Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Klebsiella pneumoniae virulence determinants using an intranasal infection model

Klebsiella pneumoniae is a Gram‐negative enterobacterium that has historically been, and currently remains, a significant cause of human disease. It is a frequent cause of urinary tract infections and pneumonia, and subsequent systemic infections can have mortality rates as high as 60%. Despite its clinical significance, few virulence factors of K. pneumoniae have been identified or characterized. In this study we present a mouse model of acute K. pneumoniae respiratory infection using an intranasal inoculation method, and examine the progression of both pulmonary and systemic disease. Wild‐type infection recapitulates many aspects of clinical disease, including significant bacterial growth in both the trachea and lungs, an inflammatory immune response characterized by dramatic neutrophil influx, and a steady progression to systemic disease with ensuing mortality. These observations are contrasted with an infection by an isogenic capsule‐deficient strain that shows an inability to cause disease in either pulmonary or systemic tissues. The consistency and clinical accuracy of the intranasal mouse model proved to be a useful tool as we conducted a genetic screen to identify novel virulence factors of K. pneumoniae. A total of 4800 independent insertional mutants were evaluated using a signature‐tagged mutagenesis protocol. A total of 106 independent mutants failed to be recovered from either the lungs or spleens of infected mice. Small scale independent infections proved to be helpful as a secondary screening method, as opposed to the more traditional competitive index assay. Those mutants showing verified attenuation contained insertions in loci with a variety of putative functions, including a large number of hypothetical open reading frames. Subsequent experiments support the premise that the central mechanism of K. pneumoniae pathogenesis is the production of a polysaccharide‐rich cell surface that provides protection from the inflammatory response.
Classification of leptospira from the eyes of horses suffering from recurrent uveitis.

Summary The pathogenesis of equine recurrent uveitis (ERU) is not completely understood. Persistent infection of pathogenic leptospires in the eyes is the probable primary cause. Consistently, we isolated and characterized in this study leptospires from 32.2% of the intraocular samples collected from 501 horses from the following Western European countries: Germany, Switzerland, Austria, The Netherlands, Luxembourg, Great Britain, Italy and Poland. The vast majority of the leptospiral isolates belonged to serogroup Grippotyphosa (78.2%). The other isolates belonged to the Australis group (14.2%), the Sejroe group (3.6%), the Pomona group (2.5%) and the Javanica group (1.5%). Apart from three isolates that likely belong to Leptospira kirschneri, serovar Dadas, all Grippotyphosa group isolates belonged to L. kirschneri, serovar Grippotyphosa. Analysis with monoclonal antibodies revealed that the isolates differed from Moskva V, the reference strain of serovar Grippotyphosa. However, the Grippotyphosa isolates closely resembled serovar Grippotyphosa, strain Duyster, which has been isolated from a Dutch patient. Because of apparent phenotypic and genotypic differences between the strains Moskva V and Duyster, we propose two different types within serovar Grippotyphosa, namely type Moskva and type Duyster. Distribution of type Duyster is restricted to Western Europe. Strikingly, only a few serovars were isolated from the eyes of horses with ERU. A number of other commonly occurring serovars, such as Copenhageni, were not found, whereas the presence of antibodies in blood and eye fluids against such serovars suggests that infection occurs. Therefore, we hypothesize that, while many pathogenic serovars might be able to penetrate the eyes, only few are capable to persist.
Immunogenicity of dormancy-related antigens in individuals infected with Mycobacterium tuberculosis in Japan.

