Miracle-dz/UniFAR-FTUs huggingface dataset:
Polarization dictates iron handling by inflammatory and alternatively activated macrophages

Background Macrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes. Design and Methods Inflammatory/M1 and alternatively activated/M2 macrophages were propagated in vitro from mouse bone-marrow precursors and polarized in the presence of recombinant interferon-γ or interleukin-4. We characterized and compared their ability to handle radioactive iron, the characteristics of the intracellular iron pools and the expression of molecules involved in internalization, storage and export of the metal. Moreover we verified the influence of iron on the relative ability of polarized macrophages to activate antigen-specific T cells. Results M1 macrophages have low iron regulatory protein 1 and 2 binding activity, express high levels of ferritin H, low levels of transferrin receptor 1 and internalize – albeit with low efficiency -iron only when its extracellular concentration is high. In contrast, M2 macrophages have high iron regulatory protein binding activity, express low levels of ferritin H and high levels of transferrin receptor 1. M2 macrophages have a larger intracellular labile iron pool, effectively take up and spontaneously release iron at low concentrations and have limited storage ability. Iron export correlates with the expression of ferroportin, which is higher in M2 macrophages. M1 and M2 cells activate antigen-specific, MHC class II-restricted T cells. In the absence of the metal, only M1 macrophages are effective. Conclusions Cytokines that drive macrophage polarization ultimately control iron handling, leading to the differentiation of macrophages into a subset which has a relatively sealed intracellular iron content (M1) or into a subset endowed with the ability to recycle the metal (M2).
Voice disorders in teachers: Occupational risk factors and psycho-emotional factors

Background. Teaching is a high-risk occupation for developing voice disorders. The purpose of this study was to investigate previously described vocal risk factors as well as to identify new risk factors related to both the personal life of the teacher (fluid intake, voice-demanding activities, family history of voice disorders, and children at home) and to environmental factors (temperature changes, chalk use, presence of curtains, carpet, or air-conditioning, acoustics in the classroom, and noise in and outside the classroom). Methods. The study group comprised 994 teachers (response rate 46.6%). All participants completed a questionnaire. Chi-square tests and logistic regression analyses were performed. Results. A total of 51.2% (509/994) of the teachers presented with voice disorders. Women reported more voice disorders compared to men (56.4% versus 40.4%, P < 0.001). Vocal risk factors were a family history of voice disorders (P = 0.005), temperature changes in the classroom (P = 0.017), the number of pupils per classroom (P = 0.001), and noise level inside the classroom (P = 0.001). Teachers with voice disorders presented a higher level of psychological distress (P < 0.001) compared to teachers without voice problems. Conclusion. Voice disorders are frequent among teachers, especially in female teachers. The results of this study emphasize that multiple factors are involved in the development of voice disorders.
Specific Amelogenin Gene Splice Products Have Signaling Effects on Cells in Culture and in Implants in Vivo *

Low molecular mass amelogenin-related polypeptides extracted from mineralized dentin have the ability to affect the differentiation pathway of embryonic muscle fibroblasts in culture and lead to the formation of mineralized matrix in in vivo implants. The objective of the present study was to determine whether the bioactive peptides could have been amelogenin protein degradation products or specific amelogenin gene splice products. Thus, the splice products were prepared, and their activities were determined in vitro and in vivo. A rat incisor tooth odontoblast pulp cDNA library was screened using probes based on the peptide amino acid sequencing data. Two specific cDNAs comprised from amelogenin gene exons 2,3,4,5,6d,7 and 2,3,5,6d,7 were identified. The corresponding recombinant proteins, designated r[A+4] (8.1 kDa) and r[A−4] (6.9 kDa), were produced. Both peptides enhanced in vitrosulfate incorporation into proteoglycan, the induction of type II collagen, and Sox9 or Cbfa1 mRNA expression. In vivoimplant assays demonstrated implant mineralization accompanied by vascularization and the presence of the bone matrix proteins, BSP and BAG-75. We postulate that during tooth development these specific amelogenin gene splice products, [A+4] and [A−4], may have a role in preodontoblast maturation. The [A+4] and [A−4] may thus be tissue-specific epithelial mesenchymal signaling molecules.
Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study.

Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case-control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05-2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16-3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78-5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56-4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers.
FOC-MUSIC method for signal parameter estimations using vector circular array

Vector circular array (VCA) is a relatively new array configuration for signal direction and polarization estimations. The objective of this study is to find a more accurate and robust DOA and polarization estimation approach for VCA. Fourth-order cumulants based MUSIC (FOC-MUSIC) method is attractive for possible high resolution in both white and colored Gaussian noise. This paper presents a study by comparing the FOC-MUSIC with conventional MUSIC for both white and colored Gaussian noise. Through stochastic simulation and error analysis, it is found that the adopted FOC-MUSIC can achieve more accurate estimations of direction and polarization in both white and colored Gaussian noise, especially for low SNR scenarios.
Human Papillomavirus 16 (HPV 16) and HPV 18 Antibody Responses Measured by Pseudovirus Neutralization and Competitive Luminex Assays in a Two- versus Three-Dose HPV Vaccine Trial

ABSTRACT Human papillomavirus 16 (HPV 16) and HPV 18 antibody responses in a 2- versus 3-dose HPV vaccine (Gardasil) trial were measured by a pseudovirus neutralizing antibody (PsV NAb) assay and by the Merck competitive Luminex immunoassay (cLIA). Eight hundred twenty-four female subjects assigned to three dosing regimens (group 1, 9 to 13 years old; 2 doses, months 0 and 6 [n = 259]; group 2, 9 to 13 years old; 3 doses, months 0, 2, and 6 [n = 260]; group 3, 16 to 26 years old; 3 doses, months 0, 2, and 6 [n = 305]) had postvaccine responses assessed 1 month after the last dose. Of 791 subjects with baseline and 7-month sera, 15 (1.9%) and 9 (1.1%) were baseline seropositive for HPV 16 and HPV 18, respectively. All baseline-seronegative vaccinees seroconverted to both HPV 16 and HPV 18. Mean anti-HPV 16 levels were similar for groups 1 and 2 (for PsV NAb, P = 0.675; for cLIA, P = 0.874), and levels for both groups 1 and 2 were approximately 2-fold higher than that for group 3 (for PsV NAb and cLIA, P < 0.001). Mean anti-HPV 18 levels were approximately 1.4-fold lower in group 1 than in group 2 (for PsV, NAb P = 0.013; for cLIA, P = 0.001), and levels for both groups 1 and 2 were approximately 2.0- to 2.5-fold higher than that for group 3 (for PsV NAb and cLIA, P < 0.001). Pearson correlation coefficients for the assays were 0.672 for HPV 16 and 0.905 for HPV 18. Most of the discordant results were observed at lower cLIA signals. These results suggest that the PsV NAb assay could be a suitable alternative to cLIA for the measurement of postvaccine antibody responses.
Varieties of Parent Involvement in Schooling

In an educational climate characterized by an enormous emphasis on accountability, our nation has been busy defining its educational goals to enable us to participate in a global economy. Even in this context, the concept of family and parent involvement in school has remained a top priority. Two examples illustrate this point. First, in 1994, Congress enacted the Goals 2000: Educate America Act. As stated in Goal Eight, “By the year 2000, every school will promote partnerships that will increase parent involvement and participation in promoting the social, emotional, and academic growth of children” (Sec. 102, 8, A). Some of the objectives of this goal included the establishment of programs to increase parent involvement, engaging parents in the support of academic work of children at home, and shared decision making at school. Second, parents are mentioned more than 300 times in various parts of the No Child Left Behind Act (2002), specifically in Section 1118, Title I. This section of the Act is devoted solely to parent involvement. More specifically, this section requires that school districts and schools receiving Title I dollars must have a written parent involvement policy and build school capacity to effectively implement the parent policy provisions. Additionally, this policy must be developed jointly with parents and the local community. For the first time in the history of the Elementary and Secondary Education Act (ESEA), the law contains a definition of parent involvement: The participation of parents in regular, two-way, and meaningful communication involving student academic learning and other school related activities including ensuring—that parents play an integral role in assisting their child’s learning; that parents are encouraged to be actively involved in their child’s education at school; that parents are full partners in their child’s education and are included, as appropriate, in decision-making and on advisory committees to assist in the education of their child; and that other activities are carried out, such as those described in section 1118 of the ESEA (Parent Involvement). [Section 9101(32). EA]
Self-adaptive fall-detection apparatus embedded in glasses

Fall injury is already a major problem in elderly health care. This work develops a self-adaptive fall-detection apparatus which is embedded in glasses for users easily to put on. The proposed system adopts a 9-axis sensing module of a triaxial magnetometer, accelerometer and gyroscope. First, the magnetometer is to filter out some normal events like head rotating, based on variations of rotation angles which are modeled by the Gaussian mixture model. Second, the sensed signals from a triaxial accelerometer are computed to obtain differential acceleration values at three directions, which are integrated and then compared with a threshold. Here, the threshold is determined by the Gaussian mixture model and optimized thresholding technique. Our system can update an adequate threshold on the fly. Third, when a fall occurs, its direction is identified using an accelerometer and a gyroscope. The experimental results reveal that the proposed system achieves accuracy rate of 92.1%, a specificity of 98.7%, and a sensitivity of 81.7%. As compared to the conventional fall-detection systems, the proposed system not only shows fairly good performance but also provides convenient, comfortable and non-intrusive wearing. Therefore, the system proposed herein can be widely spread in various head-mounted devices for health care applications.
EEG abnormalities as a biomarker for cognitive comorbidities in pharmacoresistant epilepsy

