Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix

Background The laminin alpha 5 gene (LAMA5) plays a master role in the maintenance and function of the extracellular matrix (ECM) in mammalian tissues, which is critical in developmental patterning, stem cell niches, cancer and genetic diseases. Its mutations have never been reported in human disease so far. The aim of this study was to associate the first mutation in LAMA5 gene to a novel multisystem syndrome. Methods A detailed characterisation of a three-generation family, including clinical, biochemical, instrumental and morphological analysis, together with genetics and expression (WES and RNAseq) studies, was performed. Results The heterozygous LAMA5 mutation c.9418G>A (p.V3140M) was associated with skin anomalies, impaired scarring, night blindness, muscle weakness, osteoarthritis, joint and internal organs ligaments laxity, malabsorption syndrome and hypothyroidism. We demonstrated that the mutation alters the amount of LAMA5 peptides likely derived from protein cleavage and perturbs the activation of the epithelial-mesenchymal signalling, producing an unbalanced expression of Sonic hedgehog and GLI1, which are upregulated in cells from affected individuals, and of ECM proteins (COL1A1, MMP1 and MMP3), which are strongly inhibited. Studies carried out using human skin biopsies showed alteration of dermal papilla with a reduction of the germinative layer and an early arrest of hair follicle downgrowth. The knock-in mouse model, generated in our laboratory, shows similar changes in the tissues studied so far. Conclusions This is the first report of a disease phenotype associated with LAMA5 mutation in humans.
Sentiment and Asset Volatility Dynamics: A Content Analysis Approach

This paper analyses the effects of news on the so-called 'idiosyncratic volatility puzzle'. By empirically modelling the stock return data from the Center for Research in Security Prices (CRSP) database from 2000 to 2011, we firstly find that idiosyncratic volatility has a positive effect on excess return. Existing studies suggest that both the quantity and quality of public information arrival (news flow) can significantly induce the stock return volatility. Following this idea, we employ various models to control for the potential news effects on the idiosyncratic volatility and re-visit this puzzle. Our empirical results suggest that when quantity, relevance and quality of news are all properly controlled for, the average magnitude of the idiosyncratic volatility effect on excess return can be reduced by roughly 50 percent.
The quality of COPD care in general practice in Denmark: the KVASIMODO study.

AIM We studied the quality of care for COPD patients in a large sample of general practices in Denmark. We focussed on whether participation by general practitioners (GPs) in an educational programme could enhance the use of spirometry in the diagnosis and staging of the disease and improve adherence to COPD guidelines. METHODS We performed two audit surveys of GPs' patients' notes, one year apart, before and after an educational programme for participating GPs and their staff. A total of 154 GPs participated in the study. 2549 patient records were included in the first survey and 2394 in the second. RESULTS Based on analysis of all patient records, we observed a substantial improvement in the quality of care: recording of FEV1 improved from 52.7% of cases in the first survey to 71.4% in the second (p< 0.001). There was a significant improvement in the recording of body mass index and provision of smoking cessation advice, recommendation of physical activity, checking of inhalation technique, dietary instruction, and referral to pulmonary rehabilitation. We also found a decline in the use of inhaled corticosteroids in patients with mild COPD, from 60.2% in the first survey to 48.8% in the second. When analysing the results focussing on the performance of single GPs there was an improvement in quality, but this was less than the improvement for patients overall - suggesting that improvement in quality of care was not equally distributed throughout the GPs' practices. CONCLUSION We conclude that it is possible to improve the quality of COPD care by educating GPs and their staff.
Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?

Background. Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. Methods. Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. Results. The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. Conclusions. Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.
The 70‐kd mammalian heat shock proteins are structurally and functionally related to the uncoating protein that releases clathrin triskelia from coated vesicles.

It is shown that in immunological, structural and functional terms the uncoating protein, which catalyses ATP‐dependent dissociation of clathrin triskelia from clathrin‐coated vesicles is intimately related to two major stress proteins of mammalian cells. These proteins of hitherto unknown functions have polypeptide mol. wts. of 73 kd and 72 kd, respectively. They are normal cell constituents which are synthesized in increased abundance under adverse environmental circumstances, such as non‐physiological temperatures or treatment with amino acid analogues.
Temporal distribution of transmissible mink encephalopathy virus in mink inoculated subcutaneously

