Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammation-inducing Factors of Mycoplasma pneumoniae

Mycoplasma pneumoniae, which causes mycoplasmal pneumonia in human, mainly causes pneumonia in children, although it occasionally causes disease in infants and geriatrics. Some pathogenic factors produced by M. pneumoniae, such as hydrogen peroxide and Community-Acquired Respiratory Distress Syndrome (CARDS) toxin have been well studied. However, these factors alone cannot explain this predilection. The low incidence rate of mycoplasmal pneumonia in infants and geriatrics implies that the strong inflammatory responses induced by M. pneumoniae coordinate with the pathogenic factors to induce pneumonia. However, M. pneumoniae lacks a cell wall and does not possess an inflammation-inducing endotoxin, such as lipopolysaccharide (LPS). In M. pneumoniae, lipoproteins were identified as an inflammation-inducing factor. Lipoproteins induce inflammatory responses through Toll-like receptors (TLR) 2. Because Mycoplasma species lack a cell wall and lipoproteins anchored in the membrane are exposed, lipoproteins and TLR2 have been thought to be important for the pathogenesis of M. pneumoniae. However, recent reports suggest that M. pneumoniae also induces inflammatory responses also in a TLR2-independent manner. TLR4 and autophagy are involved in this TLR2-independent inflammation. In addition, the CARDS toxin or M. pneumoniae cytadherence induces inflammatory responses through an intracellular receptor protein complex called the inflammasome. In this review, the inflammation-inducing factors of M. pneumoniae are summarized.
Looking upstream: enhancers of child nutritional status in post-flood rural settings

Background. Child undernutrition and flooding are highly prevalent public health issues in many developing countries, yet we have little understanding of preventive strategies for effective coping in these circumstances. Education has been recently highlighted as key to reduce the societal impacts of extreme weather events under climate change, but there is a lack of studies assessing to what extent parental education may prevent post-flood child undernutrition. Methods and Materials. One year after large floods in 2008, we conducted a two-stage cluster population-based survey of 6–59 months children inhabiting flooded and non-flooded communities of Jagatsinghpur district, Odisha (India), and collected anthropometric measurements on children along with child, parental and household level variables through face-to-face interviews. Using multivariate logistic regression models, we examined separately the effect of maternal and paternal education and other risk factors (mainly income, socio-demographic, and child and mother variables) on stunting and wasting in children from households inhabiting recurrently flooded communities (2006 and 2008; n = 299). As a comparison, separate analyses on children in non-flooded communities were carried out (n = 385). All analyses were adjusted by income as additional robustness check. Results. Overall, fathers with at least completed middle education (up to 14 years of age and compulsory in India) had an advantage in protecting their children from child wasting and stunting. For child stunting, the clearest result was a 100–200% lower prevalence associated with at least paternal secondary schooling (compared to no schooling) in flooded-areas. Again, only in flooded communities, an increase in per capita annual household income of 1,000 rupees was associated to a 4.7–4.9% lower prevalence of child stunting. For child wasting in flooded areas, delayed motherhood was associated to better nutritional outcomes (3.4% lower prevalence per year). In flooded communities, households dedicated to activities other than agriculture, a 50–51% lower prevalence of child wasting was estimated, suggesting farmers and fishermen as the most vulnerable livelihoods under flooding. In flooded areas, lower rank castes were at higher odds of both child wasting and stunting. Conclusions. In the short-term, protracted nutritional response in the aftermath of floods should be urgently implemented and target agricultural livelihoods and low-rank castes. Education promotion and schooling up to 14 years should have positive impacts on improving children nutritional health in the long run, especially under flooding. Policies effectively helping sustainable livelihood economic development and delayed motherhood are also recommended.
The role of ultra-mini percutaneous nephrolithotomy in the treatment of kidney stones.

OBJECTIVE In our study we aimed to evaluate outcomes of ultra-mini-percutaneous nephrolithotomy (UMP) performed for the treatment of kidney stones. MATERIAL AND METHODS Between October 2014 and September 2015, a single surgeon performed UMP on a total of 49 consecutive patients with symptomatic kidney stones at our center. Pregnants, anticogulant users, patients with bleeding diathesis pyonephrosis, and partial/complete staghorn stones were excluded from the study. Patient characteristics, operative data and postoperative outcomes were assessed in detail. RESULTS The UMP was performed on 50 (34 right/16 left) renal units of the 48 (28 male/20 female) patients included in this study. The mean age and body mass index was 36.5 (2-83) years and 26.2 (17.6-32.8) kg/m2, respectively. Mean stone size was calculated as 22.2 (10-55) mm. The mean durations of the operations and fluoroscopic examination were calculated as 65.4 (20-120) minutes and 89.4 (9-322) seconds, respectively. The mean duration of hospitalization was 1.4 (1-5) days. In 52% of the patients the procedure was terminated tubeless. Mean hemoglobin drop was 0.6 (0-3) g/dL. Our series experienced a 10% complication rate. The UMP procedure was successful in 96% of the renal units at the 1st month control visit assessment. CONCLUSION The outcomes of our study have demonstrated that UMP is an effective and safe treatment modality, especially in the treatment of medium-sized renal calculi.
A small area analysis of mortality inequalities in Scotland, 1980-2001

