tbuckley/cabot-search huggingface dataset:
Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial
Authors: Eleanor Mann, Melanie J Smith, Jennifer Hellier, Janet A Balabanovic, Hisham Hamed, Elizabeth A Grunfeld, Myra S Hunter
Journal: The Lancet Oncology (2012)

Hot flushes and night sweats (HFNS) affect 65-85% of women after breast cancer treatment; they are distressing, causing sleep problems and decreased quality of life. Hormone replacement therapy is often either undesirable or contraindicated. Safe, effective non-hormonal treatments are needed. We investigated whether cognitive behavioural therapy (CBT) can help breast cancer survivors to effectively manage HFNS.In this randomised controlled trial, we recruited women from breast clinics in London, UK, who had problematic HFNS (minimum ten problematic episodes a week) after breast-cancer treatment. Participants were randomly allocated to receive either usual care or usual care plus group CBT (1:1). Randomisation was done in blocks of 12-20 participants, stratifying by age (younger than 50 years, 50 years or older), and was done with a computer-generated sequence. The trial statistician and researchers collecting outcome measures were masked to group allocation. Group CBT comprised one 90 min session a week for 6 weeks, and included psycho-education, paced breathing, and cognitive and behavioural strategies to manage HFNS. Assessments were done at baseline, 9 weeks, and 26 weeks after randomisation. The primary outcome was the adjusted mean difference in HFNS problem rating (1-10) between CBT and usual care groups at 9 weeks after randomisation. Analysis of the primary endpoint was done by modified intention to treat. The trial is registered, ISRCTN13771934, and was closed March 15, 2011.Between May 5, 2009, and Aug 27, 2010, 96 women were randomly allocated to group CBT (n=47) or usual care (n=49). Group CBT significantly reduced HFNS problem rating at 9 weeks after randomisation compared with usual care (mean difference -1·67, 95% CI -2·43 to -0·91; p<0·0001) and improvements were maintained at 26 weeks (mean difference -1·76, -2·54 to -0·99; p<0·0001). We recorded no CBT-related adverse events.Group CBT seems to be a safe and effective treatment for women who have problematic HFNS after breast cancer treatment with additional benefits to mood, sleep, and quality of life. The treatment could be incorporated into breast cancer survivorship programmes and delivered by trained breast cancer nurses.Cancer Research UK.
Evolutionary Pattern of Gene Homogenization between Primate-Specific Paralogs after Human and Macaque Speciation Using the 4-2-4 Method
Authors: K. Ezawa, K. Ikeo, T. Gojobori, N. Saitou
Journal: Molecular Biology and Evolution (2010)

Homogenization of duplicated genes is an important factor for gene family evolution. In the previous study, we developed a method, named 4-2-4 here, to detect partial homogenization with high sensitivity and high specificity using quartets. A quartet is a set of four genes generated by a duplication event and the subsequent speciation of two closely related species. We searched the human and macaque genomes and found 430 nonredundant quartets, which correspond to primate-specific paralogs. The prevalence of homogenization in these quartets was 10.0% (43/430), which was ca. one-third of that (29.8% = 206/691) in the rodent-specific nonredundant quartets obtained through comparison of mouse and rat genomes. Part of this difference comes from the fact that primate paralogs tend to be more remotely located to each other than rodent paralogs, and the remainder may be explained by the inherent difference in the neutral evolutionary rate between the primate and rodent lineages. A statistical analysis taking account of the effects of false negatives uncovered negative correlations between sequence divergence and homogenization prevalence both in primates and rodents. Further statistical analyses controlling for false-negative rates and sequence divergences revealed two characteristics shared by the primate and rodent paralogs; 1) significant negative correlations of the homogenization prevalence with physical distances, and 2) no significant correlation between the prevalence and relative transcriptional orientations. Patterns of the homogenization in the genomic alignments of human-macaque quartets indicate that gene conversion, rather than unequal crossing-over, is the major cause of the homogenization.
Is brief advice in primary care a cost-effective way to promote physical activity?
Authors: Nana K Anokye, Joanne Lord, Julia Fox-Rushby
Journal: British Journal of Sports Medicine (2013)

