tbuckley/cabot-search huggingface dataset:
Liposomal irinotecan (nal-IRI) plus 5-fluorouracil/levoleucovorin (5 FU/LV) vs 5-FU/LV in Japanese patients (pts) with gemcitabine-refractory metastatic pancreatic cancer (mPAC)
Authors: T. Ioka, S. Nakamori, K. Sugimori, M. Kanai, M. Ikeda, M. Ozaka, M. Furukawa, T. Okusaka, K. Kawabe, J. Furuse, Y. Komatsu, A. Sato, S. Shimizu, P. Chugh, R. Tang, M. Ueno
Journal: Annals of Oncology (2019)
Environmental unpredictability, economic inequality, and dynamic nature of life history before, during, and after the Industrial Revolution
Authors: Bin-Bin Chen, Wen Han
Journal: Behavioral and Brain Sciences (2019)

Abstract It is emphasized that environmental predictability is another important condition that plays roles in slow strategies that are related to innovation; that economic inequality, except as measured by Gross Domestic Product (GDP) per capita, influences innovation; and that switching global life history from a slow to a fast strategy is a response adopted in response to new challenges during the post-Industrial Revolution period.
CX3CR1–fractalkine axis drives kinetic changes of monocytes in fibrotic interstitial lung diseases
Authors: Flavia R. Greiffo, Valeria Viteri-Alvarez, Marion Frankenberger, Daniela Dietel, Almudena Ortega-Gomez, Joyce S. Lee, Anne Hilgendorff, Jürgen Behr, Oliver Soehnlein, Oliver Eickelberg, Isis E. Fernandez
Journal: European Respiratory Journal (2019)

Circulating immune cell populations have been shown to contribute to interstitial lung disease (ILD). In this study, we analysed circulating and lung resident monocyte populations, and assessed their phenotype and recruitment from the blood to the lung in ILD. Flow cytometry analysis of blood samples for quantifying circulating monocytes was performed in 105 subjects: 83 with ILD (n=36, n=28 and n=19 for nonspecific interstitial pneumonia, hypersensitivity pneumonitis and connective-tissue disease-associated ILD, respectively), as well as 22 controls. Monocyte localisation and abundance were assessed using immunofluorescence and flow cytometry of lung tissue. Monocyte populations were cultured either alone or with endothelial cells to assess fractalkine-dependent transmigration pattern. We show that circulating classical monocytes (CM) were increased in ILD compared with controls, while nonclassical monocytes (NCM) were decreased. CM abundance correlated inversely with lung function, while NCM abundance correlated positively. Both CCL2 and CX3CL1 concentrations were increased in plasma and lungs of ILD patients. Fractalkine co-localised with ciliated bronchial epithelial cells, thereby creating a chemoattractant gradient towards the lung. Fractalkine enhanced endothelial transmigration of NCM in ILD samples only. Immunofluorescence, as well as flow cytometry, showed an increased presence of NCM in fibrotic niches in ILD lungs. Moreover, NCM in the ILD lungs expressed increased CX3CR1, M2-like and phagocytic markers. Taken together, our data support that in ILD, fractalkine drives the migration of CX3CR1 + NCM to the lungs, thereby perpetuating the local fibrotic process.
Immune dysregulation increases the incidence of delayed‐type drug hypersensitivity reactions
Authors: Dean J. Naisbitt, Anna Olsson‐Brown, Andrew Gibson, Xiaoli Meng, Monday O. Ogese, Arun Tailor, Paul Thomson
Journal: Allergy (2019)

Abstract Delayed‐type, T cell–mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human population. Drugs and drug metabolites are known to interact directly and indirectly (through irreversible protein binding and processing to the derived adducts) with HLA proteins that present the drug‐peptide complex to T cells. Multiple forms of drug hypersensitivity are strongly linked to expression of a single HLA allele, and there is increasing evidence that drugs and peptides interact selectively with the protein encoded by the HLA allele. Despite this, many individuals expressing HLA risk alleles do not develop hypersensitivity when exposed to culprit drugs suggesting a nonlinear, multifactorial relationship in which HLA risk alleles are one factor. This has prompted a search for additional susceptibility factors. Herein, we argue that immune regulatory pathways are one key determinant of susceptibility. As expression and activity of these pathways are influenced by disease, environmental and patient factors, it is currently impossible to predict whether drug exposure will result in a health benefit, hypersensitivity or both. Thus, a concerted effort is required to investigate how immune dysregulation influences susceptibility towards drug hypersensitivity.
Phase II, open-label study of pembrolizumab in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy: KEYNOTE-667
Authors: C. Mauz-koerholz, K. Kelly, F. Keller, R. Ramchandren, A. Nahar, L. Giulino-Roth
Journal: Annals of Oncology (2019)
Genomic profiling: Shared decision making and emotional well-being among patients with metastatic genitourinary cancers.
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Errol James Philip, Meghan Salgia, Nicholas Salgia, Nazli Dizman, Joann Hsu, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2019)

