tbuckley/cabot-search huggingface dataset:
Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes
Authors: Emma St Martin, Alejandro Ferrer, Abhishek A. Mangaonkar, Shakila P. Khan, Mira A. Kohorst, Avni Y. Joshi, William J. Hogan, Horatiu Olteanu, Ann M. Moyer, Aref Al‐Kali, Ayalew Tefferi, Dong Chen, Kitsada Wudhikarn, Ronald Go, David Viswanatha, Rong He, Rhett Ketterling, Phuong L. Nguyen, Jennifer L. Oliveira, Naseema Gangat, Terra Lasho, Mrinal M. Patnaik
Journal: American Journal of Hematology (2021)

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.
Factors Associated With State-Specific Medicaid Expansion and Receipt of Autologous Breast Reconstruction Among Patients Undergoing Mastectomy
Authors: Kristine A. Huynh, Mayank Jayaram, Chang Wang, Megan Lane, Lu Wang, Adeyiza O. Momoh, Kevin C. Chung
Journal: JAMA Network Open (2021)

Despite demonstrated psychosocial benefits, autologous breast reconstruction remains underutilized. An analysis of the association between Medicaid expansion and autologous breast reconstruction has yet to be performed.To compare autologous breast reconstruction rates and determine the association between Medicaid expansion and breast reconstruction.A retrospective cross-sectional study was performed using the State Inpatient Database from January 1, 2012, through September 30, 2015, and included 51 340 patients. Patients were identified using the International Classification of Diseases, Ninth Revision, codes for breast cancer, mastectomy, and autologous breast reconstruction. Data from states that expanded Medicaid (New Jersey, New York, and Washington) were compared with states that did not expand Medicaid (Florida, North Carolina, and Wisconsin). Data were analyzed from June 1, 2020, through February 28, 2021.The Patient Protection and Affordable Care Act's Medicaid expansion was implemented in 2014; the preexpansion period ranged from 2012 to 2013 (2 years), whereas the postexpansion period ranged from 2014 to 2015 quarter 3 (1.75 years).Primary outcomes included use of autologous breast reconstruction before and after expansion. Independent covariates included patient demographics, comorbidities, and state of residence.Among 45 850 patients who underwent mastectomy and 9215 patients who received autologous breast reconstruction, 36 777 (67%) were White and 32 205 (59%) had private insurance. The use of immediate or delayed autologous reconstruction increased from 18.1% (4951 of 27 290) to 23.0% (4264 of 18 560) throughout the study period. Compared with 2012, the odds of reconstruction were 64% higher in 2015 (odds ratio [OR], 1.64; 95% CI, 1.48-1.80; P < .001). African American (OR, 1.43; 95% CI, 1.33-1.55; P < .001) and Hispanic (OR, 1.44; 95% CI, 1.31-1.60; P < .001) patients had higher odds of reconstruction compared with White patients regardless of state of residence. However, Medicaid expansion was associated with a 28% decrease in the odds of reconstruction (OR, 0.72; 95% CI, 0.61-0.87; P < .001) for African American patients, a 40% decrease (OR, 0.60; 95% CI, 0.50-0.74; P < .001) for Hispanic patients, and 20% decrease (OR, 0.80; 95% CI, 0.67-0.96; P = .01) for patients with Asian, Native American, or other minority race/ethnicity. Medicaid expansion was not associated with changes in the odds of reconstruction for White patients.In this cross-sectional study, although the odds of receiving autologous breast reconstruction increased annually, Medicaid expansion was associated with decreased odds of reconstruction for African American patients, Hispanic patients, and other patients of color.
28588 Efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a randomized, double-blind, vehicle-controlled phase 2 study
Authors: Matthew Zirwas, Zoe D. Draelos, Janet DuBois, Leon Kircik, Angela Moore, Linda Stein Gold, Robert C. Higham, Lynn Navale, Patrick Burnett, David R. Berk
Journal: Journal of the American Academy of Dermatology (2021)
アリストトル試験におけるアピキサバン用量調整の臨床的および薬理学的効果【JST・京大機械翻訳】
Authors: Zeitouni Michel, Giczewska Anna, D Lopes Renato, M Wojdyla Daniel, Christersson Christina, Siegbahn Agneta, De Caterina Raffaele, Steg Philippe Gabriel, B Granger Christopher, Wallentin Lars, H Alexander John
Journal: Journal of the American College of Cardiology (2020)
Association of Surprise-Billing Legislation with Prices Paid to In-Network and Out-of-Network Anesthesiologists in California, Florida, and New York
Authors: Ambar La Forgia, Amelia M. Bond, Robert Tyler Braun, Klaus Kjaer, Manyao Zhang, Lawrence P. Casalino
Journal: JAMA Internal Medicine (2021)

