Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants.

IMPORTANCE Extubation failure is common in extremely preterm infants. The current paucity of data on the adverse long-term respiratory outcomes associated with reinitiation of mechanical ventilation prevents assessment of the risks and benefits of a trial of extubation in this population. OBJECTIVE To evaluate whether exposure to multiple courses of mechanical ventilation increases the risk of adverse respiratory outcomes before and after adjustment for the cumulative duration of mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study of extremely low-birth-weight (ELBW; birth weight <1000 g) infants born from January 1, 2006, through December 31, 2012, who were receiving mechanical ventilation. Analysis was conducted between November 2014 and February 2015. Data were obtained from the Alere Neonatal Database. EXPOSURES The primary study exposures were the cumulative duration of mechanical ventilation and the number of ventilation courses. MAIN OUTCOMES AND MEASURES The primary outcome was bronchopulmonary dysplasia (BPD) among survivors. Secondary outcomes were death, use of supplemental oxygen at discharge, and tracheostomy. RESULTS We identified 3343 ELBW infants, of whom 2867 (85.8%) survived to discharge. Among the survivors, 1695 (59.1%) were diagnosed as having BPD, 856 (29.9%) received supplemental oxygen at discharge, and 31 (1.1%) underwent tracheostomy. Exposure to a greater number of mechanical ventilation courses was associated with a progressive increase in the risk of BPD and use of supplemental oxygen at discharge. Compared with a single ventilation course, the adjusted odds ratios for BPD ranged from 1.88 (95% CI, 1.54-2.31) among infants with 2 ventilation courses to 3.81 (95% CI, 2.88-5.04) among those with 4 or more courses. After adjustment for the cumulative duration of mechanical ventilation, the odds of BPD were only increased among infants exposed to 4 or more ventilation courses (adjusted odds ratio, 1.44; 95% CI, 1.04-2.01). The number of ventilation courses was not associated with increased risk of supplemental oxygen use at discharge after adjustment for the length of ventilation. A greater number of ventilation courses did not increase the risk of tracheostomy. CONCLUSIONS AND RELEVANCE Among ELBW infants, a longer cumulative duration of mechanical ventilation largely accounts for the increased risk of chronic respiratory morbidity associated with reinitiation of mechanical ventilation. These results support attempts of extubation in ELBW infants receiving mechanical ventilation on low ventilator settings, even when success is not guaranteed.
Examining the range of normal intraindividual variability in neuropsychological test performance

Abstract Neuropsychologists often diagnose cerebral dysfunction based, in part, on marked variation in an individual's cognitive test performance. However, little is known about what constitutes the normal range of intraindividual variation. In this study, after excluding 54 individuals with significant health problems, we derived 32 z-transformed scores from 15 tests administered to 197 adult participants in a study of normal aging. The difference between each person's highest and lowest scores was computed to assess his or her maximum discrepancy (MD). The resulting MD values ranged from 1.6 to 6.1 meaning that the smallest MD shown by any person was 1.6 standard deviations (SDs) and the largest MD shown by any person was 6.1 SDs. Sixty-six percent of participants produced MD values that exceeded 3 SDs. Eliminating each person's highest and lowest test scores decreased their MDs, but 27% of the participants still produced MD values exceeding 3. Although MD values appeared to increase with age, adjusting test scores for age, which is standard in clinical practice, did not correct for this. These data reveal that marked intraindividual variability is very common in normal adults, and underscore the need to base diagnostic inferences on clinically recognizable patterns rather than psychometric variability alone. (JINS, 2003, 9, 864–870.)
Association between diurnal temperature range and respiratory tract infections.

OBJECTIVE This study aimed to assess the association between emergency-room visits for respiratory tract infection (RTI) with diurnal temperature range (DTR), a weather parameter closely associated with urbanization and global climate change. METHODS We conducted a semiparametric time-series analysis to estimate the percentage increase in emergency-room visits for RTI associated with changes in DTR after adjustment for daily weather conditions (temperature and relative humidity) and outdoor air pollution. RESULTS DTR was significantly associated with daily emergency-room visits for RTI. An increase of 1 °C in the current-day (L0) and in the 2-day moving average (L01) DTR corresponded to a 0.94% [95% confidence interval (CI), 0.34%-1.55%] and 2.08% (95% CI, 1.24%-2.93%) increase in emergency-room visits for RTI, respectively. CONCLUSION DTR was associated with increased risk of RTI. More studies are needed to understand the impact of DTR on respiratory health.
Neurological Symptoms, Not Signs,Are Common in Early HIV Infection.