This thesis examines the changing patterns of mortality in Scotland, with particular emphasis on whether there are widening mortality inequalities among small areas in Scotland. The annual number of deaths in Scotland has decreased steadily since the 1950s, yet mortality rates in Scotland are amongst the highest in Europe for many causes. Furthermore, mortality from some causes, such as suicide, has been increasing over time, particularly among young adults. Evidence suggests that inequalities in mortality have widened over time in Scotland, despite substantial investment in policies aimed at reducing inequalities. Therefore, it is important to seek geographical clues that might help explain what causes these high mortality rates. The changing patterns in Scottish mortality between 1980 and 2001 were examined for small areas, created by the author, known as Consistent Areas Through Time (CATTs). These areas have the same boundaries for each census, so that direct comparisons over time are possible. In this study, CATTs have been used to investigate three aspects of the mortality gap in Scotland. First, the widening mortality gaps between 1980-1982 and 1999-2001 are examined for the total population and for premature mortality (<65 years). Second, the influence that geographic scale and deprivation have on the relationship between population change and premature mortality are assessed. Third, suicide inequalities are examined for the younger (15-44 years), older (45+) and total population, using mortality ratios and statistical modelling. The research found that inequalities in premature mortality (<65) have widened for all causes of death studied, particularly for suicide. The negative association between mortality and population change was affected by geographic scale, but this relationship could not be fully explained by deprivation. Small area analyses found that the Highlands and Islands had higher suicide rates than elsewhere in Scotland for males, but not females, when social variables were controlled for.
Ultra Low-Power Clocking Scheme Using Energy Recovery and Clock Gating

A significant fraction of the total power in highly synchronous systems is dissipated over clock networks. Hence, low-power clocking schemes are promising approaches for low-power design. We propose four novel energy recovery clocked flip-flops that enable energy recovery from the clock network, resulting in significant energy savings. The proposed flip-flops operate with a single-phase sinusoidal clock, which can be generated with high efficiency. In the TSMC 0.25-mum CMOS technology, we implemented 1024 proposed energy recovery clocked flip-flops through an H-tree clock network driven by a resonant clock-generator to generate a sinusoidal clock. Simulation results show a power reduction of 90% on the clock-tree and total power savings of up to 83% as compared to the same implementation using the conventional square-wave clocking scheme and flip-flops. Using a sinusoidal clock signal for energy recovery prevents application of existing clock gating solutions. In this paper, we also propose clock gating solutions for energy recovery clocking. Applying our clock gating to the energy recovery clocked flip-flops reduces their power by more than 1000times in the idle mode with negligible power and delay overhead in the active mode. Finally, a test chip containing two pipelined multipliers one designed with conventional square wave clocked flip-flops and the other one with the proposed energy recovery clocked flip-flops is fabricated and measured. Based on measurement results, the energy recovery clocking scheme and flip-flops show a power reduction of 71% on the clock-tree and 39% on flip-flops, resulting in an overall power savings of 25% for the multiplier chip.
Urea kinetic modelling--are any of the 'bedside' Kt/V formulae reliable enough?

BACKGROUND Longevity on dialysis is determined by many factors. One of these has increasingly been seen to be 'dialysis dose'. There are several methods for calculating dialysis dose. We wanted prospectively to test 'gold-standard' UKM-Kt/V with various shortcut bedside formulae, to see whether reliance on the latter approach was likely to lead to errors in over- or underprescribing dialysis regimens. METHODS Ten bedside formulae for the calculation of Kt/V (urea) were compared with UKM Kt/V values, in a month-long study involving 507 dialysis sessions in 50 patients in a single-centre in-patient haemodialysis unit. RESULTS For patients with UKM Kt/V<0.8 (median 0.69, n=140), simplified formulae had a difference (delta) of 0.094-0.396 from the calculated UKM resulting in an inter-method variability ranging from 13 to 57%. The least difference was seen with the Calzavara formula (P=NS), maximum difference with the Barth formulae (P<0.05). No statistically significant differences were seen when comparing Daugirdas 1 and 2 and Keshaviah formulae with UKM, for patients with UKM Kt/V<0.8. For patients with UKM Kt/V in the range 0.8-1.4 (median 1.06, n=285) the extreme recorded values from simplified formulae were 0.012 (least different) and 0.245 (most different) from the UKM mean, with an inter-method variability ranging between 1.1% (Basile method) to 23.1% (Calzavara). No statistically significant difference were seen when comparing Daugirdas 1 and 2, Keshaviah, and Lowrie formulae with UKM, for patients with UKM Kt/V 0.8-1.4. For patients with the highest UKM Kt/V values (>1.4; median 1.58, n=72), all simplified formulae gave Kt/V values lower than UKM Kt/V: the minimum difference was 0.070 using Jindal (P=NS, intermethod variability of 4.4%), while the maximum was seen when using Calzavara (P<0.05; difference = 0.69; intermethod variability of 43.7%). There was also no statistically significant difference for Basile and Kerr methods. For the group as a whole the biggest difference from UKM mean values was obtained using Barth's and Calzavara's formulae (delta of 0.171 and 0.140 respectively (P<0.05)). CONCLUSIONS The best correlations were seen with the Daugirdas 2 formula (r2=0.953). Also, comparing grouped formulae containing ln(Co/Ct) terms with those incorporating the (Co-Ct)/Co ratio (i.e. the urea reduction) there was a better correlation for all formulae employing the logarithmic transformation (r2=0.951-0.953 cf. r2=0.939-0.940). Nevertheless no bedside formula had the accuracy of UKM-Kt/V.
Can selection explain the protective effects of farming on asthma?

