tbuckley/cabot-search huggingface dataset:
Activation of Protein Kinases in Chronically Hypoxic Infant Human and Rabbit Hearts
Authors: Parvaneh Rafiee, Yang Shi, Xiangrong Kong, Kirkwood A. Pritchard, James S. Tweddell, S. Bert Litwin, Kathleen Mussatto, Robert D. Jaquiss, Jidong Su, John E. Baker
Journal: Circulation (2002)

Background — Many infants who undergo heart surgery have a congenital cyanotic defect in which the heart is chronically perfused with hypoxic blood. However, the signaling pathways by which infant hearts adapt to chronic hypoxia and resist subsequent surgical ischemia is unknown. Method and Results — We determined the activation and translocation of protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAP kinases) in 15 infants with cyanotic (Sa o 2 &lt;85%) or acyanotic (Sa o 2 &gt;95%) heart defects undergoing surgical repair and in 80 rabbits raised from birth in a hypoxic (Sa o 2 &lt;85%) or normoxic (Sa o 2 &gt;95%) environment. Tissues from infant human and rabbit hearts were processed for Western and in vitro kinase analysis. In human infants with cyanotic heart defects, PKCε, p38 MAP kinase, and JUN kinase but not p42/44 MAP kinase were activated and translocated from the cytosolic to the particulate fraction compared with acyanotic heart defects. In rabbit infants there was a parallel response for PKCε, p38 MAP kinase, and JUN kinase similar to humans. In infant rabbit hearts inhibition of PKCε with chelerythrine, p38 MAP kinase, with SB203580 and JUN kinase with curcumin abolished the cardioprotective effects of chronic hypoxia but had no effects on normoxic hearts. Conclusions — Infant human and rabbit hearts adapt to chronic hypoxia through activation of PKCε, p38 MAP kinase, and JUN kinase signal transduction pathways. These pathways may be responsible for cardioprotection in the chronically hypoxic infant rabbit heart.
Cromolyn Sodium for Insulin-Induced Lipoatrophy: Old Drug, New Use
Authors: Eng-Joo Phua, Ximena Lopez, Julia Ramus, Allison B. Goldfine
Journal: Diabetes Care (2013)

Local insulin-induced lipoatrophy, an immune-mediated loss of subcutaneous adipose tissue at insulin administration sites, is now a rare complication of insulin therapy in patients with diabetes. Lipoatrophy incidence, previously noted in 10–55% of patients using animal-derived insulins (1), declined considerably with the advent of and improved purity of modern insulins. Yet, it continues to be reported with insulin analogs (2,3) and poses a clinical challenge owing to erratic insulin absorption at affected areas and distressing cosmetic issues.

We previously demonstrated increased degranulating tryptase/chymase-positive mast cells in biopsies from insulin-induced lipoatrophic sites and reported that topical cromolyn sodium (prepared with 4% cromolyn sodium in petrolatum solvent for topical administration twice daily to affected areas) was efficacious therapy in a small series (4). Since this report, we were contacted by 34 health care providers, caregivers, and patients worldwide, to whom we administered surveys to …
miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
Authors: Christine Esau, Scott Davis, Susan F. Murray, Xing Xian Yu, Sanjay K. Pandey, Michael Pear, Lynnetta Watts, Sheri L. Booten, Mark Graham, Robert McKay, Amuthakannan Subramaniam, Stephanie Propp, Bridget A. Lollo, Susan Freier, C. Frank Bennett, Sanjay Bhanot, Brett P. Monia
Journal: Cell Metabolism (2006)
A Systematic Examination of the Citation of Prior Research in Reports of Randomized, Controlled Trials
Authors: Karen A. Robinson, Steven N. Goodman
Journal: Annals of Internal Medicine (2011)