Information was sought on the temporal distribution of transmissible mink encephalopathy virus in royal pastel mink inoculated subcutaneously with 10(3.0) 50% intracerebral lethal doses of the Idaho strain. As determined by intracerebral assay in mink, extremely little replication of the virus occurred during the preclinical stage of infection. It seemed largely limited to lymph nodes draining the site of inoculation. Virus first appeared in the central nervous system (CNS) at 20 weeks, when all mink were still clinically normal. Early spongiform degeneration, limited to the posterior sigmoid gyrus of the frontal cortex, was first found at 28 weeks, or a few weeks before onset of clinical disease in most of the mink. Once virus reached the CNS, where greater concentrations occurred than elsewhere, it appeared in many extraneural sites (spleen, liver, kidney, intestine, mesenteric lymph node, and submandibular salivary gland). These seemingly anomalous findings, especially the limited extraneural replication of virus as a prelude to infection of the CNS, suggest that mink are not natural hosts of the virus. The results of this study support the generally held view that transmissible mink encephalopathy arises from chance or inadvertent infection of ranch mink with an exogenous virus, most likely feed-borne wild scrapie virus.
Evaluation of molecular typing techniques to assign genetic diversity among Saccharomyces cerevisiae strains

Discrimination of strains within the species Saccharomyces cerevisiae was demonstrated by the use of four different techniques to type 15 strains isolated from spoiled wine and beer. Random amplified polymorphic DNA with specific oligonucleotides and PCR fingerprinting with the microsatellite oligonucleotide primers (GAC)5 and (GTG)5 enabled discrimination between the strains tested. Additionally, restriction enzyme analysis, with TaqI and MseI, of PCR-amplified fragments from the complete internal transcribed spacer and nontranscribed spacer, both present in the rRNA-encoding gene cluster, proved to be suitable for generating intraspecies-specific patterns. Random amplified polymorphic DNA with primers 24 and OPA-11 and PCR fingerprinting with primer (GTG)5 appeared to generate the highest degree of diversity. However, the results indicated that there was no single PCR-mediated typing technique enabling discrimination on the strain level. Discrimination of each individual strain was nevertheless possible by combining the results obtained with all typing techniques.
Family Satisfaction Following the Death of a Loved One in an Inner City MICU

This study examined family satisfaction with end-of-life care in a medical intensive care unit (MICU) before and after a palliative care intervention was implemented there. This intervention consisted of early communication, family meetings, and psychosocial support. Family members of patients who died in the MICU in 2005 and 2006 were contacted 2 to 16 months after the death of their relatives. Trained interviewers used the Family Satisfaction with Care Questionnaire to assess the families' perceptions of the care given to their family members. Minorities comprised 77% of the patient population. Comparison of the levels of family satisfaction in the preintervention and postintervention groups demonstrated that the intervention significantly improved the quality of end-of-life care, particularly through increases in family members' satisfaction with decision making, communication with physicians and nurses, and the death and dying process.
Causes of Thrombocytopenia in Chronic Hepatitis C Viral Infection

We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.
Psychiatric Symptomatology and Disorders in Caregivers of Children With Asthma

OBJECTIVE. The prevalence of asthma and asthma-related mortality has increased in recent years. Data suggest an association between psychiatric symptoms in the caregiver and asthma-related hospitalizations in the child. We examined the prevalence of psychiatric symptoms and disorders and their relationship to asthma-related service utilization in caregivers of children hospitalized for asthma. PATIENTS AND METHODS. Caregivers (n = 175) were assessed during the child’s hospitalization. The number of asthma-related hospitalizations, emergency department visits, and unscheduled clinic visits in the past 12 months was obtained. The Brief Symptom Inventory, an assessment of psychiatric symptoms including somatic, anxiety, and depression subscales, and the Mini International Neuropsychiatric Interview, a structured clinical interview for psychiatric disorders, were administered. RESULTS. Mean age of the caregivers was 34.2 ± 7.3 years; 96.0% were women; 15.4% were white, 57.7% were black, and 26.3% were Hispanic. A total of 47.9% had incomes less than $25000/year. Caregivers with clinically significant elevations in 2 or more Brief Symptom Inventory subscales reported more asthma-related child hospitalizations in the past 12 months than did caregivers with lower Brief Symptom Inventory scores. Asthma-related hospitalizations correlated with Brief Symptom Inventory total, somatic, anxiety, and depression subscale scores. Caregiver diagnosis of an anxiety disorder (n = 36) was associated with more asthma-related hospitalizations in the child. Children of caregivers with current depression (n = 44) had more unscheduled clinic visits than children of caregivers without depression. CONCLUSION. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–defined psychiatric disorders, particularly depressive disorders, were common in caregivers and associated with a greater frequency of asthma-related hospitalizations in the child.
Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms.

