tbuckley/cabot-search huggingface dataset:
Collective cancer invasion forms an integrin-dependent radioresistant niche
Authors: Anna Haeger, Stephanie Alexander, Manon Vullings, Fabian M.P. Kaiser, Cornelia Veelken, Uta Flucke, Gudrun E. Koehl, Markus Hirschberg, Michael Flentje, Robert M. Hoffman, Edward K. Geissler, Stephan Kissler, Peter Friedl
Journal: The Journal of Experimental Medicine (2019)

Cancer fatalities result from metastatic dissemination and therapy resistance, both processes that depend on signals from the tumor microenvironment. To identify how invasion and resistance programs cooperate, we used intravital microscopy of orthotopic sarcoma and melanoma xenografts. We demonstrate that these tumors invade collectively and that, specifically, cells within the invasion zone acquire increased resistance to radiotherapy, rapidly normalize DNA damage, and preferentially survive. Using a candidate-based approach to identify effectors of invasion-associated resistance, we targeted β1 and αVβ3/β5 integrins, essential extracellular matrix receptors in mesenchymal tumors, which mediate cancer progression and resistance. Combining radiotherapy with β1 or αV integrin monotargeting in invading tumors led to relapse and metastasis in 40–60% of the cohort, in line with recently failed clinical trials individually targeting integrins. However, when combined, anti-β1/αV integrin dual targeting achieved relapse-free radiosensitization and prevented metastatic escape. Collectively, invading cancer cells thus withstand radiotherapy and DNA damage by β1/αVβ3/β5 integrin cross-talk, but efficient radiosensitization can be achieved by multiple integrin targeting.
Current status and future trends of clinical diagnoses via image-based deep learning
Authors: Jie Xu, Kanmin Xue, Kang Zhang
Journal: Theranostics (2019)

With the recent developments in deep learning technologies, artificial intelligence (AI) has gradually been transformed from cutting-edge technology into practical applications.AI plays an important role in disease diagnosis and treatment, health management, drug research and development, and precision medicine.Interdisciplinary collaborations will be crucial to develop new AI algorithms for medical applications.In this paper, we review the basic workflow for building an AI model, identify publicly available databases of ocular fundus images, and summarize over 60 papers contributing to the field of AI development.
OA03.08 Clinical Utility of CTDNA Driver Genomic Alterations (GA) Directing Targeted Therapy in Untreated Advanced NSCLC Patients
Authors: L. Mezquita, D. Planchard, M. Dorta, M. Aldea, C. Naltet, V. Lamberts, A.-M. Grecea, P. Martin-Romano, F. De Kievit, C. Jovelet, E. Rouleau, L. Lacroix, J. Remon, P. Lavaud, A. Gazzah, C. Morris, K. Howarth, E. Green, C. Massard, B. Besse
Journal: Journal of Thoracic Oncology (2019)
The YB-1:Notch-3 axis modulates immune cell responses and organ damage in systemic lupus erythematosus
Authors: Daniel M. Breitkopf, Vera Jankowski, Kim Ohl, Juliane Hermann, Daniela Hermert, Klaus Tenbrock, Xiyang Liu, Ina V. Martin, Jialin Wang, Fabian Groll, Elisabeth Gröne, Jürgen Floege, Tammo Ostendorf, Thomas Rauen, Ute Raffetseder
Journal: Kidney International (2019)
Urocortin 2 Gene Transfer Improves Heart Function in Aged Mice
Authors: Dimosthenis Giamouridis, Mei Hua Gao, N. Chin Lai, Tracy Guo, Atsushi Miyanohara, W. Matthijs Blankesteijn, Erik A.L. Biessen, H. Kirk Hammond
Journal: Molecular Therapy (2019)

