tbuckley/cabot-search huggingface dataset:
Where the rubber meets the road: The importance of implementation
Authors: Deanna M. Barch, Todd S. Braver
Journal: Behavioral and Brain Sciences (2003)

Abstract Phillips &amp; Silverstein argue that a range of cognitive disturbances in schizophrenia result from a deficit in cognitive coordination attributable to NMDA receptor dysfunction. We suggest that the viability of this hypothesis would be further supported by explicit implementation in a computational framework that can produce quantitative estimates of the behavior of both healthy individuals and individuals with schizophrenia.
Genetic Studies on the Etiology and Morphology of Mammary Tumors in Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: William S. Murray
Journal: JNCI Journal of the National Cancer Institute (1966)

Data on reciprocal crosses between three parental stocks of mice are presented in support of the following conclusions: 1) The milk-transported mammary tumor virus stimulates the formation of A and B type mammary adenocarcinoma in early age and early middle age. 2) The other mammary tumors found—type C, fibrosarcoma, hemangioendothelioma, and adenoacanthoma, which characteristically develop in late middle and old age and are independent of the direction in which the reciprocal crosses were made—have a separate etiology. 3) The parallel between the time of occurrence of the late mammary tumors and the time spread of appearance of tumors in the other organs suggests a common etiology for all late tumors.
Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma
Authors: Richard L. Piekarz, Robin Frye, Maria Turner, John J. Wright, Steven L. Allen, Mark H. Kirschbaum, Jasmine Zain, H. Miles Prince, John P. Leonard, Larisa J. Geskin, Craig Reeder, David Joske, William D. Figg, Erin R. Gardner, Seth M. Steinberg, Elaine S. Jaffe, Maryalice Stetler-Stevenson, Stephen Lade, A. Tito Fojo, Susan E. Bates
Journal: Journal of Clinical Oncology (2009)

PURPOSE Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. PATIENTS AND METHODS The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. CONCLUSION The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.
A case of dyspepsia and abdominal fullness
Authors: J. D. Thomas, T. M. Monaghan, J. James
Journal: Gut (2010)

A 59-year-old woman presented with a 5-month history of acid reflux symptoms which were initially relieved with a proton pump inhibitor. She complained of no weight loss, anorexia or abdominal pain but could feel a ‘fullness’ in her upper abdomen which prevented her from lying prone.

Examination revealed a hard epigastric mass which seemed separate from the liver and spleen. There was no lymphadenopathy or other positive findings.

Initial laboratory investigations showed a normal full blood count, urea and electrolytes, bilirubin and …
Clinical Implications of Receptor Sensitivity Modification
Authors: A J Friedhoff, J C Miller
Journal: Annual Review of Neuroscience (1983)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Type 2 diabetes is cardiovascular disease
Authors: K. Dhatariya
Journal: Journal of the Royal Society of Medicine (2003)

Neurologists are trying to convince generalists to avoid the term cerebrovascular accident, because many of the risk factors for stroke are modifiable: to regard the condition as an act of fate encourages inertia rather than the necessary aggressive approach including rapid brain scanning and thrombolysis in selected cases.1 Just as in myocardial infarction ‘time is muscle’, with an intracerebral event ‘time is brain’. The term ‘brain attack’ serves to remind clinicians that intervention is required long before the 24 hours required for formal definition of a stroke.2 Generalists now have to be persuaded that an equally focused and aggressive approach is required in diabetes mellitus. The day of ‘wait and see’ is past, and the term mild diabetes should be buried forever. Gaining ground is the idea that diabetes mellitus (especially type 2 diabetes) is a ‘state of accelerated cardiovascular disease that just happens to be associated with hyperglycaemia’. People with type 2 diabetes are between two and six times more likely than those without diabetes to have cardiovascular disease and are more than twice as likely to die from it. 3,4 Among diabetologists there is a widely held belief that cardiovascular risk reduction should take precedence over reduction of blood glucose. Whereas in type 1 diabetes the diagnosis is usually made quickly, in type 2 diabetes the patient will probably have had the disorder for 4‐7 years before being formally diagnosed.5 Moreover, at the time of diagnosis as many as one fifth will prove to have other risk factors for cardiovascular disease modifiable by lifestyle changes or pharmacological treatment or both.7,8 There is now ample evidence that aspirin, 9,10 statins, 11,12 and angiotensin converting enzyme (ACE) inhibitors 13 reduce the risk of death from cardiovascular disease in diabetes. Gaede and co-workers14 lately reported that, compared with ‘standard care’, an intensive combination of behavioural and pharmaceutical interventions in type 2 diabetes reduced the incidence of cardiovascular disease by 53%, nephro
Transfection of a rat cell line with the v-Ki-ras oncogene is associated with enhanced susceptibility to natural killer cell lysis.
Authors: P W Johnson, C Baubock, J C Roder
Journal: The Journal of Experimental Medicine (1985)

