tbuckley/cabot-search huggingface dataset:
An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata
Authors: Jacob W. Glickman, Celina Dubin, Dante Dahabreh, Joseph Han, Ester Del Duca, Yeriel D. Estrada, Ning Zhang, Grace W. Kimmel, Giselle Singer, James G. Krueger, Ana B. Pavel, Emma Guttman‐Yassky
Journal: Allergy (2021)

Alopecia areata (AA) is characterized by immune dysregulation in both scalp and blood, but a large-scale approach establishing biomarkers of AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize the transcriptomic signature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity.We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n = 18) and healthy individuals (n = 8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT).A total of 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false discovery rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp (p < .05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (p < .05). AA scalp demonstrated significantly greater biomarker dysregulation compared to blood. An integrated multivariate approach combining scalp and serum biomarkers improved correlations with disease severity/SALT.This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.
Former British Cycling and Team Sky doctor ordered testosterone to improve performance, tribunal finds
Authors: Clare Dyer
Journal: BMJ (2021)

L Sutherland, D Roth, P Beck, G May, K Makiyama. Systematic review of the use of oral 5-aminosalicylic acid in the induction of remission in ulcerative colitis. In: The Cochrane Library, Issue 1, 1998. Oxford: Update Software.
Unmet Needs for a Better Treatment in Patients with Peripheral T Cell Lymphoma: Data from a Nationwide, Multi-Center Prospective Registry Study (CISL 1404)
Authors: Dong-Yeop Shin, Jung Yong Hong, Koh Youngil, Seok Jin Kim, Lee Gyeong-Won, Kwak Jae-Yong, Young Rok Do, Yong Park, Joon-ho Lee, Hye Jin Kang, Won-Sik Lee, Park Byeong Bae, Min Kyoung Kim, Jae-Cheol Jo, Hyeon-Seok Eom, Jeong Seong Hyun, Kwai Han Yoo, Kwon Ji-Hyun, Won Young-Woong, Byeong Seok Sohn, Kim Hyo Jung, Sung-Soo Yoon, Cheolwon Suh, Kim Won Seog
Journal: Blood (2017)
FP13.04 KEYNOTE-042 3-Year Survival Update: 1L Pembrolizumab vs Platinum-Based Chemotherapy for PD-L1+ Locally Advanced/Metastatic NSCLC
Authors: B.C. Cho, Y. Wu, G. Lopes, I. Kudaba, D.M. Kowalski, H.Z. Turna, G. De Castro, C. Caglevic, L. Zhang, B. Karaszewska, K.K. Laktionov, V. Srimuninnimit, I. Bondarenko, K. Kubota, L. Yin, J. Lin, F. Souza, T.S.K. Mok
Journal: Journal of Thoracic Oncology (2021)

In the KEYNOTE-042 study (NCT02220894), pembrolizumab significantly improved OS vs platinum-based chemotherapy as first-line treatment for locally advanced/metastatic NSCLC without sensitizing EGFR/ALK alterations with PD-L1 tumor proportion score (TPS) ≥1%. We present updated data from KEYNOTE-042 with >3 years follow-up from randomization, including an exploratory analysis of time to progression on next-line therapy (PFS-2). Outcomes in patients who completed 35 cycles of pembrolizumab and in those who received second-course treatment are also reported.
Examining the intubation decision in randomised clinical trials
Authors: Aiman Tulaimat
Journal: European Respiratory Journal (2021)

Tobin et al. [1] pointed in their editorial to the limitations of randomised trials in determining the effect of noninvasive modalities on the intubation of patients with respiratory failure. My colleagues and I have recently examined many design aspects of 53 randomised trials that evaluated the effect of noninvasive ventilation and high flow oxygen therapy on the outcomes of patients with acute respiratory failure [2]. Our findings support many of the points highlighted in the editorial. Criteria used in clinical trials to identify patients with respiratory failure and for when to intubate them might not be applicable to clinical practice <https://bit.ly/3qAmCYt>
Abstract 19257: TRPC3 and IP3 Regulate Angiotensin II Induced Ca2+ Dependent Arrhythmias in Mouse and Human Cardiomyocytes
Authors: Michael Sacherer, Senka Ljubojevic, Philipp Stiegler, Michael Sereinigg, Burkert Pieske, Frank Heinzel
Journal: Circulation (2012)

