Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinguishing the Contribution of Type 1 Pili from That of Other QseB-Misregulated Factors when QseC Is Absent during Urinary Tract Infection

ABSTRACT Urinary tract infections (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), are one of the leading bacterial infections due to their high frequency and rate of recurrence. Both type 1 pilus adhesive organelles (fim) and the QseC sensor kinase have been implicated in UPEC virulence during UTI and have been individually reported to be promising drug targets. Deletion of qseC leads to pleiotropic effects due to unregulated activation of the cognate response regulator QseB, influencing conserved metabolic processes and diminishing expression of virulence genes, including type 1 pili. Here, we discern the type 1 pilus-dependent and -independent effects that contribute to the virulence attenuation of a UPEC qseC deletion mutant in a murine model of experimental UTI. We show that although a ΔqseC mutant restored for type 1 pilus expression regains the ability to colonize the host and initiate acute infection up to 16 h postinfection, it is rapidly outcompeted during acute infection when coinoculated with a wild-type strain. As a result, this strain has a diminished capacity to establish chronic infection. A prophylactic oral dose of a FimH small-molecular-weight antagonist (ZFH-02056) further reduced the ability of the qseC mutant to establish chronic infection. Thus, loss of QseC significantly enhances the efficacy of ZFH-02056. Collectively, our work indicates that type 1 pili and QseC become critical in different infection stages, and that dual targeting of these factors has an additive effect on ablating UPEC virulence.
Autoimmunity resulting from cytokine treatment predicts long-term survival in patients with metastatic renal cell cancer.

PURPOSE In patients undergoing cytokine therapy, systemically applied interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) have been reported to induce thyroid dysfunction as well as thyroid autoantibodies. We analyzed the correlation of thyroid autoimmunity with HLA phenotype, various other autoimmune parameters, and patient survival. PATIENTS AND METHODS For this purpose, antithyroglobulin autoantibodies, antimicrosomal thyroid autoantibodies, thyroglobulin receptor autoantibodies, thyroid dysfunction, and multiple clinical parameters were determined in 329 unselected patients with metastatic renal cell cancer before and after systemic IL-2 and IFN-alpha2 therapy. For statistical analysis, we used both univariate and multivariate Cox proportional hazards models and the two-tailed Fisher's exact test. RESULTS Antithyroglobulin autoantibodies and antimicrosomal thyroid autoantibodies were detected in 60 patients (18%); positive autoantibody titers of various other autoimmune parameters were statistically unrelated. The presence of thyroid autoantibodies was correlated with prolonged survival (P<.0001). There was a statistically significant difference in frequencies of HLA-Cw7 expression between thyroid autoantibody-positive and -negative patients (P< or =.05), and the Cw7 expression was associated with prolonged overall survival (P = .009). CONCLUSION The evaluation of thyroid autoantibodies during cytokine therapy could be a useful prognostic marker for patients with renal cell carcinoma who benefit from cytokine treatment. IL-2- and IFN-alpha2-induced tumor control and prolonged survival may require breaking of immunologic tolerance against self-antigens.
Timing of pulmonary emboli after trauma: implications for retrievable vena cava filters.

BACKGROUND Four recent reports of the retrieval of optional vena cava filters (VCF) in trauma patients had average implant durations of 10, 19, and 19 days (one not specified). Two patients in these studies had pulmonary emboli after VCF removal. No evidence-based guidelines exist on the appropriate time to remove optional VCF. The purpose of this study was to examine the timing of pulmonary emboli (PE) and determine the optimal time to remove optional VCFs. METHODS A multicenter retrospective chart review of trauma patients who had a postinjury PE between January 2001 and December 2004 was performed. We examined the demographics, prophylaxis at the time of PE (pharmacologic [unfractionated or low molecular weight heparin] or sequential compression devices [SCD]), diagnostic test used, timing of PE from the date of injury, and survival outcome. RESULTS In all, 146 patients were identified, mean age 45.1 (+/- 21.1 SD); Injury Severity Score 18.0 (+/- 12.1 SD). Diagnosis was obtained by spiral computed tomography (N = 93), pulmonary arteriogram (N = 18), V/Q (N = 26), autopsy (N = 6), clinical (N = 6), and unknown (N = 3). Overall mortality was 17.8% (N = 26). Pulmonary embolism was felt to contribute to or was the cause of death in 85% (N = 22) of these patients. Two late PE deaths occurred (days 21 and 43). Sixty (37%) patients had pharmacologic prophylaxis at the time of PE and 83 (50.9%) had SCDs. Average time from injury to PE was 7.9 days (+/- 8.1 SD), the longest being 43 days postinjury. Eleven percent of PE occurred after 21 days, including fatal PE. CONCLUSIONS Clinical criteria defining the time to remove optional VCFs without exposing patients to the risk of PE by removing a filter too soon should be determined.
The Mendelian inheritance of rare flesh and shell colour variants in the black-lipped pearl oyster (Pinctada margaritifera).

