Miracle-dz/UniFAR-FTUs huggingface dataset:
Coagulation activation markers do not correlate with the clinical risk of thrombosis in pregnant women.

OBJECTIVE Because coagulation activation markers have been shown to indicate an increased risk of thrombosis, we tested whether thrombin-antithrombin III complexes and D-dimers correlated with the risk assessment in pregnant women on the basis of clinical data. STUDY DESIGN We divided a group of 261 pregnant women (305 pregnancies) into low- and high-risk groups according to the personal and family histories of thrombosis and the presence of a hereditary or an acquired thrombophilia. Women with a thrombotic event in the current pregnancy formed a separate group. All pregnancies with or without heparin therapy were closely monitored with thrombin-antithrombin III and D-dimer values for the entire course of the pregnancy. Retrospectively, the data were then correlated with the different groups and subgroups. RESULTS The course of the mean thrombin-antithrombin III values of all 305 pregnancies was close to or slightly above the upper cutoff line, whereas the D-dimer values were well within the normal range. Independent of heparin, there was no difference in the course of the thrombin-antithrombin III and D-dimer values between the low- and high-risk groups. Only women with ongoing thrombosis during pregnancy had significantly higher thrombin-antithrombin III and D-dimer values with or without heparin therapy. Among those individuals with elevated thrombin-antithrombin III or D-dimer values, there were no specific, recognizable patients who had elevated markers more often than others. CONCLUSIONS Thrombin-antithrombin III and D-dimer values do not correlate with a risk stratification assessed by clinical criteria. There are many women at low clinical risk who have elevated markers, and there are many women at very high clinical risk who have normal markers. Thus thromboprophylaxis would often be used inadequately if the indication were based on coagulation markers.
Ferrous Campylobacter jejuni truncated hemoglobin P displays an extremely high reactivity for cyanide – a comparative study

Campylobacter jejuni hosts two hemoglobins (Hbs). The Camplylobacter jejuni single‐domain Hb (called Cgb) is homologous to the globin domain of flavohemoglobin, and it has been proposed to protect the bacterium against nitrosative stress. The second Hb is called Ctb (hereafter Cj‐trHbP), belongs to truncated Hb group III, and has been hypothesized to be involved in O2 chemistry. Here, the kinetics and thermodynamics of cyanide binding to ferric and ferrous Cj‐trHbP [Cj‐trHbP(III) and Cj‐trHbP(II), respectively] are reported and analyzed in parallel with those of related heme proteins, with particular reference to those from Mycobacterium tuberculosis. The affinity of cyanide for Cj‐trHbP(II) is higher than that reported for any known (in)vertebrate globin by more than three orders of magnitude (K = 1.2 × 10−6 m). This can be fully attributed to the highest (ever observed for a ferrous Hb) cyanide‐binding association rate constant (kon = 3.3 × 103 m−1·s−1), even though the binding process displays a rate‐limiting step (kmax = 9.1 s−1). Cj‐trHbP(III) shows a very high affinity for cyanide (L = 5.8 × 10−9 m); however, cyanide association kinetics are independent of cyanide concentration, displaying a rate‐limiting step (lmax = 2.0 × 10−3 s−1). Values of the first‐order rate constant for cyanide dissociation from Cj‐trHbP(II)–cyanide and Cj‐trHbP(III)–cyanide (koff =5.0 × 10−3 s−1 and loff ≥ 1 × 10−4 s−1, respectively) are similar to those reported for (in)vertebrate globins. The very high affinity of cyanide for Cj‐trHbP(II), reminiscent of that of horseradish peroxidase(II), suggests that this globin may participate in cyanide detoxification.
Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study.

