tbuckley/cabot-search huggingface dataset:
NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism
Authors: Chia-Lin Chen, Dinesh Babu Uthaya Kumar, Vasu Punj, Jun Xu, Linda Sher, Stanley M. Tahara, Sonja Hess, Keigo Machida
Journal: Cell Metabolism (2015)
Phase II Study of Bevacizumab Plus Uft/Lv in Elderly Patients with Metastatic Colorectal Cancer(J-Blue): Os Updated
Authors: Toshiki Masuishi, Mitsuo Shimada, Tomohiro Nishina, Toshikazu Moriwaki, Mitsuharu Ozeki, Yuji Negoro, Shunju Indo, Tadamichi Denda, Takashi Maeba, Ichinosuke Hyodo
Journal: Annals of Oncology (2014)
Novel Non-Cytotoxic Therapy in Ovarian Cancer: Current Status and Future Prospects
Authors: Lainie Martin, Russell J. Schilder
Journal: Journal of the National Comprehensive Cancer Network (2006)

Although significant improvements in standard therapy for ovarian carcinoma have been made over the past decade, current treatment is limited by the development of resistance to cytotoxic chemotherapy, and most women ultimately die of the disease. New knowledge of the biology of ovarian cancer has led to the identification of potential molecular targets that are differentially expressed in normal cells versus cancer cells, and advances in pharmacology have led to the development of novel agents that work differently from traditional cytotoxic chemotherapy by exploiting these targets. Many of these agents are being evaluated in clinical trials. This article discusses molecular targets that are important in ovarian carcinoma, including angiogenesis, tyrosine kinases, mitogen-activated protein kinases, and phosphatidylinositol-like kinases such as mammalian target of rapamycin, and the proteosome. This article reviews novel non-cytotoxic agents that target these pathways and are currently being evaluated in ovarian carcinoma treatment.
Initial drug treatment in Parkinson’s disease:
Authors: Sharon Muzerengi, Carl E Clarke
Journal: BMJ (2015)

#### The bottom line A 69 year old retired bus driver with no medical history of note presented to the outpatients department with a three year history of progressive tremor of the right hand; slowness of movement; and difficulty turning in bed at night, buttoning shirts, and using cutlery. He is keen to know what is wrong and whether it can be treated. Parkinson's disease is a progressive neurodegenerative disorder characterised by tremor, rigidity, bradykinesia, and a wide spectrum of non-motor symptoms including sleep disorders, hyposmia, bladder and bowel dysfunction, fatigue, dementia, and other neuropsychiatric symptoms.1 Although the disease has no cure, available treatments effectively control motor symptoms and improve quality of life.2 3 Several drug classes are licensed for use as monotherapy in early Parkinson's disease and adjuvant therapy in later disease:
Abstract P225: Longitudinal Association Between Body Weight Change and 6-Year Change of Serum Cholesterol Levels in Japanese Men
Authors: Shin-ya Nagasawa, Masaru Sakurai, Koshi Koshi Nakamura, Katsuyuki Miura, Yuko Morikawa, Masao Ishizaki, Teruhiko Kido, Yuchi Naruse, Yasushi Suwazono, Kazuhiro Nogawa, Hideaki Nakagawa
Journal: Circulation (2015)

Objective: To investigate the longitudinal relationship between body weight (BW) change and years-long change of cholesterol levels in a prospective cohort study.

Participants: A total of 2585 male employees aged 25-53 years without use of lipid-lowering drug in a metal products factory in Japan.

Measurements: Total cholesterol (TC) level was measured by enzymatic assay and HDL cholesterol (HDL-C) level was measured using direct methods. Physical examinations and information on lifestyle and use of medicine were annually measured or confirmed from 2003 (baseline) to 2009. The associations between difference of BW from 2003 to 2008 and 6-years change of cholesterol levels from 2003 to 2009 were analyzed with generalized estimating equation models. Covariates in full adjusted model were age, the other two cholesterol levels among TC, HDL-C, or T/H ratio, body mass index, and smoking and drinking status in baseline.

