Miracle-dz/UniFAR-FTUs huggingface dataset:
Work of breathing during CPAP and heated humidified high-flow nasal cannula

Objective To determine whether continuous positive airway pressure (CPAP) compared with heated humidified, high-flow nasal cannula (HHFNC) in infants with evolving or established bronchopulmonary dysplasia (BPD) reduced the work of breathing (WOB) and thoracoabdominal asynchrony (TAA) and improved oxygen saturation (SaO2). Design Randomised crossover study. Setting Tertiary neonatal unit. Patients 20 infants (median gestational age of 27.6 weeks (range 24.6–31.9 weeks)) were studied at a median postnatal age of 30.9 weeks (range 28.1–39.1 weeks). Interventions Infants were studied on 2 consecutive days. On the first study day, they were randomised to either CPAP or HHFNC each for 2 h, the order being reversed on the second day. Main outcome measures The WOB was assessed by measuring the pressure time product of the diaphragm (PTPdi). PTPdi, TAA and SaO2 were assessed during the final 5 min of each 2 h period and the results on the two study days were meaned. Results There were no significant differences in the results on CPAP versus HHFNC: mean PTPdi 226 (range 126–294) versus 224 cm H2O/s/min (95% CI for difference: −27 to 22; p=0.85) (range 170–318) (p=0.82), mean TAA 13.4° (range 4.51°–23.32°) versus 14.01° (range 4.25°–23.86°) (95% CI for difference: −3.9 to 2.8: p=0.73) (p=0.63) and mean SaO2 95% (range 93%–100%) versus 95% (94%–99%), (95% CI for difference −1.8 to 0.5; p=0.25) (p=0.45). Conclusion In infants with evolving or established BPD, CPAP compared with HHFNC offered no significant advantage with regard to the WOB, degree of asynchrony or oxygen saturation.
Influence of feeding schedule on the chronopharmacological aspects of sodium valproate in mice.

The role of feeding schedule on the chronopharmacological aspects of sodium valproate (valproic acid; VPA) was examined. ICR male mice were housed in a 12-hr light and 12-hr dark cycle (lights on at 0700, off at 1900) with food and water ad libitum, under a repeated time restricted feeding (feeding time: 0900-1700) for 2 wk, under fasting for 12 hr or under fasting for 12 hr and feeding for 2 hr before the experiment. VPA was used at an i.p. dose of 1200 mg/kg for toxicity, an oral dose of 600 mg/kg for electroshock seizure threshold and plasma VPA concentration, an i.v. dose of 50 mg/kg for pharmacokinetic study and at a rate of 1072.6 micrograms/hr for constant-rate administration using an osmotic minipump. The toxicity, electroshock seizure threshold and VPA concentration (probably at the absorption phase) were significantly higher in the light and lower in the dark showing rhythmicity. The rhythmicity in VPA concentration during constant-rate administration was related to that of clearance and volume of distribution. The rhythms of electroshock seizure threshold and VPA absorption were controlled easily by the temporal manipulation of feeding schedule, but the rhythms of toxicity, clearance and volume of distribution were not. The manipulation of the feeding schedule and the choice of the most appropriate time of day for drug administration may help to achieve rational chronotherapeutics of some drugs including VPA in certain experimental and clinical situations.
The embryonic vertebrate forebrain: the prosomeric model.

