tbuckley/cabot-search huggingface dataset:
Making Decisions in a COVID-19 World
Authors: Baruch Fischhoff
Journal: JAMA (2020)

Making Decisions in a COVID-19 WorldThe coronavirus disease 2019 (COVID-19) pandemic poses difficult interdependent decisions for professionals and the individuals they serve.Professionals must answer questions such as: When should clinics, schools, salons, meat-packing plants, movie theaters, and other entities open?When should they close because of proven, possible, or perceived problems?When should they be reopened?Individuals must answer complementary questions.When is it safe enough to visit a physician's office, get a dental check-up, shop for clothing, ride the bus, visit an aging or incarcerated relative, or go to the gym?What does it mean that some places are open but not others and in one state, but not in a bordering one?How do individuals make sense of conflicting advice about face masks, fomites, and foodstuffs?Risk analysis translates technical knowledge into terms that people can use. 1,2Done to a publication standard, risk analysis requires advanced training and substantial resources. 3However, even back-of-theenvelope calculations can help individuals make sense of otherwise bewildering choices.Combined with behavioral research, risk analysis can help explain why reasonable people sometimes make different decisions. 4Why do some people wear face masks and
Clinical competence is basic requirement for general practitioners
Authors: 刘岚, 邵隽一
Journal: BMJ (2011)

全科医生是接受过全科医学专门训练,执行全科医疗,为个人、家庭和社区提供优质、方便、经济有效、一体化的医疗保健服务,进行生命、健康与疾病全方位负责式管理的医生.在我国,要求一个合格的全科医生应能胜任的工作中,首要的两条是:社区各种常见病、多发病的医疗及适宜的会诊和转诊;急、危、重病人的院前急救、转诊与出院后管理[1]。
Effect of Kaiso on immune signaling of breast cancer exosomes.
Authors: Windy Marie Dean-Colomb, Shakir Ahmed, Balasubramanyanam Karanam, Honghe Wang, Melissa Davis, William E. Grizzle, Kevin Gardner, Clayton Yates
Journal: Journal of Clinical Oncology (2020)

3088 Background: Exosomes are communication vesicles that act as mediators of intracellular transfer of genetic information, an important role in intercommunication between tumor cells and immune cells. However, the mechanism underlining this cell-cell communication is not well understanding, particularly in African American breast cancer patients. Recently, our lab has demonstrated that Kaiso, a novel bi-modal transcription factor is highly expressed in African American breast cancer and notably, high Kaiso expression correlates with breast cancer aggressiveness and the disparity in survival outcomes of breast cancer patients of African American compared to European American patients. However, the differential expression and biological consequences of Kaiso in immune signaling of breast cancer exosomes has not been studied yet. Herein we demonstrate the biological role of Kaiso in immune signaling in breast cancer exosomes. Methods: In this study we utilized Nanostring immune profiling technology along with multiple in vitro and in vivo assays were used to study the role of Kaiso in breast cancer immune escape. Results: Nanostring pan cancer immune profiling demonstrated that European American breast cancer exosomes exhibited higher expression of TILs markers, T cell activation markers and CD8 + T Cells markers compared to African American (p &lt; 0.05, FDR), while we observed an increase in the expression of the anti-phagocytic molecule CD47 in breast cancer patient exosomes of African American compared to European American patients. In addition to that CD47 and SIRP-α (Signal Regulatory Protein) are highly expressed in Kaiso-scrambled MDA-MB-231 cells (sh-Scr) and exosomes, whereas THBS1, which is a regulator of CD47 expression and is regarded as angiogenesis inhibitor is significantly increased in sh-Kaiso MDA-231 cells and exosomes. Additionally, we observed that Kaiso directly binds methylated sequences in the promoter region of CD47 and THBS1 by ChIP assay. Furthermore, in vivo sh-Kaiso cells injected into athymic mice exhibited delayed tumor formation after four weeks with smaller tumor size as compared to sh-SCR cells (p &lt; 0.05), and we observed higher expression of THBS1 with lower expression of CD47 and SIRP-α molecules by IHC and exosomes isolated from in vivo tumors (p &lt; 0.05), indicating that Kaiso is associated with macrophage mediated immune escape. Conclusions: These findings demonstrate the important role of kaiso in immune signaling through exosomes which may be related with more aggressive cancer phenotype in breast cancer, especially in African Americans.
Rapid response infrastructure for pandemic preparedness in a tertiary care hospital: lessons learned from the COVID-19 outbreak in Cologne, Germany, February to March 2020
Authors: Max Augustin, Philipp Schommers, Isabelle Suárez, Philipp Koehler, Henning Gruell, Florian Klein, Christian Maurer, Petra Langerbeins, Vanessa Priesner, Kirsten Schmidt-Hellerau, Jakob J Malin, Melanie Stecher, Norma Jung, Gerhard Wiesmüller, Arne Meissner, Janine Zweigner, Georg Langebartels, Felix Kolibay, Victor Suárez, Volker Burst, Philippe Valentin, Dirk Schedler, Oliver A Cornely, Michael Hallek, Gerd Fätkenheuer, Jan Rybniker, Clara Lehmann
Journal: Eurosurveillance (2020)

The coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.
Transmissibility of influenza during the 21st-century epidemics, Spain, influenza seasons 2001/02 to 2017/18
Authors: Lidia Redondo-Bravo, Concepción Delgado-Sanz, Jesús Oliva, Tomás Vega, Jose Lozano, Amparo Larrauri
Journal: Eurosurveillance (2020)

BackgroundUnderstanding influenza seasonality is necessary for determining policies for influenza control.AimWe characterised transmissibility during seasonal influenza epidemics, including one influenza pandemic, in Spain during the 21th century by using the moving epidemic method (MEM) to calculate intensity levels and estimate differences across seasons and age groups.MethodsWe applied the MEM to Spanish Influenza Sentinel Surveillance System data from influenza seasons 2001/02 to 2017/18. A modified version of Goldstein's proxy was used as an epidemiological-virological parameter. We calculated the average starting week and peak, the length of the epidemic period and the length from the starting week to the peak of the epidemic, by age group and according to seasonal virus circulation.ResultsIndividuals under 15 years of age presented higher transmissibility, especially in the 2009 influenza A(H1N1) pandemic. Seasons with dominance/co-dominance of influenza A(H3N2) virus presented high intensities in older adults. The 2004/05 influenza season showed the highest influenza-intensity level for all age groups. In 12 seasons, the epidemic started between week 50 and week 3. Epidemics started earlier in individuals under 15 years of age (-1.8 weeks; 95% confidence interval (CI):-2.8 to -0.7) than in those over 64 years when influenza B virus circulated as dominant/co-dominant. The average time from start to peak was 4.3 weeks (95% CI: 3.6-5.0) and the average epidemic length was 8.7 weeks (95% CI: 7.9-9.6).ConclusionsThese findings provide evidence for intensity differences across seasons and age groups, and can be used guide public health actions to diminish influenza-related morbidity and mortality.
Naloxone and acute organophosphorus pesticide poisoning-related respiratory failure
Authors: Jia-guo Wu
Journal: BMJ (2008)

This study was to examine the influence of Naloxone on respiratory failure among patients with acute organophosphorus pesticide poisoning(AOPP). From June 1997 to May 2000, 106 AOPP-related respiratory failure patients were assigned to the control group. During June 2000 to September 2002, 83matched patients were assigned to the treatment group and obtained intravenous Naloxone injection. Duration of mechanical ventilation was recorded. In comparison to the treatment group, the control group showed prolonged mechanical ventilation[(342±123)h vs(235±89)h;t=6. 92, P＜0. 01], demonstrating that intravenous Naloxone injection may promote the reoccurrence of independence-breathing in AOPP-related respiratory failure patients. 

Key words: 
Poisoning; Naloxone
克拉玛依市居民家庭健康询问调查分析
Authors: 钱建荣, 杨淑梅, 马宁, 姜静, 艾尔肯
Journal: BMJ (2005)

我们于2002至2003年在克拉玛依市调查样本区居民的2周患病率、慢性病患病率和因病伤而丧失劳动力的失能率等,评价我市居民的健康水平、存在的主要健康问题及卫生服务需求量,了解居民医疗保健负担能力及医疗保障制度改革对居民卫生服务需求的影响,现报告如下。
Epithelial cell dysfunction, a major driver of asthma development
Authors: Irene H. Heijink, Virinchi N. S. Kuchibhotla, Mirjam P. Roffel, Tania Maes, Darryl A. Knight, Ian Sayers, Martijn C. Nawijn
Journal: Allergy (2020)