Transfection of the v-Ki-ras oncogene into rat-1 fibroblasts resulted in the establishment of cell lines that were transformed, tumorigenic, and sensitive to lysis by natural killer (NK) cells. Characterization of effectors indicated that the killing was not related to Lyt-1+ or Lyt-2+ cells (T cells) but was associated with cells bearing NK markers (asialo GM1, NK-1.2+, and NK-2.1+). Transfected targets were also killed by cloned NK lines. The transformation determinants on rat-1 transfectants cross-competed with YAC 1.2 lymphoma cells, suggesting a common target structure on these two diverse cell types. The results indicate that the NK surveillance system can recognize and kill cells newly transformed by a member of the ras oncogene family.
Viridans streptococcal shock in bone marrow transplantation patients
Authors: Marie Steiner, Judith Villablanca, John Kersey, Norma Ramsay, Robert Haake, Patricia Ferrieri, Daniel Weisdorf
Journal: American Journal of Hematology (1993)

Abstract We have recognized a rapidly progressive, often fatal shock syndrome associated with viridans streptococcal sepsis following bone marrow transplantation (BMT). Of 832 patients receiving a marrow transplant at the University of Minnesota between 1976 and 1988, including 123 with viridans streptococcal bacteremia, 10 patients (8%) developed clinical shock within an average of 2 days (range 0–4 days) of their first positive blood culture. Viridans streptococcal shock occurred in patients early in the transplantation course, between 1 and 28 (median 6) days following BMT when all 10 patients were neutropenic. Six of the 10 patients died as a consequence of their shock or from subsequent complications. The most frequent (6 of 10 patients) viridans streptococcal species isolated in the shock patients was Streptococcus mitis. Of multiple factors analyzed for increased risk of developing viridans streptococcal shock, only younger patient age was significantly associated with the development of shock. Although 58% of BMT recipients with viridans streptococcal bacteremia were younger than 15 years, all 10 patients comprising the shock population were &lt;15 years of age ( P &lt; 0.02). We speculate that certain streptococcal strains may trigger fulminant shock in the immunocompromised BMT patient. © 1993 Wiley‐Liss, Inc.
An Overview of the Optimal Planning, Design, and Conduct of Phase I Studies of New Therapeutics
Authors: Patricia M. LoRusso, Scott A. Boerner, Lesley Seymour
Journal: Clinical Cancer Research (2010)

Phase I clinical trials represent the first step in bringing promising new treatments from the laboratory to the clinic. Although the importance of phase I clinical trials is widely recognized, there is currently no consensus among the scientific, medical, and statistical communities on how best to do these studies in humans. With the advent of targeted therapies, it has become evident that we need to tailor the design of phase I studies for the particular drug class under investigation and any endpoints that are being defined. The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) provides broad external scientific and clinical input on the design and prioritization of early-phase clinical trials with agents for which the NCI Cancer Therapy Evaluation Program (CTEP) holds an Investigational New Drug (IND) application through the U.S. Food and Drug Administration (FDA). The IDSC has formed a number of task forces and working groups, including the Clinical Trial Design Task Force and the Biomarker Working Group, many with membership from within the IDSC as well as external experts, including participants from academia, the pharmaceutical industry, and regulatory authorities. The Clinical Trials Design Taskforce sponsored a Phase I Workshop with the primary goal being to develop consensus recommendations for the optimal design of phase I studies. The primary focus included (1) efficient trial designs, (2) phase I drug combinations, and (3) appropriate statistical and correlative endpoints. In this CCR Focus series, articles summarize key aspects and recommendations on phase I studies (including combination trials), such as design, use of biomarkers, the European Union and Japanese perspectives on design, requirements for first-in-human and other phase I studies, and ensuring regulatory and International Conference on Harmonization (ICH) compliance. A final article summarizes recommendations for the design and conduct of phase II studies.
A Hidden Markov Model approach to variation among sites in rate of evolution
Authors: J. Felsenstein, G. A. Churchill
Journal: Molecular Biology and Evolution (1996)

