tbuckley/cabot-search huggingface dataset:
Abstract 18907: Genetic Ablation of Voltage-Gated Potassium Channel β-subunit 2 Causes Distinct Physiological and Cardiac Alterations in Mice
Authors: Siva K Panguluri, Peter J Kilfoil, Kalyan C Chapalamadugu, Jared Tur, Aruni Bhatnagar, Srinivas M Tipparaju
Journal: Circulation (2013)

Voltage-gated potassium channels (Kv) are important for cardiac function. Recent studies from our group showed dysregulation of Kv4.2 and 1.4 in diabetes or hyperoxia. The activity of Kvα is regulated by β-subunits and mutations in these subunits are associated with cardiovascular diseases. Recent report suggests that Kvβ2 (Kcnab2), a dominant β-subunit in the brain modulates inactivation rates of Kv1.4 currents and can promote the trafficking of Kv1.1 and 1.2 to the cell surface. The physiological and molecular roles of Kvβ2 in cardiac functioning are unknown. Therefore, in the current study we investigated the functional alterations and assessed the molecular changes in Kvβ2KO (KO) mouse hearts. Physical assessment of heart reveals significant cardiac atrophy in KO by measure of heart weight to tibia length ratio, WT: 7.44±0.31mg/mm vs KO: 6.23±0.15mg/mm (p&lt;0.002). The shape and structure of KO mouse hearts are smaller than their littermate wild type (WT). Molecular evaluation shows significant (p≤0.05) elevation of atrophy markers such as pyruvate dehydrogenase lipoamide kinase isozyme 4, uncoupling protein 3, atrogin, insulin-like growth factor, phospholamban, calcineurin, and slow-twitch myosin heavy chain-7. Echocardiography showed significant reduction in end diastolic volume (EDV) in KO mice compared with WT (15% less in KO than WT, p&lt;0.01). Action potentials recorded at room temperature from right ventricular myocytes showed that KO (n=18) had significantly slower action potential durations than WT (n=27) at APD20 (2.04±0.08ms vs. 1.78±0.06ms, p&lt;0.025), APD50 (4.45±0.34ms vs. 3.64±0.24ms, p&lt;0.05), and APD90 (24.30±2.56ms vs. 17.42±1.22ms, p=0.01) levels. Lead II ECG recordings from anesthetized WT and KO mice were unchanged. Western blotting revealed a significant elevation of Kvβ1.2 in right ventricle and Kv1.5 in left ventricle of KO hearts. Based on functional and pathological assessment the extent of atrophy in KO hearts along with biochemical and molecular mechanisms are reported for the first time in this study. In summary our study showed that genetic deletion of Kvβ2 cause distinct physiological and cardiac changes suggesting its importance in cardiac physiology.
Correction to: Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis
Authors: Chengping Wen, Zhijun Zheng, Tiejuan Shao, Lin Liu, Zhijun Xie, Emmanuelle Le Chatelier, Zhixing He, Wendi Zhong, Yongsheng Fan, Linshuang Zhang, Haichang Li, Chunyan Wu, Changfeng Hu, Qian Xu, Jia Zhou, Shunfeng Cai, Dawei Wang, Yun Huang, Maxime Breban, Nan Qin, Stanislav Dusko Ehrlich
Journal: Genome biology (2017)

Upon publication of the original article [1], it was noted that references 11 and 22 were miscited in the reference list.
P2.16-004 Alternative Subpreural Lymph Flow Pathways in Human Lung – a Hundred Cases Experience and Analysis
Authors: T. Tokunaga, A. Takeda, Y. Watanabe, T. Umehara, S. Suzuki, G. Kamimura, K. Maeda, M. Aoki, T. Nagata, T. Otsuka, N. Yokomakura, K. Kariatsumari, K. Sakasegawa, Y. Nakamura, M. Yanagi, M. Sato
Journal: Journal of Thoracic Oncology (2017)
OA 12.02 Final Results of a Phase 2 Study of the hsp90 Inhibitor Luminespib (AUY922) in NSCLC Patients Harboring EGFR Exon 20 Insertions
Authors: Z. Piotrowska, D. Costa, M. Huberman, G. Oxnard, J. Gainor, R. Heist, I. Lennes, A. Muzikansky, A. Shaw, C. Azzoli, L. Sequist
Journal: Journal of Thoracic Oncology (2017)
METB-05. IDENTIFICATION OF A SEXUAL DIMORPHISM IN GLIOMA PYRUVATE METABOLISM
Authors: Zhepeng Wang, Joshua Rubin, Joseph Ippolito
Journal: Neuro-Oncology (2017)