Background: A randomized, controlled trial (RCT) should not be started or interpreted without accounting for evidence from preceding RCTs addressing the same question. Research has suggested that evidence from prior trials is often not accounted for in reports of subsequent RCTs. Objective: To assess the extent to which reports of RCTs cite prior trials studying the same interventions. Design: Meta-analyses published in 2004 that combined 4 or more trials were identified; within each meta-analysis, the extent to which each trial report cited the trials that preceded it by more than 1 year was assessed. Measurements: The proportion of prior trials that were cited (prior research citation index), the proportion of the total participants from prior trials that were in the cited trials (sample size citation index), and the absolute number of trials cited were calculated. Results: 227 meta-analyses were identified, comprising 1523 trials published from 1963 to 2004. The median prior research citation index was 0.21 (95% CI, 0.18 to 0.24), meaning that less than one quarter of relevant reports were cited. The median sample size citation index (0.24 [CI, 0.21 to 0.27]) was similar, suggesting that larger trials were not selectively cited. Of the 1101 RCTs that had 5 or more prior trials to cite, 254 (23%) cited no prior RCTs and 257 (23%) cited only 1. The median number of prior cited trials was 2, which did not change as the number of citable trials increased. The mean number of preceding trials cited by trials published after 2000 was 2.4, compared with 1.5 for those published before 2000 (P < 0.001). Limitation: The investigators could not ascertain why prior trials were not cited, and noncited trials may have been taken into account in the trial design and proposal stages. Conclusion: In reports of RCTs published over 4 decades, fewer than 25% of preceding trials were cited, comprising fewer than 25% of the participants enrolled in all relevant prior trials. A median of 2 trials was cited, regardless of the number of prior trials that had been conducted. Research is needed to explore the explanations for and consequences of this phenomenon. Potential implications include ethically unjustifiable trials, wasted resources, incorrect conclusions, and unnecessary risks for trial participants. Primary Funding Source: None.
Quality of Systematic Reviews of Economic Evaluations in Health Care
Authors: Tom Jefferson
Journal: JAMA (2002)

Reviews performed almost a decade ago showed considerable gaps in the quality of reporting and methods applied to economic evaluations of health care interventions. Measures taken by the research community to address the issue included the promulgation of guidelines and the publicizing of good practice in economic evaluation.To assess the quality of methods of systematic reviews, economic evaluations in health care, and reporting methods, we conducted full-text searches of private and public databases for the period 1990 through March 2001 and corresponded with researchers active in the field. A total of 102 reports were identified, but only 39 were included. Quality of systematic reviews was assessed by a 6-item checklist.Quality of review methods was reasonable, but more attention needs to be paid to search methods and standardization of evaluation instruments. The reviews found consistent evidence of serious methodological flaws in a significant number of economic evaluations. Lack of clear descriptions of methods, lack of explanation and justification for the framework and approach used, and low-quality estimates of effectiveness for the interventions evaluated were the most frequent flaws. Modest improvements in quality of conducting and reporting economic evaluations appear to have taken place in the last decade.Proper allocation of resources on the basis of economic evaluations remains uncertain. Editorial teams and regulatory bodies should perform quality assurance based on a single widely accepted and validated standard instrument.
Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice
Authors: Paul A. Crossey, Claire C. Pillai, John P. Miell
Journal: Journal of Clinical Investigation (2002)

IGF binding protein-1 (IGFBP-1) is a secretory product of decidualized endometrium and a major constituent of amniotic fluid. It is thought to modulate the actions of the IGFs on trophoblast cells and is therefore potentially important in regulating placental development and fetal growth. To investigate this hypothesis, we have studied the effects of decidual IGFBP-1 excess on fetoplacental growth in transgenic mice overexpressing human IGFBP-1. Endogenous fetal IGFBP-1 overexpression is associated with a transient impairment of fetal growth in midgestation. Maternal decidual IGFBP-1 excess is also associated with impaired fetal growth in midgestation independent of fetal genotype, indicating placental insufficiency. Our data also demonstrate that amniotic fluid IGFBP-1 is derived almost exclusively from maternal sources. Decidual IGFBP-1 overexpression has a marked effect on placental development. Placental morphology is abnormal in transgenic females due to altered trophoblast invasion and differentiation. These changes result in an increase in placental mass throughout pregnancy. This study provides the first compelling in vivo evidence that IGFBP-1 plays a role in placentation and suggests that IGFBP-1 has a pathological role in preeclampsia, a disorder characterized by shallow uterine invasion and altered placental development.
Gefitinib Versus Vinorelbine in Chemotherapy-Naïve Elderly Patients With Advanced Non–Small-Cell Lung Cancer (INVITE): A Randomized, Phase II Study
Authors: Lucio Crinò, Federico Cappuzzo, Petr Zatloukal, Martin Reck, Milos Pesek, Joyce C. Thompson, Hugo E.R. Ford, Fred R. Hirsch, Marileila Varella-Garcia, Serban Ghiorghiu, Emma L. Duffield, Alison A. Armour, Georgina Speake, Michael Cullen
Journal: Journal of Clinical Oncology (2008)