Angiotensin II (ATII) is associated with cardiac remodeling, heart failure and arrhythmia. In cardiomyocytes (CM), ATII signals primarily via the Gq-coupled ATII receptor type 1 (AT1), phospholipase C signaling pathway including IP3-mediated Ca release and diacylglycerol activation of protein kinase C. Diastolic Ca release from the sarcomplasmic reticulum (SR) triggers arrhythmogenic inward current via the sarcolemmal Na-Ca-exchanger (NCX). Recent evidence suggests that TRPC3 channels and NCX may also be regulated by ATII contributing to arrhythmogenity. We investigated the mechanisms of Ca-mediated cellular arrhythmias induced by ATII. In CM from murine or human non-failing left ventricle, [Ca] transients (Fluo4-AM) during 1 Hz, as well as SR Ca load (caffeine), SR Ca leak (Ca spark frequency,SparkF) and arrhythmic (arrh) action potentials (as synchronized diastolic Ca release) during prolonged diastole were quantified in confocal images. Action potentials (AP) were recorded (current clamp) in a subset of cells. ATII (100 nM,20 min) in combination with IP3-inhibitor 2-ABP (3 µM) or TRPC3-inhibitor Pyr3 (10 µM), or ouabain (100 nM) were used in parallel experiments. In mouse CM ATII increased [Ca] transient amplitude (F/F0: 4.1±0.3 vs. 2.7±0.2 in CTRL). ATII also induced Ca sparks (SparkF (s-1*pL-1): 277±28 vs. 48±20) and arrhAP (0.77±0.12 vs. 0.03±0.01arrhAP*s-1) despite unchanged SR [Ca]. ATII induced significantly more arrhAP than ouabain (0.06±0.02) despite similarly increased SparkF (ouabain: 284±44). ATII tended to increase AP duration from 53±6 to 92±34 ms (APD90; P=0.1). 2-APB significantly reduced ATII -induced Ca sparks and arrhAP. In CM matched for SR Ca leak (SparkF), 2-APB significantly reduced - and Pyr3 abolished ATII-induced arrhAP. ATII was also arrhythmogenic in human non-failing CM (SparkF: 407±93 vs. 90±23 in CTRL;cells with arrhAP: 6/10 vs. 2/11; p&lt;0.05). Pyr3 also effectively reduced AT-II induced arrhythmogenity in human CM (SparkF: 101±21; 0/7 cells with arrhAP; both P&lt;0.05). Conclusion: ATII facilitates Ca-dependent arrhythmias by mechanisms beyond an increase in SR Ca leak in mouse and human CM. TRPC3-channels promote the arrhythmogenity of diastolic SR Ca release in the presence of ATII.
MA08.03 Immunotherapy Alone or with Chemotherapy in Advanced NSCLC? Utility of Clinical Factors and Blood-Based Host Immune Profiling.
Authors: W. Akerley, N. Nagajothi, P. Walker, R. Mitchell, R. Page, J. Tan, J. Dubay, E. Santos, W. Brenner, P. Rich, J. Orsini, E. Pauli, E. Schaefer
Journal: Journal of Thoracic Oncology (2021)
FP12.03 SRC-Homology 2 Domain-Containing Phosphatase 2 (SHP2) in Resected Lung Adenocarcinoma (LUAD)
Authors: M. Ito, J. Codony-Servat, A. Giménez-Capitán, M. Serra-Mitjans, F. Pérez-Ochoa, D. Lligé, I. Chaib, R. Rami-Porta, C. Obiols, S. Call, J. Belda-Sanchís, X. Tarroch-Sarasa, N. Karachaliou, M.A. Molina-Vila, M. Okada, R. Rosell
Journal: Journal of Thoracic Oncology (2021)
Effect of a Birthing on Country service redesign on maternal and neonatal health outcomes for First Nations Australians: a prospective, non-randomised, interventional trial
Authors: Sue Kildea, Yu Gao, Sophie Hickey, Carmel Nelson, Sue Kruske, Adrian Carson, Jody Currie, Maree Reynolds, Kay Wilson, Kristie Watego, Jo Costello, Yvette Roe
Journal: The Lancet Global Health (2021)

