tbuckley/cabot-search huggingface dataset:
Alcohol and cholera
Authors: Janet S Guthrie, Darrel O Ho-Yen
Journal: Journal of the Royal Society of Medicine (2011)

‘Fear and humour in the art of cholera’ was stimulating. It stated ‘“cholera brandy” was one of the many unproven cures or preventive measures against the disease’.1 In 1832, the Inverness Board of Health had advocated ‘great moderation in the use of fermented and spirituous liquors’. Recently, we investigated this matter and tested the effects of alcohol on the survival of Vibrio cholerae in gin, red wine and ethanol.2

We found V. cholerae did not survive in 20% gin at 1 hour, 18.75% gin at 6 hours and 15% gin at 26 hours. Similar survival times were found with the equivalent concentrations of ethanol.3 The results were much more dramatic with red wine, V. cholerae did not survive in 6.25% wine at 30 min;2 its bactericidal effect may be attributable to polyphenols.4 Nevertheless, in 1832 the incidence of cholera was seen to be higher in the heavy drinker than among the general population.5 Some saw this higher incidence as Divine retribution.5 However, the scientific explanation, unknown in 1832, is that the heavy drinker may have reduced gastric acidity6 and the infectious dose of V. cholerae will be lower than for those with normal chlorhydria. Conversely, the moderate consumption of wine and beer stimulate the production of gastric acid and may have a protective effect against cholera.6

Fear and humour may be helped by alcohol but it can also reduce infection with cholera.
Series of Exon-Skipping Events in the Elastic Spring Region of Titin as the Structural Basis for Myofibrillar Elastic Diversity
Authors: Alexandra Freiburg, Karoly Trombitas, Wolfgang Hell, Olivier Cazorla, Francoise Fougerousse, Thomas Centner, Bernhard Kolmerer, Christian Witt, Jaques S. Beckmann, Carol C. Gregorio, Henk Granzier, Siegfried Labeit
Journal: Circulation Research (2000)

Abstract —Titins are megadalton-sized filamentous polypeptides of vertebrate striated muscle. The I-band region of titin underlies the myofibrillar passive tension response to stretch. Here, we show how titins with highly diverse I-band structures and elastic properties are expressed from a single gene. The differentially expressed tandem-Ig, PEVK, and N2B spring elements of titin are coded by 158 exons, which are contained within a 106-kb genomic segment and are all subject to tissue-specific skipping events. In ventricular heart muscle, exons 101 kb apart are joined, leading to the exclusion of 155 exons and the expression of a 2.97-MDa cardiac titin N2B isoform. The atria of mammalian hearts also express larger titins by the exclusion of 90 to 100 exons (cardiac N2BA titin with 3.3 MDa). In the soleus and psoas skeletal muscles, different exon-skipping pathways produce titin transcripts that code for 3.7- and 3.35-MDa titin isoforms, respectively. Mechanical and structural studies indicate that the exon-skipping pathways modulate the fractional extensions of the tandem Ig and PEVK segments, thereby influencing myofibrillar elasticity. Within the mammalian heart, expression of different levels of N2B and N2BA titins likely contributes to the elastic diversity of atrial and ventricular myofibrils.
The Genetics of Mood Disorders
Authors: Jennifer Y.F. Lau, Thalia C. Eley
Journal: Annual Review of Clinical Psychology (2009)

Studying the genetics of mood disorders has never been more exciting. We have moved rapidly from establishing the genetic basis of depression to asking questions about how genes are expressed. This has been made possible by the capacity to collect and sequence DNA for large samples cheaply. But "multidisciplinary" approaches investigating interrelationships between risk factors have also been increasingly adopted, encouraging collaborations between those studying genes and those studying the brain, cognition, and/or the social environment. In this review, we first describe findings from quantitative and molecular studies investigating the genetic basis of depression. Second, we present overviews of three hot topics of genetic research: gene-environment interplay, which considers how genetic factors shape exposure and responses toward the social environment; endophenotypic research, which identifies neurophysiological and psychological mediators of genetic risk; and epigenetics, which explain how early environments can foster changes in gene expression, altering subsequent emotional development.
Mesothelin confers pancreatic cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and IL-6/Mcl-1 overexpression
Authors: Uddalak Bharadwaj, Christian Marin-Muller, Min Li, Changyi Chen, Qizhi Yao
Journal: Molecular Cancer (2011)

