tbuckley/cabot-search huggingface dataset:
OS6.4 The hypoxia-induced glioma derived exosome miRNA-199a-3p promotes glioma cells proliferation and increased ischemic injury of the para-tumor neurons by inhibiting mTOR pathway— A pivotal ischemic mechanism in the proliferation and growth of glioma
Authors: J Zhao, J Hu, R Xie
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Growth of glioma cells can be promoted by hypoxia, but its underlying molecular mechanisms are not clear. Exosomes and miRNAs were reported to play crucial roles in tumor progression. Effects of exosomes and exosomal miRNAs, induced by hypoxia, on glioma cells were still unclear. MATERIAL AND METHODS Glioma samples were analyzed by HE and HIF-1α staining. Image data of these patients were also retrospectively analyzed. HT22 and C6 cell lines were co-cultured in both direct and indirect system. Hypoxia (1% oxygen) and oxygen and glucose deprivation (OGD) were applied to evaluate hypoxia effects on the growth and proliferation of cell lines, and such effects were assessed by C6/HT22 ratio, MTT and LDH assay. Hypoxia-induced glioma derived exosomes (HIGDE) and non-HIGDE (NHIGDE) were isolated and were administrated to normal culture medium to evaluate their effects on cell growing. The target miRNA was selected by performing miRNA microarray analysis. MicroRNA mimics and shRNA were constructed to overexpress or inhibit the microRNA expression. MTOR signal pathway was activated by utilizing phosphatidic acid. The RNAs expression were detected by RT-qPCR and the proteins expression was evaluated by western blotting. RESULTS Para-tumor hypoxia area shared a same region with cytotoxic edema around the glioma lesion and can be easily detected by PET/CT. The density of positive HIF-1αstaining was higher in tumor area than that in para-tumor and normal parenchyma area. In hypoxia direct co-culture system, the cell number ratio of C6/HT22 was significantly higher than that without hypoxia pretreatment; while in hypoxia mono-culture and indirect co-culture systems, the proliferation ability of HT22 was statistical lower than C6. After applying OGD, neuron cells cultured with HIGDE showed a statistical higher LDH release level than with NHIGDE or normal culture medium. The miRNA microarray analysis revealed that miRNA-199a-3p was the highest expressed in HIGDE than in NHIGDE (p &lt; 0.05; Fold Change &gt; 2). Transfected with mimics or shRNA, it was indicated that upregulation of miR-199a-3p aggravated HIGDE-induced OGD injury in HT22 cells. Moreover, we interfered mTOR signal pathway and the expression of HIF-1αin C6 cells. We found that miRNA-199a-3p aggravated HIGDE-neuron cell injury via suppressing mTOR signal pathway, and hypoxia related upregulation of miRNA-199a-3p in HIGDE was induced by the activation of HIF-1α in C6 cells. CONCLUSION The Hypoxia-Induced Glioma Derived Exosome miRNA-199a-3p can be upregulated by the activation of HIF-1α, and is able to promote glioma cells proliferation and increase ischemic injury of the para-tumor neurons via inhibiting mTOR pathway.
Building resilience of health systems to climate change in Pacific Least Developed Countries: implementation science
Authors: Kristie Ebi, Chris Boyer
Journal: The Lancet Planetary Health (2019)

