tbuckley/cabot-search huggingface dataset:
PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages
Authors: Katarzyna Okreglicka, Irina Iten, Lea Pohlmeier, Lucas Onder, Qian Feng, Michael Kurrer, Burkhard Ludewig, Peter Nielsen, Christoph Schneider, Manfred Kopf
Journal: The Journal of Experimental Medicine (2021)

Tissue-resident macrophages play a crucial role in maintaining homeostasis. Macrophage progenitors migrate to tissues perinatally, where environmental cues shape their identity and unique functions. Here, we show that the absence of PPARγ affects neonatal development and VCAM-1 expression of splenic iron-recycling red pulp macrophages (RPMs) and bone marrow erythroblastic island macrophages (EIMs). Transcriptome analysis of the few remaining Pparg-deficient RPM-like and EIM-like cells suggests that PPARγ is required for RPM and EIM identity, cell cycling, migration, and localization, but not function in mature RPMs. Notably, Spi-C, another transcription factor implicated in RPM development, was not essential for neonatal expansion of RPMs, even though the transcriptome of Spic-deficient RPMs was strongly affected and indicated a loss of identity. Similarities shared by Pparg- and Spic-deficient RPM-like cells allowed us to identify pathways that rely on both factors. PPARγ and Spi-C collaborate in inducing transcriptional changes, including VCAM-1 and integrin αD expression, which could be required for progenitor retention in the tissue, allowing access to niche-related signals that finalize differentiation.
P37.04 EGFR Mutations in US Hispanics with Lung Adenocarcinoma are Common and Portend a Worse Prognosis
Authors: J. Villena-Vargas, N. Mynard, F. Voza, A. Nasar, O. Chow, B. Lee, S. Harrison, B. Stiles, J. Port, N. Altorki
Journal: Journal of Thoracic Oncology (2021)
Structure-switching aptamer sensors for the specific detection of piperaquine and mefloquine
Authors: Erin S. Coonahan, Kyung-Ae Yang, Stevan Pecic, Maarten De Vos, Thomas E. Wellems, Michael P. Fay, John F. Andersen, Joel Tarning, Carole A. Long
Journal: Science Translational Medicine (2021)

Aptamer-based fluorescent sensors specifically detect the antimalarial drugs piperaquine and mefloquine from patient samples and crushed tablets.
Narrowband ultraviolet B therapy for refractory immune-related lichenoid dermatitis on PD-1 therapy: a case report
Authors: Khashayar Esfahani, Meagan-Helen Henderson Berg, Hanieh Zargham, Robin Billick, Kevin Pehr, Margaret Redpath, Osama Roshdy, Wilson H Miller
Journal: Journal for ImmunoTherapy of Cancer (2021)

Treatment with programmed cell death 1 inhibitors is associated with a wide range of cutaneous immune-related adverse events, with lichenoid eruptions representing one of the major cutaneous toxicities. We describe the case of an 81-year-old man with metastatic melanoma treated with pembrolizumab who subsequently developed a delayed-onset generalized lichenoid dermatitis. After failing multiple lines of systemic immunosuppression, narrowband ultraviolet B (NBUVB) phototherapy three times per week for 17 sessions resulted in a significant clinical response in his cutaneous eruption and was well tolerated. NBUVB is a safe, lower-cost modality that induces local, skin-specific immunosuppression without the toxicities of traditional systemic immunosuppressive agents. To date, this is the first report of use of NBUVB in immune-related lichenoid dermatitis resistant to multiple standard therapies.
Abstract 14811: Disparities in Prevalence of Hypertension and Hypertensive Urgency by Race and Hispanic Origin in the Wisewoman Population, 2014 to 2018
Authors: Isaac Nwaise, Isam Vaid, Ethan Blum
Journal: Circulation (2020)

