Miracle-dz/UniFAR-FTUs huggingface dataset:
Renal involvement in cystic fibrosis: diseases spectrum and clinical relevance.

BACKGROUND AND OBJECTIVES Clinically relevant kidney involvement is uncommonly described in adult patients with cystic fibrosis (CF). We sought to report on a series of patients with CF and kidney biopsy-documented renal involvement. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective study was undertaken in two referral centers for adult patients with CF in Paris, France. Patients who had undergone a biopsy of native kidneys between 1992 and 2008 were identified, and their medical records were reviewed. RESULTS We identified 13 adult patients with CF and renal disease. Proteinuria was present in all but two cases and was associated with progressive renal impairment in four patients (median serum creatinine 85 micromol/L; range 53 to 144 micromol/L). Renal biopsy disclosed a heterogeneous spectrum of nephropathies including AA amyloidosis (n = 3), diabetic glomerulopathy (n = 3), FSGS (n = 2), minimal-change disease (n = 1), postinfectious glomerulonephritis (n = 1), IgA nephropathy related to Henoch-Schönlein purpura (n = 1), membranous nephropathy (n = 1), and chronic interstitial nephropathy (n = 1). Chronic renal failure occurred in five patients, and one patient reached ESRD. CONCLUSIONS Although rare, clinically significant renal disease may arise in young adult patients with CF. Given the wide spectrum of diseases that may be encountered, definite diagnosis by kidney biopsy is mandatory to optimize clinical treatment of these complex patients, particularly in the perspective of organ transplantation.
Primary site resection is superior for incurable metastatic colorectal cancer.

AIM To investigate survival in patients treated with FOLFOX followed by primary site resection or palliative surgery for incurable metastatic colorectal cancer. METHODS Between 2001 and 2009, a total of 98 patients with colorectal adenocarcinoma and non-resectable metastases were diagnosed and treated with the new systemic agent chemotherapy regimen FOLFOX. Primary site resection was carried out in 38 patients, creation of a colostomy or bypass without resection was carried out in 36 patients, and 23 were not operated on because of advanced disease. The survival times of patients in different groups were analyzed. RESULTS There were no differences between the patients regarding their general condition, concurrent disease, or tumor stage according to AJCC classification. The median survivals of the three groups were 30.6, 20.8, and 12.7 mo (log-rank P value < 0.05), respectively. The postoperative complication rate was higher in the primary site resection group than in the palliative surgery group. CONCLUSION The results indicate that there are benefits from primary site resection for incurable metastatic colorectal cancer with systemic chemotherapy.
The Effect of Nutrition during Early Life on the Epigenetic Regulation of Transcription and Implications for Human Diseases

Epigenetic processes which include DNA methylation, histone modification and miRNAs are integral in determining when and where specific genes are expressed. There is now increasing evidence that the epigenome is susceptible to a variety of environmental cues, such as nutrition, during specific periods of development. The changes induced by early-life nutrition may reflect an adaptive response of the foetus to environmental cues acting through the process of developmental plasticity. This may allow an organism to adjust its developmental programme resulting in long-term changes in its metabolism and physiology in order to be better matched to the future environment. However, when the future environment lies outside the anticipated range, metabolic and homoeostatic capacity will be mismatched with the environment and that individual will be at increased risk of developing a range of non-communicable diseases. Thus the environmental regulation of epigenetic processes is a central component in the developmental origins of non-communicable diseases and our understanding of these processes is, therefore, critical both for the identification of individuals at risk and for the development of new intervention strategies.
Catheter Ablation of Atrial Fibrillation in Patients at Low Thrombo‐Embolic Risk: Efficacy and Safety of a Simplified Periprocedural Anticoagulation Strategy

To prevent thrombo‐embolic (TE) events during ablation of atrial fibrillation (AF), warfarin is recommended in all patients irrespective of baseline TE risk. We evaluated the efficacy and safety of a simplified periprocedural anticoagulation strategy of aspirin (ASA) and low molecular weight heparin (LMWH) in patients at low TE risk.
Impaired Transporter Associated with Antigen Processing-Dependent Peptide Transport during Productive EBV Infection1

