tbuckley/cabot-search huggingface dataset:
Occupational asthma due to different spices
Authors: J. Sastre, M. Olmo, A. Novalvos, D. Ibañez, C. Lahoz
Journal: Allergy (1996)

We describe a 27–year-old subject who developed rhinitis and asthma symptoms 1 year after starting to prepare a certain kind of sausage. He was previously diagnosed as having allergy to coconut, banana, and kiwi and allergic rhinitis to horse, cat, dog, and cow. A positive immediate skin prick test (SPT) for paprika (dry powder of Capsicum annuum [Solanaceae]), coriander (Coriandrum sutivum [umbelliferous]), and mace (shell of nutmeg, Myristica fragrans [Myristicaceae]) at a concentration of 10% (w/v) was obtained. SPT with other sausage ingredients, mites, pollens, and molds were negative. By ELISA, specific IgE antibodies to paprika, coriander, and mace were demonstrated. By ELISA-inhibition assays, a partial cross-reactivity was found among IgE-binding components from paprika and mace. The immunoblot analysis showed two IgE-reactive protein bands able to bind to IgE from mace of 20 and 40 kDa and two other bands from coriander extract of 50 and 56 kDa. No bands were detected from paprika extract. Specific bronchial inhalation challenges showed an immediate asthmatic reaction to extracts from paprika, coriander, and mace with a maximum fall in FEV, of 26%, 40%, and 31%, respectively, with no late asthmatic reactions. In summary, we demonstrate that inhalation of dust from paprika, coriander, and mace can result in an IgE-mediated reaction to these spices. In this patient, occupational asthma was due to spices from botanically unrelated species.
Correction to: Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study
Authors: Yong Yang, Ying Wang, Xin Liu, Xia He, Li-Ling Zhang, Gang Wu, Bao-Lin Qu, Li-Ting Qian, Xiao-Rong Hou, Fu-Quan Zhang, Xue-Ying Qiao, Hua Wang, Gao-Feng Li, Yuan Zhu, Jian-Zhong Cao, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Mei Shi, Li-Ming Xu, Hang Su, Yu-Qin Song, Jun Zhu, Yu-Jing Zhang, Hui-Qiang Huang, Chen Hu, Shu-Nan Qi, Ye-Xiong Li
Journal: Leukemia (2021)
Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation
Authors: Max Heckler, Lestat R. Ali, Eleanor Clancy-Thompson, Li Qiang, Katherine S. Ventre, Patrick Lenehan, Kevin Roehle, Adrienne Luoma, Kelly Boelaars, Vera Peters, Julia McCreary, Tamara Boschert, Eric S. Wang, Shengbao Suo, Francesco Marangoni, Thorsten R. Mempel, Henry W. Long, Kai W. Wucherpfennig, Michael Dougan, Nathanael S. Gray, Guo-Cheng Yuan, Shom Goel, Sara M. Tolaney, Stephanie K. Dougan
Journal: Cancer Discovery (2021)