SETTING DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their products are demonstrated to have immunogenicity in M. tuberculosis-infected individuals, suggesting that DosR regulon-encoded proteins are suitable targets for vaccines to control the reactivation of dormant M. tuberculosis. OBJECTIVE Prospective analysis of T-cell and antibody responses against DosR regulon-encoded antigens in M. tuberculosis-infected individuals in Japan to identify effective vaccine targets. DESIGN T-cell responses against 33 DosR regulon-encoded antigens were investigated in 26 consecutive M. tuberculosis-infected individuals--14 with latent tuberculosis infection (LTBI) and 12 with active pulmonary tuberculosis (PTB)--using enzyme-linked immunosorbent spot assay, and antibody responses in 42 consecutive individuals, 14 with LTBI and 28 with PTB. RESULT Six antigens (Rv0570, Rv1996, Rv2004c, Rv2028c, Rv2029c and Rv3133c) induced stronger T-cell responses in LTBI than in PTB, In contrast, antigen-specific antibody responses to five antigens (Rv0080, Rv1738, Rv2007c, Rv2031c and Rv2032) were found to be stronger in PTB than in LTBI cases. CONCLUSION T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.
Loneliness in Multiple Sclerosis: Possible Antecedents and Correlates

Purpose The prevalence and possible antecedents and correlates of loneliness in multiple sclerosis (MS) was examined. Design Cross-sectional, comparative study of MS (n = 63) and healthy adults (n = 21). Methods Data were collected using self-reports of loneliness and antecedents and correlates and analyzed using inferential statistics. Findings Those with MS had significantly higher loneliness scores than healthy adults (p < .05), and this was explained by employment status. Possible antecedents included marital status (p < .05), upper extremity function (r= −.28, p < .03), social disability frequency (r= −.49, p < .00), social disability limitations (r= −.38, p < .00), and personal disability limitations (r= −.29, p < .03). Social disability frequency (beta = −.41, p < .001) and marital status (beta = −.23, p < .046) accounted for 25% of the variance in loneliness scores. Possible correlates included depression (r= .49, p < .00), cognitive fatigue (r= .34, p < .01), psychosocial fatigue (r= .30, p < .02), and psychological quality of life (r= .44, p < .00). Conclusions We provide evidence of loneliness in persons with MS, and this is associated with possible antecedents (e.g., marital status and disability limitations) and correlates (e.g., depression and fatigue). Clinical Relevance Loneliness should be recognized clinically as an important concomitant of MS.
Analysis of digital images acquired using different phosphor storage plates (PSPs) subjected to varying reading times and storage conditions.

OBJECTIVES To assess, both objectively and subjectively, the effects of different combinations of storage conditions and varying delays in reading on digital images captured using phosphor storage plates (PSPs). METHOD Standardized images were obtained of an aluminium step wedge and a dry mandible in acrylic using GE 1000 and PSPs from the Digora (Soredex) and DenOptix (Gendex) digital systems. Twelve plates from each system were exposed and immediately scanned to produce the baseline gold standard. The plates were re-exposed and stored using three different storage combinations, (A) ambient temperature, (R) refrigeration and (S) low humidity, and then scanned after 6 h, 12 h, 18 h, 24 h, 48 h or 72 h. Objective analysis was carried out by pixel density measurements and the data were analysed statistically using analysis of variance. Subjective analysis was carried by three oral radiologists and the results were analysed using Mann-Whitney U-test. RESULTS For the DenOptix system there were no differences either objectively or subjectively in the images obtained from all the plates using different storage conditions and after varying time intervals. For Digora, objective analysis showed loss of pixel density after 6 h using all storage conditions. This loss of density was also evident subjectively after 6 h on plates stored under certain storage conditions. CONCLUSION Storage of DenOptix PSPs for up to 72 h in different conditions does not affect the quality of the digital images. However, there is a loss of image density within 6 h when using Digora PSPs, which may affect clinical image interpretation.
The linear dynamic properties of phototransduction in the fly compound eye.

