tbuckley/cabot-search huggingface dataset:
In vivo endocannabinoid dynamics at the timescale of physiological and pathological neural activity
Authors: Jordan S. Farrell, Roberto Colangeli, Ao Dong, Antis G. George, Kwaku Addo-Osafo, Philip J. Kingsley, Maria Morena, Marshal D. Wolff, Barna Dudok, Kaikai He, Toni A. Patrick, Keith A. Sharkey, Sachin Patel, Lawrence J. Marnett, Matthew N. Hill, Yulong Li, G. Campbell Teskey, Ivan Soltesz
Journal: Neuron (2021)
26750 Cumulative clinical benefits of biologic treatments for psoriasis over 1 year
Authors: Andrew Blauvelt, Melinda Gooderham, Christopher E.M. Griffiths, Baojin Zhu, Russel Burge, Gaia Gallo, Jiaying Guo, Alyssa Garrelts, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2021)
Marked progress in AL amyloidosis survival: a 40-year longitudinal natural history study
Authors: Andrew Staron, Luke Zheng, Gheorghe Doros, Lawreen H. Connors, Lisa M. Mendelson, Tracy Joshi, Vaishali Sanchorawala
Journal: Blood Cancer Journal (2021)

Abstract The recent decades have ushered in considerable advancements in the diagnosis and treatment of systemic light chain (AL) amyloidosis. As disease outcomes improve, AL amyloidosis-unrelated factors may impact mortality. In this study, we evaluated survival trends and primary causes of death among 2337 individuals with AL amyloidosis referred to the Boston University Amyloidosis Center. Outcomes were analyzed according to date of diagnosis: 1980-1989 (era 1), 1990-1999 (era 2), 2000-2009 (era 3), and 2010-2019 (era 4). Overall survival increased steadily with median values of 1.4, 2.6, 3.3, and 4.6 years for eras 1–4, respectively ( P &lt; 0.001). Six-month mortality decreased over time from 23% to 13%. Wide gaps in survival persisted amid patient subgroups; those with age at diagnosis ≥70 years had marginal improvements over time. Most deaths were attributable to disease-related factors, with cardiac failure (32%) and sudden unexpected death (23%) being the leading causes. AL amyloidosis-unrelated mortality increased across eras (from 3% to 16% of deaths) and with longer-term survival (29% of deaths occurring &gt;10 years after diagnosis). Under changing standards of care, survival improved and early mortality declined over the last 40 years. These findings support a more optimistic outlook for patients with AL amyloidosis.
The Future of Parallel Tumor and Germline Genetic Testing: Is There a Role for All Patients With Cancer?
Authors: Ying L. Liu, Zsofia K. Stadler
Journal: Journal of the National Comprehensive Cancer Network (2021)

Under the traditional paradigm of genetic testing in cancer, the role of germline testing was to assess for the inherited risk of cancer, whereas the role of tumor testing was to determine therapeutic selection. Parallel tumor-normal genetic testing uses simultaneous genetic testing of the tumor and normal tissue to identify mutations and allows their classification as either germline or somatic. The increasing adoption of parallel testing has revealed a greater number of germline findings in patients who otherwise would not have met clinical criteria for testing. This result has widespread implications for the screening and further testing of at-risk relatives and for gene discovery. It has also revealed the importance of germline testing in therapeutic actionability. Herein, we describe the pros and cons of tumor-only versus parallel tumor-normal testing and summarize the data on the prevalence of incidental actionable germline findings. Because germline testing in patients with cancer continues to expand, it is imperative that systems be in place for the proper interpretation, dissemination, and counseling for patients and at-risk relatives. We also review new therapeutic approvals with germline indications and highlight the increasing importance of germline testing in selecting therapies. Because recommendations for universal genetic testing are increasing in multiple cancer types and the number of approved therapies with germline indications is also increasing, a gradual transition toward parallel tumor-normal genetic testing in all patients with cancer is foreseeable.
O-2 Overall survival and long-term safety data from the NETTER-1 trial: 177-Lu-Dotatate vs. high-dose octreotide in patients with progressive midgut NETs
Authors: J. Strosberg, M. Caplin, P. Kunz, P. Ruszniewski, L. Bodei, A. Hendifar, E. Mittra, E. Wolin, J. Yao, M. Pavel, E. Grande Pulido, E. Van Cutsem, E. Seregni, H. Duarte, G. Gericke, A. Bartalotta, A. Demange, S. Mutevelic, E. Krenning
Journal: Annals of Oncology (2021)
A Highly Ordered, Nanostructured Fluorinated CaP‐Coated Melt Electrowritten Scaffold for Periodontal Tissue Regeneration
Authors: Arwa Daghrery, Jessica A. Ferreira, Isaac J. de Souza Araújo, Brian H. Clarkson, George J. Eckert, Sarit B. Bhaduri, Jos Malda, Marco C. Bottino
Journal: Advanced Healthcare Materials (2021)

