Miracle-dz/UniFAR-FTUs huggingface dataset:
Light and Electron Microscopic Analysis of the Central and Peripheral Nervous Systems of Acid Sphingomyelinase‐deficient Mice Resulting from Gene Targeting

The acid sphingomyelinase (aSmase)-deficient mouse line recently generated by gene targeting (Otterbach and Stoffel. 1995) develops a lethal storage disease which is phenotypically comparable to the neurovisceral form of the human sphingomyelinosis, Niemann-Pick disease type A (NPA). This report describes the progressive accumulation of uncatabolized lipid substrates at the cellular and ultrastructural level in different regions of the nervous system of homozygous aSmase−/- mice, including cerebrum, cerebellum, spinal cord, optic nerve and peripheral nerves. We saw a cytoplasmic accumulation of pleomorphic lysosomal structures in cells of all regions under study, most extensively in macrophages, vascular endothelial cells, and also in neuronal perikarya. The complete and early degeneration of Purkinje cells was particularly striking. Moreover, we found a storage material in the cytoplasm of Schwann cells and to a minor extent in oligodendrocytes. In most advanced stages of the disorder, we detected an axonal dystrophy in both the central nervous system (CNS) and peripheral nervous system (PNS), without signs of dysmyelination or demyelination. The morphological changes of the central and peripheral nervous systems in the homozygous aSmase−/- mouse line closely resemble those in human NPA.
Improving diagnostic accuracy of bacterial pharyngitis by near patient measurement of C-reactive protein (CRP)

BACKGROUND Sore throat or pharyngitis is an extremely prevalent condition in primary care. There is a diagnostic dilemma in differentiating bacterial and non-bacterial infections for adequate use of antibiotics. Standard diagnostic procedures take too long for an immediate decision. AIM To evaluate, if near patient C-reactive protein measurement in the general practice surgery improves diagnostic accuracy. METHOD One hundred and seventy-nine consecutive patients with sore throat, from 15 general practitioners (GPs) in southern Germany (phase 1) and 161 consecutive patients from 14 GPs (phase 2), were examined physically and a throat-swab was taken and white blood-cell count (WBC) and CRP-measurement were performed. In phase 1, CRP was measured centrally to assess the method's diagnostic value and the adequate threshold. In the second phase, near patient CRP was measured and CRP values were used to make a diagnosis. RESULTS Using relative operating characteristics (ROC) analysis, the diagnostic value of CRP measurement was much better than WBC count (area under curve = 0.85 versus 0.68). All diagnostic parameters improved when using the near patient CRP measurement. Sensitivity went up from 0.61 (95% confidence interval = 0.45-0.75) to 0.78 (0.61-0.90), specificity went up from 0.73 (0.65-0.81) to 0.82 (0.73-0.88). Positive and negative predictive value improved significantly as well. Diagnostic accuracy went up from 70.1% to 81.0%. Out of 1000 theoretical patients with sore throat, 109 more will be treated correctly when using CRP measurement as a diagnostic tool. CONCLUSIONS Use of near patient CRP measurement can improve diagnostic accuracy in the differentiation of bacterial and non-bacterial pharyngitis in primary care, and potentially results in a more adequate use of antibiotics.
Type-1 Diabetes Patient Decision Simulator for In Silico Testing Safety and Effectiveness of Insulin Treatments

Objective: Type-1 diabetes (T1D) treatment requires exogenous insulin administrations finely tuned based on glucose monitoring to avoid hyper/hypoglycemia. The safety and effectiveness of insulin treatments is commonly assessed in clinical trials, which are time demanding and expensive. These limitations can be overtaken by in silico clinical trials (ISCT) that require realistic patient and treatment models. The aim is to develop a T1D patient decision simulator usable to perform reliable ISCT. Methods: The T1D patient decision simulator was developed by connecting the UVA/Padova T1D model, which describes glucose, insulin, and glucagon kinetics, with modules describing glucose monitoring devices, like self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM), the patient's behavior in making treatment decisions, and insulin administration. The reliability of the simulator was assessed by comparing its predictions with data collected in 44 T1D subjects using the Dexcom G5 Mobile CGM sensor as an adjunct to the Bayer Contour Next USB SMBG device. Results: Metrics like time spent in eu/hypo/hyperglycemia of simulated data well match those observed in subjects. In particular, mean time in euglycemia, mean time in hyperglycemia, and median time in hypoglycemia are 61.75% versus 63.60% (p-value = 0.4825), 33.38% versus 33.40% (p -value = 0.9950), and 3.17% versus 2.14% (p-value = 0.1134), respectively, in real versus simulated data. Conclusion: The proposed simulator can be used to perform credible ISCT in realistic insulin treatment scenarios. Significance: The T1D patient decision simulator can be used to reliably assess novel insulin treatments, e.g., based on use of CGM only, in a realistic multiple-day scenario.
Intermediate filament expression and lectin histochemical features of canine transmissible venereal tumour

