tbuckley/cabot-search huggingface dataset:
Tumor-Contacted Neutrophils Promote Metastasis by a CD90-TIMP-1 Juxtacrine–Paracrine Loop
Authors: Ying Wang, Jianing Chen, Linbin Yang, Jiaqian Li, Wei Wu, Min Huang, Ling Lin, Shicheng Su
Journal: Clinical Cancer Research (2018)

The different prognostic values of tumor-infiltrating neutrophils (TIN) in different tissue compartments are unknown. In this study, we investigated their different prognostic roles and the underlying mechanism.Experimental Design: We evaluated CD66b+ neutrophils in primary tumors from 341 patients with breast cancer from Sun Yat-sen Memorial Hospital by IHC. The association between stromal and parenchymal neutrophil counts and clinical outcomes was assessed in a training set (170 samples), validated in an internal validation set (171 samples), and further confirmed in an external validation set (105 samples). In addition, we isolated TINs from clinical samples and screened the cytokine profile by antibody microarray. The interaction between neutrophils and tumor cells was investigated in transwell and 3D Matrigel coculture systems. The therapeutic potential of indicated cytokines was evaluated in tumor-bearing immunocompetent mice.We observed that the neutrophils in tumor parenchyma, rather than those in stroma, were an independent poor prognostic factor in the training [HR = 5.00, 95% confidence interval (CI): 2.88-8.68, P < 0.001], internal validation (HR = 3.56, 95% CI: 2.07-6.14, P < 0.001), and external validation set (HR = 5.07, 95% CI: 2.27-11.33, P < 0.001). The mechanistic study revealed that neutrophils induced breast cancer epithelial-mesenchymal transition (EMT) via tissue inhibitor of matrix metalloprotease (TIMP-1). Reciprocally, breast cancer cells undergoing EMT enhanced neutrophils' TIMP-1 secretion by CD90 in a cell-contact manner. In vivo, TIMP-1 neutralization or CD90 blockade significantly reduced metastasis. More importantly, TIMP-1 and CD90 were positively correlated in breast cancer (r2 = 0.6079; P < 0.001) and associated with poor prognosis of patients.Our findings unravel a location-dictated interaction between tumor cells and neutrophils and provide a rationale for new antimetastasis treatments.
Rational design of temperature-sensitive blood-vessel-embolic nanogels for improving hypoxic tumor microenvironment after transcatheter arterial embolization
Authors: Ling Li, Yiming Liu, Han Li, Xiaopeng Guo, Xiaojun He, Shinan Geng, Hao Zhao, Xiaole Peng, Dingwen Shi, Bin Xiong, Guofeng Zhou, Yanbing Zhao, Chuansheng Zheng, Xiangliang Yang
Journal: Theranostics (2018)

Transcatheter arterial embolization (TAE) plays an important role in clinical tumor therapy by accomplishing vessel-casting embolization of tumor arteries at all levels and suppressing tumor collateral circulation and vascular re-canalization. In this study, we describe smart blood-vessel-embolic nanogels for improving the anti-tumor efficacy of TAE therapy on hepatocellular carcinoma (HCC). Methods: In this study, an in vitro model composed of two microfluidic chips was used for simulating the tumor capillary network and analyzing artery-embolization properties. Also, blood-vessel-casting embolization of renal arteries was evaluated in normal rabbits. Using a VX2 tumor-bearing rabbit model, the therapeutic efficacy of TAE on HCC was investigated for tumor growth, necrosis, and proliferation. Neovascularization and collateral circulation were evaluated by immunofluorescent detection of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and CD31 following the TAE therapy of VX2 tumor-bearing rabbits. Results: Sufficient embolization of all eight levels of micro-channels was achieved in a tumor-vessel-mimetic model with two microfluidic chips using PIBI-2240, and was further confirmed in renal arteries of normal rabbit. Effective inhibition of tumor collateral circulation and vascular re-canalization was observed in VX2 tumor-bearing rabbits due to the reduced expression levels of HIF-1α, VEGF, and CD31. Conclusions: The exceptional anti-tumor effect of PIBI-2240 observed in this study suggested that it is an excellent blood-vessel-embolic material for tumor TAE therapy.
Chronic Opioid Use in Rheumatoid Arthritis: Prevalence and Predictors
Authors: Yvonne C. Lee, Joel Kremer, Hongshu Guan, Jeffrey Greenberg, Daniel H. Solomon
Journal: Arthritis & Rheumatology (2018)