Aim This study models the cost-effectiveness of brief advice (BA) in primary care for physical activity (PA) addressing the limitations in the current limited economic literature through the use of a time-based modelling approach. Methods A Markov model was used to compare the lifetime costs and outcomes of a cohort of 100 000 people exposed to BA versus usual care. Health outcomes were expressed in terms of quality-adjusted life years (QALYs). Costs were assessed from a health provider perspective (£2010/11 prices). Data to populate the model were derived from systematic literature reviews and the literature searches of economic evaluations that were conducted for national guidelines. Deterministic and probability sensitivity analyses explored the uncertainty in parameter estimates including short-term mental health gains associated with PA. Results Compared with usual care, BA is more expensive, incurring additional costs of £806 809 but it is more effective leading to 466 QALYs gained in the total cohort, a QALY gain of 0.0047/person. The incremental cost per QALY of BA is £1730 (including mental health gains) and thus can be considered cost-effective at a threshold of £20 000/QALY. Most changes in assumptions resulted in the incremental cost-effectiveness ratio (ICER) falling at or below £12 000/QALY gained. However, when short-term mental health gains were excluded the ICER was £27 000/QALY gained. The probabilistic sensitivity analysis showed that, at a threshold of £20 000/QALY, there was a 99.9% chance that BA would be cost-effective. Conclusions BA is a cost-effective way to improve PA among adults, provided short-term mental health gains are considered. Further research is required to provide more accurate evidence on factors contributing to the cost-effectiveness of BA.
Bilateral segmental neurofibromatosis with partial unilateral lentiginosis
Authors: S.S. WONG
Journal: British Journal of Dermatology (1997)

A 73-year-old woman presented with numerous cutaneous neurofibromas on the trunk in a bilateral dermatomal distribution (T2-T12). She also had multiple lentigines scattered on the left side of the trunk, affecting the T2-T12 dermatomes. The diagnosis of bilateral segmental neurofibromatosis (NF) was made on the basis of the clinical features and distribution of the neurofibromas and an absence of family and systemic involvement. The pattern of lentigines was consistent with that of partial unilateral lentiginosis (PUL). Bilateral segmental NF is rare and 15 cases had been reported in the literature so far. This is the first reported case of a patient with bilateral neurofibromas and PUL.
Response of unacclimatized males to repeated weekly bouts of exercise in the heat.
Authors: A Barnett, R J Maughan
Journal: British Journal of Sports Medicine (1993)

The purpose of the present study was to determine if there is an acclimation effect when unacclimatized males exercise in the heat at weekly intervals. Five subjects performed four exercise bouts, each lasting 1 h at 55% VO2max. The first trial was in moderate conditions (mean(s.d.) temperature (Ta) = 22.0(0.8)degrees C; mean(s.d.) relative humidity (rh) = 67(6)%) and the subsequent three trials were carried out at weekly intervals in the heat (mean(s.d.) Ta = 34.6(0.6)degrees C; mean(s.d.) rh = 60(7)%). There were no significant differences between trials in the heat for heart rate, rectal temperature, skin temperature or VO2 (repeated measures analysis of variance), and total sweat loss (one-way analysis of variance). As changes in these variables are seen with heat acclimation it was concluded that there was no heat acclimation effect and separating exercise bouts by 1 week was a valid method for comparing the effects of different treatments on unacclimatized males during exercise in the heat.
Pantothenic Acid and Coenzyme a in Cellular Modification of Proteins
Authors: N Plesofsky-Vig, R Brambl
Journal: Annual Review of Nutrition (1988)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Comparison of serial synovial fluid cytology in rheumatoid arthritis: delineation of subgroups with prognostic implications.
Authors: M J Davis, J Denton, A J Freemont, P J Holt
Journal: Annals of the Rheumatic Diseases (1988)