Immunocharacterization of intermediate filament proteins and lectin‐binding studies were carried out in canine transmissible venereal tumour (TVT), a unique neoplasia sharing some epidemiological features with Kaposi's sarcoma in humans. Neoplastic cells express vimentin, but neither cytokeratin nor desmin. Regarding lectins, TVT cells express receptors for Triticum vulgaris (WGA), Concanavalia ensiformis (Con A) and Ricinus communis I (RCA‐I). They appear to be negative for Ulex europaeus‐I (UEA‐I), Arachis hypogaea (PNA), Glycine maximus (SBA) and Dolichos biflorus (DBA).
Comparisons of Ultrafine and Fine Particles in Their Associations with Biomarkers Reflecting Physiological Pathways

Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics compared to before and after the Olympics, we conducted the current study to compare ultrafine particles (UFPs) and fine particles (PM2.5) in their associations with biomarkers reflecting multiple pathophysiological pathways linking exposure and cardiorespiratory events. Number concentrations of particles (13.0–764.7 nm) and mass concentrations of PM2.5 were measured at two locations within 9 km from the residence and workplace of 125 participating Beijing residents. Each participant was measured 6 times for biomarkers of autonomic function (heart rate, systolic and diastolic blood pressures), hemostasis (von Willebrand factor, soluble CD40 ligand, and P-selectin), pulmonary inflammation and oxidative stress (exhaled nitric oxide and exhaled breath condensate pH, malondialdehyde, and nitrite), and systemic inflammation and oxidative stress (urinary malondialdehyde and 8-hydroxy-2′-deoxyguanosine, plasma fibrinogen, and white blood cells). Linear mixed models were used to estimate associations of biomarkers with UFPs and PM2.5 measured 1–7 days prior to biomarker measurements (lags). We found that the correlation coefficient for UFPs at two locations (∼9 km apart) was 0.45, and at the same location, the correlation coefficient for PM2.5 vs UFPs was −0.18. Changes in biomarker levels associated with increases in UFPs and PM2.5 were comparable in magnitude. However, associations of certain biomarkers with UFPs had different lag patterns compared to those with PM2.5, suggesting that the ultrafine size fraction (≤100 nm) and the fine size fraction (∼100 nm to 2.5 μm) of PM2.5 are likely to affect PM-induced pathophysiological pathways independently.
Metabolic syndrome, insulin resistance, and periodontitis: a cross-sectional study in a middle-aged French population.

AIM Metabolic syndrome consists of a cluster of clinical and biological abnormalities, influenced by insulin resistance and promoting cardiovascular diseases. We examined the relationships between metabolic syndrome, its various components, insulin resistance, and periodontitis. MATERIALS AND METHODS The study included 276 subjects (35-74 years) recruited within a cross-sectional survey on cardiovascular risk factors. Twenty-one were excluded because of infectious risk or total tooth loss. Clinical attachment loss (CAL), probing pocket depth (PD), gingival and plaque indexes were recorded. Periodontitis was classified into moderate and severe forms. RESULTS The mean age was 58, 41% of the subjects had moderate and 39% had severe periodontitis. In univariate comparisons, periodontitis was associated with metabolic syndrome (p=0.050), most of its components, and HOMA index (homoeostasis model assessment of insulin resistance). After adjustment for confounders, only HOMA index remained associated with severe periodontitis (odds ratio [OR]=3.97 [95% confidence interval: 1.22-12.9], OR=3.78 [1.14-12.5] for third and fourth versus the first quartile of the HOMA index, respectively). The HOMA index was also associated with the number of periodontal sites with CAL>or=4 mm, CAL>or=5 mm, or PD>or=4 mm (greater number for higher HOMA-index values). This relationship disappeared in never-smokers. CONCLUSIONS Our data support the relationships between metabolic disturbances and periodontitis, with a central role of insulin resistance.
Integrating organisational and individual level performance management systems within the Indonesian public sector

