tbuckley/cabot-search huggingface dataset:
REGULATION OF IMMUNE RESPONSES THROUGH INHIBITORY RECEPTORS
Authors: Eric O. Long
Journal: Annual Review of Immunology (1999)

▪ Abstract Major histocompatibility complex class I-specific inhibitory receptors on natural killer cells prevent the lysis of healthy autologous cells. The outcome of this negative signal is not anergy or apoptosis of natural killer cells but a transient abortion of activation signals. The natural killer inhibitory receptors fulfill this function by recruiting the tyrosine phosphatase SHP-1 through a cytoplasmic immunoreceptor tyrosine-based inhibition motif. This immunoreceptor tyrosine-based inhibition motif has become the hallmark of a growing family of receptors with inhibitory potential, which are expressed in various cell types such as monocytes, macrophages, dendritic cells, leukocytes, and mast cells. Most of the natural killer inhibitory receptors and two members of a monocyte inhibitory-receptor family bind major histocompatibility complex class I molecules. Ligands for many of the other receptors have yet to be identified. The inhibitory-receptor superfamily appears to regulate many types of immune responses by blocking cellular activation signals.
A neural-symbolic perspective on analogy
Authors: Rafael V. Borges, Artur S. d'Avila Garcez, Luis C. Lamb
Journal: Behavioral and Brain Sciences (2008)

Abstract The target article criticises neural-symbolic systems as inadequate for analogical reasoning and proposes a model of analogy as transformation (i.e., learning). We accept the importance of learning, but we argue that, instead of conflicting, integrated reasoning and learning would model analogy much more adequately. In this new perspective, modern neural-symbolic systems become the natural candidates for modelling analogy.
Cancer Prevention and Control
Authors: Daniel W. Nixon
Journal: JAMA (1996)

The application of sound scientific practices to cancer prevention and control is relatively recent, but an enormous amount of data has already accumulated that supports the preventability of cancer. The editors of<i>Cancer Prevention and Control</i>have taken on the arduous task of compiling all the available current information into a book that will be a good reference source for all readers interested in this field. The book begins by introducing the reader to the history of cancer prevention and control. Dr Greenwald provides historical perspectives complete with the establishment of the two largest cancer control organizations, the American Cancer Society and the National Cancer Institute. The book is then logically organized into six sections. The first, appropriately entitled "The Burden of Cancer," describes in vivid detail the magnitude of the cancer problem in terms of statistical rates and economic impact. A chapter is devoted to cancer patterns in minorities
A Turning Point for Conflicts of Interest: The Controversy Over the National Academy of Sciences' First Conflicts of Interest Disclosure Policy
Authors: Mark Parascandola
Journal: Journal of Clinical Oncology (2007)

Conflicts of interest policies have become a part of the fabric of the conduct of biomedical research, yet such concerns are relatively recent history. Until the 1960s, concerns about conflicts of interest were confined to scientists who served as government advisors and contractors. However, in the 1970s, as a range of environmental and consumer safety issues gained public attention, the conclusions of researchers frequently came under attack because of concerns about experts' financial ties to private industry. These debates typically focused on evaluating potential carcinogens in the environment. In response, the National Academy of Sciences (NAS) developed its first conflict of interest policy, requiring committee members to disclose any "potential sources of bias" that "others might deem prejudicial." Scientists universally opposed the policy, however, for a range of reasons--while some argued that all experienced and knowledgeable experts were inherently conflicted, others were offended at the suggestion that any expert could be biased. Despite the controversy, the disclosure policy remained in place and became a model for subsequent professional and institutional policies in the biomedical sciences. However, although disclosure policies have become standard at academic medical centers and for publications in scientific journals, clinical researchers have continued to debate the content of these policies and the need for additional protections beyond disclosure. In the absence of a definitive standard, this historical case study can substantially inform ongoing discussion on conflicts of interest in clinical research.
Shape self-regulation during lung development
Authors: Raphael Clément, Benjamin Mauroy, Stéphane Douady
Journal: European Respiratory Journal (2013)

The bronchial tree results from the self-avoiding branching of lung epithelium in the mesenchyme. While the molecular basis of morphogenesis has been extensively studied, the individual branching mechanism and the organ-scale organization process remain unclear.