This phase II, open-label, parallel-group study compared gefitinib with vinorelbine in chemotherapy-naïve elderly patients with advanced non-small-cell lung cancer (NSCLC).Chemotherapy-naïve patients (age >or= 70 years) were randomly assigned to gefitinib (250 mg/d orally) or vinorelbine (30 mg/m(2) infusion on days 1 and 8 of a 21-day cycle). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and tolerability. Exploratory end points included epidermal growth factor receptor (EGFR) gene copy number by fluorescent in situ hybridization (FISH).Patients were randomly assigned to gefitinib (n = 97) or to vinorelbine (n = 99). Hazard ratios (HR; gefitinib v vinorelbine) were 1.19 (95% CI, 0.85 to 1.65) for PFS and 0.98 (95% CI, 0.66 to 1.47) for OS. ORR and disease control rates were 3.1% (95% CI, 0.6 to 8.8) and 43.3% (for gefitinib) and 5.1% (95% CI, 1.7 to 11.4) and 53.5% (for vinorelbine), respectively. Overall QOL improvement and PSI rates were 24.3% and 36.6% (for gefitinib) and 10.9% and 31.0% (for vinorelbine), respectively. In the 54 patients who were EGFR FISH-positive, HRs were 3.13 (95% CI, 1.45 to 6.76) for PFS and 2.88 (95% CI, 1.21 to 6.83) for OS. There were fewer treatment-related grade 3 to 5 adverse events with gefitinib (12.8%) than with vinorelbine (41.7%).There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy-naïve, unselected elderly patients with advanced NSCLC, but there was better tolerability with gefitinib. Individuals who were EGFR FISH-positive benefited more from vinorelbine than from gefitinib; this unexpected finding requires further study.
Cost Effectiveness of Selective Internal Radiation Therapy (SIRT) Using YTTRIUM-90 Resin Microspheres for the Treatment of Patients with Inoperable Colorectal Liver Metastases in the UK
Authors: Bester Louren, Sangro Bruno, Wasan Harpreet, Kennedy Andrew, Sennfält Karin
Journal: Annals of Oncology (2014)
RT-04 * STEREOTACTIC RADIOSURGERY (SRS) IN RECURRENT HIGH-GRADE GLIOMA
Authors: F. Bockstein, D. T. Blumenthal, B. W. Corn, E. Gez, D. Matceyevsky, A. A. Kanner
Journal: Neuro-Oncology (2014)

Despite the failure of the RTOG 9305 randomized trial to demonstrate the efficacy of SRS in newly diagnosed glioblastoma, this treatment was reported in several institutional series to be modestly effective, particularly in the setting of limited focally recurrent disease. This is a retrospective review of 55 SRS treatments in 47 patients with recurrent high-grade glioma treated at our institution between 2004 to 2013. Thirty-two (63%) patients suffered from glioblastoma and 15 from high-grade glioma. The median age was 53.3 years (24-86). The initial non-surgical treatment included Stupp protocol in 35 (74.5%), adjuvant temozolamide after RT in 3, PCV or other chemotherapy in 4 patients and in 5 patients SRS was the only postoperative intervention. The indication for SRS was locally progressing lesions in 32 (68%) patients and a new distant lesion in 15 (32%). Eight (17%) patients received a second salvage SRS treatment for a new focus. None of the repeat SRS treated patients experienced treatment related toxicity. The median target volume was 2.1 cc (0.2-9.5cc) and the median prescription dose for LINAC-based SRS treatment was 18 Gy (14-24Gy). Median time to progression was 5.1 months (1.0-96.4). Longstanding responses (> 12 months) were observed in 8 (17%) patients. One patient developed clinically significant radiation necrosis 3 months after SRS and required a surgical resection, but remained asymptomatic and without radiological evidence of active disease for more than 51 months thereafter. One additional patient developed biopsy -proven RN, which was resolved conservatively. No other treatment associated side effects were observed. Median survival time after SRS was 15.5 months (0.2-109.3) and overall median survival (since diagnosis) was 39.0 months (10.7-193.6 months). In conclusion, SRS may be considered an effective salvage procedure in selected patients with recurrent high-grade gliomas, providing long term responses in almost 20% of the cases.
Vaginal bleeding in early pregnancy
Authors: D C M. Burns
Journal: BMJ (1980)