Pinctada margaritifera is French Polynesia's most economically important aquaculture species. This pearl oyster has the specific ability to produce cultured pearls with a very wide range of colours, depending on the colour phenotypes of donor oysters used. Its aquaculture is still based on natural spat collection from wild stocks. We investigated three rare colour variants of P. margaritifera - orange flesh, and red and white shell colour phenotypes - in comparison with the wild-type black flesh and shell commonly found in this species. The study aimed to assess the geographic distribution and genetic basis of these colour variants. Colour frequencies were evaluated during transfer and graft processes of pearl oyster seed captured at collector stations. Among the collection locations studied, Mangareva Island showed the highest rate of the orange flesh phenotype, whereas Takaroa and Takume atolls had relatively high rates of red and white shell phenotypes respectively. Broodstocks were made of these rare colour variants, and crosses were performed to produce first- and second-generation progenies to investigate segregation. The results were consistent with Mendelian ratios and suggest a distinct model with no co-dominance: (i) a two-allele model for flesh trait, whereby the orange allele is recessive to the black fleshed type, and (ii) a three-allele model for shell trait, whereby the black wild-type allele is dominant to the red coloration, which is dominant to the white shell. Furthermore, the proposed model provides the basis for producing selected donor pearl oyster lines through hatchery propagation.
Molecular Biology of Exfoliation Syndrome

Exfoliation syndrome (XFS) is a common age-related matrix process resulting from excessive production and disordered assembly of elastic microfibrillar components into highly cross-linked fibrillary aggregates throughout the anterior eye segment and various organ systems. The underlying molecular pathophysiology involves a complex interplay of profibrotic protagonists including growth factors, proteolytic enzymes and inhibitors, proinflammatory cytokines, chaperones, and dysregulated stress response pathways including insufficient autophagy. Interaction between individual genetic predisposition and stress factors is a plausible theory explaining the development of XFS in the aging individual. Genome-wide association studies have identified robust genetic associations with LOXL1, CACNA1A, and 5 additional genes including POMP and TMEM136, which provide new biological insights into the pathology of XFS and highlight a role for abnormal matrix cross-linking processes, Ca2+ channel deficiency, blood-aqueous barrier dysfunction, and abnormal ubiquitin-proteasome signaling in XFS pathophysiology. However, the exact pathophysiological mechanisms, the functional role of genetic risk variants, and gene-environment interactions still remain to be characterized.
Enhanced upper respiratory tract airflow and head fanning reduce brain temperature in brain-injured, mechanically ventilated patients: a randomized, crossover, factorial trial.

BACKGROUND Heat loss from the upper airways and through the skull are physiological mechanisms of brain cooling which have not been fully explored clinically. METHODS This randomized, crossover, factorial trial in 12 brain-injured, orally intubated patients investigated the effect of enhanced nasal airflow (high flow unhumidified air with 20 p.p.m. nitric oxide gas) and bilateral head fanning on frontal lobe brain temperature and selective brain cooling. After a 30 min baseline, each patient received the four possible combinations of the interventions--airflow, fanning, both together, no intervention--in randomized order. Each combination was delivered for 30 min and followed by a 30 min washout, the last 5 min of which provided the baseline for the next intervention. RESULTS The difference in mean brain temperature over the last 5 min of the preceding washout minus the mean over the last 5 min of intervention, was 0.15 degrees C with nasal airflow (P=0.001, 95% CI 0.06-0.23 degrees C) and 0.26 degrees C with head fanning (P<0.001, 95% CI 0.17-0.34 degrees C). The estimate of the combined effect of airflow and fanning on brain temperature was 0.41 degrees C. Selective brain cooling did not occur. CONCLUSION Physiologically, this study demonstrates that heat loss through the upper airways and through the skull can reduce parenchymal brain temperature in brain-injured humans and the onset of temperature reduction is rapid. Clinically, in ischaemic stroke, a temperature decrease of 0.27 degrees C may reduce the relative risk of poor outcome by 10-20%. Head fanning may have the potential to achieve a temperature decrease of this order.
Natural Intestinal Protozoa in Rodents (Rodentia: Gerbillinae, Murinae, Cricetinae) in Northwestern Iran