We designed an innovative biophysical model of lung development. We found that the diffusion of the major growth factor (FGF10) from distal mesenchyme where Fgf10 is known to be expressed accounts for the patterning of FGF10 downstream targets (Fig. 1).

![Figure][1] 



We then developed 2D and 3D development simulations. Starting from a unique epithelial tube, and calculating local epithelial growth as a function of FGF10 reception, we found that most of the striking features of lung geometry - self-avoiding and space-filling branching, asymmetry, size dispersion, etc - emerge spontaneously through mechanisms that we detail (Fig. 2).

![Figure][1] 



Our results suggest that self-organization may play a major role in lung branching morphogenesis. They provide a direct link between genotype, phenotype, and phenotypic variability. They are consistent with morphometric data and with mutant phenotypes. Finally, they question the well-accepted scenario of a master genetic routine.

 [1]: pending:yes
Linear eruptions of the nose in childhood: a form of lichen striatus?
Authors: M-W. Lee, J-H. Choi, K-J. Sung, K-C. Moon, J-K. Koh
Journal: British Journal of Dermatology (2000)

Abstract We report four children with linear eruptions on the nose, with overlapping features of lichen striatus and linear cutaneous lupus erythematosus. However, linear lupus erythematosus has rarely been reported, and lichen striatus, although classically linear, rarely affects the face. The linear distribution of lesions from the glabella to the ala nasi may represent distribution following Blaschko’s lines.
An assessment of acute kidney injury with modified RIFLE criteria in pediatric patients with severe burns
Authors: Tina Palmieri, Athina Lavrentieva, David Greenhalgh
Journal: Intensive Care Medicine (2009)

To apply the modified pediatric RIFLE criteria for severity of acute kidney injury (AKI) to pediatric burn ICU patients and to evaluate the overall incidence of AKI, risk factors for AKI and influence of AKI on outcome.Retrospective, descriptive cohort study.10-bed burn PICU facility.All consecutive patients with a burn injury of 10% or more of total body surface area percentage (TBSA, %) admitted during a 2 year period.Data of 123 patients were studied. The incidence of AKI was 45.5%. Patients with AKI tended to have higher mortality than those without AKI (p = 0.057). All nonsurvivors attained pRIFLE AKI by combination of serum creatinine and urine output criteria. Patients with a more severe form of AKI (Failure and Injury) as well as patients with late AKI had more episodes of sepsis as compared to patients with early AKI and the Risk category of AKI. Logistic regression analysis indicated that PRISM score and TBSA were the independent risk factors for acute kidney injury in pediatric burn patients; the presence of sepsis and septic shock were the independent risk factors for the Failure class of AKI.We observed a high incidence of AKI in the burn PICU population. Sepsis seems to contribute to the development of the Failure class of AKI. Maximum Failure class of AKI is associated with high mortality.
Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study
Authors: V. Bazan, L. Bruno, C. Augello, V. Agnese, V. Calò, S. Corsale, G. Gargano, M. Terrasi, V. Schirò, G. Di Fede, V. Adamo, C. Intrivici, A. Crosta, G. Rinaldi, F. Latteri, G. Dardanoni, N. Grassi, M.R. Valerio, G. Colucci, M. Macaluso, A. Russo
Journal: Annals of Oncology (2006)
THE IMPROVED CANNULA AND TROCAR
Authors: S. W. Dickinson
Journal: JAMA (1925)

To the Editor:  —The paper by Dr. Bryce W. Fontaine (The Journal, April 18, p. 1179) interested me. During the summer of 1914, it became necessary for me to spend some days in the Lewis-Gale Hospital, Roanoke, Va. While there, Dr. S. S. Gale showed me a cannula and trocar he had devised and had made by Tiemann of New York, with holes in the sides of the cannula as shown in the illustration of Dr. Fontaine's cannula. I told Dr. Gale that when I came again to the hospital I would bring him a book more than a hundred years old in which was a description and an illustration of a cannula with holes just as in his instrument. Dr. Gale now owns this book, the title of which is A Treatise on Surgery, by Samuel Sharp, surgeon to Guy's Hospital, London, Edition 10, printed in London in 1782.
Neural Responses to Happy Facial Expressions in Major Depression Following Antidepressant Treatment
Authors: Cynthia H.Y. Fu, Steve C.R. Williams, Michael J. Brammer, John Suckling, Jieun Kim, Anthony J. Cleare, Nicholas D. Walsh, Martina T. Mitterschiffthaler, Chris M. Andrew, Emilio Merlo Pich, Edward T. Bullmore
Journal: American Journal of Psychiatry (2007)

