology, evolution and agronomic potential
Authors: M. Timothy Rabanus-Wallace, Bernd Hackauf, Martin Mascher, Thomas Lux, Thomas Wicker, Heidrun Gundlach, Mariana Baez, Andreas Houben, Klaus F. X. Mayer, Liangliang Guo, Jesse Poland, Curtis J. Pozniak, Sean Walkowiak, Joanna Melonek, Coraline R. Praz, Mona Schreiber, Hikmet Budak, Matthias Heuberger, Burkhard Steuernagel, Brande Wulff, Andreas Börner, Brook Byrns, Jana Čížková, D. Brian Fowler, Allan Fritz, Axel Himmelbach, Gemy Kaithakottil, Jens Keilwagen, Beat Keller, David Konkin, Jamie Larsen, Qiang Li, Beata Myśków, Sudharsan Padmarasu, Nidhi Rawat, Uğur Sesiz, Sezgi Biyiklioglu-Kaya, Andy Sharpe, Hana Šimková, Ian Small, David Swarbreck, Helena Toegelová, Natalia Tsvetkova, Anatoly V. Voylokov, Jan Vrána, Eva Bauer, Hanna Bolibok-Bragoszewska, Jaroslav Doležel, Anthony Hall, Jizeng Jia, Viktor Korzun, André Laroche, Xue-Feng Ma, Frank Ordon, Hakan Özkan, Monika Rakoczy-Trojanowska, Uwe Scholz, Alan H. Schulman, Dörthe Siekmann, Stefan Stojałowski, Vijay K. Tiwari, Manuel Spannagl, Nils Stein
Journal: Nature Genetics (2021)

Abstract Rye ( Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye’s incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye–wheat introgressions.
Outcomes and Risk Factors Associated With SARS-CoV-2 Infection in a North American Registry of Patients With Multiple Sclerosis
Authors: Amber Salter, Robert J. Fox, Scott D. Newsome, June Halper, David K. B. Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R. Cutter, Anne H. Cross
Journal: JAMA Neurology (2021)

Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.
P76.61 Long Follow up Study of Comparing Erlotinib (ER) with Gefitinib (GE) for Previously Treated Advanced Non-Small Cell Lung Cancer: WJOG5108LFS
Authors: R. Toyozawa, Y. Iwamoto, T. Yokoyama, Y. Sato, N. Ikeda, N. Mamesaya, H. Daga, A. Niimi, Y. Tamura, K. Nishino, S. Sugawara, M. Oki, T. Kozuki, S. Morita, M. Satouchi, N. Yamamoto, K. Nakagawa, N. Katakami
Journal: Journal of Thoracic Oncology (2021)
Abstract 10164: Stent Thrombosis With and Without Aspirin After Pci in Patients With Atrial Fibrillation
Authors: Nick D Fagel, Jean-Paul R Herrman, Freek Verheugt
Journal: Circulation (2019)

Background: Triple therapy (oral anticoagulants, P2Y12 blocker and aspirin, TT) after PCI in atrial fibrillation (AF) is associated with increased bleeding. Four randomized aspirin-controlled trial...
Abstract P235: Genetic Variants in <i>TCF7L2</i> Modulate Dietary Fat Intake on Changes in Body Composition During a Weight-Loss Intervention
Authors: Josiemer Mattei, Qibin Qi, Frank B Hu, Frank M Sacks, Lu Qi
Journal: Circulation (2012)