Abstract Background Previous studies showed that mesothelin (MSLN) plays important roles in survival of pancreatic cancer (PC) cells under anchorage dependent/independent conditions as well as resistance to chemotherapy. The recent success of intratumorally-injected adeno-encoded, chemo/radiation-inducible-promoter driven hTNF-α, (TNFerade) + gemcitabine in pre-clinical models of PC have renewed interest in use of TNF-α as a therapeutic component. To help find additional factors which might affect the therapy, we examined the resistance of MSLN-overexpressing pancreatic cancer cell lines to TNF-α-induced growth inhibition/apoptosis. Methods Stable MSLN overexpressing MIA PaCa-2 cells (MIA-MSLN), stable MSLN-silenced AsPC-1 cells (AsPC-shMSLN) and other pancreatic cells (MIA-PaCa2, Panc 28, Capan-1, BxPC3, PL 45, Hs 766T, AsPC-1, Capan-2, Panc 48) were used. NF-κB activation was examined by western blots and luciferase reporter assay. TNF-α induced growth inhibition/apoptosis was measured by MTT, TUNEL assay and caspase activation. IL-6 was measured using luminex based assay. Results Compared to low endogenous MSLN-expressing MIA PaCa-2 and Panc 28 cells, high endogenous MSLN-expressing Capan-1, BxPC3, PL 45, Hs 766T, AsPC-1, Capan-2, Panc 48 cells were resistant to TNF-α induced growth inhibition. Stable MSLN overexpressing MIA-PaCa2 cells (MIA-MSLN) were resistant to TNF-α-induced apoptosis while stable MSLN-silenced AsPC1 cells (AsPC-shMSLN) were sensitive. Interestingly, TNF-α-treated MIA-MSLN cells showed increased cell cycle progression and cyclin A induction, both of which were reversed by caspase inhibition. We further found that MIA-MSLN cells showed increased expression of anti-apoptotic Bcl-XL and Mcl-1; deactivated (p-Ser 75 ) BAD, and activated (p-Ser 70 ) Bcl-2. Constitutively activated NF-κB and Akt were evident in MIA-MSLN cells that could be suppressed by MSLN siRNA with a resultant increase in sensitivity of TNF-α induced apoptosis. Blocking NF-κB using IKK inhibitor wedelolactone also increased sensitivity to TNF-α-mediated cytotoxicity with concomitant decrease in Mcl-1. Blocking Akt using PI3K inhibitor also had a likewise effect presumably affecting cell cycle. MIA-MSLN cells produced increased IL-6 and were increased furthermore by TNF-α treatment. SiRNA-silencing of IL-6 increased TNF-α sensitivity of MIA-MSLN cells. Conclusions Our study delineates a MSLN-Akt-NF-κB-IL-6-Mcl-1 survival axis that may be operative in PC cells, and might help cancer cells' survival in the highly inflammatory milieu evident in PC. Further, for the success of TNFerade + gemcitabine to be successful, we feel the simultaneous inhibition of components of this axis is also essential.
Peer-review practices of psychological journals: The fate of published articles, submitted again
Authors: Douglas P. Peters, Stephen J. Ceci
Journal: Behavioral and Brain Sciences (1982)