Processing affective facial expressions is an important component of interpersonal relationships. However, depressed patients show impairments in this system. The present study investigated the neural correlates of implicit processing of happy facial expressions in depression and identified regions affected by antidepressant therapy.Two groups of subjects participated in a prospective study with functional magnetic resonance imaging (fMRI). The patients were 19 medication-free subjects (mean age, 43.2 years) with major depression, acute depressive episode, unipolar subtype. The comparison group contained 19 matched healthy volunteers (mean age, 42.8 years). Both groups underwent fMRI scans at baseline (week 0) and at 8 weeks. Following the baseline scan, the patients received treatment with fluoxetine, 20 mg daily. The fMRI task was implicit affect recognition with standard facial stimuli morphed to display varying intensities of happiness. The fMRI data were analyzed to estimate the average activation (overall capacity) and differential response to variable intensity (dynamic range) in brain systems involved in processing facial affect.An attenuated dynamic range of response in limbic-subcortical and extrastriate visual regions was evident in the depressed patients, relative to the comparison subjects. The attenuated extrastriate cortical activation at baseline was increased following antidepressant treatment, and symptomatic improvement was associated with greater overall capacity in the hippocampal and extrastriate regions.Impairments in the neural processing of happy facial expressions in depression were evident in the core regions of affective facial processing, which were reversed following treatment. These data complement the neural effects observed with negative affective stimuli.
Unfolded protein response in cancer: the Physician's perspective
Authors: Xuemei Li, Kezhong Zhang, Zihai Li
Journal: Journal of Hematology & Oncology (2011)

The unfolded protein response ( UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials.
Low serum levels of 1.25-dihydroxyvitamin D and histomorphometric evidence of osteomalacia after jejunoileal bypass for obesity.
Authors: L Mosekilde, F Melsen, I Hessov, M S Christensen, B J Lund, B I Lund, O H Sorensen
Journal: Gut (1980)

Twenty-seven unselected patients were investigated three to eight years after jejunoileal bypass for morbid obesity. The serum levels of calcium, magnesium, and phosphorus, and the renal excretions of calcium and magnesium were reduced. The serum alkaline phosphatase levels were increased. The serum levels of the two vitamin D metabolites 25-hydroxyvitamin D (25-OHD) and 1.25-dihydroxyvitamin D (1.25-(OHD)2D) were reduced and inversely related to the increased serum levels of immunoreactive parathyroid hormones (iPTH). Serum 1.25-(OH)2D correlated positively and serum iPTH inversely with serum concentrations and renal excretion rates of calcium. Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a reduced bone turnover with an increased amount of osteoid due to an increase in both surface extent and mean width of osteoid seams. The increased volume of osteoid was caused by a decreased osteoblastic function with a longer life-span of bone-forming sites and a prolongation of the mineralisation lag time. The amount of trabecular bone was normal. The results indicate an impaired vitamin D metabolism with osteomalacia and secondary hyperparathyroidism.
Genetic Studies on Chromosome 12 in Late-Onset Alzheimer Disease
Authors: William S. Wu
Journal: JAMA (1998)