Cognitive impairment is a common and often devastating comorbidity of pharmacoresistent epilepsy. The cognitive comorbidity can be both chronic, primarily due to the underlying etiology of the epilepsy, and dynamic or evolving because of recurrent seizures or interictal spikes. There is now considerable evidence that interictal spikes can contribute to cognitive impairment. Interictal spikes in both rodents and humans result in transient impairment of memory retrieval, whereas in immature animals, interictal spikes can result in long‐term adverse effects on brain development. Interictal spikes therefore contribute to the cognitive impairment in the pharmacoresistant epilepsies. Effective treatment of pharmacoresistant epilepsy needs to target not only the overt seizures but interictal electroencephalography (EEG) abnormalities as well.
In vivo dynamic ME‐MRI reveals differential functional responses of RA‐ and area X‐projecting neurons in the HVC of canaries exposed to conspecific song

HVC (nidopallial area, formerly known as hyperstriatum ventrale pars caudalis), a key centre for song control in oscines, responds in a selective manner to conspecific songs as indicated by electrophysiology. However, immediate–early gene induction cannot be detected in this nucleus following song stimulation. HVC contains neurons projecting either towards the nucleus robustus archistriatalis (RA; motor pathway) or area X (anterior forebrain pathway). Both RA‐ and area X‐projecting cells show auditory responses. The present study analysed these responses separately in the two types of HVC projection neurons of canaries by a new in vivo approach using manganese as a calcium analogue which can be transported anterogradely and used as a paramagnetic contrast agent for magnetic resonance imaging (MRI). Manganese was stereotaxically injected into HVC and taken up by HVC neurons. The anterograde axonal transport of manganese from HVC to RA and area X was then followed by MRI during ≈ 8 h and changes in signal intensity in these targets were fitted to sigmoid functions. Data comparing birds exposed or not to conspecific songs revealed that song stimulation specifically affected the activity of the two types of HVC projection neurons (increase in the sigmoid slope in RA and in its maximum signal intensity in area X). Dynamic manganese‐enhanced MRI thus allows assessment of the functional state of specific neuronal populations in the song system of living canaries in a manner reminiscent of functional MRI (but with higher resolution) or of 2‐deoxyglucose autoradiography (but in living subjects).
Calibration of sealed HCl cells used for TCCON instrumental line shape monitoring

Abstract. The TCCON (Total Carbon Column Observing Network) FTIR (Fourier transform infrared) network provides highly accurate observations of greenhouse gas column-averaged dry-air mole fractions. As an important component of TCCON quality assurance, sealed cells filled with approximately 5 mbar of HCl are used for instrumental line shape (ILS) monitoring at all TCCON sites. Here, we introduce a calibration procedure for the HCl cells which employs a refillable, pressure-monitored reference cell filled with C2H2. Using this method, we identify variations of HCl purity between the TCCON cells as a non-negligible disturbance. The new calibration procedure introduced here assigns effective pressure values to each individual cell to account for additional broadening of the HCl lines. This approach will improve the consistency of the network by significantly reducing possible station-to-station biases due to inconsistent ILS results from different HCl cells. We demonstrate that the proposed method is accurate enough to turn the ILS uncertainty into an error source of secondary importance from the viewpoint of network consistency.
Heart rate variability predicts mortality in peritoneal dialysis patients

Abstract Background: The predictive value of heart rate variability (HRV) in peritoneal dialysis (PD) has never been tested. Methods: In this study, the associations between HRV measures and the mortality in 81 PD patients were analyzed. HRV was measured by using 5-min recordings of a stationary system by a standardized method. Both time domain and frequency domain parameters were analyzed. Results: During a follow-up period of 43.78 ± 14.77 months, 25 patients died, four patients were transferred to hemodialysis. Of the 81 patients, the time domain parameters, such as the standard deviation of differences between adjacent normal sinus to normal sinus (NN) intervals (SDSD) and the square root of the mean of the squared differences between adjacent normal NN intervals (RMSSD), were higher; the frequency domain parameters, such as the ratio of low-frequency power to high-frequency power (LF/HF) and the normalized LF, were lower, and the normalized HF was higher in the non-survived group as compared with the survived group. A Cox proportional hazards model analysis revealed that, of the HRV measures, decrease of the normalized LF, LF/HF and increase of rMSSD, SDSD, normalized HF had significant predictive value for mortality. After adjustment for other univariate predictors including age, urine volume, renal Kt/V, high-sensitivity C-reactive protein (hs-CRP), the predictive value of decreased LF/HF remained significant. Kaplan–Meier survival analysis showed mortality rate was much higher in patients with a low LF/HF (median value of 1.56). Conclusion: The decreases of LF/HF which reflects impaired sympathetic nerve regulation is an independent predictor of mortality in PD patients.
Confirmation of ALDH2 as a Major locus of drinking behavior and of its variants regulating multiple metabolic phenotypes in a Japanese population.

