tbuckley/cabot-search huggingface dataset:
The nature and consequences of coinfection in humans
Authors: Emily C. Griffiths, Amy B. Pedersen, Andy Fenton, Owen L. Petchey
Journal: Journal of Infection (2011)

Many fundamental patterns of coinfection (multi-species infections) are undescribed, including the relative frequency of coinfection by various pathogens, differences between single-species infections and coinfection, and the burden of coinfection on human health. We aimed to address the paucity of general knowledge on coinfection by systematically collating and analysing data from recent publications to understand the types of coinfection and their effects.From an electronic search to find all publications from 2009 on coinfection and its synonyms in humans we recorded data on i) coinfecting pathogens and their effect on ii) host health and iii) intensity of infection.The most commonly reported coinfections differ from infections causing highest global mortality, with a notable lack of serious childhood infections in reported coinfections. We found that coinfection is generally reported to worsen human health (76% publications) and exacerbate infections (57% publications). Reported coinfections included all kinds of pathogens, but were most likely to contain bacteria.These results suggest differences between coinfected patients and those with single infections, with coinfection having serious health effects. There is a pressing need to quantify the tendency towards negative effects and to evaluate any sampling biases in the coverage of coinfection research.
Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial
Authors: Richard B Lipton, David W Dodick, Stephen D Silberstein, Joel R Saper, Sheena K Aurora, Starr H Pearlman, Robert E Fischell, Patricia L Ruppel, Peter J Goadsby
Journal: The Lancet Neurology (2010)
Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues
Authors: Jochem H Bernink, Charlotte P Peters, Marius Munneke, Anje A te Velde, Sybren L Meijer, Kees Weijer, Hulda S Hreggvidsdottir, Sigrid E Heinsbroek, Nicolas Legrand, Christianne J Buskens, Willem A Bemelman, Jenny M Mjösberg, Hergen Spits
Journal: Nature Immunology (2013)
Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer
Authors: Xiang-hua Liu, Ming Sun, Feng-qi Nie, Ying-bin Ge, Er-bao Zhang, Dan-dan Yin, Rong Kong, Rui Xia, Kai-hua Lu, Jin-hai Li, Wei De, Ke-ming Wang, Zhao-xia Wang
Journal: Molecular Cancer (2014)

Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.
Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes
Authors: Dwight Cordero, Ralph Marcucio, Diane Hu, William Gaffield, Minal Tapadia, Jill A. Helms
Journal: Journal of Clinical Investigation (2004)

One of the most perplexing questions in clinical genetics is why patients with identical gene mutations oftentimes exhibit radically different clinical features. This inconsistency between genotype and phenotype is illustrated in the malformation spectrum of holoprosencephaly (HPE). Family members carrying identical mutations in sonic hedgehog (SHH) can exhibit a variety of facial features ranging from cyclopia to subtle midline asymmetries. Such intrafamilial variability may arise from environmental factors acting in conjunction with gene mutations that collectively reduce SHH activity below a critical threshold. We undertook a series of experiments to test the hypothesis that modifying the activity of the SHH signaling pathway at discrete periods of embryonic development could account for the phenotypic spectrum of HPE. Exposing avian embryos to cyclopamine during critical periods of craniofacial development recreated a continuum of HPE-related defects. The craniofacial malformations included hypotelorism, midfacial hypoplasia, and facial clefting and were not the result of excessive crest cell apoptosis. Rather, they resulted from molecular reprogramming of an organizing center whose activity controls outgrowth and patterning of the mid and upper face. Collectively, these data reveal one mechanism by which the variable expressivity of a disorder such as HPE can be produced through temporal disruption of a single molecular pathway.
Relationship between acetylstrophanthidin-induced aftercontractions and the strength of contraction of canine ventricular myocardium.
Authors: G R Ferrier
Journal: Circulation Research (1977)

Contractile activity was recorded from isolated canine ventricular muscle exposed to acetylstrophanthidin (AS), 0.5 to 2 X 10(-7) g/ml. Development of the positive inotropic effect of AS was accompanied by the appearance of aftercontractions (AC) coupled to the driven responses. The amplitudes of AC increased with the number of preceding beats. Test beats occurring during the ascending limb of AC were potentiated and the potentiation increased with the amplitude of the AC. Beats falling during the descending limb decreased in strength as the amplitude of the AC increased. As eliminated the frequency dependence of restitution. However, staircase phenomena persisted and were then found to be dependent on the phase relationship of each beat to underlying AC. These findings suggest an important role for AC in the inotropic actions of digitalis and in determining strengh-interval relationships of ventricular muscle treated with digitalis.
RECOVERY OF TRANSVERSE STRAIN IN HIGH–STRESS TENDONS FOLLOWING EXERCISE
Authors: Scott Wearing, Simon Locke, Jill Cook, Craig Purdam, James Smeathers, Sue Hooper
Journal: British Journal of Sports Medicine (2013)