The only genetic locus universally accepted to be important as a risk factor for late-onset Alzheimer disease (AD) is the apolipoprotein E (APOE) locus on chromosome 19. However, this locus does not account for all the risk in late-onset disease, and a recent report has suggested a second locus on chromosome 12p11-12.To look for evidence of linkage on chromosome 12 and to test for the presence of the new locus in an independent sample of familial late-onset AD cases.Retrospective cohort study. As part of a 20-centimorgan genome screen (approximately equal to 200 markers), we tested a series of 18 genetic markers on chromosome 12 and carried out multipoint, nonparametric lod score and exclusion analyses.Clinic populations in the continental United States selected from the National Institute of Mental Health AD Genetics Consortium.We selected samples for DNA analysis from affected sibling pairs, 497 subjects from 230 families with 2 or more affected individuals with probable or definite AD with onset ages older than 60 years (mean+/-SD, 75+/-6 years). Within the families, we used the 2 probable or definitely affected individuals. In families with more than 2 such cases available, we used all of them; in families with only 2 such cases in which unaffected individuals were available, we also sampled the oldest unaffected individual and used genotype data from this unaffected individual to check for nonpaternity and genotyping errors.Presence of linkage or locus on chromosome 12.Although linkage analyses confirmed the presence of a genetic susceptibility factor at the APOE locus in these families with late-onset AD, we were unable to confirm the presence of a locus close to the marker D12S1042. A moderate lod score (1.91) was found near D12S98 close to the alpha2-macroglobulin locus in the affected pairs in which both members did not possess an APOE epsilon4 allele.APOE remains the only locus established to be a risk factor for late-onset AD. We were unable to confirm that a locus on chromosome 12p11-12 has a major effect on risk for late-onset AD, although an effect smaller than that for APOE cannot be excluded.
Three-Dimensional Prostate Mapping Biopsy Has a Potentially Significant Impact on Prostate Cancer Management
Authors: Gary Onik, Matthew Miessau, David G. Bostwick
Journal: Journal of Clinical Oncology (2009)

To compare a new staging, three-dimensional prostate mapping biopsy (3D-PMB) method with traditional transrectal ultrasound (TRUS) biopsy and assess its possible impact on patient management.One hundred eighty patients with unilateral cancer on TRUS biopsy, who were considering conservative management, underwent restaging with 3D-PMB. The 3D-PMB was carried out transperineally using a brachytherapy grid under TRUS guidance. Biopsies were taken every 5 mm throughout the volume of the prostate, and labeling of the specimen coordinates allowed accurate reconstruction of the location and extent of a patient's cancer.3D-PMB obtained a median of 50 cores (standard deviation, +/- 20.61). One hundred ten patients (61.1%) were positive bilaterally, and 41 patients (22.7%) had Gleason scores increased to 7 or higher. Thirty-six patients had negative results on 3D-PMB. Complications of 3D-PMB were self-limited and included 14 patients (7.7%) who required short-term indwelling catheter drainage and two patients with hematuria, one of whom required overnight bladder irrigation.3D-PMB is a transperineal biopsy that can be safely used to accurately stage prostate cancer patients. At the present time, when patient management is increasingly based on the extent and characteristics of prostate cancer, 3D-PMB could have a profound effect on patient management.
Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model
Authors: Aizea Morales-Kastresana, Miguel F. Sanmamed, Inmaculada Rodriguez, Asis Palazon, Ivan Martinez-Forero, Sara Labiano, Sandra Hervas-Stubbs, Bruno Sangro, Carmen Ochoa, Ana Rouzaut, Arantza Azpilikueta, Elixabet Bolaños, Maria Jure-Kunkel, Ines Gütgemann, Ignacio Melero
Journal: Clinical Cancer Research (2013)

