tbuckley/cabot-search huggingface dataset:
P14.80 Advances in radiotherapy for brain tumors (benign, malignant and pediatrics tumors)
Authors: M Theodorou
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND New techniques in radiation oncology such as VMAT (volumetric modulated arc therapy), IGRT (image guidance radiotherapy) compare 3D-conformal technique offering better coverage of the target and more safety for the organs at risk for brain tumors such as Glioblastomas, low grade gliomas, pediatric tumors, meningiomas, pituitary adenomas, brain metastasis. MATERIAL AND METHODS Compare 3D-conformal treatment plans with VMAT -IGRT plan for Glioblastoma, pituitary adenoma, pediatric tumors, low grade gliomas, brain metastasis. Clinical target definition occur with Fusion of planing-MRI with Planing-CT inclusive preoperative and postoperative MRI to exact delineation of GTV (gross tumor volume), CTV (clinical target definition, PTV (planing tumor volume). contouring of organs at risk such as brainstemm, chiasm, N. opticus right and left, eye right and left, lens right and left, brain, cerebellum, internal ears. RESULTS VMAT treatment plans offer higher coverage of the target, higher homogenize radiation index and less radiation for the organs at risk. Due to the good safety of the organs at risk less toxicity during radiation was mentioned specially for neuroaxisradiation for medulloblastoma in children. The toleration during radiotherapy with VMAT technique is is much better than 3D conformal technique CONCLUSION VMAT technique offers higher radiation dose to the target and less radiation to the organs at risk with better toleration of treatment and less toxicity inclusive late side effects such as radionecrosis.
Abstract 75: High Sensitivity C Reactive Protein in Adolescent and Young Adult Patients with Kawasaki Disease Late After Onset
Authors: Yung-Chuan Chen, Yi-Ling Huang, Ching-Tsuen Shen, Nan-Koong Wang, Shuenn-Nan Chiu, Chun-An Chen, Jou-Kou Wang, Mei-Hwan Wu, Ming-Tai Lin
Journal: Circulation (2015)

Background: In children with history of Kawasaki disease (KD), low grade inflammation was ever reported to be associated with persistent coronary artery lesions (CAL). However, this issue had rarely been checked in adolescents and young adults (10-25 years old). Methods and Results: The study cohort was comprised of 104 subjects: 22 KD patients with angiography-confirmed CAL, which persisted at an average of 12.5 years after onset of KD, 38 KD patients with regressed aneurysms, 44 KD patients without any coronary complications from the disease onset and 31 age-matched (18.7 ± 1.88 years old) healthy controls. Plasma levels of high-sensitivity C reactive protein (hs-CRP) were measured for all participants with a commercially available high-sensitivity method (Immulite, Simens, USA). Plasma levels of hs-CRP were significantly higher in KD patients, regardless of the severity of coronary artery involvement, than controls. However, there was no difference of hs-CRP level between each KD patient groups including any severity of coronary artery lesions. After adjustment for confounding factors such as body mass index, gender and levels of HDL-c, linear regression analysis showed the only independent predictor of logarithmically transformed hs-CRP levels was BMI (β=0.32, p=0.007), rather than patient grouping (p=0.126). Conclusion: Levels of hs-CRP are significantly higher in adolescent and young adult KD patients than age-matched controls. However, we failed to detect significant difference among patients with different severities of CAL. The results implied, in Taiwan, low grade inflammation might play a minor role on the persistence of coronary lesions in KD.
Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study
Authors: Rasiah Thayakaran, Nicola J Adderley, Christopher Sainsbury, Barbara Torlinska, Kristien Boelaert, Dana Šumilo, Malcolm Price, G Neil Thomas, Konstantinos A Toulis, Krishnarajah Nirantharakumar
Journal: BMJ (2019)

To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures.Retrospective cohort study.The Health Improvement Network (THIN), a database of electronic patient records from UK primary care.Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017.TSH concentration in patients with hypothyroidism.Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome.162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)).In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.
A Shared Signaling Network That Maintains Erythroid Homeostasis By Activating Stress Erythropoiesis Regulates Inflammation: Implications for the Anemia of Chronic Inflammation
Authors: James Fraser, Adwitia Dey, Shaneice Nettleford, Siyang Hao, Luming Zhao, Pamela Hankey-Giblin, K. Sandeep Prabhu, Na Xiong, Robert Paulson
Journal: Blood (2018)
Johan Mouton: international expert on the pharmacokinetics and pharmacodynamics of antimicrobial agents
Authors: Tony Sheldon
Journal: BMJ (2019)

The day before he died, Dutch medical microbiologist Johan Mouton still managed a call to the meeting of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which sets guidelines for determining the sensitivity of bacteria to antibiotics. Mouton felt passionately about this standing committee of experts he helped found. He believed that it enabled scientific knowledge on the behaviour of antibiotics to be shared for the benefit of patients.