Abstract A growing interest in and concern about the adequacy and fairness of modern peer-review practices in publication and funding are apparent across a wide range of scientific disciplines. Although questions about reliability, accountability, reviewer bias, and competence have been raised, there has been very little direct research on these variables. The present investigation was an attempt to study the peer-review process directly, in the natural setting of actual journal referee evaluations of submitted manuscripts. As test materials we selected 12 already published research articles by investigators from prestigious and highly productive American psychology departments, one article from each of 12 highly regarded and widely read American psychology journals with high rejection rates (80%) and nonblind refereeing practices. With fictitious names and institutions substituted for the original ones (e.g., Tri-Valley Center for Human Potential), the altered manuscripts were formally resubmitted to the journals that had originally refereed and published them 18 to 32 months earlier. Of the sample of 38 editors and reviewers, only three (8%) detected the resubmissions. This result allowed nine of the 12 articles to continue through the review process to receive an actual evaluation: eight of the nine were rejected. Sixteen of the 18 referees (89%) recommended against publication and the editors concurred. The grounds for rejection were in many cases described as “serious methodological flaws.” A number of possible interpretations of these data are reviewed and evaluated.
Milia and cutaneous leishmaniasis
Authors: P. Del Giudice
Journal: British Journal of Dermatology (2007)

Journal Article Milia and cutaneous leishmaniasis Get access P. Del Giudice P. Del Giudice Dermatology and Infectious Disease Department, Hôpital Bonnet, Fréjus, France E‐mail: del‐giudice‐p@chi‐frejus‐saint‐raphael.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 5, 1 May 2007, Page 1088, https://doi.org/10.1111/j.1365-2133.2007.07815.x Published: 01 May 2007
Atrial natriuretic factor-induced systemic vasoconstriction in conscious dogs, rats, and monkeys.
Authors: Y T Shen, M A Young, J Ohanian, R M Graham, S F Vatner
Journal: Circulation Research (1990)

This study addresses the hypothesis that atrial natriuretic factor (ANF) is a primary vasodilator, which reduces arterial pressure directly and increases total peripheral resistance secondarily by reflex mechanisms. The effects of 30-minute infusions of ANF (0.3 micrograms/kg/min i.v.) were examined in conscious dogs, rats, and monkeys before and after ganglionic blockade with hexamethonium. In seven intact, conscious dogs, ANF reduced mean arterial pressure by 7 +/- 1% and cardiac output by 19 +/- 3% and increased total peripheral resistance by 15 +/- 3%. After ganglionic blockade, ANF reduced mean arterial pressure by 7 +/- 2% but still increased total peripheral resistance by 15 +/- 3%. Similar results were observed in four dogs with total cardiac denervation and in six dogs with arterial baroreceptor denervation. Furthermore, in two dogs, combined ganglionic and alpha 1-adrenoceptor blockades failed to alter the rise in total peripheral resistance observed with ANF. In six intact, conscious rats, ANF reduced mean arterial pressure by 8 +/- 2% and cardiac output by 27 +/- 2% and increased total peripheral resistance by 27 +/- 5%. After ganglionic blockade, ANF still increased total peripheral resistance by 13 +/- 3%. In six intact, conscious monkeys, ANF reduced mean arterial pressure by 14 +/- 2% and cardiac output by 26 +/- 3% and increased total peripheral resistance by 17 +/- 3%. However, after ganglionic blockade. ANF decreased total peripheral resistance by 11 +/- 2%. These data provide evidence for a fundamental species difference in the vascular actions of ANF. In conscious dogs, ANF elicits "direct" vasoconstriction, which increases total peripheral resistance, even in the presence of denervation of reflexes or autonomic blockade. In conscious rats, ANF elicits both direct and reflexly mediated vasoconstriction. In conscious monkeys, although a component of direct vasoconstriction may also be present, the most prominent component appears to be reflexly mediated, since it was abolished by ganglionic blockade.
Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial
Authors: Jianping Weng, Yanbing Li, Wen Xu, Lixin Shi, Qiao Zhang, Dalong Zhu, Yun Hu, Zhiguang Zhou, Xiang Yan, Haoming Tian, Xingwu Ran, Zuojie Luo, Jing Xian, Li Yan, Fangping Li, Longyi Zeng, Yanming Chen, Liyong Yang, Sunjie Yan, Juan Liu, Ming Li, Zuzhi Fu, Hua Cheng
Journal: The Lancet (2008)
Predominant, Severe Right Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy
Authors: R. Krecki, P. Lipiec, D. Piotrowska-Kownacka, L. Chrzanowski, L. Krolicki, J. Drozdz, M. Krzeminska-Pakula, J.D. Kasprzak
Journal: Circulation (2007)
Molecular similarities between the Qa-2 alloantigen and other gene products of the 17th chromosome of the mouse.
Authors: J Michaelson, L Flaherty, E Vitetta, M D Poulik
Journal: The Journal of Experimental Medicine (1977)