Prevalence of left ventricular (LV) systolic and diastolic dysfunction increases with aging. We previously reported that urocortin 2 (Ucn2) gene transfer increases heart function in mice with heart failure with reduced ejection fraction. Here, we test the hypotheses that (1) Ucn2 gene transfer will increase LV function in aged mice and that (2) Ucn2 gene transfer given in early life will prevent age-related LV dysfunction. Nineteen-month-old (treatment study) and 3-month-old (prevention study) mice received Ucn2 gene transfer or saline. LV function was examined 3–4 months (treatment study) or 20 months (prevention study) after Ucn2 gene transfer or saline injection. In both the treatment and prevention strategies, Ucn2 gene transfer increased ejection fraction, reduced LV volume, increased LV peak −dP/dt and peak +dP/dt, and reduced global longitudinal strain. Ucn2 gene transfer—in both treatment and prevention strategies—was associated with higher levels of LV SERCA2a protein, reduced phosphorylation of LV CaMKIIa, and reduced LV α-skeletal actin mRNA expression (reflecting reduced cardiac stress). In conclusion, Ucn2 gene transfer restores normal cardiac function in mice with age-related LV dysfunction and prevents development of LV dysfunction. Prevalence of left ventricular (LV) systolic and diastolic dysfunction increases with aging. We previously reported that urocortin 2 (Ucn2) gene transfer increases heart function in mice with heart failure with reduced ejection fraction. Here, we test the hypotheses that (1) Ucn2 gene transfer will increase LV function in aged mice and that (2) Ucn2 gene transfer given in early life will prevent age-related LV dysfunction. Nineteen-month-old (treatment study) and 3-month-old (prevention study) mice received Ucn2 gene transfer or saline. LV function was examined 3–4 months (treatment study) or 20 months (prevention study) after Ucn2 gene transfer or saline injection. In both the treatment and prevention strategies, Ucn2 gene transfer increased ejection fraction, reduced LV volume, increased LV peak −dP/dt and peak +dP/dt, and reduced global longitudinal strain. Ucn2 gene transfer—in both treatment and prevention strategies—was associated with higher levels of LV SERCA2a protein, reduced phosphorylation of LV CaMKIIa, and reduced LV α-skeletal actin mRNA expression (reflecting reduced cardiac stress). In conclusion, Ucn2 gene transfer restores normal cardiac function in mice with age-related LV dysfunction and prevents development of LV dysfunction.
Clinical Outcomes of Mortality, Readmissions, and Ischemic Stroke Among Medicare Patients Undergoing Left Atrial Appendage Closure via Implanted Device
Authors: Rajesh Kabra, Saket Girotra, Mary Vaughan Sarrazin
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Left atrial appendage closure (LAAC) has emerged as a nonpharmacological alternative for stroke prevention in patients with nonvalvular atrial fibrillation. Contemporary data regarding the characteristics and outcomes of patients undergoing this procedure are limited. <h3>Objective</h3> To determine the characteristics, postprocedural mortality rate, and rates of readmission and ischemic stroke among Medicare beneficiaries who underwent LAAC via implanted device. <h3>Design, Setting, and Participants</h3> This population-based cohort study used Medicare inpatient claims from January 2015 to December 2017 for 13 627 patients older than 65 years with a diagnosis of atrial fibrillation who underwent LAAC with an implanted device from January 2015 to November 2017. Data analyses were conducted from January through August 2019. <h3>Exposure</h3> Left atrial appendage closure. <h3>Main Outcomes and Measures</h3> Mortality rates during the index admission and for 1 year after LAAC were assessed. The 30-day readmission rate and the primary reasons for readmission were also examined. In addition, the likelihood of hospitalization for ischemic stroke within 180 days among 9231 patients for whom 6 months of follow-up data were available was evaluated. <h3>Results</h3> Among the 13 627 patients undergoing LAAC, the mean (SD) age was 78.0 (6.3) years, 9406 (69.0%) were older than 75 years, 11 980 (87.9%) were white, and 5630 (41.3%) were women. The mean (SD) CHA<sub>2</sub>DS<sub>2-</sub>VASc score was 4.3 (1.4). Twenty-eight patients (0.2%) died during the index admission. Mortality rates were 0.6% (80 patients) at 30 days, 1.9% (262 patients) at 90 days, 4.0% (547 patients) at 180 days, and 7.5% (1027 patients) at 365 days. The 30-day readmission rate among 13 599 patients discharged alive was 9.4% (1284 patients). Among 9231 patients with 6 months of follow-up data, 111 (1.2%) experienced readmission for ischemic stroke or transient ischemic attack within 180 days of discharge. <h3>Conclusions and Relevance</h3> In this cohort study of patients older than 65 years with atrial fibrillation who underwent LAAC with an implanted device, readmission rates for ischemic strokes over the course of 6 months were lower than expected given the patients' CHA<sub>2</sub>DS<sub>2-</sub>VASc scores in the absence of anticoagulation therapy. Mortality at 1 year was higher than that reported in previous randomized clinical trials, likely because the patients in the present study were older, had a higher number of comorbidities, and were ineligible to receive warfarin.
Progress Toward Global Eradication of Dracunculiasis — January 2018–June 2019
Authors: Donald R. Hopkins, Adam J. Weiss, Sharon L. Roy, James Zingeser, Sarah Anne J. Guagliardo
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Dracunculiasis (also known as Guinea worm disease) is caused by the parasite Dracunculus medinensis and is acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae.The worm typically emerges through the skin on a lower limb approximately 1 year after infection, resulting in pain and disability (1).There is no vaccine or medicine to treat the disease; eradication efforts rely on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, chemical treatment of unsafe water with temephos (an organophosphate larvicide to kill copepods), and provision of safe drinking water (1,2).In 1986, with an estimated 3.5 million cases † occurring each year in 20 African and Asian countries § (3), the World Health Assembly called for dracunculiasis elimination (4).The global Guinea Worm Eradication Program (GWEP), led by The Carter Center and supported by the World Health Organization (WHO), CDC, the United Nations Children's Fund, and other partners, began assisting ministries of health in countries with dracunculiasis.This report, based on updated health ministry data, describes progress to eradicate dracunculiasis during January 2018-June 2019 and updates previous reports (2,4,5).With only five countries currently affected by dracunculiasis (Angola, Chad, TABLE 1. Number of reported indigenous dracunculiasis cases, by country -worldwide, January 2017-June 2019 Country No. of cases (% contained) % change in no. of cases, Jan-
Biology vs Access to Care—Relative Contribution to Racial Disparities in Prostate Cancer—In Reply
Authors: Robert T. Dess, Brandon A. Mahal, Daniel E. Spratt
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
Molecular Heterogeneity of Papillary Thyroid Cancer: Comparison of Primary Tumors and Synchronous Metastases in Regional Lymph Nodes by Mass Spectrometry Imaging
Authors: Marta Gawin, Agata Kurczyk, Ewa Stobiecka, Katarzyna Frątczak, Joanna Polańska, Monika Pietrowska, Piotr Widłak
Journal: Endocrine Pathology (2019)