Results: Mean ± standard deviation (SD) of age, height, and BW in 2003 was 39.3 ± 8.0 years, 170.6 ± 6.0 cm, and 68.2 ± 9.9 kg, respectively. Mean ± SD of BW in 2008 was 68.8 ± 10.2 kg. Mean and SD of TC and HDL-C levels and proportion of TC/HDL-C ratio ≥ 5 (TH5) in 2003 were 199.2 ± 33.8 and 57.5± 13.7 mg/dl and 10.5 %, respectively. These cholesterol levels in 2009 were 206.5 ± 33.5 and 58.1 ± 13.9 mg/dl and 11.4 %, respectively. In full adjusted model, 1 kg increase of BW in 5 years was significantly associated with 1.1 mg/dl higher TC (P < 0.001), 0.4 mg/dl lower HDL-C (P < 0.001), and greater TH5 (odds ratio: 1.11, P < 0.001) in 6 years.

Conclusions: Beyond relevant covariates, increasing BW significantly elevated TC and decreased HDL-C level.

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The use of IV pentamidine as second line prophylaxis for pneumocystis pneumonia
Authors: M. K. Chuk, A. A. Dabb, S. Y. Kim, D. J. Glenn, D. M. Loeb
Journal: Journal of Clinical Oncology (2006)

9043 Background: Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a serious risk to pediatric oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis greatly reduces the risk of infection, however many children cannot take TMP-SMZ because of bone marrow suppression, drug allergy or patient noncompliance in taking oral medication. Inhaled pentamidine has been used successfully as second line prophylaxis, with a breakthrough PCP rate of 2.7%. However, many centers are unable to administer this specialized respiratory treatment to pediatric patients and in very young children, there are concerns about the effectiveness of the drug delivered in this manner. We performed a retrospective analysis of the use of intravenous pentamidine to assess its efficacy as second line prophylaxis. Methods: We conducted a retrospective review of all pediatric oncology patients at our institution who received at least one dose of pentamidine in the year 2005. The total number of doses dispensed allowed us to calculate the patient-months of pentamidine used. The charts of these patients were reviewed for the justification for the change from TMP-SMZ to pentamidine. Children who developed symptoms of pneumonia underwent diagnostic bronchoscopy, allowing us to calculate the breakthrough rate. Results: A total of 100 patients received 506 doses of pentamidine (4 mg/kg) administered monthly over a twelve month period. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Two children developed PCP, resulting in a breakthrough rate of 2% (or 0.4% per patient-months of treatment). Conclusions: The use of IV pentamidine once a month as second line prophylaxis against PCP results in a breakthrough rate of 2%. These results are similar to the breakthrough rate observed with inhaled pentamidine. When possible, we encourage the use of TMP-SMZ prophylaxis, however, when needed, the use of IV pentamidine is effective as second line prophylaxis. No significant financial relationships to disclose.
The Psychosis High-Risk State
Authors: Paolo Fusar-Poli, Stefan Borgwardt, Andreas Bechdolf, Jean Addington, Anita Riecher-Rössler, Frauke Schultze-Lutter, Matcheri Keshavan, Stephen Wood, Stephan Ruhrmann, Larry J. Seidman, Lucia Valmaggia, Tyrone Cannon, Eva Velthorst, Lieuwe De Haan, Barbara Cornblatt, Ilaria Bonoldi, Max Birchwood, Thomas McGlashan, William Carpenter, Patrick McGorry, Joachim Klosterkötter, Philip McGuire, Alison Yung
Journal: JAMA Psychiatry (2012)

<h3>Context</h3>During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5.<h3>Objective</h3>To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain.<h3>Data Sources</h3>Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences.<h3>Study Selection and Data Extraction</h3>Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field.<h3>Data Synthesis</h3>Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures.<h3>Conclusions</h3>The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses.
Abstract P091: Food-Stimulated Neuronal Activation Differs by Feeding Status in Obese and Normal-Weight Women: An fMRI Study
Authors: Marie-Pierre St-Onge, Melissa Sy, Mike S Kim, Joy Hirsch
Journal: Circulation (2014)

