tbuckley/cabot-search huggingface dataset:
EPIG-03EPIGENETIC SUPPRESSION OF EGFR SIGNALING IN G-CIMP + GLIOBLASTOMAS
Authors: Jie Li, Zachary Taich, Amit Goyal, David Gonda, Johnny Akers, Bandita Adhikari, Kunal Patel, Scott Vandenberg, Wei Yan, Zhaoshi Bao, Bob Carter, Renzhi Wang, Ying Mao, Clark Chen
Journal: Neuro-Oncology (2015)

While it is understood that glioblastomas with the Glioma CpG island methylator phenotype (G-CIMP) phenotype harbor extensive methylation in the CpG islands of a large number of genetic loci, how these methylations patterns translate into the modulation intrinsic signaling cascades remain poorly understood. Using independent, published mRNA signatures associated with EGFR activation, we demonstrate that G-CIMP+ tumors harbor decreased EGFR signaling in three independent datasets, including the REMBRANDT dataset (n = 288), The Cancer Genome Atlas (TCGA; n = 406), and the Chinese Glioma Genome Atlas (CGGA; n = 155). Supporting these findings, analysis of an independent collection of 25 fresh-frozen glioblastomas confirmed lowered pERK levels in G-CIMP+ specimens (p < 0.001), supporting suppressed EGFR signaling in G-CIMP+ glioblastomas. To better understand the mechanism underlying this suppression, we analyzed the TCGA glioblastomas database for the expression level of genes required for EGFR signaling and found that G-CIMP+ glioblastomas harbored lowered mRNA levels for EGFR and H-Ras. In independent glioblastoma models, induction of G-CIMP+ state by exogenous expression of a mutated isocitrate dehydrogenase 1, IDH1-R132H, or by chronic 2-hydroxyglurate treatment suppressed EGFR and H-Ras protein expression as well as pERK accumulation. These suppressions were associated with increased deposition of the repressive histone markers, H3K9me3 and H3K27me3, in the EGFR and H-Ras promoter regions. The IDH1-R132H expression-induced pERK suppression can be reversed by exogenous expression of H-RasG12V but not be exogenous expression of EGFRvIII, suggesting epigenetic suppression H-Ras as the rate limiting step of EGFR signaling in G-CIMP+ glioblastomas. Further supporting suppressed EGFR signaling in G-CIMP+ glioblastomas, we observed increased resistance to the EGFR inhibitor, Gefitnib, in an engineered G-CIMP+ Ink4a-Arf-/- EGFRvIII glioblastoma line relative to its isogenic G-CIMP- counterpart. These results suggest that mitogenic signaling cascades in glioblastomas are epigenetically regulated and a role for IDH1 mutation serves as a predictive biomarker for EGFR inhibitor sensitivity in glioblastoma patients.
Small-subunit ribosomal RNA sequence from Naegleria gruberi supports the polyphyletic origin of amoebas.
Authors: C G Clark, G A Cross
Journal: Molecular Biology and Evolution (1988)

We have sequenced the small-subunit ribosomal RNA gene of the amoebo-flagellate protozoan Naegleria gruberi. Comparison of this sequence with the rRNA sequences of other eukaryotes resulted in a phylogenetic tree that supports the suggested polyphyletic origin of amoebas and suggests a flagellate ancestry for Naegleria.
Outcomes of androgen deprivation as sole therapy for localized prostate cancer
Authors: D. Janoff, S. Mongoue-Tchokote, C. Peterson, R. O. Parra, L. Peters, Y. Park, T. M. Beer, M. Mori, M. Garzotto
Journal: Journal of Clinical Oncology (2004)