31 Background: Little is known regarding patients’ beliefs concerning genomic profiling (GP) and its potential association with emotional well-being. We examined essential components of shared decision-making in the context of GP and their relationship to symptoms of anxiety (SAnx) and of depression (SDep) among patients with metastatic genitourinary cancers. Methods: Patients were recruited from a single institution after receiving a standardized dialogue about GP from their oncologist. Patients were included if they had received GP in the context of routine clinical care, and assessed across a range of perceptions related to GP (e.g., communication, expectations, risks associated, reasons and hopes), SAnx (PROMIS-Anxiety) and SDep (PROMIS-Depression). The Kruskal-Wallis test was used. Results: Seventy patients with incurable genitourinary cancers (60% kidney, 21% prostate and 18% bladder cancers) were surveyed. Patients reported that information about GP was presented clearly (95%), comprehensively (94%), accurately (92%), and compassionately (98%), and most felt they possessed a good understanding of GP (78%). No significant differences emerged between patients with or without SAnx or SDep. Patients reported similar reasons for pursuing GP, including to help guide treatment decision making and to follow their physician’s suggestion. Notably, those with SAnx or SDep were more likely to report a desire for information that could help predict their disease outcome (20% and 33%) compared to patients without SAnx or SDep (0%) (P &lt; 0.05). Those with SDep tended to report a desire for GP to improve their treatment response compared to those without SDep (42% vs. 21%, P = 0.04). Compared to those without SDep, patients with SDep were more likely to report a belief that GP could reveal a cure to their disease (73% vs. 50%, P = 0.01). Conclusions: Our findings reinforce the importance of effective counselling in the context of complex medical decision-making. SAnx and SDep may be associated with erroneous beliefs or expectations the role of GP in treatment. Given the complexity of GP, interventions are needed to enhance patients' understanding of these tests and therapeutic implications.
Activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in keratinocytes promotes cutaneous T-cell response in patients with vitiligo
Authors: Shuli Li, Pan Kang, Weigang Zhang, Zhe Jian, Qian Zhang, Xiuli Yi, Sen Guo, Weinan Guo, Qiong Shi, Bing Li, Yuanmin He, Pu Song, Ling Liu, Kai Li, Gang Wang, Tianwen Gao, Chunying Li
Journal: Journal of Allergy and Clinical Immunology (2019)
Exercise for preventing falls in older people living in the community: an abridged Cochrane systematic review
Authors: Cathie Sherrington, Nicola Fairhall, Geraldine Wallbank, Anne Tiedemann, Zoe A Michaleff, Kirsten Howard, Lindy Clemson, Sally Hopewell, Sarah Lamb
Journal: British Journal of Sports Medicine (2019)

To assess the effects of exercise interventions for preventing falls in older people living in the community.We included randomised controlled trials evaluating the effects of any form of exercise as a single intervention on falls in people aged 60+years living in the community.Exercise reduces the rate of falls by 23% (rate ratio (RaR) 0.77, 95% CI 0.71 to 0.83; 12 981 participants, 59 studies; high-certainty evidence). Subgroup analyses showed no evidence of a difference in effect on falls on the basis of risk of falling as a trial inclusion criterion, participant age 75 years+ or group versus individual exercise but revealed a larger effect of exercise in trials where interventions were delivered by a health professional (usually a physiotherapist). Different forms of exercise had different impacts on falls. Compared with control, balance and functional exercises reduce the rate of falls by 24% (RaR 0.76, 95% CI 0.70 to 0.81; 7920 participants, 39 studies; high-certainty evidence). Multiple types of exercise (commonly balance and functional exercises plus resistance exercises) probably reduce the rate of falls by 34% (RaR 0.66, 95% CI 0.50 to 0.88; 1374 participants, 11 studies; moderate-certainty evidence). Tai Chi may reduce the rate of falls by 19% (RaR 0.81, 95% CI 0.67 to 0.99; 2655 participants, 7 studies; low-certainty evidence). We are uncertain of the effects of programmes that primarily involve resistance training, dance or walking.Given the certainty of evidence, effective programmes should now be implemented.
Efficacy and safety of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial
Authors: J.S.-T. Pang, N. Shore, M.R. Smith, T.L. Tammela, A. Ulys, E. Vjaters, S. Polyakov, M. Jievaltas, M. Luz, B. Alekseev, I. Kuss, M.-A. Le Berre, A. Snapir, T. Sarapohja, K. Fizazi
Journal: Annals of Oncology (2019)
Predicting a “Lazarus Effect” in Patients With Advanced Cancer Near the End of Life: Prognostic Uncertainty, Oncologists’ Emotions, and Ethical Questions
Authors: Chithra R. Perumalswami, Reshma Jagsi, Susan Dorr Goold
Journal: The American Journal of Bioethics (2019)

