tbuckley/cabot-search huggingface dataset:
Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy
Authors: Kelly R. Bijanki, Joseph R. Manns, Cory S. Inman, Ki Sueng Choi, Sahar Harati, Nigel P. Pedersen, Daniel L. Drane, Allison C. Waters, Rebecca E. Fasano, Helen S. Mayberg, Jon T. Willie
Journal: Journal of Clinical Investigation (2018)

Awake neurosurgery requires patients to converse and respond to visual or verbal prompts to identify and protect brain tissue supporting essential functions such as language, primary sensory modalities, and motor function. These procedures can be poorly tolerated because of patient anxiety, yet acute anxiolytic medications typically cause sedation and impair cortical function.In this study, direct electrical stimulation of the left dorsal anterior cingulum bundle was discovered to reliably evoke positive affect and anxiolysis without sedation in a patient with epilepsy undergoing research testing during standard inpatient intracranial electrode monitoring. These effects were quantified using subjective and objective behavioral measures, and stimulation was found to evoke robust changes in local and distant neural activity.The index patient ultimately required an awake craniotomy procedure to confirm safe resection margins in the treatment of her epilepsy. During the procedure, cingulum bundle stimulation enhanced positive affect and reduced the patient's anxiety to the point that intravenous anesthetic/anxiolytic medications were discontinued and cognitive testing was completed. Behavioral responses were subsequently replicated in 2 patients with anatomically similar electrode placements localized to an approximately 1-cm span along the anterior dorsal cingulum bundle above genu of the corpus callosum.The current study demonstrates a robust anxiolytic response to cingulum bundle stimulation in 3 patients with epilepsy.The current study was not affiliated with any formal clinical trial.This project was supported by the American Foundation for Suicide Prevention and the NIH.
Is cytology sample from endobronquial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) sufficient for analysis of major known driver mutations in non-small cell lung cancer (NSCLC)?
Authors: Enric Carcereny, Carmen Centeno, Ana Munoz, Teresa Moran, Cristina Queralt, Montserrat Tierno, Felipe Andreo, Mariona Llatjos, Jose Luis Ramirez, Anna Estival, Pere Serra, Itziar de Aguirre, Eva Castella, Monica Botia, Erika Mijangos, Ana Montañes, Maria de los Llanos Gil, Laia Vila, Juan Ruiz Manzano, Rafael Rosell
Journal: Journal of Clinical Oncology (2014)

e22110 Background: Identification of distinct oncogenic driver mutations is routinely used to guide clinical care in NSCLC patients (p). Tumor tissue availability is one of the major challenges for NSCLC genotyping. Cytology samples from EBUS-TBNA are one of the main sources of tumor tissue in NSCLC. Methods: We aimed to prospectively asses the utility of cytology samples from EBUS-TBNA for molecular characterization of NSCLC p. NSCLC p with stage IIIA, IIIB and IV were included; smoker p with squamous histology excluded. Molecular analyses for EGFR, KRAS, ALK, ROS1, BRAF and HER2 were performed sequentially. Between 8 and 150 tumor cells were captured by laser microdissection. DNA sequencing for EGFR, KRAS, BRAF and HER2 was performed, and FISH for ALK and ROS1 was analyzed by the Molecular Biology Laboratory and the Pathology Department, respectively (Germans Trias i Pujol Hospital). Results: From January 2013, 21 p were included (16 male, median age 63). Sixty-three lymph nodes and 2 lung masses were analyzed and diagnosed malignant in 41%. Most frequently punctured lymph node stations were 4R, 4L, 7 and 11L. Cytology sample was sufficient in 71.4% (15/21) to perform sequential molecular analysis, either complete or until molecular alteration was detected. EGFR mutational status was possible in 21/21(100%) p, with 2 positive results (9.5%). KRAS mutations were tested in 20/20 (100%), with 3 positive results (15%). ALK rearrangements were tested in 16/19 (84.2%), with 1 positive result (1/16[6.29%]). ROS1 was analyzed in 14/18 p (77.8%) with no rearrangements found. No mutations found in HER2 and BRAF in 12/16(75%) and in 13/17 (76.5%), respectively. Conclusions: Cytology samples from EBUS-TBNA are a suitable source of material for a complete molecular genotyping in NSCLC p.
New Genomic Model Integrating Clinical Factors and Gene Mutations to Predict Overall Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP
Authors: Joo Y. Song, Anamarija M. Perry, Alex F. Herrera, Lu Chen, Pam Skrabek, Michel Nasr, Rebecca Ottesen, Janet Nikowitz, Victoria Bedell, Joyce Murata-Collins, Yuan Yuan Chen, Yuping Li, Carlos Gomez Luna, Christine McCarthy, Raju Pillai, Jinhui Wang, Xiwei Wu, Jasmine Zain, Auayporn P. Nademanee, Joyce Niland, Qiang Gong, Wing C Chan, Dennis D. Weisenburger
Journal: Blood (2018)
Efficacy of long-term treatment for &gt; 5-10 years with the LHRH analog leuprorelin acetate in patients with prostate ancer: Results from a noninterventional study.
Authors: Peter Hammerer, Manfred Wirth
Journal: Journal of Clinical Oncology (2014)