OBJECTIVE Systemic sclerosis (SSc) is characterized by widespread vascular lesions and skin and internal organs fibrosis, including the heart; all cardiac layers, endocardium, myocardium, and pericardium, may be involved. We report the relevance of cardiac MRI findings in scleroderma patients with cardiac symptoms. PATIENTS AND METHODS 50 patients, all fulfilling the ACR SSc criteria (19 with limited and 31 with diffused skin involvement) were evaluated using a 1.5T MR scanner. Images were acquired before and after contrast medium administration; the exams were considered positive with one or more of these findings: enlarged volumes, reduced EF, regional kinetic anomalies, edema, DE or pericardial effusion. RESULTS 40 patients (80%) had one or more cardiac abnormalities: 5 patients had myocardial edema; 2 an increased interventricular septum thickness; 22 dilated ventricles or reduced EF; 12 an abnormal regional ventricular motion (2 of these with akinetic segments); 17 a delayed enhancement with different patterns, all without coronary distribution; 22 a pericardial effusion CONCLUSIONS: Pathologic findings were documented in 80% of the cases confirming a high occurrence of abnormal MR data. Myocardial involvement in systemic sclerosis can be assumed by the presence of multiple pathologic MRI findings. CMR seems to be a valuable tool to identify and assess the presence of cardiac involvement.
Rice production, imports and food security in Nigeria : An application of cointegration and error correction model

Nigeria is reputed to have comparative resource advantage in rice production to ensure self-sufficiency. In spite of this, rice imports in Nigeria have represented a good proportion of total food imports over time even with increased government effort to raise domestic rice production. This paper, therefore, estimates the determinants of rice import demand in Nigeria using a dynamic regression model. Specifically, cointegration and error correction model was followed. The results show that short-run changes in domestic rice production, level of external reserves and total import value remarkably shaped rice import behaviour in Nigeria during the period under investigation. More interesting is the fact that the error correction mechanism (ECM) indicated a feed back of about 125% of the previous year’s disequilibrium from long-run elasticity of domestic production of rice, external reserves, and import value. It is recommended that efforts geared at reducing rice imports in the short-run should not only rely on increasing domestic rice production and/or reducing total imports but should also look at trade agreements between Nigeria and its trading partners as well as restriction of rice imports, at least to a level that will not lead to food insecurity.
ETHICS MANAGEMENT IN PUBLIC SECTOR FROM THE PERSPECTIVE OF PUBLIC SERVICES’ CONSUMERS

The paper analyzes ethics management in public sector through the perspective of public services’ consumers in Romania. The areas taken into account are education, medical system, parliament, police, army, public administration and other public institutions. The objective of the paper is to understand the mechanism of corruption in public sector, as the most important part of unethical behavior in this sector. The methodology used consists of a quantitative research conducted in October 2014 on a number of 171 people. The questionnaire was distributed online, respecting the confidentiality of respondents. The results of the study could be used by public managers or by government to create adequate strategies in order to increase the ethical level in public sector and also developing a better image of these institutions.
On the Functional Interchangeability, Oxidant versus Reductant, of Members of the Thioredoxin Superfamily

ABSTRACT Escherichia coli thioredoxin 1 has been characterized in vivo and in vitro as one of the most efficient reductants of disulfide bonds. Nevertheless, under some conditions, thioredoxin 1 can also act in vivo as an oxidant, promoting formation of disulfide bonds in the cytoplasm (E. J. Stewart, F. Åslund, and J. Beckwith, EMBO J. 17:5543–5550, 1998). We recently showed that when a signal sequence is attached to thioredoxin 1 it is exported to the periplasm, where it can also act as an oxidant, replacing the normal periplasmic catalyst of disulfide bond formation, DsbA, in oxidizing cell envelope proteins (L. Debarbieux and J. Beckwith, Proc. Natl. Acad. Sci. USA 95:10751–10756, 1998). Here we report pulse-chase studies of the efficiency of disulfide bond formation in strains exporting thioredoxin 1 and more-oxidizing variants of it. While the exported thioredoxin 1 itself substantially speeds up the kinetics of disulfide bond formation, a version of this protein containing the DsbA active site exhibits kinetics that are indistinguishable from those of the DsbA protein itself. Further, we confirm the findings of Jonda et al. (S. Jonda, M. Huber-Wunderlich, R. Glockshuber, and E. Mössner, EMBO J. 18:3271–3281, 1999), who found that DsbB is responsible for the oxidation of exported thioredoxin 1, and we report the detection of a disulfide-bonded DsbB-thioredoxin 1 complex. Finally, we have found that under conditions of high-level expression of exported thioredoxin 1, the protein can act as both an oxidant and a reductant.
No evidence of a higher risk of progression to AIDS in patients with HIV-1-related severe thrombocytopenia.