The method of Hidden Markov Models is used to allow for unequal and unknown evolutionary rates at different sites in molecular sequences. Rates of evolution at different sites are assumed to be drawn from a set of possible rates, with a finite number of possibilities. The overall likelihood of phylogeny is calculated as a sum of terms, each term being the probability of the data given a particular assignment of rates to sites, times the prior probability of that particular combination of rates. The probabilities of different rate combinations are specified by a stationary Markov chain that assigns rate categories to sites. While there will be a very large number of possible ways of assigning rates to sites, a simple recursive algorithm allows the contributions to the likelihood from all possible combinations of rates to be summed, in a time proportional to the number of different rates at a single site. Thus with three rates, the effort involved is no greater than three times that for a single rate. This "Hidden Markov Model" method allows for rates to differ between sites and for correlations between the rates of neighboring sites. By summing over all possibilities it does not require us to know the rates at individual sites. However, it does not allow for correlation of rates at nonadjacent sites, nor does it allow for a continuous distribution of rates over sites. It is shown how to use the Newton-Raphson method to estimate branch lengths of a phylogeny and to infer from a phylogeny what assignment of rates to sites has the largest posterior probability. An example is given using beta-hemoglobin DNA sequences in eight mammal species; the regions of high and low evolutionary rates are inferred and also the average length of patches of similar rates.
Thymosin β4 protects mice from bleomycin-induced damage in the lung
Authors: Enrico Conte, Maria Iemmolo, Elisa Gili, Tiziana Genovese, Emanuela Esposito, Evelina Fagone, Salvatore Cuzzocrea, Carlo Vancheri
Journal: European Respiratory Journal (2013)

Thymosin β4 (Tβ4) is a small ubiquitous protein that belongs to a family of highly conserved, bioactive molecules with considerable pleiotropic activities. We previously showed a protective role of Tβ4 in the lung of C57BL/6 mice treated with bleomycin. Since it has been demonstrated that bleomycin-induced pulmonary fibrosis is dependent on IL-17 produced by T cells, in this research we investigated in CD mice the effects of Tβ4 on lung damage and their correlation with the presence of IL-17 producing cells. Male CD mice were treated with bleomycin (BLEO, 1 mg/kg) in the absence or presence of Tβ4 (6 mg/kg delivered intra-peritoneally on the day of BLEO treatment and for 2 additional doses). After sacrifice one week later, measurement of fluid and collagen content in the lung, BALF analysis, lung histology, evaluation of IL17 producing cells in blood and spleen as well as RT-PCR from lung tissue homogenates were performed. Moreover, we measured IL-17 levels in the serum of 25 idiopathic pulmonary fibrosis (IPF) patients and 10 matched controls by using ELISA. As expected, BLEO-induced inflammation and lung damage were substantially reduced by Tβ4 treatment, as showed by the substantial reduction of edema, total collagen content, lung infiltration by leukocytes and histological evidence of the ongoing lung fibrosis. Importantly the bleomycin-induced increase in number of IL17 producing cells was significantly halted by Tβ4. Even though considering a small group of patients, our data show no significant differences in IL-17 serum levels of PF patients compared to controls.  This is the first report showing a Tβ4 influence on IL17 producing cells correlating with its anti-inflammatory and anti-fibrotic effects.
Molluscum contagiosum effectively treated with a topical acidified nitrite, nitric oxide liberating cream
Authors: A.D. Ormerod, M.I. White, S.A.A. Shah, N. Benjamin
Journal: British Journal of Dermatology (1999)

A double-blind, group-sequential clinical trial of acidified nitrite was performed to demonstrate the efficacy of this nitric oxide donor in treating molluscum contagiosum. Subjects received either 5% sodium nitrite co-applied with 5% salicylic acid under occlusion, or identical cream with 5% salicylic acid, omitting sodium nitrite. Active and control treatment groups were well matched for the number and duration of lesions and made a similar number of applications. We found a 75% cure rate in the active treatment group and 21% cure with control treatment (P = 0·01). The mean time to cure was 1·83 months. Staining of the skin and irritation were frequent side-effects but did not prevent successful treatment.
Confirmation of Synergy Between Urbanicity and Familial Liability in the Causation of Psychosis
Authors: Jim van Os, Carsten B Pedersen, Preben B Mortensen
Journal: American Journal of Psychiatry (2004)