C. elegans early embryos extends beyond the parallels between hunchback and glp-1 translational regulation. Both embryos contain cytoplasmic "granules" in the posterior region of the zygote that are segregated ultimately to germ cell precursors during em-bryogenesis-the polar granules of Dro-sophila (14) and the P granules of C. elegans (15) (see figure). In Drosophila, maternal nanos RNA is associated with polar granules ; perhaps in C. elegans, a homolog of nanos is associated with P granules. What about vertebrates? Does transla-tional repression in the posterior cyto-plasm establish embryonic polarity in these "higher" animals? A hint that this mechanism may indeed function in vertebrates comes from the identification of a maternal transcript that encodes a nanos-like protein called Xcat-2 in Xenopus embryos (16). Although the function of Xcat-2 is unknown , its location at the vegetal pole suggests a role in early pattern formation. Furthermore , a "germ plasm" exists in the veg-etal cytoplasm of amphibian embryos that may be analogous to P granules and polar granules of worms and flies (17). Over the past decade, a handful of molecular mechanisms have been implicated in the pattern-ing of Drosophila, C. elegans, and Xenopus embryos (1, 18, 19). On the basis of the diversity of these mechanisms, the prevailing view has been that each embryo has differentially employed a handful of common molecular mechanisms to create its own coordinate system. For example, localized transcriptional activators are utilized for patterning of both C. elegans and Dro-sophila early embryos (20-23), but the mechanisms for localization, types of DNA binding protein, and specified fates are not obviously similar. By contrast, the molecular parallels between hunchback and glp-1 regulation suggest the existence of an ancient mechanism for creating asymmetric patterns of gene expression in early embryos (see figure). This mechanism is predicted to depend on a transacting regulator similar to nanos and to act through cis-acting sequences similar to NREs in the 3'UTRs of maternal transcripts. If this molecular machinery regulates polarity in embryos as diverse as worms, flies, and frogs, it becomes plausible that it influences axis formation in all animal embryos, including mammals. "Molecu-lar tinkering" (24) may then come into play to reinforce this primitive patterning control and to derive other axes from it. Research in Drosophila has pioneered our understanding of the molecular mechanisms that can establish the body axes in an early embryo. Now, phylogenetic comparisons will tell us which mechanisms are primitive …
Particulate Matter Triggers Depressive-Like Response Associated With Modulation of Inflammatory Cytokine Homeostasis and Brain-Derived Neurotrophic Factor Signaling Pathway in Mice

Particulate matter (PM) exposure may contribute to depressive-like response in mice. However, few studies have evaluated the adaptive impacts of long-term PM exposure on depressive-like response associated with systemic inflammation and brain-derived neurotrophic factor (BDNF) signaling pathway. We studied the association among depressive-like behaviors, mRNA levels of pro and anti-inflammatory cytokines, and the expression of BDNF signaling pathway in mice by long-term PM exposure. C57BL/6 male mice were exposed to ambient air alongside control mice breathing air filtered through a high-efficiency air PM (HEPA) filter. Depressive-like behaviors were assessed together with proinflammatory, anti-inflammatory cytokine mRNA levels and the modulation of BDNF pathway in hippocampus and olfactory-bulb of mice exposed to PM for 4, 8, and 12 weeks. Exposure to HEPA-filtered air for 4 weeks may exert antidepressant like effects in mice. Proinflammatory cytokines were up-regulated while the expression of BDNF, its high-affinity receptor tropomyosin-related kinase B (TrkB), and the transcription factor (cyclic adenosine monophosphate)-response element-binding protein (CREB) were down-regulated in ambient air mice. However, after 8 weeks, there was no significant difference in the rate of depressive-like behaviors between the 2 groups. After 12 weeks, mice exposed to ambient air again had a higher rate of depressive-like behaviors, significant up-regulation of proinflammatory cytokines, down-regulation of interleukin-10, BDNF, TrkB, and CREB than HEPA mice. Ultrafine PM in brain tissues of mice exposed to ambient air was observed. Our results suggest continuous high-level PM exposure alters the depressive-like response in mice and induces a damage-repair-imbalance reaction.
The Carboxyl-terminal Domain of Closely Related Endotoxin-binding Proteins Determines the Target of Protein-Lipopolysaccharide Complexes*

The bactericidal/permeability increasing (BPI) and lipopolysaccharide (LPS)-binding (LBP) proteins are closely related two-domain proteins in which LPS binding is mediated by the NH2-terminal domain. To further define the role of the COOH-terminal domain of these proteins in delivery of LPS to specific host acceptors, we have compared interactions of LBP, BPI, LBPN-BPIC (NH2-terminal domain of LBP, COOH-terminal domain of BPI), and BPIN-LBPC with purified 3H-LPS and, subsequently, with purified leukocytes and soluble (s)CD14. The COOH-terminal domain of LBP promotes delivery of LPS to CD14 on both polymorphonuclear leukocytes and monocytes resulting in cell activation. In the presence of Ca2+ and Mg2+, LBP and BPI each promote aggregation of LPS to protein-LPS aggregates of increased size (apparent M r > 20 × 106 Da), but only LPS associated with LBP and BPIN-LBPC is disaggregated in the presence of CD14. BPI and LBPN-BPIC promote apparently CD14-independent LPS association to monocytes without cell activation. These findings demonstrate that the carboxyl-terminal domain of these closely related endotoxin-binding proteins dictates the route and host responses to complexes they form with endotoxin.
Differing trends in sexual risk behaviours in three Australian states: New South Wales, Victoria and Queensland, 1998-2006.