The opioid epidemic is a major public health concern. However, little is known about opioid use among rheumatoid arthritis (RA) patients. We undertook this study to examine trends in chronic opioid use in RA patients in 2002-2015 and to identify clinical predictors.RA patients were identified from the Corrona registry. Opioid use was ascertained from surveys obtained at clinical visits as often as every 3 months. Chronic opioid use was defined as any opioid use reported during ≥2 consecutive study visits. Annual prevalence of chronic opioid use was calculated using data from 33,739 RA patients with information on opioid use from ≥2 visits. Among the 26,288 individuals who were not taking opioids at baseline, Cox proportional hazards models identified associations between patient characteristics and incident chronic opioid use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.Chronic opioid use increased from 7.4% in 2002 to 16.9% in 2015. Severe pain (HR 2.53 [95% CI 2.19-2.92]) and antidepressant use (HR 1.79 [95% CI 1.64-1.92]) were associated with an increased risk of chronic opioid use. High disease activity (HR 1.55 [95% CI 1.30-1.84]) and a high level of disability (HR 1.45 [95% CI 1.27-1.65]) were also associated with chronic opioid use, whereas Asian ethnicity (HR 0.49 [95% CI 0.36-0.68]) was associated with a decreased risk of chronic opioid use.Among RA patients, chronic opioid use doubled from 2002 to 2015. Pain and antidepressant use were the strongest predictors of chronic opioid use. To curb the rise in chronic opioid use, strategies for stringent control of RA disease activity and management of pain and depression should be research priorities.
VIRAL FITNESS COST AND T CELL CROSS-RECOGNITION LIMIT VIRAL ESCAPE WITHIN A PROTECTIVE HLA-B27 RESTRICTED HEPATITIS C VIRUS SPECIFIC CD8+T CELL EPITOPE
Authors: C Neumann-Haefelin, E Dazert, S Bressanelli, K Fitzmaurice, J Timm, S McKiernan, D Kelleher, P Klenerman, H E Blum, R Bartenschlager, R Thimme
Journal: Hepatology (2008)
A comparison of the attitudes about the legalization of marijuana use for medical purposes by cancer patients in two cancer centers located in a legalized and a non-legalized state.
Authors: Kimberson Cochien Tanco, Donato Dumlao, Rebecca Rae Kreis, Kristy Nguyen, Seyedeh Dibaj, Diane D. Liu, Vidyasagargoud Marupakula, Ayesha Shaikh, Janet L. Williams, Hilda P. Cantu, Marie Jones, Wendy Beers, Michael McMahon, Julio A. Allo, Brenda Noggy, Walter F. Baile, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

191 Background: There is limited evidence on the perception of medical marijuana (MM) among cancer patients in a legalized vs. a non-legalized state. In this study, we compared the attitudes of cancer patients in a legalized (Arizona) vs. a non-legalized state (Texas) on legalizing marijuana for medical use and their perception of its medical usefulness. We also examined their preference of MM for pain, anxiety and depression against current treatments and examined any demographic, physical or psychosocial association with its perception. Methods: Two hundred adult cancer patients were enrolled from the outpatient palliative care centers at Banner MD Anderson Cancer Center in Gilbert, AZ and The University of Texas MD Anderson Cancer Center in Houston, TX. All patients were residents of the state where they were enrolled. Various physical and psychosocial instruments were collected including a survey designed to determine attitudes and beliefs of patient towards MM. Due to the sensitivity of information, no identifiers were associated with data recorded. Results: No significant difference was found between both locations in attitude towards legalizing MM [Arizona 92% (85 - 97%) vs. Texas 90% (82 - 95%); p = 0.81] and belief of its usefulness [Arizona 97% (92 - 99%) vs. Texas 93% (86 - 97%); p = 0.33]. Patients preferred MM over current treatments for anxiety [60% (51 – 68%); p = 0.003] but not for pain and depression. Patients who favored legalizing MM were younger (median age 59 vs. 67 y; p = 0.027) and had worse Edmonton Symptom Assessment System fatigue (median 5 vs 3; p = 0.015) and appetite (median 3 vs 0.5; p = 0.004) scores. There was a significant difference among those who have used MM (95%) and have not used MM (88%) in support of legalization of MM (p = 0.024). Conclusions: Cancer patients from both legalized and non-legalized states showed strong support for legalization of marijuana for medical purposes and strong belief in its medical use. Patient who are younger, and had worse fatigue and appetite showed higher support for medical marijuana.
Three Belgian doctors are investigated over euthanasia of woman with Asperger’s
Authors: Michael Day
Journal: BMJ (2018)

Three Belgian doctors may face trial for the unlawful killing of a woman with autism, after her family claimed that she underwent euthanasia improperly.