In many cancers including gliomas, males not only have a higher incidence but also higher mortality. Although the molecular mechanisms underlying this phenomenon have yet to be fully elucidated, there is evidence that males are characterized by enhanced central carbon metabolism relative to females from the time of fertilization through adulthood. Because of the inverse correlation between tumor glucose metabolism and patient survival, we hypothesized that sex differences in glucose metabolism underlie sex differences in survival. We developed a TCGA data mining algorithm to identify glycolytic gene expression patterns that correlated with poor sex-specific outcomes. We applied this algorithm to the lower grade glioma (LGG) transcriptome and identified multiple glycolytic transcripts that uniquely stratified male LGG. Of these, a cohort of transcripts involved in pyruvate metabolism (lactate dehydrogenase A) and transport (MCT3, MCT4) were identified. To validate this finding, we used transformed astrocytes from the Nf1-/-DNp53 mouse model for sexual dimorphism in glioblastoma. We performed quantitative nutrient deprivation studies and demonstrated that transformed male astrocytes were not only more susceptible to glucose deprivation than female astrocytes, but pyruvate supplementation as a primary carbon source had significantly more robust effects on male viability than females. Next, we tested the effects of hydrazine, a therapeutic and known pyruvate scavenger. We demonstrated sex-specific responses to hydrazine that adversely affected males more than females. This was further validated by stable isotope tracer studies of central carbon metabolism that demonstrated sex-specific differences in label incorporation. Together, these findings suggest that currently existing therapeutics and dietary modifications that target central carbon metabolism may elicit sex differences in response to therapy. Moreover, clinically-relevant metabolic imaging modalities such as FDG-PET or hyperpolarized [C-13] pyruvate MRI may identify prognostic sex differences in vivo.
Focolaio epidemico di gastroenterite da salmonella tra gli invitati all'inaugurazione di un ristorante in Grecia, Giugno 1998
Authors: C Hadjichristodoulou, E Nikolakopoulou, K Karabinis, E Karakou, A Markogiannakis, C Panoulis, M Lampiri, P Tassios
Journal: Eurosurveillance (1999)

Fino a poco tempo fa, in Grecia, il sistema di notifica delle malattie infettive era inadeguato ma, nel 1998, e stato introdotto un nuovo sistema di notifica, in cui, in tutta la Grecia, i laboratori coinvolti notificano ogni settimana, mediante posta elettronica o fax, utilizzando moduli standard e, sia il numero complessivo degli esami che i risultati positivi su determinate malattie infettive, vengono riferiti con regolarita. Nel 1997, solo 326 casi di infezione da salmonella sono stati notificati al Ministero della Sanita mentre, nel 1998, in 15 settimane, col nuovo sistema di notifica dei laboratori, sono stati notificati 662 casi.
Brote de infección por la subespecie Enterica de Salmonella enterica, serotipo Enteritidis (Salmonella Enteritidis) en un hotel del Reino Unido, 2006
Authors: N Calvert, L Murphy, A Smith, D Copeland, M Knowles
Journal: Eurosurveillance (2007)

