tbuckley/cabot-search huggingface dataset:
Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia
Authors: Ugomma C. Eze, Aparna Bhaduri, Maximilian Haeussler, Tomasz J. Nowakowski, Arnold R. Kriegstein
Journal: Nature Neuroscience (2021)

Abstract The human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.
MA01.10 MDM2 Inhibitor APG-115 Suppresses Cell Proliferation and Tumor Growth in Preclinical Models Of NSCLC Harboring STK11 Mutations
Authors: H. Sun, Q.Q. Tang, D. Fang, Y. Kong, T. Rong, D. Yang, Y. Zhai, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
BPI21-006: Timing of NTRK Gene Fusion Testing and Treatment Modifications Following NTRK+ Status Among U.S. Oncologists Treating NTRK+ Patients
Authors: Landon Z. Marshall, Andrew J. Klink, Abhishek Kavati, Ruth Antoine, Sibyl Anderson, Bruce Feinberg
Journal: Journal of the National Comprehensive Cancer Network (2021)

"BPI21-006: Timing of NTRK Gene Fusion Testing and Treatment Modifications Following NTRK+ Status Among U.S. Oncologists Treating NTRK+ Patients" published on 17 Mar 2021 by National Comprehensive Cancer Network.
P07.01 Less Accuracy of CT and PET in the Evaluation of N1 Node may Result in Overlooking Skip Metastasis of Single Station cN2 Non-Small Cell Lung Cancer
Authors: S. Shiono, J. Abe, Y. Matsumura, M. Aoki, M. Sato, H. Oura, H. Kato, M. Minowa, H. Oizumi, M. Sagawa, A. Sakurada, Y. Okada
Journal: Journal of Thoracic Oncology (2021)
Loss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling
Authors: Senka Ljubojević-Holzer, Simon Kraler, Nataša Djalinac, Mahmoud Abdellatif, Julia Voglhuber, Julia Schipke, Marlene Schmidt, Katharina-Maria Kling, Greta Therese Franke, Viktoria Herbst, Andreas Zirlik, Dirk von Lewinski, Daniel Scherr, Peter P Rainer, Michael Kohlhaas, Alexander Nickel, Christian Mühlfeld, Christoph Maack, Simon Sedej
Journal: Cardiovascular Research (2021)

Autophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.RT-qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-specific Atg5-knockout mice (Atg5-/-). Before manifesting cardiac dysfunction, Atg5-/- mice showed compromised cardiac reserve in response to β-adrenergic stimulation. Consequently, effort intolerance and maximal oxygen consumption were reduced during treadmill-based exercise tolerance testing. Mechanistically, cellular imaging revealed that Atg5 deprivation did not alter spatial and functional organization of intracellular Ca2+ stores or affect Ca2+ cycling in response to slow pacing or upon acute isoprenaline administration. However, high-frequency stimulation exposed stunted amplitude of Ca2+ transients, augmented nucleoplasmic Ca2+ load, and increased CaMKII activity, especially in the nuclear region of hypertrophied Atg5-/- cardiomyocytes. These changes in Ca2+ cycling were recapitulated in hypertrophied human cardiomyocytes. Finally, ultrastructural analysis revealed accumulation of mitochondria with reduced volume and size distribution, meanwhile functional measurements showed impaired redox balance in Atg5-/- cardiomyocytes, implying energetic unsustainability due to overcompensation of single mitochondria, particularly under increased workload.Loss of cardiac Atg5-dependent autophagy reduces mitochondrial abundance and causes subtle alterations in subcellular Ca2+ cycling upon increased workload in mice. Autophagy-related impairment of Ca2+ handling is progressively worsened by β-adrenergic signalling in ventricular cardiomyocytes, thereby leading to energetic exhaustion and compromised cardiac reserve.
MA05.04 Why are Lung Cancer Detection Rates Higher in the Manchester Lung Health Checks than in the National Lung Screening Trial?
Authors: H. Robbins, H. Zahed, H. Balata, M. Lebrett, R. Booton, A. Sharman, G. Evans, E. Crosbie, M. Johansson, P. Crosbie
Journal: Journal of Thoracic Oncology (2021)
Turning cold tumors into hot tumors by improving T-cell infiltration
Authors: Yuan-Tong Liu, Zhi-Jun Sun
Journal: Theranostics (2021)