That knowledge, principally pharmacokinetics and pharmacodynamics (PK/PD)—the interaction between antimicrobial agents, microorganisms, and the human body—was his trademark; he was known as the “PK/PD man.”

In the early 1990s, he was one of a small group of medical microbiologists to study this, then relatively new, science. In a career spanning three decades he would apply its principles to achieve the best antibiotic dose, type, and method of application to tackle a specific infection. In the Netherlands, he was one of the first to consider what was the correct dose of an antibiotic, and consequently campaigned vociferously against their overuse.

Born in Leiden in 1956, he had first sought a different path from his father, Peter Mouton, an eminent medical microbiologist, and studied biology at Utrecht University. However, after an enjoyable …
No Association between Genetic Loci near <i>IRF2</i> and <i>TBX1</i> and Acute Kidney Injury in the Critically Ill
Authors: Iris J. E. Renken, Laura M. Vilander, Mari A. Kaunisto, Suvi T. Vaara, Harold Snieder, Frederik Keus, Iwan C. C. van der Horst, Ville Pettilä
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Table 1.Bold emphasizes the nonsignificance of the findings.
P14.18 Prognostic value of serial dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine PET in patients with non-resectable malignant glioma undergoing chemoradiation
Authors: J Rosen, G Stoffels, P Lohmann, E K Bauer, J Werner, M Rapp, J Felsberg, G R Fink, K Langen, N Galldiks
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A complete resection of high-grade gliomas (HGG) is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. We here evaluated the prognostic value of serial O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in patients with newly diagnosed, non-resectable astrocytic HGG undergoing chemoradiation with temozolomide. MATERIAL AND METHODS Serial dynamic FET PET scans were performed in 18 newly diagnosed patients with molecularly defined, non-resectable HGG at baseline and after chemoradiation (8±3 weeks). Both static (tumor/brain ratios, FET tumor volumes) and dynamic FET PET parameters (time-to-peak, slope), as well as MRI changes according to RANO criteria at first follow-up after chemoradiation (8±3 weeks), were obtained. The predictive ability of FET PET parameters and RANO criteria was evaluated with regard to the progression-free survival (PFS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate and multivariate survival analyses were performed to assess their predictive power for PFS. RESULTS ROC analysis revealed that the mean tumor/brain ratio (AUC, 0.84), FET tumor volume (AUC, 0.89), and slope (AUC, 0.72) at baseline were predictive for a prolonged PFS (9.3 vs. 5.7 months, P=0.05; 10.3 vs. 5.9 months; P=0.03; 13.5 vs. 6.2 months, P=0.02, respectively). Furthermore, FET tumor volume and slope remained significant in the multivariate survival analysis (both P&lt;0.05). In contrast, relative changes of static or dynamic FET PET parameters at follow-up and MRI changes according to RANO criteria were not significant in this albeit small series of patients. CONCLUSION Results suggest that before initiation of chemoradiation FET PET parameters at baseline can be used to predict PFS in patients with non-resectable HGG.
Defining HLA-II Ligand Processing and Binding Rules with Mass Spectrometry Enhances Cancer Epitope Prediction
Authors: Jennifer G. Abelin, Dewi Harjanto, Matthew Malloy, Prerna Suri, Tyler Colson, Scott P. Goulding, Amanda L. Creech, Lia R. Serrano, Gibran Nasir, Yusuf Nasrullah, Christopher D. McGann, Diana Velez, Ying S. Ting, Asaf Poran, Daniel A. Rothenberg, Sagar Chhangawala, Alex Rubinsteyn, Jeff Hammerbacher, Richard B. Gaynor, Edward F. Fritsch, Joel Greshock, Rob C. Oslund, Dominik Barthelme, Terri A. Addona, Christina M. Arieta, Michael S. Rooney
Journal: Immunity (2019)
Understand the effect of environmental and structural migration factors on the sexual and reproductive health of youth in central Asia and Africa: a modelling study
Authors: Uma Girkar, Pragati Jaiswal, Amber Nigam, Teertha Arora
Journal: The Lancet Planetary Health (2019)