1. Photoreceptor cells in the compound eye of the fly Phormia regina were stimulated with a green light emitting diode whose output was modulated by a pseudo‐random noise generator while the resulting fluctuations in membrane potential were measured with intracellular microelectrodes. 2. The responses to repeated sequences of identical pseudorandom patterns were averaged together to give frequency response functions having a significantly improved signal to noise ratio at frequencies where the response has not previously been characterized accurately. 3. Measured frequency response functions could not be fitted by a set of simple exponential time constants but could be well fitted by a model including two under‐damped second order time constants. 4. The phase data had no detectable asymptote and could only be accounted for by a model which includes a pure time delay. 5. Residual fluctuations in the phase data with frequency suggest that a small portion of the recorded signal arises from a delayed interaction with lateral or proximal cells.
Quantifier guided aggregation using OWA operators

We consider multicriteria aggregation problems where, rather than requiring all the criteria be satisfied, we need only satisfy some portion of the criteria. The proportion of the critera required is specified in terms of a linguistic quantifier such as most. We use a fuzzy set representation of these linguistic quantifiers to obtain decision functions in the form of OWA aggregations. A methodology is suggested for including importances associated with the individual criteria. A procedure for determining the measure of “orness” directly from the quantifier is suggested. We introduce an extension of the OWA operators which involves the use of triangular norms. © 1996 John Wiley & Sons, Inc.
Using Rasch Analysis to Examine the Dimensionality Structure and Differential Item Functioning of the Arabic Version of the Perceived Physical Ability Scale for Children.

This study uses the Rasch model technique to examine the dimensionality structure and differential item functioning of the Arabic version of the Perceived Physical Ability Scale for Children (PPASC). A sample of 220 Omani fourth graders (120 males and 100 females) responded to an Arabic translated version of the PPASC. Data on students' participation in physical activity were also collected using the Participation in Physical Activity Scale (PPAS). The analyses supported the unidimensionality of the factorial structure of the PPASC. The PPASC items were found to function equivalently across male and female groups. There were significant gender differences in perceived physical ability favoring males. The PPASC correlated positively and significantly with the PPAS.
Structural Basis of p75 Transmembrane Domain Dimerization*

Dimerization of single span transmembrane receptors underlies their mechanism of activation. p75 neurotrophin receptor plays an important role in the nervous system, but the understanding of p75 activation mechanism is still incomplete. The transmembrane (TM) domain of p75 stabilizes the receptor dimers through a disulfide bond, essential for the NGF signaling. Here we solved by NMR the three-dimensional structure of the p75-TM-WT and the functionally inactive p75-TM-C257A dimers. Upon reconstitution in lipid micelles, p75-TM-WT forms the disulfide-linked dimers spontaneously. Under reducing conditions, p75-TM-WT is in a monomer-dimer equilibrium with the Cys257 residue located on the dimer interface. In contrast, p75-TM-C257A forms dimers through the AXXXG motif on the opposite face of the α-helix. Biochemical and cross-linking experiments indicate that AXXXG motif is not on the dimer interface of p75-TM-WT, suggesting that the conformation of p75-TM-C257A may be not functionally relevant. However, rather than mediating p75 homodimerization, mutagenesis of the AXXXG motif reveals its functional role in the regulated intramembrane proteolysis of p75 catalyzed by the γ-secretase complex. Our structural data provide an insight into the key role of the Cys257 in stabilization of the weak transmembrane dimer in a conformation required for the NGF signaling.
Aquaporins in the hepatobiliary tract. Which, where and what they do in health and disease

The biological importance of the aquaporin family of water channels was recently acknowledged by the 2003 Nobel Prize for Chemistry awarded to the discovering scientist Peter Agre. Among the pleiotropic roles exerted by aquaporins in nature in both health and disease, the review addresses the latest acquisitions about the expression and regulation, as well as physiology and pathophysiology of aquaporins in the hepatobiliary tract.
The risk and efficacy of chorionic villus sampling in multiple gestations

