tbuckley/cabot-search huggingface dataset:
Profile of Daily Life in Children With Brain Tumors: An Assessment of Health-Related Quality of Life
Authors: Sundeep R. Bhat, Tress L. Goodwin, Tasha M. Burwinkle, Meagan F. Lansdale, Gary V. Dahl, Stephen L. Huhn, Iris C. Gibbs, Sarah S. Donaldson, Ruth K. Rosenblum, James W. Varni, Paul G. Fisher
Journal: Journal of Clinical Oncology (2005)

Purpose The survival of children with CNS tumors approaches 70%, yet health-related quality of life (HRQOL) has not been investigated rigorously in this population. We aimed to show that universal assessment of HRQOL could be obtained easily by using the PedsQL 4.0 and to provide a composite profile of their daily lives. Patients and Methods The PedsQL was administered to all patients seen in the neuro-oncology clinic at Lucile Packard Children's Hospital (Palo Alto, CA) from December 2001, to September 2002. Patients were compared with healthy controls by using two-sided t tests to evaluate statistically significant differences. Results One hundred thirty-four patients (73 male; mean age ± standard deviation, 11.8 ± 5.4 years; 55 had low-grade glioma, 32 had medulloblastoma/primitive neuroectodermal tumor/embryonal tumor, 17 had malignant astrocytoma, nine had germ-cell tumor, and 21 had other types of tumors) were assessed, each in less than 20 minutes. Scores on both child and parent-proxy reports for the total HRQOL, psychosocial, physical, emotional, social, and school-functioning scales were all significantly lower than controls (P &lt; .01). Patients with low-grade glioma were reported to have the highest total HRQOL. Children receiving radiation therapy (XRT) but no chemotherapy had significantly lower total, psychosocial, emotional, and social functioning than those receiving other treatments, including XRT plus chemotherapy. Conclusion The PedsQL can be used to assess HRQOL rapidly and easily in children with CNS tumors, who have significantly worse HRQOL than healthy children. Children receiving XRT fare worse overall; chemotherapy added to XRT does not seem to worsen HRQOL. Assessment of HRQOL should be included as an outcome in future clinical trials.
Standard versus patient-centred asthma education in the emergency department: a randomised study
Authors: S. Smith, C. Mitchell, S. Bowler
Journal: European Respiratory Journal (2008)

Brain region-specific deposition of extracellular amyloid plaques principally composed of aggregated amyloid-β (Aβ) peptide is a pathological signature of Alzheimer9s disease (AD). Recent human neuroimaging data suggest that resting-state functional connectivity strength is reduced in patients with AD, cognitively normal elderly harboring elevated amyloid burden, and in advanced aging. Interestingly, there exists a striking spatial correlation between functional connectivity strength in cognitively normal adults and the location of Aβ plaque deposition in AD. However, technical limitations have heretofore precluded examination of the relationship between functional connectivity, Aβ deposition, and normal aging in mouse models. Using a novel functional connectivity optical intrinsic signal (fcOIS) imaging technique, we demonstrate that Aβ deposition is associated with significantly reduced bilateral functional connectivity in multiple brain regions of older APP/PS1 transgenic mice. The amount of Aβ deposition in each brain region was associated with the degree of local, age-related bilateral functional connectivity decline. Normal aging was associated with reduced bilateral functional connectivity specifically in retrosplenial cortex. Furthermore, we found that the magnitude of regional bilateral functional correlation in young APP/PS1 mice before Aβ plaque formation was proportional to the amount of region-specific plaque deposition seen later in older APP/PS1 mice. Together, these findings suggest that Aβ deposition and normal aging are associated with region-specific disruption of functional connectivity and that the magnitude of local bilateral functional connectivity predicts regional vulnerability to subsequent Aβ deposition in mouse brain.
U.S. Food and Drug Administration Approval Summary: Brentuximab Vedotin for the Treatment of Relapsed Hodgkin Lymphoma or Relapsed Systemic Anaplastic Large-Cell Lymphoma
Authors: R. Angelo de Claro, Karen McGinn, Virginia Kwitkowski, Julie Bullock, Aakanksha Khandelwal, Bahru Habtemariam, Yanli Ouyang, Haleh Saber, Kyung Lee, Kallappa Koti, Mark Rothmann, Marjorie Shapiro, Francisco Borrego, Kathleen Clouse, Xiao Hong Chen, Janice Brown, Lara Akinsanya, Robert Kane, Edvardas Kaminskas, Ann Farrell, Richard Pazdur
Journal: Clinical Cancer Research (2012)