This PhD study aims to contribute to the literature on integrated performance management systems (PMSs) development. By examining comprehensively the elements of organisational and individual level PMSs and the linkages between the elements that make up those PMSs, this study responds to the call for management accounting research to pay more attention to management control aspects beyond accounting measures (Otley, 1999, 2001, 2008, 2016). To examine the elements and integration of PMSs, this study conducted a critical realist-based explanatory case study in a single, large government organisation in Indonesia. The design of the study and the data analysis drew on Ferreira and Otley’s (2009) PMSs theoretical framework. Data were captured from electronic and printed document archives, online written interviews with participants across the Indonesian public sector, and face-to-face interviews with organisational personnel at different hierarchical levels and within different functional areas of the case study organisation. The data from these various sources were triangulated and analysed
Effect of dietary supplementation of vitamin E on the antioxidant status of broilers and the oxidative stability of its cooled meat.

Facultad de Agronomía e Ingeniería Forestal/Animal Science Department/Pontificia Universidad Católica de Chile/Av. Vicuña Mackenna 4860, Macul, Santiago, Chile. 2 Facultad de Ciencias Químicas y Farmaceúticas, Universidad de Chile. Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile. * Corresponding autor: mafellen@uc.cl __________________________________________________________________________________
Effect in the conscious dog of constriction of the renal artery to a sole remaining kidney on haemodynamics, sodium balance, body fluid volumes, plasma renin concentration and pressor responsiveness to angiotensin.

1. The renal artery to a lone remaining kidney was constricted in fourteen concious dogs. The following variables were measured in all animals: blood pressure (BP), cardiac rate (CR), plasma renin concentration (PRC), plasma volume (PV), extracellular fluid volume (ECFV) and plasma non-protein nitrogen (NPN). Sodium balance was estimated in eleven dogs. Cardiac output (CO), total peripheral resistence (TPR) and stroke volume (SV) were measured in nine dogs. Angiotensin responsiveness (AR) was measured in six animals. 2. Within 2 hr the following changes occurred: a sharp increment of BP, PRC and TPR, with initial reduction or no change in CO and CR; SV and PV were not changed. The linear regression of BP changes on PRC changes did not differ statistically from the one previously obtained during the infusion of exogenous renin in the conscious dog. AR was much depressed at 2 hr. 3. After 24 hr a slight but significant sodium retention developed, while PV and ECFV and SV increased, CO remained unchanged owing to a decrease of CR. PRC tended to return toward normal while BP remained high. Thus the linear regression between these two variables disappeared. At this stage AR increased toward normal and in two dogs exceeded normal. 4. On days 3–4 and 6–7 after constriction, CO increased owing to a rise of SV, while TPR decreased. PV and ECFV were expanded while sodium balance was maintained. AR varied very much in the individual dogs according mainly to changes of PRC, sodium balance and PV. 5. On days 12–14 sodium balance became positive again, PRC returned within normal levels in almost all the dogs. PV and ECFV also tended to decrease to normal. CO and AR were measured in only two dogs at this stage. 6. It is suggested that the early rise of blood pressure might be produced by the increase of PRC, while 3–6 days after the constriction the expansion of PV with the increase of CO contributed to the maintenance of the hypertension.
Dentate Granule Cells in Reeler Mutants and VLDLR and ApoER2 Knockout Mice