Chorionic villus sampling (CVS) in the first trimester of pregnancy provides a safe and effective method for the early prenatal diagnosis of cytogenetic abnormalities in multiple gestations. In this multicentre study involving 126 twin and 2 triplet gestations primarily at risk because of advanced maternal age, the overall success rate of obtaining an adequate villus sample from each fetus was 99.2 per cent. For women of advanced maternal age, the rate of combined losses of chromosomally normal fetuses due to spontaneous abortion, stillbirths, and neonatal deaths was 5.0 per cent, compared with a 4.0 per cent total loss rate following CVS in singleton pregnancies derived from the same population (Rhoads et al., 1989). There was a 100 per cent success rate in obtaining a cytogenetic analysis; a cytogenetic abnormality was present in five of the multiple gestations (3.9 per cent) and involved seven fetuses (2.7 per cent). There were no diagnostic errors and no cases of normal cytogenetic diagnosis followed by the birth of a cytogenetically abnormal newborn. Based on cases of XX/XY admixture, cell contamination derived either from maternal decidua or the other twin occurred in 6 of 256 samples (2.3 per cent), giving an overall estimate of the frequency of cell contamination of 4.6 per cent; these cases did not present a diagnostic problem. However, there were two cases (0.8 per cent) in which the fetal sex was incorrect, due either to complete maternal cell contamination or to the possibility that in error one twin was sampled twice.
Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE‐HS.
Interaction of exogenous liposomal insulin‐like growth factor‐I cDNA gene transfer with growth factors on collagen expression in acute wounds

Growth factors have been shown to modulate the complex cascade of wound healing, however, interaction between different growth factors during dermal and epidermal regeneration is still not entirely defined. We have recently shown that exogenous liposomal gene transfer of cDNA results in physiologic expression and response in an acute wound. In the present study we determined the interaction between insulin‐like growth factor‐I (IGF‐I), a mesenchymal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors on collagen synthesis in an acute wound. Sprague‐Dawley rats were given a scald burn to inflict an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus a β‐galactosidase containing plasmid (Lac Z [0.2 µg, vehicle]), or liposomes plus the IGF‐I cDNA containing plasmid (2.2 µg) and Lac Z (0.2 µg). Immunological assays, histological and immunohistochemical techniques were used to determine growth factor concentration and different types of collagen (I, III, and IV) after IGF‐I cDNA gene transfer. IGF‐I cDNA transfer accelerated reepithelization and was associated with increased levels of IGF‐I, fibroblast growth factor, keratinocyte growth factor, vascular endothelial cell growth factor, and platelet‐derived growth factor protein expression. IGF‐I cDNA had no effect on transforming growth factor‐β. IGF‐I cDNA significantly increased type IV collagen while it had no effect on types I and III collagen. Exogenously administered IGF‐I cDNA increased protein concentrations of keratinocyte growth factor, fibroblast growth factor, platelet‐derived growth factor, and type IV collagen. We conclude that liposomal IGF‐I gene transfer can accelerate wound healing without causing an increase in types I and III collagen expression.
Intracranial Hypertension in 2 Children With Marfan Syndrome

Two unrelated children with Marfan syndrome presented with recurrent intracranial hypertension. Both children complained of headache, nausea, and vomiting and one of them had papilledema. Both had increased cerebrospinal fluid pressure, and their complaints disappeared after lumbar puncture. Although severe headache has been reported in Marfan syndrome due to intracranial hypotension, this is to our knowledge the first report of intracranial hypertension in Marfan patients.
Optical detection of nanometric thermal fluctuations to measure the stiffness of rigid superparamagnetic microrods