The U.S. Food and Drug Administration (FDA) describes the accelerated approval of brentuximab vedotin for patients with relapsed Hodgkin lymphoma and relapsed systemic anaplastic large-cell lymphoma (sALCL). FDA analyzed the results of two single-arm trials, enrolling 102 patients with Hodgkin lymphoma and 58 patients with sALCL. Both trials had primary endpoints of objective response rate (ORR) and key secondary endpoints of response duration and complete response (CR) rate. For patients with Hodgkin lymphoma, ORR was 73% (95% CI, 65-83%); median response duration was 6.7 months, and CR was 32% (95% CI, 23-42%). For patients with sALCL, ORR was 86% (95% CI, 77-95%), median response duration was 12.6 months, and CR was 57% (95% CI, 44-70%). The most common adverse reactions were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting. FDA granted accelerated approval of brentuximab vedotin for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplantation (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates, and for the treatment of patients with sALCL after failure of at least one prior multiagent chemotherapy regimen.
Sylvia Ray Ingold
Authors: L. Ivermee
Journal: BMJ (2003)

GP principal South Woodham Ferrers, near Cheltenham, 1967-92 (b London 1927; q University College London 1950; FRCOG), died from heart failure on 1 May 2003.​2003.




Figure 1




Sylvia was a registrar in obstetrics and gynaecology in Nottingham and London and assistant county medical officer in Essex before becoming a GP principal. Her previous experience in obstetrics and gynaecology was put to good use and she played a major role in the development of both clinical and academic needs within the department at St John's Hospital, Chelmsford, where she worked as a hospital practitioner. Sylvia was the first female doctor in the United Kingdom to complete the advanced hyperbaric medicine course and was an enthusiastic scuba diver. She leaves three children and five grandchildren.
miR-204 mediated loss of Myeloid cell leukemia-1 results in pancreatic cancer cell death
Authors: Zhiyu Chen, Veena Sangwan, Sulagna Banerjee, Tiffany Mackenzie, Vikas Dudeja, Xiaowu Li, Huaizhi Wang, Selwyn M Vickers, Ashok K Saluja
Journal: Molecular Cancer (2013)

Pancreatic cancer is one of the most lethal human malignancies, with an all-stage 5-year survival of <5%, mainly due to lack of effective available therapies. Cancer cell survival is dependent upon up-regulation of the pro-survival response, mediated by anti-apoptotic proteins such as Mcl-1.Here we show that over-expression of Mcl-1 in pancreatic patient tumor samples is linked to advancement of the disease. We have previously shown that triptolide, a diterpene triepoxide, is effective both in vitro and in vivo, in killing pancreatic cancer cells. Decrease of Mcl-1 levels, either by siRNA or by treatment with triptolide results in cell death. Using pancreatic cancer cell lines, we have shown that miR-204, a putative regulator of Mcl-1, is repressed in cancer cell lines compared to normal cells. Over-expression of miR-204, either by a miR-204 mimic, or by triptolide treatment results in a decrease in Mcl-1 levels, and a subsequent decrease in cell viability. Using luciferase reporter assays, we confirmed the ability of miR-204 to down-regulate Mcl-1 by directly binding to the Mcl-1 3' UTR. Using human xenograft samples treated with Minnelide, a water soluble variant of triptolide, we have shown that miR-204 is up-regulated and Mcl-1 is down-regulated in treated vs. control tumors.Triptolide mediated miR-204 increase causes pancreatic cancer cell death via loss of Mcl-1.
Cough, dyspnoea and purulent sputum in a 66-yr-old nonsmoking female
Authors: D Jager, KM Muller, A Gillissen, G Schultze-Werninghaus
Journal: European Respiratory Journal (1999)