Periodontitis is a chronic inflammatory, bacteria-triggered disorder affecting nearly half of American adults. Although some level of tissue regeneration is realized, its low success in complex cases demands superior strategies to amplify regenerative capacity. Herein, highly ordered scaffolds are engineered via Melt ElectroWriting (MEW), and the effects of strand spacing, as well as the presence of a nanostructured fluorinated calcium phosphate (F/CaP) coating on the adhesion/proliferation, and osteogenic differentiation of human-derived periodontal ligament stem cells, are investigated. Upon initial cell-scaffold interaction screening aimed at defining the most suitable design, MEW poly(ε-caprolactone) scaffolds with 500 µm strand spacing are chosen. Following an alkali treatment, scaffolds are immersed in a pre-established solution to allow for coating formation. The presence of a nanostructured F/CaP coating leads to a marked upregulation of osteogenic genes and attenuated bacterial growth. In vivo findings confirm that the F/CaP-coated scaffolds are biocompatible and lead to periodontal regeneration when implanted in a rat mandibular periodontal fenestration defect model. In aggregate, it is considered that this work can contribute to the development of personalized scaffolds capable of enabling tissue-specific differentiation of progenitor cells, and thus guide simultaneous and coordinated regeneration of soft and hard periodontal tissues, while providing antimicrobial protection.
Deep learning methods for automatic evaluation of delayed enhancement-MRI. The results of the EMIDEC challenge
Authors: Alain Lalande, Zhihao Chen, Thibaut Pommier, Thomas Decourselle, Abdul Qayyum, Michel Salomon, Dominique Ginhac, Youssef Skandarani, Arnaud Boucher, Khawla Brahim, Marleen de Bruijne, Robin Camarasa, Teresa M. Correia, Xue Feng, Kibrom B. Girum, Anja Hennemuth, Markus Huellebrand, Raabid Hussain, Matthias Ivantsits, Jun Ma, Craig Meyer, Rishabh Sharma, Jixi Shi, Nikolaos V. Tsekos, Marta Varela, Xiyue Wang, Sen Yang, Hannu Zhang, Yichi Zhang, Yuncheng Zhou, Xiahai Zhuang, Raphael Couturier, Fabrice Meriaudeau
Journal: Medical Image Analysis (2022)
Abstract 16192: Protective Effects of the Mechanistic Target of Rapamycin Against Excess Iron and Ferroptosis in Cardiomyocytes
Authors: Yuichi Baba, Briana K Shimada, Kate M Horiuchi, Tomohiro Suhara, Motoi Kobayashi, Jason K Higa, Hiroaki Kitaoka, Takashi Matsui
Journal: Circulation (2017)

Clinical studies using cardiac magnetic resonance showed that myocardial iron around the infarct zone is a risk factor for adverse left ventricular remodeling in patients with reperfusion therapy a...
Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset
Authors: Danielle N. Huggins, Rebecca S. LaRue, Ying Wang, Todd P. Knutson, Yingzheng Xu, Jesse W. Williams, Kathryn L. Schwertfeger
Journal: Cancer Research (2021)