Abstract CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8+ T cells during early stages of activation. Mice receiving tumor-specific CD8+ T cells treated with CDK4/6 inhibitors displayed increased T-cell persistence and immunologic memory. CDK4/6 inhibition upregulated MXD4, a negative regulator of MYC, in both mouse and human CD8+ T cells. Silencing of Mxd4 or Myc in mouse CD8+ T cells demonstrated the importance of this axis for memory formation. We used single-cell transcriptional profiling and T-cell receptor clonotype tracking to evaluate recently activated human CD8+ T cells in patients with breast cancer before and during treatment with either palbociclib or abemaciclib. CDK4/6 inhibitor therapy in humans increases the frequency of CD8+ memory precursors and downregulates their expression of MYC target genes, suggesting that CDK4/6 inhibitors in patients with cancer may augment long-term protective immunity. Significance: CDK4/6 inhibition skews newly activated CD8+ T cells toward a memory phenotype in mice and humans with breast cancer. CDK4/6 inhibitors may have broad utility outside breast cancer, particularly in the neoadjuvant setting to augment CD8+ T-cell priming to tumor antigens prior to dosing with checkpoint blockade. This article is highlighted in the In This Issue feature, p. 2355
OP0091 What is the Evidence for the Presence of a Therapeutic Window of Opportunity in Rheumatoid Arthritis? A Systematic Literature Review
Authors: J. A. B. Van Nies, A. Krabben, J. W. Schoones, T. W. J. Huizinga, M. Kloppenburg, A. H. M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Initiation of DMARD-therapy in the 'window of opportunity' is thought to result in more effective modification of the processes underlying Rheumatoid Arthritis (RA). <h3>Objectives</h3> We questioned whether this effect is true or hyped and therefore performed a systematic literature review. <h3>Methods</h3> Medical literature databases up to June 2012 were systematically reviewed for cohort studies and randomized controlled trials reporting outcome data of early RA in relation with symptom duration at treatment initiation. The quality of these studies was assessed by two independent reviewers using a criteria scoring system of 15 items. Studies were dichotomized with the median score (79%) as cut-off. Best-evidence synthesis was applied to determine the level of evidence per outcome category. A meta-analysis was performed on the studies reporting on achieving DMARD-free sustained remission (the reverse of disease persistency). <h3>Results</h3> Out of 836 screened articles, 18 fulfilled the selection criteria and were not duplicates. Nine were scored as high-quality. Remission (various definitions) and radiographic progression were frequently studied outcomes. There was strong evidence for an association between symptom duration and radiographic progression. A meta-analysis on datasets evaluating DMARD-free sustained remission showed that symptom duration was independently associated with such remission both univariable and multivariable after adjustment of age, sex, treatment, rheumatoid factor and erythrocyte sedimentation rate; HR 0.989 (95%CI 0.983-0.995) per week increase in symptom duration (see figure 1 ). A moderate level of evidence was observed for studies on various other remission outcomes. <h3>Image/graph</h3> <h3>Conclusions</h3> There is strong evidence that prolonged symptom duration is associated with radiographic progression. Furthermore, symptom duration is associated with disease persistency in a meta-analysis, supporting the presence of a 'window of opportunity'-effect. <h3>Disclosure of Interest</h3> None Declared
Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors
Authors: Razvan Cristescu, Deepti Aurora-Garg, Andrew Albright, Lei Xu, Xiao Qiao Liu, Andrey Loboda, Lixin Lang, Fan Jin, Eric H Rubin, Alexandra Snyder, Jared Lunceford
Journal: Journal for ImmunoTherapy of Cancer (2022)

Several studies have evaluated the relationship between tumor mutational burden (TMB) and outcomes of immune checkpoint inhibitors. In the phase II KEYNOTE-158 study of pembrolizumab monotherapy for previously treated recurrent or metastatic cancer, high TMB as assessed by the FoundationOne CDx was associated with an improved objective response rate (ORR).We retrospectively assessed the relationship between TMB and efficacy in participants with previously treated advanced solid tumors enrolled in 12 trials that evaluated pembrolizumab monotherapy, including 3 randomized trials that compared pembrolizumab with chemotherapy. TMB was assessed in formalin-fixed, paraffin-embedded pretreatment tumor samples by whole-exome sequencing. High TMB was defined as ≥175 mutations/exome. Microsatellite instability (MSI) phenotype was based on whole-exome sequencing results. Programmed death ligand 1 (PD-L1) expression was assessed by immunohistochemistry. The primary end point was ORR assessed per RECIST V.1.1 by independent central review. Other end points included progression-free survival (PFS) assessed per RECIST V.1.1 by independent central review and overall survival (OS).Of the 2234 participants in the analysis, 1772 received pembrolizumab monotherapy and 462 received chemotherapy. Among the pembrolizumab-treated participants, ORR was 31.4% (95% CI 27.1 to 36.0) in the 433 participants with TMB ≥175 mutations/exome and 9.5% (95% CI 8.0 to 11.2) in the 1339 participants with TMB <175 mutations/exome. The association of TMB with ORR was observed regardless of PD-L1 expression and not driven by specific tumor types or participants with very high TMB or high MSI. In the 3 randomized controlled trials, TMB was associated with ORR (p≤0.016), PFS (p≤0.005), and OS (p≤0.029) of pembrolizumab but not of chemotherapy (p≥0.340, p≥0.643, and p≥0.174, respectively), and pembrolizumab improved efficacy versus chemotherapy in participants with TMB ≥175 mutations/exome.TMB ≥175 mutations/exome is associated with clinically meaningful improvement in the efficacy of pembrolizumab monotherapy and improved outcomes for pembrolizumab versus chemotherapy across a wide range of previously treated advanced solid tumor types. These data suggest TMB has broad clinical utility irrespective of tumor type, PD-L1 expression, or MSI status and support its use as a predictive biomarker for pembrolizumab monotherapy in participants with previously treated advanced solid tumors.
Food-specific IgG4 is elevated throughout the upper gastrointestinal tract in eosinophilic esophagitis
Authors: Mia Masuda, William LeSuer, Temeka Simmons, Jennifer Horsley-Silva, Alfred Doyle, Benjamin Wright
Journal: Journal of Allergy and Clinical Immunology (2022)