Background This study evaluated the time course of recovery of transverse strain in the Achilles and patellar tendons following a bout of resistance exercise. Methods Seventeen healthy adults underwent sonographic examination of the right patellar (n=9) or Achilles (n=8) tendons immediately prior to and following 90 repetitions of weight–bearing exercise. Quadriceps and gastrocnemius exercise were performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the tendon enthesis and transverse strain was repeatedly monitored over a 24 hour recovery period. Results Resistance exercise resulted in an immediate decrease in Achilles (t7=10.6, P&lt;.01) and patellar (t8=8.9, P&lt;.01) tendon thickness, resulting in an average transverse strain of 0.14±0.04 and 0.18±0.05. While the average strain was not significantly different between tendons, older age was associated with a reduced transverse strain response (r=0.63, P&lt;.01). Recovery of transverse strain, in contrast, was prolonged compared with the duration of loading and exponential in nature. The mean primary recovery time was not significantly different between Achilles (6.5±3.2 hours) and patellar (7.1±3.2 hours) tendons and body weight accounted for 62% and 64% of the variation in recovery time, respectively. Discussion Despite structural and biochemical differences between the Achilles and patellar tendons, 1 the mechanisms underlying transverse creep–recovery in vivo appear similar and are highly time dependent. Primary recovery required about 7 hours in healthy tendons, with full recovery requiring up to 24 hours. These in vivo recovery times are similar to those reported for axial creep recovery of the vertebral disc in vitro, 2 and may be used clinically to guide physical activity to rest ratios in healthy adults. Optimal ratios for high–stress tendons in clinical populations, however, remain unknown and require further attention in light of the knowledge gained in this study.
Is exercise effective treatment for osteoarthritis of the knee?
Authors: Robert J Petrella
Journal: British Journal of Sports Medicine (2000)

Objective —To review and determine the effectiveness of exercise treatment in osteoarthritis of the knee. Methods —A computerised literature search of Medline was carried out searching between June 1966 and January 2000. Results —Twenty three randomised controlled trials were identified from the literature. Only three trials were sufficiently powered. Small to moderate beneficial effects of exercise treatment were found for pain, small beneficial effects on disability outcome measures, and moderate to great beneficial effects were observed according to patient global assessment of effect. It was not possible to obtain evidence on the content of exercise interventions, as studies were hampered by lack of attention to proper concealment, reporting of adverse effects, and long term effects of exercise treatment. The lack of standard outcomes measures is also noted. Conclusions —The available evidence indicates beneficial short term effects of exercise treatment in patients with osteoarthritis of the knee. However, the number of available studies is limited, and more research is needed to expand this recommendation. Specifically, additional trials should provide information on adherence, home based interventions, interaction with pharmacological treatments, functional outcomes measures relevant to exercise treatment in these patients, and long term effects. At present, doctors should recommend exercise to all patients with mild/moderate disease. Further study should be encouraged and exercise should be continued to be recommended as a mainstay of non-pharmacological treatment of osteoarthritis of the knee.
Docetaxel–cisplatin might be superior to docetaxel–capecitabine in the first-line treatment of metastatic triple-negative breast cancer
Authors: Y. Fan, B.H. Xu, P. Yuan, F. Ma, J.Y. Wang, X.Y. Ding, P. Zhang, Q. Li, R.G. Cai
Journal: Annals of Oncology (2012)
The Exposure–Response Curve for Ozone and Risk of Mortality and the Adequacy of Current Ozone Regulations
Authors: Michelle L. Bell, Roger D. Peng, Francesca Dominici
Journal: Environmental Health Perspectives (2006)