Abstract While macrophages are among the most abundant immune cell type found within primary and metastatic mammary tumors, how their complexity and heterogeneity change with metastatic progression remains unknown. Here, macrophages were isolated from the lungs of mice bearing orthotopic mammary tumors for single-cell RNA sequencing (scRNA-seq). Seven distinct macrophage clusters were identified, including populations exhibiting enhanced differential expression of genes related to antigen presentation (H2-Aa, Cd74), cell cycle (Stmn1, Cdk1), and interferon signaling (Isg15, Ifitm3). Interestingly, one cluster demonstrated a profile concordant with lipid-associated macrophages (Lgals3, Trem2). Compared with nontumor-bearing controls, the number of these cells per gram of tissue was significantly increased in lungs from tumor-bearing mice, with the vast majority costaining positively with the alveolar macrophage marker Siglec-F. Enrichment of genes implicated in pathways related to lipid metabolism as well extracellular matrix remodeling and immunosuppression was observed. In addition, these cells displayed reduced capacity for phagocytosis. Collectively, these findings highlight the diversity of macrophages present within metastatic lesions and characterize a lipid-associated macrophage subset previously unidentified in lung metastases. Significance: scRNA-seq of macrophages isolated from lung metastases reveals extensive macrophage heterogeneity and identifies a novel subpopulation enriched for genes involved in lipid metabolism, extracellular matrix remodeling, and immunosuppression.
Unrecognized Clonal Hematopoiesis of Indeterminate Potential in Solid Tumors: Implications for Interpretation of Molecular Testing
Authors: Eric A Severson, Caitlin F Connelly, Shakti Ramkissoon, Garrett M Frampton, Sugganth Daniel, Julia A Elvin, James Suh, Vincent A Miller, Philip J Stephens, Siraj M Ali, Jeffrey S Ross, Jo-Anne Vergilio
Journal: Blood (2017)
Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes
Authors: Ahmad Ghorab, Preetesh Jain, Hagop M. Kantarjian, Rashmi Kanagal-Shamanna, Elias J. Jabbour, Koji Sasaki, Tapan Kadia, Guillermo Garcia-Manero, Prithviraj Bose, Musa Yilmaz, Kiran Naqvi, William G Wierda, Srdan Verstovsek, Nitin Jain, Zeev Estrov, Farhad Ravandi, Susan M. O'Brien, Jorge E. Cortes
Journal: Blood (2017)
深層学習画像処理を用いた自動サイズ特異的線量推定【JST・京大機械翻訳】
Authors: Juszczyk Jan, Badura Pawel, Czajkowska Joanna, Wijata Agata, Andrzejewski Jacek, Bozek Pawel, Smolinski Michal, Biesok Marta, Sage Agata, Rudzki Marcin, Wieclawek Wojciech
Journal: Medical Image Analysis (2021)
cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages
Authors: Peifa Yu, Zhijiang Miao, Yang Li, Ruchi Bansal, Maikel P. Peppelenbosch, Qiuwei Pan
Journal: Gut Microbes (2021)

Although cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling has been well recognized in defending DNA viruses, the role of cGAS-STING signaling in regulating infection of RNA viruses remains largely elusive. Noroviruses, as single-stranded RNA viruses, are the main causative agents of acute viral gastroenteritis worldwide. This study comprehensively investigated the role of cGAS-STING in response to murine norovirus (MNV) infection. We found that STING agonists potently inhibited MNV replication in mouse macrophages partially requiring the JAK/STAT pathway that induced transcription of interferon (IFN)-stimulated genes (ISGs). Loss- and gain-function assays revealed that both cGAS and STING were necessary for host defense against MNV propagation. Knocking out cGAS or STING in mouse macrophages led to defects in induction of antiviral ISGs upon MNV infection. Overexpression of cGAS and STING moderately increased ISG transcription but potently inhibited MNV replication in human HEK293T cells ectopically expressing the viral receptor CD300lf. This inhibitory effect was not affected by JAK inhibitor treatment or expression of different MNV viral proteins. Interestingly, STING but not cGAS interacted with mouse RIG-I, and attenuated its N-terminus-mediated anti-MNV effects. Our results implicate an essential role for mouse cGAS and STING in regulating innate immune response and defending MNV infection. This further strengthens the evidence of cGAS-STING signaling in response to RNA virus infection.
Deregulation of HLA-I in cancer and its central importance for immunotherapy
Authors: Ahmet Hazini, Kerry Fisher, Len Seymour
Journal: Journal for ImmunoTherapy of Cancer (2021)