Introduction: Neurological responses to food stimuli are complex and differ between lean, obese, and post-obese (weight-reduced) individuals. However, the neurological systems that regulate feeding in relation to weight status are not understood. The purpose of this study was to compare satiety mechanisms (fed&gt;fasted) in obese and lean women. Hypothesis: We assessed the hypotheses that food-specific neural signals affected by satiety are more active in lean than obese women. Methods: Eleven normal weight (BMI 22.8 ± 1.5 kg/m2) and 9 obese (BMI 33.0 ± 3.4 kg/m2) women completed a functional magnetic resonance imaging (fMRI) study. Fasted state scans were performed after an 8-h daytime fast for normal weight women whereas obese women were scanned after an overnight fast. Fed state scans were started 30 min after consumption of a liquid meal replacement providing 35% of resting energy requirements. Testing days were held 2 wk apart. Results: Overall, the neuronal activity in response to food stimuli was higher in the fed state than the fasted state for both groups. However, normal weight women had a greater number of activated regions than obese women in both the fed and fasted state. When fed and fasted states were contrasted (fed&gt;fasted) and compared between groups (normal weight&gt;obese), normal weight women had greater activation in the insula, cuneus, lingual gyrus, pre- and post-central gyrus, superior and middle temporal gyrus, and inferior frontal gyrus in the fed state than the obese. Conclusions: In conclusion, the findings of this study suggest that obese individuals recruit fewer brain centers in response to food stimuli when fed. This may be associated with a reduced ability to respond to internal satiety signals.
Abstract P311: Impact Of Income Level On The Care Of Senile Aortic Stenosis Under Universal Health Coverage
Authors: Seitetsu Lee, Hideki Hashimoto, Hideo Yasunaga, Hiromasa Horiguchi, Takahide Kohro, Satoshi Iimuro, Daisuke Koide, Issei Komuro, Tsutomu Yamazaki
Journal: Circulation (2014)

Background: Population aging results in increased volume of aortic stenosis (AS) patients. Although, income is an independent factor of operative mortality for patients undergoing aortic valve surgery in the US, it remains unknown to date whether individual income affects treatment decision to undergo surgery and survivorship after surgery under the universal health coverage in Japan. Methods: Using the Japanese Diagnosis Procedure Combination database, we extracted a total of 16079 isolated AS patients aged ≥ 65 years hospitalized between July 2010 and March 2012. Individual income was represented by patients’ residential mean household income. Income was categorized into quartiles with approximately equal numbers of patients. First, decision over undergoing valve surgery was regressed on income level with adjustments for hospital volume, regional medical supplying factor and patients’ individual variables. Moreover, survivorship was regressed on income level with adjustment for types of surgery and combined surgery besides the abovementioned variables. Results: Of the 16079 AS patients, 6803 underwent aortic valve surgery. In the multivariable regression analysis for decision over undergoing surgery, the odds ratios for the 2nd, 3rd, 4th quartiles with reference to the 1st quartile of income were 0.79[95% CI: 0.61-1.02], 0.90[0.69-1.17], 0.99[0.77-1.28], respectively. In the multivariable regression analysis for post-operative mortality, the odds ratios for the 2nd, 3rd, 4th quartiles were 1.47 [0.47-4.6], 1.10 [0.30-3.70] and 1.50 [0.50-4.60], respectively. Hospital volume was significantly associated with higher likelihood of surgical intervention and lower post-operative mortality. Conclusions: Under universal health coverage in Japan, treatment decision for surgical intervention and postoperative survivorship of aortic valve surgery was equal regardless of patients’ income levels, while hospital volumes exerted a significant influence on the treatment choice and the outcome of the surgery.
Abstract #1738: Curcumin decreases Sp protein expression and pancreatic cancer cell and tumor growth
Authors: Indira Jutooru, Gayathri Chadalapaka, Stephen Safe
Journal: Cancer Research (2009)

