tbuckley/cabot-search huggingface dataset:
Interleukin-1β and Risk of Premature Death in Patients With Myocardial Infarction
Authors: Johanne Silvain, Mathieu Kerneis, Michel Zeitouni, Benoit Lattuca, Sophie Galier, Delphine Brugier, Emilie Mertens, Niki Procopi, Gaspard Suc, Tomy Salloum, Eric Frisdal, Wilfried Le Goff, Jean-Philippe Collet, Eric Vicaut, Philippe Lesnik, Gilles Montalescot, Maryse Guerin
Journal: Journal of the American College of Cardiology (2020)
Dietary patterns in childhood and their effect on gut microbiota—an Asian perspective on atopy risk
Authors: Intan Hakimah Ismail, Christophe Lay, Noorizan H.A. Majid, Way Seah Lee, Bee Wah Lee, Amir Hamzah Abdul Latiff, Hern Tze Tina Tan, Jan Knol, Yeong Yeh Lee
Journal: Journal of Allergy and Clinical Immunology (2020)
Tiotropium Inhibits Airway Inflammation And Goblet Cell Metaplasia In A House Dust Mite (hdm)-Induced Rechallenge Model Of Allergic Airway Disease
Authors: S. de Kleijn, Y. van Wijck, V. Kremer, H. Smits, M. Pieper, P. Hiemstra, C. Taube
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
18F-Fluorodeoxyglucose PET/CT-Guided Palliative Radiotherapy Provides Durable Responses to Over a Dozen Sites of Disease in Relapsed Myeloid Sarcoma
Authors: Charles Shuttleworth, Eva A. Wegner, Stephen R. Thompson, Giselle Kidson-Gerber
Journal: Clinical Nuclear Medicine (2020)

Myeloid sarcoma (MS) is a rare entity, and FDG PET/CT is a useful tool for staging at diagnosis and response assessment. We present a case of a 72-year-old woman diagnosed with multifocal extramedullary MS, using FDG PET/CT to guide palliative radiotherapy to 13 sites of disease over 2 separate relapses with complete and durable local responses and minimal toxicity. This case represents the largest reported burden of disease in MS successfully treated with FDG PET/CT-guided radiotherapy.
Declines in physical function from androgen deprivation therapy (ADT) in men with nonmetastatic prostate cancer: A matched cohort study
Authors: H. Breunis, N. Timilshina, G. Tomlinson, G. Naglie, I. Tannock, N. Fleshner, M. Krahn, S. Duff Canning, P. Warde, S. Alibhai
Journal: Journal of Clinical Oncology (2009)

9526 Background: Although prolonged use of ADT is hypothesized to adversely affect physical function, few studies have examined this relationship longitudinally using objective measures of physical function. Methods: Men age 50+ with non-metastatic prostate cancer (PC) starting continuous ADT were enrolled in this prospective longitudinal matched cohort study. Physical function was assessed with the six-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test, representing endurance, upper extremity strength, and lower extremity strength, respectively. Self-reported physical function was measured with the Medical Outcomes Study SF-36. Assessments were done at baseline, 3 months, 6 months, and 12 months. Two control groups, matched on age, education, and baseline function were also enrolled. One control group had PC but did not receive ADT, and the other group did not have PC. Linear mixed effects regression models were fitted adjusting for baseline covariates. Results: 85 patients on ADT, 86 PC controls, and 86 healthy controls were enrolled. All 3 groups were similar in age (mean age 69.1 y, range 50–87) and physical function (all ANOVA p&gt;0.05). The 6MWT distance improved in both control groups (p=0.05 and 0.05 for PC and healthy controls, respectively) but remained stable in the ADT group (p=0.96)). Grip strength declined in the ADT group (p=0.04), remained stable in the PC control group (p=0.31), and improved in the healthy control group (p=0.008). TUG scores remained stable over time and across groups (p&gt;0.10). SF-36 physical function declined in the ADT group (p&lt;0.001) but increased in both control groups (p&lt;0.001). Negative effects on outcomes were noted within 3–6 months of starting ADT and were larger with older age. Conclusions: Endurance, upper extremity strength, and self-reported physical function are affected within 3–6 months of starting ADT, particularly in older men. Declines persist at 12 months after adjustment for baseline function and covariates. Exercise intervention studies to counteract these losses are warranted. No significant financial relationships to disclose.
Characterization of an antitumor immune response after light-activated drug therapy using talaporfin sodium in a spontaneously metastasizing mammary tumor model
Authors: E. Bromley, B. Owczarczak, L. Keltner, S. Wang, S. O. Gollnick
Journal: Journal of Clinical Oncology (2009)