Background: Hypertension is a preventable risk factor for heart disease and stroke. Patients with hypertensive urgency should seek immediate medical assistance to prevent organ damage, injury, disability, or death. Objective: This study examined disparities in the prevalence of hypertension (blood pressure (BP) ≥130/80 mm Hg) and hypertensive urgency (BP ≥180/110 mm Hg) in the WISEWOMAN population. WISEWOMAN represents the Well-Integrated Screening and Evaluation for Women Across the Nation programs that serve a diverse uninsured and underinsured population in the United States. Methods: WISEWOMAN data (January 2014- December 2018) were obtained from 19 state health departments and two Alaska tribal organizations. Women aged 40-64 years with hypertension or hypertensive urgency were identified based on BP readings at a screening visit. The data were stratified, and prevalence was calculated by race and Hispanic origin. Results: In the WISEWOMAN population there were 25,098 women with hypertension. Overall prevalence of hypertension was 38.5 percent and the prevalence of hypertensive urgency was 4.6 percent. Non-Hispanic black (NHB) women had the highest prevalence of hypertension (67.1 percent) followed by non-Hispanic White (NHW) women (40.2 percent) and Hispanic women (26.5 percent). NHB women (6.1 percent) had the highest prevalence of hypertensive urgency followed by NHW women (4.5 percent) and Hispanic women (3.4 percent). Conclusion: Differences in prevalence of women with hypertension and hypertension urgency were statistically significant among race and Hispanic origin. Furthermore, NHB women had disproportionally higher prevalence of hypertension and hypertensive urgency than NHW women and Hispanic women.Keywords: Hypertension, Hypertensive urgency, WISEWOMAN Table 1: Mean Age, Number and Percentages of Women Screened, Women with Hypertension and those with Hypertensive Urgency among WISEWOMAN Participants, 40-64 years old, January 2014- June 2018. By Race and Hispanic origin
CLO21-025: Benefit of Deep Inspiratory Breath Hold for Right Breast Cancer When Regional Lymph Nodes Are Irradiated
Authors: Gabrielle W. Peters, Sarah J. Gao, Christin Knowlton, Andrew Zhang, Suzanne B. Evans, Susan Higgins, Lynn D. Wilson, Nicholas Saltmarsh, Martha Picone, Meena S. Moran
Journal: Journal of the National Comprehensive Cancer Network (2021)
Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation
Authors: Roger S. McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff, Gerard Sanacora, James W. Murrough, Michael Berk, Elisa Brietzke, Seetal Dodd, Philip Gorwood, Roger Ho, Dan V. Iosifescu, Carlos Lopez Jaramillo, Siegfried Kasper, Kevin Kratiuk, Jung Goo Lee, Yena Lee, Leanna M.W. Lui, Rodrigo B. Mansur, George I. Papakostas, Mehala Subramaniapillai, Michael Thase, Eduard Vieta, Allan H. Young, Carlos A. Zarate, Stephen Stahl
Journal: American Journal of Psychiatry (2021)

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.
P86.11 A Real-World Feasibility Study of Patients with Solid Tumors Harboring NRG1 Gene Fusions: NSCLC Subset Analysis
Authors: A. Gajra, A. Klink, J. Kaufman, J. Laney, A. Cseh, K. Fernamberg, B. Moehring, S. Jonna
Journal: Journal of Thoracic Oncology (2021)
<i>P</i><sub>aO<sub>2</sub></sub>/<i>F</i><sub>IO<sub>2</sub></sub>ratio: the mismeasure of oxygenation in COVID-19
Authors: Martin J. Tobin, Amal Jubran, Franco Laghi
Journal: European Respiratory Journal (2021)

