tbuckley/cabot-search huggingface dataset:
The Efficacy of Light Therapy in the Treatment of Mood Disorders: A Review and Meta-Analysis of the Evidence
Authors: Robert N. Golden, Bradley N. Gaynes, R. David Ekstrom, Robert M. Hamer, Frederick M. Jacobsen, Trisha Suppes, Katherine L. Wisner, Charles B. Nemeroff
Journal: American Journal of Psychiatry (2005)

The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders.The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category.Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34).Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy's specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.
Attitudes of patients with metastatic breast cancer toward research biopsies
Authors: D.S. Seah, S.M. Scott, J. Najita, T. Openshaw, K. Krag, E. Frank, J. Sohl, Z.K. Stadler, M. Garrett, S.G. Silverman, J. Peppercorn, E.P. Winer, S.E. Come, Nancy U. Lin
Journal: Annals of Oncology (2013)
DEATHS FOLLOWING GASTRO-JEJUNOSTOMY NOT DUE TO THE ANASTOMOSIS
Authors: C. H. Whiteford
Journal: BMJ (1911)

This patiept has never been troubled with the old symptoms since the operation, and is a healthy, happy young woman.From this history we see that over four years of suffering was endured before it was possible to determine the true seat of disease.The second case is one with more purely gastric symptoms.CASE II.Mrs. D., aged 36, came to me on October 13th, 1910, giving a history, of epigastric pain and discomfort, and constant vomiting after meals for the past two years.Sbe had not been able to eat any solid food, and subsisted upon milk and broths.She
Pyruvate kinase M2 is a target of the tumor-suppressive microRNA-326 and regulates the survival of glioma cells
Authors: B. Kefas, L. Comeau, N. Erdle, E. Montgomery, S. Amos, B. Purow
Journal: Neuro-Oncology (2010)

Emerging studies have identified microRNAs (miRNAs) as possible therapeutic tools for the treatment of glioma, the most aggressive brain tumor. Their important targets in this tumor are not well understood. We recently found that the Notch pathway is a target of miRNA-326. Ectopic expression of miRNA-326 in glioma and glioma stem cells induced their apoptosis and reduced their metabolic activity. Computational target gene prediction revealed pyruvate kinase type M2 (PKM2) as another target of miRNA-326. PKM2 has recently been shown to play a key role in cancer cell metabolism. To investigate whether it might be a functionally important target of miR-326, we used RNA interference to knockdown PKM2 expression in glioma cells. Transfection of the established glioma and glioma stem cells with PKM2 siRNA reduced their growth, cellular invasion, metabolic activity, ATP and glutathione levels, and activated AMP-activated protein kinase. The cytotoxic effects exhibited by PKM2 knockdown in glioma and glioma stem cells were not observed in transformed human astrocytes. Western blot analysis of human glioblastoma specimens showed high levels of PKM2 protein, but none was observed in normal brain samples. Strikingly, cells with high levels of PKM2 expressed lower levels of miR-326, suggestive of endogenous regulation of PKM2 by miR-326. Our data suggest PKM2 inhibition as a therapy for glioblastoma, with the potential for minimal toxicity to the brain.
<i>TSP50</i> Encodes a Testis-Specific Protease and Is Negatively Regulated by <i>p53</i>
Authors: Haopeng Xu, Jidong Shan, Vladimir Jurukovski, Liming Yuan, Jianhua Li, Kegui Tian
Journal: Cancer Research (2007)

