Miracle-dz/UniFAR-FTUs huggingface dataset:
Voice-related quality of life in organic and functional voice disorders

The voice-related quality of life (V-RQOL) questionnaire was proposed as a disease specific measure of patients’ subjective burden elicited by a voice disorder. The purpose of this study was to investigate the influence of gender and aetiology (benign organic versus functional) on V-RQOL results. Fifty-two German-speaking patients completed the questionnaire without prior information about their individual diagnosis. Results allow for the conclusion that women score lower indicating a poorer voice status. Differences between patients diagnosed with an organic or a functional voice disorder revealed no universal difference. This has to be investigated in future, especially against the degree of the voice disorder, the individual personality, health belief and social background.
Pulmonary Blood Flow Distribution in Sheep: Effects of Anesthesia, Mechanical Ventilation, and Change in Posture

Background: Recent studies providing high‐resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. Methods: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 micro meter) in six sheep studied in four conditions: prone and awake, prone with pentobarbital‐anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. Results: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar‐to‐peripheral gradient in breathing spontaneously (P < 0.05). Conclusions: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.
Multiple Mechanisms Contribute to Impairment of Type 1 Interferon Production during Chronic Lymphocytic Choriomeningitis Virus Infection of Mice1

Type 1 IFNs, innate cytokines with important effector and immunomodulatory properties, are rapidly induced in the acute phase of many virus infections; however, this is generally a transient response that is not sustained during virus persistence. To gain insight into mechanisms that can contribute to down-regulation of type 1 IFN production during virus persistence, we analyzed type 1 IFN production during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. High-level type 1 IFN production was transiently up-regulated in cells including plasmacytoid and conventional dendritic cells (DCs) following LCMV infection of mice, but LCMV persistence was associated with only low-level type 1 IFN production. Nonetheless, chronically infected mice were able to up-regulate type 1 IFN production in response to TLR3, 7, and 9 ligands, albeit less efficiently than uninfected mice. Splenic DC numbers in mice chronically infected with LCMV were decreased, and the remaining cells exhibited a reduced response to TLR stimulation. LCMV-infected cell lines efficiently up-regulated type 1 IFN production following TLR ligation and infection with a DNA virus, but exhibited a defect in type 1 IFN induction following infection with Sendai, an RNA virus. This block in type 1 IFN production by infected cells, together with abnormalities in DC numbers and functions, likely contribute to the low-level type 1 IFN production in mice chronically infected with LCMV. Impairment of type 1 IFN production may both promote virus persistence and impact on host immunocompetence. Understanding the mechanisms involved may assist in development of strategies for control of virus persistence and superinfection.
Effect of pregnancy on the pharmacokinetics of acetaminophen in rats.

Acetaminophen (A), in single doses of 15 mg/kg and 300 mg/kg, was administered by i.v. injection to nonpregnant (180-240 g) and 20 days pregnant Lewis rats (250-330 g). Blood samples (for plasma) and urine were collected serially and analyzed by high-performance liquid chromatography for A, A glucuronide and A sulfate. Serum inorganic sulfate concentrations were determined in a separate study. With respect to the 300-mg/kg dose, pregnant animals exhibited a significant decrease in relative (body weight normalized) total clearance and no change in absolute total clearance, no change in relative apparent volume of distribution and a significantly increased biological half-life. As a fraction of the administered dose, pregnant animals excreted more A, less A sulfate and the same fraction of A glucuronide as did nonpregnant animals. Pregnancy had no apparent effect on base-line serum inorganic sulfate concentration. Both normal and pregnant rats became inorganic sulfate-depleted after injection of A, 300 mg/kg. The relative total clearance of the 300-mg/kg dose of A decreased with increasing litter size, whereas the relative apparent volume of distribution was unaffected. The relative total clearance of a 15 mg/kg dose of A was much higher than that of the 300-mg/kg dose and approximated liver plasma flow rate; it was not changed by pregnancy. The relative renal clearances of A glucuronide, A sulfate and creatinine were decreased in pregnancy, whereas the absolute renal clearances of the two conjugates and creatinine were unaffected. Comparative assessment of the effect of pregnancy on the pharmacokinetics of A and other drugs in different species requires consideration of possible dose dependence and of the implications of normalizing clearance and volume of distribution values.
Factors influencing foreign direct investment in South Asian economies