e16077 Background: LHRH analogs (LHRHa) are standard of care in the treatment of advanced and metastatic prostate cancer (PCa). The most widely prescribed LHRHa leuprorelin acetate is in clinical use over 20 years. This study investigates the efficacy of long term treatment with depot formulations (1, 3, and 6 months) of leuprorelin in microcapsules in advanced PCa patients for >10 years. Methods: The design was an observational, retrospective study of efficacy/safety carried out by 30 office-based urologists in Germany in 647 patients with an observation period from 1992 to 2012. Three subgroups are described: patients who received treatment for ≥5/<10 years (n=363), patients who received treatment for ≥ 10 years (n=173), a control group (≥5 years of urologic treatment, no cancer, only QoL assessment; n=111). Results: See Table. In the treatment group response rate according to EORTC criteria was 94,4 % after 6 mths of LHRHa treatment and remained above 90% for 10 years of treatment. PSA levels fell from 8,09 ng/ml (median, IR [3,02-19,00]) to 0,40 ng/ml (IR [0,10-1,31]) after 6 mths and stayed below this level for up to 13 years. Testosterone levels were at baseline 3,97 ng/ml (median, IR [2,02-4,80]), dropped to castration level (< 0,5 ng/mL) within 6 mths and were suppressed ≤ 0,20ng/mL (median) at all time points until 13 years of treatment. Conclusions: More than 90% of the observed patients showed response (EORTC crit.) for > 10 years of treatment. Median testosterone level was suppressed considerably below castration level, PSA declined subsequently and remained low for all time points of observation up to 13 years. Thus, leuprorelin acetate in microcapsules is an effective long term treatment for patients with advanced prostate cancer. Clinical trial information: ENA E005 / DE-N-LEU-019. Duration of treatment (months) Response (EORTC crit.) (%) PSA (ng/ml), median [IR] Testosterone (ng/ml), median [IR] Baseline - 8,09 [3,02-19,00]; n= 514 3,97 [2,02-4,80]; n=22 0-6 94,4; n=504 0,40 [0,10-1,31]; n= 512 0,21 [0,10-0,49]; n=81 55-60 90,6; n=476 0,17 [0,05-0,91]; n= 516 0,20 [0,10-0,26]; n=128 115-120 90,2; n=165 0,30 [0,05-1,70]; n=175 0,17 [0,10-0,30]; n=41 151-156 86,2; n=25 0,35 [0,03-2,93]; n=28 0,15 [0,08-0,29]; n=7
Mutations in the RNA Splicing Factor SF3B1 Promote Transformation through MYC Stabilization
Authors: Akihide Yoshimi, Zhaoqi Liu, Wang Jiguang, Hana Cho, Stanley C Lee, Michelle Ki, Lillian E Bitner, Timothy Chu, Anthony R Mato, Peter P. Ruvolo, Giulia Fabbri, Laura Pasqualucci, Raul Rabadan, Omar I Abdel-Wahab
Journal: Blood (2018)
Abstract 18807: Use of Mechanical Circulatory Support and Transcatheter Aortic Valve Replacement (TAVR): Insights From Nationwide Inpatient Sample
Authors: Samir V Patel, Vikas Singh, Chirag Savani, Rajesh Sonani, sidakpal S Panaich, Nileshkumar J Patel, Sopan Lahewala, Achint Patel, Nilay Patel, Badal Thakkar, Shilpkumar Arora, Dhaval Pau, Maheshkumar K Desai, Sunny Jhamnani, Abhishek Deshmukh, Apurva O Badheka
Journal: Circulation (2015)

