tbuckley/cabot-search huggingface dataset:
Serious motor vehicle crashes: the cost of untreated sleep apnoea
Authors: L J FINDLEY
Journal: Thorax (2001)

Motor vehicle crashes are the leading cause of injury morbidity and mortality in the United States, accounting for more than 40 000 deaths and 6 million injuries every year.1 Sleep related accidents comprise 15–20% of all motor vehicle crashes and result in thousands of serious injuries and death.2 Many of these sleep related accidents could be prevented by treatment of sleep related respiratory disorders.

Sleep apnoea is a common problem and affects at least 4% of working men and 2% of women; it has been reported to occur in 5% of commercial drivers.3 4 Unfortunately, more than 80% of people with sleep apnoea have not yet been diagnosed or treated. Sleep apnoea severely disrupts sleep and causes daytime sleepiness and inattentiveness, as well as cognitive impairment, poor performance on driving simulators, and a motor vehicle crash rate that is 2–4 …
Rigor in Monitoring Clinical Trials Is Ethical
Authors: Steven Piantadosi
Journal: Journal of Clinical Oncology (2008)

Wells focuses our attention on confidentiality of preliminary data in ongoing clinical trials. Based on his views of circumstance, regulation, and ethics, he concludes “. . . the medical and scientific community is being dishonest with patients and research subjects. . . engaging in unethical research practices and undermining ethical standards of research.” Restriction of information has the potential to be a thorny problem. However, current clinical trials principles and practices do not sink to the level of damnation suggested by Wells. In 1865, Claude Bernard said: Man is by nature metaphysical and arrogant. Accordingly, he thinks that the idealistic creations of his mind, which correspond to his feelings, are identical with reality. From this it follows that the experimental method is not really natural to him. . . This view is apposite to the spirit and foundations of Wells’ criticisms. Since the early 1980s when I began as a clinical trialist, we have seen the emergence and wide application of formal administrative and quantitative methods for monitoring trials to minimize errors of interpretation. Clinical trials have permeated nearly every area of medicine, encountering numerous circumstances that require the needs of society to be balanced with the rights of research subjects. Rigorous trial monitoring methods, including restraints on data dissemination, have evolved to improve the balance of needs and the ethics properties of studies rather than to aggravate them. The proper view of such matters hinges on four points: (1) the unreliability of early information, (2) the fact that research subjects are not disadvantaged by a temporary lack of access to preliminary data, (3) the ethics imperatives for good design and investigator competence, and (4) the obligation of physician scientists to acquire definitive information and make it available to everyone. I will return to these topics after a critical review of Wells’ arguments.
Mitochondrial Creatine Kinase
Authors: C. Jack Bark
Journal: JAMA (1980)

A serum creatine kinase (CK) isoenzyme band cathodic to MM, thought to represent mitochondrial CK, was found in eight patients in shock, six of whom died within 12 days. Severe tissue damage appears to be required to release this isoenzyme to detectable levels in the serum.
Strategies to Enhance Epidermal Growth Factor Inhibition: Targeting the Mevalonate Pathway
Authors: Jim Dimitroulakos, Ian A. Lorimer, Glenwood Goss
Journal: Clinical Cancer Research (2006)

Abstract Mevalonate metabolites play an essential role in transducing epidermal growth factor (EGF) receptor (EGFR)–mediated signaling, as several of these metabolites are required for the function of this receptor and the components of its signaling cascades. Thus, the depletion of mevalonate metabolites may have a significant effect on EGFR function. Lovastatin is a specific and potent inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Targeting 3-hydroxy-3-methylglutaryl CoA reductase using lovastatin induces a potent tumor-specific apoptotic response in a variety of tumor types at therapeutically achievable levels of this drug. The effects of lovastatin on EGFR function and the potential combination effects with EGFR tyrosine kinase inhibitors, such as gefitinib, were evaluated. Lovastatin treatment inhibited EGF-induced EGFR autophosphorylation and its downstream signaling cascades by 24 hours. Combining lovastatin and gefitinib showed enhanced inhibition and cooperative cytotoxicity in a variety of cell lines that included all eight squamous cell carcinomas, four non–small cell lung carcinoma, and four colon carcinoma cell lines tested. Isobologram analyses confirmed that this combination was synergistic, inducing a potent apoptotic response. A phase I study has shown the safety and potential clinical benefit of high-dose lovastatin in patients with recurrent squamous cell carcinoma. The use of lovastatin, which is metabolized by CYP3A4, is contraindicated with drugs, such as gefitinib and erlotinib, which are also metabolized by CYP3A4 due to greatly enhanced toxicity. Rosuvastatin, a relatively novel potent mevalonate pathway inhibitor that is not metabolized significantly by CYP3A4, is a more appropriate statin to combine with either erlotinib or gefitinib. The combination of erlotinib and rosuvastatin has been proposed for a phase I/II study in advanced non–small cell lung carcinoma.
DNAM-1 controls NK cell activation via an ITT-like motif
Authors: Zhanguang Zhang, Ning Wu, Yan Lu, Dominique Davidson, Marco Colonna, André Veillette
Journal: The Journal of Experimental Medicine (2015)

DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon recognition of its ligands, CD155 and CD112, DNAM-1 promotes NK cell-mediated elimination of transformed and virus-infected cells. It also has a key role in expansion and maintenance of virus-specific memory NK cells. Herein, the mechanism by which DNAM-1 controls NK cell-mediated cytotoxicity and cytokine production was elucidated. Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. Upon phosphorylation by Src kinases, this motif enabled binding of DNAM-1 to adaptor Grb2, leading to activation of enzymes Vav-1, phosphatidylinositol 3' kinase, and phospholipase C-γ1. It also promoted activation of kinases Erk and Akt, and calcium fluxes. Although, as reported, DNAM-1 promoted adhesion, this function was signal-independent and insufficient to promote cytotoxicity. DNAM-1 signaling was also required to enhance cytotoxicity, by increasing actin polymerization and granule polarization. We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)-like motif coupling DNAM-1 to Grb2 and other downstream effectors.
Invoking narrative transmission in oral societies
Authors: Ileana Benga
Journal: Behavioral and Brain Sciences (2006)

The ethnographic description of story-telling and narrative transmission of cultural facts is an aspect of Locke &amp; Bogin's (L&amp;B's) article that should be amplified. Innate shared gene patrimony is biased by the kinship structure of particular societies and interacts with the transmission of narratives. Trance experiences are another interesting aspect of verbal and agonistic “performances.”
The Clinical Spectrum of Renal Tubular Acidosis
Authors: L L Rocher, R L Tannen
Journal: Annual Review of Medicine (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Are some diets "mass murder"? Mediterranean diet is not to blame for increased carbohydrate intake
Authors: J. D. Spence
Journal: BMJ (2015)

Smith implied that much of the blame for the harmful increase in carbohydrate intake was attributable to Ancel Keys’s promotion of the Cretan Mediterranean diet.1

However, this diet is not a low fat one, being high in beneficial fat (~40% of calories from fat, mainly olive oil)2; low in harmful animal fat and cholesterol; and high in fruits, …
Hyperactive Vasopressin Receptors and Disturbed Water Homeostasis
Authors: Nine V.A.M. Knoers
Journal: New England Journal of Medicine (2005)

Regulation of water homeostasis is of vital importance for all terrestrial organisms. In most mammals, including humans, the maintenance of water balance is critically dependent on water intake, the sensation of thirst, and the regulation of water excretion in the kidney, which is under the control of the antidiuretic hormone arginine vasopressin (AVP).1 In the past decade, our insight into the AVP-mediated renal concentration mechanism has substantially improved with the elucidation of the roles of crucial molecular players in this process. The identification of disease-causing genes in hereditary disorders of water balance has been extremely helpful in identifying these pivotal . . .
Nitrite Reductase Function of Deoxymyoglobin
Authors: Tienush Rassaf, Ulrich Flögel, Christine Drexhage, Ulrike Hendgen-Cotta, Malte Kelm, Jürgen Schrader
Journal: Circulation Research (2007)

Although the primary function of myoglobin (Mb) has been considered to be cellular oxygen storage and supply, recent studies have suggested to classify Mb as a multifunctional allosteric enzyme. In the heart, Mb acts as a potent scavenger of nitric oxide (NO) and contributes to the attenuation of oxidative damage. Here we report that a dynamic cycle exists in which a decrease in tissue oxygen tension drives the conversion of Mb from being an NO scavenger in normoxia to an NO producer in hypoxia. The NO generated by reaction of deoxygenated Mb with nitrite is functionally relevant and leads to a downregulation of cardiac energy status, which was not observed in mice lacking Mb. As a consequence, myocardial oxygen consumption is reduced and cardiac contractility is dampened in wild-type mice. We propose that this pathway represents a novel homeostatic mechanism by which a mismatch between oxygen supply and demand in muscle is translated into the fractional increase of deoxygenated Mb exhibiting enhanced nitrite reductase activity. Thus, Mb may act as an oxygen sensor which through NO can adjust muscle energetics to limited oxygen supply.
A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis*1
Authors: B COMBES
Journal: Hepatology (1995)