The prognostic role of platelet (PLT) counts was evaluated in a cohort of 1,533 HIV-1-infected subjects followed for a median of 21 months. Thrombocytopenia (TCP), defined as a PLT count < or = 100 x 10(9)/L was present at enrollment in 11.2% of cases, with counts < or = 50 x 10(9)/L (severe TCP) in 5.3%. With the subjects with normal PLT counts (PLT >150 x 10(9)/L) as the reference group, the relative risk of developing acquired immunodeficiency syndrome (AIDS) was 0.8 [95% confidence interval (CI) 0.5-1.3, p = 0.4] for subjects with severe TCP, 2.1 (95% CI 1.4-3.1, p = 0.002) for those with PLT counts ranging from 51 to 100 x 10(9)/L (moderate TCP), and 1.6 (95% CI 1.2-2.1, p = 0.0004) for those with borderline PLT values (PLT ranging from 101 to 150 x 10(9)/L). Most of the risk increase associated with moderate TCP and borderline PLT values was explained by a higher prevalence of subjects with an older age and lower CD4+ cell counts. However, at multivariable analysis considering age, sex, risk group, and zidovudine (ZDV) treatment, the risk for subjects with severe TCP remained significantly lower than that for subjects with moderate TCP and borderline values. These results suggest the existence of different types of HIV-1-associated TCP and also suggest that severe TCP (which often arises in the early phases of infection) is not related to disease progression.
Reduction of false-negative results in inferior petrosal sinus sampling with simultaneous prolactin and corticotropin measurement.

OBJECTIVE To investigate the value of prolactin as an independent marker of catheter placement to improve the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with corticotropin-dependent Cushing syndrome. METHODS In this retrospective cohort study, we reviewed hospital records of patients who underwent IPSS procedures at the Cleveland Clinic between 1997 and 2009. Serum prolactin and plasma corticotropin levels were measured prospectively in peripheral and inferior petrosal sinus (IPS) samples. RESULTS Forty-one patients underwent 42 IPSS procedures at our institution during the study period. Among 35 patients with Cushing disease, 1 patient had erroneous IPSS results: all pre-corticotropin-releasing hormone (CRH) and post-CRH IPS to peripheral (IPS:P) ACTH ratios were less than 2 and less than 3, respectively. Despite radiologic evidence of appropriate IPS catheter placement, concurrent IPS:P prolactin ratios indicated that successful IPS venous sampling was not achieved. A second case with equivocal IPSS results could also be explained by corresponding IPS:P prolactin ratios. During IPSS, all patients with an identifiable ACTH-staining adenoma localizing to 1 side of the pituitary gland (n = 22) who demonstrated absent IPS:P ACTH gradients (<2 before or <3 after CRH administration) on the ipsilateral side of the corticotroph adenoma had corresponding IPS:P prolactin ratios less than 1.3. CONCLUSIONS Measurement of prolactin during IPSS testing may reduce false-negative results in patients with Cushing disease who do not demonstrate an appropriate central-to-peripheral ACTH gradient. In our series, all false-negative IPS:P ACTH ratios had a corresponding IPS:P prolactin ratio less than 1.3.
Leveraging Standards to Promote Program Quality

Standards provide a foundation for thinking about leadership development and practice. This article explores three sets of standards that impact educational leadership preparation: (a) the recently revised Interstate School Leaders Licensure Consortium (ISLLC) standards, which are now known as the Practice Standards for Educational Leaders (PSEL); (b) the Educational Leadership Constituent Council (ELCC) standards, which are currently under revision; and (c) the University Council for Educational Administration (UCEA) standards. In addition to reviewing each set, how they are used, and how they differ, we share findings from a survey of preparation program directors focused on how influential and beneficial these standards are in promoting leadership preparation program improvement.