stood Mendelian inheritance well.They found it virtually impossible to accept the concept of the healthy carrier.The usual response was to agree politely that the child was perfectly healthy and did not need any treatment, but that children should be tested as young as possible-"so that it can be treated in time."Since completing this study we have been aware of the comparative simplicity of coun- selling families who come for testing, or have already been tested, if there is prior knowledge of their condition.They might, for example, have relatives with a haemoglobinopathy or trait, might have been tested themselves in pregnancy, or might have been referred by a doctor of their own ethnic background.We conclude that mass screening for haemo- globinopathy is unjustified, at least in this country.We advocate instead further health education about haemoglobinopathies together with financial support for hospitals recognised as able to offer both adequate testing and coun- selling.
Omeprazole:<i>Helicobacter pylori</i> makes thee greater yet
Authors: D PANTOFLICKOVA, A L BLUM, P BERCIK
Journal: Gut (1999)

<h3>Objectives</h3> The current global health crisis of the COVID-19 pandemic has drastically affected the whole population, but healthcare workers are particularly exposed to high levels of physical and mental stress. This enormous burden requires both the continuous monitoring of their health conditions and research into various protective factors. <h3>Design</h3> Cross-sectional surveys. <h3>Setting and participants</h3> Self-administered questionnaires were constructed assessing COVID-19-related worries of health workers in Hungary. The surveys were conducted during two consecutive waves of the COVID-19 pandemic (N-first wave=376, N-second wave=406), between 17 July 2020 and 31 December 2020. <h3>Primary and secondary outcome measures</h3> COVID-19-related worry, well-being and distress levels of healthcare workers. We also tested whether psychological resilience mediates the association of worry with well-being and distress. Multiple linear regression analyses were performed. <h3>Results</h3> The results indicated that healthcare workers had high levels of worry and distress in both pandemic waves. When comparing the two waves, enhanced levels of worry (Wald’s χ<sup>2</sup>=4.36, p=0.04) and distress (Wald’s χ<sup>2</sup>=25.18, p&lt;0.001), as well as compromised well-being (Wald’s χ<sup>2</sup>=58.64, p&lt;0.001), were found in the second wave. However, not all types of worries worsened to the same extent across the waves drawing attention to some specific COVID-19-sensitive concerns. Finally, the protective role of psychological resilience was shown by a mediator analysis suggesting the importance of increasing resilience as a key factor in maintaining the mental health of healthcare workers in the burden of the COVID-19 pandemic. <h3>Conclusions</h3> Our results render the need for regular psychological surveillance in healthcare workers. <h3>Registration</h3> Hungarian Scientific and Research Ethics Committee of the Medical Research Council (IV/5079-2/2020/EKU).
Prefrontal cortex and the generation of oscillatory visual persistence
Authors: Mark A. Elliott, Markus Conci, Hermann J. Müller
Journal: Behavioral and Brain Sciences (2003)