BACKGROUND We previously reported results of the phase 2, multicenter PINNACLE study, which confirmed the substantial single-agent activity of bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL). MATERIALS AND METHODS We report updated time-to-event data, in all patients and by response to treatment, after extended follow-up (median 26.4 months). RESULTS Median time to progression (TTP) was 6.7 months. Median time to next therapy (TTNT) was 7.4 months. Median overall survival (OS) was 23.5 months. In responding patients, median TTP was 12.4 months, median duration of response (DOR) was 9.2 months, median TTNT was 14.3 months, and median OS was 35.4 months. Patients achieving complete response had heterogeneous disease characteristics; among these patients, median TTP and DOR were not reached, and median OS was 36.0 months. One-year survival rate was 69% overall and 91% in responding patients. Median OS from diagnosis was 61.1 months, after median follow-up of 63.7 months. Activity was seen in patients with refractory disease and patients relapsing following high-intensity treatment. Toxicity was generally manageable. CONCLUSIONS Single-agent bortezomib is associated with lengthy responses and notable survival in patients with relapsed or refractory MCL, with considerable TTP and TTNT in responding patients, suggesting substantial clinical benefit.
MYH-9 Related Platelet Disorders: Strategies for Management and Diagnosis

MYH-9 related platelet disorders belong to the group of inherited giant platelet disorders. The MYH-9 gene encodes the non-muscular myosin heavy chain IIA (NMMHCIIA), a cytoskeletal contractile protein. Several mutations in the MYH-9 gene lead to macrothrombocytopenia, and cytoplasmic inclusion bodies within leukocytes, while the number of megakaryocytes in the bone marrow is normal. Four overlapping syndromes, known as May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome and Sebastian platelet syndrome, describe different clinical manifestations of MYH9 gene mutations. Macrothrombocytopenia is present in all affected individuals, whereas only some develop additional clinical manifestations such as renal failure, hearing loss and presenile cataracts. The bleeding tendency is usually moderate, with menorrhagia and easy bruising being most frequent. The biggest risk for the individual is inappropriate treatment due to misdiagnosis of chronic autoimmune thrombocytopenia. More than 30 mutations within the 40 exons of the MYH-9 gene leading to macrothrombocytopenia have been identified, of which the upstream mutations up to amino acid ∼1400 are more likely associated with syndromic manifestations than the downstream mutations. Diagnosis is based on identification of the granulocyte inclusion bodies using blood smears and immunofluorescence and is finally confirmed by identifying the mutation. Treatment is supportive and should be aimed to prevent iron deficiency anemia. Beside renal failure, the biggest risk for patients affected by a MYH-9 disorder are the adverse effects resulting form treatment based on the misdiagnosis of immune thrombocytopenia.
Audit Quality, Earnings Management, and Cost of Equity Capital: Evidence from India

This study examines the effect of audit quality on earnings management and cost of equity capital of listed companies in India. Our results show that companies employing a high-quality auditor have a lower degree of earnings management and lower cost of equity capital. The results also show that companies belonging to business groups have a lower degree of earnings management and lower cost of equity capital than do stand-alone companies but that they benefit less from employing a high-quality auditor. Our results are based on a large sample of 7,303 firm-year observations on listed companies in India and are robust to alternative measures for our main variables – audit quality, earnings management, and cost of capital – and to tests for endogeneity and the impact of the global financial crisis (GFC). Given the distinctive and unique institutional features of the Indian market such as the dominant role of family business groups in the national economy, large market share of domestic audit firms, less litigious environment, and less effective professional accounting bodies in checking audit failure, our findings make a significant contribution to the literature on the role of audit quality as a corporate governance monitoring mechanism as reflected in the impact on earnings management and cost of equity capital.
Crystal structure of the phosphatidylinositol-specific phospholipase C from the human pathogen Listeria monocytogenes.