Human herpesviruses, including EBV, persist for life in infected individuals. During the lytic replicative cycle that is required for the production of infectious virus and transmission to another host, many viral Ags are expressed. Especially at this stage, immune evasion strategies are likely to be advantageous to avoid elimination of virus-producing cells. However, little is known about immune escape during productive EBV infection because no fully permissive infection model is available. In this study, we have developed a novel strategy to isolate populations of cells in an EBV lytic cycle based on the expression of a reporter gene under the control of an EBV early lytic cycle promoter. Thus, induction of the viral lytic cycle in transfected EBV+ B lymphoma cells resulted in concomitant reporter expression, allowing us, for the first time, to isolate highly purified cell populations in lytic cycle for biochemical and functional studies. Compared with latently infected B cells, cells supporting EBV lytic cycle displayed down-regulation of surface HLA class I, class II, and CD20, whereas expression levels of other surface markers remained unaffected. Moreover, during lytic cycle peptide transport into the endoplasmic reticulum, was reduced to <30% of levels found in latent infection. Because steady-state levels of TAP proteins were unaffected, these results point toward EBV-induced interference with TAP function as a specific mechanism contributing to the reduced levels of cell surface HLA class I. Our data implicate that EBV lytic cycle genes encode functions to evade T cell recognition, thereby creating a window for the generation of viral progeny.
Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins

The dog bile salt export pump (BSEP; ABCB11) was cloned and expressed in a Sf9 insect cell system. The deduced amino acid sequence encodes a 1325‐amino‐acid protein, which shows 89.4% and 80.2% homology with human BSEP and rat Bsep, respectively. The transcript of the dog Bsep gene was detected at a high level in liver, but not other tissues, by quantitative RT‐PCR. The BSEP‐expressing membrane vesicles isolated from Sf9 cells exhibited saturable uptake of [3H]taurocholic acid with Michaelis constants (Km) of 33.7, 22.2 and 19.9 µM for the dog, rat and human transporters, respectively. The uptake of [3H]taurocholic acid by all three transporters was significantly inhibited by troglitazone, glibenclamide, and other several inhibitors, while pravastatin inhibited dog Bsep and human BSEP, but not rat Bsep at 100 µM. The IC50 of troglitazone for dog Bsep, human BSEP, and rat Bsep were 32, 20, and 60 µM, and those of pravastatin were 441, 240 and >1,000 µM, respectively. In conclusion, while dog Bsep shows similar ATP‐dependent bile acid transport characteristics to human BSEP and rat Bsep, there is a species difference in affinity for drugs such as pravastatin and troglitazone. Copyright © 2008 John Wiley & Sons, Ltd.
Corporate Governance and the Asymmetrical Behavior of Selling, General and Administrative Costs: Further Evidence from State Antitakeover Laws

While both the economic and agency theory have been proposed to explain cost stickiness, Chen, Lu, and Sougiannis (2012) is the first study that provides evidence to support the agency explanation. To address the endogeneity concern, we extend Chen et al. (2012) by employing state antitakeover laws (ATLs) as an exogenous shock to the corporate governance environment and examine whether the behavior of selling, general and administrative (SG&A) costs changes around the passage of the ATLs. Using the difference-in-differences methodology, we report two primary findings. First, when sales increase, SG&A costs increase significantly more after the enactment of the ATLs, which is consistent with the ATL literature that managers enjoy the “quiet life” after being insulated from an active takeover market. Second and more importantly, we do not find evidence to suggest that managers reduce SG&A costs less in response to sales decline after the passage of the ATLs, which is inconsistent with the agency explanation of cost stickiness. These results hold in settings where we expect the effect of ATLs to be stronger and are robust to sensitivity analyses. Although we would not rule out the agency explanation, our study does cast doubt on the explanation and calls for further research into the reasons behind cost stickiness.
HUMAN GENETIC STUDY: Association analysis of genes encoding the nociceptin receptor (OPRL1) and its endogenous ligand (PNOC) with alcohol or illicit drug dependence

Recent studies in animal models have shown that the nociceptin system, comprising nociceptin (or OFQ/N, encoded by PNOC) and the nociceptin receptor (an opioid receptor‐like protein encoded by OPRL1), may be involved in alcohol and other drug reward pathways. To determine whether the nociceptin system is associated with alcohol or illicit drug dependence in humans, we analyzed 10 single nucleotide polymorphisms (SNPs) in OPRL1 and 15 SNPs in PNOC in a sample of 1923 European Americans from 219 multiplex alcohol dependent families ascertained by the Collaborative Study on the Genetics of Alcoholism. The SNPs spanned both genes and several kb of their flanking sequences, and were in high linkage disequilibrium. Neither gene was associated with alcohol or illicit drug dependence, although two SNPs in PNOC showed marginal association with alcoholism and one with illicit drug dependence (P = 0.04–0.05). Secondary analyses suggested that two adjacent SNPs in intron 1 of OPRL1 were marginally associated with opioid dependence (P = 0.05); none of the SNPs in PNOC were associated with opioid dependence.
Effectiveness of a brief physician counselling session on improving smoking behaviour in the workplace.