Abstract Earlier studies suggested that TSP50 is a testis-specific gene that encodes a protein, which is homologous to serine proteases but differs in that threonine replaces serine in its catalytic triad. Most importantly, it was abnormally reactivated in many breast cancer biopsies tested. While further investigating its biochemical and cell biological natures, we found that TSP50 exhibited enzyme activity and was located in the endoplasmic reticulum and cytosol membrane. During our studies to elucidate the regulatory mechanisms related to its differential expression, we discovered a putative p53-binding site and several Sp1-binding sites in the TSP50 promoter, which led us to test if it was regulated by the p53 gene. We found that the p53 transgene negatively regulated the TSP50 promoter in diverse types of cell lines. This result was consistent with other observations: (a) p53 overexpression reduced endogenous TSP50 expression; and (b) breast cancer cell lines containing mutated p53, such as MCF7/Adr, or normal p53, such as MCF7, produced high or low levels of TSP50 transcripts, which was consistent with the fact that TSP50 promoter activity was much higher in MCF7/Adr than that in MCF7 cells. We also found that the quantity of Sp1 transcription factor was lower in MCF7/Adr than in MCF7 cells, which suggested that another mechanism (i.e., transcription factor modulation) was also involved in TSP50 differential expression. [Cancer Res 2007;67(3):1239–45]
Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver.
Authors: M Suematsu, N Goda, T Sano, S Kashiwagi, T Egawa, Y Shinoda, Y Ishimura
Journal: Journal of Clinical Investigation (1995)

Heme oxygenase is a heme-oxidizing enzyme which gener- ates biliverdin and carbon monoxide (CO).The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation.Microvasculature of the iso- lated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells.In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver.Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 ,uM) eliminated the baseline CO gen- eration, and the vascular resistance exhibited a 30% eleva- tion concurrent with discrete patterns of constriction in si- nusoids and reduction of the sinusoidal perfusion velocity.The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cells which were identified by imaging their vitamin A autofluorescence.The increase in the vascular resistance and sinusoidal constric- tion were attenuated significantly by adding CO (1 ,uM) or a cGMP analogue 8-bromo-cGMP (1 ,uM) in the perfusate.From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.(
The AMPA Receptor GluR2 C Terminus Can Mediate a Reversible, ATP-Dependent Interaction with NSF and α- and β-SNAPs
Authors: P Osten, S Srivastava, G.J Inman, F.S Vilim, L Khatri, L.M Lee, B.A States, S Einheber, T.A Milner, P.I Hanson, E.B Ziff
Journal: Neuron (1998)

In this study, we demonstrate specific interaction of the GluR2 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit C-terminal peptide with an ATPase N-ethylmaleimide–sensitive fusion protein (NSF) and α- and β-soluble NSF attachment proteins (SNAPs), as well as dendritic colocalization of these proteins. The assembly of the GluR2–NSF–SNAP complex is ATP hydrolysis reversible and resembles the binding of NSF and SNAP with the SNAP receptor (SNARE) membrane fusion apparatus. We provide evidence that the molar ratio of NSF to SNAP in the GluR2–NSF–SNAP complex is similar to that of the t-SNARE syntaxin–NSF–SNAP complex. NSF is known to disassemble the SNARE protein complex in a chaperone-like interaction driven by ATP hydrolysis. We propose a model in which NSF functions as a chaperone in the molecular processing of the AMPA receptor.
Long-Term Survivors of Gastric Cancer: A California Population-Based Study
Authors: Pamela L. Kunz, Matthew Gubens, George A. Fisher, James M. Ford, Daphne Y. Lichtensztajn, Christina A. Clarke
Journal: Journal of Clinical Oncology (2012)

In the United States, gastric cancer is rapidly fatal with a 25% 5-year survival. Of the few patients who survive, little is known about their demographic, clinical, and tumor characteristics.Data regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed in California between 1988 and 2005 were obtained from the California Cancer Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. A Cox proportional hazards model was constructed to understand the independent relationships of patient demographic, disease, and treatment factors with survival.We identified 47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%) survived at least 3 years. Variables associated with longer survival were localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85), fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease-specific survival (DSS) in patients with tumors originating in the fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months). Intestinal histology had significantly longer median DSS (28.9 months) compared with other (11.0 months) or diffuse (10.1 months) histology.Patients who survive gastric and GEJ cancer more than 3 years after diagnosis have demographic and pathologic characteristics distinct from those who do not survive.
Prevalence and pattern of familial disease in primary biliary cirrhosis.
Authors: A M Brind, G P Bray, B C Portmann, R Williams
Journal: Gut (1995)