Food-specific IgG4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether its production is limited to the esophagus. The objective of this study was to assess food-specific IgG4 levels in the plasma and upper gastrointestinal tract and compare these with endoscopic disease severity and tissue eosinophil counts.
Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial
Authors: Samuel A. Funt, Michael Lattanzi, Karissa Whiting, Hikmat Al-Ahmadie, Colleen Quinlan, Min Yuen Teo, Chung-Han Lee, David Aggen, Danielle Zimmerman, Deaglan McHugh, Arlyn Apollo, Trey D. Durdin, Hong Truong, Jeffrey Kamradt, Maged Khalil, Bradley Lash, Irina Ostrovnaya, Asia S. McCoy, Grace Hettich, Ashley Regazzi, Marwah Jihad, Neha Ratna, Abigail Boswell, Kaitlyn Francese, Yuanquan Yang, Edmund Folefac, Harry W. Herr, S. Machele Donat, Eugene Pietzak, Eugene K. Cha, Timothy F. Donahue, Alvin C. Goh, William C. Huang, Dean F. Bajorin, Gopa Iyer, Bernard H. Bochner, Arjun V. Balar, Amir Mortazavi, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2022)

PURPOSE Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC. METHODS Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non–muscle-invasive downstaging to &lt; pT2N0. RESULTS Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) &lt; pT2N0, including 16 (41%) pT0N0. No patient with &lt; pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)–positive tumors and were all &lt; pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved &lt; pT2N0 and 11 of 34 (32%) were ≥ pT2N0 ( P = .3 for association between PD-L1 and &lt; pT2N0). CONCLUSION Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with &lt; pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker.
House dust mite sensitization and exposure affects bronchial epithelial anti‐microbial response to viral stimuli in patients with asthma
Authors: Samuel Cerps, Asger Sverrild, Sangeetha Ramu, Juan José Nieto‐Fontarigo, Hamid Akbarshahi, Mandy Menzel, Cecilia Andersson, Sofia Tillgren, Morten Hvidtfeldt, Celeste Porsbjerg, Lena Uller
Journal: Allergy (2022)