4627 Background: Recent studies indicate increasing use of androgen deprivation (AD) as primary therapy for localized prostate cancer. The utility of this approach is not well known; thus, we sought to characterize the outcomes and determine independent predictors of disease progression with this approach. Methods: The records of all patients with cT1–2, N0, M0 adenocarcinoma of the prostate treated with AD as sole initial therapy at the Portland VA between 1993 and 2000 were reviewed. Age, race, Charlson health index (CHI), family history, PSA, PSA density (PSAD, PSA/prostate volume), digital rectal exam findings, Gleason score, and % of positive biopsy cores at diagnosis were recorded. Outcomes included PSA failure (confirmed with 2 rising PSAs), PSA nadir, bone fractures, local failure, distant failure, and overall survival. Kaplan-Meier method and log rank test (univariate analysis) and stepwise Cox regression (multivariate analysis) were used to estimate time to each end point. Results: 81 patients with a median age of 73 (58 to 84), median CHI of 1, and median PSA of 13.8 ng/ml were followed for a median of 54 months (6 to 115). Rates of endpoints were: local failure = 9.9%, distant failure = 7.4%, bone fractures= 24.7% (18 osteopenic, 2 pathologic), PSA failure = 21.0%, and death = 40.7%. Factors associated with PSA failure by univariate analysis were % positive biopsy cores ≥ 83% (p=0.0008), age < 70 (p= 0.006), Gleason score ≥ 7 (p= 0.015), abnormal DRE (p= 0.025), and PSA nadir ≥ 0.2 ng/ml (p=0.044). The multivariate analysis identified age < 70 (HR= 6.52, 95% CI = 2.29–18.55) and Gleason score ≥ 6 (HR = 4.00, 95% CI = 2.00–12.00) as independent risk factors of PSA failure after AD therapy. Kaplan-Meier estimate of PSA failure at 5 years was 25%±6%. None of the variables were predictive of overall survival. Conclusions: AD therapy resulted in reasonable control of localized prostate cancer; however, younger patients and those with Gleason ≥ 6 cancers were at higher risk for treatment failure. Bone fracture were relatively frequent, perhaps due to prolonged treatment. The efficacy and toxicity of AD for localized prostate cancer requires further study before this modality can be recommended. No significant financial relationships to disclose.
The efficacy of COPD detection by using a community-based annual screening program for lung cancer
Authors: Yasuo Sekine, Kiminori Suzuki, Kazuko Kubota, Hiroshi Ikegami, Yuji Isobe, Mitsugu Nakamura, Yuichi Takiguchi, Koichiro Tatsumi, Takehiko Fujisawa
Journal: European Respiratory Journal (2012)

Study objectives: The aim of this study was to clarify the usefulness of COPD screening by using a community-based lung cancer screening program.  Methods: In Japan, community-based lung cancer screening by chest X-ray has been established. Japanese residents who are 40 years old or higher can freely receive chest X-ray every year. We utilized this screening system in Chiba City in order to detect COPD. From April 2010 to March 2011, 83,924 participants received regular lung cancer screening by chest X-ray at the first examination centers, which was approximately 30% of objective residents. We set the criteria of suspicious of COPD indicating 60 years or older, positive smoking history and having any chronic respiratory symptoms. 1,170 (1.3%) were recognized as suspicious of COPD and 551 of them (56.2%) received further examination including pulmonary function test (PFT) and/or chest computed tomography (CT) as the second close examination at 39 second examination centers.  Results: 138 participants (25.0%) were reported as COPD from the second examination centers and 42.2% of them were necessary for COPD treatment. Only eight participants (5.8%) were already diagnosed COPD before screening. PFT data could be collected from 173 participants, and 43 (24.9%) were diagnosed as COPD (FEV1 less than 70%). Emphysema grades according to Goddard classification on CT revealed that 21.1% was radiological emphysema. One patient with normal chest X-ray was detected lung cancer by CT and could receive curative surgery.  Conclusion: COPD screening by using a community-based lung cancer screening program may be effective for detection of COPD. These patients can be treated COPD as early as possible.
Author's reply
Authors: J. C. McLachlan
Journal: BMJ (2011)