Several states have passed surprise-billing legislation to protect patients from unanticipated out-of-network medical bills, yet little is known about how state laws influence out-of-network prices and whether spillovers exist to in-network prices.
Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells
Authors: Nianci Chen, Yingxi Xu, Junli Mou, Qing Rao, Haiyan Xing, Zheng Tian, Kejing Tang, Min Wang, Jiangxiang Wang
Journal: Blood Cancer Journal (2021)

Abstract Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous disease with a dismal prognosis and limited treatment options. Chimeric antigen receptor (CAR) T cells have achieved unprecedented clinical responses in patients with B cell malignancies but a dismal consequences in AML. In our previous study, we found that interleukin-10 receptor (IL-10R) was overexpressed in most AML cells, and played an important role in promoting the stemness of leukemia cells. In this study, we developed a novel ligand-based CAR-T cell targeting IL-10R, which displayed striking cytotoxicity both in vitro and in vivo against AML cells. Except for monocytes, it had no significant adverse effects on the normal hematopoietic system, including CD34 + hematopoietic stem and progenitor cells (HSPCs). In addition, even though the incorporation of IL-10 in the CAR cassette led to phenotypes change, it had few adverse effects on the survival and biological activity of IL-10 CAR-T cells and did not cause excessive proliferation of leukemia cells. Therefore, we propose IL-10R is a novel promising therapeutic candidate for AML, and IL-10R targeted CAR-T therapy provides a new treatment strategy to improve the prognosis of AML.
Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling
Authors: Jin Qian, Bauer L. LeSavage, Kelsea M. Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T. Eggold, Yiren Xiao, Katherine C. Fuh, Venkatesh Krishnan, Annika Enejder, Sarah C. Heilshorn, Oliver Dorigo, Erinn B. Rankin
Journal: Journal of Clinical Investigation (2021)

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression and secretion by mesothelial cells through TGF-β signaling. Osteopontin facilitated ovarian cancer cell chemoresistance via the activation of the CD44 receptor, PI3K/AKT signaling, and ABC drug efflux transporter activity. Importantly, therapeutic inhibition of osteopontin markedly improved the efficacy of cisplatin in both human and mouse ovarian tumor xenografts. Collectively, our results highlight mesothelial cells as a key driver of ovarian cancer chemoresistance and suggest that therapeutic targeting of osteopontin may be an effective strategy for enhancing platinum sensitivity in ovarian cancer.
Response to: “Methotrexate Use and Liver Outcomes in Psoriasis and Rheumatoid Arthritis Patients: A Commentary on ‘Risk of liver disease in patients with psoriasis, psoriatic arthritis and rheumatoid arthritis receiving methotrexate: A population-based study'”
Authors: Joel M. Gelfand, Maha N. Syed
Journal: Journal of the American Academy of Dermatology (2021)
Health Care Worker Strikes and the Covid Pandemic
Authors: Ryan Essex, Sharon M Weldon
Journal: New England Journal of Medicine (2021)