Significance Under the influence of thermal forces, microscopic rod-shaped objects immersed in a fluid exhibit fluctuations: They deform mechanically. The energy provided by the thermal forces being well known, the measure of these fluctuations provides a convenient means of probing the rigidity of many biological filaments (DNA, microtubules, etc.) or synthetic microrods such as carbon nanotubes. However, only relatively flexible items could be studied by this technique: If they are too rigid, the fluctuations are too small to be detected. We substantially improved the method and measured the rigidity of rods 1,000 times stiffer than in previous studies. The method could henceforth be applied to numerous harder microscopic objects. The rigidity of numerous biological filaments and crafted microrods has been conveniently deduced from the analysis of their thermal fluctuations. However, the difficulty of measuring nanometric displacements with an optical microscope has so far limited such studies to sufficiently flexible rods, of which the persistence length (Lp) rarely exceeds 1 m at room temperature. Here, we demonstrate the possibility to probe 10-fold stiffer rods by a combination of superresolutive optical methods and a statistical analysis of the data based on a recent theoretical model that predicts the amplitude of the fluctuations at any location of the rod [Benetatos P, Frey E (2003) Phys Rev E Stat Nonlin Soft Matter Phys 67(5):051108]. Using this approach, we report measures of Lp up to 0.5 km. We obtained these measurements on recently designed superparamagnetic ∼40-μm-long microrods containing iron-oxide nanoparticles connected by a polymer mesh. Using their magnetic properties, we provide an alternative proof of validity of these thermal measurements: For each individual studied rod, we performed a second measure of its rigidity by deflecting it with a uniform magnetic field. The agreement between the thermal and the magnetoelastic measures was realized with more than a decade of values of Lp from 5.1 m to 129 m, corresponding to a bending modulus ranging from 2.2 to 54 (×10−20 Jm). Despite the apparent homogeneity of the analyzed microrods, their Young modulus follows a broad distribution from 1.9 MPa to 59 MPa and up to 200 MPa, depending on the size of the nanoparticles.
Skinfold thicknesses associated with distance running performance in highly trained runners

Abstract It has been postulated that additional adiposity has a negative effect on performance in heterogeneous groups of runners. Previous studies have not tested this hypothesis in homogeneous groups of elite runners. The purpose of this study was to determine whether the sum of skinfold thicknesses and specific single skinfold sites were related to competitive running performance in homogeneous groups of male and female elite athletes. In total, 184 top-class runners (130 males and 54 females) volunteered to participate in the study. Skinfolds were measured at the following sites: biceps, triceps, subscapular, pectoral, iliac crest, abdominal, front thigh and medial calf. Runners were classified into groups in accordance with their best performance times. Correlation analysis and partial correlation coefficients that controlled for age and weight were applied to each single skinfold, the sum of six skinfolds (excluding biceps) and the extremity (sum of triceps, front thigh, medial calf) to trunk (sum of subscapular, iliac crest, abdominal) ratio and performance. Performance was rated by the scoring procedures of the International Amateur Athletics Federation. In male runners, the pectoral, iliac crest, abdominal, biceps, triceps, subscapular skinfolds and the sum of six skinfolds were not associated with performance score for any of the distances. High correlations were found between the front thigh (r = 0.78, P = 0.000) and medial calf (r = 0.55, P = 0.018) skinfolds and 1500 m run time, and between the front thigh (r = 0.59, P = 0.014) and medial calf (r = 0.57, P = 0.017) skinfolds and 10,000 m run time. In female runners, the front thigh and medial calf skinfolds were highly correlated with 400 m run time (r = 0.71, P = 0.022 and r = 0.81, P = 0.005, respectively). The results of this study indicate that skinfold thicknesses in the lower limb are positively associated with running time over several distances, and may be a useful predictor of athletic performance.
Medical women in academia: the silences we keep.

I come here today … to tell you that coeducation has proved an absolute failure, from our standpoint. When I tell you that 33.3 per cent of the ladies, students, admitted to Johns Hopkins Hospital at the end of our short session are to be married, then I tell you that coeducation is a failure
Alloalbuminemia in two Brazilian populations: a possible new variant.

The number of albumin variants that can be distinguished electrophoretically is increasing rapidly [1]. We hereby report results obtained after the screening of plasma samples from persons living in the Brazilian cities of Porto Alegre and Belem. In the first population no variability was observed at this locus, while in the second, three instances of bisalbuminemia were found. Comparison with previously described types [1] indicates that at least one of them may probably be new. Information about studies performed on plasma from these carriers, as well as from members of their families, is also presented.