It is now well accepted that many tumors undergo a process of clonal selection which means that tumor antigens arising at various stages of tumor progression are likely to be represented in just a subset of tumor cells. This process is thought to be driven by constant immunosurveillance which applies selective pressure by eliminating tumor cells expressing antigens that are recognized by T cells. It is becoming increasingly clear that the same selective pressure may also select for tumor cells that evade immune detection by acquiring deficiencies in their human leucocyte antigen (HLA) presentation pathways, allowing important tumor antigens to persist within cells undetected by the immune system. Deficiencies in antigen presentation pathway can arise by a variety of mechanisms, including genetic and epigenetic changes, and functional antigen presentation is a hard phenomenon to assess using our standard analytical techniques. Nevertheless, it is likely to have profound clinical significance and could well define whether an individual patient will respond to a particular type of therapy or not. In this review we consider the mechanisms by which HLA function may be lost in clinical disease, we assess the implications for current immunotherapy approaches using checkpoint inhibitors and examine the prognostic impact of HLA loss demonstrated in clinical trials so far. Finally, we propose strategies that might be explored for possible patient stratification.
Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study
Authors: Núria Rodríguez de Dios, Felipe Couñago, Mauricio Murcia-Mejía, Mikel Rico-Oses, Patricia Calvo-Crespo, Pilar Samper, Carmen Vallejo, Javier Luna, Itziar Trueba, Amalia Sotoca, Cristina Cigarral, Núria Farré, Rosa M. Manero, Xavier Durán, Juan Domigo Gispert, Gonzalo Sánchez-Benavides, Teresa Rognoni, Margarita Torrente, Jaume Capellades, Mar Jiménez, Teresa Cabada, Miguel Blanco, Ana Alonso, Juan Martínez-San Millán, José Escribano, Beatriz González, José Luis López-Guerra
Journal: Journal of Clinical Oncology (2021)

Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone.This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI.Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different.Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.
Abstract 16570: Left Ventricular Concentric Remodeling As A Cause Of Impaired Cardiorespiratory Fitness In Patients With Heart Failure And Preserved Ejection Fraction
Authors: Justin Heizer, Justin M Canada, Salvatore Carbone, Benjamin W Van Tassell, Ross Arena, Antonio Abbate
Journal: Circulation (2019)

Introduction: Left ventricular (LV) concentric remodeling refers to a process by which increased LV relative wall thickness alters myocardial geometry, resulting in reduced LV end-diastolic volume ...
The ECLIPSE Study: Efficacy of Cryoablation on Metastatic Lung Tumors With a 5-Year Follow-Up
Authors: Thierry de Baère, David Woodrum, Lambros Tselikas, Fereidoun Abtin, Peter Littrup, Frederic Deschamps, Robert Suh, Hussein D. Aoun, Matthew Callstrom
Journal: Journal of Thoracic Oncology (2021)

IntroductionThe ECLIPSE study aimed to evaluate the feasibility and efficacy of cryoablation (CA) for local tumor control in patients with pulmonary metastatic disease in 5 years of follow-up.MethodsECLIPSE was a prospective, multicenter, single-arm study that included patients treated with CA if they had one to five metastatic lung tumors, each with a diameter of less than or equal to 3.5 cm. Patients were followed up in the course of 5 years. The primary end point was local tumor control, both per tumor and per patient; secondary end points included cancer-specific survival, overall survival, and quality of life (QoL). QoL was evaluated using the Karnofsky Performance Score, the Eastern Cooperative Oncology Group performance score, and the Short Form-12 health survey.ResultsThe study included 40 patients across four sites (three in United States and one in Europe). A total of 60 metastatic pulmonary tumors were treated with 48 CA procedures. Overall local tumor control rates were 87.9% (29 of 33) and 79.2% (19 of 24) per tumor, 83.3% (20 of 24) and 75.0% (15 of 20) per patient, at 3 and 5 years, respectively. A total of five treated patients had local progression throughout the duration of the study. Disease-specific survival rate was 74.8% at 3 years and 55.3% at 5 years, whereas overall survival at 3 and 5 years was 63.2% and 46.7%, respectively. Patient QoL scores did not reach statistical significance.ConclusionsCA is an effective means of long-term local tumor control in patients with metastatic pulmonary tumors.
IRE1β does not affect mucus secretion during allergic asthma development in a house dust mite murine model
Authors: Eva Cloots, Nincy Debeuf, Kim Deswarte, Farzaneh Fayazpour, Manon Vanheerswynghels, Caroline De Wolf, Evelien Van De Velde, Hamida Hammad, Bart N. Lambrecht, Sven Eyckerman, Sophie Janssens
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Corrigendum to “A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: Enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway” [Bioact. Mater. 6 2 (February 2021) 375–385]
Authors: Yinping Zhao, Guangchao Zang, Tieying Yin, Xiaoyi Ma, Lifeng Zhou, Lingjuan Wu, Richard Daniel, Yunbing Wang, Juhui Qiu, Guixue Wang
Journal: Bioactive Materials (2021)