BACKGROUND Brief physician counselling has been shown to be effective in improving smokers' behaviour. If the counselling sessions can be given at the workplace, this would benefit a larger number of smokers. This study aimed to determine the effectiveness of a ten-minute physician counseling session at the workplace in improving smoking behaviour. MATERIALS AND METHODS This prospective randomised control trial was conducted on smokers in a factory. A total of 163 participants were recruited and randomised into control and intervention groups using a table of random numbers. The intervention group received a ten-minute brief physician counselling session to quit smoking. Stages of smoking behaviour were measured in both groups using a translated and validated questionnaire at baseline, one month and three months post intervention. RESULTS There was a significant improvement in smoking behaviour at one-month post intervention (p=0.024, intention to treat analysis; OR=2.525; CI=1.109-5.747). This was not significant at three-month post intervention (p=0.946, intention to treat analysis; OR=1.026; 95% CI=0.486-2.168). CONCLUSIONS A session of brief physician counselling was effective in improving smokers' behaviour at workplace, but the effect was not sustained.
Insulin resistance in type 1 diabetes

Insulin resistance plays a larger role in the type 1 diabetes disease process than is commonly recognized. The onset of type 1 diabetes is often heralded by an antecedent illness and/or the onset of puberty, both conditions associated with insulin resistance. In the face of a damaged β‐cell and thus reduced insulin secretion, this change is enough to manifest hyperglycemia. During the first year of clinical disease, considerable evidence suggests that the occurrence of clinical remission or ‘honeymoon period’ is due to a temporary resolution of the insulin‐resistant state present at diagnosis. Intensive diabetes management is associated with both improved insulin sensitivity and β‐cell function. This indicates that the historical data on the changes in insulin secretion post‐diagnosis may be inappropriate when designing current studies. The known physiological relationship between β‐cell function and insulin sensitivity complicates interpretation of insulin secretion data obtained as part of prevention or intervention trials. While it is recommended that at least a subset of subjects participating in these trials undergo formal measurements of insulin sensitivity to evaluate effects of therapy on this parameter independent of effects on the β‐cell, the sample size must be sufficient to determine an effect if present. Finally, one could speculate that it is possible that subsets of people with mild manifestations of the type 1 autoimmune disease process could benefit from treatments aimed at improving the insulin‐resistant state. Copyright © 2002 John Wiley & Sons, Ltd.
Licensed Nurses Disciplined in Oregon Between September 1996 and June 2008

This study is undertaken to better identify the types of errors being made by nurses in Oregon, to have a more thorough understanding of who is making the errors, and to examine how the Board is sanctioning nurses through Board (Board of Nursing) discipline. Results show that older nurses, and a disproportionately high number of male nurses, are being disciplined. RNs tend to be disciplined more for substance abuse and LPNs for substandard or inadequate care or for unprofessional conduct. RNs tend to be reprimanded more often than other licensure types, and LPNs receive more licensure suspensions. It may be helpful for administrators and nurse managers to use the information for staff education and development decisions. It may also inform Oregon nursing regulators, charged with protecting the public, when developing strategies aimed at ensuring equity and consistency in Board actions.
Transcription by an Archaeal RNA Polymerase Is Slowed but Not Blocked by an Archaeal Nucleosome

ABSTRACT Archaeal RNA polymerases (RNAPs) are closely related to eukaryotic RNAPs, and in Euryarchaea, genomic DNA is wrapped and compacted by histones into archaeal nucleosomes. In eukaryotes, transcription of DNA bound into nucleosomes is facilitated by histone tail modifications and chromatin remodeling complexes, but archaeal histones do not have histone tails and archaeal genome sequences provide no evidence for archaeal homologs of eukaryotic chromatin remodeling complexes. We have therefore investigated the ability of an archaeal RNAP, purified from Methanothermobacter thermautotrophicus, to transcribe DNA bound into an archaeal nucleosome by HMtA2, an archaeal histone from M. thermautotrophicus. To do so, we constructed a template that allows transcript elongation to be separated from transcription initiation, on which archaeal nucleosome assembly is positioned downstream from the site of transcription initiation. At 58°C, in the absence of an archaeal nucleosome, M. thermautotrophicus RNAP transcribed this template DNA at a rate of ∼20 nucleotides per second. With an archaeal nucleosome present, transcript elongation was slowed but not blocked, with transcription pausing at sites before and within the archaeal nucleosome. With additional HMtA2 binding, complexes were obtained that also incorporated the upstream regulatory region. This inhibited transcription presumably by preventing archaeal TATA-box binding protein, general transcription factor TFB, and RNAP access and thus inhibiting transcription initiation.
CPAP suppression of awake right-to-left shunting through patent foramen ovale in a patient with obstructive sleep apnoea