We read with interest A. Tulaimat's letter concerning our recent editorial in the European Respiratory Journal [1]. A. Tulaimat makes several insightful comments on problems with criteria used for entering patients into randomised controlled trials of noninvasive ventilation. Among these, he notes that arterial-to-inspired oxygen ( P aO2/ F IO2) ratio varied between 170 and 400 among enrollees [2]. P aO2 is the most precise measurement of patient oxygenation in COVID-19, but its accuracy is corrupted when communicated as P aO2/ F IO2 ratio <https://bit.ly/3tNipTJ>
P21.16 Do Patients who Underwent Lung Resection for Non-Small Cell Lung Cancer and Skip-N2 Metastases Show Better Survival?
Authors: A. Libreros, D. Sánchez-Lorente, M. Boada, A. Guirao, R. Gúzman, C. Guerrero, L. Grando, P. Paglialunga, M. Azarola, A. Gómez-Caro, L. Molins
Journal: Journal of Thoracic Oncology (2021)
HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study
Authors: Ivonne Haffner, Katrin Schierle, Elba Raimúndez, Birgitta Geier, Dieter Maier, Jan Hasenauer, Birgit Luber, Axel Walch, Katharina Kolbe, Jorge Riera Knorrenschild, Albrecht Kretzschmar, Beate Rau, Ludwig Fischer von Weikersthal, Miriam Ahlborn, Gabriele Siegler, Stefan Fuxius, Thomas Decker, Christian Wittekind, Florian Lordick
Journal: Journal of Clinical Oncology (2021)

Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC.Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR.Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2- mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab.Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.
Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors
Authors: Hyo Jung Park, Kyung Won Kim, Sang Eun Won, Shinkyo Yoon, Young Kwang Chae, Sree Harsha Tirumani, Nikhil H. Ramaiya
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Hyperprogressive disease (HPD) is a recognized pattern of rapid tumor progression during immune checkpoint inhibitor (ICI) treatment. Definitions of HPD have not been standardized, posing the risk of capturing different tumoral behaviors. <h3>Objectives</h3> To provide a systematic summary of definitions and the incidence of HPD in patients undergoing ICI treatment and discuss the challenges of current assessment of HPD. <h3>Data Sources</h3> Articles that evaluated HPD published before March 3, 2020, were identified from MEDLINE and EMBASE. <h3>Study Selection</h3> Clinical trials and observational studies providing the incidence and definition of HPD from patients with cancer treated with ICIs. <h3>Data Extraction and Synthesis</h3> Factors included in the analysis comprised authors, year of publication, cancer type, ICI type, number of previous treatment lines, definition of HPD, time frame used to assess HPD, number of patients with HPD, onset of HPD, and prognosis of patients with HPD. Quantitative and qualitative syntheses for the incidence of HPD were performed. <h3>Main Outcomes and Measures</h3> Definitions of HPD were categorized and the range of incidence of HPD was evaluated. Subgroup analysis on the incidence of HPD according to the category was performed and the challenges associated with current HPD assessment were evaluated. <h3>Results</h3> Twenty-four studies with 3109 patients were analyzed. The incidence of HPD varied from 5.9% to 43.1%. The definitions were divided into 4 categories based on the calculation of tumor growth acceleration: tumor growth rate ratio (pooled incidence of HPD, 9.4%; 95% CI, 6.9%-12.0%), tumor growth kinetics ratio (pooled incidence, 15.8%; 95% CI, 8.0%-23.7%), early tumor burden increase (pooled incidence, 20.6%; 95% CI, 9.3%-31.8%), and combinations of the above (pooled incidence, 12.4%; 95% CI, 7.3%-17.5%). Hyperprogressive disease could be overestimated or underestimated if the assessment was limited to tumor growth rate or tumor growth kinetics ratio, target lesions, or response evaluation criteria in solid tumors (RECIST)–defined progressors, or if the assessment time frame conformed to RECIST. Study results on clinical outcome were heterogeneous on discriminating patients with HPD from those with natural progressive disease. <h3>Conclusions and Relevance</h3> Definitions of HPD appear to be diverse, with the incidence of HPD varying from 5.9% to 43.1% across studies examined in this meta-analysis. Varying incidence and definitions of HPD indicate the need for establishing its uniform and clinically relevant criteria based on currently available evidence.
MicroRNA-146a switches microglial phenotypes to resist the pathological processes and cognitive degradation of Alzheimer's disease
Authors: Chunmei Liang, Ting Zou, Miaoping Zhang, Weihao Fan, Tianzhen Zhang, Yuling Jiang, Yujie Cai, Feng Chen, Xiongjin Chen, Yuanhong Sun, Bin Zhao, Yan Wang, Lili Cui
Journal: Theranostics (2021)

