tbuckley/cabot-search huggingface dataset:
PEAK: A randomized phase II study to compare the efficacy of panitumumab plus mFOLFOX6 to bevacizumab plus mFOLFOX6 in patients (pts) with previously untreated, unresectable metastatic colorectal cancer (mCRC) expressing wild-type <i>KRAS</i>.
Authors: L. S. Schwartzberg, V. J. Wagner
Journal: Journal of Clinical Oncology (2010)

TPS189 Background: Panitumumab, a high-affinity, fully human monoclonal antibody against human epidermal growth factor receptor, has demonstrated efficacy with respect to objective tumor response and progression-free survival (PFS) with an acceptable safety profile in pts with mCRC expressing wild-type KRAS when used as monotherapy and in combination with chemotherapy. This study will provide comparative data on efficacy and safety of panitumumab plus mFOLFOX6 relative to a current standard of care (bevacizumab plus mFOLFOX6) as first-line treatment in pts with mCRC tumors expressing wild-type KRAS. Methods: This phase II, open-label, randomized, multicenter study is being conducted in the US, Canada, Belgium, Germany, Spain, and Italy; 50 of 280 planned pts have enrolled. Pts ≥ 18 years with adenocarcinoma of the colon or rectum with unresectable metastatic disease expressing wild-type KRAS are eligible. Pts must have Eastern Cooperative Oncology Group (ECOG) status 0 or 1 and at least 1 unidimensionally measurable lesion. Pts may not have had prior chemotherapy or other systemic anticancer therapy for mCRC or prior adjuvant chemotherapy for the treatment of colorectal cancer ≤ 52 weeks prior to randomization, or be unable to receive panitumumab, bevacizumab, or mFOLFOX6. Fixed, paraffin-embedded primary or metastatic tumor tissue and blood samples will be collected for biomarker analyses. The primary objective is to estimate the treatment effect on PFS of panitumumab relative to bevacizumab in combination with mFOLFOX6. Secondary objectives include the evaluation of overall survival, objective response, duration of response, time to progression, time to response, resection rate, and safety. Exploratory objectives include investigation of correlations between tumor protein levels (e.g., PTEN) and tumor RNA levels (e.g., epiregulin, amphiregulin) with efficacy; effect of tumor genetic variation in signal transduction genes, cancer-associated genes, drug target genes, and other biomarker genes on efficacy (also in subsets of pts). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen
Abstract 19128: Quantitative Spatial Cardiac Localization of PVCs Using the 12 Lead ECG
Authors: Peter van Dam, Roderick Tung, Kalyanam Shivkumar, Michael Laks
Journal: Circulation (2013)

Introduction: The precise localization of the site of origin of a PVC or VT prior to ablation would facilitate the planning and execution of the electrophysiological procedure. Current electrocardiographic imaging (ECGI) techniques uses body surface mapping that is costly, complex, and requires as many as 256 leads to localize the PVC origin. We developed and tested a novel myocardial activation based ECGI technique utilizing the readily available 12 lead ECG to localize the PVC origin. Method: The myocardial activation based ECGI requires a patient specific model of the heart and thorax. For the PVC or VT origin localization, the fastest route algorithm is used on patient specific models created by newly developed morphing software. Result: Eight patients that underwent electrophysiological mapping and ablation of PVCs were studied. The PVCs origins were localized on the endocardium of the mid left lateral wall, the anterior RVOT, the LV superior septum, septal RVOT and mid wall of the RVOT. In one patient the PVC origin was located on the epicardial RVOT. PVC localization by the 12-lead ECGI was correlated to the site of successful ablation. All patients (8/8) had accurate prediction of the PVC origin. However, in two patients without patient specific models the localization was reversed between the RV free wall and septum of the RVOT. With patient specific models, these latter two cases would likely be localized correctly. Conclusion: This feasibility study of the modified myocardial activation based ECGI shows ability to localize the PVC origin based on only the standard 12 lead ECG. This ECGI method yields activation estimates of isochrones on both ventricles from which the PVC origin location is derived. This new ECGI technique can localize the PVC from any part of the ventricular endocardium, intra-myocardium or epicardium.
Effects of d-amphetamine on urinary metabolites of dopamine and norepinephrine in hyperactive boys
Authors: W O Shekim, J Javaid, H Dekirmenjian, J L Chapel, J M Davis
Journal: American Journal of Psychiatry (1982)