Abstract Intra-tumor heterogeneity results from both genetic heterogeneity of cancer (sub)clones and phenotypic plasticity of cancer cells that could be induced by different local microenvironments. Here, we used mass spectrometry imaging (MSI) to compare molecular profiles of primary tumors located in the thyroid gland and their synchronous metastases in regional lymph nodes to analyze phenotypic heterogeneity in papillary thyroid cancer. Two types of cancerous (primary tumor and metastasis) and two types of not cancerous (thyroid gland and lymph node) regions of interest (ROIs) were delineated in postoperative material from 11 patients, then the distribution of tryptic peptides (spectral components) was analyzed by MSI in all tissue regions. Moreover, tryptic peptides identified by shotgun proteomics in corresponding tissue lysates were matched to components detected by MSI to enable their hypothetical protein annotation. Unsupervised segmentation of all cancer ROIs revealed that different clusters dominated in tumor ROIs and metastasis ROIs. The intra-patient similarity between thyroid and tumor ROIs was higher than the intra-patient similarity between tumor and metastasis ROIs. Moreover, the similarity between tumor and its metastasis from the same patients was lower than similarities among tumors and among metastases from different patients (inter-patient similarity was higher for metastasis ROIs than for tumor ROIs). Components differentiating between tumor and its metastases were annotated as proteins involved in the organization of the cytoskeleton and chromatin, as well as proteins involved in immunity-related functions. We concluded that phenotypical heterogeneity between primary tumor and lymph node metastases from the same patient was higher than inter-tumor heterogeneity between primary tumors from different patients.
Jagged1-mediated myeloid Notch1 signaling activates HSF1/Snail and controls NLRP3 inflammasome activation in liver inflammatory injury
Authors: Yuting Jin, Changyong Li, Dongwei Xu, Jianjun Zhu, Song Wei, Andrew Zhong, Mingwei Sheng, Sergio Duarte, Ana J. Coito, Ronald W. Busuttil, Qiang Xia, Jerzy W. Kupiec-Weglinski, Bibo Ke
Journal: Cellular and Molecular Immunology (2019)