Recent studies have shown that Specificity protein 1 (Sp1) is overexpressed in pancreatic tumors and is associated with poor prognosis for these patients. In addition to Sp1, Sp3 and Sp4 are also overexpressed in many tumors and together Sp1, Sp3 and Sp4 regulate many genes that play an important role in tumor growth, angiogenesis, survival and metastasis. Since Sp proteins are overexpressed in tumor tissue when compared to the normal tissues, this suggests that Sp transcription factors are excellent targets for cancer chemotherapy. Recent studies showed that phytochemical curcumin (diferuloylmethane), a spice component, inhibited tumor growth and proliferation in various cancer cell lines and is reported to act through inhibition of NFkB. In this study we show that curcumin inhibited proliferation of Panc-28 and L3.6pL pancreatic cancer cell lines and growth inhibitory IC 50  values were 12.4 and 9.7 µM for Panc-28 and L3.6pL cells respectively. Curcumin also induced apoptosis and decreased expression of cyclin D1, survivin, vascular endothelial growth factor (VEGF) and its receptor VEGFR1 & VEGFR2 and epidermal growth factor receptor (EGFR). Curcumin also decreased constitutive levels of NFkB and this was associated with down regulation of p65. Sp knockdown by RNA interference also decreased p65 expression demonstrating that in pancreatic cancer cells p65 is an Sp dependent gene. Treatment with 10 - 50 µM curcumin decreased Sp1, Sp3 and Sp4 protein expression in both Panc-28 and L3.6pL cells and curcumin induced Sp downregulation was not inhibited by the proteosome inhibitor MG132. We also observed that at a dose of 100 mg/kg/day given intraperitoneally, curcumin decreased pancreatic tumor weight and growth in athymic nude mice bearing L3.6pL cells as xenografts. In addition, we also observed decrease in Sp-dependent genes such as VEGF, survivin, cyclin D1 in both in vivo and in vitro studies. The mechanism responsible for curcumin-dependent Sp proteins degradation is currently under investigation.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1738.
Abstract 12176: Higher CHADS2 Score is Associated With Impairment of Coronary Flow Reserve Evaluated by Phase-Contrast Cine Cardiovascular Magnetic Resonance Imaging
Authors: Hidekuni Kirigaya, Shingo Kato, Daiki Gyoutoku, Nao Yamada, Naoki Iinuma, Yuka Kusakawa, Kouhei Iguchi, Yuko Miki, Tatsuya Nakachi, Kazuki Fukui, Kazuo Kimura, Satoshi Umemura
Journal: Circulation (2014)

Background: The CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke) score is used to evaluate the risk of ischemic stroke in patients with atrial fibrillation (AF). Recent study showed that the CHADS2 score was associated with higher rate of mortality and stroke in patients with acute coronary syndrome (ACS), irrespective of the presence or absence of AF. Phase contrast (PC) cine magnetic resonance imaging (MRI) allows for non-invasive and accurate assessment of coronary flow reserve (CFR). The hypothesis of this study is that CHADS2 score can predict impairment of CFR in patients with known or suspected coronary artery disease (CAD). Materials and Methods: One hundred forty three patients with known or suspected CAD (mean age 70.3 ± 9.5 years) without significant coronary arterial stenosis on X-ray coronary angiography (CAG) were studied. By using 1.5T MR scanner, breath-hold PC cine MR images of coronary sinus (CS) were obtained to assess the blood flow of CS both at ...
Ethical Debate: Should doctors be more proactive as advocates for victims of violence?: The moral philosopher’s view: The victim should decide
Authors: Grant Gillett
Journal: BMJ (1995)

This paper examines the ethical aspect of the recommended cooperative arrangement between accident and emergency and criminal justice services in the prevention of injury.  The justification for this arrangement is that increasing rates of conviction is an effective public health measure in injury prevention.  However there is a problem when the victim is reluctant to pursue the complaint.  Conflict comes in between the respect of autonomy and protection from harm and the ethics of intervention in the face of uncertainty.  There are however exceptions to this rule of clinical conduct.  One exception is created when in the doctors opinion the safety of the community is at stake or the community needs to be protected.  Another exception concerns the extent to which someone needs protection from his or her own bad choices such as suicide.  Most importantly health personnel should consider the efficacy of the measures to take before attempting to provide interventions.
Identification and optimisation of next generation inhibitors of IDO1 and TDO
Authors: Alan Wise, Phillip Cowley, Barry McGuinness, Sarah E Trewick, Thomas Brown
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO1) catalyse oxidation of the essential amino acid tryptophan (Trp) leading to the formation of immunosuppressive kynurenine (Kyn) pathway metabolites that dampen the immune response in the tumour
TCT-92 Transcatheter Aortic Valve Replacement in Asian Pacific Countries
Authors: Sung-Han Yoon, Jung-Min Ahn, Motoharu Araki, Futoshi Yamanaka, Mao-Shin Lin, Jason Leung Kwai Chan, Edgar L. Tay, Yung Tsai Lee, Taku Inohara, Ryo Yanagisawa, Jun-Bean Park, Yusuke Watanabe, Shinichi Shirai, Michael K. Lee, Paul Hsien-Li Kao, Wei-Hsian Yin, Gerald Yong, Kentaro Hayashida, Toshiya Muramatsu, Hyo-Soo Kim, Shigeru Saito, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2015)
Developmental changes of cardiac repolarization in rabbits Implications for the role of sex hormones
Authors: E Valverde
Journal: Cardiovascular Research (2003)