The authors measured the urinary metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in 21 hyperactive boys and 12 matched healthy boys. The hyperactive boys excreted lower amounts of MHPG than control boys. Hyperactive drug responders excreted lower amounts of HVA than control boys and hyperactive nonresponders. Drug responders with normal MHPG excreted low amounts of HVA and those with normal HVA excreted low amounts of MHPG. d-Amphetamine decreased MHPG in all drug responders and HVA in drug responders with normal HVA levels, although it tended to increase HVA in those with low HVA levels. The authors discuss their data in terms of the possible involvement of norepinephrine and dopamine in the etiology of hyperactivity in children.
ECT-induced status epilepticus and further ECT: a case report
Authors: R D Weiner
Journal: American Journal of Psychiatry (1981)

The author describes an occurrence of ECT-induced status epilepticus in a patient who was psychotically depressed and unresponsive to tricyclic and neuroleptic medication. After an extensive evaluation and further unsuccessful use of treatment alternatives the patient then received a course of specially modified ECT; he had no further sequelae and had a good clinical response.
Comparative Carcinogenicity of 5-Nitrothiophenes and 5-Nitrofurans in Rats 2 3
Authors: Samuel M. Cohen, E. Ertürk, George T. Bryan
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Comparative Carcinogenicity of 5-Nitrothiophenes and 5-Nitrofurans in Rats Get access Samuel M. Cohen, Samuel M. Cohen Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Ertürk, E. Ertürk Search for other works by this author on: Oxford Academic PubMed Google Scholar George T. Bryan George T. Bryan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 2, August 1976, Pages 277–282, https://doi.org/10.1093/jnci/57.2.277 Published: 01 August 1976 Article history Revision received: 20 January 1975 Received: 13 June 1975 Accepted: 30 January 1976 Published: 01 August 1976
STEM-16SONODYNAMIC 5-ALA PLUS ULTRASOUND THERAPY AUGMENTS ANTI-TUMOR EFFECTS IN THE ONCOGENE KNOCK-IN GLIOMA STEM CELLS
Authors: Kenji Shono, Teruyoshi Kageji, Yoshihumi Mizobuchi, Toshitaka Fujihara, Keiko Kitazato, Kohei Nakajima, Hideo Mure, Kazuyuki Kuwayama, Shinji Nagahiro
Journal: Neuro-Oncology (2015)

STEM-16. SONODYNAMIC 5-ALA PLUS ULTRASOUND THERAPY AUGMENTS ANTI-TUMOR EFFECTS IN THE ONCOGENE KNOCK-IN GLIOMA STEM CELLS Kenji Shono, Teruyoshi Kageji, Yoshihumi Mizobuchi, Toshitaka Fujihara, Keiko Kitazato, Kohei Nakajima, Hideo Mure, Kazuyuki Kuwayama, and Shinji Nagahiro; Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima UniversityGraduateSchool, Tokushima City,Tokusima Prefecture, Japan INTRODUCTION: To overcome the chemoand radiation resistance of glioblastoma multiforme (GBM), new therapeutic strategies are needed. Sonodynamic therapy (SDT) is efficacious in several types of tumor and cancer. However, there are few studies in oncogene knock-in glioma stem cells (GSCs), which are thought to be implicated in the therapeutic resistance of GBM. We tested our hypothesis that SDT is effective in GSCs and GBM cells. METHODS: Using GSCs and U251 MG cells we assessed the efficacy of SDT in vitro. We also studied the anti-tumor effects of SDT in GSC-bearing mice. We compared the efficacy of SDT delivered in a single ultrasound session (1 MHz, 2W/cm) with the results obtained with 5-ALA delivered at 1 mM/well. RESULTS: While no significant effects were observed when cells were exposed to 5-ALA, ultrasound-treated cells lost viability immediately after exposure. SDT enhanced the effects of ultrasonography. Our findings suggest that SDT may be effective in GBM cells and GSCs. CONCLUSION: Ours is the first study to show the efficacy of SDT in GSCs. The mechanisms mediated by SDT and by photodynamic therapy may be different. Studies are underway to confirm the beneficial effects of SDT in GSC-bearing mice and to elucidate the mechanisms underlying its efficacy. Neuro-Oncology 17:v208–v213, 2015. doi:10.1093/neuonc/nov234.16 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Abstract 404: MK2461 suppress progression of pancreatic cancer disrupting interaction between pancreatic cancer cells and stellate cells
Authors: Koetsu Inoue, Hideo Ohtsuka, Fuyuhiko Motoi, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Shinobu Ohnuma, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno
Journal: Cancer Research (2015)