Case historyA 66-yr-old female presented with dyspnoea on exercise, severe cough, purulent sputum and intermittent chest pain under both costal arches for the last 14 days.Five months prior to admission, pulmonary tuberculosis of both lower lobes had been diagnosed microscopically as the cause of recurrent bilateral pleural and pericardial effusions and pericardial thickening, and the patient was still under a two-drug antituberculous regimen.Loss of weight and fever were denied.She was a nonsmoker.Physical examination revealed wheeze over the left lower chest.The chest radiograph on admission was normal except for pleural thickening at the left lower chest wall associated with a small pleural effusion.Pulmonary function tests showed the following results: total lung capacity (TLC) 4.5 L (70% pred), forced expiratory volume in one second (FEV1) 1.3 L (45% pred), forced vital capacity (FVC) 2.2 L (59% pred), peak expiratory flow (PEF) 51%, maximal expiratory flow when 75% of the FVC remains to be exhaled (MEF75%) 36% pred; FEV1/FVC 83% pred, airway resistance (Raw) 0.55 kPa .L -1 .s and a slight hypoxaemia (9.1 kPa).Because a swab of the throat when cultured grew Escherichia coli, Pseudomonas fluorescens and Staphylococcus epidermidis, oral antibiotics were added to a routine antiobstructive therapy.There was some improvement in the symptoms, but residual cough and dyspnoea persisted.Owing to the development of haemoptysis, fibreoptic bronchoscopy was performed, which showed a tumour almost occluding the entrance of the lingula bronchus (fig.1).The biopsy of the tumour area is shown in figure 2. Subsequently, the chest radiograph as well as a computed tomographic (CT) scan changed from almost normal to the states shown in figures 3 and 4.After a second bronchoscopy to gain a definitive histology the patient experienced severe paroxysms of coughing.
Mitochondrial SIRT3 and heart disease
Authors: V. B. Pillai, N. R. Sundaresan, V. Jeevanandam, M. P. Gupta
Journal: Cardiovascular Research (2010)

Sirtuins are emerging as key regulators of many cellular functions including metabolism, cell growth, apoptosis, and genetic control of ageing. In mammals there are seven sirtuin analogues, SIRT1 to SIRT7. Among them SIRT3 is unique because this is the only analogue whose increased expression has been found to be associated with extended lifespan of humans. SIRT3 levels have been shown to be elevated by exercise and calorie restriction. Although the role of SIRT3 in cell biology is only beginning to be understood, initial studies have shown that SIRT3 plays a major role in free fatty acid oxidation and maintenance of cellular ATP levels. In the heart SIRT3 has been found to block development of cardiac hypertrophy and protect cardiomyocytes from oxidative stress-mediated cell death. Similarly, SIRT3 has been reported to have tumour-suppressive characteristics. In this article, we review the known effects of SIRT3 in different tissues and relate them to the protection of cardiomyocytes under stress.
Physiotherapy for stress urinary incontinence: a national survey.
Authors: J Mantle, E Versi
Journal: BMJ (1991)

To study the physiotherapeutic treatment of urinary stress incontinence in England.Postal questionnaire survey.All 192 English district health authorities.One physiotherapist from each district who was primarily concerned with urinary incontinence. A consensus view was requested.Responses to questionnaire and analysis of a visual analogue scale to indicate effectiveness.There was a 98% response rate. Treatment was often by senior physiotherapists (108 senior I grade or above) who, in 117 districts, claimed to have made a specialty of treating the condition. Gynaecologists and obstetricians were far more likely to refer patients than any other agency (147 respondents said that they were the commonest source of referral). One hundred and fifty four respondents stated that physiotherapy was usually used as the first line of treatment. Pelvic floor exercises and interferential treatment were most commonly used (by 178 and 144 respondents respectively) and thought to be the most effective, especially in combination, though various techniques were used in applying them. Positive motivation (108), recent onset of symptoms (55), and youth (40) were viewed optimistically, and obesity (60), previous surgery (59), prolapse (42), and a chronic cough (36) were considered to be bad prognostic features. The number of patients treated varied greatly (range 10-360) between districts and was poorly correlated with catchment size (correlation coefficient 0.3).As physiotherapists are treating considerable numbers of patients with stress incontinence research is urgently needed to produce efficacy data to enable rationalisation of resources to cater for the whole population.
Six Months of Treatment for Depression: Outcome and Predictors of the Course of Illness
Authors: Roger T. Mulder, Peter R. Joyce, Christopher M.A. Frampton, Suzanne E. Luty, Patrick F. Sullivan
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: The goals of this study were to determine the course of illness in a cohort of depressed patients undergoing treatment for 6 months and whether there are clinically useful predictors of their course of illness. METHOD: A cohort of 175 depressed outpatients undergoing drug treatment were followed prospectively for 6 months. Patients were initially randomly assigned to fluoxetine or nortriptyline. Those who responded were encouraged to continue taking their drugs for the 6 months. Those who did not were switched to other drugs or drug combinations. RESULTS: Of the 175 patients, 101 (58%) had a good outcome (achieved recovery and remained well), 54 (31%) had a fluctuating outcome (achieved recovery or remission but suffered a relapse or recurrence), and 20 (11%) had a poor outcome (remained depressed for the 6 months). Factors predicting good outcome included early response and a low level of schizoid personality disorder symptoms, and variables predicting poor outcome included a high score for harm avoidance and the absence of an early response. CONCLUSIONS: Depression is a recurring and chronic disorder. Personality factors such as a high harm avoidance score and schizoid traits were associated with a worse outcome, but demographic features, depression characteristics, depression subtypes, and comorbidity were not. Early response was strongly associated with the course of illness, but none of these features added significantly to the clinicians' ability to predict outcome.
Role of Fluoropyrimidine Schedule and (6 R , S )Leucovorin Dose in a Preclinical Animal Model of Colorectal Carcinoma
Authors: Shousong Cao, Cheryl Frank, Youcef M. Rustum
Journal: JNCI Journal of the National Cancer Institute (1996)