I think if the crystal ball is telling me this guy is going to die in a week no matter what you do, you don’t treat him. Period. But it’s just not always that clear cut.—Oncologist. (Bluhm et al. 2...
Dynamic change of anti‐inflammatory cytokine IL‐35 in allergen immune therapy for Japanese cedar pollinosis
Authors: Hideaki Kouzaki, Masahiko Arikata, Matsumoto Koji, Hiroyuki Arai, Sayuri Yamamoto, Hirotaka Kikuoka, Noriki Fujimoto, Yukiko Ogawa, Atsushi Yuta, Takeshi Shimizu
Journal: Allergy (2019)

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Allergen-specific IgE levels and the ability of IgE-allergen complexes to cross-link determine the extent of CD23-mediated T-cell activation
Authors: Sergio Villazala-Merino, Azahara Rodriguez-Dominguez, Victoria Stanek, Nicholas J. Campion, Pia Gattinger, Gerhard Hofer, Renate Froeschl, Ingrid Fae, Christian Lupinek, Susanne Vrtala, Heimo Breiteneder, Walter Keller, Thomas Perkmann, Ryosuke Nakamura, Winfried F. Pickl, Rudolf Valenta, Julia Eckl-Dorna, Verena Niederberger
Journal: Journal of Allergy and Clinical Immunology (2019)

CD23 mediates IgE-facilitated allergen presentation and subsequent allergen-specific T-cell activation in allergic patients.We sought to investigate key factors regulating IgE-facilitated allergen presentation through CD23 and subsequent T-cell activation.To study T-cell activation by free allergens and different types of IgE-Bet v 1 complexes, we used a molecular model based on monoclonal human Bet v 1-specific IgE, monomeric and oligomeric Bet v 1 allergen, an MHC-matched CD23-expressing B-cell line, and a T-cell line expressing a human Bet v 1-specific T-cell receptor. The ability to cross-link Fcε receptors of complexes consisting of either IgE and monomeric Bet v 1 or IgE and oligomeric Bet v 1 was studied in human FcεRI-expressing basophils. T-cell proliferation by monomeric or oligomeric Bet v 1, which cross-links Fcε receptors to a different extent, was studied in allergic patients' PBMCs with and without CD23-expressing B cells.In our model non-cross-linking IgE-Bet v 1 monomer complexes, as well as cross-linking IgE-Bet v 1 oligomer complexes, induced T-cell activation, which was dependent on the concentration of specific IgE. However, T-cell activation by cross-linking IgE-Bet v 1 oligomer complexes was approximately 125-fold more efficient. Relevant T-cell proliferation occurred in allergic patients' PBMCs only in the presence of B cells, and its magnitude depended on the ability of IgE-Bet v 1 complexes to cross-link CD23.The extent of CD23-mediated T-cell activation depends on the concentration of allergen-specific IgE and the cross-linking ability of IgE-allergen complexes.
Facial Dermatitis in Male Patients Referred for Patch Testing
Authors: Erin M. Warshaw, Jamie P. Schlarbaum, Howard I. Maibach, Jonathan I. Silverberg, James S. Taylor, Amber R. Atwater, Margo J. Reeder, Joel G. DeKoven, Melanie D. Pratt, Vincent A. DeLeo, Kathryn A. Zug, Anthony F. Fransway, Donald V. Belsito, Toby Mathias, Joseph F. Fowler, James G. Marks, Denis Sasseville, Matthew J. Zirwas
Journal: JAMA Dermatology (2019)