3052 Background: An innovative light-activated drug therapy (Litx) is a cytoreductive treatment that uses light-emitting diodes to activate talaporfin sodium (LS11), a water-soluble drug, resulting in the production of singlet oxygen. Tumor destruction involves direct and indirect tumor kill through apoptosis, vascular occlusion, and potentially antitumor immunologic effects. To provide evidence for the potential antitumor immunologic effects, we have used the therapy to treat primary tumors and examine prevention of metastases in the 4T1 tumor model, an aggressive, spontaneously metastasizing murine mammary tumor model that mirrors human breast cancer. When grown in the mammary fat pad of BALB/c mice, untreated 4T1 tumors rapidly metastasize to lung, liver, lymph nodes, and brain. Methods: To confirm tumor kill by this therapy, the primary 4T1 tumors grown in mice were treated and animal survival was followed. To determine whether the therapy could enhance antitumor immunity and reduce metastases, the lymph node (LN) cells from treated and control mice were transferred to naïve recipient mice. Recipients were challenged with a tumorigenic dose of 4T1 cells 3 days after adoptive transfer and primary and secondary tumor growth in the recipients was examined. Results: Treatment of primary tumors significantly increased survival (p≤0.01) when compared to animals treated with either light or drug alone. LN cells isolated from treated mice, but not control mice, significantly inhibited primary tumor growth in recipients (p≤0.0001) and dramatically reduced the number of lung metastases present 40d after tumor challenge (p≤0.02). The ability to inhibit primary and secondary tumor growth in recipients depended on the presence of CD8 + T cells; depletion of CD8 + T cells from the LN abolished the effect. Preliminary evidence for such effect on untreated tumors has been observed in human trials of this therapy. Conclusions: These results indicated that this light-activated drug therapy not only destroyed the treated tumors directly but also controlled growth of untreated tumors through induction of a specific host antitumor immune response mediated by CD8 + T cells. [Table: see text]
Mapping mania symptoms based on focal brain damage
Authors: Gonçalo Cotovio, Daniel Talmasov, J. Bernardo Barahona-Corrêa, Joey Hsu, Suhan Senova, Ricardo Ribeiro, Louis Soussand, Ana Velosa, Vera Cruz e Silva, Natalia Rost, Ona Wu, Alexander L. Cohen, Albino J. Oliveira-Maia, Michael D. Fox
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.
GP numbers in England fell by more than 600 in past year, data show
Authors: Abi Rimmer
Journal: BMJ (2020)

The BMA has called for better support for general practice ahead of a potential second wave of covid-19, after figures showed a fall in the number of full time equivalent (FTE) GPs in the past year.

Data published by NHS Digital on 27 August1 showed that, from June 2019 to June 2020, …
The involvement of exosomes in the diagnosis and treatment of pancreatic cancer
Authors: Abakundana Nsenga Ariston Gabriel, Fang Wang, Qinlian Jiao, Umwali Yvette, Xuemei Yang, Samed Ahmed Al-Ameri, Lutao Du, Yun-shan Wang, Chuanxin Wang
Journal: Molecular Cancer (2020)

At the moment, pancreatic cancer is among the deadliest gastrointestinal diseases, and pancreatic cancer growth is a complex biological process that is based on different kinds of genes. Exosomes are extracellular vesicles containing microRNAs (miRNAs), messenger RNA (mRNA), and proteins, they act as the most prominent mediator of intercellular communication, and they regulate, instruct, and re-educate their surrounding microenvironment and target specific organs. Due to accumulative evidence proved that exosomes are involved in metastasis, cell proliferation, EMT, angiogenesis, and TME of pancreatic cancer, exosomes are crucial potential candidates to detect pancreatic cancer early. This review aims to convey the current understanding of the main functions employed by exosomes in early diagnosis and treatment of pancreatic cancer.
Flutamide ameliorates oxidative DNA damage caused by dihydrotestosterone (DHT) in human prostate cancer cells
Authors: Sanjeev K. Pathak, Ricky A. Sharma, Raj Singh, Peter B. Farmer, William P. Steward, Andreas J. Gescher, Kilian Mellon
Journal: Cancer Research (2004)

