Miracle-dz/UniFAR-FTUs huggingface dataset:
ISSa4-Based Differentiation of Streptococcus agalactiae Strains and Identification of Multiple Target Sites for ISSa4 Insertions

ABSTRACT A collection of 113 epidemiologically unrelated Streptococcus agalactiae strains were studied (group B streptococcus; GBS): they belonged to different serotypes and were isolated from pregnant women in China and Russia. The insertion sequence ISSa4 was found in 21 of 113 strains (18,6%). All of the strains with ISSa4 belonged to serotypes II and II/c and were characterized by the presence of IS1381 and IS861 as well as the absence of IS1548 and GBSi1. All of the strains with ISSa4 possessed both bca and bac virulence genes coding for α and β antigens, respectively. Among 21 ISSa4-positive strains, 13 different HindIII patterns (D1 to D13) hybridizing with an ISSa4 probe were found. One of them (D13) contained a single HindIII hybridization fragment 6.5 kb in size that was found to be specific for all ISSa4-positive GBS strains. Multiple target sites for insertions of ISSa4 were identified and included a putative pathogenicity island, “housekeeping” genes, and intergenic regions, as well as the genes for hypothetical proteins. No significant similarity was observed in the sequences of the target genes for ISSa4 insertions, in the relative location of the target genes on the chromosome, or the biological functions of the encoded proteins. The possible significance of ISSa4-based differentiation of the strains and the presence of possible “hot spots” for insertions of ISSa4 in GBS genome are discussed.
Elderly Patients Affected by Glioblastoma Treated With Radiotherapy: The Role of Serum Hemoglobin Level

ABSTRACT Objective: To investigate the role of serum hemoglobin level for elderly patients with glioblastoma treated with radiotherapy (RT). Methods: Patients older than 65 years with glioblastoma, who underwent surgical resection/biopsy and RT, were evaluated. Total doses were 30 or 60 Gy:30 Gy in 10 or 5 fractions (palliative approach) and 60 Gy in 30 fractions (standard approach). In the standard approach, temozolomide was administered concomitantly and adjuvantly to RT. Before starting and weekly during RT, serum hemoglobin level was assessed for all patients. Recursive partitioning analysis (RPA) was used to classify patients. Results: From 2005 to 2011, 45 patients (median age 71 years) were treated in our institution. Hemoglobin level less than 12 was confirmed in 11 patients. Median progression-free survival (PFS) and overall survival (OS) were 8 and 13 months, respectively. Only RPA class and extent of surgery correlated to PFS (p = .002, p = .04, respectively). RPA class, surgery, and RT dose affected OS (p = .003, p = .02, p = .03, respectively), whereas age (<70 vs. ≥70 years) and hemoglobin level (<12 vs. ≥12) did not influenced outcome (p = 0.2, p = 0.5, respectively). Conclusion: Our data suggested that extent of surgery and RPA class remain independent prognostic factor, whereas patients’ anemia did not adversely affect prognosis in glioblastoma elderly patients.
Efficient Approximate Query Answering over Sensor Data with Deterministic Error Guarantees

With the recent proliferation of sensor data, there is an increasing need for the efficient evaluation of analytical queries over multiple sensor datasets. The magnitude of such datasets makes exact query answering infeasible, leading researchers into the development of approximate query answering approaches. However, existing approximate query answering algorithms are not suited for the efficient processing of queries over sensor data, as they exhibit at least one of the following shortcomings: (a) They do not provide deterministic error guarantees, resorting to weaker probabilistic error guarantees that are in many cases not acceptable, (b) they allow queries only over a single dataset, thus not supporting the multitude of queries over multiple datasets that appear in practice, such as correlation or cross-correlation and (c) they support relational data in general and thus miss speedup opportunities created by the special nature of sensor data, which are not random but follow a typically smooth underlying phenomenon. To address these problems, we propose PlatoDB; a system that exploits the nature of sensor data to compress them and provide efficient processing of queries over multiple sensor datasets, while providing deterministic error guarantees. PlatoDB achieves the above through a novel architecture that (a) at data import time pre-processes each dataset, creating for it an intermediate hierarchical data structure that provides a hierarchy of summarizations of the dataset together with appropriate error measures and (b) at query processing time leverages the pre-computed data structures to compute an approximate answer and deterministic error guarantees for ad hoc queries even when these combine multiple datasets.
Contributions of the large hydrophobic amino acids to the stability of staphylococcal nuclease.