BackgroundThe Pacific Least Developed Countries (LDCs)—Kiribati, the Solomon Islands, Tuvalu, and Vanuatu—are among the countries most vulnerable to climate variability and change. Key climate change risks include loss of livelihoods, coastal settlements, infrastructure, ecosystem services, and economic stability; and interaction of sea level rise with high-water-level events, threatening low-lying coastal areas. These risks result in increased health impacts, including deaths and injuries from extreme events (eg, heatwaves, storms, and floods); increased risks of infectious diseases (including food-borne, water-borne, and vector-borne); food insecurity and malnutrition; and diffuse impacts from loss of livelihoods and migration. The young, older adults, women of reproductive age, and people with disabilities are most vulnerable.MethodsBuilding resilience to climate change requires that these countries develop National Climate Change and Health Action Plans, including Vulnerability and Adaptation assessments.FindingsTemperature, precipitation, and extreme weather events can influence the incidence, geographic distribution, and seasonality of climate-sensitive health outcomes. In addition, many hospitals and community health centres are highly vulnerable to cyclones, floods, storm surges, sea level rise, and disturbances in water supply caused by drought or salination of aquifers. The capacity to provide health services, particularly in emergency situations, is substantially affected if buildings and essential supplies and amenities are damaged. The majority of health facilities are not resilient to climate-induced pressures in terms of structural, non-structural, and functional safety.InterpretationThe most effective measures to reduce vulnerability are (i) short-term programmes that implement and improve basic public health measures, including the provision of safe water and improved sanitation, secure essential health care, and increase capacity for disaster preparedness and response; and (ii) longer-term programs that enhance national health systems and institutions with climate change-related risks integrated into health governance, strengthen health information management systems, and ensure effective and accessible delivery of health services.FundingLeast Developed Countries Fund under the United Nations Framework Convention on Climate Change.
P13.13 Clinical factors involved in brain metastasis edema: results of a retrospective cohort and evaluation of the best edema descriptor
Authors: Y Pin, M Loo, W Waissi, A Paix, J Todeschi, D Antoni, F Proust, G Ahle, G Noël
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Brain metastasis (BM) are frequently surrounded by brain edema with a variable extension. This pathological increase in the water mass from the interstitial or intracellular space is the source of neurological symptoms but some studies also showed a prognosis impact of this edema. Nevertheless, the current edema evaluation methods are poorly reproducible and were not extensively evaluated. From a series of patients with brain metastasis, we analyzed factors influencing perilesional edema extension in function of three edema descriptors which were qualitatively evaluated: the absolute cumulative intracranial edema volume (CIEV, in mL), the edema on tumor volume ratio (ER), and the Edema Theoretical Thickness (ETT, in mm), new factor designed to be more independent from geometrical considerations. MATERIAL AND METHODS Clinical, biological and imaging factors were retrospectively recorded from patients referred for upfront stereotactic radiotherapy of one to three BMs. CIEV, ER and ETT were calculated for each patient. Non-colinear factors were selected using the Farrar-Glauber test. Impact of these factors on edema was tested with an univariate then a multivariate linear regression for each edema descriptor. Each resulting regression model was qualitatively evaluated using the F-test, R square value and residuals calculation. RESULTS Between January 2012 to December 2017, 182 patients were included. Upon 20 potentially prognostic factors recorded, 10 were kept, including clinical, biological and imaging factors. In the multivariate analysis, the CIEV was influenced by the cumulative intracranial tumor volume (CITV) (coefficient of 1.95, p&lt;.001). The CIEV F-statistic p-value and R square were &lt;10–15 and 0.30, respectively. The ETT was significantly influenced by the CITV (0.31, p&lt;.001) and the extracerebral disease control (-1.58, p=.049). The F-test p-value and R square were &lt;10-10 and 0.25, respectively. No significant linear regression was found for the ER. Residuals were more clinically relevant for the ETT compared to the CIEV. CONCLUSION Being significantly influenced by the cumulative brain tumor volume and the extracerebral disease control, the ETT might be a factor to include in future BM works because its strong relationships with confounding factors and its ability to provide robust intra and inter subjects comparisons.
Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy
Authors: Lauren Elizabeth Walker, Federica Frigerio, Teresa Ravizza, Emanuele Ricci, Karen Tse, Rosalind E. Jenkins, Graeme John Sills, Andrea Jorgensen, Luca Porcu, Thimmasettappa Thippeswamy, Tiina Alapirtti, Jukka Peltola, Martin J. Brodie, Brian Kevin Park, Anthony Guy Marson, Daniel James Antoine, Annamaria Vezzani, Munir Pirmohamed
Journal: Journal of Clinical Investigation (2019)
Abstract 19350: The Decline of the Montreal Cognitive Test Can Detect Post-stroke Cognitive Decline Determined by a Formal Neuropsychological Evaluation
Authors: Kenny Xu, Catherine Dong, Christopher Chen
Journal: Circulation (2015)

Objective: We aimed to establish the association of decline in cognitive screening tests scores, the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), with the decline in neuropsychological diagnostic status from 3-6 months to a year later. Method: Patients with ischemic stroke/ Transient Ischemic Attack (TIA) received the MoCA and MMSE within 14 days after stroke, then 3-6 months and 1 year later. The decline in MoCA and MMSE scores were defined by reduction of 2 points or more in total scores, while stable/improved MoCA scores referred to reduction of MoCA scores less than 2 or improved scores. The decline in neuropsychological diagnostic status was defined by category transition from no cognitive impairment to any cognitive impairment (≥1 domain), from mild cognitive impairment (impairment in 1-2 domains) to moderate cognitive impairment (impairment &gt;2 domains) and dementia (i.e., functional loss associated with cognitive impairment, DSM-IV criteria), as well as from moderate cognitive impairment to dementia. Results: At baseline, most patients were Chinese (70.3%) and males (69.8%) with age of 59.8 ± 11.6 years and education of 7.7 ± 4.3 years. 327 out of 400 stroke/TIA patients completed neuropsychological assessments at 3-6 months and 275 completed at 1 year after their index cerebrovascular events. Of these, 31 (11.3%) had decline in neuropsychological diagnostic status. Logistic regression was used to model the association between probability of decline in neuropsychological diagnostic status and the decline in MMSE or MoCA scores. There were not significant associations between the decline of neuropsychological diagnostic status and the decline in MMSE scores. Controlling baseline MoCA scores and the change scores of MoCA from baseline to 3-6 months, patients with decline in MoCA scores (reduction of 2 points or more) were associated with higher risks of decline in neuropsychological diagnostic status, relative to those with stable/ improved MoCA scores (odd ratio=3.21, p=0.004). Conclusion: The decline in MoCA scores are associated with a higher risks for decline in neuropsychological diagnostic status from 3-6 months to 1 year, therefore may be used to detect post-stroke cognitive decline.
Perinatal Outcomes in Medicaid Expansion and Nonexpansion States Among Hispanic Women—Reply
Authors: Clare C. Brown, J. Mick Tilford
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Image Gallery: Lichen planus pigmentosus of the tongue
Authors: Y. Wang, H. Jin
Journal: British Journal of Dermatology (2019)