In response to the recent Perspective article by Essex and Weldon (June 17 issue), 1 I wish to make some clarifications and set the record straight.First, the government of the Hong Kong Special Administrative Region has been committed to protecting the safety of health care workers.We have allocated an additional $1 billion (U.S. dollars) to our hospital authority since the onset of the pandemic to procure personal protective equipment and enhance support for frontline staff, and nonemergency services have been reduced to reprioritize resources.Although, sadly, as of this writing, 209 patients with Covid-19 have died in Hong Kong, there have been no fatalities among health care workers.Second, the claim that we "failed to act" on border closure is groundless.In fact, Hong Kong was among the first places to restrict crossborder travel.On January 27, 2020, people from Hubei Province were barred from entering Hong Kong, after which cross-boundary travel between Hong Kong and the rest of China (and elsewhere) was substantially reduced.More than 85% of cross-border travelers to Hong Kong are local residents.We continue to monitor the situation while allowing our residents to travel across borders where possible.
Empagliflozin in Heart Failure with a Preserved Ejection Fraction
Authors: Stefan D Anker, Javed Butler, Gerasimos Filippatos, João P Ferreira, Edimar Bocchi, Michael Böhm, Hans-Peter Brunner-La Rocca, Dong-Ju Choi, Vijay Chopra, Eduardo Chuquiure-Valenzuela, Nadia Giannetti, Juan Esteban Gomez-Mesa, Stefan Janssens, James L Januzzi, Jose R Gonzalez-Juanatey, Bela Merkely, Stephen J Nicholls, Sergio V Perrone, Ileana L Piña, Piotr Ponikowski, Michele Senni, David Sim, Jindrich Spinar, Iain Squire, Stefano Taddei, Hiroyuki Tsutsui, Subodh Verma, Dragos Vinereanu, Jian Zhang, Peter Carson, Carolyn Su Ping Lam, Nikolaus Marx, Cordula Zeller, Naveed Sattar, Waheed Jamal, Sven Schnaidt, Janet M Schnee, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer
Journal: New England Journal of Medicine (2021)

Sodium–glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.
Mechanosensitive TRPV4 is required for crystal-induced inflammation
Authors: Zhou Lan, Lvyi Chen, Jing Feng, Zili Xie, Zhiyong Liu, Fang Wang, Peng Liu, Xueping Yue, Lixia Du, Yonghui Zhao, Pu Yang, Jialie Luo, Zhe Zhu, Xueming Hu, Liang Cao, Ping Lu, Rajan Sah, Kory Lavine, Brian Kim, Hongzhen Hu
Journal: Annals of the Rheumatic Diseases (2021)

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4 eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca 2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1β which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.
Disparities in nonmelanoma skin cancer in Hispanic/Latino patients based on Mohs micrographic surgery defect size: A multicenter retrospective study
Authors: Laura Y. Blumenthal, Julia Arzeno, Nicole Syder, Sina Rabi, Margaret Huang, Erick Castellanos, Patrick Tran, Trevor A. Pickering, Emily J. Dantus, Gino K. In, Teresa Soriano, Jenny C. Hu
Journal: Journal of the American Academy of Dermatology (2021)
Effect of Training on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Masatsugu Okamura, Shunsuke Taito, Shuhei Yamamoto
Journal: JAMA (2021)

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Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial
Authors: Eugene I Gusev, Mikhail Yu Martynov, Alexey A Nikonov, Nikolay A Shamalov, Michail P Semenov, Eugene A Gerasimets, Elena B Yarovaya, Andrey M Semenov, Alexander I Archakov, Sergey S Markin, Eugene I Gusev, Mikhail Yu Martynov, Alexey A Nikonov, Nikolay A Shamalov, Michail P Semenov, Eugene A Gerasimets, Elena B Yarovaya, Andrey M Semenov, Alexander I Archakov, Sergey S Markin, Sergey B Aksentiev, Denis S. Yunevich, Andrey M Alasheev, Olga V Androfagina, Vladimir V Bobkov, Ksenia V Choroshavina, Janna Yu Chefranova, Yuriy A Lykov, Svetlana E Chuprina, Andrey A Vorobev, Alexey V Dobrovolskiy, Ulukpan A Elemanov, Sergey A Fedaynin, Vladimir I Gorbachev, Ivan V Korobeinikov, Irina V Greshnova, Larisa L Korsunskaya, Anastasiya A Nikonova, Vasily A Kudinov, Rafael I Artyushev, Vladimir A Kutsenko, Valentina N Nesterova, Alexey A Nizov, Alexey I Girivenko, Alexey A Orlovsky, Eduard A Ponomarev, Dmitriy V Popov, Sergey A Pribylov, Alexander S Semikhin, Ludmila V Timchenko, Olga N Jadan, Sergey A Zakharov, Alexander N Chirkov, Natalya V Zhukovskaya
Journal: The Lancet Neurology (2021)
BCI glossary and functional model by the IEEE P2731 working group
Authors: Chuck Easttom
Journal: Brain-Computer Interfaces (2021)