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on the infiltration of T cells capable of recognizing and killing tumor cells. ICIs are not effective in "cold tumors", which are characterized by the lack of T-cell infiltration. To realize the full potential of immunotherapy and solve this obstacle, it is essential to understand the drivers of T-cell infiltration into tumors. We present a critical review of our understanding of the mechanisms underlying "cold tumors", including impaired T-cell priming and deficient T-cell homing to tumor beds. "Hot tumors" with significant T-cell infiltration are associated with better ICI efficacy. In this review, we summarize multiple strategies that promote the transformation of "cold tumors" into "hot tumors" and discuss the mechanisms by which these strategies lead to increased T-cell infiltration. Finally, we discuss the application of nanomaterials to tumor immunotherapy and provide an outlook on the future of this emerging field. The combination of nanomedicines and immunotherapy enhances cross-presentation of tumor antigens and promotes T-cell priming and infiltration. A deeper understanding of these mechanisms opens new possibilities for the development of multiple T cell-based combination therapies to improve ICI effectiveness.
Family building desires among transgender and gender expansive adolescents: A longitudinal family-level analysis
Authors: Brett Stark, Shea A. Nagle, Adam Hunter, Brittany M. Charlton, Sabra L. Katz-Wise
Journal: International Journal of Transgender Health (2021)

Introduction Professional societies state that Transgender and gender expansive (TGE) adolescents and their families should be counseled about future family building options prior to initiating gender affirming therapy. While emerging data show that TGE adolescents have diverse desires regarding future family building, little is known regarding how these preferences are developed in a larger ecological context.Aim The current study used Ecological Systems Theory as a framework to describe the family building attitudes of TGE adolescents, their caregivers, and their siblings.Methods Participants were recruited from community-based venues in the New England region of the U.S. to participate in the TTFN Project, a longitudinal community-based mixed methods study. The sample for the current study included 84 family members from 30 families (30 TGE adolescents, 11 siblings, 44 caregivers). All participants completed a semi-structured qualitative interview about family building attitudes and desires for TGE and cisgender adolescents at two waves across 6-8 months. Interview transcripts were analyzed using a combination of immersion/crystallization, thematic analysis, and template organizing style approaches. The Transgender Youth Fertility Attitudes Questionnaire (TYFAQ) was employed to quantitatively describe the family building attitudes of TGE adolescents and their families.Results Eight themes corresponding to the levels of the ecological systems model – individual-level (perceived reproductive potential, reproductive identity), family-level (communication about family building, familial experiences and expectations), community-level (community support and role models; community expectations and norms), and societal/institutional-level (medicalization of family building, external sociopolitical factors) – were developed from the interviews. Results from the TYFAQ indicated that compared to cisgender adolescents, TGE adolescents were less likely to value having biological children and more likely to consider adoption in comparison to their cisgender siblings.Discussion Findings emphasize the importance of using Ecological Systems Theory to understand the family building attitudes and desires of TGE adolescents and their families.
The Occupational Depression Inventory—A Solution for Breaking the Impasse of Burnout Measurement
Authors: Renzo Bianchi, Irvin Sam Schonfeld
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
High-fat diet induces a predisposition to follicular hyperkeratosis and neutrophilic folliculitis in mice
Authors: Satoshi Nakamizo, Tetsuya Honda, Tomohito Sato, Md. Al Mamun, Zachary Chow, Kaibo Duan, Josephine Lum, Kahbing Jasmine Tan, Kaori Tomari, Reiko Sato, Akihiko Kitoh, Angeline S.L. Tay, John E.A. Common, Ng Lai Guan, Mitsutoshi Setou, Florent Ginhoux, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2021)
Evolution of the Randomized Clinical Trial in the Era of Precision Oncology
Authors: Joseph C. Del Paggio, John S. Berry, Wilma M. Hopman, Elizabeth A. Eisenhauer, Vinay Prasad, Bishal Gyawali, Christopher M. Booth
Journal: JAMA Oncology (2021)