The doctors from East Flanders are being investigated on suspicion of having “poisoned” 38 year old Tine Nys in 2010. It is the first time a case of euthanasia has been criminally investigated since the practice was legalised in Belgium in 2002.

Nys had been diagnosed with Asperger’s syndrome two months before she died in an apparently legal killing by a doctor.

Belgium is one of two countries, along with the Netherlands, where euthanasia of people for psychiatric reasons is allowed if they can …
Mobile detection of autism through machine learning on home video: A development and prospective validation study
Authors: Qandeel Tariq, Jena Daniels, Jessey Nicole Schwartz, Peter Washington, Haik Kalantarian, Dennis Paul Wall
Journal: PLoS Medicine (2018)

Background The standard approaches to diagnosing autism spectrum disorder (ASD) evaluate between 20 and 100 behaviors and take several hours to complete. This has in part contributed to long wait times for a diagnosis and subsequent delays in access to therapy. We hypothesize that the use of machine learning analysis on home video can speed the diagnosis without compromising accuracy. We have analyzed item-level records from 2 standard diagnostic instruments to construct machine learning classifiers optimized for sparsity, interpretability, and accuracy. In the present study, we prospectively test whether the features from these optimized models can be extracted by blinded nonexpert raters from 3-minute home videos of children with and without ASD to arrive at a rapid and accurate machine learning autism classification. Methods and findings We created a mobile web portal for video raters to assess 30 behavioral features (e.g., eye contact, social smile) that are used by 8 independent machine learning models for identifying ASD, each with >94% accuracy in cross-validation testing and subsequent independent validation from previous work. We then collected 116 short home videos of children with autism (mean age = 4 years 10 months, SD = 2 years 3 months) and 46 videos of typically developing children (mean age = 2 years 11 months, SD = 1 year 2 months). Three raters blind to the diagnosis independently measured each of the 30 features from the 8 models, with a median time to completion of 4 minutes. Although several models (consisting of alternating decision trees, support vector machine [SVM], logistic regression (LR), radial kernel, and linear SVM) performed well, a sparse 5-feature LR classifier (LR5) yielded the highest accuracy (area under the curve [AUC]: 92% [95% CI 88%–97%]) across all ages tested. We used a prospectively collected independent validation set of 66 videos (33 ASD and 33 non-ASD) and 3 independent rater measurements to validate the outcome, achieving lower but comparable accuracy (AUC: 89% [95% CI 81%–95%]). Finally, we applied LR to the 162-video-feature matrix to construct an 8-feature model, which achieved 0.93 AUC (95% CI 0.90–0.97) on the held-out test set and 0.86 on the validation set of 66 videos. Validation on children with an existing diagnosis limited the ability to generalize the performance to undiagnosed populations. Conclusions These results support the hypothesis that feature tagging of home videos for machine learning classification of autism can yield accurate outcomes in short time frames, using mobile devices. Further work will be needed to confirm that this approach can accelerate autism diagnosis at scale.
Hypoxia-triggered single molecule probe for high-contrast NIR II/PA tumor imaging and robust photothermal therapy
Authors: Xiaoqing Meng, Jiali Zhang, Zhihong Sun, Lihua Zhou, Guanjun Deng, Sanpeng Li, Wenjun Li, Ping Gong, Lintao Cai
Journal: Theranostics (2018)