Introduction: Polymorphisms mapping to TCF7L2 have been associated with increased risk of type 2 diabetes, impaired glucose and insulin metabolism, and adiposity. Recent observational studies and short-term randomized trials suggest dietary factors, especially fat, may modify TCF7L2 genotype in relation to weight loss. The effect has yet to be verified in long-term intervention settings. Hypothesis: We assessed the hypothesis that two well-recognized TCF7L2 single nucleotide polymorphisms (SNPs) modulate the response to diets of different fat content, in relation to long-term changes in anthropometry and body composition in a 2 year weight-loss intervention trial. Methods: The effect of TCF7L2 SNPs rs7903146 and rs12255372 on changes at 6 months and 2 years in body mass and body composition measures obtained from DEXA scans was evaluated in 590 overweight/obese Caucasian participants of Pounds Lost, a 2-year weight-loss randomized clinical trial of diets differing in macronutrient proportions. Adjusted means were obtained for variant main effect and for interaction with assigned diet group as low-fat (20% from calories) vs. high-fat diet (40%). Results: After adjusting for age, sex, center, and baseline measure, rs12255372 TT (risk allele) carriers had significantly greater decrease at 6 months in BMI, total body fat and trunk fat mass, and marginal decrease in weight ( P for interaction= 0.042, 0.029, 0.033 and 0.056, respectively), than those without this genotype, when following a low-fat diet. A significant interaction ( P =0.035) with the randomized diet was observed for rs7903146 and change in lean mass at 6 months. No significant associations were observed at 2 years. Conclusion: In conclusion, overweight/obese individuals with the risk genotype of TCF7L2 rs12255372 may reduce their body mass and adiposity by following a diet lower in total fat.
Nasal reconstruction with one-stage dermal regeneration template and full-thickness skin graft: Long-term patient outcomes and complications
Authors: Inge J. Veldhuizen, Shenara Musthaq, Joseph J. Disa, Anthony Rossi, Kishwer S. Nehal, Babak J. Mehrara, Erica H. Lee
Journal: Journal of the American Academy of Dermatology (2021)
MAIT cell activation is associated with disease severity markers in acute hantavirus infection
Authors: Kimia T. Maleki, Johanna Tauriainen, Marina García, Priscilla F. Kerkman, Wanda Christ, Joana Dias, Julia Wigren Byström, Edwin Leeansyah, Mattias N. Forsell, Hans-Gustaf Ljunggren, Clas Ahlm, Niklas K. Björkström, Johan K. Sandberg, Jonas Klingström
Journal: Cell Reports Medicine (2021)

Hantaviruses are zoonotic RNA viruses that cause severe acute disease in humans. Infected individuals have strong inflammatory responses that likely cause immunopathology. Here, we studied the response of mucosal-associated invariant T (MAIT) cells in peripheral blood of individuals with hemorrhagic fever with renal syndrome (HFRS) caused by Puumala orthohantavirus, a hantavirus endemic in Europe. We show that MAIT cell levels decrease in the blood during HFRS and that residual MAIT cells are highly activated. This activation correlates with HFRS severity markers. In vitro activation of MAIT cells by hantavirus-exposed antigen-presenting cells is dependent on type I interferons (IFNs) and independent of interleukin-18 (IL-18). These findings highlight the role of type I IFNs in virus-driven MAIT cell activation and suggest a potential role of MAIT cells in the disease pathogenesis of viral infections.
Disability in children and adolescents must be integrated into the global health agenda
Authors: Alarcos Cieza, Kaloyan Kamenov, Mariano Gacto Sanchez, Somnath Chatterji, Mangai Balasegaram, Ornella Lincetto, Chiara Servili, Raoul Bermejo, David A Ross
Journal: BMJ (2021)

Disability in children and adolescents must be integrated into the global health agendaAlarcos Cieza and colleagues argue that services for children and young people with disability need greater priority• Services that do exist are invariably of poor quality or under-resourced.
Serum Metabolomics Identifies Dysregulated Pathways and Potential Metabolic Biomarkers for Hyperuricemia and Gout
Authors: Xia Shen, Can Wang, Ningning Liang, Zhen Liu, Xinde Li, Zheng‐Jiang Zhu, Tony R. Merriman, Nicola Dalbeth, Robert Terkeltaub, Changgui Li, Huiyong Yin
Journal: Arthritis & Rheumatology (2021)