Abstract Notch signaling plays important roles in the regulation of immune cell functioning during the inflammatory response. Activation of the innate immune signaling receptor NLRP3 promotes inflammation in injured tissue. However, it remains unknown whether Jagged1 (JAG1)-mediated myeloid Notch1 signaling regulates NLRP3 function in acute liver injury. Here, we report that myeloid Notch1 signaling regulates the NLRP3-driven inflammatory response in ischemia/reperfusion (IR)-induced liver injury. In a mouse model of liver IR injury, Notch1-proficient (Notch1 FL/FL ) mice receiving recombinant JAG1 showed a reduction in IR-induced liver injury and increased Notch intracellular domain (NICD) and heat shock transcription factor 1 (HSF1) expression, whereas myeloid-specific Notch1 knockout (Notch1 M-KO ) aggravated hepatocellular damage even with concomitant JAG1 treatment. Compared to JAG1-treated Notch1 FL/FL controls, Notch1 M-KO mice showed diminished HSF1 and Snail activity but augmented NLRP3/caspase-1 activity in ischemic liver. The disruption of HSF1 reduced Snail activation and enhanced NLRP3 activation, while the adoptive transfer of HSF1-expressing macrophages to Notch1 M-KO mice augmented Snail activation and mitigated IR-triggered liver inflammation. Moreover, the knockdown of Snail in JAG1-treated Notch1 FL/FL livers worsened hepatocellular functioning, reduced TRX1 expression and increased TXNIP/NLRP3 expression. Ablation of myeloid Notch1 or Snail increased ASK1 activation and hepatocellular apoptosis, whereas the activation of Snail increased TRX1 expression and reduced TXNIP, NLRP3/caspase-1, and ROS production. Our findings demonstrated that JAG1-mediated myeloid Notch1 signaling promotes HSF1 and Snail activation, which in turn inhibits NLRP3 function and hepatocellular apoptosis leading to the alleviation of IR-induced liver injury. Hence, the Notch1/HSF1/Snail signaling axis represents a novel regulator of and a potential therapeutic target for liver inflammatory injury.
Cancer screening equipment will be upgraded at 78 NHS trusts over next two years
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The government has announced that 78 NHS trusts in England will receive funding over the next two years to replace, refurbish, or upgrade computed tomography (CT) machines, magnetic resonance imaging (MRI) scanners, and breast screening imaging and assessment equipment.

The £200m (€232m; $258m) funding was first announced last month, to help improve the quality of cancer screening and the speed of diagnosis. The government has now revealed which trusts are in line to receive the money …
Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment
Authors: Jooho Park, Yongwhan Choi, Hyeyoun Chang, Wooram Um, Ju Hee Ryu, Ick Chan Kwon
Journal: Theranostics (2019)

The use of nanomedicine for cancer treatment takes advantage of its preferential accumulation in tumors owing to the enhanced permeability and retention (EPR) effect.The development of cancer nanomedicine has promised highly effective treatment options unprecedented by standard therapeutics.However, the therapeutic efficacy of passively targeted nanomedicine is not always satisfactory because it is largely influenced by the heterogeneity of the intensity of the EPR effect exhibited within a tumor, at different stages of a tumor, and among individual tumors.In addition, limited data on EPR effectiveness in human hinders further clinical translation of nanomedicine.This unsatisfactory therapeutic outcome in mice and humans necessitates novel approaches to improve the EPR effect.This review focuses on current attempts at overcoming the limitations of traditional EPR-dependent nanomedicine by incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling of the tumor microenvironment.This review will provide valuable insight to researchers who seek to overcome the limitations of relying on the EPR effect alone in cancer nanomedicine and go "beyond the EPR effect".
Genomic analyses of PMBL reveal new drivers and mechanisms of sensitivity to PD-1 blockade
Authors: Bjoern Chapuy, Chip Stewart, Andrew J. Dunford, Jaegil Kim, Kirsty Wienand, Atanas Kamburov, Gabriel K. Griffin, Pei-Hsuan Chen, Ana Lako, Robert A. Redd, Claire M. Cote, Matthew D. Ducar, Aaron R. Thorner, Scott J. Rodig, Gad Getz, Margaret A. Shipp
Journal: Blood (2019)
Which specific modes of exercise training are most effective for treating low back pain? Network meta-analysis
Authors: Patrick J Owen, Clint T Miller, Niamh L Mundell, Simone J J M Verswijveren, Scott D Tagliaferri, Helena Brisby, Steven J Bowe, Daniel L Belavy
Journal: British Journal of Sports Medicine (2019)