There is an urgency to redress unacceptable maternal and infant health outcomes for First Nations families in Australia. A multi-agency partnership between two Aboriginal Community-controlled health services and a tertiary hospital in urban Australia designed, implemented, and evaluated the new Birthing in Our Community (BiOC) service. In this study, we aimed to assess and report the clinical effectiveness of the BiOC service on key maternal and infant health outcomes compared with that of standard care.
FP01.05 The ASCENT Trial: A Phase II Study of Neoadjuvant/Adjuvant Afatinib, Chemoradiation +/- Surgery for Stage III EGFR-Mutant NSCLC
Authors: A. Piper-Vallillo, R. Mak, M. Lanuti, A. Muzikansky, J. Rotow, P. Jänne, M. Mino-Kenudson, S. Swanson, C. Wright, D. Kozono, J. Marcoux, Z. Piotrowska, H. Willers, L. Sequist
Journal: Journal of Thoracic Oncology (2021)
MARCKS cooperates with NKAP to activate NF-kB signaling in smoke-related lung cancer
Authors: Jun Liu, Szu-Jung Chen, Ssu-Wei Hsu, Jun Zhang, Ji-Min Li, David C Yang, Shenwen Gu, Kent E Pinkerton, Ching-Hsien Chen
Journal: Theranostics (2021)

Rationale: Cigarette smoking is a major risk factor for lung cancer development and progression; however, the mechanism of how cigarette smoke activates signaling pathways in promoting cancer malignancy remains to be established. Herein, we aimed to determine the contribution of a signaling protein, myristoylated alanine-rich C kinase substrate (MARCKS), in smoke-mediated lung cancer. Methods: We firstly examined the levels of phosphorylated MARCKS (phospho-MARCKS) in smoke-exposed human lung cancer cells and specimens as well as non-human primate airway epithelium. Next, the MARCKS-interactome and its gene networks were identified. We also used genetic and pharmacological approaches to verify the functionality and molecular mechanism of smoke-induced phospho-MARCKS. Results: We observed that MARCKS becomes activated in airway epithelium and lung cancer cells in response to cigarette smoke. Functional proteomics revealed MARCKS protein directly binds to NF-κB-activating protein (NKAP). Following MARCKS phosphorylation at ser159 and ser163, the MARCKS-NKAP interaction was inhibited, leading to the activation of NF-κB signaling. In a screen of two cohorts of lung cancer patients, we confirmed that phospho-MARCKS is positively correlated with phospho-NF-κB (phospho-p65), and poor survival. Surprisingly, smoke-induced phospho-MARCKS upregulated the expression of pro-inflammatory cytokines, epithelial-mesenchymal transition, and stem-like properties. Conversely, targeting of MARCKS phosphorylation with MPS peptide, a specific MARCKS phosphorylation inhibitor, suppressed smoke-mediated NF-κB signaling activity, pro-inflammatory cytokines expression, aggressiveness and stemness of lung cancer cells. Conclusion: Our results suggest that phospho-MARCKS is a novel NF-kB activator in smoke-mediated lung cancer progression and provide a promising molecular model for developing new anticancer strategies.
HLA-E–restricted, Gag-specific CD8 <sup>+</sup> T cells can suppress HIV-1 infection, offering vaccine opportunities
Authors: Hongbing Yang, Margarida Rei, Simon Brackenridge, Elena Brenna, Hong Sun, Shaheed Abdulhaqq, Michael K. P. Liu, Weiwei Ma, Prathiba Kurupati, Xiaoning Xu, Vincenzo Cerundolo, Edward Jenkins, Simon J. Davis, Jonah B. Sacha, Klaus Früh, Louis J. Picker, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael
Journal: Science Immunology (2021)

Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)-restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1-specific, HLA-E-restricted T cells have not been observed in HIV-1-infected individuals. Here, HLA-E-restricted, HIV-1-specific CD8
P76.15 Osimertinib Improved Overall Survival in mEGFR NSCLC Patients With Leptomeningeal Metastases Regardless of T790M Mutational Status
Authors: J. Lee, Y.L. Choi, J. Han, S. Park, H.A. Jung, J. Sun, S. Lee, J.S. Ahn, K. Park, M. Ahn
Journal: Journal of Thoracic Oncology (2021)
Maxillomandibular advancement versus multilevel surgery for treatment of obstructive sleep apnea: A systematic review and meta-analysis
Authors: Ning Zhou, Jean-Pierre T.F. Ho, Zhengfei Huang, René Spijker, Nico de Vries, Ghizlane Aarab, Frank Lobbezoo, Madeline J.L. Ravesloot, Jan de Lange
Journal: Sleep Medicine Reviews (2021)