The X-ray crystal structure of the phosphatidylinositol-specific phospholipase C (PI-PLC) from the human pathogen Listeria monocytogenes has been determined both in free form at 2.0 A resolution, and in complex with the competitive inhibitor myo-inositol at 2.6 A resolution. The structure was solved by a combination of molecular replacement using the structure of Bacillus cereus PI-PLC and single isomorphous replacement. The enzyme consists of a single (beta alpha)8-barrel domain with the active site located at the C-terminal side of the beta-barrel. Unlike other (beta alpha)8-barrels, the barrel in PI-PLC is open because it lacks hydrogen bonding interactions between beta-strands V and VI. myo-Inositol binds to the active site pocket by making specific hydrogen bonding interactions with a number of charged amino acid side-chains as well as a coplanar stacking interaction with a tyrosine residue. Despite a relatively low sequence identity of approximately 24%, the structure is highly homologous to that of B.cereus PI-PLC with an r.m.s. deviation for 228 common C alpha positions of 1.46 A. Larger differences are found for loop regions that accommodate most of the numerous amino acid insertions and deletions. The active site pocket is also well conserved with only two amino acid replacements directly implicated in inositol binding.
Insights from analysing tourist expenditure using quantile regression

Mature tourism destinations are increasingly needing to diversify their products and markets. To be successful, such strategies require a very detailed understanding of potential tourists’ levels and patterns of spending. Empirical studies of tourist expenditure have tended to employ ordinary least squares regression for this purpose. There are, however, a number of important limitations to this technique, chief among which is its inability to distinguish between tourists who have higher- and lower-than-average levels of spending. As such, some researchers recommend the use of an alternative estimation technique, known as quantile regression, which does allow such distinctions to be made. This study uses a single data set, collected among rural tourists in Madeira, to analyse the determinants of tourist expenditure using both techniques. This enables direct comparison to be made and illustrates the additional insights to be gained using quantile regression.
Prosurvival and proapoptotic intracellular signaling in rat spiral ganglion neurons in vivo after the loss of hair cells

Neurons depend on afferent input for survival. Rats were given daily kanamycin injections from P8 to P16 to destroy hair cells, the sole afferent input to spiral ganglion neurons (SGNs). Most SGNs die over an ∼14‐week period after deafferentation. During this period, the SGN population is heterogeneous. At any given time, some SGNs exhibit apoptotic markers—TUNEL and cytochrome c loss—whereas others appear nonapoptotic. We asked whether differences among SGNs in intracellular signaling relevant to apoptotic regulation could account for this heterogeneity. cAMP response element binding protein (CREB) phosphorylation, which reflects neurotrophic signaling, is reduced in many SGNs at P16, P23, and P32, when SGNs begin to die. In particular, nearly all apoptotic SGNs exhibit reduced phospho‐CREB, implying that apoptosis is due to insufficient neurotrophic support. However, >32% of SGNs maintain high phospho‐CREB levels, implying access to neurotrophic support. By P60, when ∼50% of the SGNs have died, phospho‐CREB levels in surviving neurons are not reduced, and SGN death is no longer correlated with reduced phospho‐CREB. Activity in the proapoptotic Jun N‐terminal kinase (JNK)‐Jun signaling pathway is elevated in SGNs during the cell death period. This too is heterogeneous: <42% of the SGNs exhibited high phospho‐Jun levels, but nearly all SGNs undergoing apoptosis exhibited elevated phospho‐Jun. Thus, heterogeneity among SGNs in prosurvival and proapoptotic signaling is correlated with apoptosis. SGN death following deafferentation has an early phase in which apoptosis is correlated with reduced phospho‐CREB and a later phase in which it is not. Proapoptotic JNK‐Jun signaling is tightly correlated with SGN apoptosis. J. Comp. Neurol. 503:832–852, 2007. © 2007 Wiley‐Liss, Inc.
Detection of Aspergillus species in bone marrow transplant patients.