Introduction: Short-term use of Mechanical Circulatory Support (MCS) has the potential to benefit the patients undergoing Transcatheter Aortic Valve Replacement (TAVR) who may be high-risk or suffer complications. The present study was conducted to address the contemporary use of MCS in TAVR procedures. Methods: The study included a total of 1794 TAVR procedures in the years 2011-2012 from Nationwide Inpatient Sample (NIS) database. Use of MCS was identified using ICD-9-CM codes. The patients were divided based on use of MCS devices. The primary outcome of the study was in-hospital mortality and the secondary outcomes were complications, length of stay (LOS) and cost. Multi-variate simple logistic regression models were used to identify independent predictors of the outcomes. Results: Out of total 1794 TAVR procedures, 190 (10.6 %) utilized a MCS device (MCS group) and 1,604 (89.4%) did not (non-MCS group). The use of MCS devices with TAVR was associated with increase in the in-hospital mortality (14.9% vs. 3.5%, p&lt;0.01) with same results obtained in multi-variate models. The rates of complications were significantly higher in MCS group so as the mean length of stay (11.8±0.8 vs. 8.1±0.2 days, p&lt;0.01) and cost ($68,997±3,656 vs. $55,878±653, p=0.03). Conclusion: Use of MCS in TAVR predicts increase in-hospital mortality, complications, LOS and cost of care.
Predictors of 90-Day Mortality after Admission to Intensive Care Unit (ICU) in Patients with Acute Myeloid Leukemia (AML): Application of a Novel, Recently Validated AML-Specific Risk Model
Authors: Ylinne Lynch, Shirali Agarwal, Matthew Modes, Matthew Triplette, Masumi Ueda, Barry E. Storer, Mary-Elizabeth M. Percival, Pamela S. Becker, Brenda M. Sandmaier, Frederick R. Appelbaum, Elihu H. Estey, Mohamed L. Sorror
Journal: Blood (2018)
Application of a dynamic retraining for each patient using case-specific training cohorts to predict survival in breast cancer patients.
Authors: Balazs Gyorffy, Thomas Karn, Zsofia Sztupinszki, Boglarka Weltz, Volkmar Muller, Lajos Pusztai
Journal: Journal of Clinical Oncology (2014)

1065 Background: To exceed prediction accuracy of previous multigene prognostic classifiers, we propose a new dynamic predictor. Our classifier does not use a single universal training cohort and an identical list of informative genes to predict the prognosis of new cases but a case-specific predictor is developed for each test case. Methods: Gene expression data from 3,534 breast cancers with clinical annotation including survival was analyzed. For each test case we select a case-specific training subset including only molecularly similar cases and a case-specific predictor is generated. This method yields different training sets and different predictors for each new patient but preserves the independence of model building and validation. The model performance was assessed in leave-one-out validation and also in 325 independent cases. Results: Prognostic discrimination was high for all cases (n=3,534, HR=3.68, p=1.67E-56). The dynamic predictor showed higher overall accuracy (0.68) than the 21-gene predictor (0.64), the 97-gene genomic grade index (0.55) or the 70-gene prognostic signature (0.41). The dynamic predictor was also effective in triple-negative cancers (n=427, HR=3.08, p=0.0093) where the above classifiers all failed. Validation in independent patients yielded similar classification power (HR=3.57). The dynamic classifier is available online at http://www.recurrenceonline.com/?q=Re_training. Conclusions: In summary, we developed a new method to make personalized prognostic prediction using case-specific training cohorts. The dynamic predictors outperform static models developed from single historical training cohorts and they also predict well in triple-negative cancers.
Glucose transporter 1 critically controls microglial activation through facilitating glycolysis
Authors: Luxi Wang, Sofia Pavlou, Xuan Du, Mohajeet Bhuckory, Heping Xu, Mei Chen
Journal: Molecular Neurodegeneration (2019)