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and currently has no effective treatment. Mainstream research on the mechanisms and therapeutic targets of AD is focused on the two most important hallmarks, Aβ and Tau, but the results from clinical studies are not encouraging. Abnormal microglial polarization is a clear typical pathological feature in the progression of AD. Microglia can be neuroprotective by degrading and removing Aβ and Tau. However, under AD conditions, microglia transform into a pro-inflammatory phenotype that decreases the phagocytic activity of microglia, damages neurons and promotes the pathology of AD. We previously reported that a miR-146a polymorphism is associated with sporadic AD risk, and the nasal administration of miR-146a mimics reduced cognitive impairment and the main pathological features of AD. However, it is not clear by what mechanism miR-146a resists the pathological process of AD. In this study, we discovered that microglia-specific miR-146a overexpression reduced cognitive deficits in learning and memory, attenuated neuroinflammation, reduced Aβ levels, ameliorated plaque-associated neuritic pathology, and prevented neuronal loss in APP/PS1 transgenic mice. In addition, we found that miR-146a switched the microglial phenotype, reduced pro-inflammatory cytokines and enhanced phagocytic function to protect neurons in vitro and in vivo. Moreover, transcriptional analysis confirmed that miR-146a opposed the pathological process of AD mainly through neuroinflammation-related pathways. In summary, our results provide sufficient evidence for the mechanism by which miR-146a opposes AD and strengthen the conclusion that miR-146a is a promising target for AD and other microglia-related diseases.
P35.29 The Genomic Landscape of Lung Cancer Patients Highlights Age-Dependent Mutation Frequencies and Clinical Actionability in Young Patients
Authors: L. Cai, Y. Chen, X. Tong, X. Wu, H. Bao, Y. Shao, Z. Luo, X. Wang, Y. Cao
Journal: Journal of Thoracic Oncology (2021)
P85.04 Capmatinib in Patients with METex14-Mutated Non-Small Cell Lung Cancer: GEOMETRY Mono-1 Asian Subgroup Analysis
Authors: J. Han, J. Wolf, E. Garon, H. Groen, R. Heist, M. Ang, K. Ohashi, R. Toyozawa, T.M. Kim, T. Hida, M. Takeda, S. Sugawara, W. Chang, C. Yu, S. Moizumi, A. Robeva, S. Le Mouhaer, M. Waldron-Lynch, A. Chassot Agostinho, A. Myers, M. Nishio
Journal: Journal of Thoracic Oncology (2021)
P76.52 Liquid Biopsy and PET Parameters as Predictive Factors of Osimertinib Treatment in Advanced EGFR-Mutated NSCLC
Authors: A. Leonetti, S. Bola, R. Minari, M. Scarlattei, S. Buti, P. Bordi, G. Baldari, L. Gnetti, A. Sammartano, S. Migliari, A. Cosenza, L. Ferri, F. Bonatti, L. Mastrodomenico, L. Ruffini, M. Tiseo
Journal: Journal of Thoracic Oncology (2021)
Cannabidiol attenuates pulmonary arterial hypertension by improving vascular smooth muscle cells mitochondrial function
Authors: Xiaohui Lu, Jingyuan Zhang, Huijiao Liu, Wenqiang Ma, Leo Yu, Xin Tan, Shubin Wang, Fazheng Ren, Xiru Li, Xiangdong Li
Journal: Theranostics (2021)

