tbuckley/cabot-search huggingface dataset:
Neural images and neural coding
Authors: Antonio L. Perrone, Gianfranco Basti
Journal: Behavioral and Brain Sciences (1995)

Abstract In Posner &amp; Raichle's (1994) book, two essential and strictly related limitations of cognitive neurophysiology are not sufficiently enhanced: (1) The problem of “coding,” namely the capability of a natural brain to redefine its own “basic symbols” as a function of a changing environment; (2) the inadequacy of a Hebbian rule to reckon with complex computational problems such as those solved by real brains.
A STUDY OF THE ADDITION OF CHOLESTERIN TO THE ALCOHOLIC EXTRACTS OF TISSUES USED FOR ANTIGENS IN THE WASSERMANN REACTION
Authors: I. C. Walker, Homer F. Swift
Journal: The Journal of Experimental Medicine (1913)

1. The addition of cholesterin to an alcoholic extract of heart or fetal liver increases the antigenic value of the extracts in the Wassermann reaction. 2. The optimum amount of cholesterin to be added to heart extract or fetal liver extract was found to be 0.4 per cent. 3. Cholesterin-heart extracts are superior to cholesterin-liver extracts and to alcoholic extracts of syphilitic livers, as well as to ether extracts of dried hearts. 4. Cholesterin-heart extracts prepared from different human hearts are practically equal in anticomplementary and antigenic value. Similar extracts prepared from guinea pig hearts have the same antigenic value as those prepared from human hearts. Both the human heart and the guinea pig heart extracts are superior to beef heart extract when the same amount of cholesterin is added to each of the extracts. 5. In testing blood serum for diagnostic purposes, it is not safe to use more than one fourth of the anticomplementary dose of the 0.4 per cent. cholesterin heart extract. In the work here presented, this consisted of a 1 in 10 emulsion. 6. In testing cerebrospinal fluids, 1 in 10 emulsions give slightly better reactions with smaller quantities of the fluid than do 1 in 6 emulsions. 7. Because of the simple preparation, the superior antigenic property, and the constant antigen value of cholesterin-heart extracts prepared from human hearts, we agree with McIntosh and Fildes that this form of extract fulfills the requirements of a standard antigen.
New insights into the proximal tendons of adductor longus, adductor brevis and gracilis
Authors: J A Davis, M D Stringer, S J Woodley
Journal: British Journal of Sports Medicine (2011)

The adductor muscles are implicated in the pathogenesis of groin strain, but the proximal morphology of this muscle group is poorly defined. The purpose of this study was to investigate the detailed anatomy of the entheses and proximal musculotendinous junctions (MTJs) of adductor longus (AL), adductor brevis (AB) and gracilis.The adductors were dissected bilaterally in 10 embalmed cadavers (7 females, mean age at death 79 years (range 57-93 years)), focusing on the type of enthesis, and architecture of the proximal tendons and MTJs. Histology was used to determine if the entheses contained fibrocartilage and to semiquantitatively assess the vascularity of each proximal tendon.All entheses were fibrocartilaginous. The proximal tendons of AB and gracilis were fused, forming a common tendinous insertion in all specimens. AL and AB both contained extensive intramuscular tendons of variable length (AL 11.1 ± 1.5 cm; AB 5.4 ± 1.1 cm); this has not been recorded previously. The vascularity of AL and AB tendons decreased significantly towards the enthesis (p < 0.05), and their entheses were significantly less vascular than that of gracilis (p < 0.05).The proximal anatomy of AL, AB and gracilis is more complex than previously described. The arrangement and fusion of these muscles, their fibrocartilaginous entheses and differences in vascularity of their proximal tendons may be important anatomical considerations in the pathogenesis and pattern of adductor-related groin pain.
High cell surface CD26-associated activities and low plasma adenosine concentration in fibromyalgia
Authors: Régis Guieu, Eric Guedj, Roch Giorgi, Alix Dousset, Veronique Tuzzolino, Youlet By, Jean Marc Leveque, Jean Claude Peragut, Jean Régis, Jean Ruf, Emmanuel Fenouillet, Philippe Roussel
Journal: Annals of the Rheumatic Diseases (2012)

