tbuckley/cabot-search huggingface dataset:
A Randomized Phase IIb Trial of Anethole Dithiolethione in Smokers with Bronchial Dysplasia
Authors: Stephen Lam, Calum MacAulay, Jean C. Le Riche, Yulia Dyachkova, Andy Coldman, Martial Guillaud, Ernest Hawk, Marie Odile Christen, Adi F. Gazdar
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Results from preclinical studies have suggested that the organosulfur compound anethole dithiolethione (ADT) may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of ADT in smokers with bronchial dysplasia. Methods: One hundred twelve current and former smokers with a smoking history of at least 30 pack-years and at least one site of bronchial dysplasia identified by an autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive placebo or ADT at 25 mg orally thrice daily for 6 months. Each subject then underwent a follow-up bronchoscopy-directed biopsy. We used changes in histopathologic grade and nuclear morphometry index (MI) as the primary and secondary end point biomarkers, respectively. Chi-square tests with continuity correction were used to compare response rates on a lesion- and person-specific basis between the two study groups. All statistical tests were two-sided. Results: One hundred one subjects had a follow-up bronchoscopy. In the lesion-specific analysis, progression rate of pre-existing dysplastic lesions by two or more grades and/or the appearance of new lesions was statistically significantly lower in the ADT group (8%) than in the placebo group (17%) (P<.001; difference = 9%, 95% confidence interval [CI] = 4% to 15%). In the person-specific analysis, the disease progression rate was statistically significantly lower in the ADT group (32%) than in the placebo group (59%) (P = .013; difference = 27%, 95% CI = 6% to 48%). The two treatment groups did not differ statistically significantly in terms of nuclear MI. Among individuals with an abnormal nuclear MI before treatment (29 in the ADT group and 25 in the placebo group), the progression rate in the ADT group (41%) was substantially lower than that in the placebo group (60%), although the difference was not statistically significant (P = .28; difference = 19%, 95% CI = –11% to 49%). Adverse events were mostly minor gastrointestinal symptoms that resolved with dose reduction or discontinuation of the medication. Conclusion: Our results suggest that, in smokers, ADT is a potentially efficacious chemoprevention agent for lung cancer.
NASAL OBSTRUCTION, A CAUSE OF SUDDEN UNEXPECTED DEATH?
Authors: Eli Gold
Journal: JAMA (1968)

The unexpected death of a young infant previously well or ill with a minor respiratory infection occurs with considerable frequency. Sudden unexpected death (SUD) is estimated to account for 15,000 fatalities per year in the United States, or twice the number caused by congenital abnormalities. In Cleveland, with a population of approximately 1.8 million, there are about 100 such cases a year. This loss of young lives with no apparent cause has provoked numerous hypotheses which, as Shaw states in a recent communication in the<i>American Journal of Diseases of Children</i>,<sup>1</sup>"are in large part speculative and unproven." There are several observations common to most studies of the SUD syndrome; these must include the clues to its etiology and must fit any explanation: (1) Infants are usually between 2 weeks and 6 months of age, with a peak incidence at age 3 to 4 months. (2) Deaths occur in
Lymphocyte-Depleted Classical Hodgkin's Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group
Authors: Beate Klimm, Jeremy Franklin, Harald Stein, Dennis A. Eichenauer, Heinz Haverkamp, Volker Diehl, Michael Fuchs, Peter Borchmann, Andreas Engert
Journal: Journal of Clinical Oncology (2011)