744  Reactive oxygen species (ROS) are mechanistically implicated in the development and progression of prostate cancer. They may cause peroxidation of membrane lipids and oxidative DNA damage, resulting in the formation of DNA adducts such as 8-oxo-deoxyguanosine (8-oxo-dG) and the pyrimidopurinone adduct of deoxyguanosine (M1G), both of which have been associated with carcinogenesis. It has been shown that DHT increases ROS levels in androgen-sensitive human prostate cancer cells (Ripple et al, J Natl Cancer Inst. 89: 40-48, 1997). We determined the influence of DHT on levels of oxidative DNA adducts in human prostate cancer cell lines and tested the hypothesis that flutamide, a competitive anti-androgen, inhibits DHT-induced changes. Human prostate cancer cells LNCaP (androgen-sensitive), PC3 and DU145 cells (both androgen-insensitive) were treated with DHT (100 nM) daily for 7 days. Levels of M1G and 8-oxo-dG adducts in extracted genomic DNA were determined by immunoslot blot and liquid chromatography-tandem mass spectrometry, respectively. In LNCaP cells, the effect of DHT at 2.5, 10, 25 and 50 nM was also studied. To exclude any interference by endogenous androgens, cells were cultured without serum when the effect of 2.5 nM DHT was studied. The flutamide concentrations used were 5 μM and 10 μM. In the following, mean M1G and 8-oxo-dG levels are expressed as adducts per 107 and 106 nucleotides, respectively. M1G levels in control DU145, PC3 and LNCaP cells were 7.5±5.6, 6.9±4.7, and 12.6±5.6, respectively. In DU145 and PC3 cells treated with 100 nM DHT, M1G levels were not significantly different from control levels. In LNCaP cells exposed to 100 nM DHT, M1G levels were 17.2±8.6, thus significantly different from untreated cells (p
Prognostic significance of preoperative serum tumor markers in the patients with curatively resected advanced gastric cancers
Authors: S. Yoon, C. Yoo, I. Park, H. Chang, T. Kim, J. Lee, J. Yook, S. Oh, B. Kim, Y. Kang
Journal: Journal of Clinical Oncology (2009)

e15515 Background: We evaluated the prognostic significance of preoperative tumor markers, carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA19–9), and carbohydrate antigen 72–4 (CA72–4), in the patients with curatively resected advanced gastric cancers (AGC). Methods: Preoperative serum tumor markers were available for 667 patients who had been enrolled in a phase III trial of adjuvant chemotherapy (AMC0201). We compared the relapse free survival (RFS) and overall survival (OS) according to patient's pre-treatment clinical characteristics and serum tumor markers by using log rank test and Cox proportional hazard model. Results: Of total 667 patients, 3 year RFS rate and OS rate were 67.4% and 75.0%, respectively. Postoperative pathologic stage was II in 353 (52.9%), IIIA in 202 (30.3%), IIIB in 61 (9.1%), and IV (M0) in 51 (7.6%). CEA, CA19–9, CA72–4 were elevated pre-operatively in 64 of 665 patients (9.6%), 75 of 664 patients (11.3%), and 121 of 639 patients (18.9%), respectively. After the median follow-up of 38.4 months, 209 patients (31.3%) had recurrence, and 164 patients (24.6%) died. In the univariate analysis, location of tumor, type of surgery, Borrmann type, TNM stage, the elevation of CEA and CA72–4 level were significant prognostic factors for RFS and OS. In the multivariate analysis, serum CA72–4 was independent significant prognostic factor for RFS and OS as well as tumor location, Borrmann type, and stage Conclusions: Pre-operative serum CEA and CA72–4 levels were independent prognostic factors as well as clinical characteristics of pathologic stage, tumor location and Borrmann type in patients with curatively resected AGC. No significant financial relationships to disclose.
A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis
Authors: Satoshi Ikeda, Terufumi Kato, Hirotsugu Kenmotsu, Takashi Ogura, Shunichiro Iwasawa, Yuki Sato, Toshiyuki Harada, Kaoru Kubota, Takaaki Tokito, Isamu Okamoto, Naoki Furuya, Toshihide Yokoyama, Shinobu Hosokawa, Tae Iwasawa, Takeharu Yamanaka, Hiroaki Okamoto
Journal: Journal of Thoracic Oncology (2020)
Role of mixed lineage kinase 3 in response of head and neck squamous cancer cell lines to epidermal growth factor receptor (EGFR) inhibition
Authors: B. A. Conley, C. M. Leece, S. Chandana, S. Dowlashati
Journal: Journal of Clinical Oncology (2009)