Abstract Pancreatic cancer is characterized excessive desmoplasia, which occupies 80% of pancreatic cancer tissue and mainly consists of pancreatic stellate cells (PSCs). Desmoplasia has been shown to play an important role in the progression, invasion, and metastasis of pancreatic cancer and has been implicated in the development of resistance to chemotherapy and radiotherapy. Growth factors are one of the components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. Therefore, blocking growth factor signaling could suppress cancer progression. In this study, we profiled the expression of receptor tyrosine kinases (RTKs) with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry (LC-MS/MS) in PCCs and PSCs. In PCCs, epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) levels were elevated compared with those in PSCs. In PSCs, platelet-derived growth factor receptor beta (PDGFRβ) and MET were upregulated compared with other RTKs. Conditioned medium from PSCs promoted the proliferation of PCCs, and vice versa. In addition, MK2461, a multikinase inhibitor targeting MET and PDGFRβ, suppressed the effects of conditioned medium on PCCs and PSCs. In addition, MK2461 significantly inhibited tumor growth in mice xenograft model. In conclusion, PDGFRβ and MET may play a critical role in the interaction between PCCs and PSCs. Moreover, MK2461 may have therapeutic potential in the treatment of pancreatic cancer by targeting the interaction between PCCs and PSCs. Citation Format: Koetsu Inoue, Hideo Ohtsuka, Fuyuhiko Motoi, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Shinobu Ohnuma, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno. MK2461 suppress progression of pancreatic cancer disrupting interaction between pancreatic cancer cells and stellate cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 404. doi:10.1158/1538-7445.AM2015-404
Secondary mania with focal cerebrovascular lesions
Authors: J L Cummings, M F Mendez
Journal: American Journal of Psychiatry (1984)

The authors describe two patients with secondary mania associated with right thalamic infarctions. Both patients exhibited hemisensory loss, denial of illness, and amnesia for the manic episode. One improved with lithium therapy and the other recovered without specific pharmacologic intervention. A review of reported cases reveals that most focal lesions associated with secondary mania involve the diencephalic region and that the majority of lateralized lesions are on the right side.
複合先天性心疾患に対する心内修復術後末期患者の心房性頻脈のNon-contact mapping及びカテーテルアブレーション
Authors: Manaka Tetsuyuki, Shoda Morio, Yanagishita Daigo, Ejima Koichiro, Satoh Takahiro, Futagawa Keisuke, Hagiwara Nobuhisa, Takahashi Kazuhiro, Takeuchi Daiji, Fujita Shuhei
Journal: Circulation (2009)
Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes
Authors: Berit E. Inkster, Nicola N. Zammitt, Stuart J. Ritchie, Ian J. Deary, Ian Morrison, Brian M. Frier
Journal: Diabetes Care (2016)

OBJECTIVE To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. RESEARCH DESIGN AND METHODS Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. RESULTS Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non–sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P &amp;lt; 0.001) and hypoglycemia symptom scores were significantly higher (P &amp;lt; 0.001), even when symptoms that may have been caused by sleep deprivation, such as tiredness, were removed. CONCLUSIONS Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period.
Guidelines for management of hypertension
Authors: P. T Sawicki
Journal: BMJ (1994)