Fried makes two points.1 2 Firstly, that the abstract was accepted because of my credentials.But that was one of the points I was trying to make.My impression is that the world of alternative medicine is peculiarly susceptible to "arguments from authority," while rational science and medicine ought to focus solely on evidence.The second point relates to "fraud."I would distinguish between fraud and "comic hoax," with the distinction lying in intent.A comic hoax always intends to reveal the truth in time, but fraud is meant to remain secret.Hoax tactics can be legitimate, even when the subject is not comic.The subject of the "lie," the idea that the buttocks map meaningfully to body organs is intrinsically risible to believers in rational medicine but not to believers in "alternative universe medicine."One commentator on the internet said: "Once you open your mind wide enough to find reflexology or homoeopathy 'not implausible,' then you have no defence against any nonsense that might wander in"-this is a fair summary of my position.I thought seriously about the ethical aspects and had helpful discussions with colleagues, friends, and BMJ editorial staff.But part of my motivation was to create a "true anecdote" as an antidote to the simplified and false anecdotes used in alternative universe medicine, increasingly disguised in integrative medicine clothing, and I hope I did this.I did think about attending the conference and would have revealed the hoax during the presentation.I don't think it would have been one of the last conferences that I could have participated in.My motives for not attending were as described, and not as imputed by Fried.Those who hold positions that are not supported by rational means cannot readily be challenged by rationality.How then to address these positions?Surely a little humour is not misplaced?
Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans
Authors: Zhanghua Chen, Muhammad T. Salam, Claudia Toledo-Corral, Richard M. Watanabe, Anny H. Xiang, Thomas A. Buchanan, Rima Habre, Theresa M. Bastain, Fred Lurmann, John P. Wilson, Enrique Trigo, Frank D. Gilliland
Journal: Diabetes Care (2016)

OBJECTIVE Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels. RESEARCH DESIGN AND METHODS Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits. RESULTS Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P ≤ 0.043). The effects of short-term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes. CONCLUSIONS Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae.
Labeling of the Internal Pool of GP IIb-IIIa in Platelets by c7E3 Fab Fragments (abciximab): Flow and Endocytic Mechanisms Contribute to the Transport
Authors: Paquita Nurden, Christel Poujol, Catherine Durrieu-Jais, Joëlle Winckler, Robert Combrié, Laurent Macchi, Claude Bihour, Carrie Wagner, Robert Jordan, Alan T. Nurden
Journal: Blood (1999)
The use of capnometry for alveolar ventilation assessment in COPD patients
Authors: Yuriy Feshchenko, Liudmyla Iashyna, Svitlana Opimakh
Journal: European Respiratory Journal (2014)

Introduction:  Alveolar ventilation – is the part of the minute ventilation, that take place in gas exchange. Alveolar hypoventilation is one of the mechanisms of respiratory failure, a serious complication of chronic obstructive pulmonary disease (COPD).   Aim  :  To explore the possibilities of capnometry to assess the effectiveness of alveolar ventilation in COPD patients.   Methods  :  A totalof 100 COPD patients were examined (30 subjects with GOLD II, 45 – with GOLD III, and 25 – with GOLD IV stages) with the use of capnometry. An unique opportunity of capnometry to calculate CO2-free portion in exhaled air and integration to pneumotachometer allow determining: minute ventilation (VE), «dead» space volume (Vd) and «dead» space/tidal volume ratio (Vd%VT). Data are presented as mean±standard error.   Results  :  The highest VE is in COPD IV patients – (12.6±0.6) l/min, the smallest –in COPD II patients (11.1±0.4) l/min, p   Conclusions:  On the average in COPD III patients increasing in minute ventilation are accompanied by improvement of alveolar ventilation, in COPD IV patients increasing VE goes through the waste dead space ventilation with decrease effective alveolar ventilation. Capnometry can be a useful tool to assess the effectiveness of alveolar ventilation in COPD patients.
HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition
Authors: Heather A. Prentice, Georgia D. Tomaras, Daniel E. Geraghty, Richard Apps, Youyi Fong, Philip K. Ehrenberg, Morgane Rolland, Gustavo H. Kijak, Shelly J. Krebs, Wyatt Nelson, Allan DeCamp, Xiaoying Shen, Nicole L. Yates, Susan Zolla-Pazner, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Guido Ferrari, M. Juliana McElrath, David C. Montefiori, Robert T. Bailer, Richard A. Koup, Robert J. O’Connell, Merlin L. Robb, Nelson L. Michael, Peter B. Gilbert, Jerome H. Kim, Rasmi Thomas
Journal: Science Translational Medicine (2015)

HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 HIV vaccine trial.
Psychiatric combat reactions during the Yom Kippur War
Authors: I Levav, H Greenfeld, E Baruch
Journal: American Journal of Psychiatry (1979)

The authors explore the stress of war by reporting some selected epidemiological aspects of the psychiatric combat reactions among Israeli troops during a period of intensive hostilities in the Yom Kippur War of 1973. They examined the distribution of these casualties according to intensity of fire, age, rank, sociopsychological grading, and military assignment and measured treatment outcome at the end of the war and 18 months later.
An intraoperative sentinel lymph node identification in breast cancer patients guided by near-infrared fluorescence imaging: Preliminary results
Authors: N. Tagaya, R. Yamazaki, A. Nakagawa, S. Mori, K. Hamada, K. Kubota
Journal: Journal of Clinical Oncology (2006)

10776 Background: Recently, radioactive tracer, a vital dye, or a combination of both has been applied to detect intraoperative sentinel lymph nodes (SLN) in early breast cancers. In this study, we present a novel method in SLN identification that provides with high detection and low false-negative rates. Methods: This study enrolled 19 patients with a tumor less than 3 cm in diameter. Their mean age was 49.6 years. Preoperative TNM stage was I in 13 cases, IIa in 4, and IIb in 2, respectively. Initially the combination dye of indocyanine green and indigocarmine was injected subdermally in the areolar. Fluorescence imaging (photodynamic eye: Hamamatsu Photonics Co.) was obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. After incising the axillary skin on the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence. Results: In all patient, lymphatic channels and SLN were successfully visualized. SLN was observed before skin incision in two patients. The number of fluorescence SLN ranged from 2 to 11 (mean: 5.5) and blue dyed SLN ranged from o to 6 (mean: 2.3). In the latter, SLN was not identified in one patient. Six patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, however, in two patients LN with metastasis were not identified by a vital dye. There were no intra- or postoperative complications associated with SLN identification. Conclusions: This method is feasible and safe to detect SLN intraoperatively with less invasive, real-time observation and no requirement of training. We hope that this method will provide with high detection and low false-negative rates in SLN navigation surgery. No significant financial relationships to disclose.
Ebola virus disease in children in Sierra Leone: a retrospective cohort study
Authors: Felicity Fitzgerald, Asad Naveed, Kevin Wing, Musa Gbessay, Gareth Ross, Francesco Checchi, Daniel Youkee, Mohammed Jalloh, David Baion, Ayeshatu Mustapha, Hawanatu Jah, Sandra Lako, Shefali Oza, Sabah Boufkhed, Reynold Feury, Julia Bielicki, Diana Gibb, Nigel Klein, Foday Sahr, Shunmay Yeung
Journal: The Lancet (2016)
Rice based oral rehydration solutions [letter]
Authors: Greenough Wb d
Journal: BMJ (1992)