BACKGROUND In Australia, the HIV epidemic is concentrated among gay men. In recent years, the number of new diagnoses stabilised in New South Wales (NSW), but increased in other states. We reviewed the trends in sexual behaviours to explain this difference. METHODS We used the Gay Community Periodic Surveys in NSW, Victoria and Queensland during 1998-2006 and restricted analyses to the 30-49 year olds who contribute most of the HIV cases. We used the chi(2)-test for trends in unprotected anal intercourse with casual partners (UAIC) and regular partners, number of partners, type of relationships, knowledge of HIV serostatus and its disclosure. We compared behaviours of HIV-positive and -negative men and men across states using logistic regression adjusted for the year of report. RESULTS Trends in behaviours differed across the states: following a period of increase, UAIC prevalence declined in NSW since 2001, but continued to increase in Victoria and Queensland. There were other changes in NSW that were not observed in Victoria and Queensland: a decline in factors increasing HIV risk (the proportions of men with multiple sex partners and men engaging in UAIC and not knowing or not disclosing HIV serostatus) and an increase in behaviours reducing it (the proportions of men in monogamous relationships and men disclosing HIV serostatus while having UAIC). CONCLUSION There were patterns of declining HIV risk behaviours in NSW, and increasing risk behaviours elsewhere, that mirrored recent changes in HIV case notifications in Australia. These data suggest that behavioural surveillance can predict changes in HIV epidemiology.
Modulation of the antigenic phenotype of early‐passage human melanoma cells derived from multiple autologous metastases by recombinant human leukocyte, fibroblast and immune interferon

We have investigated the relationship between in vitro cultivation of autologous melanoma metastases derived from different patients and their levels of expression of class‐l and‐11 major histocompatibility complex (MHC) antigens and melanoma‐associated antigens (MAAS). Cell cultures were established from 23 individual metastatic melanoma lesions from 10 patients and were tested early after isolation (between 3rd and 10th passages) for both constitutive expression and modulation by recombinant human leukocyte (IFN‐α), fibroblast (IFN‐β) or immune (IFN‐γ) interferon of MHC antigens and MAA. All of the melanoma cell lines displayed altered antigen expression following IFN treatment. While in vitro cultures derived from different individuals varied in both constitutive and IFN‐modified antigenic expression. cultures of autologous metatases derived from the same patient were very similar. In addition, differences in antigenic profile were apparent when early‐passage in vitro cultures were compared with the same melanoma lesion, not established in culture, from which they were derived. The unique de novo and IFN‐modified antigenic phenotype of cultures derived from different patients indicates that the antigenic phenotype displayed by melanoma cultures grown in vitro is genetically determined. The differences found between in vitro cultures and their corresponding in vivo lesions, as well as the antigenic heterogeneity displayed by multiple autologous melanoma lesions in vivo, suggest that the in vivo antigenic phenotype may be determined, at least in part, at an epigenetic level.
Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography

Background— The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event. Methods and Results— Between August 2010 and December 2014, 64 patients were investigated at the time point of VLST as part of an international optical coherence tomography registry. Optical coherence tomography pullbacks were performed after restoration of flow and analyzed at 0.4 mm. A total of 38 early- and 20 newer-generation drug-eluting stents were suitable for analysis. VLST occurred at a median of 4.7 years (interquartile range, 3.1–7.5 years). An underlying putative cause by optical coherence tomography was identified in 98% of cases. The most frequent findings were strut malapposition (34.5%), neoatherosclerosis (27.6%), uncovered struts (12.1%), and stent underexpansion (6.9%). Uncovered and malapposed struts were more frequent in thrombosed compared with nonthrombosed regions (ratio of percentages, 8.26; 95% confidence interval, 6.82–10.04; P<0.001 and 13.03; 95% confidence interval, 10.13–16.93; P<0.001, respectively). The maximal length of malapposed or uncovered struts (3.40 mm; 95% confidence interval, 2.55–4.25; versus 1.29 mm; 95% confidence interval, 0.81–1.77; P<0.001), but not the maximal or average axial malapposition distance, was greater in thrombosed compared with nonthrombosed segments. The associations of both uncovered and malapposed struts with thrombus were consistent among early- and newer-generation drug-eluting stents. Conclusions— The leading associated findings in VLST patients in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent underexpansion without differences between patients treated with early- and new-generation drug-eluting stents. The longitudinal extension of malapposed and uncovered stent was the most important correlate of thrombus formation in VLST.
Decentralized tuning regulators: An application to solve the load and frequency control problem for a large power system

This paper describes the application of decentralized tuning regulators [1] to solve the load and frequency control problem (automatic generation control problem) of a large power system consisting of three interconnected areas with nine synchronous machines. In this problem, it is assumed that the power system is completely unknown, i.e. it is assumed that a mathematical model describing the power system is not available, and it is desired to find a robust decentralized controller for the power system so that the power flow and frequency of the system are regulated, independent of any constant disturbances (load changes) which may affect the system. It is shown that the resultant control system obtained by using decentralized tuning regulator theory is in fact virtually identical to the controller obtained assuming a full knowledge of the mathematical model describing the system. This in turn implies that the conventional way of solving the load and frequency control problem is not likely to be significantly improved on by assuming that a detailed mathematical description of the power system is available or by using more complex controllers.
Cerebellum segmentation in MRI using atlas registration and local multi-scale image descriptors

We propose a novel cerebellum segmentation method for MRI, based on a combination of statistical models of the structure's expected location in the brain and its local appearance. The appearance model is obtained from a k-nearest-neighbor classifier, which uses a set of multi-scale local image descriptors as features. The spatial model is constructed by registering multiple manually annotated datasets to the unlabeled target image. The two components are then combined in a Bayesian framework. The method is quantitatively validated in a leave-one-out experiment using 18 MR images of elderly subjects. The experiment showed that the method produces accurate segmentations. The mean Dice similarity index compared to the manual reference was 0.953 for left and right, and the mean surface distance was 0.49 mm for left and 0.50 mm for right. The combined atlas- and appearance-based method was found to be more accurate than a method based on atlas-registration alone.
Course of HbA1c in non-diabetic pregnancy related to birth weight.

BACKGROUND Despite good glycaemic control (according to the internationally accepted level of HbA1c < 7% (53.0 mmol/mol)) the incidence of macrosomia in pregnant women with diabetes is still very high. We measured HbA1c levels in each of the three trimesters of pregnancy in a cohort of healthy women to determine whether the upper reference level for good glycaemic control in diabetic pregnant females should be lower than the internationally accepted level. Secondly we investigated whether changes in HbA1c values in the course of pregnancy are associated with birth weight. METHODS We determined HbA1c by high-performance liquid chromatography in 103 healthy pregnant women. The results were corrected with a method which was certified by the National Glycohaemoglobin Standardisation Program (NGSP) and standardised to the Diabetes Control and Complication trial reference assay. All women had a body mass index (BMI) < 30, none of the women had diabetes in the family in the first and/or second degree. The multiparous women had no history of macrosomia or small for gestational age infants. RESULTS In the first trimester mean ± SD (range) HbA1c (n=93) was 4.7 ± 1.25% (27.9 ± 13.7 mmol/mol) (3.9-5.4% (19.1-35.5 mmol/mol)), in the second trimester (n=86) 4.6 ± 1.33% (26.8 ± 14.6 mmol/mol) (3.7-5.7% (16.9-38.8 mmol/mol)) and in the third trimester (n=71) 4.9 ± 1.39% (30.1 ± 15.2 mmol/mol) (4.0-6.0% (20.2-42.1 mmol/mol)). The calculated upper reference HbA1c values for the three trimesters were 5.4, 5.5 and 5.8% (35.5, 36.6 and 39.9 mmol/mol), respectively, compared with 6.5% (47.5 mmol/mol) in non-pregnant women in our hospital. We found a significant correlation between the differences of the first and second trimester HbA1c values and the birth weight percentiles (r=-0.251; p=0.032). All 44 women with a decrease in the HbA1c value from the first to the second trimester had a birth weight percentile ≤ 90. In the 30 women with no change or an increase in the HbA1c value from the first to the second trimester there was no relation between HbA1c values and birth weight percentiles, but seven of the 30 (23.3%) had a birth weight percentile of > 90. CONCLUSIONS HbA1c is lower in all three trimesters of normal pregnancy compared with the level in non-pregnant women, and the change in HbA1c from the first to the second trimester predicts (the percentile of) birth weight. This could implicate that in order to prevent macrosomia in pregnant women with diabetes one should aim at lower HbA1c levels than the internationally accepted level, and at a decrease in HbA1c from the first to the second trimester.
Starches from A to C (Chlamydomonas reinhardtii as a Model Microbial System to Investigate the Biosynthesis of the Plant Amylopectin Crystal)

