Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection by Meningococcal Outer Membrane Protein PorA-Specific Antibodies and a Serogroup B Capsular Polysaccharide-Specific Antibody in Complement-Sufficient and C6-Deficient Infant Rats

ABSTRACT The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c−) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c− rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.
Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS).

BACKGROUND Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (ASCUS), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage. METHODS We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thin-layer cytopathology in 2198 women with ASCUS and in 848 women with LSIL enrolled in ALTS from November 1996 through December 1998. We analyzed results by age and at two thresholds for HPV load and repeat cytopathology. RESULTS For ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with ASCUS, referral for repeat cytopathology of ASCUS had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity. CONCLUSION For women with ASCUS, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL.
Microscopic colitis demonstrates a T helper cell type 1 mucosal cytokine profile

Background: Microscopic colitis (MC) is an inflammatory disorder of unknown aetiology. Aim: To characterise the mucosal cytokine profile of MC, with a view to understanding its potential pathogenic mechanisms. Methods: Cytokine profiles of mucosal biopse specimens taken at flexible sigmoidoscopy from 18 patients (8 with lymphocytic colitis and 10 with collagenous colitis) were analysed using real-time reverse transcriptase-PCR, in comparison with those from 13 aged-matched controls with diarrhoea-predominant irritable bowel syndrome. Biopsy specimens from six patients with histologically documented remission were available for comparative analysis. Biopsy specimens were also taken to determine the cellular expression of cytokine and cytokine-related proteins using immunohistochemistry. Results: Mucosal mRNA levels were 100 times greater for interferon (IFN)γ and interleukin (IL) 15, 60 times greater for tumour necrosis factor α, and 35 times greater for inducible nitric oxide synthase in MC compared with controls. Apart from a trend for increased levels of IL10, levels of other T helper cell type 2 (TH2) cytokines including IL2 and IL4 were too low to be accurately quantified. Mucosal IFNγ mRNA levels correlated with the degree of diarrhoea, and returned to normal in remission. The immunohistochemical expression of cell junction proteins E-cadherin and ZO-1 was reduced in active disease. No differences were noted between lymphocytic and collagenous colitis for any of the above parameters. Conclusions: MC demonstrates a TH1 mucosal cytokine profile with IFNγ as the predominantly upregulated cytokine, with concurrent induction of nitric oxide synthase and down regulation of IFNγ-related cell junction proteins. This pattern is similar to that in coeliac disease and suggests that it might represent a response to a luminal antigen.
Survival prediction of distressed firms: evidence from the Chinese special treatment firms

ABSTRACT In the Chinese stock market, firms experiencing financial distress have been imposed on a Special Treatment (ST) cap by the China Securities Regulatory Commission. Using a sample of 441 ST firms tracked from 1998 to 2011, this paper employs a Cox proportional hazards model to predict turnaround probability for a distressed firm to remove the ST cap. The predictor variables incorporate (1) accounting-driven ratios, (2) market-driven variables, and (3) information on ownership structure and restructuring status throughout the process. In contrast to previous distress studies, this paper finds that market variables do not add predictive power to the model when combined with accounting variables. Also, incorporating the time effect, the results show that the survivor function for an ST firm's survival is negatively related to the duration, and that the Cox hazards model outperforms the logit model in the out-of-sample forecast.
[Non-invasive fetal RhD typing and RhD negative pregnant women--preliminary observations].