To systematically profile metabolic alterations and dysregulated metabolic pathways in hyperuricemia and gout, and to identify potential metabolite biomarkers to discriminate gout from asymptomatic hyperuricemia.Serum samples from 330 participants, including 109 with gout, 102 with asymptomatic hyperuricemia, and 119 normouricemic controls, were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate principal components analysis and orthogonal partial least squares discriminant analysis were performed to explore differential metabolites and pathways. A multivariate methods with Unbiased Variable selection in R (MUVR) algorithm was performed to identify potential biomarkers and build multivariate diagnostic models using 3 machine learning algorithms: random forest, support vector machine, and logistic regression.Univariate analysis demonstrated that there was a greater difference between the metabolic profiles of patients with gout and normouricemic controls than between the metabolic profiles of individuals with hyperuricemia and normouricemic controls, while gout and hyperuricemia showed clear metabolomic differences. Pathway enrichment analysis found diverse significantly dysregulated pathways in individuals with hyperuricemia and patients with gout compared to normouricemic controls, among which arginine metabolism appeared to play a critical role. The multivariate diagnostic model using MUVR found 13 metabolites as potential biomarkers to differentiate hyperuricemia and gout from normouricemia. Two-thirds of the samples were randomly selected as a training set, and the remainder were used as a validation set. Receiver operating characteristic analysis of 7 metabolites yielded an area under the curve of 0.83-0.87 in the training set and 0.78-0.84 in the validation set for distinguishing gout from asymptomatic hyperuricemia by 3 machine learning algorithms.Gout and hyperuricemia have distinct serum metabolomic signatures. This diagnostic model has the potential to improve current gout care through early detection or prediction of progression to gout from hyperuricemia.
Altered endocytosis in cellular senescence
Authors: Eun-Young Shin, Nak-Kyun Soung, Martin Alexander Schwartz, Eung-Gook Kim
Journal: Ageing Research Reviews (2021)

Cellular senescence occurs in response to diverse stresses (e.g., telomere shortening, DNA damage, oxidative stress, oncogene activation). A growing body of evidence indicates that alterations in multiple components of endocytic pathways contribute to cellular senescence. Clathrin-mediated endocytosis (CME) and caveolae-mediated endocytosis (CavME) represent major types of endocytosis that are implicated in senescence. More recent research has also identified a chromatin modifier and tumor suppressor that contributes to the induction of senescence via altered endocytosis. Here, molecular regulators of aberrant endocytosis-induced senescence are reviewed and discussed in the context of their capacity to serve as senescence-inducing stressors or modifiers.
FP14.16 Phase 2 Trial of the Alternating Therapy with Osimertinib and Afatinib for Treatment-Naive Patients with EGFR-Mutated Advanced Non–Small Cell Lung Cancer (WJOG10818L/Alt Trial)
Authors: H. Hayashi, K. Yonesaka, S. Sugawara, Y. Sato, K. Azuma, S. Sakata, M. Tachihara, S. Ikeda, T. Yokoyama, O. Hataji, Y. Yano, K. Hirano, H. Daga, H. Okada, K. Sakai, Y. Chiba, K. Nishio, N. Yamamoto, K. Nakagawa
Journal: Journal of Thoracic Oncology (2021)
<i>BRAF</i>V600E Mutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data From the ARCAD Database
Authors: Romain Cohen, Heshan Liu, Jack Fiskum, Richard Adams, Benoist Chibaudel, Timothy S Maughan, Eric Van Cutsem, Alan Venook, Jean-Yves Douillard, Volker Heinemann, Cornelis Ja Punt, Alfredo Falcone, Carsten Bokemeyer, Richard Kaplan, Heinz-Josef Lenz, Miriam Koopman, Takayuki Yoshino, John Zalcberg, Alex Grothey, Aimery de Gramont, Qian Shi, Thierry André
Journal: JNCI Journal of the National Cancer Institute (2021)

First-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed to assess the prognostic and predictive impact of BRAFmt on the efficacy of targeted therapies with first-line chemotherapy.