Allergen exposure worsens viral-triggered asthma exacerbations and could predispose the host to secondary bacterial infections. We have previously demonstrated that exposure to house dust mite (HDM) reduced TLR-3-induced IFN-β in human bronchial epithelial cells (HBECs) from healthy donors. We hypothesize that HDM sensitization in different ways may be involved in both viral and bacterial resistance of HBECs in asthma. In this study, the role of HDM sensitization and effects of HDM exposure on viral stimulus-challenged HBECs from asthmatic donors have been explored with regard to expression and release of molecules involved in anti-viral and anti-bacterial responses, respectively.HBECs from HDM-sensitized (HDM+) and unsensitized (HDM-) patients with asthma were used. HBECs were exposed to HDM or heat inactivated (hi)-HDM (20 μg/ml) for 24 h prior to stimulation with the viral infection mimic, Poly(I:C), for 3 or 24 h. Samples were analyzed with ELISA and RT-qPCR for β-defensin-2, IFN-β, TSLP, and neutrophil-recruiting mediators: IL-8 and TNF-⍺. NFκB signaling proteins p105, p65, and IκB-⍺ were analyzed by Western blot.Poly(I:C)-induced IFN-β expression was reduced in HBECs from HDM + compared to HDM- patients (p = 0.05). In vitro exposure of HBECs to HDM furthermore reduced anti-microbial responses to Poly(I:C) including β-defensin-2, IL-8, and TNF-⍺, along with reduced NFκB activity. This was observed in HBECs from asthma patients sensitized to HDM, as well as in non-sensitized patients. By contrast, Poly (I:C)-induced release of TSLP, a driver of T2 inflammation, was not reduced with exposure to HDM.Using HBECs challenged with viral infection mimic, Poly(I:C), we demonstrated that allergic sensitization to HDM was associated with impaired anti-viral immunity and that HDM exposure reduced anti-viral and anti-bacterial defense molecules, but not TSLP, across non-allergic as well as allergic asthma. These data suggest a role of HDM in the pathogenesis of asthma exacerbations evoked by viral infections including sequential viral-bacterial and viral-viral infections.
Viral Hepatitis
Authors: Albert B. Knapp
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes20 July 1999Viral HepatitisAlbert B. Knapp, MDAlbert B. Knapp, MDNew York University School of Medicine, New York, New York. (Knapp)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-2-199907200-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Second edition. Zuckerman AJ, Thomas HC; eds. 649 pages. London: Churchill Livingstone; 1998. $195.00. ISBN 0443057974. Order phone 800-543-1918.Field of medicine: Gastroenterology and hepatology.Format: Hardcover book.Audience: Gastroenterologists, hepatologists, virologists, internists, family practitioners, pathologists, epidemiologists, and medical trainees.Purpose: To serve as a clinical and basic science resource text on viral hepatitis.Content: This textbook provides a broad overview of the field, as well as complete clinical and basic science reviews of hepatitis A, B, C, D, E, and G. Each section is subdivided systematically into chapters on viral structure, molecular virology, epidemiology, diagnosis, treatment, and prevention. The ... Author, Article, and Disclosure InformationAffiliations: New York University School of Medicine, New York, New York. (Knapp) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 July 1999Volume 131, Issue 2Page: 159-160KeywordsClinical epidemiologyGastroenterology and hepatologyHepatitisHepatitis ALiver diseasesMolecular epidemiologyPathologistsPediatric infectionsSystematic reviewsVirology ePublished: 15 August 2000 Issue Published: 20 July 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Ligand activation of LXRβ reverses atherosclerosis and cellular cholesterol overload in mice lacking LXRα and apoE
Authors: Michelle N. Bradley, Cynthia Hong, Mingyi Chen, Sean B. Joseph, Damien C. Wilpitz, Xuping Wang, Aldons J. Lusis, Allan Collins, Willa A. Hseuh, Jon L. Collins, Rajendra K. Tangirala, Peter Tontonoz
Journal: Journal of Clinical Investigation (2007)

Liver X receptors (LXRs) α and β are transcriptional regulators of cholesterol homeostasis and potential targets for the development of antiatherosclerosis drugs. However, the specific roles of individual LXR isotypes in atherosclerosis and the pharmacological effects of synthetic agonists remain unclear. Previous work has shown that mice lacking LXRα accumulate cholesterol in the liver but not in peripheral tissues. In striking contrast, we demonstrate here that LXRα–/–apoE–/– mice exhibit extreme cholesterol accumulation in peripheral tissues, a dramatic increase in whole-body cholesterol burden, and accelerated atherosclerosis. The phenotype of these mice suggests that the level of LXR pathway activation in macrophages achieved by LXRβ and endogenous ligand is unable to maintain homeostasis in the setting of hypercholesterolemia. Surprisingly, however, a highly efficacious synthetic agonist was able to compensate for the loss of LXRα. Treatment of LXRα–/–apoE–/– mice with synthetic LXR ligand ameliorates the cholesterol overload phenotype and reduces atherosclerosis. These observations indicate that LXRα has an essential role in maintaining peripheral cholesterol homeostasis in the context of hypercholesterolemia and provide in vivo support for drug development strategies targeting LXRβ.
Radioimmunotherapy
Authors: R. P. Baum, V. Prasad, J. P. Oliva
Journal: Clinical Nuclear Medicine (2008)