Background Fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd), used alone or in combination with other cytotoxic agents, exhibit limited efficacy in the treatment of advanced gastrointestinal cancer. (6 R , S )Leucovorin (LV), a source of reduced folate cofactor, can modulate (i.e., enhance) the therapeutic efficacy of treatment with these fluoropyrimidines (FPs). The role of FP schedule and LV dose in modulating FP antitumor activity, using clinically relevant drug doses and schedules, has not been fully documented.
Traumatic Distress Among Support-Seeking Female Victims of Stalking
Authors: Jan H. Kamphuis, Paul M.G. Emmelkamp
Journal: American Journal of Psychiatry (2001)

The authors examined the nature and prevalence of stalking behaviors, victims' coping responses, and the psychomedical impact of stalking on its victims.Widely accepted self-report measures, including the 12-item General Health Questionnaire and the Impact of Event Scale, were used to assess characteristics of the stalking history and its outcome in terms of general psychomedical distress and posttraumatic stress in a community study group of 201 female stalking victims.The majority of the victims had undergone multiple forms of harassment, including threats of violence in 74% (N=148) and actual violence in 55% (N=111). More than half of the victims met the criterion for clinically significant pathology on the General Health QUESTIONNAIRE: Stalking often yielded substantial posttraumatic stress symptoms, commensurate with levels found in other studies of traumatized subjects.Support-seeking female stalking victims experience pervasive and persistent threat and intrusion; these experiences lead to high levels of psychological morbidity.
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers
Authors: Anneleen Decock, Maté Ongenaert, Jasmien Hoebeeck, Katleen De Preter, Gert Van Peer, Wim Van Criekinge, Ruth Ladenstein, Johannes Hubertus Schulte, Rosa Noguera, Raymond R.L. Stallings, An Van Damme, Geneviève Laureys, Joëlle Vermeulen, Tom Van Maerken, Frank Speleman, Jo Vandesompele
Journal: Genome biology (2012)

Accurate outcome prediction in neuroblastoma, which is necessary to enable the optimal choice of risk-related therapy, remains a challenge. To improve neuroblastoma patient stratification, this study aimed to identify prognostic tumor DNA methylation biomarkers. To identify genes silenced by promoter methylation, we first applied two independent genome-wide methylation screening methodologies to eight neuroblastoma cell lines. Specifically, we used re-expression profiling upon 5-aza-2'-deoxycytidine (DAC) treatment and massively parallel sequencing after capturing with a methyl-CpG-binding domain (MBD-seq). Putative methylation markers were selected from DAC-upregulated genes through a literature search and an upfront methylation-specific PCR on 20 primary neuroblastoma tumors, as well as through MBD- seq in combination with publicly available neuroblastoma tumor gene expression data. This yielded 43 candidate biomarkers that were subsequently tested by high-throughput methylation-specific PCR on an independent cohort of 89 primary neuroblastoma tumors that had been selected for risk classification and survival. Based on this analysis, methylation of KRT19, FAS, PRPH, CNR1, QPCT, HIST1H3C, ACSS3 and GRB10 was found to be associated with at least one of the classical risk factors, namely age, stage or MYCN status. Importantly, HIST1H3C and GNAS methylation was associated with overall and/or event-free survival. This study combines two genome-wide methylation discovery methodologies and is the most extensive validation study in neuroblastoma performed thus far. We identified several novel prognostic DNA methylation markers and provide a basis for the development of a DNA methylation-based prognostic classifier in neuroblastoma.
C-Reactive Protein as a Predictor of Cardiovascular Risk in a Population With a High Prevalence of Diabetes
Authors: Lyle G. Best, Ying Zhang, Elisa T. Lee, Jeun-Liang Yeh, Linda Cowan, Vittorio Palmieri, Mary Roman, Richard B. Devereux, Richard R. Fabsitz, Russell P. Tracy, David Robbins, Michael Davidson, Aftab Ahmed, Barbara V. Howard
Journal: Circulation (2005)