Uncontrolled microglial activation contributes to the pathogenesis of various neurodegenerative diseases. Previous studies have shown that proinflammatory microglia are powered by glycolysis, which relays on high levels of glucose uptake. This study aimed to understand how glucose uptake is facilitated in active microglia and whether microglial activation can be controlled by restricting glucose uptake.Primary murine brain microglia, BV2 cells and the newly established microglial cell line B6M7 were treated with LPS (100 ng/ml) + IFNγ (100 ng/ml) or IL-4 (20 ng/ml) for 24 h. The expression of glucose transporters (GLUTs) was examined by PCR and Western blot. Glucose uptake by microglia was inhibited using the GLUT1-specific inhibitor STF31. The metabolic profiles were tested using the Glycolysis Stress Test and Mito Stress Test Kits using the Seahorse XFe96 Analyser. Inflammatory gene expression was examined by real-time RT-PCR and protein secretion by cytokine beads array. The effect of STF31 on microglial activation and neurodegeneraion was further tested in a mouse model of light-induced retinal degeneration.The mRNA and protein of GLUT1, 3, 4, 5, 6, 8, 9, 10, 12, and 13 were detected in microglia. The expression level of GLUT1 was the highest among all GLUTs detected. LPS + IFNγ treatment further increased GLUT1 expression. STF31 dose-dependently reduced glucose uptake and suppressed Extracellular Acidification Rate (ECAR) in naïve, M(LPS + IFNγ) and M(IL-4) microglia. The treatment also prevented the upregulation of inflammatory cytokines including TNFα, IL-1β, IL-6, and CCL2 in M(LPS + IFNγ) microglia. Interestingly, the Oxygen Consumption Rates (OCR) was increased in M(LPS + IFNγ) microglia but reduced in M(IL-4) microglia by STF31 treatment. Intraperitoneal injection of STF31 reduced light-induced microglial activation and retinal degeneration.Glucose uptake in microglia is facilitated predominately by GLUT1, particularly under inflammatory conditions. Targeting GLUT1 could be an effective approach to control neuroinflammation.
Molecular profiling in NSCLC: A pilot study to screen for new therapeutic targets.
Authors: Veldore H. Vidya, Tejaswi Routhu, Shilpa A. Prabhudesai, Naveen Krishnamoorthy, Diganta Hazarika, Syed m Rahaman, Tejaswini BN, Payal Shrivastava, Radheshyam Naik, Shashidhara SP, Satheesh Chiradoni Thungappa, Shekar Patil, Rao M. Raghavendra, Basavalinga S. Ajaikumar
Journal: Journal of Clinical Oncology (2014)