OBJECTIVES For a follow up of a pregnancy in a RhD neg women it is crucial to learn whether her fetus is RhD pos or neg. AIM Detection of fetal RHD gene in the plasma of RhD neg mother in various periods of pregnancy and a comparison with RhD of a newborn. 45 plasma samples from various periods of pregnancy from 28 RhD neg women. MATERIAL AND METHODS Examination of: RHD (exon 7 and 10), SRY, GSTM1 and ACE using real-time PCR. RESULTS Fetal RHD was detected in all 23 mothers with RhD pos child; in one of them, in the 12th week of gestation, RHD was detected only using primers for exon 7, however in the 21st--the presence of both RHD exons was confirmed. Five mothers delivered RhD neg newborns--both RHD exons were not detected. In all 5 cases other fetal genes were examined to be certain that the fetal DNA was analysed. In all 3 mothers who delivered RhD neg boys, the SRY was detected. Among 2 mothers who delivered RhD neg girls, the presence of fetal DNA was confirmed in one, by GSTM1 detection. CONCLUSIONS 1) Real-time PCR is an appropriate, non-invasive method for fetal RhD examination. 2) Two RHD exons should be examined. 3) Control genes should be investigated and found to be sure that negative result of the RHD was not false negative due to the lack of fetal DNA; SRY is an appropriate control for boys, while for girls further investigations are needed, which are in progress.
Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34–expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292–301. ©2017 AACR.
Contribution of Selected Traditional and Market Foods to the Diet of Nunavik Inuit Women.

Food composition data were determined for food consumed by 226 Inuit women in Nunavik, estimating the relative contribution of traditional and market food for energy, protein, lipid, carbohydrate, vitamin A, vitamin D, iron, calcium, magnesium, phosphorus, selenium, zinc, and eicosapentaenoic and docosahexaenoic acids. Traditional Inuit food was an important source of protein, vitamin D, iron, selenium, and phosphorus, as well as the main source of eicosapentaenoic and docosahexaenoic acids. The mean contribution of traditional and market food to energy and nutrients was analyzed according to age groups (18-39 and 40-74). Analysis of Inuit women's nutrient intake showed that the contribution of traditional food was greater in the older group than in the younger group, for whom the contribution of market food was greater. Market food contributed the most to Inuit women's energy intake, while 40% of the intake of several nutrients, including protein, vitamin D, iron, phosphorus, and zinc, was derived from traditional food. Inuit women had low vitamin A and calcium intakes. Traditional food had low calcium and vitamin A concentrations, and the Inuit infrequently consumed market food such as milk, dairy products, and yellow and green vegetables. Thus, even though the present study showed that traditional food was the major source of many nutrients in the Inuit diet, market food was also important for the nutritional status of this population, particularly young women. In promoting safe nutritional habits among the Inuit, dietitians must help them maintain traditional food use, which has provided some health advantages (e.g., a lower incidence of cardiovascular disease); encourage consumption of nutritious market foods; and consider the societal values reflected in the traditional diet.
Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma‐glutamyl transpeptidase levels

The aim of the present study was to investigate the association of serum gamma‐glutamyltransferase (GGT) levels with all‐cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population‐based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis. GGT was divided into age‐ and sex‐dependent quintiles to calculate overall and sex‐specific crude incidence mortality rates. Hepatic steatosis was defined by elevated GGT levels (>80%) and the presence of hyperechogenic liver ultrasound. We used multiple‐adjusted Cox proportional hazards regression models, first, to assess the direct effect of GGT on all‐cause mortality, second, to stratify according to the ultrasonographic finding, and third, to investigate potential mediating effects of cardiometabolic risk factors. During 29,810 person‐years (7.3 years, median) of follow‐up, 307 individuals (7.5%) died, resulting in a death rate of 0.86 deaths per 1000 person‐years. Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.08–2.05), but not in women (HR 1.30; 95% CI, 0.80–2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21–3.27). Cause‐specific mortality analysis by cardiovascular disease deaths confirmed the sex‐specific association. Adjustment for cardiometabolic risk factors did not affect the estimates. Conclusion: In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification. (HEPATOLOGY 2009.)
Stable high-order delta-sigma digital-to-analog converters

Stability analysis of high-order delta-sigma loops is a challenge. In this brief, a sufficient design criterion is presented for high-order multibit error-feedback digital-to-analog converters (DACs) which are especially suitable for high-speed operation. This analytical criterion might be too conservative, but it allows for the design of stable, robust, and high-resolution delta-sigma DACs. Both analytical and numerical analysis are performed for verification. Also, experimental results of a discrete-component multiplier-free prototype demonstrate 10-b operation at a very low oversampling ratio of 4.
Functional segregation and temporal hierarchy of the visual perceptive systems