Time-series analyses have shown that ozone is associated with increased risk of premature mortality, but little is known about how O3 affects health at low concentrations. A critical scientific and policy question is whether a threshold level exists below which O3 does not adversely affect mortality. We developed and applied several statistical models to data on air pollution, weather, and mortality for 98 U.S. urban communities for the period 1987–2000 to estimate the exposure–response curve for tropospheric O3 and risk of mortality and to evaluate whether a "safe" threshold level exists. Methods included a linear approach and subset, threshold, and spline models. All results indicate that any threshold would exist at very low concentrations, far below current U.S. and international regulations and nearing background levels. For example, under a scenario in which the U.S. Environmental Protection Agency's 8-hr regulation is met every day in each community, there was still a 0.30% increase in mortality per 10-ppb increase in the average of the same and previous days' O3 levels (95% posterior interval, 0.15–0.45%). Our findings indicate that even low levels of tropospheric O3 are associated with increased risk of premature mortality. Interventions to further reduce O3 pollution would benefit public health, even in regions that meet current regulatory standards and guidelines.
One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density
Authors: J A Hughes, B G Conry, S M Male, R Eastell
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Inhaled corticosteroids are recognised as the most effective agents in the treatment of asthma. However, concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation. This study measures the effects of two inhaled corticosteroids on bone markers and bone mineral density (BMD) over one year. <h3>METHODS</h3> A one year randomised, prospective, open parallel study comparing inhaled fluticasone propionate (FP), 500 μg twice daily in 30 patients, and budesonide (BUD), 800 μg twice daily in 29 patients, delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma. Biochemical markers of bone turnover (osteocalcin, procollagen type 1 C-terminal propeptide (PICP), immunoreactive free deoxypyridinoline (iFDpd), N-terminal crosslinked telopeptides of type I collagen (NTx)), BMD at the spine and femoral neck, and serum cortisol concentrations were measured at baseline and 12 months later. <h3>RESULTS</h3> There were no significant differences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density. Bone mineral density of the spine increased slightly in both groups over the 12 month period. Serum osteocalcin levels increased from baseline in both treatment groups (FP 16.9%, p = 0.02; BUD 14.3%, p = 0.04). PICP did not differ significantly from baseline. Both markers of bone resorption (iFDpd, NTx) varied considerably with no significant changes after one year. There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months (<i>r</i> = 0.4, p = 0.017). Mean serum cortisol levels remained within the normal range in both groups following treatment. <h3>CONCLUSION</h3> There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD. The change in spine BMD correlated with the increase in osteocalcin. Studies extending over several years are needed to establish whether these findings persist.
THE CRIME OF MENTICIDE
Authors: JOOST A. M. MEERLOO
Journal: American Journal of Psychiatry (1951)

The concept of "menticide" indicates an organized system of judicial perversion and psychological intervention, in which a powerful tyrant transfers his own thoughts and words into the minds and mouths of the victims he plans to destroy or to use for his own propaganda. Modern psychiatry may deliver him several tools for this perversion. Our psychiatric standpoint toward this challenge has to be formulated. Examples of menticide are described and ways of protection indicated.
Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia without producing significant side effects
Authors: M T Cerenzia, L Fiume, W De Bernardi Venon, B Lavezzo, M R Brunetto, A Ponzetto, G Di Stefano, C Busi, A Mattioli, G B Gervasi, F Bonino, G Verme
Journal: Hepatology (1996)

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (approximately 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week period of treatment with the free drug.
Determination of Doxorubicin Levels in Whole Tumor and Tumor Nuclei in Murine Breast Cancer Tumors
Authors: Kimberley M. Laginha, Sylvia Verwoert, Gregory J.R. Charrois, Theresa M. Allen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Pharmacokinetic studies on liposomal drugs have previously measured total drug levels in tumors, which include nonbioavailable drug. However, drugs must be released from liposomes to have activity. We have developed a method for measuring levels of bioavailable (released) doxorubicin in vivo in tumors that will allow therapeutic activity to be correlated with bioavailable drug levels. Experimental Design: Mice orthotopically implanted with mammary carcinoma (4T1) were injected i.v. 10 days after implantation with free doxorubicin or formulations of liposomal doxorubicin with different drug release rates. Tumors were excised at various times after injection, and total tumor doxorubicin levels were determined by acidified isopropanol extraction of whole tumor homogenates. Bioavailable doxorubicin levels were determined by extraction of doxorubicin from isolated tumor nuclei. Results: Free doxorubicin had high levels of bioavailability in tumor tissue; 95% of the total doxorubicin in tumors was bound to nuclear DNA by 24 hours after injection. Administration of Doxil, a slow release liposomal formulation of doxorubicin, gave an area under the time-versus-concentration curve (AUC) for total doxorubicin 7 days after injection that was 87-fold higher than that obtained for free doxorubicin, and 49% of the liposomal doxorubicin was bioavailable. For liposomes with a more rapid doxorubicin release rate, by 7 days after injection, the AUC0-7 days for total doxorubicin was only 14-fold higher than that for free doxorubicin and only 27% of liposomal doxorubicin was bioavailable. Conclusions: This technique allows correlations to be made between drug bioavailability and therapeutic activity and will help in the rational design of drug carriers.
Ultrasound performs better than radiographs
Authors: E. Agricola, C. Arbelot, M. Blaivas, B. Bouhemad, R. Copetti, A. Dean, S. Dulchavsky, M. Elbarbary, L. Gargani, R. Hoppmann, A. W. Kirkpatrick, D. Lichtenstein, A. Liteplo, G. Mathis, L. Melniker, L. Neri, V. E. Noble, T. Petrovic, A. Reissig, J. J. Rouby, A. Seibel, G. Soldati, E. Storti, J. W. Tsung, G. Via, G. Volpicelli
Journal: Thorax (2010)