Funding sources: this study was funded by the CAMS Initiative for Innovative Medicine (2017‐I2M‐B&R‐01). Conflicts of interest: none to declare. Dear Editor, A 62‐year‐old woman presented with a 1‐month history of asymptomatic gray‐blue patches on the lips and tongue (a). The lesions of the tongue were annular with partial normal central areas. The patient also reported a 4‐year history of symmetrically distributed brown pruritic patches on her inguinal folds and lower abdomen (b). She had no history of contact or medication. A skin biopsy of mucosal tissue showed hyperkeratosis accompanied by parakeratosis, vacuolar alteration of the basal layer, bandlike infiltration of lymphocytes, pigmentary incontinence, and melanophages in the superficial dermis. These findings supported a diagnosis of lichen planus pigmentosus (LPP). In the present case, the normal central areas of the tongue expanded, and most of the lesions on the trunk disappeared spontaneously after a 3‐month follow‐up. LPP affects mainly the face, neck and flexural areas. Tongue involvement has never been reported. Treatment with topical calcineurin inhibitors and corticosteroids was recommended.1 ...
MITRE: inferring features from microbiota time-series data linked to host status
Authors: Elijah Bogart, Richard Creswell, Georg K. Gerber
Journal: Genome biology (2019)

Longitudinal studies are crucial for discovering causal relationships between the microbiome and human disease. We present MITRE, the Microbiome Interpretable Temporal Rule Engine, a supervised machine learning method for microbiome time-series analysis that infers human-interpretable rules linking changes in abundance of clades of microbes over time windows to binary descriptions of host status, such as the presence/absence of disease. We validate MITRE's performance on semi-synthetic data and five real datasets. MITRE performs on par or outperforms conventional difficult-to-interpret machine learning approaches, providing a powerful new tool enabling the discovery of biologically interpretable relationships between microbiome and human host ( https://github.com/gerberlab/mitre/ ).
Biomaterial-based platforms for in situ dendritic cell programming and their use in antitumor immunotherapy
Authors: João Calmeiro, Mylène Carrascal, Célia Gomes, Amílcar Falcão, Maria Teresa Cruz, Bruno Miguel Neves
Journal: Journal for ImmunoTherapy of Cancer (2019)

Dendritic cells (DCs) are central players in the immune system, with an exquisite capacity to initiate and modulate immune responses. These functional characteristics have led to intense research on the development of DC-based immunotherapies, particularly for oncologic diseases. During recent decades, DC-based vaccines have generated very promising results in animal studies, and more than 300 clinical assays have demonstrated the safety profile of this approach. However, clinical data are inconsistent, and clear evidence of meaningful efficacy is still lacking. One of the reasons for this lack of evidence is the limited functional abilities of the used ex vivo-differentiated DCs. Therefore, alternative approaches for targeting and modulating endogenous DC subpopulations have emerged as an attractive concept. Here, we sought to revise the evolution of several strategies for the in situ mobilization and modulation of DCs. The first approaches using chemokine-secreting irradiated tumor cells are addressed, and special attention is given to the cutting-edge injectable bioengineered platforms, programmed to release chemoattractants, tumor antigens and DC maturating agents. Finally, we discuss how our increasing knowledge of DC biology, the use of neoantigens and their combination with immune checkpoint inhibitors can leverage the refinement of these polymeric vaccines to boost their antitumor efficacy.
P14.21 Tehila Kaisman-Elbaz MD/PhD
Authors: T Kaisman-Elbaz, Y Elbaz, V Merkin, L Dym, A Noy, M Atar-Vardi, R Bari, S Turiel, K Lavrenkov, I Melamed
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is known for its dismal prognosis though its dependency on patients’ readily available RBCs parameters defining the patient’s anemic status such as hemoglobin level and Red blood cells distribution Width (RDW) is not fully established. Several works demonstrated a connection between low hemoglobin level or high RDW values to overall glioblastoma patient’s survival, but in other works, a clear connection was not found. This study addresses this unclarity. MATERIAL AND METHODS In this work, 170 glioblastoma patients, diagnosed and treated in Soroka University Medical Center (SUMC) in the last 12 years were retrospectively inspected for their survival dependency on pre-operative RBCs parameters using multivariate analysis followed by false discovery rate procedure due to the multiple hypothesis testing. A survival stratification tree and Kaplan-Meier survival curves that indicate the patient’s prognosis according to these parameters were prepared. RESULTS Beside KPS&gt;70 and tumor resection supplemented by oncological treatment, age&lt;70 (HR=0.4, 95% CI 0.24–0.65), low hemoglobin level (HR=1.79, 95% CI 1.06–2.99) and RDW&lt;14% (HR=0.57, 95% CI 0.37–0.88) were found to be prognostic to patients’ overall survival in multivariate analysis, accounting for false discovery rate of less than 5%. CONCLUSION A survival stratification highlighted a non-anemic subgroup of nearly 30% of the cohort’s patients whose median overall survival was 21.1 months (95% CI 16.2–27.2) - higher than the average Stupp protocol overall median survival of about 15 months. A discussion on the beneficial or detrimental effect of RBCs parameters on glioblastoma prognosis and its possible causes is given.
Morphologic and Hemodynamic Changes in the Smaller Blood Vessels in Diabetes Mellitus
Authors: Jörn Ditzel
Journal: New England Journal of Medicine (1954)