UNLABELLED Objective. To examine the cross-sectional prevalence of neurological symptoms and signs in a large cohort of human immunodeficiency virus (HIV)-seropositive men, and determine the relationship of the symptoms to disease stage, immunologic markers, and independent variables from neuropsychological (NP) testing and psychiatric interview. METHODS One hundred-nine controls and 386 HIV-infected volunteers enrolled in the HIV Neurobehavioral Research Center (HNRC) longitudinal study. The majority, without acquired immune deficiency syndrome (AIDS), were screened for alcohol/substance abuse; previous diagnosis of HIV-associated dementia; and HIV-unrelated developmental, neurological, medical, and neurobehavioral conditions which potentially impair cognition; and underwent a structured neurological interview and examination, standardized NP testing, and psychiatric interview as part of a more extensive battery. A large subset (N = 377) underwent lumbar puncture for cerebrospinal fluid (CFS) examination. We examined the relationship of sixteen select but independent variables, using stepwise multiple regressions, from demographic/staging, immunological, NP, and psychiatric domains to neurological symptoms in an effort to identify possible predictors of subclinical nervous systems involvement. Results. All categories of neurological symptoms were significantly more prevalent among medically asymptomatic (CDC stage A) subjects than controls, with a further rise in prevalence in those with more advanced stages of infection. The most marked rise was seen in cognitive and sensorimotor complaints. In contrast, significant findings on neurological examination were evident in only the sicker (stage C) subjects. Stage of illness, serum β2-microglobulin, psychiatric indices of depressed mood or anxiety, and NP "motor" performance were the most significant independent variables associated with the presence of neurological symptoms. CSF pleocytosis was seen early (CDC stage A), and may reflect the presence of HIV in the central nervous system (CNS) at the least stages of infection. We also confirmed the value of CSF β2m and neopterin as important markers of advancing disease stage. Whether they predict subclinical CNS involvement is to be determined by longitudinal observations. Conclusion. Neurological complains are common in medically asymptomatic HIV subjects whereas signs are not. The symptoms correlate with commonly determined independent measures of depression, anxiety, NP tests of fine motor speed and strength, as well as indices of disease worsening (CDC stage, serum β2m).
Optimizing Salmonella enterica serovar Typhimurium for bacteria-mediated tumor therapy

ABSTARCT Bacteria-mediated tumor therapy using Salmonella enterica serovar Typhimurium is a therapeutic option with great potential. Numerous studies explored the potential of Salmonella Typhimurium for therapeutic applications, however reconciling safety with vectorial efficacy remains a major issue. Recently we have described a conditionally attenuated Salmonella vector that is based on genetic lipopolysaccharide modification. This vector combines strong attenuation with appropriate anti-tumor properties by targeting various cancerous tissues in vivo. Therefore, it was promoted as an anti-tumor agent. In this addendum, we summarize these findings and demonstrate additional optimization steps that may further improve the therapeutic efficacy of our vector strain.
An Antimicrobial Cathelicidin Peptide, Human CAP18/LL-37, Suppresses Neutrophil Apoptosis via the Activation of Formyl-Peptide Receptor-Like 1 and P2X71

Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to the innate host defense. An antibacterial cathelicidin, human cationic antibacterial protein of 18 kDa/LL-37, not only exhibits potent bactericidal activities against Gram-negative and Gram-positive bacteria, but also functions as a chemoattractant for immune cells, including neutrophils. During bacterial infections, the life span of neutrophils is regulated by various pathogen- and host-derived substances. In this study, to further evaluate the role of LL-37 in innate immunity, we investigated the action of LL-37 on neutrophil apoptosis. Neutrophil apoptosis was assessed using human blood neutrophils based on the morphological changes. Of note, LL-37 dose dependently (0.01–5 μg/ml) suppressed neutrophil apoptosis, accompanied with the phosphorylation of ERK-1/2, expression of Bcl-xL (an antiapoptotic protein), and inhibition of caspase 3 activity. Interestingly, LL-37-induced suppression of neutrophil apoptosis was attenuated by the antagonists for formyl-peptide receptor-like 1 (FPRL1) and P2X7 nucleotide receptor. Of importance, the agonists for FPRL1 and P2X7 apparently suppressed neutrophil apoptosis. Collectively, these observations indicate that LL-37 cannot only kill bacteria, but also modulate (suppress) neutrophil apoptosis via the activation of FPRL1 and P2X7 in bacterial infections. Suppression of neutrophil apoptosis results in the prolongation of their life span, and may be advantageous for host defense against bacterial invasion.
A role for adrenomedullin as a pain-related peptide in the rat