Facial dermatitis in women is well characterized. However, recent shifts in the men's grooming industry may have important implications for male facial dermatitis.To characterize male patients with facial dermatitis.A 22-year retrospective cross-sectional analysis (1994-2016) of North American Contact Dermatitis Group (NACDG) data, including 50 507 patients who underwent patch testing by a group of dermatology board-certified patch test experts at multiple centers was carried out. Facial dermatitis was defined as involvement of the eyes, eyelids, lips, nose, or face (not otherwise specified).The main outcome was to compare characteristics (including demographics and allergens) between male patients with facial dermatitis (MFD) and those without facial dermatitis (MNoFD) using statistical analysis (relative risk, CIs). Secondary outcomes included sources of allergic and irritant contact dermatitis and, for occupationally related cases, specific occupations and industries in MFD.Overall, 1332 male patients (8.0%) were included in the MFD group and 13 732 male patients (82.0%) were included in MNoFD. The mean (SD) age of participants was 47 (17.2) years in the MFD group and 50 (17.6) years in the MNoFD group. The most common facial sites were face (not otherwise specified, 817 [48.9%]), eyelids (392 [23.5%]), and lips (210 [12.6%]). Participants in the MFD group were significantly younger than MNoFD (mean age, 47 vs 50 years; P < .001). Those in the MFD group were less likely to be white (relative risk [RR], 0.92; 95% CI, -0.90 to 0.95) or have occupationally related skin disease (RR, 0.49; 95% CI, -0.42 to 0.58; P < .001) than MNoFD. The most common allergens that were associated with clinically relevant reactions among MFD included methylisothiazolinone (n = 113; 9.9%), fragrance mix I (n = 27; 8.5%), and balsam of Peru (n = 90; 6.8%). Compared with MNoFD, MFD were more likely to react to use of dimethylaminopropylamine (RR, 2.49; 95% CI, -1.42 to 4.37]) and paraphenylenediamine (RR, 1.43; 95% CI, -1.00 to 2.04; P < .001). Overall, 60.5% of NACDG allergen sources were personal care products.Although many allergens were similar in both groups, MFD were more likely to react to use of dimethylaminopropylamine and paraphenylenediamine, presumably owing to their higher prevalence in hair products. Most sources of allergic and irritant contact dermatitis in MFD were personal care products. This study provides insight into the risks and exposures of the increasing number of grooming products used by male dermatology patients. This will enable clinicians to better identify male patients who would benefit from patch testing and treat those with facial dermatitis.
Perioperative Eltrombopag or Intravenous Immune Globulin for Patients with Immune Thrombocytopenia: A Multicenter Randomized Trial
Authors: Donald M. Arnold, Nancy Heddle, Richard Cook, Cyrus C. Hsia, Mark Blostein, Erin Jamula, Michelle Sholzberg, Yulia Lin, Jeannine Kassis, Loree Larratt, Sufia Amini, Martin R. Schipperus, Wendy Lim, Prakash Vishnu, Margaret Warner, Julie Carruthers, Shannon J Lane, Na Li, John G. Kelton
Journal: Blood (2019)
Going Beyond Results of the PEMBRO-RT Trial
Authors: Bo Zhang, Baohui Han
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Reliability of Leukostasis Grading Score to Identify High Risk Patients with Hyperleukocytic Leukemia
Authors: Nicola Piccirillo, Luca Laurenti, Patrizia Chiusolo, Federica Sorà, Maria Bianchi, Silvia De Matteis, Livio Pagano, Gina Zini, Giuseppe d’Onofrio, Giuseppe Leone, Simona Sica
Journal: Blood (2008)
Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management
Authors: Natasha Szuber, Michelle Elliott, Ayalew Tefferi
Journal: American Journal of Hematology (2019)

Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow granulocyte hyperplasia, and frequent hepatosplenomegaly. The seminal discovery of oncogenic driver mutations in colony-stimulating factor 3 receptor (CSF3R) in the majority of patients with CNL in 2013 anchored a new scientific framework, deepening our understanding of its molecular pathogenesis, providing a diagnostic biomarker, and rationalizing the use of pharmacological targeting.In 2016, the World Health Organization (WHO) included the presence of activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 × 109 /L comprising >80% neutrophils with <10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN.Increasingly comprehensive genetic profiling of CNL has disclosed a complex genomic landscape and additional prognostically relevant mutational combinations. Though prognostic determination and therapeutic decision-making remain challenging, emerging data on prognostic markers and the use of newer therapeutic agents, such as JAK inhibitors, are helping to define state-of-the-art management in CNL.
Measles: Samoa declares emergency as cases continue to spike worldwide
Authors: Owen Dyer
Journal: BMJ (2019)

Samoa is fighting a “huge outbreak” of measles, the World Health Organization has said, a year after a vaccine scare resulted in a collapse of immunisation rates.