The results of a metaanalysis of 13 clinical trials of rice based oral rehydration solution (ORS) reported in an earlier edition of this journal documented 10 years of observations.  They suggest that rice or other cereal based ORS reduced fluid loss and duration of diarrhea more so than glucose or sucrose based ORS.  This effect is especially evident in cases where fluid loss is considerable such as in chlorea.  Nevertheless the conclusion of the metaanalysis is that rice based ORS does not have a convincing advantage over the glucose based ORS recommended by WHO.  A diarrhea specialist believes the researchers of the metanalysis arrived at this conclusion prematurely.  They should consider that even minor diarrheal episodes seriously disrupts absorption of nutrients sometimes over a considerable period.  Even though glucose based ORS given consistently to children in Philippines during each episode improved nutritional status studies of consistent use of rice and maize based ORS in Kenya and Bangladesh indicate that is resulted in more rapid recovery and improved nutritional status.  Further many mother in most developing countries already use cereal based soups or gruels to treat children with diarrhea.  Health nutritionalists can inform mothers how to alter these foods enough to make them act as ORS.  This would keep ORS costs down since caretakers must buy ORS packets which are not produced in most developing countries.  Even though one should consider the cost of fuel used to heat all cereal based ORS one can also consider the benefit of boiling the water.  The specialist hopes that the international health community does not wait another 10 years to support rice and other cereal based ORS since it is inexpensive safe and more effective than glucose based ORS.  The community should not join the sluggishness to move forward of the large scale ORS programs.
Rhodiola Rosea Extract Reduces Autophagy In Acute Myeloid Leukemia Transformed From Myelodysplastic Syndromes Tumor Xenograft Model
Authors: Cristiane Okuda Torello, Joao Machado-Neto, Karla P. Veira, Victor Maso, Andrana Calgarotto, Gilberto Carlos Franchi-Junior, Mariana Lazarini, Mary L. S. Queiroz, Sara Teresinha Saad
Journal: Blood (2013)
Early treatment decisions with interferon-alfa therapy in early chronic-phase chronic myelogenous leukemia.
Authors: S Sacchi, H M Kantarjian, T L Smith, S O'Brien, S Pierce, S Kornblau, M Beran, M J Keating, M Talpaz
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine, in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) on interferon alfa (IFNalpha), whether combining pretreatment characteristics and early response profiles would distinguish patients with differential benefits that would allow better decisions on subsequent therapy. PATIENTS AND METHODS A total of 274 patients treated from 1982 through 1990 with IFNalpha regimens were analyzed. A second group of 137 patients treated with IFNalpha and low-dose cytarabine (ara-C) between 1990 and 1994 was later used to confirm the guidelines derived from the original study group analysis. Patients' pretreatment factors and response to IFNalpha therapy at 3, 6, and 12 months were analyzed in relation to subsequent achievement of major cytogenetic response. After univariate analysis of prognostic factors, a multivariate analysis selected, at 6 months, independent pretreatment factors that added to the response status in predicting subsequent outcome. The results were then applied at the 3- and 12-month periods and confirmed in the subsequent population. RESULTS Response to IFNalpha therapy at 3, 6, and 12 months was a significant predictor of later major cytogenetic response. The presence of splenomegaly &gt; or = 5 cm below the costal margin (BCM) or thrombocytosis &gt; or = 700 x 10(9)/L pretreatment added significant independent prediction to response. At 6 months, patients with a partial hematologic response (PHR) or resistant disease had a less than 10% chance of achieving a later major cytogenetic response, as were those in complete hematologic response (CHR) and who had pretreatment splenomegaly and thrombocytosis. Applying the model at 3 months showed that only patients with &lt; or = PHR and pretreatment splenomegaly or thrombocytosis at 3 months had such a low major cytogenetic response rate. Finally, at 12 months, patients with CHR still had a 15% to 25% chance of having a major cytogenetic response later if they did not have pretreatment splenomegaly and thrombocytosis. CONCLUSION This analysis allows better selection of patients with Ph-positive CML on IFNalpha therapy for continuation of IFNalpha versus changing therapy early in the course of CML. For treatment programs that choose to change patients to other investigational therapies (eg, intensive chemotherapy and/or autologous stem-cell transplantation [SCT]), baseline outcome expectations are provided for patients continued on IFNalpha therapy, against which the results of new approaches can be compared.