Editor,--Recently, the World Health Organisation and International Society of Hypertension published guidelines on the management of mild hypertension. Peter H Winocour is concerned that these guidelines place too little emphasis on the impact of metabolic control on the management of essential hypertension.1 He fears that treatment with diuretics and β blockers as the first among equal agents of choice in the guidelines could lead to an 11-fold increase …
Preterm rupture of membranes.
Authors: Myron Schultz
Journal: BMJ (1982)

About 10% of babies in the United States are born prior to 36 weeks of pregnancy, and about 3% are born before 32 weeks. Preterm rupture of the membranes, prior to 36 weeks, occurs in about 2½% of all pregnancies or about 1 in 40. Causes. Sometimes, we will be able to identify a cause for preterm rupture of the membranes. Labor itself can cause rupture of the membranes. Other causes for preterm rupture of the membranes include infection within the uterus, uterine overdistension because of conditions causing an excess amount of amniotic fluid, and cervical weakness (“cervical incompetence”). For most Moms with preterm rupture of the membranes, no cause is apparent. Diagnosis. Mom usually experiences a gush of amniotic fluid from the vagina, although occasionally there will only be small amounts of leakage. The fluid coming out can be examined under the microscope; amniotic fluid shows a typical “fern” pattern. After membranes rupture, a sterile speculum exam is sometimes done to obtain a fluid sample and to look at the cervix to determine whether it is open or not, and an ultrasound scan is used to check baby’s position and the amount of fluid left inside. If at all possible digital examination is avoided, since this can introduce infection. Management. Treatment for pregnancies complicated by preterm rupture of the membranes depends upon the stage in the pregnancy. After membranes rupture, there are risks for baby staying inside, specifically of development of infection around the baby, compression of the umbilical cord due to the lack of cushioning effect of the amniotic fluid and rapid labor. Also, placental separation occurs in about 2% of pregnancies with preterm rupture of the membranes. These risks need to be balanced against the risks of prematurity. Newborn outcomes depend upon baby’s size and stage in the pregnancy, as well as lung maturity. Babies born at or beyond 36 weeks rarely have any significant problems related to prematurity. Babies born at 35 to 36 weeks typically weigh between 5 and 6½ pounds. They may have short-term problems from lung
Graphene Quantum Dots: Effects of Graphene Quantum Dots on the Self-Renewal and Differentiation of Mesenchymal Stem Cells (Adv. Healthcare Mater. 6/2016)
Authors: Jichuan Qiu, Deshuai Li, Xiaoning Mou, Jianhua Li, Weibo Guo, Shu Wang, Xin Yu, Baojin Ma, Shan Zhang, Wei Tang, Yuanhua Sang, Pilar Rivera Gil, Hong Liu
Journal: Advanced Healthcare Materials (2016)

Fluorescent graphene quantum dots (GQDs) with good biocompatibility have great potential applications in biomedical areas. P. R. Gil, H. Liu, and co-workers' investigation of the interactions between GQDs and mesenchymal stem cells (MSCs) is presented on page 702. When exposed to MSCs, GQDs can be ingested by MSCs and within a certain concentration range GQDs have no significant influence on self-renewal potential of MSCs, but even promote and enhance their osteogenic and adipogenic differentiation at the level of mRNA and protein expression.
Hemispheric asymmetries and schizophrenia
Authors: N C Andreasen, J W Dennert, S A Olsen, A R Damasio
Journal: American Journal of Psychiatry (1982)