Wide-angle powder x-ray diffraction analysis was carried out on starch extracted from wild-type and mutant Chlamydomonas reinhardtii cells. Strains containing no defective starch synthases as well as mutants carrying a disrupted granule-bound starch synthase structural gene displayed the A type of diffraction pattern with a high degree of crystallinity. Mutants carrying a defect for the major soluble starch synthase (SSS), SSS II, were characterized by a switch to the B type of diffraction pattern with very low crystallinity. Mutant strains carrying SSS I as the only glucan elongation enzyme regained some of their crystallinity but switched to the C type of diffraction pattern. Differential scanning calorimetry analysis correlated tightly with the x-ray diffraction results. Together with the electron microscopy analyses, these results establish C. reinhardtii as a microbial model system displaying all aspects of cereal starch synthesis and structure. We further show that SSS II is the major enzyme involved in the synthesis of crystalline structures in starch and demonstrate that SSS I alone builds a new type of amylopectin structure.
Decreased Expression and Activity of Neprilysin in Alzheimer Disease Are Associated With Cerebral Amyloid Angiopathy

Neprilysin (NEP) degrades amyloid-&bgr; (A&bgr;) and is thought to contribute to its clearance from the brain. In Alzheimer disease (AD), downregulation of NEP has been suggested to contribute to the development of cerebral amyloid angiopathy (CAA). We examined the relationship among NEP, CAA, and APOE status in AD and elderly control cases. NEP was most abundant in the tunica media of cerebrocortical blood vessels and in pyramidal neurons. In homogenates of the frontal cortex, NEP protein levels were reduced in AD but not significantly; NEP enzymatic activity was significantly reduced in AD. Immunohistochemistry revealed a reduction of both vascular and parenchymal NEP. The loss of vessel-associated NEP in AD was inversely related to the severity of CAA, and analysis of cases with severe CAA showed that levels of vascular NEP were reduced to the same extent in A&bgr;-free and A&bgr;-laden vessels, strongly suggesting that the reduction in NEP is not simply secondary to CAA. Possession of APOE &egr;4 was associated with significantly lower levels of both parenchymal and vascular NEP. Colinearity of &egr;4 with the presence of moderate to severe CAA precluded assessment of the independence of this association from NEP levels. However, logistic regression analysis showed low NEP levels to be a significant independent predictor of moderate to severe CAA.
Toxic Gangrenous Megacolon : A Novel Surgical Emergency in MELAS

MELAS syndrome (mitochondrial cytopathy, encephalomyopathy, lactic acidosis and stroke like episodes) is a syndrome in which signs and symptoms of gastro-intestinal disease are uncommon, if not rare. We describe a young female patient who presented as an acute surgical emergency, diagnosed as toxic mega colon necessitating an emergency total colectomy; the diagnosis of MELAS syndrome was made post-operatively. This diagnosis should be considered in patients presenting with acute ischemic colitis or toxic mega colon who have persistent lactic acidosis with encephalopathy and a stormy post-operative course.