Purpose The purpose of this paper is to investigate the macroeconomic determinants of foreign direct investment (FDI) for the top five South Asian economies, namely, Bangladesh, India, Pakistan, Sri Lanka, and Nepal, and to examine whether these factors are the same for each. Design/methodology/approach This study employs fully modified ordinary least squares and two-stage least squares estimation methods. Findings This study shows that South Asian economies have a number of FDI determinants in common. For example, market size and human capital are the two most common factors attracting FDI in each country (except for Nepal, which revealed a negative correlation between FDI and market size). Other factors, such as infrastructure, domestic investment, lending rates, exchange rates, inflation, financial stability/crisis, and stock turnover entered into regression with both positive and negative signs, thereby indicating that the underlying theories on FDI do not provide a clear prediction of the direction of the effect of a particular variable on FDI. Research limitations/implications This paper studied the effects of demand-side factors on FDI. A comparative study of the supply-side factors may add further knowledge. Practical implications This paper provides evidence to show that the determinants of FDI are indeed country-specific. Thus, to design a suitable FDI policy, it would not be wise to solely rely on other economies’ FDI experiences. Originality/value This paper provides updated evidence on factors that are essential to promoting or deterring FDI in South Asian economies.
Hypertonic sodium bicarbonate for Taxus media-induced cardiac toxicity in swine.

OBJECTIVE To determine whether intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication. METHODS Seventeen anesthetized and instrumented swine were poisoned with an IV extract of Taxus media until doubling of the QRS interval on electrocardiography was achieved. After poisoning (time zero), the animals received either 4 mL/kg IV 8.4% sodium bicarbonate (experimental group; 6 animals), a similar volume of 0.7% NaCl in 10% mannitol (mannitol group; 6 animals), or nothing (control group; 5 animals). The main outcome parameter was QRS duration. Secondary outcome parameters were mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI = cardiac output/kg). Additionally, arterial pH, partial pressure of carbon dioxide (pCO(2)), and plasma-ionized calcium, sodium, and potassium were monitored. RESULTS Taxus toxicity, defined as a 100% increase in QRS duration, was produced in all animals. The animals were similar in regard to baseline and time 0 physiologic parameters as well as amount of Taxus media extract administered. From times 5 through 30 minutes, following assigned treatment, significant increases in QRS duration were detected in the experimental and mannitol groups compared with the control group. A significant lowering of MAP was found in the experimental group compared with the control group. No significant difference between groups was noted in HR or CI. The swine treated with hypertonic sodium bicarbonate had a statistically significant increase in pH, plasma sodium concentration, and base excess compared with the other groups. CONCLUSIONS Hypertonic sodium bicarbonate was ineffective in reversing the widening of QRS interval associated with Taxus poisoning in this swine model.
Interests of refocused images calibrated in depth with a multi-view camera for control by vision

This work shows the interests of the refocusing technics in the domain of industrial vision. A prototype of light field camera is used for computing refocused images, which are calibrated in depth. These images are computed with a method previously presented, using a multi-view camera modeled following the “variable homography” principles. The camera prototype is composed by 4 mini-lenses placed behind a single CCD sensor, calibrated and able to perform 3D measurements. As the device is calibrated in depth, we link refocused images to a selected depth. Contrary to the conventional imaging, with refocused depth calibrated images, it is possible to highlight planes of interest to facilitate vision inspection. Objects can be distinguished from others according to their depths. We also show that a pixel metric scale can be estimated at different depths, avoiding the use of other measurement devices. Two standard vision examples are presented to illustrate the interests of this approach.
Immunohistochemical Characterization of Hemangiopericytomas and Other Spindle Cell Tumors in the Dog

The immunohistochemical expression of muscle actin has been studied in 45 canine hemangiopericytomas (CHP) using a monoclonal antibody (HHF35) and formalin-fixed, paraffin-embedded specimens. The distribution of vimentin, desmin, cytokeratins, lysozyme, factor VIII-related antigen, S-100 protein, and glial fibrillary acidic protein was studied both in CHP and in some canine soft-tissue neoplasms (seven fibrosarcomas, seven benign schwannomas, seven benign fibrous histiocytomas, and six leiomyosarcomas) used as controls for differential diagnosis. All CHP and control tumors expressed vimentin. Twenty-three CHP expressed muscle actin, whereas all control tumors analyzed were muscle actin-negative, with the exception of leiomyosarcomas. Among muscle actin- and vimentin-positive CHP, one case could be reclassified as leiomyosarcoma because it was desmin-positive, two cases expressed lysozyme, and nine cases expressed S-100 protein. Among muscle actin-negative and vimentin-positive CHP, seven expressed S-100 protein. In addition, S-100 protein was detected in five schwannomas. All CHP and control tumors analyzed were negative for cytokeratins, factor VIII-related antigen, and glial fibrillary acidic protein. Our results support the hypothesis of a pericytic origin of CHP, and suggest that muscle actin, desmin, vimentin, and lysozyme could be useful for the differential diagnosis of canine spindle cell tumors, but not all these neoplasms can be identified with these tumor tissue markers.
Antigenic Divergence Suggested by Correlation between Antigenic Variation and Pulsed-Field Gel Electrophoresis Profiles of Bordetella pertussis Isolates in Japan