To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-depleted classical Hodgkin's lymphoma (LDCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL).From a total of 12,155 evaluable patients with biopsy-proven HL treated within the German Hodgkin Study Group trials HD4 to HD15, 10,019 patients underwent central expert pathology review. Eighty-four patients with LDCHL (< 1%) were identified and confirmed. The median follow-up time was 67 months.Patients with LDCHL, compared with patients with other histologic subtypes, presented more often with advanced disease (74% v 42%, respectively; P < .001) and "B" symptoms (76% v 41%, respectively; P < .001). Other risk factors were also more frequent in patients with LDCHL. Complete remission or unconfirmed complete remission was achieved in 82% of patients with LDCHL compared with 93% of patients with other HL subtypes (P < .001), and more patients with LDCHL had progressive disease. At 5 years, progression-free survival (PFS) and overall survival (OS) were significantly lower in patients with LDCHL compared with patients with other HL subtypes (PFS, 71% v 85%, respectively; P < .001; OS, 83% v 92%, respectively; P = .0018). However, when analyzing the subgroup of patients who underwent treatment with intensified or dose-dense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, patients with LDCHL (n = 39) had similar outcomes when compared with patients with other subtypes of HL (n = 3,564; P = .61).LDCHL has a different pattern from other HL subtypes with more clinical risk factors at initial diagnosis and significantly poorer prognosis. Patients with LDCHL should be treated with modern dose-intense treatment strategies.
Scottish expert group finds no link between MMR and autism
Authors: B. Christie
Journal: BMJ (2002)

An expert group's review of the use of the measles, mumps, and rubella (MMR) vaccine in Scotland has concluded that it is the best method of protecting children against these diseases.

The group also rejected the use of single vaccines, after finding that they have no safety advantages and are likely to be less effective in immunising children.

Uptake of the MMR vaccine fell throughout the United Kingdom after unconfirmed reports of a link between the vaccine and cases of autism and inflammatory bowel disease. Some 3000 parents who believe that their children were damaged by MMR are pursuing legal action against …
Reduced reliance on the trace element selenium during evolution of mammals
Authors: Alexey V Lobanov, Dolph L Hatfield, Vadim N Gladyshev
Journal: Genome biology (2008)

Abstract Background Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status. Results Here, we report that the amino-terminal domain of SelP is distantly related to ancestral bacterial thiol oxidoreductases of the thioredoxin superfamily, and that its carboxy-terminal Se transport domain may have originated in early metazoan evolution by de novo accumulation of Sec residues. Reconstruction of evolutionary changes in the Se transport domain indicates a decrease in Sec content of SelP specifically in the mammalian lineage via replacement of Sec with cysteine (Cys). Sec content of mammalian SelPs varies more than two-fold and is lowest in rodents and primates. Compared to mammals, fish show higher Sec content of SelP, larger selenoproteomes, elevated SelP gene expression, and higher levels of tissue Se. In addition, mammals replaced Sec with Cys in several proteins and lost several selenoproteins altogether, whereas such events are not found in fish. Conclusion These data suggest that evolution from fish to mammals was accompanied by decreased use of Sec and that analyses of SelP, selenoproteomes and Sec/Cys transitions provide a genetic marker of utilization of this trace element in vertebrates. The evolved reduced reliance on Se raises questions regarding the need to maximize selenoprotein expression by Se dietary supplements in situations when pathology is not imminent, a currently accepted practice.
Hierarchically Porous Chitosan–PEG–Silica Biohybrid: Synthesis and Rapid Cell Adsorption
Authors: Changkui Fu, Shiqi Wang, Lin Feng, Xiaoqi Liu, Yan Ji, Lei Tao, Shuxi Li, Yen Wei
Journal: Advanced Healthcare Materials (2012)

A hierarchically porous chitosan–PEG–silica (CPS) biohybrid has been prepared in a facile synthesis through in situ silica polycondensation within a chitosan–PEG hydrogel. This organic–inorganic composite is almost non-toxic and has quick cell-adsorptivity. As a result of its unique hierarchical structure and excellent biocompatibility, this CPS biohybrid has the potential to be used as a new biomaterial. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Race and Hormone Receptor–Positive Breast Cancer Outcomes in a Randomized Chemotherapy Trial
Authors: Joseph A. Sparano, Molin Wang, Fengmin Zhao, Vered Stearns, Silvana Martino, Jennifer A. Ligibel, Edith A. Perez, Tom Saphner, Antonio C. Wolff, George W. Sledge, William C. Wood, Nancy E. Davidson
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundThe association between black race and worse outcomes in operable breast cancer reported in previous studies has been attributed to a higher incidence of more aggressive triple-negative disease, disparities in care, and comorbidities. We evaluated associations between black race and outcomes, by tumor hormone receptor and HER2 expression, in patients who were treated with contemporary adjuvant therapy.
Hospital clinicians use of smoking AAAs
Authors: Burhan Khan, Linda Smith
Journal: European Respiratory Journal (2011)