So far 42 people have died from measles, almost all young children, and 3149 cases have been reported on the six islands that make up the Pacific nation, inhabited by about 200 000 people. Every day about 200 people with suspected cases arrive at hospital, said Ian Norton of WHO’s emergency medical unit, speaking to reporters from Geneva. The main hospital in the capital, Apia, which normally has four beds in its intensive care ward, currently has 14 children on ventilators, he said.

The government has closed …
Immunoscore predicts significant differences in time to recurrence in stage I colon cancer patients
Authors: J. Galon, F. Hermitte, B. Mlecnik, F. Marliot, C. Bifulco, A. Lugli, I. Nagtegaal, A. Hartmann, M. van den Eynde, M. Roehrl, P. Ohashi, E. Zavadova, T. Torigoe, P. Patel, Y. Wang, Y. Kawakami, F. Marincola, P. Ascierto, B. Fox, F. Pagès
Journal: Annals of Oncology (2019)
Abstract 360: Effects of Different Doses of Pralidoxime Administered During Cardiopulmonary Resuscitation and the Role of Alpha-Adrenergic Receptors in its Pressor Action
Authors: Najmiddin Mamadjonov, Yong Hun Jung, Hyoung Youn Lee, Kyung Woon Jeung, Byung Kook Lee, Chun Song YOUN, Tag Heo, Yong Il Min
Journal: Circulation (2019)

Introduction: We previously reported that pralidoxime potentiated the pressor effect of epinephrine and improved restoration of spontaneous circulation (ROSC) rate and short-term survival in pigs undergoing cardiopulmonary resuscitation (CPR). We sought to explore the optimal dose of pralidoxime to be used during CPR and to evaluate the involvement of α-adrenoceptors in its pressor action. Methods: In the first substudy, 44 pigs randomly received one of three doses of pralidoxime (40, 80, or 120 mg/kg) or saline placebo during CPR. All animals were given epinephrine every 3 minutes. In the second substudy, 49 rats were divided into 7 groups. In the first 4 groups, the effects of 40 mg/kg pralidoxime on arterial pressure were determined after pretreatment with saline, guanethidine, phenoxybenzamine, or phentolamine. In the other 3 groups, the effects of 200 mg/kg pralidoxime were determined after pretreatment with saline, propranolol, or phentolamine. Results: In the first substudy, 40 mg/kg pralidoxime resulted in the highest coronary perfusion pressure (CPP) among the groups, while 120 mg/kg pralidoxime resulted in the lowest CPP (group effect P &lt;0.001). Sustained ROSC was attained in 4 (36.4%), 11 (100%), 9 (81.8%), and 3 (27.3%) animals in the saline, 40 mg/kg, 80 mg/kg, and 120 mg/kg groups, respectively ( P &lt;0.001). In the second substudy, 40 mg/kg pralidoxime elicited a pressor response. Phenoxybenzamine completely inhibited the pressor response, but guanethidine and phentolamine did not. The pressor response of pralidoxime was even greater after pretreatment with guanethidine or phentolamine. Two-hundred mg/kg pralidoxime produced an initial vasodepressor response followed by a delayed pressor response. Phentolamine eliminated the initial vasodepressor response and reversed it into a pressor response. Conclusions: Forty mg/kg of pralidoxime administered with epinephrine led to a significantly higher ROSC rate by improving CPP in a pig model of cardiac arrest, whereas 120 mg/kg did not improve CPP or the ROSC rate. Our findings suggest that the pressor effect of pralidoxime is unrelated to α-adrenoceptors and that its pressor effect is buffered by its vasodepressor action mediated by the inhibition of the sympathetic nervous system.
Simultaneous detection of genotype and phenotype enables rapid and accurate antibiotic susceptibility determination
Authors: Roby P. Bhattacharyya, Nirmalya Bandyopadhyay, Peijun Ma, Sophie S. Son, Jamin Liu, Lorrie L. He, Lidan Wu, Rustem Khafizov, Rich Boykin, Gustavo C. Cerqueira, Alejandro Pironti, Robert F. Rudy, Milesh M. Patel, Rui Yang, Jennifer Skerry, Elizabeth Nazarian, Kimberly A. Musser, Jill Taylor, Virginia M. Pierce, Ashlee M. Earl, Lisa A. Cosimi, Noam Shoresh, Joseph Beechem, Jonathan Livny, Deborah T. Hung
Journal: Nature Medicine (2019)