6076 Background: More efficacious treatments of head and neck squamous cancers (HNSCC) are urgently needed. HNSCC overexpress EGFR, yet the efficacy of EGFR inhibitors is marginal, with minimal effect on patient survival. Mixed lineage kinases (MLKs) are members of a large family of mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs) that activate MAPK pathways, involving JNK, ERK 1/2 and p38 cell signaling pathways. (Gallo KA, Johnson GL, Nat Rev Mol Cell Biol. 2002;3:663–72) We explored the role of MLK3 in HNSCC as a possible therapeutic target. Methods: The requirement of MLK3 for cell proliferation and survival of HNSCC cell lines UM-SCC-38 and -47 (HPV+) (obtained from TE Carey, U Michigan) was investigated using RNA interference (siRNA) and MLK3 inhibitor K252a to inhibit the expression and activity of MLK3. Cells were also exposed to EGFR inhibitor Compound 56 at various concentrations. Proliferation was assessed with MTT after 72 h exposure. The effect of MLK3 inhibition on relevant cell signaling pathways was assessed by immunoblotting with activation-specific phosphoantibodies directed against MAPKs, the prosurvival kinase Akt and apoptotic proteins. Results: MLK3 is overexpressed in malignant HNSCC cell lines compared to normal tonsil lysate, and its expression can be inhibited by siRNA or K 252a. Inhibition of MLK3 expression is associated with downregulation of phospho-Akt and with decreased proliferation. Compound 56 inhibits proliferation at lower concentrations in HPV+ cell line UM-SCC-47 (10 microM) compared with UM-SCC-38 (25 microM), inhibits expression of pErk, and decreases expression of pAkt. Combining siRNA or K252a and compound 56 showed less pAkt expression and increased apoptosis (caspase 3 or PARP cleavage) compared with compound 56 alone. Conclusions: MLK3 may have a role in avoiding apoptosis in HNSCC cells. Its inhibition may enhance the effects of EGFR inhibition in HNSCC. No significant financial relationships to disclose.
Highly efficient phototheranostics of macrophage-engulfed Gram-positive bacteria using a NIR luminogen with aggregation-induced emission characteristics
Authors: Michelle M.S. Lee, Dingyuan Yan, Joe H.C. Chau, Hojeong Park, Charlie C.H. Ma, Ryan T.K. Kwok, Jacky W.Y. Lam, Dong Wang, Ben Zhong Tang
Journal: Biomaterials (2020)
The final results of the United Kingdom sentinel node training program: New Start
Authors: R. E. Mansel, F. McNeill
Journal: Journal of Clinical Oncology (2009)

629 Background: Formal introduction of new surgicaltechniques is rare, but the rate of technological advances in cancer surgery mandates that surgeons in current practice will need to learn new techniques in an enviroment less rigorous than residency programs. The rapid introduction of sentinel node biopsy in breast cancer is a classic exemplar of the problematic issues around quality assurance and patient safety in new technology. In the UK this technique was introduced in a unique formal program –The New Start training program –which utilised educational methods with a mandatory quality assurance system for each individual surgical team prior to routine introduction of the technique in practice. Methods: Every hospital had to submit the breast team to a formal program consisting of a theory training day followed by in house supervised training for the first 5 cases in the operating room in their instituition.Surgical teams performed 5 directly supervised procedures followed by 25 further audited cases with data being submitted centrally. All sentinel procedures were combination isotope/blue dye, (Nanocoll 99 Tm and a blue dye (Patent Blue V- laboratoires Guerbert Paris, France). In order to be approved each team had to achieve a localisation rate of at least 90% and a false negative rate of less than 10%. Results: The program has now trained 242 surgeons performing a total of 6341 audited sentinel node validation procedures. The localisation rate was 99% and the false negative rate was &lt;8%. The median number of sentinel nodes was 2 and in 54% of the node positive patients, the sentinel node was the only positive node. Preoperative scintigraphy showed hotspots in 83% of patients. Blue dye reactions in this large dataset were lower than quoted in the literature, (&lt;1% of patients), suggesting over-reporting in smaller trials. There was short learning curve for false negativity falling to &lt;4% after 40 audited cases. Failure to find a sentinel node correlated strongly with a higher rate of histological node positivity. Conclusions: This major national training program with in house practical training has shown a high localisation rate and a shortened learning curve for false negative cases, and has demonstrated the value of a formal training program, which can form the template for the introduction of new surgical techniques. No significant financial relationships to disclose.
Fulvestrant in the treatment of advanced breast cancer: A systematic review and meta-analysis of randomized controlled trials
Authors: D. Mauri, A. Valachis, N. P. Polyzos, D. Mavroudis, V. Georgoulias, G. Casazza
Journal: Journal of Clinical Oncology (2009)