Background: Majority of parasitic infections in rodents have zoonotic importance. This study aimed to determine the frequency and intensity of intestinal protozoa infections of rodents including Meriones persicus, Mus musculus and, Cricetulus migratorius. Methods: This survey was conducted in Meshkin Shahr district in northwestern Iran from Mar. to Dec. of 2014. Intestinal samples of 204 rodents including M. persicus (n=117), M. musculus (n=63) and C. migratorius (n=24) were parasitologically examined. Formalin-ether concentration method was done for all of rodents stool samples and observed with light microscope. All of suspected cases were stained with trichorome staining Method. Cultivation in dichromate potassium 2.5% was carried out for all of coccidian positive samples. Acid fast and aniline blue staining methods were used for detecting of coccidian oocysts and intestinal microsporidial spores, respectively. Results: About 121(59.3%) of the caught rodents were generally infected with intestinal protozoa. Entamoeba muris 14(6.9%), Trichomonas muris 55(27.0%), Chilomastix betencourtti 17 (8.3%), Giardia muris 19(9.3%), Eimeria spp. 46(22.5%), Isospora spp. 4(2%) and Cryptosporidium spp. 1(0.5%) were found from the collected rodents. Microsporidian spores were identified in 63 (31%) out of the 204 collected rodents using aniline blue staining method. Conclusion: Since some of the infections are zoonotic importance thus, control of rodents can be decreased new cases of the parasitic zoonoses in humans.
Laboratory Diagnosis of Zika Virus Infection.

CONTEXT -The rapid and accurate diagnosis of Zika virus infection is an international priority. OBJECTIVE -To review current recommendations, methods, limitations, and priorities for Zika virus testing. DATA SOURCES -Sources include published literature, public health recommendations, laboratory procedures, and testing experience. CONCLUSIONS -Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited. Furthermore, Zika cross-reacts serologically with other flaviviruses, such as dengue, West Nile, and yellow fever. Current or past infection, or even vaccination with another flavivirus, will often cause false-positive or uninterpretable Zika serology results. Detection of viral RNA during acute infection using nucleic acid amplification tests provides more specific results, and a number of commercial nucleic acid amplification tests have received emergency use authorization. In addition to serum, testing of whole blood and urine is recommended because of the higher vial loads and longer duration of shedding. However, nucleic acid amplification testing has limited utility because many patients are asymptomatic or present for testing after the brief period of Zika shedding has passed. Thus, the greatest need and most difficult challenge is development of accurate antibody tests for the diagnosis of recent Zika infection. Research is urgently needed to identify Zika virus epitopes that do not cross-react with other flavivirus antigens. New information is emerging at a rapid pace and, with ongoing public-private and international collaborations and government support, it is hoped that rapid progress will be made in developing robust and widely applicable diagnostic tools.
Feature Selective Normalized Mutual Information Index for the validation of computational electromagnetics

An important concern in the validation of computational electromagnetics (CEM) is to incorporate quantitative indicators in order to perform conclusive comparisons between model predictions with respect to a reference expected response, such as data obtained from measurements, closed-form equations references or standard reference problems values. Besides, the aforementioned index must be qualitatively interpreted using established and objective criteria, mimicking the perception of individuals or teams of expert engineers and aiding them in the interpretation process. So far, this problem has been addressed by the standardized Feature Selective Validation (FSV) method which has become the most widespread technique in the validation of CEM. Nonetheless, the FSV has some drawbacks which have driven subsequent and non consolidated enhancements proposed to improve its performance under specific situations. This paper proposes a global and normalized mutual information based index that includes feature selective considerations as an alternative to evaluate and compare datasets involved in the validation of CEM. Finally, three numerical examples are developed using the presented methodology and the results are compared with the overall indicator for the amplitude and the feature measures obtained using the FSV. The results suggest that the proposed index is able to provide intuitive, consistent and compressive interpretation about the global results of the validation process. Nevertheless, research must be continued in order to refine the proposed method and testing its complete range of applicability and suitability.
Diagnostic accuracy of microbial keratitis with in vivo scanning laser confocal microscopy