The alloantigen Qa-2, whose gene is located on the 17th chromosome between H-2D and Tla, is identified as a molecule of 43,000 daltons which is associated with beta 2-microglobulin. Qa-2 comprises approximately 0.15% of the iodinateable cell surface protein of lymph node cells. Sequential precipitations demonstrated that Qa-2 is distinct from H-2D and H-2K molecules.
Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis
Authors: Akari Suzuki, Ryo Yamada, Xiaotian Chang, Shinya Tokuhiro, Tetsuji Sawada, Masakatsu Suzuki, Miyuki Nagasaki, Makiko Nakayama-Hamada, Reimi Kawaida, Mitsuru Ono, Masahiko Ohtsuki, Hidehiko Furukawa, Shinichi Yoshino, Masao Yukioka, Shigeto Tohma, Tsukasa Matsubara, Shigeyuki Wakitani, Ryota Teshima, Yuichi Nishioka, Akihiro Sekine, Aritoshi Iida, Atsushi Takahashi, Tatsuhiko Tsunoda, Yusuke Nakamura, Kazuhiko Yamamoto
Journal: Nature Genetics (2003)
Palmar fasciitis and polyarthritis as a paraneoplastic syndrome associated with tubal carcinoma: a case report
Authors: D Denschlag, E Riener, P Vaith, C Tempfer, C Keck
Journal: Annals of the Rheumatic Diseases (2004)

<h3>Abstract</h3> Homologous mesophilic and thermophilic enzymes with identical folds often exhibit different thermal and kinetic behaviors. Understanding how enzyme sequence encodes catalytic activity at functionally optimal temperatures is a fundamental problem in biophysics. Recently it was shown that the residues that tune catalytic activities of thermophilic/mesophilic variants of the C-terminal domain of bacterial Enzyme I (EIC) are largely localized within disordered loops, offering a model system with which to investigate this phenomenon. In this work, we employ molecular dynamics simulations and mutagenesis experiments to reveal a mechanism of sequence-dependent catalytic temperature tuning of EIC homologs. We find that a network of contacts in the catalytic loops is particularly sensitive to changes in temperature, with some contacts exhibiting distinct linear or parabolic temperature-dependent trends. Moreover, these trends define structurally clustered dynamical modes and can distinguish regions that tend toward order or disorder at higher temperatures. Assaying several thermophilic EIC mutants, we show that complementary mesophilic mutations to the most temperature-sensitive positions exhibit the most enhanced activity while mutations to relatively temperature insensitive positions exhibit the least enhanced activities. These results provide a mechanistic explanation of sequence-dependent temperature tuning and offer a computational method for rational enzyme modification. <h3>Significance</h3> Temperature affects the catalytic rates of all enzymes. The impact of temperature on the catalytic activity of an enzyme, however, is convoluted from contributions of protein sequence, structure and dynamics. As such, understanding and designing the molecular features of enzymes which tune catalytic rates at different temperatures remains a fundamental challenge in biophysics. In this work we have employed molecular simulations and mutagenesis experiments to reveal the temperature tuning mechanism of mesophilic and thermophilic homologues of the C domain of bacterial Enzyme l. We find that enzymes can be tuned to their physiological temperatures through a network of temperature sensitive residue contacts localized in the disordered loops. Furthermore, we find that among temperature sensitive contacts some exhibit linear and others parabolic dependence on temperature. These clues offer a promising physics-based approach for tuning enzyme activity.
Receptor-Mediated DNA-Targeted Photoimmunotherapy
Authors: Tom C. Karagiannis, Pavel N. Lobachevsky, Brenda K.Y. Leung, Jonathan M. White, Roger F. Martin
Journal: Cancer Research (2006)