Multilevel surgery (MLS) and maxillomandibular advancement surgery (MMA) are two established options in surgical management of obstructive sleep apnea (OSA), which target different levels of airway obstruction. The objective of this review was to comparatively evaluate the clinical efficacy and safety of MMA and MLS in the treatment of OSA. MEDLINE and Embase databases were searched for studies on MMA and/or MLS in OSA patients. Twenty MMA studies and 39 MLS studies were identified. OSA patients who underwent MMA showed significant improvements in AHI, LSAT, ODI, and ESS by -46.2/h, 13.5%, -30.3/h, and -8.5, respectively. The pooled rates of surgical success and cure for MMA were 85.0% and 46.3%, respectively. Patients who underwent MLS showed significant improvements in AHI, LSAT, ODI, and ESS by -24.7/h, 8.7%, -19.1/h, and -5.8, respectively. The pooled surgical success and cure rates for MLS were 65.1% and 28.1%, respectively. The rates of major complication of MMA and MLS were 3.2% and 1.1%, respectively, and the rate of minor complication of MMA was higher than that of MLS. We conclude that both MMA and MLS are effective treatment options for OSA. Compared to MLS, MMA may be more effective in improving OSA. However, the complication rate of MMA is higher.
P84.03 GLASS: Global Lorlatinib for ALK(+) and ROS1(+) Retrospective Study: Real World Data of 123 NSCLC Patients
Authors: N. Peled, R. Gillis, S. Kilickap, P. Froesch, S. Orlov, E. Filippova, U. Demirci, P. Christopoulos, I. Cicin, F. Bugdayci Basal, C. Yilmaz, M. Fedor, T. Korkmaz, S. Paydas, O. Gautschi, A. Zirtiloglu, Y. Eralp, H.Y. Cinkir, A. Sezer, M. Erman, D. Tural, H.Z. Turna, J. Mazieres, E. Dudnik, N. Reguart, R. Camidge, T.L. Ng, F. Cay Senler, İ. Beypınar, D. Yazılıtaş, A. Demirkazik, A. Karaoğlu, K. Okutur, H. Şenol Coşkun, M.A. Nahit Şendur, A. Isikdogan, D. Cabuk, P.F. Yumuk, I. Yıldız, M.A. Kaplan, Ö. Özyılkan, İ. Öztop, O.F. Olmez, K. Aydin, A. Aydıner, N. Meydan, R. Grinberg, L. Roisman
Journal: Journal of Thoracic Oncology (2021)
A comprehensive review of integrative pharmacology-based investigation: A paradigm shift in traditional Chinese medicine
Authors: Haiyu Xu, Yanqiong Zhang, Ping Wang, Junhong Zhang, Hong Chen, Luoqi Zhang, Xia Du, Chunhui Zhao, Dan Wu, Feng Liu, Hongjun Yang, Changxiao Liu
Journal: Acta Pharmaceutica Sinica B (2021)

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics–pharmacodynamics (PK–PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK–PD processes in vivo. Then, the main research contents of TCMIP are introduced as follows: chemical and ADME/PK profiles of TCM formulas; confirming the three forms of active substances and the three action modes; establishing the qualitative PK–PD correlation; and building the quantitative PK–PD correlations, etc. After that, we summarize the existing data resources, computational models and experimental methods of TCMIP and highlight the urgent establishment of mathematical modeling and experimental methods. Finally, we further discuss the applications of TCMIP for the improvement of TCM quality control, clarification of the molecular mechanisms underlying the actions of TCMs and discovery of potential new drugs, especially TCM-related combination drug discovery.
Regulation of Monocyte Adhesion and Type I Interferon Signaling by CD52 in Patients With Systemic Sclerosis
Authors: Michał Rudnik, Filip Rolski, Suzana Jordan, Tonja Mertelj, Mara Stellato, Oliver Distler, Przemysław Blyszczuk, Gabriela Kania
Journal: Arthritis & Rheumatology (2021)