The fibromyalgia syndrome (FMS) affects 2%–10% of the population. Its diagnosis is only based on a history of widespread pain involving limbs and trunk and mild or greater tenderness to digital palpation of tender points.1 While the role of several neurotransmitters including serotonin, dopamine and SP has been suggested, the influence of endogenous adenosine has never been investigated. Adenosine exerts strong antinociceptive effects mostly via the activation of A1 adenosine receptors2 following its release by endothelial cells and myocytes3 into the extracellular space where it is degraded by the enzyme adenosine deaminase (ADA). Large amounts of ADA are found at the surface of mononuclear cells …
Association of Pre-Onset Cannabis, Alcohol, and Tobacco Use With Age at Onset of Prodrome and Age at Onset of Psychosis in First-Episode Patients
Authors: Michael T. Compton, Mary E. Kelley, Claire E. Ramsay, Makenya Pringle, Sandra M. Goulding, Michelle L. Esterberg, Tarianna Stewart, Elaine F. Walker
Journal: American Journal of Psychiatry (2009)

Objective: Several reports suggest that cannabis use is associated with an earlier age at onset of psychosis, although not all studies have operationalized cannabis use as occurring prior to onset of symptoms. This study addressed whether pre-onset cannabis use, alcohol use, and tobacco use are associated with an earlier age at onset of prodromal and psychotic symptoms. Effects of the progression of frequency of use were examined through time-dependent covariates in survival analyses. Method: First-episode patients (N=109) hospitalized in three public-sector inpatient psychiatric units underwent in-depth cross-sectional retrospective assessments. Prior substance use and ages at onset of prodromal and psychotic symptoms were determined by standardized methods, and analyses were conducted using Cox regression modeling. Results: Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of onset, analysis of change in frequency of use prior to onset indicated that progression to daily cannabis and tobacco use was associated with an increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness or prodromal symptoms was the outcome. A gender-by-daily-cannabis-use interaction was observed; progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than in males. Conclusions: Pre-onset cannabis use may hasten the onset of psychotic as well as prodromal symptoms. Age at onset is a key prognostic factor in schizophrenia, and discovering modifiable predictors of age at onset is crucial.
Hepatic arterial infusion using pirarubicin combined with systemic chemotherapy: a phase II study in patients with nonresectable liver metastases from colorectal cancer
Authors: D. Fallik, M. Ychou, J. Jacob, P. Colin, J.F. Seitz, J. Baulieux, A. Adenis, J.Y. Douillard, P. Couzigou, R. Mahjoubi, M. Ducreux, M. Mahjoubi, P. Rougier
Journal: Annals of Oncology (2003)
Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial
Authors: A Straumann, S Conus, P Grzonka, H Kita, G Kephart, C Bussmann, C Beglinger, D A Smith, J Patel, M Byrne, H-U Simon
Journal: Gut (2009)

<h3>Objective:</h3> Eosinophilic oesophagitis (EoO) is a clinicopathological condition defined by proton pump inhibitor-refractory oesophageal symptoms combined with oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated. <h3>Methods:</h3> Eleven adults with active EoO (&gt;20 peak eosinophil number/high power field (hpf) and dysphagia) were randomised to 750 mg of mepolizumab (n = 5) or placebo (n = 6) and received two intravenous infusions, 1 week apart. Those not in complete remission (&lt;5 peak eosinophil number/hpf) after 8 weeks received two further doses 4 weeks apart, 1500 mg of mepolizumab or placebo. The effect of mepolizumab was assessed clinically, endoscopically, histologically, and via blood and tissue biomarkers. <h3>Results:</h3> As assessed by immunofluorescence, a marked reduction of mean oesophageal eosinophilia (p = 0.03) was seen in the mepolizumab group (−54%) compared with the placebo group (−5%) 4 weeks after initiation of treatment. No further reduction of eosinophil numbers was observed in response to the two additional infusions in either group. Mepolizumab reduced tenascin C (p = 0.033) and transforming growth factor β1 (p = 0.05) expression in the oesophageal epithelial layer 13 weeks after initiation of treatment. Clinically, limited improvement of symptoms was seen, although a trend was seen between 4 and 13 weeks after initiation of mepolizumab treatment. Mepolizumab was well tolerated. <h3>Conclusions:</h3> Mepolizumab significantly reduced eosinophil numbers in oesophageal tissues in adult patients with active EoO, and changes in the expression of molecules associated with oesophageal remodelling were reversed. Minimal clinical improvement was achieved in a subgroup of patients with EoO. Mepolizumab had an acceptable safety profile, even at the high 1500 mg dose level. <h3>Trial registration number:</h3> NCT00274703
Copper and liver disease
Authors: C E Eapen
Journal: Gut (2011)