INTRODUCTION Invasive aspergillosis is a severe complication of cytotoxic chemotherapies and bone marrow transplantation (BMT). The aim of this study was to assess the utility of a real-time PCR assay for the early diagnosis of Aspergillus species in blood samples from BMT patients. METHODOLOGY Blood specimens (n = 993) from patients (n = 82) scheduled for BMT were collected prior to transplant and for 100 days post transplantation. The specimens were later tested using an Aspergillus-specific real-time PCR assay. Cultures of clinical samples, along with sonography and computerized tomographic scans, were performed as standard of care. RESULTS Aspergillus DNA was positive in 94 sequential blood samples from 13 patients with clinical and radiological signs of infection. Samples from three of these patients were PCR-positive for Aspergillus in the first week of admission, prior to transplantation. Four patients with aspergillosis were cured with antifungal agents and nine died. An additional 12 patients without clinical signs of infection were PCR-positive on one occasion each, while two patients with clinical signs of infection were PCR-negative. Compared to routine methods of aspergillosis diagnosis, the respective sensitivity, specificity, negative, and positive predictive values of the PCR method by patient were 86.6%, 82%, 96.5% and 52%. CONCLUSIONS The results show that Aspergillus infections in the blood of bone marrow transplant patients can be dectected by PCR methods. Early detection of Aspergillus infections by PCR has the potential to positively impact patient mortality rate and provide cost savings to hospitals.
Relationship Between Plantar Pressure and Soft Tissue Strain under Metatarsal Heads with Different Heel Heights

Background: Metatarsalgia due to increased plantar pressure under the metatarsal head (MTH) is often seen with wearing high-heeled shoes. However, the concomitant soft tissue strain has not been well discussed. The objective of our study was to explore the standing plantar pressure and corresponding soft tissue strain under the metatarsal heads (MTHs) with different heel heights. Materials and Methods: Twenty-one healthy subjects (10 male and 11 female) participated. The plantar pressure and soft-tissue thicknesses were measured simultaneously with a load cell and a 10-MHz linear-array ultrasound (US) transducer respectively. The changes in plantar pressure and soft tissue strain under the MTHs were analyzed for different heel heights. Results: As hypothesized, plantar metatarsal pressure significantly increased and shifted to the first and second MTHs with increasing heel height from 2 cm to 4 cm(p < 0.05). However, the change in soft tissue strain under the medial forefoot became insignificant when the heel height was greater than 2 cm (p = 0.473 and 0.517). Conclusions: Increased heel height resulted in increasing medial forefoot loading pressure; however, the soft tissue exhibited stationary compressibility when the heel height was greater than 2 cm. Clinical Relevance: Our finding provides an understanding of the biomechanical changes with wearing high-heeled shoes and suggests possible strategies to reducing discomfort and risk of injury, such as limiting heel height to no greater than 2 cm and using medial padding under MTHs.
An Analysis of Factors Affecting Mature Age Students’ Academic Success in Undergraduate Nursing Programs: A Critical Literature Review

Abstract The population of mature age students entering university nursing programs has steadily increased in both Australia and worldwide. The objective of the literature review was to explore how mature age students perform academically and to analyse the factors associated with their academic performance in nursing programs. A literature search was conducted in the following databases: CINAHL, ProQuest, Medline, Cochrane, Mosby’s Index, Joanna Briggs Institute (JBI), and Scopus. Twenty-six (26) research papers published between 2000 and 2014 have met the selection criteria of this review. The key themes identified include; 1) ambiguity in definition of mature age and academic success, 2) age and academic success, 3) intrinsic factors (life experiences, emotional intelligence, and motivation and volition), and 4) extrinsic factors (peer, academic and family support; and learning style, components of the modules and mode of delivery). Current literature provides evidence that mature age nursing students perform at a higher level within the methodological issues discussed in this paper. Future research is warranted to advance the understanding of the complex relationship between extrinsic and intrinsic factors of mature age students and their academic success in higher education. Nursing educators will benefit from novel evidence, ideas and opportunities to explore and implement in nursing education.
Distribution of CGG repeats and FRAXAC1/DXS548 alleles in South American populations.