We have studied the organization and cellular differentiation of dentate granule cells and their axons, the mossy fibers, in reeler mutant mice lacking reelin and in mutants lacking the reelin receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). We show that granule cells in reeler mice do not form a densely packed granular layer, but are loosely distributed throughout the hilar region. Immunolabeling for calbindin and calretinin revealed that the sharp border between dentate granule cells and hilar mossy cells is completely lost in reeler mice. ApoER2/VLDLR double-knockout mice copy the reeler phenotype. Mice deficient only in VLDLR showed minor alterations of dentate organization; migration defects were more prominent in ApoER2 knockout mice. Tracing of the mossy fibers with Phaseolus vulgaris leukoagglutinin and calbindin immunolabeling revealed an irregular broad projection in reeler mice and ApoER2/VLDLR double knockouts, likely caused by the irregular wide distribution of granule cell somata. Mutants lacking only one of the lipoprotein receptors showed only minor changes in the mossy fiber projection. In all mutants, mossy fibers respected the CA3-CA1 border. Retrograde labeling with DiI showed that malpositioned granule cells also projected as normal to the CA3 region. These results indicate that ( 1 ) reelin signaling via ApoER2 and VLDLR is required for the normal positioning of dentate granule cells and (2) the reelin signaling pathway is not involved in pathfinding and target recognition of granule cell axons.
Faktor-faktor yang Mempengaruhi Kualitas Laba pada Perusahaan Manufaktur

The purpose of the study is to get empirical evidence about factors that affect earnings quality of manufacturing listed company. Eight selected variables are board of directors, board size, managerial ownership, firm size, capital structure, liquidity, dividend payment, and profitability. Multiple regression method was applied on samples of 35 manufacturing listed companies that have been listed in Indonesia Stock Exchange (BEI) from period 2012 until 2015. Samples were selected based on purposive sampling method. The results showed that dividend payment and profitability had influence on earnings quality. Meanwhile, board of directors, board size, managerial ownership, firm size, capital structure, and liquidity had no effect on earnings quality.
Primary Health Care Performance Measurement and Accountability in Ontario

Ontario was used to explore the meaning, approaches, and measures of accountability, and examine the connection between primary health care (PHC) key attributes, performance measurement and accountability. This research study used qualitative research methods design and a theoretical framework to guide the inquiry, collection, analysis and interpretation of data (i.e., documents and 28 semi-structured interviews). This study offers empirical knowledge about the scope of accountability in PHC—who is accountable to whom, for what and how is accountability implemented and measured. These insights are valuable lessons for other jurisdictions, and suggest future research topics for scholars. This study found that in a public contract model, the key aspects of the PHC system performance measurement are: access to and utilization of insured services; and cost of reimbursing private providers. These are components of financial and political accountability of the funder. PHC providers and clinics have multiple lines of accountability. Clinical performance accountability is implicit and not routinely monitored. PHC providers are selfregulated and trust is placed on them to deliver evidence based care to achieve desirable patient outcomes. In this governance structure, metrics used in PHC are those that are easy to measure and within the control of clinicians. Metrics involving co-production of services and tacit use of clinical knowledge are iii left out because it is complex to get access to this data from disparate standalone systems, which results in low measurability of many services. If data sources could be linked, it may be feasible to align PHC performance and accountability with the four key PHC attributes: access, personfocused care, coordination and comprehensiveness. With this, relevant metrics can be fed back to PHC providers and publicly reported to enable patients to exercise their right as consumers to select care from high performing PHC teams. The latter could advance accountability in PHC.
Aminoglycosides Monotherapy as First-Line Treatment for Febrile Urinary Tract Infection in Children

We report a retrospective monocentric descriptive study performed in CHI Creteil for 20 months to describe the management and outcome of amikacin monotherapy as an alternative to third-generation cephalosporins for empiric treatment of febrile urinary tract infection (FUTI) in children. Data were analyzed for 151 children, and 90 selected cases were classified as certain or highly probable FUTI. Escherichia coli infection was found in 89 cases. In all patients, fever was resolved within 72 hours after beginning amikacin treatment. Only 5.3% of children were febrile after 48 hours. The mean amikacin treatment duration was 3.05 ± 0.13 days before oral treatment began (guided by antibiotic susceptibility testing). Amikacin monotherapy seems effective for the initial management of FUTI in children.
A transect of 200 shallow shear velocity profiles across the Los Angeles Basin: submitted to Bull