The IEEE P2731 working group has spent much of 2020 working on a lexicography for Brain Computer Interface research. Concomitant with that glossary, has been work on a functional model for BCI. This special issue contains articles written by teams of the P2731 working group, each focusing on a different aspect of that functional model.
Empagliflozin and Major Renal Outcomes in Heart Failure
Authors: Milton Packer, Javed Butler, Faiez Zannad, Stuart Pocock, Gerasimos Filippatos, João Ferreira, Martina Brueckmann, Waheed Jamal, Cordula Zeller, Christoph Wanner, Stefan Anker
Journal: New England Journal of Medicine (2021)

Empagliflozin and Renal Outcomes in Heart Failure In a planned pooled analysis of two trials that evaluated empagliflozin in patients with heart failure, major adverse renal outcomes occurred in 2....
Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?
Authors: Lisa Derosa, Bertrand Routy, Antoine Desilets, Romain Daillère, Safae Terrisse, Guido Kroemer, Laurence Zitvogel
Journal: Cancer Discovery (2021)

The cancer-immune dialogue subject to immuno-oncological intervention is profoundly influenced by microenvironmental factors. Indeed, the mucosal microbiota-and more specifically, the intestinal ecosystem-influences the tone of anticancer immune responses and the clinical benefit of immunotherapy. Antibiotics blunt the efficacy of immune checkpoint inhibitors (ICI), and fecal microbial transplantation may restore responsiveness of ICI-resistant melanoma. Here, we review the yin and yang of intestinal bacteria at the crossroads between the intestinal barrier, metabolism, and local or systemic immune responses during anticancer therapies. We discuss diagnostic tools to identify gut dysbiosis and the future prospects of microbiota-based therapeutic interventions. SIGNIFICANCE: Given the recent proof of concept of the potential efficacy of fecal microbial transplantation in patients with melanoma primarily resistant to PD-1 blockade, it is timely to discuss how and why antibiotics compromise the efficacy of cancer immunotherapy, describe the balance between beneficial and harmful microbial species in play during therapies, and introduce the potential for microbiota-centered interventions for the future of immuno-oncology.
Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma
Authors: Samantha J. Seitter, Richard M. Sherry, James C. Yang, Paul F. Robbins, Mackenzie L. Shindorf, Amy R. Copeland, Christine T. McGowan, Monica Epstein, Thomas E. Shelton, Michelle M. Langhan, Zulmarie Franco, David N. Danforth, Donald E. White, Steven A. Rosenberg, Stephanie L. Goff
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can mediate durable responses in patients with metastatic melanoma. This retrospective analysis provides long-term follow-up and describes the effect of prior therapy on outcomes after ACT-TIL. Patients and Methods: Patients with metastatic melanoma underwent surgical resection of a tumor for generation of TILs and were treated with a lymphodepleting preparative regimen followed by adoptive transfer of TILs and intravenous IL2. Clinical characteristics of enrolled patients and treatment characteristics of TIL infusion products over two decades of ACT were analyzed to identify predictors of objective response. Results: Adoptive transfer of TILs mediated an objective response rate of 56% (108/192) and median melanoma-specific survival of 28.5 months in patients naïve to anti–programmed cell death-1 (PD-1) therapy compared with 24% (8/34) and 11.6 months in patients refractory to anti–PD-1 (aPD-1). Among patients with BRAF V600E/K–mutated disease, prior treatment with targeted molecular therapy was also associated with a decreased response rate (21% vs. 60%) and decreased survival (9.3 vs. 50.7 months) when compared with those patients naïve to targeted therapy. With a median potential follow-up of 89 months, 46 of 48 complete responders in the aPD-1–naïve cohort have ongoing responses after a single treatment and 10-year melanoma-specific survival of 96%. Conclusions: Patients previously treated with PD-1 or MAPK inhibition are significantly less likely to develop durable objective responses to ACT-TIL. While ACT-TIL is currently being investigated for treatment-refractory patients, it should also be considered as an initial treatment option for eligible patients with metastatic melanoma. See related commentary by Sznol, p. 5156