Serial synovial fluid samples were obtained from patients with rheumatoid arthritis and analysed cytologically. Positive correlations in the serial samples between proportions of polymorphs and ragocytes were found. Based upon the serial synovial fluid cytology, distinct subgroups of rheumatoid joints emerged. Comparison of clinical findings in these subgroups showed that the joints with high ragocyte proportion had a significantly poorer outcome. This study therefore identifies two distinct subgroups of rheumatoid joints on the basis of the nature of the cellular reaction within the joint fluid, which usually holds true during subsequent clinical relapse. Identification of these groups may have prognostic significance.
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Authors: Alexandre Chlenski, Lisa J Guerrero, Radhika Peddinti, Jared A Spitz, Payton T Leonhardt, Qiwei Yang, Yufeng Tian, Helen R Salwen, Susan L Cohn
Journal: Molecular Cancer (2010)

Abstract Background New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E) potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic. Results In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo , although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization. Conclusion Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.
Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat
Authors: Meng Fang, Sylviane Dewaele, Yun-peng Zhao, Peter Stärkel, Valerie Vanhooren, Yue-ming Chen, Xin Ji, Ming Luo, Bao-mu Sun, Yves Horsmans, Anne Dell, Stuart M Haslam, Paola Grassi, Claude Libert, Chun-fang Gao, Cuiying Chitty Chen
Journal: Molecular Cancer (2010)

Abstract Background There is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model. Results Rat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory. In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p &lt; 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. Conclusions : We found an increase in core-α-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.
Efficacy of the “tennis ball technique” in patients with positional obstructive sleep apnoea syndrome
Authors: G.E. de Vries, P.M. Meijer, J.H. van der Hoeven, R.A. Feijen, B. Stegenga, P.J. Wijkstra
Journal: European Respiratory Journal (2011)

Introduction: In obstructive sleep apnoea (OSA) collapsibility of the upper airway is increased in the supine sleeping position, resulting in an increase of apnoea-hypopnoea index (AHI) and severity of apnoeic events.

Aim: To assess whether the “tennis ball technique” (TBT) prevents positional OSAS-patients from lying on their back and whether this therapy is effective in reducing AHI, severity of events and excessive daytime sleepiness (EDS).

Methods: Thirty three patients with positional OSA at baseline (14 mild, 17 moderate, 2 severe) were treated with TBT. After at least 4 weeks a second sleep study under treatment was performed to assess differences between baseline and follow-up percentage in supine position, AHI, minimal oxygen saturation and EDS. Treatment was considered successful when AHI reduced < 5/hour or reduced at least 50%.

Results: Supine sleeping position reduced from a median (IQR) of 33.2 (23.6-43.7)% to 6.6 (0.0-13.4)%, p<.001. AHI decreased from a median (IQR) of 15.4 (12.1-19.9)/hour to 6.0 (3.4-10.0)/hour, p<.001. Minimal saturation improved from a median (IQR) of 86.0 (83.3-87.8)% to 87.0 (84.3-89.0)%, p=.047. The Epworth Sleepiness Scale decreased from a mean (SD) of 11.2 (5.3) to 9.2 (5.3), p=.002. TBT treatment was successful in 23 of the 33 patients.

![Figure][1] 



Conclusion: TBT is effective in reducing time spent in supine sleeping position and in reducing AHI and EDS, at least on the short-term.