This study assesses a 60 km north-northeast–south-southwest transect along the San Gabriel River for shallow shear velocities, in San Gabriel Valley and the Los Angeles Basin of southern California. We assessed a total of 214 sites, 199 along the transect at 300-m spacing, during a one-week field campaign with the refraction microtremor (ReMi) technique. The transect9s maximum 30-m shear velocity (Vs30) occurs in coarse alluvium of San Gabriel Valley where the San Gabriel River exits the San Gabriel Mountains, at 730 m/sec, upper National Earthquake Hazards Reduction Program (nehrp) site class C. Much of the northeast section of the transect (in San Gabriel Valley) is also nehrp class C, or near the CD class boundary. The section of the transect south from Whittier Narrows to Seal Beach shows nehrp-D velocities in active alluvium. The transect9s lowest Vs30, 230 m/ sec at the Alamitos Bay estuary, is also classed as nehrp-D. An increase toward the nehrp CD class boundary occurs at the shoreline beach outside Alamitos Bay, confirmed by additional measurements on Seal Beach. Our measured Vs30 values generally show good correlation with published site-classification maps and existing borehole data sets. There is no evidence in our data for an increase in velocity predicted by Wills et al. (2000) at their CD to BC site classification boundary at the San Gabriel Mountains front, nor for any decrease at their D to DE class boundary at Alamitos Bay. Very large Vs30 variations exist in soil and geologic units sampled by our survey. The Vs30 variations we measured are smaller than Vs30 variations of 30% or more we found between closely spaced (
Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor‐9 in human lung adenocarcinomas

We had previously reported that aryl hydrocarbon receptors (AhRs) are overexpressed in lung adenocarcinomas. Benzo[a]pyrene (BaP), an AhR agonist, increased FGF‐9 expression in human lung adenocarcinoma cells. Similarly, several AhR agonists increased FGF‐9 mRNA levels, and BaP‐induced FGF‐9 expression was prevented by cotreatment with AhR antagonist in human lung adenocarcinoma cells. Furthermore, AhR agonists increased transcriptional activity of FGF‐9 promoter. Modulation of AhR expression via RNA interference or transient overexpression respectively reduced or increased both constitutive and BaP‐induced FGF‐9 expression in human lung cells. These results suggested that AhR activation and overexpression increased FGF‐9 expression in lung cells. FGF‐9 increased growth of lung fibroblasts but not that of lung adenocarcinoma cells. However, conditioned media collected from FGF‐9‐treated fibroblasts increased cell growth of lung adenocarcinoma cells. Furthermore, lung adenocarcinoma cells expressed FGF receptor 2 and cotreatment with anti‐FGF receptor 2 prevented the interaction between fibroblasts and tumor cells. It is likely that FGF‐9‐stimulated fibroblasts secreted unknown factors, which activated FGF receptor 2 and subsequently promoted growth of lung adenocarcinoma cells. We further compared AhR and FGF‐9 expression in 146 non‐small cell lung cancer (NSCLC) cases by immunohistochemistry. FGF‐9 expression was more common in adenocarcinomas than in squamous cell carcinomas. Furthermore, FGF‐9 and AhR expression were well correlated in lung adenocarcinomas. These results suggest that AhR expression correlated positively with FGF‐9 expression in lung adenocarcinomas, which might promote tumor growth by modulating communication between tumor cells and fibroblasts. Preventing AhR overexpression or disturbing FGF‐9 function may reduce the development of lung adenocarcinomas. © 2009 UICC
Corps de transseries

Le but principal de cette these est la construction de corps de transseries munis des iterateurs de l'exponentielle. Une fonction e est dite iterateur de l'exponentielle, lorsqu'elle verifie l'equation fonctionnelle e(x + 1) = exp e(x). Une telle fonction croit plus vite que n'importe quelle iteree de l'exponentielle. De la meme maniere on considera des iterateurs de e et ainsi de suite. Les iterateurs de l'exponentielle interviennent naturellement lorsque l'on s'emploie a resoudre des equations de composition dans un cadre fortement monotone. Un exemple classique d'un cadre fortement monotone est donne par les corps de hardy. D'autres exemples sont les theories algebriques des transseries et analytiques des fonctions analysables, qui se sont revelees tres utiles pour la resolution des equations differentielles. Dans cette these, nous construirons des corps de transseries plus generales qui peuvent egalement contenir des iterateurs de l'exponentielle et du logarithme. Ceci est un premier pas vers la resolution des equations fonctionnelles generales dans un cadre fortement monotone, au moins du point de vue algebrique.