[This corrects the article DOI: 10.1016/j.bioactmat.2020.08.018.].
Antibody response in individuals infected with SARS-CoV-2 early after the first dose of the BNT162b2 mRNA vaccine
Authors: Federico Gobbi, Dora Buonfrate, Ronaldo Silva, Davide Martini, Zeno Bisoffi, Chiara Piubelli, Silvia Riccetti, Alessandro Sinigaglia, Luisa Barzon
Journal: Journal of Infection (2021)
SARS-CoV-2 Variants in Patients with Immunosuppression
Authors: Lawrence Corey, Chris Beyrer, Myron S Cohen, Nelson L Michael, Trevor Bedford, Morgane Rolland
Journal: New England Journal of Medicine (2021)

SARS-CoV-2 and Immunosuppression In this article, the authors discuss the challenges of SARS-CoV-2 infection in patients with a weakened immune system, including the potential implications regardin...
Sheila Cameron Fowler
Authors: Alison Fowler
Journal: BMJ (2021)

Sheila Cameron Fowler started her career as a GP in the early 1960s as an assistant to Dr Kirchenberger at the Mill Hill Lane Surgery, Derby. There was an open fire in the waiting room. There were no appointments—patients would just turn up and wait to see the doctor. Very few people had telephones, so they had to come and ask for visits.

After the sudden death of Dr Kirchenberger, Sheila joined the practice at 13 Vernon Street. Many of her former patients went with her. As well as her career, Sheila and her husband adopted four children. She was very much from …
Hospital Use for Myocardial Infarction and Stroke Among Medicare Beneficiaries From March to December 2020
Authors: Kate A. Stewart, Laura Blue, Keith Kranker, Sandi Nelson, Nancy McCall, Patricia Markovich, G. Gregory Peterson
Journal: JAMA Cardiology (2021)

Hospitalizations for acute myocardial infarction (AMI) and stroke declined nationwide among adults during the early COVID-19 period, suggesting some patients did not receive timely care for these emergencies. 1-4Declines in AMI and stroke hospitalizations might be particularly large for Medicare patients who, because they are older or physically disabled and have more comorbidities, are both more likely to have cardiovascular events and have concerns about contracting COVID-19 during a hospitalization.However, to our knowledge, no studies have examined this population specifically to date.We compared weekly rates of hospital use for AMI and stroke in 2020 with weekly rates in 2018 and 2019 among Medicare fee-for-service (FFS) beneficiaries nationally.Methods | We used the Medicare Beneficiary Summary File to identify all beneficiaries enrolled in Medicare FFS since 2018.We constructed a beneficiary week-level file with demographic and enrollment characteristics and an indicator for whether beneficiaries' claims data were observable that week because they were alive and enrolled in Medicare FFS at the start of the week.For each observable week, we used inpatient and outpatient claims to identify hospitalizations, outpatient emergency department visits, or observation stays with a diagnosis code for new AMI or stroke, including transient ischemic attack.For each week, we calculated the unduplicated number of new AMI and stroke events per 100 000 observable beneficiaries and compared weekly rates in 2020 vs the mean rate for the same weeks across 2018 and 2019.We repeated these analyses for subgroups defined by sex, race, Medicaid dual-eligibility status, and number of chronic conditions.Analyses were conducted using SAS version 9.4 (SAS Institute) and Excel version 2008 (Microsoft).See eMethods 1, 2, and 3 in the Supplement for the definition of week for each year, the list of claims-based AMI and stroke diagnosis codes, and subgroup definitions by presence of chronic conditions, respectively.