One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin (<2 mg/dL vs. 2 mg/dL or greater) and liver histology (stages I, II vs. stages III, IV—Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodioltreated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin <2), but had less effect on laboratory tests in patients with entry serum bilirubin of ≥2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trial was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated with ursodiol tended to develop a treatment failure less frequently than those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients. Major complications of liver disease, progression to liver transplantation or death, occurred in 10.5% and 76.6%, respectively, in patients who had an entry serum bilirubin of <2 or ≥2 mg/dL. The incidence of these complications was comparable in ursodiol- and placebo-treated patients. Treatment failure occurred sooner in placebo than in ursodiol-treated patients in strata 1 and 2 but at the same rate in similarly treated patients in strata 3 and 4. Patients with advanced disease are unlikely to benefit from ursodiol. Trials longer than 2 years will likely be needed to determine whether ursodiol reduces major complications of liver disease in patients with milder disease.
Diabetes and Cancer
Authors: Edward Giovannucci, David M. Harlan, Michael C. Archer, Richard M. Bergenstal, Susan M. Gapstur, Laurel A. Habel, Michael Pollak, Judith G. Regensteiner, Douglas Yee
Journal: Diabetes Care (2010)

Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments.This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis.In addition, key unanswered questions for future research are posed.
Advanced breast cancer incidence following population-based mammographic screening
Authors: P. Autier, M. Boniol, R. Middleton, J.-F. Doré, C. Héry, T. Zheng, A. Gavin
Journal: Annals of Oncology (2011)

Breast cancer mortality is declining in many Western countries. If mammography screening contributed to decreases in mortality, then decreases in advanced breast cancer incidence should also be noticeable.We assessed incidence trends of advanced breast cancer in areas where mammography screening is practiced for at least 7 years with 60% minimum participation and where population-based registration of advanced breast cancer existed. Through a systematic Medline search, we identified relevant published data for Australia, Italy, Norway, Switzerland, The Netherlands, U.K. and the U.S.A. Data from cancer registries in Northern Ireland, Scotland, the U.S.A. (Surveillance, Epidemiology and End Results (SEER), and Connecticut), and Tasmania (Australia) were available for the study. Criterion for advanced cancer was the tumour size, and if not available, spread to regional/distant sites.Age-adjusted annual percent changes (APCs) were stable or increasing in ten areas (APCs of -0.5% to 1.7%). In four areas (Firenze, the Netherlands, SEER and Connecticut) there were transient downward trends followed by increases back to pre-screening rates.In areas with widespread sustained mammographic screening, trends in advanced breast cancer incidence do not support a substantial role for screening in the decrease in mortality.
Genome science and health disparities: a growing success story?
Authors: Charles Rotimi, Daniel Shriner, Adebowale Adeyemo
Journal: Genome Medicine (2013)

Ten years after the completion of the Human Genome Project, researchers are using DNA to shed light on human history and health.A signifi cant fi nding of the Human Genome Project and subsequent spinoff projects is that human populations are considerably more similar than diff erent at the DNA level, yet it is now well recognized that genetic diff erences between ancestral and ethnic groups can have important evolutionary and medical relevance.Here, we refl ect on how scientists are taking advantage of these observations to provide insight into complex social and medical issues, such as health disparities and variable drug response.
Peers call for guaranteed minimum income to lift children out of poverty
Authors: H. Mooney
Journal: BMJ (2010)

The government must introduce minimum income standards in its Child Poverty Bill if it is to succeed in lifting children out of poverty and improve the long term health of the nation.

An amendment to the bill, introduced at the parliamentary committee stage last month in the House of Lords by Ilora Finlay, a cross bencher and immediate past president of the Royal Society of Medicine, calls on the government to take into account recent research that estimates the minimum weekly cost of a healthy diet for pregnant mothers.

The research cited by Baroness Finlay, by the Joseph Rowntree Foundation, found that the minimum amount needed for adequate nutrition is …
The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
Authors: Vijay A K Rathinam, Zhaozhao Jiang, Stephen N Waggoner, Shruti Sharma, Leah E Cole, Lisa Waggoner, Sivapriya Kailasan Vanaja, Brian G Monks, Sandhya Ganesan, Eicke Latz, Veit Hornung, Stefanie N Vogel, Eva Szomolanyi-Tsuda, Katherine A Fitzgerald
Journal: Nature Immunology (2010)
Tumor-Targeted Nanomedicines: Enhanced Antitumor Efficacy <i>In vivo</i> of Doxorubicin-Loaded, Long-Circulating Liposomes Modified with Cancer-Specific Monoclonal Antibody
Authors: Tamer A. ElBayoumi, Vladimir P. Torchilin
Journal: Clinical Cancer Research (2009)