The prevalence of an echocardiographically visible patent foramen ovale (PFO) is higher in patients with obstructive sleep apnoea syndrome (OSAS) than in normal controls. We report a patient who presented with OSAS and right-to-left shunting (RLS) through the PFO in whom the RLS disappeared after treatment for 1 week with nocturnal continuous positive airway pressure (CPAP). This case shows the role of OSA in generating an awake RLS through a PFO and its possible reversibility by CPAP. The mechanism of reversible awake RLS through PFO in OSAS is discussed.
Data-Driven Models for the Spatio-Temporal Interpolation of Satellite-Derived SST Fields

Satellite-derived products are of key importance for the high-resolution monitoring of the ocean surface on a global scale. Due to the sensitivity of spaceborne sensors to the atmospheric conditions as well as the associated spatio-temporal sampling, ocean remote sensing data may be subject to high-missing data rates. The spatio-temporal interpolation of these data remains a key challenge to deliver L4 gridded products to end-users. Whereas operational products mostly rely on model-driven approaches, especially optimal interpolation based on Gaussian process priors, the availability of large-scale observation and simulation datasets calls for the development of novel data-driven models. This study investigates such models. We extend the recently introduced analog data assimilation to high-dimensional spatio-temporal fields using a multiscale patch-based decomposition. Using an observing system simulation experiment for sea surface temperature, we demonstrate the relevance of the proposed data-driven scheme for the real missing data patterns of the high-resolution infrared METOP sensor. It has resulted in a significant improvement w.r. t. state-of-the-art techniques in terms of interpolation error (about 50% of relative gain) and spectral characteristics for horizontal scales smaller than 100 km. We further discuss the key features and parameterizations of the proposed data-driven approach as well as its relevance with respect to classical interpolation techniques.
Disentangling the Effects of Social Network Density on Electronic Word-of-Mouth (eWOM) Intention

A widely accepted notion in diffusion literature is that individuals’ word-of-mouth behavior is constrained by the properties of social structures (e.g., tie strength, positions in a network) they belong to. Although many studies have indeed confirmed the existence of such social influence, little is known about how the social structural effects are produced and work at a psychological level. This study attempts to present how one's electronic word-of-mouth (eWOM) intention is shaped by 2 key factors—the valence of product-related information and the social coherence of the communication network in which s/he belongs. To understand the process through which the network structures moderate the impact of information valence on eWOM intention, 2 different moderation processes—a) mediated moderation and b) moderated mediation—were tested in a 2 × 2 factorial experiment. The experimental results supported the moderated mediation model, and the implications of the results were discussed.
Comamonas testosteroni uses a chemoreceptor for tricarboxylic acid cycle intermediates to trigger chemotactic responses towards aromatic compounds

Bacterial chemotaxis towards aromatic compounds has been frequently observed; however, knowledge of how bacteria sense aromatic compounds is limited. Comamonas testosteroni CNB‐1 is able to grow on a range of aromatic compounds. This study investigated the chemotactic responses of CNB‐1 to 10 aromatic compounds. We constructed a chemoreceptor‐free, non‐chemotactic mutant, CNB‐1Δ20, by disruption of all 19 putative methyl‐accepting chemotaxis proteins (MCPs) and the atypical chemoreceptor in strain CNB‐1. Individual complementation revealed that a putative MCP (tagged MCP2201) was involved in triggering chemotaxis towards all 10 aromatic compounds. The recombinant sensory domain of MCP2201 did not bind to 3‐ or 4‐hydroxybenzoate, protocatechuate, catechol, benzoate, vanillate and gentisate, but bound oxaloacetate, citrate, cis‐aconitate, isocitrate, α‐ketoglutarate, succinate, fumarate and malate. The mutant CNB‐1ΔpmdF that lost the ability to metabolize 4‐hydroxybenzoate and protocatechuate also lost its chemotactic response to these compounds, suggesting that taxis towards aromatic compounds is metabolism‐dependent. Based on the ligand profile, we proposed that MCP2201 triggers taxis towards aromatic compounds by sensing TCA cycle intermediates. Our hypothesis was further supported by the finding that introduction of the previously characterized pseudomonad chemoreceptor (McpS) for TCA cycle intermediates into CNB‐1Δ20 likewise triggered chemotaxis towards aromatic compounds.
Cholecystokinin Receptor Antagonist Halts Progression of Pancreatic Cancer Precursor Lesions and Fibrosis in Mice

Objectives Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved in the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. Methods The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-KrasG12D transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK receptor antagonist (proglumide, 0.1 mg/mL). Pancreas from the mice were removed and examined histologically for number and grade of PanINs after 1, 2, or 4 months of antagonist therapy. Results Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed, and progression to advanced lesions arrested in mice treated with proglumide compared with the controls (P = 0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared with vehicle (P < 0.001). Conclusions These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. The use of CCK receptor antagonists may have a role in cancer prophylaxis in high-risk subjects and may reduce fibrosis in the microenvironment.