Objective Examine the effectiveness of specific modes of exercise training in non-specific chronic low back pain (NSCLBP). Design Network meta-analysis (NMA). Data sources MEDLINE, CINAHL, SPORTDiscus, EMBASE, CENTRAL. Eligibility criteria Exercise training randomised controlled/clinical trials in adults with NSCLBP. Results Among 9543 records, 89 studies (patients=5578) were eligible for qualitative synthesis and 70 (pain), 63 (physical function), 16 (mental health) and 4 (trunk muscle strength) for NMA. The NMA consistency model revealed that the following exercise training modalities had the highest probability (surface under the cumulative ranking (SUCRA)) of being best when compared with true control: Pilates for pain (SUCRA=100%; pooled standardised mean difference (95% CI): −1.86 (–2.54 to –1.19)), resistance (SUCRA=80%; −1.14 (–1.71 to –0.56)) and stabilisation/motor control (SUCRA=80%; −1.13 (–1.53 to –0.74)) for physical function and resistance (SUCRA=80%; −1.26 (–2.10 to –0.41)) and aerobic (SUCRA=80%; −1.18 (–2.20 to –0.15)) for mental health. True control was most likely (SUCRA≤10%) to be the worst treatment for all outcomes, followed by therapist hands-off control for pain (SUCRA=10%; 0.09 (–0.71 to 0.89)) and physical function (SUCRA=20%; −0.31 (–0.94 to 0.32)) and therapist hands-on control for mental health (SUCRA=20%; −0.31 (–1.31 to 0.70)). Stretching and McKenzie exercise effect sizes did not differ to true control for pain or function (p&gt;0.095; SUCRA&lt;40%). NMA was not possible for trunk muscle endurance or analgesic medication. The quality of the synthesised evidence was low according to Grading of Recommendations Assessment, Development and Evaluation criteria. Summary/conclusion There is low quality evidence that Pilates, stabilisation/motor control, resistance training and aerobic exercise training are the most effective treatments, pending outcome of interest, for adults with NSCLBP. Exercise training may also be more effective than therapist hands-on treatment. Heterogeneity among studies and the fact that there are few studies with low risk of bias are both limitations.
Association of Bariatric Surgery With Skin Cancer Incidence in Adults With Obesity
Authors: Magdalena Taube, Markku Peltonen, Kajsa Sjöholm, Åsa Anveden, Johanna C. Andersson-Assarsson, Peter Jacobson, Per-Arne Svensson, Martin O. Bergo, Lena M. S. Carlsson
Journal: JAMA Dermatology (2019)

Obesity is a cancer risk factor, and bariatric surgery in patients with obesity is associated with reduced cancer risk. However, evidence of an association among obesity, bariatric surgery, and skin cancer, including melanoma, is limited.To investigate the association of bariatric surgery with skin cancer (squamous cell carcinoma and melanoma) and melanoma incidence.This nonrandomized controlled trial, the Swedish Obese Subjects (SOS) study, is ongoing at 25 surgical departments and 480 primary health care centers in Sweden and was designed to examine outcomes after bariatric surgery. The study included 2007 patients with obesity who underwent bariatric surgery and 2040 contemporaneously matched controls who received conventional obesity treatment. Patients were enrolled between September 1, 1987, and January 31, 2001. Data analysis was performed from June 29, 2018, to November 22, 2018.Patients in the surgery group underwent gastric bypass (n = 266), banding (n = 376), or vertical banded gastroplasty (n = 1365). The control group (n = 2040) received the customary treatment for obesity at their primary health care centers.The SOS study was cross-linked to the Swedish National Cancer Registry, the Cause of Death Registry, and the Registry of the Total Population for data on cancer incidence, death, and emigration.The study included 4047 participants (mean [SD] age, 47.9 [6.1] years; 2867 [70.8%] female). Information on cancer events was available for 4042 patients. The study found that bariatric surgery was associated with a markedly reduced risk of melanoma (adjusted subhazard ratio, 0.43; 95% CI, 0.21-0.87; P = .02; median follow-up, 18.1 years) and risk of skin cancer in general (adjusted subhazard ratio, 0.59; 95% CI, 0.35-0.99; P = .047). The skin cancer risk reduction was not associated with baseline body mass index or weight; insulin, glucose, lipid, and creatinine levels; diabetes; blood pressure; alcohol intake; or smoking.The results of this study suggest that bariatric surgery in individuals with obesity is associated with a reduced risk of skin cancer, including melanoma.ClinicalTrials.gov identifier: NCT01479452.