ABSTRACT Antigenic divergence has been found between Bordetella pertussis vaccine strains and circulating strains in several countries. In the present study, we analyzed B. pertussis isolates collected in Japan from 1988 to 2001 using pulsed-field gel electrophoresis (PFGE) and sequencing of two virulence-associated proteins. The 107 isolates were classified into three major groups by PFGE analysis; 87 (81%) were type A, 19 (18%) were type B, and 1 (1%) was type C. Sequence analysis of the S1 subunit of pertussis toxin (ptxS1) and adhesion pertactin (prn) genes revealed the presence of two (ptxS1A and ptxS1B) and three (prn1, prn2, and prn3) variants, respectively, in the isolates. Among those isolates, 82 (95%) of the 87 type A strains and the type C strain had the same combination of ptxS1B and prn1 alleles (ptxS1B/prn1) as the Japanese vaccine strain. On the other hand, 17 (90%) of 19 type B strains had an allele (ptxS1A/prn2) distinct from that of the vaccine strain. A correlation was found between the antigenic variation and the PFGE profile in the isolates. In addition, the frequency of the type B strain was 0, 27, 0, 42, and 37% of the isolates in the periods 1988 to 1993, 1994 to 1995, 1996 to 1997, 1998 to 1999, and 2000 to 2001, respectively. In contrast, the number of reported pertussis-like and pertussis cases decreased gradually from 1991 on, suggesting that the antigenic divergence did not affect the efficacy of pertussis vaccination in Japan.
Photopolymerized poly(ethylene glycol)/poly(L-lysine) hydrogels for the delivery of neural progenitor cells

Neural progenitor cells (NPCs) have shown promise in a number of models of disease and injury, but for these cells to be safe and effective, they must be directed to differentiate appropriately following transplantation. We have developed a photopolymerized hydrogel composed of macromers of poly(ethylene glycol) (PEG) bound to poly(L-lysine) (PLL) that supports NPC survival and directs differentiation. Green fluorescent protein (GFP) positive NPCs were encapsulated in these gels and demonstrated survival up to 17 days. When encapsulated in the gels at a photoinitiator concentration of 5.0 mg/ml, few NPCs (0.5 ± 0.25%) demonstrated apoptosis. Furthermore, 55 ± 6% of the NPCs cultured within the gels in epidermal growth factor (EGF) containing media differentiated into a mature neuronal cell type (neurofilament 200 positive) while the remainder 44 ± 8% were undifferentiated (nestin positive). A small percentage, 1 ± 0.4%, expressed the astrocytic marker glial acidic fibrilary protein. Photopolymerized PEG/PLL gels promote the survival and direct the differentiation of NPCs, making this system a promising delivery vehicle for NPCs in the treatment of injuries and diseases of the central nervous system.
Wavenumber Explicit Convergence Analysis for Galerkin Discretizations of the Helmholtz Equation

We develop a stability and convergence theory for a class of highly indefinite elliptic boundary value problems (bvps) by considering the Helmholtz equation at high wavenumber $k$ as our model problem. The key element in this theory is a novel $k$-explicit regularity theory for Helmholtz bvps that is based on decomposing the solution into two parts: the first part has the Sobolev regularity properties expected of second order elliptic PDEs but features $k$-independent regularity constants; the second part is an analytic function for which $k$-explicit bounds for all derivatives are given. This decomposition is worked out in detail for several types of bvps, namely, the Helmholtz equation in bounded smooth domains or convex polygonal domains with Robin boundary conditions and in exterior domains with Dirichlet boundary conditions. We present an error analysis for the classical $hp$-version of the finite element method ($hp$-FEM) where the dependence on the mesh width $h$, the approximation order $p$, and the wavenumber $k$ is given explicitly. In particular, under the assumption that the solution operator for Helmholtz problems is polynomially bounded in $k$, it is shown that quasi optimality is obtained under the conditions that $kh/p$ is sufficiently small and the polynomial degree $p$ is at least O(log $k$).
Detection of oncogenic DNA viruses in colorectal cancer.