<h3>Background/aims</h3> Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis. <h3>Methods</h3> Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA. <h3>Results</h3> There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab. <h3>Conclusions</h3> Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept. <h3>Trial registration number</h3> NCT02173873.
CD4<b>+</b>CD25<b>+</b> regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner
Authors: François Ghiringhelli, Cédric Ménard, Magali Terme, Caroline Flament, Julien Taieb, Nathalie Chaput, Pierre E. Puig, Sophie Novault, Bernard Escudier, Eric Vivier, Axel Lecesne, Caroline Robert, Jean-Yves Blay, Jacky Bernard, Sophie Caillat-Zucman, Antonio Freitas, Thomas Tursz, Orianne Wagner-Ballon, Claude Capron, William Vainchencker, François Martin, Laurence Zitvogel
Journal: The Journal of Experimental Medicine (2005)

Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system.
THE BIOSYNTHESIS OF HEMOGLOBIN FROM IRON, PROTOPORPHYRIN AND GLOBIN*†
Authors: Herbert C. Schwartz, Robert Goudsmit, Robert L. Hill, George E. Cartwright, Maxwell M. Wintrobe
Journal: Journal of Clinical Investigation (1961)

The formation of heme in a system containing protoporphyrin, iron and a soluble preparation from avian erythrocytes has been studied by sev- eral investigators (3-6).The observations that the biosynthetic reaction is inactivated by heating at 560 C for 30 minutes, has a pH of optimal ac- tivity and stability near neutrality with a lower rate on each side of this optimum, and that the rate of heme synthesis is proportional to enzyme concentration, suggest, although admittedly do not prove, that the reaction is enzyme-dependent (4-6).The enzyme has been tentatively named "heme synthetase" (2, 5).However, since more than one enzyme may be involved in this reaction, the name "heme synthetase system" would be more appropriate until it can be shown that a single en- zyme is involved.The activity of the heme synthetase system is increased by reduced glutathione, cysteine, or other reducing agents (4-7).Inhibition with p-chloromercuriphenylsulfonate and with iodoacetamide suggests that active sulfhydryl groups are required for enzyme activity (5).Purification of the heme synthetase system and augmentation of heme synthesis by globin are de- scribed in the present studies.Although several
1291 ANALYSIS OF CIRCULATING CD4+ AND CD8+ T MEMORY SUBSETS IN ACTIVE TYPE I AUTOIMMUNE HEPATITIS AND DURING ITS BIOCHEMICAL REMISSION
Authors: N.E. Ferreyra Solari, D. Levi, A. Villamil, P. Baz, A. Billordo, A.C. Cherñavsky
Journal: Journal of Hepatology (2011)
Pretreatment Epidermal Growth Factor Receptor (<i>EGFR</i>) T790M Mutation Predicts Shorter EGFR Tyrosine Kinase Inhibitor Response Duration in Patients With Non–Small-Cell Lung Cancer
Authors: Kang-Yi Su, Hsuan-Yu Chen, Ker-Chau Li, Min-Liang Kuo, James Chih-Hsin Yang, Wing-Kai Chan, Bing-Ching Ho, Gee-Chen Chang, Jin-Yuan Shih, Sung-Liang Yu, Pan-Chyr Yang
Journal: Journal of Clinical Oncology (2012)