Investigators have hypothesized that schizophrenic patients have abnormal left hemisphere function or deviations from normal function asymmetry. It has also been suggested that schizophrenic patients have reversal of normal structural asymmetries. The authors measured frontal and occipital petalia and frontal and occipital width of each hemisphere on the CT scans of 43 right-handed schizophrenic patients and 40 right-handed control subjects. There were no significant differences in structural asymmetry between the groups. The 8 left-handed schizophrenic patients may have had abnormal functional asymmetries; their mean ventricular-brain ratio, a possible indirect indicator of cerebral atrophy, was higher than that of the right-handed patients.
Outcome analysis after post-chemotherapy surgery in patients with non-seminomatous germ cell tumours
Authors: A. Gerl, C. Clemm, N. Schmeller, H. Dienemann, R. Lamerz, M. Kriegmair, W. Wilmanns
Journal: Annals of Oncology (1995)

The goal of the study was to analyse long-term outcome after post-chemotherapy surgery in male patients with non-seminomatous germ cell tumours (NSGCT).We reviewed the charts of 111 patients with metastatic NSGCT treated at a single institution from 1979 to 1993 who underwent post-chemotherapy resection of residual masses after normalisation of tumour markers. The prognostic relevance of the extent of tumour residuals, the comprehensiveness of surgery and the histology at resection was analysed.Thirteen patients (12%) harboured viable cancer, and 46 patients (41%) mature teratoma at post-chemotherapy surgery. Only seven (54%) of the 13 patients with viable cancer remained continuously disease-free. Incomplete surgery predicted an impaired outcome (62% vs. 86% survival), although only one recurrence was observed at a site of an incompletely resected mass. Moreover, a progression-free interval < or = 3 months after post-chemotherapy surgery was correlated with worse subsequent survival (p = 0.0001).Post-chemotherapy surgery remains an essential part of the treatment for metastatic NSGCT. Resection of viable cancer and mature teratoma is of therapeutic benefit. Viable cancer at surgery defines the need for further chemotherapy.
Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trials in patients with moderate to severe psoriasis
Authors: Robert Bissonnette, David M. Pariser, Norman R. Wasel, Joana Goncalves, Robert M. Day, Rongdean Chen, Michael Sebastian
Journal: Journal of the American Academy of Dermatology (2016)

BackgroundDifficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life.ObjectiveWe evaluated the efficacy and safety of apremilast in palmoplantar psoriasis.MethodsA post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1).ResultsSignificantly more patients taking apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P = .021). At week 16, 46% of the apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group (P < .001); 59% of the apremilast group had a PPPGA score of 0 or 1 with 1-point or more improvement versus 39% receiving placebo (P < .001).LimitationsThis post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement.ConclusionApremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.
Genomic anatomy of the t(15;17): Significant subclustering of genomic breakpoints within RAR alpha intron 2.
Authors: A Reiter, S Saussele, David Grimwade, J L Wiemels, M Segal, A Weisser, A Hochhaus, A Willer, A Reichert, T Buchner, E Lengfelder, R Hehlmann, N C P Cross
Journal: Blood (2001)
Is “DevoManc” devolution, delegation, or dismantling of the NHS?
Authors: Fiona Godlee
Journal: BMJ (2016)

It’s been said that only two things will survive a nuclear holocaust: cockroaches and regional health authorities. Does the Greater Manchester experiment in devolution—otherwise known as DevoManc—show the extraordinary regenerative powers of NHS regions, as they once more refuse to lie down and die?

Reduced in number from 14 to eight in 1994, England’s regional health authorities were transmogrified into 10 strategic health authorities in 2006, only to be vapourised altogether by the Lansley reforms in 2013.

Now, in what Richard Vize (doi:10.1136/bmj.i1611) calls “one of …
The importance of p53 pathway genetics in inherited and somatic cancer genomes
Authors: Giovanni Stracquadanio, Xuting Wang, Marsha D. Wallace, Anna M. Grawenda, Ping Zhang, Juliet Hewitt, Jorge Zeron-Medina, Francesc Castro-Giner, Ian P. Tomlinson, Colin R. Goding, Kamil J. Cygan, William G. Fairbrother, Laurent F. Thomas, Pål Sætrom, Federica Gemignani, Stefano Landi, Benjamin Schuster-Böckler, Douglas A. Bell, Gareth L. Bond
Journal: Nature reviews. Cancer (2016)