BACKGROUND As a part of our search for oncogenic viruses as potential etiological agents in human malignancies, our studies on human papillomaviruses (HPV) were extended to analysis of the 3 polyomaviruses (SV40, BKV and JCV) in colorectal carcinomas. PATIENTS AND METHODS Archival tumour samples from 71 patients with colorectal cancer were analyzed for the sequences of SV40, BKV, JCV and HPV using PCR-based techniques. HPV genotypes were determined using sequencing and reverse blot hybridization (InnoLipa). RESULTS Amplification of BKV and JCV with the primer pair PEP-1 and PEP-2 and subsequent restriction digestion of the amplified products with BamH I disclosed BKV in 6/66 (9%) of the samples, whereas none contained JCV. SV40 was amplified in 10/66 (15.1%) samples and confirmed by sequencing analysis. In pair-wise analysis for co-infections, the samples were significantly different in their BKV-JCV and JCV-SV40 status, in contrast to their BKV-SV40 co-infection status. HPV DNA was detected in 22/66 (33.3%) of the samples analysed with either the MY09/11 or SPF primer mix. Of these 22 HPV infections, 7 were single-type infections and 15 contained multiple HPV types. HPV detection or type distribution showed no relationship to the gender of the patients or histological grade of the tumour. HPV status was not significantly related to detection of BKV, JCV or SV40. Similarly, in pair-wise analysis for co-infections, the samples were significantly different in their status of HPV-BKV (p=0.0006), HPV-JCV (p=0.0001), and HPV-SV40 (p=0.019), implicating that HPV and the 3 polyomaviruses are rarely detected concomitantly in the same samples. CONCLUSION Taking the known molecular mechanisms of action of these individual viruses, there is a chance that these viruses could alter the mechanisms of cell cycle control and inhibit apoptosis, thus potentially causing chromosomal instability and promoting colorectal oncogenesis.
Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Localization Acts in Concert with Substrate Targeting to Create Spatial Restriction for Phosphorylation*

Ca2+/calmodulin-dependent protein kinase II (CaMKII) acts in diverse cell types by phosphorylating proteins with key calcium-dependent functions such as synaptic plasticity, electrical excitability, and neurotransmitter synthesis. CaMKII displays calcium-dependent binding to proteins in vitro and translocation to synaptic sites after glutamatergic activity in neurons. We therefore hypothesized that subcellular targeting of CaMKII can direct its substrate specificity in an activity-dependent fashion. Here, we examined whether activity-dependent colocalization of CaMKII and its substrates could result in regulation of substrate phosphorylation in cells. We find that substrates localized at cellular membranes required CaMKII translocation to these compartments to achieve effective phosphorylation. Spatial barriers to phosphorylation could be overcome by translocation and anchoring to the substrate itself or to nearby target proteins within the membrane compartment. In contrast, phosphorylation of a cytoplasmic counterpart of the substrate does not require CaMKII translocation or stable protein-protein binding. Cytosolic phosphorylation is more permissive, exhibiting partial calcium-independence. Localization-dependent substrate specificity can also show more graded levels of regulation within signaling microdomains. We find that colocalization of translocated CaMKII and its substrate to lipid rafts in the plasma membrane can modulate the magnitude of phosphorylation. Thus, dynamic regulation of both substrate and kinase localization provides a powerful and nuanced way to regulate CaMKII signal specificity.
A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis.

OBJECTIVE Improved outcome measures in systemic sclerosis (SSc) are critical to finding active therapeutics for this disease. The modified Rodnan skin thickness score (MRSS) is the current standard for evaluating skin disease in SSc, but it is not commonly used in the clinical setting, in part because it requires specialized training to perform accurately and consistently. The purpose of this study was to investigate whether skin gene expression might serve as a more objective surrogate outcome measure to supplement skin score evaluations. METHODS Skin RNAs from a group of patients with diffuse cutaneous SSc were studied for expression levels of genes known to be regulated by transforming growth factor beta (TGFbeta) and interferon (IFN). These levels were correlated with the MRSS, using multiple regression analyses to obtain best-fit models. RESULTS Skin expression of the TGFbeta-regulated genes cartilage oligomeric matrix protein (COMP) and thrombospondin 1 (TSP-1) correlated moderately well with the MRSS, but the addition of other TGFbeta-regulated genes failed to significantly improve best-fit models. IFN-regulated genes were also found to correlate with the MRSS, and the addition of interferon-inducible 44 (IFI44) and sialoadhesin (Siglec-1) to COMP and TSP-1 in multiple regression analyses significantly improved best-fit models, achieving an R(2) value of 0.89. These results were validated using an independent group of skin biopsy samples. Longitudinal scores using this 4-gene biomarker indicated that it detects change over time that corresponds to changes in the MRSS. CONCLUSION We describe a 4-gene predictor of the MRSS and validate its performance. This objective measure of skin disease could provide a strong surrogate outcome measure for patient care and for clinical trials.