Aims To determine the accuracy of diagnosing microbial keratitis by masked medical and non-medical observers using the Heidelberg Retina Tomograph II/Rostock Cornea Module in vivo confocal microscope. Methods Confocal images were selected for 62 eyes with culture- or biopsy-proven infections. The cases comprised 26 Acanthamoeba, 12 fungus, three Microsporidia, two Nocardia and 19 bacterial infections (controls). The reference standard for comparison was a positive tissue diagnosis. These images were assessed on two separate occasions by four observers who were masked to the tissue diagnosis. Diagnostic accuracy indices, κ statistic and percentage agreement values were calculated. The Spearman correlation coefficient (rs) was calculated for the number of correct diagnoses versus duration of disease. Results The highest sensitivity and specificity values were 55.8% and 84.2%, respectively, and the lowest sensitivity and specificity values were 27.9% and 42.1%, respectively. The highest positive and lowest negative likelihood ratios were 2.94 and 0.59, respectively. Agreement values were: fair to moderate (κ 0.22–0.44) for reference standard versus observer diagnosis, moderate to good in intraobserver variability (repeatability, κ 0.56–0.88) and poor to moderate in interobserver variability (reproducibility, κ 0.15–0.47). The correct diagnosis was associated with duration of disease for Acanthamoeba keratitis (rs=0.60, p=0.001). Conclusions The diagnostic accuracy of microbial keratitis by confocal microscopy is dependent on observer experience. Intraobserver repeatability was better than interobserver reproducibility. Difficulty in distinguishing host cells from pathogenic organisms limits the value of confocal microscopy as a stand-alone tool in diagnosing microbial keratitis.
Lack of ICAM-1 on APCs during T Cell Priming Leads to Poor Generation of Central Memory Cells1

ICAM-1/LFA-1 interactions are known to enhance T cell/APC interactions and to promote T cell activation and cytokine secretion. We have analyzed the consequences of ICAM-1-mediated signaling on the generation of memory T cell subsets. We report that lack of ICAM-1 on APCs, but not on T cells, leads to poor T cell activation and proliferation in vitro and in vivo, and that the defect can be compensated by Ag dose, exogenous IL-2, additional costimulation, and by increasing responder T cell density on APCs. ICAM-1-null mice do not respond to immunization with OVA peptide, but immunization with OVA or with Salmonella typhimurium leads to good T cell proliferation 7–10 days later, and clearance of a challenge infection is equivalent to that of wild-type mice. However, when followed over time, recall proliferation and antibacterial immunity decay rapidly in ICAM-1-null mice, while recall cytokine responses are unaffected. The decline in immunity is not related to poor survival of T cells activated on ICAM-1-null APCs, or to poor generation of effectors in ICAM-1-null mice. Phenotypic analysis of T cells stimulated on ICAM-1-null APCs reveals preferential generation of CD44highCD62Llow effector memory cells (TEM) over CD44highCD62Lhigh central memory cells (TCM). Further, while the proportion of naive:memory T cells is similar in unmanipulated wild-type and ICAM-1-null mice, there is an accumulation of TEM cells, and a high TEM: TCM ratio in aging ICAM-1-null mice. Together, the data indicate that signaling through LFA-1 during T cell activation may be involved in commitment to a proliferation-competent memory pool.
Assessment of sympathetic index from the Valsalva maneuver