Hypoxia is a common characteristic of solid tumors. This important feature is associated with resistance to radio-chemotherapy, which results in poor prognosis and probability of tumor recurrence. Taking advantage of background-free NIR II fluorescence imaging and deeper-penetrating photoacoustic (PA) imaging, we developed a hypoxia-triggered and nitroreductase (NTR) enzyme-responsive single molecule probe for high-contrast NIR II/PA tumor imaging and hypoxia-activated photothermal therapy (PTT), which will overcome cellular resistance during hypoxia. Methods: The single molecule probe IR1048-MZ was synthesized by conjugating a nitro imidazole group as a specific hypoxia trigger with an IR-1048 dye as a NIR II/PA signal reporter. We investigated the NIR II fluorescence, NIR absorbance and photothermal effect in different hypoxia conditions in vitro, and performed NIR II/PA tumor imaging and hypoxia-activated photothermal therapy in mice. Results: This versatile molecular probe IR1048-MZ not only realized high-contrast tumor visualization with a clear boundary by NIR II fluorescence imaging, but also afforded deep-tissue penetration at the centimeter level by 3D PA imaging. Moreover, after being activated by NTR that is overexpressed in hypoxic tumors, the probe exhibited a significant photothermal effect for curative tumor ablation with no recurrence. Conclusions: We have developed the first hypoxia-triggered and NTR enzyme-responsive single molecule probe for high-contrast NIR II/PA tumor imaging and hypoxia-activated photothermal therapy. By tracing the activity of NTR, IR1048-MZ may be a promising contrast agent and theranostic formulation for other hypoxia-related diseases (such as cancer, inflammation, stroke, and cardiac ischemia).
When is the best time to transfer terminally ill cancer patients from hospitals to palliative hospice home care? Analysis of a questionnaire survey of 1,055 surviving families.
Authors: Maria Michiko Nakajima, Shuhei James Nakajima, Noboru Horikoshi, Akihiro Isogawa, Yurin Kondo, Go Nakajima, Nobuhiro Takeshita, Kazuyuki Kawakami, Shigehiro Suga, Michiko Nakajima, Kazuhiko Hayashi
Journal: Journal of Clinical Oncology (2018)

61 Background: It is difficult to know when the best timing is to transfer terminally ill cancer patients from hospitals to palliative hospice home care for their quality of life to death. This study aimed to articulate the best time for medical teams working in hospitals to refer their terminally ill cancer patients to palliative home care. Methods: A statistical analysis of a survey was conducted with 1,055 surviving families whose members had died with palliative home care from 1995 to 2014. The questionnaire included the following 8 contents: 1. transfer timing from hospitalization to the home care; A. appropriate, B. too late, C. too early; and the contextual items ware, 2. peacefulness of patient at dying, 3. peacefulness of patient all through the care, 4. physical pain, 5. mental pain, 6. spiritual pain, 7. alleviation of family sufferings, 8. satisfaction of family as care-givers. The response rate is 31% (311 persons). However, we excluded responses without names on the questionnaire, of non-cancer patients, with death location out of home, and without answer to question 1, resulting in 166 responses for analysis. Results: Focusing on the question 1, number of responders are A; 113 (68%), B; 52 (31%), C; 1 (0.6%). The medians of home care days to death are A; 66, B; 23, C; analysis impossible. Comparison of respondents’ satisfaction according to number of days of palliative home care revealed that 89.4% people with two months or more before their patients’ death were satisfied (A), while 10.6% of those who had less than two month were unsatisfied (B+C). Conclusions: Most surviving families were satisfied if they had two months or more for palliative home care. This survey suggests the relevancy to start preparation for discharge that enables the patients to stay home with their family members for two months or more. [Table: see text]
New health standards aim to improve care of homeless people
Authors: Jacqui Wise
Journal: BMJ (2018)

NHS trusts and clinical commissioning groups must do better to improve the healthcare of homeless and other excluded people, says a new report that sets out standards for the best practice.1

The standards, which have been endorsed by 14 UK medical royal colleges and health bodies, recommend that health services for the most excluded people focus on compassion and continuity of care. These marginalised groups include homeless people, vulnerable migrants, sex …
FBXW7 mutations reduce binding of NOTCH1, leading to cleaved NOTCH1 accumulation and target gene activation in CLL
Authors: Viola Close, William Close, Sabrina Julia Kugler, Michaela Reichenzeller, Deyan Yordanov Yosifov, Johannes Bloehdorn, Leiling Pan, Eugen Tausch, Mike-Andrew Westhoff, Hartmut Döhner, Stephan Stilgenbauer, Franz Oswald, Daniel Mertens
Journal: Blood (2018)
Abstract 18366: Glucose And Insuline Interaction During Experimental Cardiac Arrest
Authors: Roman Skulec, David Astapenko, Anatolij Truhlar, Renata Cerna Parizkova, Vladimir Cerny
Journal: Circulation (2017)