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations have excellent response to EGFR tyrosine kinase inhibitors (TKIs), but T790M mutation accounts for most TKI drug resistance. This study used highly sensitive methods to detect T790M before and after TKI therapy and investigated the association of T790M and its mutation frequencies with clinical outcome.Direct sequencing, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and next-generation sequencing (NGS) were used to assess T790M in the following two cohorts of patients with NSCLC: TKI-naive patients (n = 107) and TKI-treated patients (n = 85). Results were correlated with TKI treatment response and survival.MALDI-TOF MS was highly sensitive in detecting and quantifying the frequency of EGFR-activating mutations and T790M (detection limits, 0.4% to 2.2%). MALDI-TOF MS identified more T790M than direct sequencing in TKI-naive patients with NSCLC (27 of 107 patients, 25.2% v three of 107 patients, 2.8%, respectively; P < .001) and in TKI-treated patients (before TKI: 23 of 73 patients, 31.5% v two of 73 patients, 2.7%, respectively; P < .001; and after TKI: 10 of 12 patients, 83.3% v four of 12 patients, 33.3%, respectively; P = .0143). The EGFR mutations and their frequencies were confirmed by NGS. T790M was an independent predictor of decreased progression-free survival (PFS) in patients with NSCLC who received TKI treatment (P < .05, multivariate Cox regression).T790M may not be a rare event before or after TKI therapy in patients with NSCLC with EGFR-activating mutations. The pretreatment T790M mutation was associated with shorter PFS with EGFR TKI therapy in patients with NSCLC.
Molecular Profiling of Patient-Matched Brain and Extracranial Melanoma Metastases Implicates the PI3K Pathway as a Therapeutic Target
Authors: Guo Chen, Nitin Chakravarti, Kimberly Aardalen, Alexander J. Lazar, Michael T. Tetzlaff, Bradley Wubbenhorst, Sang-Bae Kim, Scott Kopetz, Alicia A. Ledoux, Y.N. Vashisht Gopal, Cristiano Goncalves Pereira, Wanleng Deng, Ju-Seog Lee, Katherine L. Nathanson, Kenneth D. Aldape, Victor G. Prieto, Darrin Stuart, Michael A. Davies
Journal: Clinical Cancer Research (2014)

An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches.Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and quantitative analysis of protein expression and activation by reverse-phase protein array (RPPA) analysis were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors.The status of 154 previously reported hotspot mutations, including driver mutations in BRAF and NRAS, were concordant in all evaluable patient-matched pairs of tumors. Overall patterns of CNV, mRNA expression, and protein expression were largely similar between the paired samples for individual patients. However, brain metastases demonstrated increased expression of several activation-specific protein markers in the PI3K/AKT pathway compared with the extracranial metastases.These results add to the understanding of the molecular characteristics of melanoma brain metastases and support the rationale for additional testing of the PI3K/AKT pathway as a therapeutic target in these highly aggressive tumors.
Canine spontaneous glioma: A translational model system for convection-enhanced delivery
Authors: P. J. Dickinson, R. A. LeCouteur, R. J. Higgins, J. R. Bringas, R. F. Larson, Y. Yamashita, M. T. Krauze, J. Forsayeth, C. O. Noble, D. C. Drummond, D. B. Kirpotin, J. W. Park, M. S. Berger, K. S. Bankiewicz
Journal: Neuro-Oncology (2010)

Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes.
Bridging Behavior and Biology to Reduce Socioeconomic Disparities in Colorectal Cancer Risk
Authors: J. Z. Ayanian, J. M. Carethers
Journal: JNCI Journal of the National Cancer Institute (2012)

During the last quarter of the 20th century, the incidence of colorectal cancer in the United States declined by 22%. Half of this decline has been attributed to changes in health behaviors, such as red meat consumption and physical activity, and the other half has been ascribed to increased screening with fecal occult blood testing, sigmoidoscopy, and colonoscopy (1). The declining incidence of colorectal cancer accelerated from 1999 to 2008 with average annual reductions of 2%–3% for both men and women (2), representing a shared accomplishment of public health and health care. These improvements, however, have been disproportionately concentrated among more educated and affluent Americans. In 2000, rates of obesity were higher and rates of colorectal cancer screening were substantially lower among adults with less education, as reported in the National Health Interview Survey (3). As a result, even though the overall incidence of colorectal cancer has declined in recent decades, socioeconomic disparities in colorectal cancer incidence remain substantial (4). Moreover, disparities in colorectal cancer mortality by education and race have actually increased since 1993 and thus represent a growing concern (5).
The Cancer and Leukemia Group B Transplant Committee
Authors: Charles Linker, David Hurd
Journal: Clinical Cancer Research (2006)

Abstract The Transplant Committee of the Cancer and Leukemia Group B has a robust portfolio of studies and is poised to make significant contributions to the field. We are working in collaboration with the Cancer and Leukemia Group B Leukemia and Lymphoma Disease Committees and importantly in collaboration with other groups to define the role of both autologous and reduced-intensity allogeneic transplantation in the management of selected hematologic malignancies. Some of our studies have the potential to change the standard of care in areas such as the maintenance therapy for multiple myeloma after autologous transplantation and to generate the data that could lead to acceptance of new approaches to the initial post-remission therapy of older adults with acute myeloid leukemia. The cooperative group setting allows us to advance the transplant field by showing which approaches are successful outside of single institutions and are therefore feasible on a generalized basis.