INTRODUCTION AND OBJECTIVE Reduced asthma and allergy risks in farmers have been ascribed to microbial exposures. However, selection may also play a role and this was assessed in two Scandinavian farming populations. MATERIALS AND METHODS Asthma prevalence in 739 Danish farming students was compared to that of 1,105 siblings. 8,482 Norwegian farmers were also compared with 349 early retired farmers. RESULTS The prevalence of ever-asthma was 5.4% in farming students and 5.2% in siblings (OR 1.1; 95%CI 0.73-1.7). Current asthma in farmers was 3.0% compared to 6.3% in farmers who had retired early (OR 1.8, 95%CI 1.1-2.9). Adjustments for early retirement increased the asthma prevalence by 0.3-0.6%. Farmers who had changed production were more likely to have asthma (OR 9.8, 95% CI 6.0-16). CONCLUSIONS No healthy worker selection into farming was observed and changes in asthma prevalence due to early retirement were small. Selection effects are therefore unlikely to explain the protective effects of farming on asthma.
Basic Autonomy as a Fundamental Step in the Synthesis of Life

In the search for the primary roots of autonomy (a pivotal concept in Varela's comprehensive understanding of living beings), the theory of autopoiesis provided an explicit criterion to define minimal life in universal terms, and was taken as a guideline in the research program for the artificial synthesis of biological systems. Acknowledging the invaluable contribution of the autopoietic school to present biological thinking, we offer an alternative way of conceiving the most basic forms of autonomy. We give a bottom-up account of the origins of self-production (or self-construction, as we propose to call it), pointing out which are the minimal material and energetic requirements for the constitution of basic autonomous systems. This account is, indeed, committed to the project of developing a general theory of biology, but well grounded in the universal laws of physics and chemistry. We consider that the autopoietic theory was formulated in highly abstract terms and, in order to advance in the implementation of minimal autonomous systems (and, at the same time, make major progress in exploring the origins of life), a more specific characterization of minimal autonomous systems is required. Such a characterization will not be drawn from a review of the autopoietic criteria and terminology ( la Fleischaker) but demands a whole reformulation of the question: a proper naturalization of the concept of autonomy. Finally, we also discuss why basic autonomy, according to our account, is necessary but not sufficient for life, in contrast with Varela's idea that autopoiesis was a necessary and sufficient condition for it.
Biomarker evaluation and comparison using the controls as a reference population.

The classification accuracy of a continuous marker is typically evaluated with the receiver operating characteristic (ROC) curve. In this paper, we study an alternative conceptual framework, the "percentile value. " In this framework, the controls only provide a reference distribution to standardize the marker. The analysis proceeds by analyzing the standardized marker in cases. The approach is shown to be equivalent to ROC analysis. Advantages are that it provides a framework familiar to a broad spectrum of biostatisticians and it opens up avenues for new statistical techniques in biomarker evaluation. We develop several new procedures based on this framework for comparing biomarkers and biomarker performance in different populations. We develop methods that adjust such comparisons for covariates. The methods are illustrated on data from 2 cancer biomarker studies.
Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity.