High-sensitivity C-reactive protein (CRP) has been investigated extensively as a marker for predicting the risk of cardiovascular disease (CVD). CVD accounts for a large proportion of mortality and morbidity in American Indians; we sought to test the association of CRP and CVD in a population-based American Indian cohort 45 to 74 years old.Of 3277 participants who were CVD-free at baseline, 542 had CRP >10 mg/L and were excluded from analysis; 50.1% of those included had diabetes. There were 343 CVD events among this cohort during a median follow-up of 6.2 years. Multiple CVD risk factors were used as covariates in Cox proportional-hazard models. After exclusions, the median CRP (3.2 mg/L) was higher than reported in many other populations. CRP predicted CVD in models adjusted for traditional risk factors, but not when albuminuria and fibrinogen were included. In subgroup analysis, CRP was strongly related to incident CVD among nondiabetic women participants, even after adjustment for traditional CVD risk factors and other indicators of inflammation. Conversely, CRP was elevated beyond the useful range of the American Heart Association/Centers for Disease Control and Prevention clinical guidelines in 16% of this population, and CRP was not predictive of CVD in important subgroups, such as those with diabetes.CRP was a predictor of CVD in this American Indian population with a high prevalence of diabetes and other risk factors. The predictive ability of CRP varies considerably among subgroups with different risk factor profiles.
In defense of enculturation
Authors: Penelope G. Vinden
Journal: Behavioral and Brain Sciences (2004)

Carpendale &amp; Lewis (C&amp;L) view enculturation as the internalization of cultural concepts given in social interactions. They claim that enculturation implies relativism and fails to take into account both the constructive activity of the child and the gradual nature of development. Their view is contrasted with the notion of the child as both enculturated and enculturing throughout the course of development.
Putting the interaction back into dialogue
Authors: Emanuel A. Schegloff
Journal: Behavioral and Brain Sciences (2004)

I share the authors' stance on the dialogic or interactional character of language. The authors, however, have left actual interaction out of their conception of dialogue. I sketch a number of organizations of practices of talking and understanding that supply the basic arena for talk-in-interaction. It is by reference to these that mechanisms for speech production and understanding need to be understood.
Molecular Basis of Incomplete <i>O</i>-Glycan Synthesis in MCF-7 Breast Cancer Cells: Putative Role of MUC6 in Tn Antigen Expression
Authors: Teresa Freire, Sylvie Bay, Silvia von Mensdorff-Pouilly, Eduardo Osinaga
Journal: Cancer Research (2005)

Abstract An incomplete elongation of O-glycan saccharide chains in mucins have been found in epithelial cancers, leading to the expression of shorter carbohydrate structures, such as the Tn antigen (GalNAc-O-Ser/Thr). This antigen is one of the most specific human cancer–associated structures and is capable of inducing effective immune responses against cancer cells. We aimed to investigate the causes of the expression of Tn antigen in the Tn-rich MCF-7 breast cancer cell line focusing on the first step of the O-glycosylation process. Interestingly, amino acid sequences derived from “nonmammary” apomucins (MUC5B and MUC6) were very good acceptor substrates for ppGalNAc-Ts, which are the enzymes catalyzing the Tn antigen synthesis. MUC6 peptide glycosylation with MCF-7 microsome extracts as source of ppGalNAc-T activity yielded 95% conversion of the peptide into MUC6-Tn. In addition, the MUC6-Tn glycopeptide was a poor acceptor substrate for core 1 β3Gal-T, the next enzyme involved in the saccharide chain biosynthesis, yielding only 5% conversion of MUC6-Tn into MUC6-TF. These results indicate that nonmammary apomucin expression could be responsible, at least in part, for Tn antigen expression in MCF-7 breast cancer cells due to a combined action on glycosyltransferases: an increase of ppGalNAc-T activity and a decrease of core 1 β3Gal-T activity. Our hypothesis is supported by experiments in vivo showing that (a) native MUC6 glycoproteins express the Tn antigen in MCF-7 cells and (b) Tn antigen expression is increased after transfection with a construct encoding for a MUC6 recombinant protein into the low Tn-expressing breast cancer cell T47D. These results open new horizons in breast cancer glycoimmunology, stressing the potential role of nonmammary apomucins.