e22158 Background: NSCLC is a broad category of lung cancer with multiple subsets of molecular abnormalities. EGFR mutation positive patients constitute 30-50% of NSCLC, and hence they derive the benefit of targeted/personalized therapy. The remaining 50% of the NSCLC subgroup is heterogeneous with molecular abnormalities such as EML4-ALK, ROS1-ALK, KIP4-ALK, RET and so on. Due to the low prevalence of ALK translocations, most of the EGFR non-mutated patients do not get the benefit of personalized therapy. In this pilot study, we propose to screen for oncogenic driver mutations in a panel of 46 cancer related genes (Ampliseq Panel V1.0) in 20 cases of non-small cell lung cancer with EGFR non mutated in the TK domain. Methods: Genomic DNA was isolated from the FFPE tumor tissues using QIA Amp DNA Mini kit (QIAGEN Inc). Tumor Samples which had atleast 40% tumor burden were selected for this study. 100ng of DNA from each of the 20 patients was pooled and the quality was verified by Fluorimetry. 10ng of pooled DNA was used as input for Next Generation Sequencing (NGS) on Ion Torrent platform. Results: The NGS raw data was analyzed by Torrent suite software and Mutation Assessor. The pathological role of all the variants (SNP/Indels) were predicted using SIFT/PROVEAN structure-function prediction program. We identified 28 somatic mutations in the study subset with high confidence level, of which 4 were in the non-coding. 9 were novel mutations, of which 8 predicted to be deleterious and damaging on the structure-function of the protein. In summary, we found 10 pathogenic mutations in 6 different genes; C420R mutation in PIK3CA, Q472H mutation in VEGFR2 (KDR), C630W and C634R in RET, K367M mutation in FGFR2 and G12C in KRAS. Also, there were 4 pathogenic mutations in TP53 (E285K, R213L, R175H, V173G). Conclusions: To conclude, we observe a potential role of PIK3CA, VEGFR2, RET and FGFR2 as therapeutic targets in EGFR non-mutated lung cancer patients. However, further validation of these mutations in a large cohort of NSCLC patients is warranted to confirm their role in targeted therapy.
ISO-CC-005: A phase I/II study of Modufolin (MTHF) in combination with 5-FU, irinotecan, and oxaliplatin ± bevacizumab in patients with metastasizing colorectal cancer.
Authors: Helena Anna Taflin, Karin M E Ganlov, Tormod Kyrre Guren, Christos Papadimitrou, Nikolaos K. Kentepozidis, Johan Haux, Per Pfeiffer, Goran Ulf Carlsson
Journal: Journal of Clinical Oncology (2018)

838 Background: Chemotherapy treatment of Colorectal Cancer, often include 5-Fluorouracil (5- FU). 5-FU inhibits the enzyme thymidylate synthase (TS), stopping the supply of thymidine for DNA synthesis. 5-FU is always combined with a folate, which enhances the 5-FU effect. Marketed folates such as LV/L-LV are prodrugs needing enzymatic conversion. Modufolin is the natural, biologically active form of the folates and is expected to be efficacious in a larger proportion of patients with less inter- and intra-individual variability Methods: ISO-CC-005 is a multi-center, phase I/II study in mCRC patients eligible for 5-FU/folate therapy alone or in combination with irinotecan or oxaliplatin ± bevacizumab. The study investigates safety and tolerability of Modufolin at 4 dose levels by analysing the number and severity of AEs, SAEs and DLTs. Efficacy is evaluated as ORR after four cycles of chemotherapy. Gene expression, deoxyuridine levels as an indirect marker of TS inhibition and time to death is also investigated. Three to six patients per cohort are included. All receives Modufolin twice every two weeks during at least four cycles of chemotherapy. Results: Today, 42 patients have been enrolled and 40 have initiated treatment. 13 are 1 st line patients, 16 are in 2 nd line, 10 are in 3 rd line and 1 is in 5 th treatment line. 19 SAEs have been reported in 12 patients, 3 of these were judged as at least possibly related to Modufolin. No SAE were judged as solely related to Modufolin. 31 patients have today been evaluated for efficacy. ORR 1 st line patients (n=12) All 50% (6 PR, 6 SD) Patients with Modufolin dose ≥60 mg/m2 71% (5 PR, 2 SD) Patients with Modufolin dose ≥60 mg/m2 + oxaliplatin 100% (3 PR) Conclusions: The lack of need for metabolic activation makes Modufolin a better candidate than LV/L-LV for improved outcome of 5-FU-based chemotherapy regimens in mCRC. The ISO-CC-005 study evaluates Modufolin in combination with 5-FU, irinotecan, oxaliplatin ± bevacizumab in mCRC patients in 4 countries in Europe. The results, so far, for both safety and efficacy seems promising. Clinical trial information: NCT02244632.
Cleanliness, hygienic habits, and aeroallergen sensitization: German Bitterfeld 3 study
Authors: Iana Markevych, Gayan Bowatte, Marie Standl, Joachim Heinrich
Journal: Allergy (2018)