Airway epithelial barrier dysfunction is frequently observed in asthma and may have important implications. The physical barrier function of the airway epithelium is tightly interwoven with its immunomodulatory actions, while abnormal epithelial repair responses may contribute to remodelling of the airway wall. We propose that abnormalities in the airway epithelial barrier play a crucial role in the sensitization to allergens and pathogenesis of asthma. Many of the identified susceptibility genes for asthma are expressed in the airway epithelium, supporting the notion that events at the airway epithelial surface are critical for the development of the disease. However, the exact mechanisms by which the expression of epithelial susceptibility genes translates into a functionally altered response to environmental risk factors of asthma are still unknown. Interactions between genetic factors and epigenetic regulatory mechanisms may be crucial for asthma susceptibility. Understanding these mechanisms may lead to identification of novel targets for asthma intervention by targeting the airway epithelium. Moreover, exciting new insights have come from recent studies using single-cell RNA sequencing (scRNA-Seq) to study the airway epithelium in asthma. This review focuses on the role of airway epithelial barrier function in the susceptibility to develop asthma and novel insights in the modulation of epithelial cell dysfunction in asthma.
A new understanding of glucocorticoids in treatment of autoimmune diseases
Authors: Jinquan Yu, Xiuyan Yang
Journal: BMJ (2017)

糖皮质激素是临床上应用最广、争议最多的药物。通过介绍糖皮质激素的种类，讨论如何选择和应用糖皮质激素，以降低其不良反应，同时讨论了自身免疫性疾病如何由过去的强调终生使用糖皮质激素，演变为目前的争取减停，以期提高临床医生对临床应用糖皮质激素的再认识。
Phase IIa study of marrow infiltrating lymphocytes (MILs), an adoptive T cell therapy, alone or in combination with nivolumab in non-small cell lung cancer (NSCLC).
Authors: Martin Edelman, Aaron Elliott Lisberg, Marianna Koczywas, Ben C. Creelan, Amanda Seiz, Eric Lutz, Lakshmi Rudraraju, Elizabeth DeOliveria, Monil Shah, Kim Noonan, Melissa Lynne Johnson
Journal: Journal of Clinical Oncology (2020)

TPS9630 Background: Primary or secondary resistance to anti-PD-1 may be due to loss of T cell function. Persistent antigen stimulation can lead to impaired CD8+ T cell function, which often results in acquired resistance to PD-1 inhibition. It is unclear whether reinvigoration of tumor infiltrating cells or recruitment of novel T cells impart the activity of anti-PD-1 therapy. The bone marrow is a reservoir for antigen experienced memory T cells. We have previously shown that MILs can be generated for patients with hematologic malignancies and solid tumors including patients with NSCLC. MILs are the product of the activation and expansion of bone marrow T cells with a polyantigenic memory phenotype that recognize tumor antigens, are cytotoxic to autologous tumor and are able to persist over a long period of time. In a pre-clinical study of NSCLC, MILs were able to be expanded in all patients tested. Furthermore, all of the NSCLC products tested showed specificity to shared NSCLC antigens. The combination of adoptive cell therapy (ACT) with checkpoint inhibitors (CPIs) has distinctive positive effects on CD8 and CD4 T cell subsets, with the possibility for complete tumor control. We hypothesize that patients with NSCLC who have relapsed on anti-PD-1 treatment could benefit from an infusion of non-exhausted, central memory-enhanced, antigen specific T cells i.e. MILs which can delay the induction of tumor-associated anergy and augment the overall effectiveness of immunotherapy. Methods: Patients with advanced NSCLC who have progressed following prior anti-PD-1 therapy, with sufficient bone marrow reserve and an ECOG 0-1 are eligible. In eligible patients, bone marrow (200 mL) will be harvested and processed. Patients will undergo lymphodepletion (fludarabine 300 mg/m 2 /day and cyclophosphamide 30 mg/m 2 /day on days -5,-4,-3) followed by infusion of MILs on day 0. In Part 1, up to 6 patients will be administered MILs alone on day 0. In Part 2, approximately 20 subjects will be administered MILs on day 0 followed by NIVO 480 mg Q4W starting on day 1. The objectives of the study are to assess safety of MILs alone and in combination with NIVO, as well as efficacy. The first patient was treated in December 2019. Clinical trial information: NCT04069936 .
Gastric Bypass vs Medical Treatment in Renoprotection for Patients with Class 1 Obesity, Type 2 Diabetes, and Albuminuria
Authors: Paulina Salminen, Pirjo Nuutila
Journal: JAMA Surgery (2020)