<h3>Importance</h3> The randomized clinical trial (RCT) in oncology has evolved since its widespread adoption in the 1970s. In recent years, concerns have emerged regarding the use of putative surrogate end points, such as progression-free survival (PFS), and marginal effect sizes. <h3>Objective</h3> To describe contemporary trends in oncology RCTs and compare these findings with earlier eras of RCT design and output. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of systemic therapy RCTs in breast, colorectal, and non–small cell lung cancer published in 7 major journals between 2010 and 2020. This strategy replicates prior work and allows for comparison of trends with RCTs published between 1995 to 2004 and 2005 to 2009. <h3>Main Outcomes and Measures</h3> Data on RCT design, funding, results, and reporting were extracted from the published RCT report. Findings from the current period (2010-2020) were compared with data from RCTs published from 1995 to 2004 and 2005 to 2009. Descriptive and bivariate statistics were used to analyze temporal trends. <h3>Results</h3> The cohort included 298 RCTs (132 [44%] breast, 111 [37%] non–small cell lung cancer, 55 [19%] colorectal cancer). Experimental treatment included molecular inhibitor (171 of 298 [57%]), cytotoxic (83 of 298 [28%]), hormone (15 of 298 [5%]), and immune (24 of 298 [8%]) therapies. Sixty-nine percent (206 of 298) of RCTs were of palliative intent. The most common primary end point is now PFS; this has increased substantially over time (from 0% [0 of 167] to 18% [25 of 137] to 42% [125 of 298];<i>P</i> &lt; .001). Of 298 RCTs, 265 (89%) are now funded by industry (previously 95 of 167 [57%] and 107 of 137 [78%];<i>P</i> &lt; .001). Fifty-eight percent (173 of 298) of trials met their primary end point. Among positive trials, median improvement in overall survival and PFS was 3.4 and 2.9 months, respectively. More than one-third (117 of 298 [39%]) of reports used a professional medical writer; this increased substantially during the study period (from 3 of 27 [11%] in 2010 to 12 of 18 [67%] in 2020;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This cohort study suggests that contemporary oncology RCTs now largely measure putative surrogate end points and are almost exclusively funded by the pharmaceutical industry. The increasing role of medical writers warrants attention. To demonstrate that new cancer treatments are high value, the oncology community needs to consider the extent to which study end points and target effect size provide meaningful benefit to patients.
P47.09 Quantification and Classification of Tumor Infiltrating Leukocytes (TILs) and its Impact on Prognosis in Small Cell Lung Cancer (SCLC)
Authors: L. Yang, Y. Guo, L. Liu, J. Zhang, J. Wei, X. Wang, F. Teng, P. Xing, J. Li
Journal: Journal of Thoracic Oncology (2021)
Intratumor heterogeneity of breast cancer detected by epialleles shows association with hypoxic microenvironment
Authors: Yihan Wang, Yan Zhang, Yan Huang, Chuangeng Chen, Xingda Zhang, Ying Xing, Yue Gu, Mengyan Zhang, Li Cai, Shouping Xu, Baoqing Sun
Journal: Theranostics (2021)

Rationale: In breast cancer, high intratumor DNA methylation heterogeneity can lead to drug-resistant, metastasis and poor prognosis of tumors, which increases the complexity of cancer diagnosis and treatment. However, most studies are limited to average DNA methylation level of individual CpGs and ignore heterogeneous DNA methylation patterns of cell subpopulations within the tumor. Thus, quantifying the variability in DNA methylation pattern in sequencing reads is valuable for understanding intratumor heterogeneity. Methods: We performed Reduced Representation Bisulfite Sequencing and RNA sequencing for tumor core and tumor periphery regions within one breast tumor. By developing a method named "epialleJS" based on Jensen-Shannon divergence, we detected the differential epialleles between tumor core and tumor periphery (CPDEs). We then explored the correlation between intratumor methylation heterogeneity and hypoxic microenvironment in TCGA breast cancer cohort. Results: More than 70% of CPDEs had higher epipolymorphism in tumor core than tumor periphery, and these CPDEs had lower methylation in tumor core. The CPDEs with lower methylation in tumor core may associate with hypoxic tumor microenvironment. Moreover, we identified a signature of five hypoxia-related DNA methylation markers which can predict the prognosis of breast cancer patients, including a CpG site cg15190451 in gene SLC16A5. Furthermore, immunohistochemical analysis confirmed that the expression of SLC16A5 was associated with clinicopathological characteristics and survival of breast cancer patients. Conclusions: The analysis of intratumor DNA methylation heterogeneity based on epialleles reveals that disordered methylation patterns in tumor core are associated with hypoxic microenvironment, which provides a framework for understanding biological heterogeneous behavior and guidance for developing effective treatment schemes for breast cancer patients.
Safety and efficacy of the BRAF inhibitor dabrafenib in relapsed or refractory hairy cell leukemia: a pilot phase-2 clinical trial
Authors: Enrico Tiacci, Luca De Carolis, Edoardo Simonetti, Mara Merluzzi, Antonio Bennati, Vincenzo Maria Perriello, Alessandra Pucciarini, Alessia Santi, Alessandra Venanzi, Valentina Pettirossi, Gianluca Schiavoni, Luisa Tasselli, Stefano Ascani, Stefano Volpetti, Brunangelo Falini
Journal: Leukemia (2021)
Ultrasonography Tight Control and Monitoring in Crohn’s Disease During Different Biological Therapies: A Multicenter Study
Authors: Emma Calabrese, Antonio Rispo, Francesca Zorzi, Elena De Cristofaro, Anna Testa, Giuseppe Costantino, Anna Viola, Cristina Bezzio, Chiara Ricci, Simonetta Prencipe, Chiara Racchini, Gianpiero Stefanelli, Mariangela Allocca, Salvatore Scotto di Santolo, Mauro Valeriano D’Auria, Paola Balestrieri, Angelo Ricchiuti, Maria Cappello, Flaminia Cavallaro, Alessia Dalila Guarino, Giovanni Maconi, Alessandra Spagnoli, Giovanni Monteleone, Fabiana Castiglione
Journal: Clinical Gastroenterology and Hepatology (2021)

Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies.Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies.One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)].Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.
The chemistry and toxicology of vaping
Authors: Emily Bonner, Yvonne Chang, Emerson Christie, Victoria Colvin, Brittany Cunningham, Daniel Elson, Christine Ghetu, Juliana Huizenga, Sara J. Hutton, Siva K. Kolluri, Stephanie Maggio, Ian Moran, Bethany Parker, Yvonne Rericha, Brianna N. Rivera, Samantha Samon, Trever Schwichtenberg, Prarthana Shankar, Michael T. Simonich, Lindsay B. Wilson, Robyn L. Tanguay
Journal: Pharmacology & Therapeutics (2021)
The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING–IFN-β pathway
Authors: Mariko Takahashi, Chan-Wang J. Lio, Anaamika Campeau, Martin Steger, Ferhat Ay, Matthias Mann, David J. Gonzalez, Mohit Jain, Sonia Sharma
Journal: Nature Immunology (2021)
E2F1 and E2F2-Mediated Repression of CPT2 Establishes a Lipid-Rich Tumor-Promoting Environment
Authors: Francisco González-Romero, Daniela Mestre, Igor Aurrekoetxea, Colm J. O'Rourke, Jesper B. Andersen, Ashwin Woodhoo, Miguel Tamayo-Caro, Marta Varela-Rey, Marta Palomo-Irigoyen, Beatriz Gómez-Santos, Diego Sáenz de Urturi, Maitane Núñez-García, Juan L. García-Rodríguez, Larraitz Fernández-Ares, Xabier Buqué, Ainhoa Iglesias-Ara, Irantzu Bernales, Virginia Gutierrez De Juan, Teresa C. Delgado, Naroa Goikoetxea-Usandizaga, Richard Lee, Sanjay Bhanot, Igotz Delgado, Maria J. Perugorria, Gaizka Errazti, Lorena Mosteiro, Sonia Gaztambide, Idoia Martinez de la Piscina, Paula Iruzubieta, Javier Crespo, Jesus M. Banales, Maria L. Martínez-Chantar, Luis Castaño, Ana M. Zubiaga, Patricia Aspichueta
Journal: Cancer Research (2021)

Lipid metabolism rearrangements in nonalcoholic fatty liver disease (NAFLD) contribute to disease progression. NAFLD has emerged as a major risk for hepatocellular carcinoma (HCC), where metabolic reprogramming is a hallmark. Identification of metabolic drivers might reveal therapeutic targets to improve HCC treatment. Here, we investigated the contribution of transcription factors E2F1 and E2F2 to NAFLD-related HCC and their involvement in metabolic rewiring during disease progression. In mice receiving a high-fat diet (HFD) and diethylnitrosamine (DEN) administration, E2f1 and E2f2 expressions were increased in NAFLD-related HCC. In human NAFLD, E2F1 and E2F2 levels were also increased and positively correlated. E2f1-/- and E2f2-/- mice were resistant to DEN-HFD-induced hepatocarcinogenesis and associated lipid accumulation. Administration of DEN-HFD in E2f1-/- and E2f2-/- mice enhanced fatty acid oxidation (FAO) and increased expression of Cpt2, an enzyme essential for FAO, whose downregulation is linked to NAFLD-related hepatocarcinogenesis. These results were recapitulated following E2f2 knockdown in liver, and overexpression of E2f2 elicited opposing effects. E2F2 binding to the Cpt2 promoter was enhanced in DEN-HFD-administered mouse livers compared with controls, implying a direct role for E2F2 in transcriptional repression. In human HCC, E2F1 and E2F2 expressions inversely correlated with CPT2 expression. Collectively, these results indicate that activation of the E2F1-E2F2-CPT2 axis provides a lipid-rich environment required for hepatocarcinogenesis. SIGNIFICANCE: These findings identify E2F1 and E2F2 transcription factors as metabolic drivers of hepatocellular carcinoma, where deletion of just one is sufficient to prevent disease. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/11/2874/F1.large.jpg.