In order to assess the molecular variability related to fragile X (FMR1 locus), we investigated the distribution of CGG repeats and DXS548/FRAXAC1 haplotypes in normal South American populations of different ethnic backgrounds. Special attention was given to Amerindian Wai-Wai (Northern Brazil) and Ache (Paraguay), as well as to Brazilian isolated communities of African ancestry, the remnants of quilombos. Comparison of samples from quilombos, Amerindians, and the ethnically mixed, but mainly European-derived population of São Paulo revealed that the 30-copy allele of the fragile X gene is the most frequent in all groups. A second peak at 20 repeats was present in the population of São Paulo only, confirming this as a European peculiarity. The distribution of DXS548 and FRAXAC1 alleles led to a high expected heterozygosity in African Brazilians, followed by that observed in the population of São Paulo. Amerindians showed the lowest diversity in CGG repeats and DXS548/FRAXAC1 haplotypes. Some rare alleles, for example, the 148-bp (FRAXAC1) or 200-bp (DXS548) variants, which seem to be almost absent in Europe, occurred in higher frequencies among African Brazilians. This suggests a general trend for higher genetic diversity among Africans; these rarer alleles could be African in origin and would have been lost or possibly were not present in the groups that gave rise to the Europeans.
Are the mentally ill homeless a distinct homeless subgroup?

The question has been raised whether it is useful or meaningful to dichotomize the homeless population by mental illness - i.e., to consider the mentally ill homeless as distinct from other homeless people. The current article presents evidence from a single data set to address this question empirically. Data from a randomly sampled population of 900 homeless men and women systemically interviewed using the Diagnostic Interview Schedule were examined to determine associations of mental illness with the problems of homelessness, controlling for the presence of substance abuse in the analyses. Although a few clinically meaningful associations with mental illness were found that might suggest directions for appropriate interventions, mental illness did not differentiate individuals in many important demographic and biographic respects. Individual diagnoses did not perform much better in differentiating the homeless by mental illness. Schizophrenia and bipolar mania showed a few significant associations not identified by the "major mental illness" construct. Major depression, constituting the majority of nonsubstance Axis I disorder in the homeless, provided no association beyond that obtained with the "major mental illness" category. The data provide little support for conceptualizing homeless subgroups or homelessness in general on the basis of mental illness alone. To do so also risks neglecting the emotional distress of the majority without major mental illness and the other problems that homeless persons share regardless of psychiatric illness. While serious mental illness is overrepresented among the homeless, it represents just one of many important vulnerability factors for homelessness. Substance abuse is far more prevalent than other Axis I disorders. Media images equating homelessness with major mental illness unnecessarily stigmatize homeless people and encourage oversimplified and narrowly conceived psychiatric interventions. While continuing attention is needed on improving identification and management of serious mental illness among the homeless, this must be accomplished within the broader context of social and economic aspects of homelessness.
High PCA3 scores in urine correlate with poor-prognosis factors in prostate cancer patients.

BACKGROUND To improve the prediction of prostate cancer (PCA) risk and pathological type of PCA by non-invasive approaches before performing prostatic biopsy are the current challenges for the management of PCA. The aim of this present study was evaluate the clinical validity of prostate cancer associated 3 (PCA3) gene in the prediction of PCA and the correlations between the PCA3 level and prognostic factors. METHODS A total of 207 patients with suspected prostate cancer in Ningbo No. 2 hospital between June 2012 and July 2014 were enrolled in this study. All patients included underwent prostate biopsy under the direction of digital rectal examination (DRE) and were divided into PCA group and no evidence of malignancy (NEM) group according to the pathological diagnosis. We analyzed the association between PCA3 score and indicators of prognosis (Gleason score, percentage of positive cores and clinical stage) by multivariate analysis. RESULTS The levels of total prostate-specific antigen (t-PSA), prostate health index (PHI) and PCA3 score in patients with PCA were significantly higher than those in NEM group (P<0.05). In PCA group, PHI value and t-PSA were both factors significantly correlated with high Gleason score and clinical stage (P<0.05). A high PCA3 score in urine was significantly correlated with a high Gleason score, % positive cores and an advanced clinical stage (P<0.05). CONCLUSION PCA3 score might be one of useful diagnostic tools for determining suitable therapeutic programs for PCa and predicting the prognosis.