Firstly, to compare gender-dependent differences of cardiac repolarization in both adult and young rabbits. Secondly, to analyze the effect of gonadectomy on these gender differences in cardiac repolarization.We evaluated potential gender differences in cardiac repolarization with both microelectrode and ECG recordings. QT(end), JT(end), and T(peak-end) intervals and action potential durations at 30%, 50% and 90% of full repolarization were used to assess ventricular repolarization in adult (normal and gonadectomized) and young rabbits of both sexes.Adult rabbits exhibited clear gender-related differences in repolarization evidenced by significantly longer JT(end) and T(peak-end) intervals and significantly longer APD30, APD50 and APD90 in females. These gender-related differences in repolarization were absent in young rabbits and were abolished by gonadectomy.Developmental changes of repolarization are present in rabbits. These changes are in agreement with those reported in humans and may further support the role played by sex hormones in the modulation of cardiac repolarization.
Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial
Authors: A Keech, R J Simes, P Barter, J Best, R Scott, M R Taskinen, P Forder, A Pillai, T Davis, P Glasziou, P Drury, Y A Kesäniemi, D Sullivan, D Hunt, P Colman, M d'Emden, M Whiting, C Ehnholm, M Laakso
Journal: The Lancet (2005)
Lymphoblastic lymphoma in children--a randomized trial comparing LSA2-L2 with the A-COP+ therapeutic regimen: a Pediatric Oncology Group Study.
Authors: E V Hvizdala, C Berard, T Callihan, J Falletta, H Sabio, J J Shuster, M Sullivan, M D Wharam
Journal: Journal of Clinical Oncology (1988)

From May 1979 to March 1983, 76 evaluable patients with lymphoblastic lymphoma (LBL) were treated by members of the Pediatric Oncology Group (POG). Forty-six children treated by the six-drug A-COP+ regimen (Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], vincristine, prednisone, cyclophosphamide, methotrexate, and hydrocortisone) were compared in a prospective randomized trial with 30 patients receiving the modified ten-drug LSA2-L2 (cyclosphosphamide, vincristine, methotrexate, Daunomycin [daunorubicin cerubidine; Wyeth Laboratories, Philadelphia], prednisone, cytarabine, thioguanine, asparaginase, hydroxyurea, and carmustine) regimen. After adjusting for stage (I and II v III v IV), there was no statistically significant difference (P = .19) between A-COP+ and LSA2-L2 regimens on the basis of 3-year survival and disease-free survival (62% v 72% and 53% v 58%, respectively for the two treatment regimens) but the power of analysis and thus the ability to detect a clinically meaningful difference in the outcome with the two regimens was limited by the small number of patients. Neither therapy was effective for most patients with stage IV disease, with failure occurring in six of seven children receiving A-COP+ regimen and eight of 11 patients receiving LSA2-L2. Although the LSA2-L2 regimen was more toxic during the induction of remission, the toxicity during maintenance was acceptable and similar for both treatments. CNS relapse was not a significant problem whether cranial radiation with intrathecal (IT) therapy (A-COP+) or IT therapy alone (LSA2-L2) were used. Our results confirm the overall effectiveness of the LSA2-L2 regimen in children with LBLs, especially those initially free of bone marrow or CNS involvement, but were inconclusive as to the inferiority or superiority of this regimen over the A-COP+ regimen.