El verano de 2006 se declaro un brote de salmonelosis alimentaria causada por Salmonella Enteritidis PT4 en Cumbria, al noroeste de Inglaterra. Quince personas, todas ellas con muestras de heces positivas, correspondian a la definicion de caso; tres de estas fueron hospitalizadas y una de ellas fallecio.
P1.13-011 Prospective Cohort Study of Patterns of Staging and Treatment Selection with or Without Multidisciplinary (MD) Care
Authors: F. Rugless, M. Ray, M. Smeltzer, B. Jackson, C. Foust, A. Patel, N. Boateng, N. Faris, C. Houston-Harris, C. Fehnel, M. Meadows, K. Roark, L. Mchugh, R. Signore, E. Robbins, R. Fox, R. Osarogiagbon
Journal: Journal of Thoracic Oncology (2017)
ACTR-93. A PHASE I STUDY OF MLN0128 (TAK-228) AND BEVACIZUMAB IN PATIENTS WITH ADVANCED SOLID TUMORS INCLUDING GLIOBLASTOMA
Authors: Lakshmi Nayak, John Hays, Khanh Do, Alona Muzikansky, Sarah Gaffey, Eudocia Lee, Mikael Rinne, Andrew Norden, Rameen Beroukhim, Vinay Puduvalli, Patrick Wen, L Austin Doyle, Helen Chen, Geoffrey Shapiro, David Reardon
Journal: Neuro-Oncology (2017)

The P13K/Akt/mTOR signaling axis plays a central role in cell growth and survival in a variety of cancers. MLN0128(TAK-228) is an oral inhibitor of TORC1/2 complexes. Bevacizumab is a monoclonal antibody targeting VEGF with activity in some cancers. We conducted a Cancer Therapeutic Evaluation Program (CTEP)-sponsored phase I trial of TAK-228 and bevacizumab. Eligibility criteria included histologically confirmed recurrent glioblastoma(rGBM) and advanced solid tumors, >18 years old, ECOG≤2, adequate bone marrow and organ function. The study had 2 stages; dose escalation using a 3 + 3 design to estimate MTD defined as the highest dose at which <2/6 patients experience dose-limiting toxicity (DLT); followed by dose expansion at MTD to include up to 40 patients with rGBM, endometrial and ovarian cancer. A total of 49 patients received study treatment including 18 with rGBM, 17 with ovarian cancer and 14 with endometrial cancer. Median age and ECOG score were 59 years and 1. Three TAK-228 dose levels were evaluated in stage 1, including 3,4 and 5 mg daily with bevacizumab (10mg/kg intravenously bi-weekly) in 28-day cycles. At 5 mg dose level, 1/6 pts experienced a DLT of grade 3 fatigue. Median number of cycles was 3(1–22). Twenty-five patients (51%) required dose-reduction after cycle 1. The most common ≥grade 3 toxicities included fatigue, rash and gastrointestinal complaints. Reasons for discontinuing treatment included disease progression(26), consent withdrawal(10), and toxicity(9). Four patients remain on treatment while 32 have died. Median PFS for rGBM patients was 82 days(95% CI, 57, 223), and for ovarian and endometrial cancer patients was 317 days(95% CI, 163,617). The MTD of oral, daily TAK-228 when administered with biweekly bevacizumab was 5 mg, but many patients required dose reduction on extended treatment. Although activity was limited for rGBM, encouraging activity was noted for recurrent endometrial and ovarian cancer.
MA 19.05 Pegylated Arginine Deiminase Potentiates PD-1/PD-L1 Immune Checkpoint Blockade in Malignant Mesothelioma
Authors: P. Szlosarek, R. Khadeir, M. Sheaff, M. Locke, K. Lau, B. Wu, J. Bomalaski, S. Martin, S. Quezada
Journal: Journal of Thoracic Oncology (2017)
P3.02-036 Feasibility Study to Evaluate Patterns of Metastases and Effect of Surgery on Lung Cancer Xenografts with Differing Sensitivity to EGFR TKI
Authors: S. Jiwnani, C. Pramesh, G. Karimundackal, R. Badwe, P. Choudhari
Journal: Journal of Thoracic Oncology (2017)
Predictive power of hepatitis B viral mutations in plasma of chronic carriers for liver cancer development.
Authors: Jian Guo Chen, Shuang Yuan Kuang, Patricia Egner, Jian Hua Lu, Yuan Rong Zhu, Jin Bing Wang, Yong Hui Zhang, Tao Yang Chen, Alvaro Munoz, Thomas Kensler, John D. Groopman
Journal: Cancer Research (2006)