Susceptibility to primary biliary cirrhosis (PBC) may be partly inherited although instances of PBC within families are only infrequently described. The records of 736 patients with PBC seen over a 25 year period were examined to identify those with a positive family history. Ten patients originating from eight families were identified, giving a frequency of 1.33%. They comprised mother and daughter pairs; in two families both mother and daughter had been seen at our clinic. The daughters presented at an earlier age, median 36 years (range 24-54), than the mothers, 52 years (50-81). During follow up one daughter (45 years) and six mothers have died (range 53-81 years) and two mothers and one daughter have had a transplant aged 57, 57, and 30 years respectively. It is concluded that familial PBC is not rare, that it is related to maternally inherited factors, and that disease tends to present earlier in the second generation.
Molecular mechanisms of probiotic action: it's all in the strains!
Authors: F. Shanahan
Journal: Gut (2011)

The influence of the commensal microbiota on intestinal and extra-intestinal development has been evident since the first studies of germ-free animals over a half-century ago. Microbial signals from the lumen of the gut are trophic for the digestive, immune and other systems, including the developing brain.1 2 In later life, reciprocal host–microbe interactions remain critical for mucosal homeostasis. Probiotic therapy is, in essence, an attempt to harness the beneficial effects of the commensal microbiota for the host.3 In most instances, the molecular underpinning of these exchanges remains to be defined but represents an intriguing strategy for identifying therapeutic targets and drug discovery.4 While the therapeutic potential of immunomodulatory molecules from pathogens is well recognised, the pursuit of bioactive molecules from the commensal gut microbiota is a more recent venture; examples include the discovery of bacteriocins with activity against Clostridium difficile and bacterial-derived immunomodulatory molecules.4 However, much more remains to be mined from the commensal microbiota.

The study by Fernandez and colleagues published in this issue of Gut ( see page 1050 …
Understanding human parturition
Authors: Lisa Barrie Schwartz
Journal: The Lancet (1997)

Despite remarkable advances in the science and technology of reproduction, the signals initiating human parturition remain elusive. Scientists had initially been thrown off the scent by the relative simplicity of the hormonal regulation of sheep parturition. In sheep fetal cortisol triggers parturition by inducing placental enzymatic activities that enable progesterone (P4) conversion to oestradiol (E2). 1 Flint APF Anderson ABM Steele PA Turnbull AC The mechanism by which fetal cortisol controls the onset of parturition in the sheep. Biochem Soc Trans. 1975; 3: 1189-1194 Google Scholar The resultant rise in E2/P4 ratio stimulates myometrial oxytocin receptors, gap junctions, prostaglandin production, and maternal pituitary oxytocin synthesis and release, events leading directly to labour and delivery. 1 Flint APF Anderson ABM Steele PA Turnbull AC The mechanism by which fetal cortisol controls the onset of parturition in the sheep. Biochem Soc Trans. 1975; 3: 1189-1194 Google Scholar
Sleep is for rest, waking consciousness is for learning and memory – of any kind
Authors: Robert P. Vertes
Journal: Behavioral and Brain Sciences (2005)