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A pilot study evaluating the safety, tolerability, and efficacy of doxorubicin and pembrolizumab in patients with metastatic or unresectable soft tissue sarcoma.
Authors: Michael B. Livingston, Megan Jagosky, Myra M. Robinson, William Ahrens, Jennifer H Benbow, Carol J. Farhangfar, David Foureau, Deirdre Maxwell, Emily Baldrige, Nury Steuerwald, Colin J Anderson, Joshua Patt, Jeffrey Kneisl, Edward S. Kim
Journal: Journal of Clinical Oncology (2020)

11519 Background: Doxorubicin has been the traditional standard therapy for treatment of advanced soft tissue sarcoma (STS). The addition of cytotoxic agents leads to increased toxicity with minimal improvement in efficacy. Pembrolizumab monotherapy has demonstrated activity and tolerability in previous study of advanced STS. This study combined pembrolizumab with doxorubicin to determine safety and efficacy in the frontline setting. Methods: This single-center, single-arm, phase 2 trial enrolled subjects with unresectable or metastatic STS and no prior anthracycline therapy. Subjects were treated with pembrolizumab 200 mg IV and doxorubicin 60 mg/m2 (75 mg/m2 dose escalation per investigator discretion) IV every 3 weeks. The primary endpoint of safety, based on Bayesian stopping rules, evaluated if the severe or life-threatening treatment emergent adverse event (TEAE) rate exceeded 0.55. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression free survival (PFS). Efficacy and safety were based on RECIST 1.1 and CTCAE v 4.0, respectively. Kaplan-Meier methods evaluated time to event outcomes. Results: From 4/2017 to 12/2019, 30 subjects (53% female, median age 61.5 years, 10 patients &gt; 70 years (33%)) were enrolled in the study with 6 (20%) patients still on treatment and 27 evaluable for response. The most common histologic subtypes were leiomyosarcoma (33%) and liposarcoma (23%), and a majority of patients demonstrated high grade disease (60%). Current analysis shows a median follow-up of 9.9 months. One subject experienced a stopping rule event (grade 3 autoimmune disorder). ORR was 33% (95% CI 17-54%), with documented disease control in 78% (95% CI 57.7-91.4%) of patients. Eight (30%) patients achieved a partial response, one (4%) patient achieved a complete response and 12 (44%) patients had stable disease. Preliminary results demonstrate median PFS of 6.9 months (PFS-6 mo: 52%) and median OS of 15 months (OS-6 mo: 81%) compared to historical PFS-6mo of 4.6 months and OS of 12.8 months with doxorubicin alone. 1 Most common grade 3+ TEAEs included neutropenia (11 [37%]), febrile neutropenia (6 [20%]), anemia (5 [17%]), and nausea (4 [13%]). Molecular and biomarker analysis is currently in progress. Conclusions: The combination of pembrolizumab with doxorubicin has manageable toxicity and preliminary promising activity in the treatment of anthracycline-naive advanced soft tissue sarcomas. Ref: 1. Lancet Oncol. 2014 Apr; 15(4):415-23. Clinical trial information: NCT03056001 .
A randomized phase II multi-institutional trial of anlotinib plus docetaxel versus docetaxel in EGFR-wild-type non-small cell lung cancer (NSCLC) patients after progression on first-line platinum-base chemotherapy: ALTER-L018.
Authors: Lin Wu, Zhijun Wu, Zemin Xiao, Jie Weng, Zhongsha Ma, Yanhua Chen, Maoliang Xiao, Yongqing Cao, Huaxin Duan, Peiguo Cao, Hui Zhang, Qianzhi Wang, Jia Li, Yan Xu, Xingxiang Pu, Kang Li
Journal: Journal of Clinical Oncology (2020)