In extending our previous work, we addressed the question of whether different visual attributes are perceived separately when they belong to different objects, rather than the same one. Using our earlier psychophysical method, but separating the attributes to be paired in the two different halves of the screen, we found that human subjects misbind the colour and the direction of motion, or the colour and the orientation of lines, because colour, form, and motion are perceived separately and at different times. The results therefore show that there is a perceptual temporal hierarchy in vision.
Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck

VEGF proteins and their receptors are involved in tumor vessel neoformation. The third VEGF receptor, VEGFR3 (flt‐4) is important during both blood vessel development and lymphatic vessel formation. Because HNSCC preferentially metastasizes to regional lymph nodes, we investigated the expression of VEGFR3 and its ligand VEGF‐C in head and neck squamous cell carcinomas by semiquantitative RT‐PCR (4 HNSCC cells lines and 6 HNSCC specimens) and by immunohistochemistry (18 HNSCC specimens). VEGFR3 protein expression was confirmed by Western blotting in four HNSCC cell lines and six HNSCC specimens.
Glacial/Interglacial Changes in Subarctic North Pacific Stratification

Since the first evidence of low algal productivity during ice ages in the Antarctic Zone of the Southern Ocean was discovered, there has been debate as to whether it was associated with increased polar ocean stratification or with sea-ice cover, shortening the productive season. The sediment concentration of biogenic barium at Ocean Drilling Program site 882 indicates low algal productivity during ice ages in the Subarctic North Pacific as well. Site 882 is located southeast of the summer sea-ice extent even during glacial maxima, ruling out sea-ice–driven light limitation and supporting stratification as the explanation, with implications for the glacial cycles of atmospheric carbon dioxide concentration.
Cytokine Gene Expression in Regenerating Haematopoietic Tissues of Mice after Cyclophosphamide Treatment

The goal of the study was to investigate changes in expression of selected growth factors tentatively involved in regeneration of haematopoietic tissues (bone marrow and spleen) following cyclophosphamide (CY) damage in the mouse. The bone marrow (BM) and spleen were examined separately, since the regenerating pattern for haematopoietic progenitor cells (HPC) markedly differs in these two haematopoietically active organs after CY. Cytokines assumed to have a stimulatory effect on HPC – stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (flt3-ligand), thrombopoietin (TPO), stromal cell-derived factor 1 (SDF-1), oncostatin M (OSM) –, a suppressive effect on HPC proliferation – macrophage inflammatory protein-1α (MIP-1α), transforming growth factor-β1 (TGFβ1), tumour necrosis factor-α (TNFα) – and to be involved in migration of HPC (SCF, flt3-ligand, MIP1α, SDF-1) were examined at the level of mRNA expression by means of real-time RT-PCR. The expression of a particular cytokine appears to be similar in both BM and spleen of untreated mice. CY administration changed the expression pattern of the studied genes in BM and spleen. In BM, the levels of mRNAs for SCF and SDF-1 were increased and that for TGFβ1 decreased at time intervals at which HPC are known to proliferate intensively during BM regeneration. In contrast, stimulated proliferation of HPC in spleen was accompanied by increased expression of flt3-ligand and oncostatin M. Upon mobilization of HPC from BM into blood after CY, the expression of SCF, TPO, SDF-1 and TGFβ1 tends to decrease in BM. Accumulation of HPC in spleen is accompanied by increased mRNA for flt3-ligand and OSM. Our findings demonstrate that different cytokines may be involved in the proliferation and mobilization/homing of HPC during recovery after CY damage in BM and spleen.
Kinematics of the Thoracic Spine in Trunk Rotation: In Vivo 3-Dimensional Analysis