To quantitate the contributions of the large hydrophobic residues in staphylococcal nuclease to the stability of its native state, single alanine and glycine substitutions were constructed by site-directed mutagenesis for each of the 11 leucine, 9 valine, 7 tyrosine, 5 isoleucine, 4 methionine, and 3 phenylalanine residues. In addition, each isoleucine was also mutated to valine. The resulting collection of 83 mutant nucleases was submitted to guanidine hydrochloride denaturation using intrinsic tryptophan fluorescence to monitor the equilibrium constant between the native and denatured states. From analysis of these data, each mutant protein's stability to reversible denaturation (delta GH2O) and sensitivity to guanidine hydrochloride (mGuHCl or d(delta G)/d[GuHCl]) were obtained. Four unexpected trends were observed. (1) A striking bipartite distribution was found for sites of mutations that altered mGuHCl: mutations that increased this parameter only involved residues that contribute side chains to the major hydrophobic core centered around a five-strand beta-barrel, whereas mutations that caused mGuHCl to decrease clustered around a second, smaller and less well-defined hydrophobic core. (2) The average stability loss for mutants in each of the six residue classes was 2-3 times greater than that estimated on the basis of the free energy of transfer of the hydrophobic side chain from water to n-octanol. (3) The magnitude of the stability loss on substituting Ala or Gly for a particular type of amino acid varied extensively among the different sites of its occurrence in nuclease, indicating that the environment surrounding a specific residue determines how large a stability contribution its side chain will make. (ABSTRACT TRUNCATED AT 250 WORDS)
Reduced Levels of Nitric Oxide Metabolites in Cerebrospinal Fluid Are Associated with Equine Protozoal Myeloencephalitis

ABSTRACT Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NOx−) in the cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NOx− levels were measured before and after transport-stressed, acclimated, or dexamethasone-treated horses (n = 3 per group) were experimentally infected with S. neurona sporocysts. CSF NOx− levels were also compared between horses that were diagnosed with EPM after natural infection with S. neurona and horses that did not have clinical signs of disease or that showed no evidence of infection with the parasite (n = 105). Among the experimentally infected animals, the mean CSF NOx− levels of the transport-stressed group, which had the most severe clinical signs, was reduced after infection, while these values were found to increase after infection in the remaining groups that had less severe signs of EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF NOx− concentration than clinically normal horses with antibodies (Abs) against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had a significantly lower mean CSF NOx− concentration than horses that did not have neurologic signs (n = 24). In conclusion, lower CSF NOx− levels were associated with clinical EPM, suggesting that measurement of CSF NOx− levels could improve the accuracy of diagnostic tests that are based upon detection of S. neurona-specific Abs in CSF alone and that reduced NO levels could be causatively related to the development of EPM.
Validly Interpreting Patients’ Reports: Using Bifactor and Multidimensional Models to Determine Whether Surveys and Scales Measure One or More Constructs