This study replicated a previous report that there may be substantial synergism between urbanicity (a proxy environmental risk factor) and familial clustering of psychotic disorder (a proxy genetic risk factor).The amount of synergism was estimated from the additive statistical interaction between urbanicity of place of birth and family history of schizophrenia or family history of any severe mental disorder in a population-based Danish cohort of 1,020,063 individuals.There was significant interaction between urbanicity and family history; between 20% and 35% of individuals who had been exposed to both of these risk factors had schizophrenia possibly because of their synergistic effects.The results suggest that a substantial proportion of the population morbidity force of schizophrenia may be the result of gene-environment interactions associated with urbanicity.
An Empirical Test of Convergent Evolution in Rhodopsins
Authors: Kristine A. Mackin, Richard A. Roy, Douglas L. Theobald
Journal: Molecular Biology and Evolution (2013)

Rhodopsins are photochemically reactive membrane proteins that covalently bind retinal chromophores. Type I rhodopsins are found in both prokaryotes and eukaryotic microbes, whereas type II rhodopsins function as photoactivated G-protein coupled receptors (GPCRs) in animal vision. Both rhodopsin families share the seven transmembrane α-helix GPCR fold and a Schiff base linkage from a conserved lysine to retinal in helix G. Nevertheless, rhodopsins are widely cited as a striking example of evolutionary convergence, largely because the two families lack detectable sequence similarity and differ in many structural and mechanistic details. Convergence entails that the shared rhodopsin fold is so especially suited to photosensitive function that proteins from separate origins were selected for this architecture twice. Here we show, however, that the rhodopsin fold is not required for photosensitive activity. We engineered functional bacteriorhodopsin variants with novel folds, including radical noncircular permutations of the α-helices, circular permutations of an eight-helix construct, and retinal linkages relocated to other helices. These results contradict a key prediction of convergence and thereby provide an experimental attack on one of the most intractable problems in molecular evolution: how to establish structural homology for proteins devoid of discernible sequence similarity.
Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial
Authors: Marinus H. J. van Oers, Richard Klasa, Robert E. Marcus, Max Wolf, Eva Kimby, Randy D. Gascoyne, Andrew Jack, Mars van't Veer, Andrej Vranovsky, Harald Holte, Martine van Glabbeke, Ivana Teodorovic, Cynthia Rozewicz, Anton Hagenbeek
Journal: Blood (2006)
Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T-cells
Authors: J.A. Preston, A.N. Thorburn, M.R. Starkey, E.L. Beckett, J.C. Horvat, M.A. Wade, B.J. O'Sullivan, R. Thomas, K.W. Beagley, P.G. Gibson, P.S. Foster, P.M. Hansbro
Journal: European Respiratory Journal (2010)

An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae -induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae .
Diabetic Peripheral Neuropathy Is Associated With Increased Arterial Stiffness Without Changes in Carotid Intima–Media Thickness in Type 2 Diabetes
Authors: Eun Sook Kim, Sung-dae Moon, Hun-Sung Kim, Dong Jun Lim, Jae Hyoung Cho, Hyuk Sang Kwon, Chul Woo Ahn, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Ho Young Son
Journal: Diabetes Care (2011)

OBJECTIVE This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima–media thickness (IMT). RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography. RESULTS Patients with DPN had higher CAVI than those without DPN in multivariate-adjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13–1.65], P = 0.001). CONCLUSIONS DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes.
Control of transient lower oesophageal sphincter relaxations and reflux by the GABAB agonist baclofen in patients with gastro-oesophageal reflux disease
Authors: Q Zhang, A Lehmann, R Rigda, J Dent, R H Holloway
Journal: Gut (2002)

Background and aims: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. Methods: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. Results: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8–18.3) to 9 (5.8–13.3) per three hours (p&lt;0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0–12.0) to 4.0 (1.5–9) per three hours (median (interquartile range); p&lt;0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7–12.4) <i>v</i> placebo 5.0% (2.7–15.5)). Conclusions: In patients with reflux disease, the GABA<sub>B</sub> agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA<sub>B</sub> agonists may be useful as therapeutic agents for the management of reflux disease.