Adrenomedullin (AM) belongs to the calcitonin gene-related peptide (CGRP) family and is a well known potent vasodilator. We show here that AM is a powerful pain-inducing neuropeptide. AM-like immunoreactivity is widely distributed in both CGRP-containing and lectin IB4-binding nociceptors in dorsal root ganglion and axon terminals in the superficial dorsal horn of the rat spinal cord. Specific binding sites for the radioligand, [125I]AM13–52 as well as immunoreactivity for receptor markers such as the calcitonin receptor-like receptor and three receptor-activity-modifying proteins are localized in the superficial dorsal horn, demonstrating the existence of AM/CGRP receptors in this region. Intrathecal injection of rat AM1–50, dose- and time-dependently, induced long-lasting heat hyperalgesia and increased the phosphorylation of Akt and GSK3β in the dorsal horn. Pre- and posttreatments with the AM receptor antagonist AM22–52 and PI3 kinase inhibitors (LY294002 and Wortmannin) significantly blocked or reversed AM-induced heat hyperalgesia. Pre- and posttreatments with AM22–52 and Wortmannin also significantly blocked or reversed intraplantar capsaicin-induced heat hyperalgesia. Taken together, our results demonstrate that AM acts as a pain-inducing peptide in the dorsal horn. By activating specific receptors (likely AM2) and the PI3K/Akt/GSK3β signaling pathway, AM could play a significant role in long-lasting heat hypersensitivity and inflammatory heat hyperalgesia.
Perceptually Motivated Real-Time Compression of Motion Data Enhanced by Incremental Encoding and Parameter Tuning

We address the problem of efﬁcient real-time motion data compression considering human perception. Using incremental encoding plus a database of motion primitives for each key point, our method achieves a higher or competitive compression rate with less online overhead. Trade-off between visual quality and bandwidth usage can be tuned by varying a single threshold value. A user study was performed to measure the sensitivity of human subjects to reconstruction errors in key rotation angles. Based on these evaluations we are able to perform lossy compression on the motion data without noticeable degradation in rendered qualities. While achieving real-time performance, our technique outperforms other methods in our experiments by achieving a compression ratio exceeding 50 : 1 on regular sequences.
Regulation of the Versican Promoter by the β-Catenin-T-cell Factor Complex in Vascular Smooth Muscle Cells*

The proteoglycan versican is pro-atherogenic and central to vascular injury and repair events. We identified the signaling pathways and promoter elements involved in regulation of versican expression in vascular smooth muscle cells. Phosphatidylinositol 3-kinase inhibitor, LY294002, significantly decreased versican-luciferase (Luc) promoter activity and endogenous mRNA levels. We further examined the roles of protein kinase B and glycogen synthase kinase (GSK)-3β, downstream effectors of phosphatidylinositol 3-kinase, in the regulation of versican transcription. Co-transfection of dominant negative and constitutively active protein kinase B constructs with a versican-Luc construct decreased and increased promoter activity, respectively. Inhibition of GSK-3β activity by LiCl augmented accumulation of β-catenin and caused induction of versican-Luc activity as well as versican mRNA levels. β-Catenin has no DNA binding domain, therefore it cannot directly induce transcription of the versican promoter. Software analysis of the versican promoter revealed two potential binding sites for T-cell factors (TCFs), proteins that confer transcriptional activation of β-catenin. Electrophoretic mobility shift and supershift assays revealed specific binding of human TCF-4 and β-catenin to oligonucleotides corresponding to a potential TCF binding site in the versican promoter. In addition to binding assays, we directly assessed the dependence of versican promoter activity on TCF binding sites. Site-directed mutagenesis of the TCF site located -492 bp relative to the transcription start site markedly diminished versican-Luc activity. Co-transfection of TCF-4 with versican-Luc did not increase promoter activity, but addition of β-catenin and TCF-4 significantly stimulated basal versican promoter activity. Our findings suggest that versican transcription is predominantly mediated by the GSK-3β pathway via the β-catenin-TCF transcription factor complex in smooth muscle cells, wherein such regulation contributes to the normal or aberrant formation of provisional matrix in vascular injury and repair events.
Efficient Transmission of Two Different Sheep Scrapie Isolates in Transgenic Mice Expressing the Ovine PrP Gene

ABSTRACT We produced transgenic mice expressing the sheep prion protein to obtain a sensitive model for sheep spongiform encephalopathies (scrapie). The complete open reading frame, with alanine, arginine, and glutamine at susceptibility codons 136, 154, and 171, respectively, was inserted downstream from the neuron-specific enolase promoter. A mouse line, Tg(OvPrP4), devoid of the murine PrP gene, was obtained by crossing with PrP knockout mice. Tg(OvPrP4) mice were shown to selectively express sheep PrP in their brains, as demonstrated in mRNA and protein analysis. We showed that these mice were susceptible to infection by sheep scrapie following intracerebral inoculation with two natural sheep scrapie isolates, as demonstrated not only by the occurrence of neurological signs but also by the presence of the spongiform changes and abnormal prion protein accumulation in their brains. Mean times to death of 238 and 290 days were observed with these isolates, but the clinical course of the disease was strikingly different in the two cases. One isolate led to a very early onset of neurological signs which could last for prolonged periods before death. Independently of the incubation periods, some of the mice inoculated with this isolate showed low or undetectable levels of PrPsc, as detected by both Western blotting and immunohistochemistry. The development of experimental scrapie in these mice following inoculation of the scrapie infectious agent further confirms that neuronal expression of the PrP open reading frame alone is sufficient to mediate susceptibility to spongiform encephalopathies. More importantly, these mice provide a new and promising tool for studying the infectious agents in sheep spongiform encephalopathies.
Effect of heat treatment on copper removal onto manure-compost-activated carbons