Abstract We show the efficacy of a therapeutic strategy that combines the potency of a DNA-binding photosensitizer, UVASens, with the tumor-targeting potential of receptor-mediated endocytosis. The photosensitizer is an iodinated bibenzimidazole, which, when bound in the minor groove of DNA and excited by UVA irradiation, induces cytotoxic lesions attributed to a radical species resulting from photodehalogenation. Although reminiscent of photochemotherapy using psoralens and UVA irradiation, an established treatment modality in dermatology particularly for the treatment of psoriasis and cutaneous T-cell lymphoma, a critical difference is the extreme photopotency of the iodinated bibenzimidazole, ∼1,000-fold that of psoralens. This feature prompted consideration of combination with the specificity of receptor-mediated targeting. Using two in vitro model systems, we show the UVA cytotoxicity of iodo ligand/protein conjugates, implying binding of the conjugate to cell receptors, internalization, and degradation of the conjugate-receptor complex, with release and translocation of the ligand to nuclear DNA. For ligand-transferrin conjugates, phototoxicity was inhibited by coincubation with excess native transferrin. Receptor-mediated UVA-induced cytotoxicity was also shown with the iodo ligand conjugate of an anti-human epidermal growth factor receptor monoclonal antibody, exemplifying the potential application of the strategy to other cancer-specific targets to thus improve the specificity of phototherapy of superficial lesions and for extracorporeal treatments. (Cancer Res 2006; 66(21): 10548-52)
Reassessing the status of antiphospholipid syndrome in systemic lupus erythematosus.
Authors: J L Vianna, H J Haga, P Tripathi, R Cervera, M A Khamashta, G R Hughes
Journal: Annals of the Rheumatic Diseases (1992)