In this commentary, the formation of “pre-iconic” visual-prime persistence is described in the context of prime-specific, independent-component activation at prefrontal and posterior EEG-recording sites. Although this activity subserves neural systems that are near identical to those described by Ruchkin and colleagues, we consider priming to be a dynamic process, identified with patterns of coherence and temporal structure of very high precision.
Rapid Diagnosis of Tuberculosis and Multidrug Resistance by the Microscopic-Observation Drug-Susceptibility Assay
Authors: N. Sarita Shah, Prashini Moodley, Palav Babaria, Salona Moodley, Melissa Ramtahal, Jessica Richardson, Scott Heysell, Xuan Li, Anthony Moll, Gerald Friedland, A. Willem Sturm, Neel R. Gandhi
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Mortality is exceedingly high and rapid among patients infected with HIV and tuberculosis (TB), in part because of limited access to appropriate TB diagnostics. The microscopic observation drug-susceptibility (MODS) assay is a simple, rapid, low-cost test for TB and multidrug-resistant (MDR) TB, but data in individuals infected with HIV and in Africa are limited.Objectives: To evaluate the MODS assay in a high-HIV-prevalence setting.Methods: We performed a prospective diagnostic accuracy study of consecutive adults suspected to have TB from outpatient and inpatient settings at a district hospital in rural South Africa. Sputum was tested by concentrated smear microscopy; agar (Middlebrook 7H11) and liquid (mycobacterial growth indicator tube) culture; and the MODS assay. Drug-susceptibility testing (DST) was by indirect 1% proportion method and MODS. Reference standard for Mycobacterium tuberculosis detection was growth on Middlebrook or mycobacterial growth indicator tube culture; 1% proportion was the reference standard for isoniazid and rifampin DST.Measurements and Main Results: Among 534 adults enrolled, 388 (73%) were HIV-positive, with a median CD4 count of 161 cells/mm3 (interquartile range [IQR]: 72–307). TB was diagnosed by the reference standard culture in 113 (21%). MODS sensitivity was 85% (95% confidence interval [CI], 78–92%), and specificity was 97% (CI, 95–99%). MODS test performance did not differ by patients' HIV status (sensitivity 88% vs. 90%, specificity 97% vs. 100% for HIV-positive versus HIV-negative, respectively). For MDR-TB diagnosis (n = 11), sensitivity was 100% (one-sided CI, 68–100%) and specificity was 94% (CI, 82–98%). Median turnaround time for MDR-TB diagnosis was 7 days (IQR: 6–9) with MODS versus 70 days (IQR: 49–96) with indirect proportion method (P < 0.001).Conclusions: Among adult TB suspects predominantly infected with HIV, MODS provided high sensitivity and specificity for rapid diagnosis of TB and MDR-TB. Given the high mortality from TB and MDR-TB and prolonged opportunity for TB transmission before diagnosis, the MODS assay warrants serious consideration for use in similar high-HIV-prevalence, resource-limited settings.
Published models and local data can bridge the gap between reference values of lung function for children and adults
Authors: K Nysom, CS Ulrik, B Hesse, A Dirksen
Journal: European Respiratory Journal (1997)

The aim of this study was to create reference equations for pulmonary function tests (PFTs) that span the age range from childhood to young adulthood. PFT results (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), ratio of FEV1 to FVC (FEV1/FVC), total lung capacity (TLC), transfer factor) of 348 healthy 13-24 yr old Caucasian never-smokers from a local population study were compared with 13 selected sets of published reference equations. Predicted and observed PFT results differed significantly for 63 of 92 reference equations tested, and most equations accounted poorly for the increase in PFT variables which takes place during adolescence. We selected the equations with the best fit and adjusted their parameters, so that the level and variance of predicted values agreed with the local data. For subjects older than 18 yrs, we selected the European Community for Steel and Coal (ECSC) equations. For subjects younger than 18 yrs, we chose European summary equations for FVC, FEV1, and FEV1/FVC, and recent British equations for TLC and transfer factor. The customized reference equations are the best available (maximum likelihood) for analysing PFTs of patients tested in our laboratory. Our approach can be used whenever generally accepted reference equations are lacking and a local sample of normal subjects is available.
Lack of Evidence for Horizontal Transfer of the lac Operon into Escherichia coli
Authors: Daniel M. Stoebel
Journal: Molecular Biology and Evolution (2004)

The idea that Escherichia coli gained the lac operon via horizontal transfer, allowing it to invade a new niche and form a new species, has become a paradigmatic example of bacterial nonpathogenic adaptation and speciation catalyzed by horizontal transfer. Surprisingly, empirical evidence for this event is essentially nonexistent. To see whether horizontal transfer occurred, I compared a phylogeny of 14 Enterobacteriaceae based on two housekeeping genes to a phylogeny of a part of their lac operon. Although several species in this clade appear to have acquired some or all of the operon via horizontal transfer, there is no evidence of horizontal transfer into E. coli. It is not clear whether the horizontal transfer events for which there is evidence were adaptive because those species which have acquired the operon are not thought to live in high lactose environments. I propose that vertical transmission from the common ancestor of the Enterobacteriaceae, with subsequent loss of these genes in many species can explain much of the patchy distribution of lactose use in this clade. Finally, I argue that we need new, well-supported examples of horizontal transfer spurring niche expansion and speciation, particularly in nonpathogenic cases, before we can accept claims that horizontal transfer is a hallmark of bacterial adaptation.