5669  Liver cancer is the leading cause of cancer death in many regions of the economically developing world and its impact is exacerbated by a median age of diagnosis of between 45 and 50 years. Due to its very poor prognosis and lack of generally effective therapies, most people diagnosed with liver cancer succumb in less than one-year. In some cancers, early detection screening techniques have proven to be effective tools for identifying at-risk individuals for therapeutic interventions. Unfortunately, this strategy has yet to emerge in high liver cancer risk populations. In this investigation, we have taken advantage of a male cohort of 5581 hepatitis B surface antigen (HBsAg) carriers who at baseline sampling in 1989 or 1992 were between the ages of 30 and 69. These men were all residents of Qidong County, China and they have been passively followed using the Qidong Cancer Registry; the mean time from diagnosis to death from liver cancer was 6 months. Six hundred sixty-seven liver cancer cases emerging over the course of 10–15 years in this cohort were identified. Baseline plasma samples containing fragments of DNA shed from the turnover of hepatocytes were then examined for specific acquired mutations in the hepatitis B viral (HBV) genome following integration into these patients’ liver cells. DNA from plasma was isolated in 512 samples and HBV DNA was found in 371 (72.5%). Using mass spectrometry, mutations in HBV were determined and 294 (79.2%) of these samples contained a two nucleotide 1762T/1764A mutation. Thirty-seven of the 294 samples had an additional double mutation in the HBV X-gene coding sequence. 16 samples had novel mutations in the 1761 to 1767 region of the HBV genome. Since the progression to liver cancer following enrollment into the study occurred at a relatively constant rate, we explored the relationship of HBV mutations at baseline to both time to death from liver cancer and age at death. Analysis showed that samples from individuals succumbed at longer intervals after plasma collection had a higher probability (P
P3.08-005 Hereditary Familial Overlap Syndrome with Multiple Synchronous Lung Tumors
Authors: A. Cardona, S. Martínez, O. Arrieta, A. Serna, R. Barrios, J. Garzón, C. Navarrete, A. Balaguera, O. Reyes, D. Galvis, Z. Zatarain-Barron, L. Rojas
Journal: Journal of Thoracic Oncology (2017)
<scp>NUT</scp> Co Reactivity ‐ ACquiring Knowledge for Elimination Recommendations (NUT CRACKER) study
Authors: A. Elizur, M. Y. Appel, L. Nachshon, M. B. Levy, N. Epstein‐Rigbi, K. Golobov, M. R. Goldberg
Journal: Allergy (2017)