Objective: Blood pressure (BP) decline and recovery during the Valsalva maneuver (VM) are used to evaluate the degree of sympathetic failure (SF) but a reliable sympathetic index (SI) derived from VM is lacking. Methods: Patients with mild (n = 20), moderate (n = 65), and severe (n = 60) SF and 23 healthy controls were evaluated using a standardized battery of autonomic tests. SF was defined as mild (associated with reduced sudomotor volumes at distal leg); moderate (associated with a fall in systolic BP ≥ 10 < 30 mm Hg during the tilt test); and severe (associated with a fall in systolic BP ≥30 mm Hg during the tilt test). Six SIs were compared: SI1 (BP fall during phase 2), SI2 (BP recovery during phase 2), SI3 (the difference in BP between baseline and the end of phase 2), SI4 (the magnitude of phase 4), SI5 (BP recovery time), and SI6 (baroreflex sensitivity index). Results: All indexes showed overall significant differences among tested groups (p < 0.05). Only SI3 differentiated all subject groups. Compared to other SIs, SI3 correlated the most with orthostatic hypotension (OH; r = 0.62, p < 0.05) during the tilt. Conclusions: SI3 is the optimal method for calculation of SI since it 1) easily differentiates between healthy controls and those with SF; 2) correlates with the OH, a proxy for a sympathetic failure; 3) tracks the full spectrum of SF (mild–moderate–severe). SI3 expands the utility of quantitative autonomic testing.
Receptor‐mediated activation of gastric vagal afferents by glucagon‐like peptide‐1 in the rat

Abstract The vagus nerve plays a role in mediating effects of the two glucagon‐like peptides GLP‐1 and GLP‐2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP‐1 receptors and GLP‐2 receptors in the nodose ganglion were examined in Sprague–Dawley rats. Intravenous administration of GLP‐1 (30–1000 pmol kg−1), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13–52% above basal level, P < 0.05) 3–5 min after injection. Repeated administration of GLP‐1 (1000 pmol kg−1; five times, 15 min intervals) elicited similar responses. Pretreatment with GLP‐1 receptor antagonist exendin(9‐39)amide (500 pmol kg−1) abolished the GLP‐1 response to doses 30–300 pmol kg−1 but had no effect on the vagal response to gastric distension. For comparison, GLP‐2 (1000 pmol kg−1) had no effect on vagal afferent activity. Vagal chemoreception of GLP‐1 is supported by expression of the GLP‐1 receptor gene in the nodose ganglion. However, the GLP‐2 receptor was also expressed. To conclude, our results show that peripherally administered GLP‐1, differently from GLP‐2, activates vagal afferents, with no evidence of desensitisation. The GLP‐1 effect was blocked by exendin(9‐39)amide, suggesting that GLP‐1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP‐2 receptors appear not be functionally expressed on vagal afferents.
Frequent HPRT mutations in paroxysmal nocturnal haemoglobinuria reflect T cell clonal expansion, not genomic instability

Paroxysmal nocturnal haemoglobinuria (PNH) results from acquired mutations in the PIG‐A gene of an haematopoietic stem cell, leading to defective biosynthesis of glycosylphosphatidylinositol (GPI) anchors and deficient expression of GPI‐anchored proteins on the surface of the cell's progeny. Some laboratory and clinical findings have suggested genomic instability to be intrinsic in PNH; this possibility has been supported by mutation analysis of hypoxanthine‐guanine phosphoribosyltransferase (HPRT) gene abnormalities. However, the HPRT assay examines lymphocytes in peripheral blood (PB), and T cells may be related to the pathophysiology of PNH. We analysed the molecular and functional features of HPRT mutants in PB mononuclear cells from eleven PNH patients. CD8 T cells predominated in these samples; approximately half of the CD8 cells lacked GPI‐anchored protein expression, while only a small proportion of CD4 cells appeared to derive from the PNH clone. The HPRT mutant frequency (Mf) in T lymphocytes from PNH patients was significantly higher than in healthy controls. The majority of the mutant T lymphocyte clones were of CD4 phenotype, and they had phenotypically normal GPI‐anchored protein expression. In PNH patients, the majority of HPRT mutant clones were contained within the Vβ2 T cell receptor (TCR) subfamily, which was oligoclonal by complementarity‐determining region three (CDR3) size analysis. Our results are more consistent with detection of uniform populations of expanded T cell clones, which presumably acquired HPRT mutations during antigen‐driven cell proliferation, and not due to an increased Mf in PNH. HPRT mutant analysis does not support underlying genomic instability in PNH.