Although considerable attention has been paid to the possible involvement of sleep in memory processing, there is no substantial evidence for it. Walker describes a phenomenon of consolidation-based enhancement (CBE), whereby performance on select procedural tasks improves with overnight sleep; that is, without additional practice on the tasks. CBE, however, appears restricted to a few tasks, and even with these tasks CBE is not confined to sleep but also occurs during wakefulness. Sleep serves no unique role in this process. At best, CBE is a slow, time-dependent process of consolidation that begins with task acquisition in waking and can under some circumstances extend to sleep.
Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study
Authors: Martin Andersen, Karen Ellegaard, Josephine B Hebsgaard, Robin Christensen, Søren Torp-Pedersen, Peter H Kvist, Niels Søe, John Rømer, Nina Vendel, Else Marie Bartels, Bente Danneskiold-Samsøe, Henning Bliddal
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Little is known regarding the association between ultrasound-determined pathological synovial blood flow and synovial pathology in rheumatoid arthritis (RA). We therefore examined the association between colour Doppler ultrasound imaging and synovitis assessed by histopathology and specific cell markers by immunohistochemistry in patients with RA. <h3>Methods</h3> 81 synovial sites from wrist and finger joints from 29 RA patients were evaluated by ultrasound colour Doppler and subsequently biopsied by needle arthroscopy. The association between ultrasound colour fraction and an overall synovitis score and immunohistochemical staining for CD3, CD68, Ki67 and von Willebrand factor was investigated, including repeated samples from the same patients. The overall synovitis score (total 0–9) assessed synovial lining hyperplasia (0–3), stromal activation (0–3) and inflammatory infiltration (0–3). Data were clustered within patients, thus a linear mixed model was applied for the statistical tests. Parsimony in the statistical models was achieved omitting covariates from the model in the case of what was judged no statistical significance (p&gt;0.1). <h3>Results</h3> Doppler colour fraction showed an association with the overall synovitis score (approximated Spearman, approximately r=0.43, p=0.003). The density of all immunohistochemical stainings showed a significant association with Doppler colour fraction: von Willebrand factor (approximately r=0.44, p=0.01), CD68 (approximately r=0.53, p=0.02), Ki67 (approximately r=0.57, p=0.05) and CD3 (approximately r=0.57, p=0.0003). <h3>Conclusions</h3> Colour Doppler activity is associated with the extent of inflammation present in the synovial biopsies from RA patients. However, synovial pathology was also seen in biopsies taken from Doppler negative sites.
Molecular Evolution of the Toll-Like Receptor Multigene Family in Birds
Authors: M. Alcaide, S. V. Edwards
Journal: Molecular Biology and Evolution (2011)

Toll-like receptors (TLR) are membrane-bound sensors of the innate immune system that recognize invariant and distinctive molecular features of invading microbes and are also essential for initiating adaptive immunity in vertebrates. The genetic variation at TLR genes has been directly related to differential pathogen outcomes in humans and livestock. Nonetheless, new insights about the impact of TLRs polymorphism on the evolutionary ecology of infectious diseases can be gained through the investigation of additional vertebrate groups not yet investigated in detail. In this study, we have conducted the first characterization of the entire TLR multigene family (N = 10 genes) in non-model avian species. Using primers targeting conserved coding regions, we aimed at amplifying large segments of the extracellular domains (275–435 aa) involved in pathogen recognition across seven phylogenetically diverse bird species. Our analyses suggest avian TLRs are dominated by stabilizing selection, suggesting that slow rates of nonsynonymous substitution help preserve biological function. Overall, mean values of ω (= dn/ds) at each TLR locus ranged from 0.196 to 0.517. However, we also found patterns of positive selection acting on specific amino acid sites that could be linked to species-specific differences in pathogen-associated molecular pattern recognition. Only 39 of 2,875 (∼1.35%) of the codons analyzed exhibited significant patterns of positive selection. At least one half of these positively selected codons can be mapped to putative ligand-binding regions, as suggested by crystallographic structures of TLRs and their ligands and mutagenic analyses. We also surveyed TLR polymorphism in wild populations of two bird species, the Lesser Kestrel Falco naumanni and the House Finch Carpodacus mexicanus. In general, avian TLRs displayed low to moderate single nucleotide polymorphism levels and an excess of silent nucleotide substitutions, but also conspicuous instances of positive directional selection. In particular, TLR5 and TLR15 exhibited the highest degree of genetic polymorphism and the highest occurrence of nonconservative amino acid substitutions. This study provides critical primers and a first look at the evolutionary patterns and implications of TLR polymorphism in non-model avian species and extends the list of candidate loci for avian eco-immunogenetics beyond the widely employed genes of the Major Histocompatibility Complex (MHC).
Para-Aortic Nodal Irradiation: Practical Concerns for the Radiation Oncologist
Authors: Malolan S. Rajagopalan, Sushil Beriwal
Journal: Journal of Clinical Oncology (2013)