The antiphospholipid syndrome was initially described in 1986. To reassess the validity of antiphospholipid antibodies in systemic lupus erythematosus (SLE), 95 patients with SLE were studied. Their antiphospholipid antibody profile was analysed and correlated with clinical findings such as thrombosis, abortions, or thrombocytopenia. A low prevalence of these antibodies was found (13 patients; 14%) with a high specificity for thrombosis (92%) and abortions (92%). The importance of anticardiolipin antibodies as a risk factor for thrombosis or abortions, or both, in patients with SLE is reaffirmed by this work.
Early Trends Among Seven Recommendations From the Choosing Wisely Campaign
Authors: Alan Rosenberg, Abiy Agiro, Marc Gottlieb, John Barron, Peter Brady, Ying Liu, Cindy Li, Andrea DeVries
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> The Choosing Wisely campaign consists of more than 70 lists produced by specialty societies of medical practices or procedures of minimal clinical benefit to patients in most situations, with recommendations regarding judicious use. <h3>Objective</h3> To quantify the frequency and trends of some of the earliest Choosing Wisely recommendations using nationwide commercial health plan population-level data. <h3>Design, Setting, and Participants</h3> Retrospective analysis of claims data for members of Anthem-affiliated commercial health plans. The low-value services selected were (1) imaging tests for uncomplicated headache; (2) cardiac imaging without history of cardiac conditions; (3) low back pain imaging without red-flag conditions; (4) preoperative chest x-rays with unremarkable history and physical examination results; (5) human papillomavirus testing for women younger than 30 years; (6) use of antibiotics for acute sinusitis; and (7) use of prescription nonsteroidal anti-inflammatory drugs (NSAIDs) for members with hypertension, heart failure, or chronic kidney disease. <h3>Main Outcomes and Measures</h3> The number of members with medical and/or pharmacy claims for the included low-value services was assessed quarterly over a 2- to 3-year span through 2013. Trend changes in recommendations were evaluated across all quarters using Poisson regression with denominators as offsets. <h3>Results</h3> Two services had declines: Use of imaging for headache decreased from 14.9% to 13.4% (trend estimate, 0.99 [95% CI, 0.98-0.99];<i>P</i> &lt; .001), and cardiac imaging decreased from 10.8% to 9.7% (trend estimate, 0.99 [95% CI, 0.99-0.99];<i>P</i> &lt; .001). Two services had increases: Use of NSAIDs in select conditions increased from 14.4% to 16.2% (trend estimate, 1.02 [95% CI, 1.01-1.02];<i>P</i> &lt; .001), and human papillomavirus testing in younger women increased from 4.8% to 6.0% (trend estimate, 1.01 [95% CI, 1.00-1.01];<i>P</i> &lt; .001). Use of antibiotics for sinusitis remained stable (0.8% decrease from 84.5% to 83.7%; trend estimate, 1.00 [95% CI, 1.00-1.00];<i>P</i> = .16). Use of preoperative chest x-rays (0.2% decrease, ending utilization 91.5%; trend estimate, 1.00 [95% CI, 1.00-1.00];<i>P</i>= .70) and imaging for low back pain (53.7% utilization throughout study;<i>P</i>= .71) remained high with no statistically significant changes. <h3>Conclusions and Relevance</h3> For this population-level analysis of 7 low-value services analyzed, changes were modest but showed a desirable decrease for 2 recommendations (imaging for headache, cardiac imaging for low-risk patients). The effect sizes were marginal, however, and although 4 of the 7 lists had statistically significant changes—unsurprising given the large sample size—the clinical significance is uncertain. These results suggest that additional interventions are necessary for wider implementation of Choosing Wisely recommendations.
Activation of TAK1 by MYD88 L265P drives malignant B-cell Growth in non-Hodgkin lymphoma
Authors: S M Ansell, L S Hodge, F J Secreto, M Manske, E Braggio, T Price-Troska, S Ziesmer, Y Li, S H Johnson, S N Hart, J-P A Kocher, G Vasmatzis, A Chanan-Kahn, M Gertz, R Fonseca, A Dogan, J R Cerhan, A J Novak
Journal: Blood Cancer Journal (2014)

Massively parallel sequencing analyses have revealed a common mutation within the MYD88 gene (MYD88L265P) occurring at high frequencies in many non-Hodgkin lymphomas (NHLs) including the rare lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia (WM). Using whole-exome sequencing, Sanger sequencing and allele-specific PCR, we validate the initial studies and detect the MYD88L265P mutation in the tumor genome of 97% of WM patients analyzed (n=39). Due to the high frequency of MYD88 mutation in WM and other NHL, and its known effects on malignant B-cell survival, therapeutic targeting of MYD88 signaling pathways may be clinically useful. However, we are lacking a thorough characterization of the role of intermediary signaling proteins on the biology of MYD88L265P-expressing B cells. We report here that MYD88L265P signaling is constitutively active in both WM and diffuse large B-cell lymphoma cells leading to heightened MYD88L265P, IRAK and TRAF6 oligomerization and NF-κB activation. Furthermore, we have identified the signaling protein, TAK1, to be an essential mediator of MYD88L265P-driven signaling, cellular proliferation and cytokine secretion in malignant B cells. Our studies highlight the biological significance of MYD88L265P in NHL and reveal TAK1 inhibition to be a potential therapeutic strategy for the treatment of WM and other diseases characterized by MYD88L265P.