Introduction: A little is known about glucose and insulin metabolism during cardiac arrest. Thus, we decided to evaluate plasmatic glucose (P-GL) and insulin (P-IN) levels during experimental cardi...
Immunotherapy-related toxicities: More common than originally reported?
Authors: Elizabeth Jane Cathcart-Rake, Lindsey R. Sangaralingham, Nilay Shah, Aaron Scott Mansfield
Journal: Journal of Clinical Oncology (2018)

184 Background: Population level data regarding incidence of immune-related adverse events (irAE) is lacking. This study evaluated the frequency of irAEs among a large population of patients with non-small cell lung cancer (NSCLC) who received immune checkpoint inhibitors. Methods: Administrative claims data from a large U.S. commercial insurance database (OptumLabs Data Warehouse) were used to retrospectively identify patients with NSCLC who received PD-1 or PD-L1 inhibitors between January 1, 2015 to December 31, 2017. The frequencies of irAEs were reported, identified by having a new medical claim with a corresponding ICD-9 or ICD-10 code during the time period in which the patient was on immunotherapy. Results: Of 2,798 patients with NSCLC (median age at PD-(L)1 initiation: 69 years, interquartile range: 60-75, 1558 male [55.7%], 1240 [44.3%] female), 1,998 (71.4%) received nivolumab, 699 (25.0%) received pembrolizumab, and 101 (3.6%) received atezolizumab. Most patients (1463, 52.3%) received a PD-(L)1 inhibitor as second line therapy; the majority of patients (744) received alkylating agents and antimetabolites prior to receiving PD-(L)1 therapy. See Table 1 for frequencies of irAEs. Conclusions: The current study suggests that the frequencies of some irAEs related to immune checkpoint inhibitor therapies may be higher than those which were reported in the initial trials that led to the FDA approvals for immunotherapies. For example, hypophysitis was noted to occur in 0.6% of patients in the KEYNOTE-024 trial, but was identified in 2.4% of patients in this large cohort. Real world data may refine provider and patient expectations for outcomes beyond what is observed in clinical trials. [Table: see text]
New IOC Certificate in Drugs in Sport supports healthcare professionals to lead on effective clinical drug use and doping prevention in athletes
Authors: Mark Stuart, David Mottram
Journal: British Journal of Sports Medicine (2018)

The International Olympic Committee has recently launched the IOC Certificate in Drugs inSport. This review outlines the current need and learning objectives of the course, which has been developed for healthcare professionals and other athlete support personnel who require specialist knowledge and understanding on the use of drugs in sport.1 The postgraduate-level 6-month online course aims to protect the health of the athlete by ensuring medicines and supplements are used in a safe and effective way. It primarily focuses on the medical aspects of drug use in sport with emphasis on the role of healthcare professionals in the prevention of doping.

Healthcare professionals are often the first people consulted by athletes on issues relating to drug use, from both clinical and antidoping perspectives. Athletes may require advice on the drug treatment for acute or chronic medical conditions, the pharmacological management of sport injuries, the use of dietary or ergogenic supplements, or the status of treatment according to the WADA List of Prohibited Substances and Methods.2 The World Anti-Doping Code recognises that healthcare professionals should play a significant …
Long-term immunogenicity and immune persistence of live attenuated and inactivated hepatitis a vaccines: a report on additional observations from a phase IV study
Authors: J. Luo, X. Wang, F. Ma, G. Kang, Z. Ding, C. Ye, Y. Pan, Y. Zhao, S. Hong, J. Chen, J. Xi, S. Wen, Y. Lin, X. Li, L. Qiu, X. Yang, G. Li, J. Yang, Q. Sun
Journal: Clinical Microbiology and Infection (2018)
Omalizumab discontinuation in children with severe allergic asthma: An observational real‐life study
Authors: Antoine Deschildre, Juliette Roussel, Elodie Drumez, Rola Abou‐Taam, Cinthia Rames, Pascal Le Roux, Guillaume Pouessel, Manuëla Scalbert, Cecile Bonnel, Sarah Mitha, Sophie Boileau, Clémence Mordacq, Caroline Thumerelle, Julien Labreuche, Stéphanie Lejeune, Christophe Marguet
Journal: Allergy (2018)

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