Ambiguities exist regarding the diagnosis of tree-nut allergy, necessitating either their elimination or the performance of oral food challenges (OFCs).To examine the coincidences of allergies among tree-nuts and improve diagnostic testing to minimize the need for OFC.Eighty-three patients prospectively evaluated for walnut, pecan, cashew, pistachio, hazelnut, and almond allergy. A history of previous reactions was obtained, and standardized skin prick tests (SPTs) using finely ground tree-nut solution and basophil activation tests (BAT) were performed. Patients underwent OFC for each tree-nut they eliminated and to which a reaction in the previous 2 years was not documented.While most patients were sensitized to 5-6 tree-nuts, over 50% were allergic to only 1-2 tree-nuts. The highest rate of allergy in sensitized patients was observed for walnut (74.6%) and cashew (65.6%). The rate of co-allergy for most tree-nuts was <30%. Two-thirds of walnut- and cashew-allergic patients were also allergic to pecan and pistachio, respectively, while all pecan- and pistachio-allergic patients were allergic to walnut and cashew, respectively. Receiver-operating characteristic analysis for SPT and BAT was tree-nut dependent and yielded area under the curve (AUC) values ranging from 0.75 to 0.94. Knowledge of coincident allergies in these pairs along with the combination of SPT and BAT correctly distinguished allergic from tolerant patients for walnut (87%), pecan (66%), cashew (71%), and pistachio (79%).The data presented here should assist in differentiating between allergic and tolerant patients, decrease the need for OFC, and allow for appropriate elimination recommendations.
P2.16-022 Initiative for Early Lung Cancer Research on Treatment: Pilot Implementation
Authors: R. Flores, E. Taioli, D. Yankelevitz, R. Yip, B. Becker, A. Jirapatnakul, A. Reeves, R. Schwartz, K. Tam, C. Henschke
Journal: Journal of Thoracic Oncology (2017)
MNGI-06. MENINGEAL BASED TUMORS: ROLE OF STAT6 EXPRESSION
Authors: Ayushi Sahay, Vinayak Kadam, Aliasgar Moiyadi, Tejpal Gupta, JayantSastri Goda, Prakash Shetty, Rakesh Jalali, Sridhar Epari
Journal: Neuro-Oncology (2017)

Updated 2016 WHO classification of CNS tumors has unified solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) as a single entity (SFT/HPC) with grades I-III, in view of common genetic alteration viz. fusion of NAB2 and STAT6 genes. We undertook a pilot study in a cohort of meningeal based tumors to evaluate the role of STAT6 immunohistochemical expression, and its correlation with other pathological parameters. Fifty-eight adult meningeal based tumors were studied including 37 HPC/SFT (1 grade I, 27 grade II and 9 grade III), 13 meningioma (2 grade I, 9 atypical meningioma, 2 anaplastic meningioma, 3 meningeal sarcoma, and 5 cases with overlapping features between HPC and meningioma. Expression pattern of STAT6 and other pathological findings were noted. Nuclear or nuclear + cytoplasmic STAT6 positivity was seen in 36/36 HPC (100%), diffuse in 26 and focal in 10 cases. Single SFT showed strong nuclear STAT6. Only 1/13 cases of meningioma (7.6%) showed weak nuclear positivity. All meningiomas and 2/3 meningeal sarcoma showed cytoplasmic positivity. Of the five borderline cases, four showed nuclear STAT6 positivity, based on which they were reclassified as HPC. Interestingly, of the 36 STAT6 positive HPC, 3 showed epithelial differentiation (AE1/AE3 and/or EMA). CD34 was negative in 5/33 HPC- all of which were nuclear STAT6 positive. CD34 was focally positive in 3/5 borderline cases, two of which were focally EMA positive as well, and both cases showed nuclear STAT6 positivity. BCl2 was negative in 4/20 HPC, all of which were nuclear STAT6 positive. Nuclear expression of STAT6 is a useful diagnostic marker for SFT/HPC, especially in CD34 and BCl2 negative cases and cases with EMA/keratin positivity where meningioma forms a diagnostic dilemma. Additionally, nuclear STAT6 expression is also useful in differentiating high grade HPC of sarcomatous morphology from meningeal sarcoma, NOS.
NIMG-22. RAPID ACCURATE INTRAOPERATIVE DIAGNOSIS OF PEDIATRIC BRAIN TUMORS USING STIMULATED RAMAN HISTOLOGY
Authors: Todd C Hollon, Spencer Lewis, Balaji Pandian, Yashar Niknafs, Hugh J L Garton, Cormac O Maher, Karin Muraszko, Sandra Camelo-Piragua, Daniel A Orringer
Journal: Neuro-Oncology (2017)