The efficacy of drug delivery systems can be enhanced by making them target specific via the attachment of various ligands. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded, long-circulating, polyethylene glycol-coated liposomes (Doxil, ALZA Corp.) by coupling to their surface the anticancer monoclonal antibody (mAb) 2C5 with nucleosome-restricted activity that can recognize the surface of various tumors but not normal cells and specifically targets pharmaceutical carriers to tumor cells in vitro and in vivo. Following earlier in vitro results with various cancer cell lines, the mAb 2C5 liposomes were studied in vivo versus plain and nonspecific-IgG liposomes.Antibody coupling to Doxil was done via the "postinsertion" technique. Using (111)In-labeled liposomes, the tissue biodistribution and pharmacokinetic profile were studied, as well as their accumulation in tumors in mice, followed by the whole-body gamma-scintigraphic imaging. Therapeutic efficacy of mAb 2C5-targeted Doxil versus nonspecific IgG-modified and original Doxil controls was followed by registering live tumor growth and determining tumor weights upon mice sacrifice.mAb 2C5-targeted liposomes showed enhanced accumulation in tumors, and the in vivo therapeutic activity of the mAb 2C5-Doxil treatment was found to be significantly superior, resulting in final tumor weights of only 25% to 40% compared with all Doxil control treatments, when tested against the s.c. primary murine tumors of 4T1 and C26 and human PC3 tumor in nude mice.Our results showed the remarkable capability of 2C5-targeted Doxil to specifically deliver its cargo into various tumors, significantly increasing the efficacy of therapy.
Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy
Authors: A. Losi, C. Longo, A.M. Cesinaro, E. Benati, A. Witkowski, P. Guitera, G. Pellacani
Journal: British Journal of Dermatology (2013)

Amelanotic melanoma represents a diagnostic challenge both clinically and dermoscopically. Few studies based on case series have explored the possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic melanoma.To validate a new confocal feature, named hyporeflective pagetoid cells (HPCs), for the diagnosis of amelanotic melanoma.A group of 20 amelanotic melanomas and a control population of nonpigmented melanocytic naevi (10), hypo/nonpigmented nonmelanocytic lesions (20) and pigmented melanomas (20), imaged by RCM, were retrospectively evaluated. The presence of HPCs and other diagnosis-specific confocal features was assessed and correlated with histopathology.HPCs were present, and usually abundant, in the majority of amelanotic melanomas (85%). As expected, they were also observed in Spitz naevi. On histopathology, they were correlated with pagetoid infiltration of hypomelanotic melanocytes in all melanocytic lesions. Few nonmelanocytic lesions (three squamous cell carcinomas, two seborrhoeic keratoses and one basal cell carcinoma) showed the presence of HPCs. In these cases, they corresponded to enlarged or dyskeratotic keratinocytes by histopathology.The identification of HPCs in the epidermis is a new parameter that is frequently found in amelanotic melanoma. Possible confounders are represented by atypical keratinocytes that can be present in nonmelanocytic lesions. However, the whole architecture and the presence of additional diagnostic criteria should be considered in order to obtain a correct diagnosis.
Visuospatial Processing and the Function of Prefrontal-Parietal Networks in Autism Spectrum Disorders: A Functional MRI Study
Authors: Timothy J. Silk, Nicole Rinehart, John L. Bradshaw, Bruce Tonge, Gary Egan, Michael W. O’Boyle, Ross Cunnington
Journal: American Journal of Psychiatry (2006)

Individuals with autism spectrum disorders typically have normal visuospatial abilities but impaired executive functioning, particularly in abilities related to working memory and attention. The aim of this study was to elucidate the functioning of frontoparietal networks underlying spatial working memory processes during mental rotation in persons with autism spectrum disorders.Seven adolescent males with normal IQ with an autism spectrum disorder and nine age- and IQ-matched male comparison subjects underwent functional magnetic resonance imaging scans while performing a mental rotation task.The autism spectrum disorders group showed less activation in lateral and medial premotor cortex, dorsolateral prefrontal cortex, anterior cingulate gyrus, and caudate nucleus.The finding of less activation in prefrontal regions but not in parietal regions supports a model of dysfunction of frontostriatal networks in autism spectrum disorders.
Do Clozapine and Risperidone Affect Social Competence and Problem Solving?
Authors: Alan S. Bellack, Nina R. Schooler, Stephen R. Marder, John M. Kane, Clayton H. Brown, Ye Yang
Journal: American Journal of Psychiatry (2004)

The purpose of this investigation was to evaluate the effects of clozapine and risperidone on social skill and problem solving in patients with schizophrenia.The Wisconsin Card Sorting Test and the Maryland Assessment of Social Competence were administered at baseline, week 17, and week 29 of a multisite clinical trial.Despite evidence of clinical improvement with both medications, there was virtually no medication effect on either social competence or problem solving.These findings underscore the circumscribed nature of symptomatic improvement in the broader spectrum of clinical outcomes and suggest that new-generation medications may not be expected to produce substantial changes in social role functioning or social problem-solving capacity in the community. The generalizability of the findings should be viewed cautiously because of the low power of this trial, and replication is warranted.