Introduction:  All health care professionals have a responsibility to identify, recommend, and assist smokers to stop smoking. Unfortunately, despite having infrastructures in place, use of the 3As is underutilised.   Aim:  Ascertain clinicians use of 3A9s: Ask, Advise, Act during Outpatient clinic consultations.   Method:  Patient survey completed within the department post consultation.   Results:  Of 224 respondents, self-reported smoking prevalence was 26% (53/204). 49% were correctly identified as current smokers, but only 10/26 (38.5%) were advised to stop and only 6 patients were given instructions albeit none were referred to NHS Stop Smoking Services.   Conclusions:  Anecdotal information and assumptions regarding suspecting poor clinician usage of smoking 3As appears to be substantiated. Despite an interaction with a healthcare profession, smokers are not identified, and thus not advised ror referred to smoking cessation. Identification of smokers needs to be systematic and availed at every health care interaction when health is a major salient concern for the patient.
RetrogeneDB—A Database of Animal Retrogenes
Authors: Michał Kabza, Joanna Ciomborowska, Izabela Makałowska
Journal: Molecular Biology and Evolution (2014)

Retrocopies of protein-coding genes, reverse transcribed and inserted into the genome copies of mature RNA, have commonly been categorized as pseudogenes with no biological importance. However, recent studies showed that they play important role in the genomes evolution and shaping interspecies differences. Here, we present RetrogeneDB, a database of retrocopies in 62 animal genomes. RetrogeneDB contains information about retrocopies, their genomic localization, parental genes, ORF conservation, and expression. To our best knowledge, this is the most complete retrocopies database providing information for dozens of species previously never analyzed in the context of protein-coding genes retroposition. The database is available at http://retrogenedb.amu.edu.pl.
Obstructed Labour with Complicated Presentation and Exomphalos
Authors: D. J. Thompson
Journal: BMJ (1944)

MEDICAL JO5RNALerythrocytes in post-mortem human material, although with Zenker's fluid this can be partially avoided by omitting the acetic acid.The following method is suggested as the best formalin-free fixation for human malarial tissue:Fix in an aqueous solution of 2.5% potassium bichromate and 5%,' mercuric chloride for about 6 hours, and then transfer the tissues directly to aqueous 5% mercuric chloride; in this, fixation continues without the danger of spoiling the common methods of staining, as may regult from the prolonged action of bichromate.This method gives the minimum of lysis of erythrocytes other than by the use of formalin, preserves the malarial pigment, and of course avoids the fallacy of formalin deposit.
Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience
Authors: D. Olmos, H.-T. Arkenau, J.E. Ang, I. Ledaki, G. Attard, C.P. Carden, A.H.M. Reid, R. A'Hern, P.C. Fong, N.B. Oomen, R. Molife, D. Dearnaley, C. Parker, L.W.M.M. Terstappen, J.S. de Bono
Journal: Annals of Oncology (2008)
Cumulative risks and rates of subsequent basal cell carcinomas in the Netherlands
Authors: S.C. Flohil, S. Koljenović, E.R.M. de Haas, L.I.H. Overbeek, E. de Vries, T. Nijsten
Journal: British Journal of Dermatology (2011)

The incidence of multiple basal cell carcinomas (BCCs) is not well documented.To calculate the cumulative risks, rates and risk factors for the development of subsequent histologically confirmed BCCs.For this cohort study the Dutch nationwide network and registry of histopathology and cytopathology (PALGA) was used. The first 2483 patients diagnosed with a first histologically confirmed BCC in the year 2004 were followed for 5years. Multifailure survival models were used to study whether gender or age affected the risk of developing subsequent tumours.During our observational period, the 2483 patients developed a total of 3793 histologically confirmed BCCs. The 5-year cumulative risk of developing one or more subsequent BCCs was 29·2%. Incidence rates were 25,318 per 100,000person-years in the first 6months after first BCC diagnosis, decreasing to 6953 per 100,000person-years after 5years of follow-up. Males compared with females had a 30% [adjusted hazard ratio (HR) 1·30, 95% CI (confidence interval) 1·11-1·53] higher risk of developing multiple BCCs and those aged 65-79years had more than 80% (adjusted HR 1·81, 95% CI 1·37-2·41) higher risk of having subsequent tumours compared with patients younger than 50years.The high incidence rate of subsequent BCCs among patients with a first BCC is highest in the first months after diagnosis of the first BCC but persists long term, indicating that patients with BCC should undergo full-body skin examinations at first presentation and subsequent follow-up visits. Special attention should be paid to males and persons of older age at index lesion.
Emerging Role of RAB GTPases in Cancer and Human Disease
Authors: Kwai W. Cheng, John P. Lahad, Joseph W. Gray, Gordon B. Mills
Journal: Cancer Research (2005)