Accurate histopathologic diagnosis is essential for providing optimal surgical management of pediatric brain tumors. Current methods for intraoperative histology are time- and labor-intensive intensive and often introduce artifact that complicates interpretation. The ideal system of intraoperative histology would be built on a rapid, standardized workflow with minimal tissue processing and diagnostic-quality images. Stimulated Raman histology (SRH) is a new label-free imaging technique that provides intraoperative histologic images of fresh, unprocessed surgical specimens. Here, we evaluate the capacity of SRH for use in the intraoperative diagnosis of pediatric brain tumors. SRH revealed key diagnostic features in fresh tissue specimens collected from 33 prospectively enrolled pediatric brain tumor patients, preserving tumor cytology and histoarchitecture in all specimens. We simulated an intraoperative neuropathology consultation for 25 patients with specimens imaged using both SRH and standard H&E histology. SRH-based diagnoses achieve near-perfect diagnostic concordance (Cohen’s kappa, κ > 0.90) and an accuracy of 92-96%. Leveraging the image contrast generated by the intrinsic biochemical data embedded in SRH images, we developed a quantitative histologic method that allows for rapid image feature extraction. Nuclear density, tumor-associated macrophage infiltration, and nuclear morphology parameters extracted from 3337 SRH fields of view were used to develop and train a decision tree machine-learning model. Using SRH image features, our model correctly identified normal versus lesional tissue and low-grade versus high-grade tumors in 25 fresh pediatric surgical specimens with 100% accuracy. Our results provide insight into how SRH can deliver rapid diagnostic histologic data during pediatric brain tumor surgery.
Forte augmentation d'infections à Salmonella en 2003 aux Pays-Bas : conséquence de la vague de chaleur ou de l'épidémie de grippe aviaire ?
Authors: W van Pelt, D. J Mevius, H G Stoelhorst, S Kovats, A. W van de Giessen, W J B Wannet, Y T H P Duynhoven
Journal: Eurosurveillance (2004)

En juin 2003, le centre national neerlandais des salmonellas a rapporte une augmentation significative du taux d'isolats de Salmonella Enteritidis compare aux annees precedentes dans la plupart des laboratoires regionaux de sante publique.
MNGI-01. KIF11 AS A NOVEL THERAPEUTIC TARGET IN MENINGIOMA
Authors: Gerhard Jungwirth, Steffen Dettling, Rolf Warta, Katrin Lamszus, Matthias Simon, Andreas Unterberg, Christel Herold-Mende
Journal: Neuro-Oncology (2017)

The kinesin superfamily (KIF) members are highly conserved motor proteins, which play an important role in cellular functions including transport of vesicles and mitosis. Kinesin proteins are involved in multiple cancer types including melanoma, retinoblastoma, and glioma. Additionally, several kinesin inhibitors are available and are currently tested in clinical studies. So far, kinesin family members have not been investigated in meningiomas. As a first step, we selected differentially expressed kinesin family members from our initial gene expression array including 75 WHO°I-III meningioma for further validation by qRT-PCR. We assessed the mRNA expression levels of the kinesins KIFC1, KIF4A, KIF11, KIF14, and KIF20A in meningiomas WHO°I (n=24), °II (n=20), and °III (n=31). The mRNA levels of all investigated kinesins showed a statistically significant increase with WHO grade. High expression of KIFC1 (p=.026), KIF11 (p=.048), and KIF14 (p=.017) was associated with a shorter progression-free survival of meningioma patients. Depletion of KIF11 via two different siRNAs inhibited cell proliferation by 91% and 95% on day 3 and 5 (p<.001) in the benign cell line Ben-Men-1 and by 56%, 72%, and 71% on day 1, 3 and 5 in the malignant cell line NCH93 (p<.001), respectively. Filanesib and Ispinesib are small molecule inhibitors for KIF11. Dose-curve analysis revealed IC50 values of less than 1 nM in both cell lines. Inhibitor dosage of 10 nM and higher lead to an average inhibition of Ben-Men-1 cells by 58% and 66% on day 1 and 2 for Filanesib and by 63% and 60% for Ispinesib. NCH93 cells decreased in proliferation by 63% and 84% for Filanesib and by 67% and 89% for Ispinesib (p<.001). Taken together, KIF11 seems to play an important role in meningioma pathogenesis and thus may become a feasible target for meningioma therapy.