Gouy et al 1 recently reported a prospective study in locally advanced cervical cancer in which patients with negative positron emission tomography-computed tomography (PET/CT) of the para-aortic (PA) area underwent laparoscopic PA staging.The authors found a 12% false negative rate of PET/CT in the PA region.Prognostic factors of PA nodal involvement included the presence of pelvic uptake on PET/CT.The authors found that the rate of pathologically positive PA nodes was 9% in those with negative pelvic lymph nodes and 24% in those with positive pelvic nodes by PET/CT.These rates are similar to those from other published reports. 2,3 The implication for the radiation oncologist is multifold.In patients who are found to have positive pelvic nodes on PET/CT and do not undergo surgical PA staging, the risk of PA nodal involvement is sufficiently high to warrant extended field radiation therapy.In addition, there appears to be a subset of those with negative pelvic nodes by PET/CT who harbor PA nodal disease and may be receiving insufficient treatment.To clarify some of the practical ramifications, we have several questions for the authors.First, In the subset of patients with negative pelvic lymph nodes and positive PA nodes, what was ithe distribution of size of the nodal metastases?In the entire cohort, the authors found that those with PA nodal metastases Յ 5 mm had outcomes comparable to those without PA nodal disease.If the PA disease is primarily microscopic in the subset, perhaps it is reasonable to expect chemotherapy to sterilize this disease.Otherwise, perhaps treatment intensi-
Pioglitazone Increases Macrophage Apoptosis and Plaque Necrosis in Advanced Atherosclerotic Lesions of Nondiabetic Low-Density Lipoprotein Receptor–Null Mice
Authors: Edward Thorp, George Kuriakose, Yatrik M. Shah, Frank J. Gonzalez, Ira Tabas
Journal: Circulation (2007)

Background— Thiazolidinediones (TZDs), which have actions that involve both peroxisome proliferator–activated receptor (PPAR)-γ–dependent and –independent effects, improve insulin sensitivity in type II diabetes and inhibit early atherogenesis in mice. However, the effects of TZDs on advanced lesion progression are unknown. Methods and Results— Pioglitazone and rosiglitazone enhanced macrophage apoptosis by a number of stimuli, including those thought to be important in advanced atherosclerosis. Macrophage death was not enhanced by non-TZD PPARγ activators, and TZD-induced apoptosis was still observed in PPARγ-deficient macrophages. In wild-type macrophages, death enhancement was associated with reduced activation of the cell-survival mediator nuclear factor-κB. TZDs also increased the ability of macrophages to phagocytically clear apoptotic cells, which is proposed to protect against plaque necrosis in advanced lesions. The mechanism of this effect was complex, involving both PPARγ-dependent and -independent mechanisms. To explore the net effect on advanced atherosclerosis in vivo, Ldlr −/− mice were fed a nondiabetogenic cholesterol-enriched diet to promote midstage lesions. Then, pioglitazone was administered with the diet for an additional 10 weeks. Aortic root lesions from the pioglitazone-treated mice showed a substantial increase in apoptotic cells and plaque necrosis compared with lesions from non–drug-treated mice. Conclusions— The potential atheroprotective effects of TZDs conferred by insulin sensitization may be partially offset by adverse effects on advanced atherosclerosis. Because the mechanisms of the beneficial and proposed adverse effects may differ, these findings have potentially important implications for drug optimization.