Capsule summary: Less frequent bathing and showering appears to be protective against aeroallergen sensitization in children without current allergy from the German Bitterfeld 3 study.
Enhancing the prognostic power of the Nottingham tumor grading system.
Authors: Ritu Aneja, Guilherme Henrique Cantuaria, Vaishali Pannu, Sergey Klimov, Padmashree C.G. Rida, Colleen S. Austin, Michelle D. Reid
Journal: Journal of Clinical Oncology (2014)

11021 Background: The terms “actively proliferating cell” and “mitotically dividing cell” are often used synonymously in breast clinical pathology. Mitotic and Ki-67 indices (MI and KI, respectively) are evaluated in different fields and at different scales, despite their mutual non-exclusivity. Pathology-centric view regards Ki-67-positive cells as “actively dividing”, leading to the mistaken view that an increase in KI reflects an increased proportion of mitotic cells. Since MI is an equally-weighted component of the Nottingham grading system (NGS), we examined contribution of mitotic scores to the prognostic value of tumor grade and evaluated if a modified score called Ki-67–adjusted mitotic score (KAMS), could replace MI in NGS to re-stratify GII patients and strengthen the prognostic power of tumor grade. Methods: In a retrospective study of 2,200 breast carcinoma patient records from Northside Hospital, Atlanta, GA, KAMS was calculated by transforming monotonic ordinal MI into percent mitotic cells and dividing it by KI. Grade wise trends in KAMS were evaluated and survival stratification was done via Kaplan-Meier estimator. An adjustment principle based on each patient's KAMS and mitotic score was applied to the MI component of the Nottingham sum to re-stratify Grade II patients. Results: Average KAMS decreased significantly (p< 0.0001) from 0.153 to 0.132 to 0.085 for Nottingham grades GI, GII and GIII, respectively. KAMS was then used to stratify GII patients into two groups whose survival probabilities were significantly different (p= .01):
Cardio-respiratory fitness and functional performance in patients with a recent diagnosis of colorectal cancer.
Authors: Alejandro Alvarez-Bustos, Lourdes Gutierrez Gutierrez Sanz, Beatriz Nuñez García, Maria Soriano, Carmen Fiuza-Luces, Javier Ramos, Jorge D. Sen, Antonio Carlos Sánchez-Ruiz, Raquel Gomez-Bravo, Blanca De La Puente, Alejandro Lucia, Ana Ruiz-Casado
Journal: Journal of Clinical Oncology (2018)

804 Background: Physical capability describes the ability to do the physical tasks of everyday living. Oncologists usually evaluate physical capability through anamnesis generating a performance status (PS) score. Some authors have proposed the use of cardiorespiratory reserve, muscular strength and objective evaluation of physical activity to avoid the subjective, unreliable and non-reproducible condition of PS. Methods: Patients with a recent diagnosis of colorectal cancer who accepted to participate were evaluated at the hospital setting. Walking speed was evaluated through both one-mile walk test and six-minute walk test. VO 2max was calculated through the Kilne formula. Muscular strength was measured through dynamometry (hand-grip) and “sit to stand” test. Physical activity was objectively evaluated with accelerometers. Fatigue was evaluated through the PERFORM questionnaire (12-60). ECOG was evaluated by the medical oncologist. Results: 100 pats were recruited between March 15 and Jul 17. ECOG O/1/2 (80/14/2). 40 (40 %) were metastatic. Mean age 66 (25-81), Sex M/F; 68/32. Conclusions: Objective evaluation of physical condition is feasible at the hospital setting. There were no differences in BMI, heart rate, fatigue, muscular strength and objective functional performance (weekly PA) between localized and metastatic CRC. In metastatic pts with an excellent ECOG-PS the time to walk one mile and the estimated VO 2max could be more sensitive than ECOG to evaluate the functional capacity impairment. In pts with cancer the One- mile walk test could be superior to the Six-minute walk to estimate the cardiorespiratory fitness. The objective evaluation of physical condition is a useful additional tool to select pts for aggressive therapies. [Table: see text]