SINCE the most serious problem in diabetes mellitus today is the associated vascular degeneration, a proper understanding of the pathology and pathogenesis of these changes is essential. This is particularly true in the light of the recent report that the retinal changes in diabetes may be reversible,1 giving hope that a rational therapy may be found if causative factors are known. There is rapidly accumulating evidence that the lesions in the smaller blood vessels are most characteristic of the generalized abnormality of the vessel walls. The structural integrity of the walls of the larger vessels is dependent on the function . . .
Safety of cabazitaxel in elderly patients with metastatic castrate resistant prostate cancer (mCRPC) previously treated with docetaxel therapy.
Authors: Angela Gernone, Giuseppe Calderoni, Simona Vallarelli, Elisa Montagna, Arcangelo Pagliarulo, Francesco Silvestris
Journal: Journal of Clinical Oncology (2013)

e16081 Background: Cabazitaxel (Cab) is a novel taxane for treatment of mCRPC in progression during or after Docetaxel therapy. However, the management of elderly pts also depends on comorbidities that may impact the performance status and influence the treatment decisions. This study was aimed to assess both activity and safety of Cab in a cohort of ≥ 65 yrs aged patients with mCRPC unresponsive to Docetaxel. Methods: Between 11/2011 and 01/2013, 26 pts with mCRPC relapsing after Docetaxel as first line treatment were enrolled following their comprehensive geriatric assessment for eligibility to the study also extended as EAP. The Cab schedule included 25 mg/m 2 every three weeks plus 10 mg Prednisone (P) daily. Comorbidities were assessed using the cumulative illness rating geriatric scale (CIRS-G) with 0-4 score. Median age was 73 yrs (65-89), ECOG PS 0-2, median baseline PSA was 107 ng/ml, whereas comorbidities included pneumonia, arterial hypertension, arrhythmias and diabetes. Pts were managed every 3 months by CT, whereas both response rate (RR) and correlations between comorbidities and toxicity were the endpoints of the study. Results: Pts received the CabP schedule with none dose reduction. Minimal adverse effects were recorded as grade 3-4 anemia whereas no episodes of neutropenic fever were observed. Sexteen/26 pts entered in EAP study. Comorbidities were recorded as GIRS-G1-2 in 17 pts, G3 in 7, and G4 in 2. 9/26 pts received total previous docetaxel dose &lt; 1200 mg/tot and 17/26 pts received ≥ 1200 mg/toto. Among the CabP-treated pts, 3 of them showed partial response with one year of median duration and PSA response ≥ 50%, whereas 8 maintained a stable disease with 9 months of median duration and PSA response &lt; 50%. Conversely, 15 pts underwent progression after 5 months of CabP treatment. Conclusions: Our data suggest that comorbidities in mCRPC ≥ 65 yrs aged pts do not interfere with the toxicity of CabP thus supporting its efficacy and safety in older pts unresponsive to previous Docetaxel therapy. Therefore, CabP does not impact the quality of life and emphasizes a proper disease control (PR+SD) in 11/26 pts.
P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions
Authors: T Kazda, R Lakomy, I Selingerova, P Pospisil, L Hynkova, R Belanova, P Slampa
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or &amp;gt;25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p&amp;lt;0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.