Introduction:Validly interpreting scores based on patients’ reports of their experiences using scales depends on a valid scoring system. The possibility exists that, although the creators of a scale intended to create a scale measuring a single construct, the questions may seem to measure more than one construct. However, the possibility also exists that the questions do generally measure one construct, but several “nuisance” constructs influence the measurement of the construct indirectly. Unidimensional, multidimensional, and bifactor analytical models offer a method for establishing scale dimensionality and subsequently developing valid scoring systems. In this paper, we take an applied perspective, discuss these models and their implications, and use real data to provide an example. Methods:We used unidimensional, multidimensional, and bifactor analyses to examine the measurement structure of the Consumer Assessments of Healthcare Providers and Systems Cultural Competence (CAHPS-CC) Survey. Participants came from a 2008 sample of 2 Medicaid managed care plans, in New York and California. Results:Both unidimensional and bifactor models failed to fit the data well. A multidimensional model, with 7 factors corresponding to 7 cultural competence domains fit the data well (root mean square error of approximation=0.064; Tucker-Lewis Index=0.98; comparative fit index=0.97). Discussion:Results indicate that the CAHPS-CC does not seem to measure a single construct. Rather, the CAHPS-CC seems to measure 7 separable domains, suggesting the need for 7 separate scale scores. Our findings highlight the importance of conducting dimensionality analyses.
Crystal‐state 3D‐structural characterization of novel, Aib‐based, turn and helical peptides

The crystal‐state conformations of the hexapeptide amide Pht‐(Aib)6‐NH‐C(CH3)2‐O‐OtBu (7), the hexapeptide Ac‐L‐aIle‐(Aib)5‐OtBu (6), the pentapeptide Z‐(Aib)3‐L‐Glu(OtBu)‐Aib‐O‐(CH2)2‐(1)Nap (5), the tetrapeptides Z‐(Aib)2‐L‐His(Nτ‐Trt)‐Aib‐OMe (4 I) and Z‐(Aib)2‐L‐Nva‐Aib‐OtBu (4 II), the tripeptide Pyr‐(Aib)3‐OtBu (3 I), the dipeptide amides Pyr‐(Aib)2‐(4)NH‐TEMPO (3 II) and Piv‐(Aib)2‐NH‐C(CH3)2‐O‐OtBu (3 III), and the dipeptides Pht‐Aib‐βAc6c‐OtBu (2 I), Pht‐Aib‐NH‐C(CH3)2‐O‐OtBu (2 II) and Boc‐gGly‐mAib‐OH (2 III) have been determined by X‐ray diffraction analyses. All peptides investigated are characterized by one or more turn/helix forming Aib residues. Except the three short dipeptides, all are folded into CO···HN intramolecularly H‐bonded 310‐helices, or into various types of β‐turns. In the structure of 6, two independent molecules of opposite screw sense were observed in the asymmetric unit, generating diastereomeric 310‐helices. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Environmental Aerobiological Studies in Allergic Bronchopulmonary Aspergillosis

An aerobiological pilot study was undertaken to measure airborne concentrations of Aspergillus spores in and around the dwellings of two patients with allergic broncho‐pulmonary aspergillosis (ABPA). The aim of the investigation was 1) to find a specific source of Aspergillus antigen, and 2) to find out whether disease activity, or exacerbation, paralleled Aspergillus spore prevalence. In the environment of the first patient heavy spore contaminated air was found in a cow‐shed, and the adjacent hayloft and scullery. The patient experienced no typical exacerbation during the study period, probably because she now scrupulously avoided this source. The environment of the second patient contained lower spore concentrations in and around the house, and the patient had no typical exacerbation, possibly due to low‐intensity exposure. Both patients, however, had increased bronchial obstruction during periods with high Aspergillus spore content in the outside air. The results suggest that avoidance of Aspergillus spore sources and low overall exposure may play a major role in preventing exacerbation of the disease.
Grass Pollen Immunotherapy Induces Mucosal and Peripheral IL-10 Responses and Blocking IgG Activity1

T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA+ cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3+ T cells and CD68+ macrophages, respectively, whereas only 1–2% of total CD3+ cells and 4% of macrophages expressed IL-10. Following immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG “blocking” activity correlated with the patients’ overall assessment of improvement. Thus, grass pollen immunotherapy may induce allergen-specific, IL-10-dependent “protective” IgG4 responses.
Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