BACKGROUND Normative alcohol use (or drinking behavior) influences the risk of cardiovascular disease in a multi-faceted manner. To identify susceptibility gene variants for drinking behavior, a 2-staged genome-wide association study was performed in a Japanese population. METHODS AND RESULTS In the stage-1 scan, 733 cases and 729 controls were genotyped with 456,827 SNP markers. The associated loci without redundancy of linkage disequilibrium were further examined in the stage-2 general population panel comprising 2,794 drinkers (≥ once per week), 1,521 chance drinkers (< once per week), and 1,351 non-drinkers. Along with genome-wide exploration, we aimed to replicate the trait association of a candidate gene SNP previously reported (rs1229984 in ADH1B). A cluster of 12 SNPs on 12q24 were found to significantly (P<5×10(-8)) associate with drinking behavior in stage 1, among which rs671 (a Glu-to-Lys substitution at position 504) in the ALDH2 gene showed the strongest association (odds ratio (OR)=0.16, P=3.6×10(-211) in the joint analysis). The association was also replicated for rs1229984 (OR=1.20, P<3.6×10(-4)). Furthermore, ALDH2 504Lys was associated with several metabolic traits, eg, lower levels of high-density lipoprotein cholesterol and liver enzymes-AST, ALT, and γGTP-by interacting with alcohol intake. CONCLUSIONS Our results confirm ALDH2 as a major locus regulating drinking behavior in the Japanese, indicating that the ALDH2 504Lys variant exerts pleiotropic effects on risk factors of cardiovascular disease among drinkers.
Preclinical Testing of Candidate Topical Microbicides for Anti-Human Immunodeficiency Virus Type 1 Activity and Tissue Toxicity in a Human Cervical Explant Culture

ABSTRACT A human cervical explant culture was utilized for the preclinical assessment of anti-human immunodeficiency virus type 1 (HIV-1) activity and tissue toxicity of formulated, candidate topical microbicides. Products tested included cellulose acetate 1,2-benzene dicarboxylate (CAP), a carrageenan-based product (PC-515), a naphthalene sulfonate polymer (PRO 2000), a lysine dendrimer (SPL7013), a nonnucleoside reverse transcriptase inhibitor (UC781), and an antimicrobial peptide (D2A21), along with their placebos. Cervical explants were cultured overnight with HIV-1 with or without product, washed, and monitored for signs of HIV-1 infection. HIV-1 infection was determined by p24gag levels in the basolateral medium and by immunohistochemical analysis of the explant. Product toxicity was measured by the MTT [1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan] assay and histology. CAP, PRO 2000, SPL7013, and UC781 consistently prevented HIV-1 infection in all explants tested. PC-515 and D2A21 prevented HIV-1 infection in 50% or fewer of the explants tested. Placebos did not prevent infection in any of the explants tested. With the exception of PRO 2000 (4%), the MTT assay and histological analysis of the other products and placebos showed minimal toxicity to the epithelium and submucosa. Collectively, these data suggest that this culture system can be used for evaluating the safety and efficacy of topical microbicides designed for vaginal use.
Variations in 'avoidable' mortality: a reflection of variations in incidence?

BACKGROUND Variations in 'avoidable' mortality may reflect variations in the quality of care, but they may also be due to variations in incidence or severity of diseases. We studied the association between regional variations in 'avoidable' mortality and variations in disease incidence. For a selection of conditions we also analysed whether the proportion of in-hospital deaths can explain the regional variations in incidence-adjusted mortality. METHODS Relative risks for mortality, incidence, incidence-adjusted mortality and in-hospital mortality (1984-1994) were calculated by log-linear regression. Linear regression was used to examine the relationship between mortality and incidence on the one hand, and between incidence-adjusted mortality and in-hospital mortality on the other. RESULTS Significant regional mortality variations were found for cervical cancer, cancer of the testis, hypertensive and cerebrovascular disease, influenza/pneumonia, cholecystitis/lithiasis, perinatal causes and congenital cardiovascular anomalies. Regional mortality differences in general were only partly accounted for by incidence variations. The only exception was cervical cancer, which no longer showed significant variations after adjustment for incidence. The contribution of inhospital mortality variations to total cause-specific mortality variations varied between conditions: the highest percentage of explained variance was found for mortality from CVA (60.1%) and appendicitis (29.2%). CONCLUSIONS Incidence data are a worthy addition to studies on 'avoidable' mortality. It is to be expected that the incidence-adjusted mortality rates are more sensitive for quality-of-care variations than the 'crude' mortality variations. Nevertheless, further research at the individual level is needed to identify possible deficiencies in health care delivery.