Abstract Emerging evidence implicates alterations in the RAB small GTPases and their associated regulatory proteins and effectors in multiple human diseases including cancer. We have recently shown that RAB25, located at chromosome 1q22, is amplified at the DNA level and overexpressed at the RNA level in ovarian and breast cancer. These changes correlated with a worsened outcome in both diseases. In addition, enforced expression of RAB25 in both breast and ovarian cancer cells decreased apoptosis and increased proliferation and aggressiveness in vivo, potentially explaining the worsened prognosis. A better understanding of genetic alterations as well as the physiologic and pathophysiologic roles of RAB GTPases may open new opportunities for therapeutic intervention and better outcomes.
Screening for the Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)
Authors: Heather Hampel, Wendy L. Frankel, Edward Martin, Mark Arnold, Karamjit Khanduja, Philip Kuebler, Hidewaki Nakagawa, Kaisa Sotamaa, Thomas W. Prior, Judith Westman, Jenny Panescu, Dan Fix, Janet Lockman, Ilene Comeras, Albert de la Chapelle
Journal: New England Journal of Medicine (2005)

Germ-line mutations in the mismatch-repair genes MLH1, MSH2, MSH6, and PMS2 lead to the development of the Lynch syndrome (hereditary nonpolyposis colorectal cancer), conferring a strong susceptibility to cancer. We assessed the frequency of such mutations in patients with colorectal cancer and examined strategies for molecular screening to identify patients with the syndrome.Patients with a new diagnosis of colorectal adenocarcinoma at the major hospitals in metropolitan Columbus, Ohio, were eligible for the study. Genotyping of the tumor for microsatellite instability was the primary screening method. Among patients whose screening results were positive for microsatellite instability, we searched for germ-line mutations in the MLH1, MSH2, MSH6, and PMS2 genes with the use of immunohistochemical staining for mismatch-repair proteins, genomic sequencing, and deletion studies. Family members of carriers of the mutations were counseled, and those found to be at risk were offered mutation testing.Of 1066 patients enrolled in the study, 208 (19.5 percent) had microsatellite instability, and 23 of these patients had a mutation causing the Lynch syndrome (2.2 percent). Among the 23 probands with the Lynch syndrome, 10 were more than 50 years of age and 5 did not meet the Amsterdam criteria or the Bethesda guidelines for the diagnosis of hereditary nonpolyposis colorectal cancer (including the use of age and family history to identify patients at high risk for the Lynch syndrome). Genotyping for microsatellite instability alone and immunohistochemical analysis alone each failed to identify two probands. In the families of 21 of the probands, 117 persons at risk were tested, and of these, 52 had Lynch syndrome mutations and 65 did not.Routine molecular screening of patients with colorectal adenocarcinoma for the Lynch syndrome identified mutations in patients and their family members that otherwise would not have been detected. These data suggest that the effectiveness of screening with immunohistochemical analysis of the mismatch-repair proteins would be similar to that of the more complex strategy of genotyping for microsatellite instability.
What does it mean to predict one's own utterances?
Authors: Antje S. Meyer, Peter Hagoort
Journal: Behavioral and Brain Sciences (2013)

Abstract Many authors have recently highlighted the importance of prediction for language comprehension. Pickering &amp; Garrod (P&amp;G) are the first to propose a central role for prediction in language production. This is an intriguing idea, but it is not clear what it means for speakers to predict their own utterances, and how prediction during production can be empirically distinguished from production proper.
Isolation and molecular characterization of hepatitis B virus X-protein from a baculovirus expression system
Authors: S Urban, E Hildt, C Eckerskorn, H Sirma, A Kekule, P H Hofschneider
Journal: Hepatology (1997)