Chemotherapy is widely used in non-small cell lung cancer (NSCLC) treatment, yet multidrug resistance (MDR) is a major chemotherapeutic obstacle in both resectable and advanced NSCLC. Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, is an endothelial cell-derived secreted factor that regulates vascular tube formulation. The aim of this study was to investigate the potential relationships between EGFL7 and MDR in NSCLC cells. We first obtained the CDDP-based MDR phenotype cell line A549/CDDP by repeated exposure to a proper concentration of CDDP (cisplatin) from original A549 cells. These A549/CDDP cells, which maintained relative high levels of EGFL7 and P-glycoprotein (P-gp), were resistant to other chemotherapy drugs, such as carboplatin (CBP), paclitaxel (TAX), and gemcitabine (GEM) (p < 0.05). We also found that hypoxia significantly reduced the chemosensitivity of NSCLC cells, and hypoxia-induced MDR was mediated by P-gp and EGFL7 (p < 0.05). EGFL7 was veryy relevant to NSCLC cell MDR, and downregulation of EGFL7 could significantly increase the chemosensitivity of NSCLC cells (p < 0.05). Thus, our findings first indicate that hypoxia induced NSCLC cell MDR at least partly by enhancing the expression of EGFL7 protein. EGFL7 might be a feasible target for reversing hypoxia-mediated MDR in NSCLC cells and a promising biomarker for predicting the development of MDR in NSCLC patients on chemotherapy.
Azathioprine maintains long‐term steroid‐free remission through 3 years in patients with steroid‐dependent ulcerative colitis†

Background: Studies assessing the efficacy of azathioprine (AZA) in steroid‐dependent ulcerative colitis (SD‐UC) are scarce. The purpose of this trial was to explore the efficacy of AZA in maintaining steroid‐free remission in SD‐UC patients and the factors associated with sustained response. Methods: In this observational cohort study, 42 subjects with SD‐UC were recruited for AZA therapy during a 3‐year period. AZA was adjusted for a target dose of 2–3 mg/kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the annual rate of steroid‐free response to AZA. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. Results: On an intention‐to‐treat basis, the proportion of patients remaining in steroid‐free remission at 12, 24, and 36 months was 0.55, 0.52, and 0.45, respectively. A significant decrease in the flare‐ups rate and in requirement for steroids were observed during 3 years on AZA compared with the previous year (P = 0.000 for both). Patients with and without sustained response were comparable according to demographics, extent of disease, dose of AZA, steroids, and 5‐aminosalicylate (5‐ASA) use. Only disease duration <36 months was associated with off‐steroids remission (P = 0.02, odds ratio [OR] 3.12, 95% confidence interval [CI] 1.89–7.64). The AZA benefit‐risk profile was favorable. Conclusions: In this open‐label observational trial AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 3 years of therapy in SD‐UC. Patients with earlier UC are those who most probably will have sustained steroid‐free remission at the end of 12 months while on AZA. Inflamm Bowel Dis 2009
External morphology of Trichogramma dendrolimi matsumura (hymenoptera: Trichogrammatidae) organ and ultrastructure of the sensilla

In this article, we described the ultrastructure of the sensilla on the antenna, eyes, mouthparts, wings, legs, and external genitalia of female and male Trichogramma dendrolimi using scanning electron microscopy (SEM). The antenna possessed the most sensilla types. We found 13 types of sensilla on female antenna, which were trichoid sensilla (TS) type 1‐4, chaetica sensilla (ChS) type 1‐2, campaniform sensilla (CaS), falcate sensilla, placoid sensilla (PS) type 1‐2, basiconic capitate peg sensilla (BCPS) type 1, coeloconic sensilla (CoS), and styloconic sensilla. Ten types of sensilla were found on the male antenna, some were the same as that on female T. dendrolimi antenna, such as TS types 1 and 3, CaS, PS type 1, BCPS type 1, and CoS, but TS types 5 and 6, ChS type 3, and BCPS 2 were specific to male T. dendrolimi antenna. The leg possesses eight types of sensilla and a kind of tympana structure. Four types of TSs were found on the wings. On the mouthparts, sensilla on the maxillary and labial palps were unique, including two TSs and one ChS. The ovipositor possesses three types of sensilla, and the copulatory organ possesses two types. The eyes had only one kind of TS. Furthermore, external morphology of antenna and external genitalia revealed distinct sexual dimorphisms. According to their morphology, the possible functions of these sensilla were discussed. These results may further our understanding of the sensory mechanisms of T. dendrolimi in response to infochemicals within the environment. Microsc. Res. Tech., 2012. © 2012 Wiley Periodicals, Inc.
Multidrug resistance in Lactococcus lactis: evidence for ATP‐dependent drug extrusion from the inner leaflet of the cytoplasmic membrane.