Since Paul Ehrlich proposed the hypothesis (Scitenkettentheorie) more than a century ago that bacteria can be killed by selective usage of certain compounds having specific affinity to the bacteria and thus acting as a "magic bullet," antibodies have captured the imagination of scientists dealing with diseases. Cancer was and still remains among the most intriguing and challenging of diseases for which the exact cure for its many forms is not available to date. Parallel to the development of certain compounds such as sulfur and nitrogen mustard, with the capacity to modify the DNA and thus retard and kill the growth of cancer cells (Sausville and Longo 2005), Pressman and colleagues showed that radiolabeled antibodies had the potential to localize tumors in rabbits (Pressman and Keighley 1948; Pressman und Korngold 1953; Pressman et al. 1957). This was soon followed by first attempts by Beierwaltes and his colleagues at curing cancer in patients using radiolabeled polyclonal antibodies. An inability to find a way to purify the antitumor globulin from other globulins in order to increase the specificity was the major limitation of the study (Bale and Spar 1957; Pressman and Korngold 1953).
WASHINGTON NEWS
Journal: JAMA (1965)

<h3>Regional Centers Advisors.—</h3> President Johnson named a National Advisory Council on Regional Medical Programs to advise the surgeon general on programs authorized by the Heart Disease, Cancer and Stroke Act. Named to it were: Michael E. De Bakey, MD, of Houston; John Willis Hurst, MD, of Atlanta; George E. Moore, MD, of Buffalo; Clark M. Millikan, MD, of the Mayo Clinic; Cornelius M. Traeger, MD, of New York; Leonidas H. Better, MD, of Chicago; Mary I. Bunting, president of Radcliffe College; Gordon Cumming, of Sacramento; Bruce Everist, MD, of Ruston, La; William Peeples, MD, Maryland health commissioner, of Baltimore; Robert J. Slater, MD, of Burlington, Vt; and James T. Howell, MD, of Detroit. William H. Stewart, MD, the surgeon general, will be chairman of the committee. <h3>Hill-Burton Controversy.—</h3> State mental health officials have written Congress protesting a federal regulation barring Hill-Burton funds for state mental institutions if the state has
Correction
Journal: BMJ (1949)

ANY QUESTIONS?I Cl.Welchii and Gas Embolism Q.-(a) What is the chemical nature of the gas produced in man by the gas-gangrene organisms (Clostridium welchii, etc.)?(b) Could the equivalent of "air embolism" be produced by this gas and lead to death from acute heart failure ?I have in mind a case in which a clostridial infection followed a septic abortion, and death took place comparatively rapidly, wit/h collapse, low blood pressure, and intenise dyspnoea, clinicallv resembling pulmontary embolus.On opening the innominate veins at necropsy large bubbles of gas escaped.A.-(a) Hydrogen and carbon dioxide in the proportion of about three parts to one. (b) No. Gas is found in consider- able quantity only in tissues rich in fermenable carbohydrate -that is, muscle and liver.It is true that a small amount would be formed from blood sugar, and the accumulation of
Bacterial Infections of Humans: Epidemiology and Control.
Journal: Annals of Internal Medicine (1983)

The Infectious Disease Society of America (1995).He was a renowned poet, but never published any of his works.He enjoyed reciting them in the classroom, in private discussions, and at social events.During his life, he set standards to which others will aspire.The world is richer for the activities of Alfred Spring Evans, and we will all be better scientists and humanitarians because of his contributions.The contents of this book were written by experts in the specific topics of each chapter, many of whom Al knew personally.
Error in Units of Measure Reported In Methods Section of the Text
Journal: JAMA Oncology (2020)

Michelle E. Melisko, MD; Mindy E. Goldman, MD; Jimmy Hwang, PhD; Amy De Luca, BA; Sally Fang, BA; Laura J. Esserman, MD; Amy J. Chien, MD; John W. Park, MD; Hope S. Rugo, MD
Leprosy in Canton
Journal: JAMA (1941)

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