BackgroundEvery year millions of young people between the ages of 10 and 24 years in central Asia and Africa migrate to urban areas in search of better opportunities. Common factors driving youth migration include environmental degradation, war and conflict, and lack of economic opportunity and poverty. In collaboration with the United Nations Population Fund (UNFPA), our aim was to study the effect of migration on the sexual and reproductive health (SRH) needs of youth in Nairobi, Cairo, Beirut, and Tunis through the development of technological solutions for data collection and identification of youth most vulnerable to SRH issues.MethodsWe designed a web application useful for both migrants and researchers that contains a 27-question survey to collect migrant data on basic profile metrics such as their geographical journey and their sexual relations. This data can be used to inform the UNFPA's service, delivery, and policy efforts. The website also features a geographical healthcare centres map and safety tips for migrants. Additionally, we artificially created a dataset of 1000 migrant profiles to train a machine learning model to predict SRH vulnerabilities in young people.FindingsThe neural network model and the support vector machines algorithm demonstrated high accuracies of 0·92 and 0·90 respectively in predicting the most vulnerable youth. We optimised our algorithm to minimise false-negatives, even at the cost of a few false-positives.InterpretationOur results provide an opportunity to identify vulnerable youth for local officials to potentially reach out to in order to prevent SRH issues and to understand how such vulnerabilities might stem from their environmental and structural migration factors. Furthermore, researchers can investigate based on data collected from the web application how overcrowding of migrants in urban areas outstrips the areas of resources to further compromise the SRH health of the migrants.FundingNone.
P09.04 Natural history of meningiomas: review with meta-analyses
Authors: S Nakasu, Y Nakasu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A recent investigation using MRI showed 2.5% frequency of meningioma as an incidental finding in the population-based neuroimaging study. Although observation has been a mainstay in asymptomatic meningiomas, it may increase the risk of surgery due to enlargement of the tumors and aging of patients. It is important to characterize tumors that will grow to be symptomatic in order to select appropriate treatments and radiological follow-up. MATERIAL AND METHODS We reviewed 26 studies (3 from the same institute) that analyzed natural courses in asymptomatic or untreated meningiomas. Radiological progression of tumor was redefined as tumor growth by 15% of initial volume or more whenever possible. To adjust the difference of follow-up interval in each study, the percentages of growing tumors in each study were compared with each mean follow-up period. Individual data were extracted from seven studies for univariate or multivariate analyses. Weighted meta-analyses were performed using the 25 studies. RESULTS In time-growth rate analysis, nearly 70% of meningiomas showed radiological progression defined by a volume criteria and the rate approached plateau at 5–6 years. Meta-analyses showed that each radiological progression, growth speed (annual volume change (AVC) or relative growth rate (RGR)) and symptomatic progression had different factors related to their progression. Age, calcification and high intensity on T2 weighted image related to radiological progression and growth speed but not to clinical progression. In individual data analyses, tumor size (diameter 2.6cm (AUC 0.773; specificity 0.759, sensitivity 0.800), volume 5.6cm3 (AUC 0.775, specificity 0.717, sensitivity 0.800)) was a possible marker for symptomatic growth.AVC (&gt;= 2.1cm3/year) was the strongest indicator for clinical progression. In the group of &gt;=2.1cm3/year, Kaplan-Meier analysis showed that progression free rate was 69.3% at 3 years, and reached to 55.4% at 6 years whereas 100% in slower growth group. CONCLUSION Radiological features may not be very much useful for prediction of clinical progression except for perifocal edema. This may be due to dynamic changes of these radiological markers in a long term. Initial quantitative tumor size and growth speed especially AVC were reliable factors for decision of treatment for asymptomatic meningiomas.
Impaired NF-κB signalling underlies cyclophilin D-mediated mitochondrial permeability transition pore opening in doxorubicin cardiomyopathy
Authors: Rimpy Dhingra, Matthew Guberman, Inna Rabinovich-Nikitin, Jonathon Gerstein, Victoria Margulets, Hongying Gang, Nicholas Madden, James Thliveris, Lorrie A Kirshenbaum
Journal: Cardiovascular Research (2019)