Study Design. In vivo 3-dimensional (3D) study of the thoracic spine. Objective. To demonstrate axial rotations (ARs) and coupled motions of the thoracic spine. Summary of Background Data. In vivo 3D kinematics of the thoracic spine in trunk rotation with intact thorax and soft tissues has not been well-known. There were no quantitative data of AR in the consecutive thoracic spinal segments. Patterns of coupled motion with AR have been controversial. Methods. Thirteen healthy volunteers underwent 3D computed tomography of the thoracic spine in 3 positions; neutral, right, and left maximum trunk rotation. Relative motions of vertebrae were calculated by automatically superimposing the vertebrae in a neutral position over images in rotational positions, using voxel-based registration. Motions were represented with 6 degrees of freedom by Euler angles and translations on the local coordinate system. Results. Mean (±SD) relative rotational angles of T1 with respect to L1 to 1 side were 24.9° ± 4.9° in maximum trunk rotation. AR of each thoracic segment with respect to the inferior adjacent vertebra to 1 side was 1.2° ± 0.8° at T1–T2, 1.6° ± 0.7° at T2–T3, 1.4° ± 0.9° at T3–T4, 1.6° ± 0.8° at T4–T5, 1.8° ± 0.7° at T5–T6, 1.9° ± 0.6° at T6–T7, 2.3° ± 0.7° at T7–T8, 2.5° ± 0.8° at T8–T9, 2.7° ± 0.6° at T9–T10, 2.6° ± 0.8° at T10–T11, 1.3° ± 0.7° at T11–T12, and 0.5° ± 0.4° at T12–L1. Significantly larger segmental AR was observed at the middle thoracic segments (T6–T11) than at the upper (T1–T6) and lower (T11–L1) segments. At the upper thoracic segments, coupled lateral bending with AR was observed in the same direction as AR. However, at the middle and lower thoracic segments, coupled lateral bending occurred both in the same and opposite directions. Conclusion. In vivo 3D ARs and coupled motions of the consecutive thoracic spinal segments in trunk rotation were investigated accurately for the first time.
Disentangling Components of Flexibility via the Hexaflex Model: Development and Validation of the Multidimensional Psychological Flexibility Inventory (MPFI)

The current study developed the 60-item Multidimensional Psychological Flexibility Inventory (MPFI)—a scale assessing the 12 dimensions of the Hexaflex model. We created an exhaustive pool of 554 items including 22 of the most widely used measures from the acceptance and commitment therapy and mindfulness literatures. Exploratory and confirmatory factor analyses were used in combination with item response theory and responsiveness to change analyses in 3,040 online respondents across three studies (NStudy 1 = 372; NStudy 2 = 2,150; NStudy 3 = 518) to create the MPFI. Associations between the MPFI subscales and an array of existing measures supported its convergent and discriminant validities. The MPFI offers acceptance and commitment therapy researchers new tools for elaborating treatment effects.
Transient Ca2+‐permeable AMPA receptors in postnatal rat primary auditory neurons

Fast excitatory transmission in the nervous system is mostly mediated by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors whose subunit composition governs physiological characteristics such as ligand affinity and ion conductance properties. Here, we report that AMPA receptors at inner hair cell (IHC) synapses lack the GluR2 subunit and are transiently Ca2+‐permeable before hearing onset as evidenced using agonist‐induced Co2+ accumulation, Western blots and GluR2 confocal microscopy in the rat cochlea. AMPA (100 µm) induced Co2+ accumulation in primary auditory neurons until postnatal day (PND) 10. This accumulation was concentration‐dependent, strengthened by cyclothiazide (50 µm) and blocked by GYKI 52466 (80 µm) and Joro spider toxin (1 µm). It was unaffected by D‐AP5 (50 µm), and it could not be elicited by 56 mm K+ or 1 mm NMDA + 10 µm glycine. Western blots showed that GluR1 immunoreactivity, present in homogenates of immature cochleas, had disappeared by PND12. GluR2 immunoreactivity was not detected until PND10 and GluR3 and GluR4 immunoreactivities were detected at all the ages examined. Confocal microscopy confirmed that the GluR2 immunofluorescence was not located postsynatically to IHCs before PND10. In conclusion, AMPA receptors on maturing primary auditory neurons differ from those on adult neurons. They are probably composed of GluR1, GluR3 and GluR4 subunits and have a high Ca2+ permeability. The postsynaptic expression of GluR2 subunits may be continuously regulated by the presynaptic activity allowing for variations in the Ca2+ permeability and physiological properties of the receptor.