the absence of published data specifically relating to serotype distribution of pneumococcal pneumonia for children, this is the only up-to-date national reference source available spanning our study time frame. 2 3It provides data on pneumococcal serotype distribution for cases of invasive pneumococcal disease for 2000/1 to 2005/6 and shows the most common serotypes present prior to the introduction of PCV7, which was relevant to our study.We agree that it is not possible to determine fully the exact aetiology of pneumonia from an HES diagnosis, although we have made every attempt to do so.However, we do think the trends in diagnosed pneumonia following the introduction of PCV7 remain of interest.
Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients
Authors: Bart Barlogie, Raman Desikan, Paul Eddlemon, Trey Spencer, Jerome Zeldis, Nikhil Munshi, Ashrof Badros, Maurizio Zangari, Elias Anaissie, Joshua Epstein, John Shaughnessy, Dan Ayers, Dan Spoon, Guido Tricot
Journal: Blood (2001)
The prognostic value of quality of life scores during treatment for oesophageal cancer
Authors: J M Blazeby, S T Brookes, D Alderson
Journal: Gut (2001)

BACKGROUND Quality of life (QL) data are useful to evaluate the effectiveness of treatment. Accumulating evidence suggests that QL data may predict survival. AIMS In this study we investigated if baseline QL scores and changes in QL scores before and after intervention are prognostic for patients with oesophageal cancer. PATIENTS Between 1993 and 1995, 92 consecutive new patients with oesophageal cancer were studied; 89 were followed until death or the end of the study period (survival of seven patients was censored in May 1999). METHODS All patients completed the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC QLQ-C30) and the dysphagia scale of the oesophageal module (EORTC QLQ-OES24) before treatment and at regular intervals throughout the study. Cox's proportional hazards models assessed the impact of baseline QL variables and changes in QL scores on survival. RESULTS Cox's proportional hazards models, adjusting for associations between QL scores, age, and TNM stage, found that physical function at baseline was significantly associated with survival (p=0.002). An increase in physical function score of 10 points corresponded to a 12% reduction in the likelihood of death at any given time (95% confidence intervals 4–18%). Further exploratory multivariable analyses suggested that improvement in emotional function six months after treatment was significantly related to longer survival (p&lt;0.0001). CONCLUSIONS These data provide evidence to support a relationship between patient rated scores of QL and survival. Further understanding of the associations between QL and clinical variables is needed.
If You Could Only Choose Five Psychotropic Medicines: Updating the Interagency Emergency Health Kit
Authors: Mark van Ommeren, Corrado Barbui, Kaz de Jong, Tarun Dua, Lynne Jones, Pau Perez-Sales, Marian Schilperoord, Peter Ventevogel, M. Taghi Yasamy, Shekhar Saxena
Journal: PLoS Medicine (2011)

Mark van Ommeren and colleagues describe how they chose five psychotropic medicines to add to the Interagency Emergency Health Kit, which is a box with medicines and medical supplies designed to help people in major humanitarian emergencies.
Protective Role of Superoxide Dismutase against Diabetogenic Drugs
Authors: Samuel E. Gandy, Maria G. Buse, Rosalie K. Crouch
Journal: Journal of Clinical Investigation (1982)

Copper-zinc superoxide dismutase (SOD) is present in relatively high concentrations in the β-cells of human islets. The activity of the extracted enzyme is partially inhibited upon incubation with the diabetogenic drugs alloxan, streptozotocin, or Vacor. The role of this enzyme in protecting β-cells against chemically induced diabetes was further investigated.