The chemotherapy drug doxorubicin (Dox) is commonly used for treating a variety of human cancers; however, it is highly cardiotoxic and induces heart failure. We previously reported that the Bcl-2 mitochondrial death protein Bcl-2/19kDa interaction protein 3 (Bnip3), is critical for provoking mitochondrial perturbations and necrotic cell death in response to Dox; however, the underlying mechanisms had not been elucidated. Herein, we investigated mechanism that drives Bnip3 gene activation and downstream effectors of Bnip3-mediated mitochondrial perturbations and cell death in cardiac myocytes treated with Dox.Nuclear factor-κB (NF-κB) signalling, which transcriptionally silences Bnip3 activation under basal states in cardiac myocytes was dramatically reduced following Dox treatment. This was accompanied by Bnip3 gene activation, mitochondrial injury including calcium influx, permeability transition pore (mPTP) opening, loss of nuclear high mobility group protein 1, reactive oxygen species production, and cell death. Interestingly, impaired NF-κB signalling in cells treated with Dox was accompanied by protein complexes between Bnip3 and cyclophilin D (CypD). Notably, Bnip3-mediated mPTP opening was suppressed by inhibition of CypD-demonstrating that CypD functionally operates downstream of Bnip3. Moreover, restoring IKKβ-NF-κB activity in cardiac myocytes treated with Dox suppressed Bnip3 expression, mitochondrial perturbations, and necrotic cell death.The findings of the present study reveal a novel signalling pathway that functionally couples NF-κB and Dox cardiomyopathy to a mechanism that is mutually dependent upon and obligatorily linked to the transcriptional control of Bnip3. Our findings further demonstrate that mitochondrial injury and necrotic cell death induced by Bnip3 is contingent upon CypD. Hence, maintaining NF-κB signalling may prove beneficial in reducing mitochondrial dysfunction and heart failure in cancer patients undergoing Dox chemotherapy.
Erratum to: ‘Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia’
Authors: Chien-Hung Yeh, Xue Tao Bai, Ramona Moles, Lee Ratner, Thomas A. Waldmann, Toshiki Watanabe, Christophe Nicot
Journal: Molecular Cancer (2016)
Association of Cavum Septum Pellucidum and Cavum Vergae With Cognition, Mood, and Brain Volumes in Professional Fighters
Authors: Jonathan K. Lee, Jenny Wu, Jennifer Bullen, Sarah Banks, Charles Bernick, Michael T. Modic, Paul Ruggieri, Lauren Bennett, Stephen E. Jones
Journal: JAMA Neurology (2019)

Many studies have investigated the imaging findings showing sequelae of repetitive head trauma, with mixed results.To determine whether fighters (boxers and mixed martial arts fighters) with cavum septum pellucidum (CSP) and cavum vergae (CV) have reduced volumes in various brain structures or worse clinical outcomes on cognitive and mood testing.This cohort study assessed participants from the Professional Fighters Brain Health Study. Data were collected from April 14, 2011, to January 17, 2018, and were analyzed from September 1, 2018, to May 23, 2019. This study involved a referred sample of 476 active and retired professional fighters. Eligible participants were at least 18 years of age and had at least a fourth-grade reading level. Healthy age-matched controls with no history of trauma were also enrolled.Presence of CSP, CV, and their total (additive) length (CSPV length).Information regarding depression, impulsivity, and sleepiness among study participants was obtained using the Patient Health Questionnaire depression scale, Barrett Impulsiveness Scale, and the Epworth Sleepiness Scale. Cognition was assessed using raw scores from CNS Vital Signs. Volumes of various brain structures were measured via magnetic resonance imaging.A total of 476 fighters (440 men, 36 women; mean [SD] age, 30.0 [8.2] years [range, 18-72 years]) and 63 control participants (57 men, 6 women; mean [SD] age, 30.8 [9.6] years [range, 18-58 years]) were enrolled in the study. Compared with fighters without CV, fighters with CV had significantly lower mean psychomotor speed (estimated difference, -11.3; 95% CI, -17.4 to -5.2; P = .004) and lower mean volumes in the supratentorium (estimated difference, -31 191 mm3; 95% CI, -61 903 to -479 mm3; P = .05) and other structures. Longer CSPV length was associated with lower processing speed (slope, -0.39; 95% CI, -0.49 to -0.28; P < .001), psychomotor speed (slope, -0.43; 95% CI, -0.53 to -0.32; P < .001), and lower brain volumes in the supratentorium (slope, -1072 mm3 for every 1-mm increase in CSPV length; 95% CI, -1655 to -489 mm3; P < .001) and other structures.This study suggests that the presence of CSP and CV is associated with lower regional brain volumes and cognitive performance in a cohort exposed to repetitive head trauma.
Insulin promotes sodium transport but suppresses gluconeogenesis via distinct cellular pathways in human and rat renal proximal tubules
Authors: Motonobu Nakamura, Hiroyuki Tsukada, George Seki, Nobuhiko Satoh, Tomohito Mizuno, Wataru Fujii, Shoko Horita, Kyoji Moriya, Yusuke Sato, Haruki Kume, Masaomi Nangaku, Masashi Suzuki
Journal: Kidney International (2019)