1087 Background: The purpose of the study was to compare efficacy and tolerability of fulvestrant with aromatase inhibitors and tamoxifen that actually represent the standard of care in hormonesensitive breast cancer. Methods: Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, time to progression, clinical outcome, and objective response. Secondary outcome was the tolerability profile of the drugs. Results: Four trials were identified with 2,125 eligible patients. There was no statistically significant difference between fulvestrant and other hormonal agents in terms of overall survival (pooled HR: 1.047, 95% CI: 0.688 to 1.592), time to progression (pooled HR: 0.994, 95% CI: 0.691 to 1.431), clinical benefit (pooled OR: 1.044, 95% CI: 0.828 to 1.315), or objective response rate (pooled OR: 0.949, 95% CI: 0.736 to 1.224). A higher incidence of joint disorders (pooled OR: 0.621, 95% CI: 0.424 to 0.909; p = 0.014) was noted in patients receiving hormonal agents other than fulvestrant. Conclusions: Fulvestrant was similar to other hormonal agents with respect to efficacy measures, with good tolerability profile. No significant financial relationships to disclose.
Aerosol Generation from the Respiratory Tract with Various Modes of Oxygen Delivery
Authors: Nathaniel T. Gaeckle, Jihyeon Lee, Yensil Park, Gean Kreykes, Michael D. Evans, Christopher J. Hogan
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Aerosol generation with modes of oxygen therapy such as high-flow nasal cannula and noninvasive positive-pressure ventilation is a concern for healthcare workers during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The amount of aerosol generation from the respiratory tract with these various oxygen modalities is unknown.
CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia
Authors: Melinda A. Biernacki, Kimberly A. Foster, Kyle B. Woodward, Michael E. Coon, Carrie Cummings, Tanya M. Cunningham, Robson G. Dossa, Michelle Brault, Jamie Stokke, Tayla M. Olsen, Kelda Gardner, Elihu Estey, Soheil Meshinchi, Anthony Rongvaux, Marie Bleakley
Journal: Journal of Clinical Investigation (2020)

Proteins created from recurrent fusion genes like CBFB-MYH11 are prevalent in acute myeloid leukemia (AML), often necessary for leukemogenesis, persistent throughout the disease course, and highly leukemia specific, making them attractive neoantigen targets for immunotherapy. A nonameric peptide derived from a prevalent CBFB-MYH11 fusion protein was found to be immunogenic in HLA-B*40:01+ donors. High-avidity CD8+ T cell clones isolated from healthy donors killed CBFB-MYH11+ HLA-B*40:01+ AML cell lines and primary human AML samples in vitro. CBFB-MYH11–specific T cells also controlled CBFB-MYH11+ HLA-B*40:01+ AML in vivo in a patient-derived murine xenograft model. High-avidity CBFB-MYH11 epitope–specific T cell receptors (TCRs) transduced into CD8+ T cells conferred antileukemic activity in vitro. Our data indicate that the CBFB-MYH11 fusion neoantigen is naturally presented on AML blasts and enables T cell recognition and killing of AML. We provide proof of principle for immunologically targeting AML-initiating fusions and demonstrate that targeting neoantigens has clinical relevance even in low–mutational frequency cancers like fusion-driven AML. This work also represents a first critical step toward the development of TCR T cell immunotherapy targeting fusion gene–driven AML.