The X protein (HBx) of the human Hepatitis B Virus (HBV) is a regulatory protein that exercises a transcriptional activator function on a variety of regulatory elements and is therefore considered to be involved in the development of human hepatocellular carcinoma (HCC). So far, most attempts at elucidating HBx function have been undertaken at the genetic level, reflecting the difficulties in detecting the very low amounts of the protein in infected livers. Consequently, the questions of intracellular localization and posttranslational modification have not yet been completely answered. We therefore constructed recombinant baculoviruses that allowed expression of HBx and the hexa histidine HBx fusion protein HBxHis in insect cells. Cell fractionation experiments revealed that only a minor part of HBx is detectable in a soluble form in the cytosolic fraction, whereas most of the protein forms intracellular aggregates. These results could be confirmed by confocal laser immunofluorescence. The fusion of a hexa-histidine tag to the amino terminus of HBx allowed a rapid one-step purification by metal chelate affinity chromatography. The detailed analysis of purified HBxHis using electrospray ionization mass spectrometry uncovered two major components: the unmodified, monomeric, fully oxidized form with five intramolecular disulfide bridges, and its N-acetylated modification. Additionally, two minor peaks with mass differences of delta m = +80 da suggested that a small fraction of HBx becomes posttranslationally phosphorylated in insect cells. No further modifications could be observed, indicating that only phosphorylation might play a role in a possible posttranslational regulation of this viral activator.
THE LYMPHOCYTE IN NATURAL AND INDUCED RESISTANCE TO TRANSPLANTED CANCER
Authors: James B. Murphy, Waro Nakahara
Journal: The Journal of Experimental Medicine (1920)

Mice immunized against cancer by means of an injection of defibrinated blood show in the germinal centers of the lymphoid organs a marked increase in the numbers of mitotic figures. The increase becomes evident 48 hours after the injection in the majority of instances and reaches its climax at about the 5th day. After this time it subsides, returning to the normal rate about the 10th day. These immunized animals, when inoculated with a cancer graft 10 days after the injection, show a second stimulation of the lymphoid centers similar to the first but more intense in character. This increase in the number of mitotic figures becomes evident as early as 24 hours after the cancer inoculation and persists in a marked degree for a week, after which there is a gradual return to the normal rate. The lymphocytes of the circulating blood during the establishment of the immunity show frequent examples of amitotic division, and many examples of irregular and lobulated nuclei. These changes suggest intensified functional activity. Contrary to the statement of Da Fano, cellular reaction in the subcutaneous tissues of immunized animals is present only in the region infiltrated by the injected cells. This fact becomes conspicuous when the immunizing injection is given intraperitoneally, in which case no cellular accumulations are noted in the loose connective tissues. No constant cellular changes were noted in the bone marrow, thymus or thyroid gland, liver, or kidney of the treated animals.
Rubella-associated arthritis. II. Relationship between circulating immune complex levels and joint manifestations.
Authors: V K Singh, A J Tingle, M Schulzer
Journal: Annals of the Rheumatic Diseases (1986)

The role played by raised circulating immune complex (CIC) levels in the pathogenesis of rubella-associated joint reactions has been assessed during the course of RA 27/3 rubella immunisation and epidemic wild rubella infection. CIC levels were evaluated by C1q microplate enzyme-linked immunosorbent assay (ELISA) and Raji cell ELISA techniques. Mean CIC levels were generally higher both before and after immunisation among individuals developing vaccine-associated arthritis than among those developing arthralgia or no joint symptoms. However, these differences reached statistical significance only with CIC (Raji) techniques at six and 12 weeks postimmunisation. The proportion of individuals within each group having raised CIC levels (greater than or equal to 2SD above normal control values) was also higher in the postvaccine arthritis group, though statistically significant differences were not found with either Raji or C1q techniques. These data do not support a direct role for raised CIC levels in the pathogenesis of rubella-associated arthritis or arthralgia.