Rationale: Pulmonary arterial hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, and the clinical therapeutic option for PAH is very limited. Recent studies showed that cannabidiol (CBD), a non-psychoactive constituent of cannabinoids, possessed antioxidant effect towards several cardiovascular diseases, whereas the mechanistic effect of CBD in PAH is unknown. Methods: In this study, the effects of CBD in PAH were determined by analyzing its preventive and therapeutic actions in PAH rodent models in vivo and PASMCs' proliferation test in vitro. Additionally, CBD's roles in mitochondrial function and oxidant stress were also assessed in PASMCs. Results: We found that CBD reversed the pathological changes observed in both Sugen-hypoxia and monocrotaline-induced PAH rodent models in a cannabinoid receptors-independent manner. Our results also demonstrated that CBD significantly inhibited the PASMCs' proliferation in PAH mice with less inflammation and reactive oxygen species levels. Moreover, CBD alleviated rodent PAH by recovering mitochondrial energy metabolism, normalizing the hypoxia-induced oxidant stress, reducing the lactate overaccumulation and abnormal glycolysis. Conclusions: Taken together, these findings confirm an important role for CBD in PAH pathobiology.
Abstract 17346: Loss of Neuropilin 2 Impairs Lymphangiogenesis and Exacerbates Lymphedema
Authors: Yao Gao, Yang LEE, Asma Almazyad, Amy Birsner, David Li, Scott Wong, Aiyun Wen, Robert D'Amato, Rosalyn adam, Sathish Srinivasan, Hong Chen, Diane Bielenberg
Journal: Circulation (2020)

Dysfunctional lymphatic networks can lead to lymphatic diseases such as lymphedema as well as aggravate cardiovascular diseases such as atherosclerosis and hypertension. Some primary lymphedema patients have mutations in the Neuropilin 2 ( NRP2 ) gene, which encodes a transmembrane receptor that acts with VEGFR3 for the ligands VEGF-C and VEGF-D. Nrp2 has been shown to be a key regulator of lymphatic vessel development in the neonate as global Nrp2 -deficient mice suffer from reduced lymphatic density. However, Nrp2 protein expression is dramatically downregulated after birth and its role in adult lymphangiogenesis or its relevance in lymphedema is less clear. Our hypothesis is that Nrp2 expression is necessary for optimal lymphangiogenesis and proper lymphatic drainage function in the adult, and that loss of Nrp2 , either genetically or transcriptionally via down-regulation by specific transcription factors, may worsen lymphedema. In acute and chronic mouse inflammation models, we found that loss of Nrp2 specifically in the lymphatic endothelium ( prox1-cre ERT2 ;Nrp2 f/f ) resulted in prolonged swelling and reduced lymphatic drainage compared to control mice. Using the VEGFC-induced corneal lymphangiogenesis model and the tail wound-induced secondary lymphedema model, LEC-Nrp2-iKO mice showed diminished lymphangiogenesis and reduced lymphatic drainage compared to littermate controls. Furthermore, primary mouse dermal LEC isolated from Nrp2-iKO mice reveal suppressed VEGFR3 activation, signaling, and proliferation following VEGF-C stimulation, compared to LEC isolated from control mice. Collectively, our results identify Nrp2 as a critical mediator of lymphangiogenesis and homeostatic lymphatic drainage function in adult tissues.
Acute Myeloid Leukemia Classification System That Associates Normal Myeloid-Cell Subset Gene Signatures with Prognosis
Authors: Anna Amanda Schönherz, Julie Støve Bødker, Alexander Schmitz, Rasmus Froberg Brøndum, Lasse Hjort Jakobsen, Marianne Tang Severinsen, Tarec Christoffer El-Galaly, Karen Dybkær, Martin Bøgsted, Hans Erik Johnsen
Journal: Blood (2017)
HSR21-046: A Novel Oncology Telepharmacy Service With Improved Medication Access for a More Seamless Patient Experience: A Randomized Controlled Trial
Authors: Gail Chia Yang Chang, Meiyi Loke, Felicia Chong, Seyed Ehsan Saffari, Sungwon Yoon, Yixuan Chua, Raymond Ng, Sheow Lei Lim, Ray Tng, Sharon Cohan Sung, Lamoureux Ecosse
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-046: A Novel Oncology Telepharmacy Service With Improved Medication Access for a More Seamless Patient Experience: A Randomized Controlled Trial" published on 17 Mar 2021 by National Comprehensive Cancer Network.