Six linear, two-coordinate cationic Au(I) N-heterocyclic carbene complexes of the form [(R2Im)2Au]+ (R = Me 1, Me, Et 2, i-Pr 3, n-Bu 4, t-Bu 5 and Cy 6) have been prepared by the reaction of two equivalents of the appropriate dialkylimidazol-2-ylidene (R2Im) with (Me2S)AuCl in dmf. Single crystal structural studies for 1.PF6, 2.PF6), 3.Cl and 4-6.PF6 show that for all six complexes the gold(I) centres have quasi-linear C-Au-C coordination, with quasi-parallel pairs of aromatic imidazole planes, except in 5.PF6 where they are quasi-normal; in the latter, Au-C are 2.038(3), 2.033(3) A, cf. (e.g.) 2.027(2) A. Inter-cation Au.Au are close at 3.487(2), 3.525(2) A in 1PF6 and 2.PF6. The structural studies and low temperature NMR experiments provide no supportive evidence for the presence of pi back-bonding within this series of complexes. The lipophilicities of the six compounds, as estimated from the logarithm of the n-octanol-water partition coefficients (log P), varied across the series within the range -1.09 to 1.73. To investigate their potential as possible anti-mitochondrial anti-tumour agents, five of the compounds have been evaluated for their propensities to induce mitochondrial membrane permeabilization (MMP) in isolated rat liver mitochondria. At concentrations between 1-10 microM compounds 1.Br and 3-6.Cl induced dose-dependent, Ca2+-sensitive mitochondrial swelling at rates that increased with the lipophilicities of the complexes, with the most lipophilic compounds inducing the most rapid onset of swelling. The swelling was completely inhibited by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore.
Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar‐to‐ductal metaplasia and fibrosis during pancreatitis

Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor‐β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ‐RII) using a Cre–LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein‐induced pancreatitis. We show that TGFβ‐RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ‐RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell‐autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ‐RII signalling stimulates the expression of cyclin‐dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ‐RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ‐based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Suppression of Cyclin-Dependent Kinase 5 Activation by Amyloid Precursor Protein: A Novel Excitoprotective Mechanism Involving Modulation of Tau Phosphorylation

Alzheimer's disease is cytopathologically characterized by loss of synapses and neurons, neuritic amyloid plaques consisting of β-amyloid (Aβ) peptides, and neurofibrillary tangles consisting of hyperphosphorylated tau protein in susceptible brain regions. Aβ, which triggers a cascade of pathogenic events including tau phosphorylation and neuronal excitotoxicity, is proteolytically derived from β-amyloid precursor protein (APP); the pathological and physiological functions of APP, however, remain undefined. Here we demonstrate that the level of tau phosphorylation in cells and brains deficient in APP is significantly higher than that in wild-type controls, resulting from activation of cyclin-dependent kinase 5 (CDK5) but not glycogen synthase kinase 3, the two major tau kinases. In addition, we show that overexpression of APP or its non-amyloidogenic homolog amyloid precursor-like protein 1 suppresses both basal and stress-induced CDK5 activation. The ectodomain of APP, sAPPα, is responsible for inhibiting CDK5 activation. Furthermore, neurons derived from APP-deficient mice exhibit reduced metabolism and survival rates and are more susceptible to excitotoxic glutamate-induced apoptosis. These neurons also manifest significant defects in neurite outgrowth compared with neurons from the wild-type littermates. The observed neuronal excitotoxicity/apoptosis is mediated through a mechanism involving CDK5 activation. Our study defines a novel neuroprotective function for APP in preventing tau hyperphosphorylation via suppressing overactivation of CDK5. We suggest that CDK5 activation, through a calcium/calpain/p25 pathway, plays a key role in neuronal excitotoxicity and represents an underlying mechanism for the physiological functions of APP.
Parvovirus-Induced Depletion of Cyclin B1 Prevents Mitotic Entry of Infected Cells

Parvoviruses halt cell cycle progression following initiation of their replication during S-phase and continue to replicate their genomes for extended periods of time in arrested cells. The parvovirus minute virus of mice (MVM) induces a DNA damage response that is required for viral replication and induction of the S/G2 cell cycle block. However, p21 and Chk1, major effectors typically associated with S-phase and G2-phase cell cycle arrest in response to diverse DNA damage stimuli, are either down-regulated, or inactivated, respectively, during MVM infection. This suggested that parvoviruses can modulate cell cycle progression by another mechanism. In this work we show that the MVM-induced, p21- and Chk1-independent, cell cycle block proceeds via a two-step process unlike that seen in response to other DNA-damaging agents or virus infections. MVM infection induced Chk2 activation early in infection which led to a transient S-phase block associated with proteasome-mediated CDC25A degradation. This step was necessary for efficient viral replication; however, Chk2 activation and CDC25A loss were not sufficient to keep infected cells in the sustained G2-arrested state which characterizes this infection. Rather, although the phosphorylation of CDK1 that normally inhibits entry into mitosis was lost, the MVM induced DDR resulted first in a targeted mis-localization and then significant depletion of cyclin B1, thus directly inhibiting cyclin B1-CDK1 complex function and preventing mitotic entry. MVM infection thus uses a novel strategy to ensure a pseudo S-phase, pre-mitotic, nuclear environment for sustained viral replication.