Lactococcus lactis possesses an ATP‐dependent drug extrusion system which shares functional properties with the mammalian multidrug resistance (MDR) transporter P‐glycoprotein. One of the intriguing aspects of both transporters is their ability to interact with a broad range of structurally unrelated amphiphilic compounds. It has been suggested that P‐glycoprotein removes drugs directly from the membrane. Evidence is presented that this model is correct for the lactococcal multidrug transporter through studies of the extrusion mechanism of BCECF‐AM and cationic diphenylhexatriene (DPH) derivatives from the membrane. The non‐fluorescent probe BCECF‐AM can be converted intracellularly into its fluorescent derivative, BCECF, by non‐specific esterase activities. The development of fluorescence was decreased upon energization of the cells. These and kinetic studies showed that BCECF‐AM is actively extruded from the membrane before it can be hydrolysed intracellularly. The increase in fluorescence intensity due to the distribution of TMA‐DPH into the phospholipid bilayer is a biphasic process. This behaviour reflects the fast entry of TMA‐DPH into the outer leaflet followed by a slower transbilayer movement to the inner leaflet of the membrane. The initial rate of TMA‐DPH extrusion correlates with the amount of probe associated with the inner leaflet. Taken together, these results demonstrate that the lactococcal MDR transporter functions as a ‘hydrophobic vacuum cleaner’, expelling drugs from the inner leaflet of the lipid bilayer. Thus, the ability of amphiphilic substrates to partition in the inner leaflet of the membrane is a prerequisite for recognition by multidrug transporters.
Provider Type and the Receipt of General and Diabetes-Related Preventive Health Services Among Patients With Diabetes

Objective.Using a measure of provider type that includes “shared care” to determine the contribution of provider type on receipt of general and diabetes-related preventive health services. Methods.Automated clinical and administrative data were used to identify adult patients with type 1 and 2 diabetes receiving care from a multispecialty, salaried group practice and enrolled in a large health maintenance organization between 3/97 and 2/98 (n = 10,991). Logistic regression models were fit using generalized estimating equation approaches to evaluate the contribution of provider type on service receipt. Measures.Preventive service receipt included receipt of glycated hemoglobin and lipid testing, retinal examinations, pneumococcal vaccines, Papanicolaou (Pap) smears, and mammograms. Multivariable analyses adjusted for age, sex, race, marital status, household income, diabetes-related comorbidities and complications, prescription drug use, laboratory testing results, and frequency of medical care contact. Results.Patients seeing an endocrinologist and primary care physician (PCP) were more likely than those seeing endocrinologists alone to receive glycated hemoglobin testing (OR, 1.42), lipid testing (OR, 1.72), mammograms (OR, 2.12), and Pap smears (OR, 2.36), and more likely than those seeing PCPs alone to receive glycated hemoglobin testing (OR, 1.79), lipid testing (OR, 1.54), retinal examinations (OR, 1.33), and mammograms (OR, 1.43). Compared with patients seeing PCPs only, patient’s seeing endocrinologists only were more likely to receive retinal examinations (OR, 1.37) and less likely to receive Pap smears (OR, 0.46). Conclusions.Care delivered by no one single provider type is associated with greater receipt of all recommended services. Instead, patients seeing both an endocrinologist and a PCP are most likely to receive recommended services.