Immunostimulatory monoclonal antibodies (ISmAb) that unleash antitumor immune responses are showing efficacy in cancer clinical trials. Anti-B7-H1 (PD-L1) monoclonal antibodies (mAb) block a critical inhibitory pathway in T cells, whereas anti-CD137 and OX40 mAbs provide T-cell costimulation. A combination of these ISmAbs (anti-CD137 + anti-OX40 + anti-B7-H1) was tested using a transgenic mouse model of multifocal and rapidly progressing hepatocellular carcinoma, in which c-myc drives transformation and cytosolic ovalbumin (OVA) is expressed in tumor cells as a model antigen.Flow-cytometry and immunohistochemistry were used to quantify tumor-infiltrating lymphocytes (TIL) elicited by treatment and assess their activation status and cytolytic potential. Tolerance induction and its prevention/reversal by treatment with the combination of ISmAbs were revealed by in vivo killing assays.The triple combination of ISmAbs extended survival of mice bearing hepatocellular carcinomas in a CD8-dependent fashion and synergized with adoptive T-cell therapy using activated OVA-specific TCR-transgenic OT-1 and OT-2 lymphocytes. Mice undergoing therapy showed clear increases in tumor infiltration by activated and blastic CD8(+) and CD4(+) T lymphocytes containing perforin/granzyme B and expressing the ISmAb-targeted receptors on their surface. The triple combination of ISmAbs did not result in enhanced OVA-specific cytotoxic T lymphocyte (CTL) activity but other antigens expressed by cell lines derived from such hepatocellular carcinomas were recognized by endogenous TILs. Adoptively transferred OVA-specific OT-1 lymphocytes into tumor-bearing mice were rendered tolerant, unless given the triple mAb therapy.Extension of survival and dense T-cell infiltrates emphasize the translational potential of combinational immunotherapy strategies for hepatocellular carcinoma. Clin Cancer Res; 19(22); 6151-62. ©2013 AACR.
Clinical Significance of Cytokeratin 20-Positive Circulating Tumor Cells Detected by a Refined Immunomagnetic Enrichment Assay in Colorectal Cancer Patients
Authors: Sze Chuen Cesar Wong, Charles Ming Lok Chan, Brigette Buig Yue Ma, Edwin Pun Hui, Simon Siu Man Ng, Paul Bo San Lai, Moon Tong Cheung, Elena Siu Fong Lo, Amanda Kit Ching Chan, Money Yan Yee Lam, Thomas Chi Chuen Au, Anthony Tak Cheung Chan
Journal: Clinical Cancer Research (2009)

Current immunomagnetic enrichment method can only detect general epithelial antigens of circulating tumor cells (CTC). Further characterization of the CTCs to provide specific information on the tumor type is not possible. We attempted to overcome this drawback by developing the methodology for using a gastrointestinal-specific anti-cytokeratin (CK) 20 antibody to detect CTCs in colorectal cancer patients' blood.The protocol was validated using a colorectal cancer SW480 cell line. The clinical significance of findings in colorectal cancer was investigated by detecting CK20-positive CTCs (pCTC) in patients with colorectal cancer, other common cancers, colorectal adenoma, benign colorectal diseases, and normal subjects. Moreover, the malignant nature of CK20 pCTCs was examined by comparing chromosome 17 aberration patterns with those from the corresponding primary tumors.The assay successfully showed CK20-positive SW480 cells. When applied in patient samples, the detection rates were 62% (132 colorectal cancer patients; median number = 11 CTCs), 0% (120 patients with other common cancers), 6% (50 colorectal adenoma patients), 0% (120 patients with benign colorectal diseases), and 0% (40 normal subjects). Furthermore, statistical analysis showed that CK20 pCTC numbers were associated with tumor-node-metastasis stage and lymph node status. Using the median CK20 pCTC numbers as the cutoff points, stratified groups of colorectal cancer patients had significant differences in their recurrence, metastasis, and survival. Finally, chromosome 17 aneusomy in 90% of colorectal cancer patients with CK20 pCTCs matched with those from the primary tumors.Detection of CK20 pCTCs using the new protocol could generate clinically important information for colorectal cancer patients.
Diagnosis and Treatment of Aphasia
Authors: M L Albert, N Helm-Estabrooks
Journal: JAMA (1988)

IN PART I of this article, published in the previous issue, we reviewed the classification of aphasic syndromes, described key clinical features of each syndrome, and discussed neurodiagnostic techniques developed to improve clinical diagnosis and facilitate our understanding of brain-language relationships. We emphasized that although gross clinicoanatomic correlations can be useful, there is no one-to-one correspondence between specific parts of the brain and specific components of language. A comprehensive neurological theory of language must involve both hemispheres and subcortical structures as well. In part II we focus on diagnostic aphasia tests and developments in therapy for aphasia. <h3>APHASIA TESTS</h3> Much of what we know about clinical features of aphasia comes from informal, but thorough, bedside examinations of individual patients. This form of evaluation, although highly informative when conducted by an experienced aphasiologist, is by its nature nonstandardized. A few short clinical tests, such as Marie's 3-Paper Test,<sup>126</sup>have long