e21703 Background: Anlotinib is an oral VEGFR, FGFR, PDGFR and c-Kit tyrosine kinase inhibitor, which can prolong both PFS and OS of refractory advanced NSCLC patients in phase III trial: ALTER0303. The combination of docetaxel and ramucirumab/nintedanib had been demonstrated activity in the second line therapy setting for NSCLC. We performed ALTER-L018 to assessed the safety and efficacy of anlotinib with docetaxel in EGFR-wild type refractory advanced NSCLC (NCT03624309). Methods: Patients (pts) with EGFR-wild type refractory advanced NSCLC, who failed to first-line platinum-based chemotherapy, were randomized to group A(anlotinib: 12mg QD from day 1 to 14 of a 21-day cycle +docetaxel: 75mg/m2 Q3W) and group B(docetaxel: 75mg/m2 Q3W). The primary end points is PFS, and secondary end points include OS, ORR, DCR and safety. Results: Between January and December 2019, 36 pts were enrolled at 10 institutions in Hunan China, with 31(15 in group A, 16 in group B) of these individuals being evaluable for treatment efficacy and safety. Pt characteristics(group A/ group B): median age: 55(39-70)/57(44-67); male: 73%/81%; non-squamous NSCLC: 86%/75%. Median PFS were 5.3 months (95%CI:2.76-7.85) in group A and 2.3 months (95%CI, 1.14-3.46) in group B (HR 0.42; 95% CI:0.16-1.13; p = 0.047); In group A and B, ORR and DCR were 26.67% versus 0%(p = 0.043), 60.00% versus 31.25%(p = 0.16), respectively. Among 31 pts, 89% of treatment-related AEs (TRAEs) were grade 1 or 2, and the most common TRAEs in group A were hand-foot syndrome, pruritus and insomnia of 13%(2/15) each; in group B were alopecia, constipation and anemia of 12%(1/16) each. Toxicities≥grade 3(TRAEs) included: neutropenia, leukopenia, diarrhea and hrombocytopenia, 6.6%(1/15) each in group A. There was 1 grade 5 AE in group A. Conclusions: This combination of anlotinib and docetaxel with significant difference PFS prolonging and manageable safety profile, is a viable option in relapsed NSCLC, should be considered following progression on platinum-based chemotherapy. It will be further explored in a randomized phase III trial. Clinical trial information: NCT03624309.
The pattern of time to onset and resolution of immune-related adverse events caused by immune checkpoint inhibitors in cancer: A pooled analysis of 23 clinical trials and 8,436 patients.
Authors: Si-Qi Tang, Cheng Xu, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Lei Chen, Yuan Zhang, Ying Guo, Qing Liu, Ying Sun, Jun Ma
Journal: Journal of Clinical Oncology (2020)

e15110 Background: Immune checkpoint inhibitors (ICIs) yield remarkable clinical efficacy in the treatment of cancer. With the increasing use of ICI therapies, the dissemination of immune-related adverse events (irAEs) data is essential. This study aimed to investigate the pattern of onset and resolution of ICI-induced irAEs in cancer. Methods: Phase II–III clinical trials with single or multiple arms studying ICI-based treatments in cancer published between January 2007 and December 2019 were included. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were analyzed based on irAE categories and severity grades using the metamedian package of the R software. Subgroup analyses were performed based on different ICI drugs, ICI doses, and cancer types. Results: Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. On average, irAEs occurred at 6.1 weeks (95% confidence interval [95% CI], 5.7–7.4) after the initial ICI-based treatment. The first four irAEs with the shortest PMT-O were hypersensitivity/infusion reaction (3.1 weeks), neurological (4.0 weeks), skin (4.1 weeks), and gastrointestinal (6.1 weeks) events. IrAEs were resolved within 4.5 weeks (95% CI, 4.0–6.1), with the shortest and longest PMT-R for hypersensitivity/infusion reaction (0.1 weeks) and endocrine events (28.7 weeks), respectively. The application of immune-modulation drugs prolonged the general resolution time to 5.9 weeks, with the shortest and longest PMT-IMR for hypersensitivity/infusion reaction (0.2 weeks) and endocrine events (56.6 weeks), respectively. Grade ≥ 3 irAEs showed a significantly longer PMT-O (7.9 vs. 6.1 weeks; P &lt; 0.01) compared with all grade irAEs. Nivolumab + ipilimumab had a significantly shorter PMT-O than nivolumab alone (6.0 vs. 8.2 weeks; P &lt; 0.01). A significantly shorter PMT-O was observed for lung cancer compared with that for melanoma (4.7 vs. 6.1 weeks; P = 0.02). Conclusions: This study revealed the pattern and kinetics of the time to onset and resolution of irAEs in pan-cancers, which will promote the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.