 [1]: pending:yes
Neuronal and Vascular Interactions
Authors: Benjamin J. Andreone, Baptiste Lacoste, Chenghua Gu
Journal: Annual Review of Neuroscience (2015)

The brain, which represents 2% of body mass but consumes 20% of body energy at rest, has a limited capacity to store energy and is therefore highly dependent on oxygen and glucose supply from the blood stream. Normal functioning of neural circuits thus relies on adequate matching between metabolic needs and blood supply. Moreover, not only does the brain need to be densely vascularized, it also requires a tightly controlled environment free of toxins and pathogens to provide the proper chemical composition for synaptic transmission and neuronal function. In this review, we focus on three major factors that ensure optimal brain perfusion and function: the patterning of vascular networks to efficiently deliver blood and nutrients, the function of the blood-brain barrier to maintain brain homeostasis, and the regulation of cerebral blood flow to adequately couple energy supply to neural function.
Germline SDHB Mutations and Familial Renal Cell Carcinoma
Authors: C. Ricketts, E. R. Woodward, P. Killick, M. R. Morris, D. Astuti, F. Latif, E. R. Maher
Journal: JNCI Journal of the National Cancer Institute (2008)

Familial renal cell carcinoma (RCC) is a heterogeneous disorder that is most commonly caused by germline mutations in the VHL , MET , and FLCN genes or by constitutional chromosome 3 translocations. However, for many patients with familial RCC, the genetic basis of the disease is undefined. We investigated whether germline mutations in fumarate hydratase ( FH ) or succinate dehydrogenase subunit genes ( SDHB , SDHC , SDHD ) were associated with RCC susceptibility in 68 patients with no clinical evidence of an RCC susceptibility syndrome. No mutations in FH , SDHC , or SDHD were identified in probands, but 3 of the 68 (4.4%) probands had a germline SDHB mutation. Patients with a germline SDHB mutation presented with familial RCC (n = 1) or bilateral RCC (n = 2) and no personal or family history of pheochromocytoma or head and neck paraganglioma. Age at diagnosis of RCC in SDHB mutation carriers ranged from 24 to 73 years. These findings 1) demonstrate that patients with suspected inherited RCC should be examined for germline SDHB mutations, 2) suggest that all identified SDHB mutation carriers should be offered surveillance for RCC, and 3) provide a further link between familial RCC and activation of hypoxic-gene response pathways.
Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231
Authors: Shannon M. Gallagher, John J. Castorino, Dian Wang, Nancy J. Philp
Journal: Cancer Research (2007)