The work was aimed to investigate the effect of heat treatment of manure-compost-based activated carbons on the adsorption of copper from aqueous solution. Activated carbons were characterized according to physical structures and surface functional groups. All equilibrium data of activated carbons formerly treated at different temperatures obeyed Langmuir model to linear approximation. Results showed that copper ions favorably adsorbed onto the mesopores at lower equilibrium concentrations and subsequently changed to the micropores at higher equilibrium concentrations. It was found that the increase in electron density upon heat treatment offered higher tendency for the uniform amount of protons to occupy the surface sites. Analysis of Scatchard plots suggested that the affinity driven by the mesopores toward copper ions was stronger than that of the micropores.
Galantamine in AD

Background: Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD. Methods: A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable. Results: Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity. Conclusions: Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.
Robust Multi-Sensor Detection of Polymorphic NQR Signals

Nuclear quadrupole resonance (NQR) is a radio frequency (RF) technique, able to distinguish between polymorphic forms of compounds containing quadrupolar nuclei, a requirement fulfilled by many high explosives and narcotics. To alleviate the problems of low signal to noise ratio and strong RF interference in NQR detection, various multi-sensor NQR signal detection algorithms have recently been proposed. These algorithms, however, assume the presence of a single polymorph with its associated amplitudes known to within a scaling, and any error in this a priori information will lead to performance degradation. In this paper, we develop a robust multi-sensor hybrid algorithm able to process NQR signals from multiple polymorphs while allowing the associated amplitudes to vary within an uncertainty hyper-sphere. Numerical investigations indicate that the proposed algorithm provides significant performance gains as compared to existing algorithms when there are multiple polymorphs present and/or when uncertainties in the amplitudes exist.
Physical Chemistry of the H2SO4/HNO3/H2O System: Implications for Polar Stratospheric Clouds

Polar stratospheric clouds (PSCs) play a key role in stratospheric ozone depletion. Surface-catalyzed reactions on PSC particles generate chlorine compounds that photolyze readily to yield chlorine radicals, which in turn destroy ozone very efficiently. The most prevalent PSCs form at temperatures several degrees above the ice frost point and are believed to consist of HNO3 hydrates; however, their formation mechanism is unclear. Results of laboratory experiments are presented which indicate that the background stratospheric H2SO4/H2O aerosols provide an essential link in this mechanism: These liquid aerosols absorb significant amounts of HNO3 vapor, leading most likely to the crystallization of nitric acid trihydrate (NAT). The frozen particles then grow to form PSCs by condensation of additional amounts of HNO3 and H2O vapor. Furthermore, reaction probability measurements reveal that the chlorine radical precursors are formed readily at polar stratospheric temperatures not just on NAT and ice crystals, but also on liquid H2SO4 solutions and on solid H2SO4 hydrates. These results imply that the chlorine activation efficiency of the aerosol particles increases rapidly as the temperature approaches the ice frost point regardless of the phase or composition of the particles.
Protein pattern of Xenopus laevis embryos grown in simulated microgravity

Numerous studies indicate that microgravity affects cell growth and differentiation in many living organisms, and various processes are modified when cells are placed under conditions of weightlessness. However, until now, there is no coherent explanation for these observations, and little information is available concerning the biomolecules involved. Our aim has been to investigate the protein pattern of Xenopus laevis embryos exposed to simulated microgravity during the first 6 days of development. A proteomic approach was applied to compare the protein profiles of Xenopus embryos developed in simulated microgravity and in normal conditions. Attention was focused on embryos that do not present visible malformations in order to investigate if weightlessness has effects at protein level in the absence of macroscopic alterations. The data presented strongly suggest that some of the major components of the cytoskeleton vary in such conditions. Three major findings are described for the first time: (i) the expression of important factors involved in the organization and stabilization of the cytoskeleton, such as Arp (actin‐related protein) 3 and stathmin, is heavily affected by microgravity; (ii) the amount of the two major cytoskeletal proteins, actin and tubulin, do not change in such conditions; however, (iii) an increase in the tyrosine nitration of these two proteins can be detected. The data suggest that, in the absence of morphological alterations, simulated microgravity affects the intracellular movement system of cells by altering cytoskeletal proteins heavily involved in the regulation of cytoskeleton remodelling.