Objective Systemic sclerosis (SSc) is characterized by dysregulation of type I interferon (IFN) signaling. CD52 is known for its immunosuppressive functions in T cells. This study was undertaken to investigate the role of CD52 in monocyte adhesion and type I IFN signaling in patients with SSc. Methods Transcriptome profiles of circulating CD14+ monocytes from patients with limited cutaneous SSc (lcSSc), patients with diffuse cutaneous SSc (dcSSs), and healthy controls were analyzed by RNA sequencing. Levels of CD52, CD11b/integrin αΜ, and CD18/integrin β2 in whole blood were assessed by flow cytometry. CD52 expression was analyzed in relation to disease phenotype (early, lcSSc, dcSSc) and autoantibody profiles. The impact of overexpression, knockdown, and antibody blocking of CD52 was analyzed by gene and protein expression assays and functional assays. Results Pathway enrichment analysis indicated an increase in adhesion‐ and type I IFN–related genes in monocytes from SSc patients. These cells displayed up‐regulated expression of CD11b/CD18, reduced expression of CD52, and enhanced adhesion to intercellular adhesion molecule 1 and endothelial cells. Changes in CD52 expression were consistent with the SSc subtypes, as well as with immunosuppressive treatments, autoantibody profiles, and monocyte adhesion properties in patients with SSc. Overexpression of CD52 led to decreased levels of CD18 and monocyte adhesion, while knockdown of CD52 increased monocyte adhesion. Experiments with the humanized anti‐CD52 monoclonal antibody alemtuzumab in blood samples from healthy controls increased monocyte adhesion and CD11b/CD18 expression, and enhanced type I IFN responses. Monocytic CD52 expression was up‐regulated by interleukin‐4 (IL‐4)/IL‐13 via the STAT6 pathway, and was down‐regulated by lipopolysaccharide and IFNs α, β, and γ in a JAK1 and histone deacetylase IIa (HDAC IIa)–dependent manner. Conclusion Down‐regulation of the antiadhesion CD52 antigen in CD14+ monocytes represents a novel mechanism in the pathogenesis of SSc. Targeting of the IFN–HDAC–CD52 axis in monocytes might represent a new therapeutic option for patients with early SSc.
Association of Patients Reading Clinical Notes With Perception of Medication Adherence Among Persons With Serious Mental Illness
Authors: Charlotte Blease, Zhiyong Dong, John Torous, Jan Walker, Maria Hägglund, Catherine M. DesRoches
Journal: JAMA Network Open (2021)

Among patients with SMI, access to clinicians' notes may help clarify why medications have been prescribed and improve understanding of possible side effects.The findings of this study are promising in light of evidence that rates of psychotropic medication adherence for patients with major depressive disorders, bipolar disorders, and schizophrenia are only approximately 50%. 6 This study has several limitations.The survey did not determine the kinds of medication on which participants based their responses.While the definition we used for SMI was supported by the literature and the Substance Abuse and Mental Health Administration, the results may vary based on the definition.Because the survey was reliant on self-report measures, it was unknown whether response biases affected the survey.While the response rate was moderate for an online survey, the demographic breakdown and sampling restriction to 3 US health systems were further limitations.Sharing mental health notes will present challenges, and understandably, clinicians express concerns about patient access to their notes.However, access to clinical notes may benefit patients'understanding and knowledge about their medications, including among persons with SMI.
Bortezomib-Based Induction Treatment for Patients with Multiple Myeloma Ineligible for Autologous Stem Cell Transplantation: A Retrospective Multicenter Study in Czech Republic
Authors: Viera Sandecka, Ludek Pour, Sabina Sevcikova, Lucie Brozova, Jan Straub, Vlastimil Scudla, Vladimir Maisnar, Petr Pavlicek, Zdenek Adam, Marta Krejci, Martin Stork, Tomas Jelinek, Hana Plonkova, Roman Hajek
Journal: Blood (2017)
Multifocal and Accommodating Intraocular Lenses for the Treatment of Presbyopia
Authors: Julie M. Schallhorn, Seth M. Pantanelli, Charles C. Lin, Zaina N. Al-Mohtaseb, Walter Allan Steigleman, Marcony R. Santhiago, Timothy W. Olsen, Stephen J. Kim, Aaron M. Waite, Jennifer R. Rose-Nussbaumer
Journal: Ophthalmology (2021)
The Rise and Fall of Surgical Telehealth—Can Lack of Patient Connection Be Blamed?
Authors: Muneera R. Kapadia, Ian M. Kratzke, Sonia L. Sugg
Journal: JAMA Surgery (2021)

Grace F. Chao, MD, MSc; Kathleen Y. Li, MD, MSc; Ziwei Zhu, MS; Jeff McCullough, PhD; Mike Thompson, PhD; Jake Claflin, MD; Maximilian Fliegner, BA; Emma Steppe, MPH; Andrew Ryan, PhD; Chad Ellimoottil, MD, MSc
Federally Qualified Health Centers and Related Primary Care Workforce Issues
Authors: Mary Wakefield
Journal: JAMA (2021)

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MA04.09 Impacts of Multidisciplinary Meeting Presentation: Drivers and Outcomes from a Population Registry Retrospective Cohort study
Authors: T. Lin, J. Pham, E. Paul, M. Conron, G. Wright, D. Ball, P. Mitchell, N. Atkin, S. Harden, M. Brand, J. Zalcberg, R. Stirling
Journal: Journal of Thoracic Oncology (2021)