Abstract Metastatic cancer cells increase glucose consumption and metabolism via glycolysis, producing large quantities of lactate. Recent work has shown that lactate efflux is mediated by monocarboxylate transporters (MCT), which are composed of a catalytic unit (MCT) and an accessory subunit (CD147), comprising the functional lactate transporter. CD147, an extracellular matrix metalloproteinase (MMP) inducer, is highly expressed in metastatic cancer cells. Because aerobic glycolysis is a hallmark of metastatic cancer, we examined whether increases in CD147 expression were linked to MCT expression in MDA-MB-231, a highly metastatic breast cancer cell line. MCT4 mRNA and protein expression were increased in MDA-MB-231 cells compared with cells derived from normal mammary tissue. MCT4 colocalized with CD147 in the plasma membrane and in membrane blebs shed from the cell surface. Small interfering RNA–mediated silencing of MCT4 impaired the maturation and trafficking of CD147 to the cell surface, resulting in accumulation of CD147 in the endoplasmic reticulum. Silencing MCT4 also resulted in fewer membrane blebs and decreased migration of MDA-MB-231 cells in vitro. Knockdown of CD147 resulted in loss of MCT4 in the plasma membrane and accumulation of the transporter in endolysosomes. These studies establish for the first time that increased expression of CD147 in metastatic cancer cells is coupled to the up-regulation of MCT4. The synergistic activities of the MCT/CD147 complex could facilitate migration of tumor cells by CD147-mediated MMP induction and lactate-stimulated angiogenesis and hyaluronan production. These data provide a molecular link between two hallmarks of metastatic cancer: the glycolytic switch and increased expression of CD147. [Cancer Res 2007;67(9):4182–9]
Both Gene Amplification and Allelic Loss Occur at 14q13.3 in Lung Cancer
Authors: Thomas Harris, Qiulu Pan, Juan Sironi, Dionne Lutz, Jianmin Tian, Jana Sapkar, Roman Perez-Soler, Steven Keller, Joseph Locker
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Because loss of Nkx2-8 increases lung cancer in the mouse, we studied suppressive mechanisms in human lung cancer. Experimental Design: NKX2-8 is located within 14q13.3, adjacent to its close relative TTF1/NKX2-1. We first analyzed LOH of 14q13.3 in forty-five matched human lung cancer and control specimens. DNA from tumors with LOH was then analyzed with high-density single-nucleotide polymorphism (SNP) arrays. For correlation with this genetic analysis, we quantified expression of Nkx2-8 and TTF1 mRNA in tumors. Finally, suppressive function of Nkx2-8 was assessed via colony formation assays in five lung cancer cell lines. Results: Thirteen of forty-five (29%) tumors had LOH. In six tumors, most adenocarcinomas, LOH was caused by gene amplification. The 0.8-Mb common region of amplification included MBIP, SFTA, TTF1, NKX2-8, and PAX9. In 4 squamous or adenosquamous cancers, LOH was caused by deletion. In three other tumors, LOH resulted from whole chromosome mechanisms (14−, 14+, or aneuploidy). The 1.2-Mb common region of deletion included MBIP, SFTA, TTF1, NKX2-8, PAX9, SLC25A21, and MIPOL1. Most tumors had low expression of Nkx2-8. Nevertheless, sequencing did not show NKX2-8 mutations that could explain the low expression. TTF1 overexpression, in contrast, was common and usually independent of Nkx2-8 expression. Finally, stable transfection of Nkx2-8 selectively inhibited growth of H522 lung cancer cells. Conclusions: 14q13.3, which contains NKX2-8, is subject to both amplification and deletion in lung cancer. Most tumors have low expression of Nkx2-8, and its expression can inhibit growth of some lung cancer cells. Clin Cancer Res; 17(4); 690–9. ©2010 AACR.
Cardiovascular mechanisms of death in severe COPD exacerbation: time to think and act beyond guidelines
Authors: L. M. Fabbri, B. Beghe, A. Agusti
Journal: Thorax (2011)

Three important studies on acute exacerbations of chronic obstructive pulmonary disease (ECOPD)have been published in Thorax . Two of them, by Chang et al 1( see page 764 ) and Hoiset et al 2 ( see page 775 ), show the importance of the cardiac biomarkers troponin T and NT-BNP (N-terminal pro-B-type natriuretic peptide) as strong predictors of the increased risk of death of patients hospitalised because of ECOPD.1 2 The third, by Maclay et al 3 ( see page 769 ), provides evidence that patients with stable chronic obstructive pulmonary disease (COPD) have increased circulating platelet–monocyte aggregates—a potential specific pathogenic mechanism of atherosclerosis. These aggregates further increase during exacerbations, suggesting a plausible biological mechanism to explain the increased cardiovascular risk seen in ECOPD. Taken together, these studies confirm the view that ECOPD episodes requiring hospitalisation must be considered very severe events in the natural course of the disease because they are associated with such important outcomes as increased risk of mortality, reduced health status, impaired lung function, muscle weakness, and cardiopulmonary complications.4 The studies also suggest that the increased risk of death is often due to acute cardiovascular involvement, and they highlight the limitations of the current definition of ECOPD and the need to move towards a more comprehensive definition, diagnostic approach and treatment.

Several previous studies have clearly established that episodes of ECOPD are a major driver of mortality in this disease, especially during and immediately after the acute event. (The long-term effects are discussed in next paragraph.) For instance, in a cohort of 1016 patients hospitalised because of ECOPD with hypercarbia (PaCO2≥50 mm Hg), Connors et al 5 …