Miracle-dz/UniFAR-FTUs huggingface dataset:
SPG4 Founder Effect in French Canadians with Hereditary Spastic Paraplegia

Background: The most common cause of autosomal dominant Hereditary Spastic Paraplegia (HSP) is mutations in the SPG4 gene. We have previously identified novel SPG4 mutations in a collection of North American families including the c.G1801A mutation present in two families from Quebec. The aim of this study is to estimate the frequency of the c.G1801A mutation in the French Canadian (FC) population and to determine whether this mutation originates from a common ancestor. Methods: We collected and sequenced exon 15 in probands of 37 families. Genotypes of markers flanking the SPG4 gene were used to construct haplotypes in five families. Clinical information was reviewed by a neurologist with expertise in HSP. Results: We have identified three additional unrelated families with the c.G1801A mutation and haplotype analysis revealed that all five families share a common ancestor. The mutation is present in 7% of all our FC families and explains half of our spastin linked FC families. The phenotype associated with the c.G1801A genotype is pure HSP with bladder involvement. Conclusion: In this study we have determined that the relative frequency of the c.G1801A mutation in our FC collection is 7%, and approximately 50% in the spastin positive FC group. This mutation is the most common HSP mutation identified in this population to date and is suggestive of a founder effect in Quebec.
Impact of HIV-1 viral subtype on CD4+ T-cell decline and clinical outcomes in antiretroviral naive patients receiving universal healthcare

Objective:The influence of viral subtype on the natural history of HIV is unclear and confounded by socioeconomic and host factors that vary between groups harboring different clades. We compared Canadians (clade B), with recent immigrants from Haiti (clade B) and sub-Saharan Africa (clades non-B) to determine whether there were differences in disease progression attributable to viral subtype. Methods:We conducted a retrospective cohort study in a universal healthcare setting between 1996 and 2007. The rate of CD4+ T-lymphocyte decline prior to initiation of antiretroviral therapy was determined in all participants with at least two CD4+ T-lymphocyte measures using mixed linear regression models. Time to first AIDS-defining illness was compared using adjusted Cox proportional hazards models. Results:Two hundred and eighty-nine Canadians, 44 Haitians, and 123 Africans were studied for a median of 260 days (2 days–11 years). Africans and Haitians were demographically and clinically similar. However, the adjusted slope of square root CD4+ T-lymphocyte decline was significantly lower in Africans [−0.04/year; 95% confidence interval (CI) = −0.08 to −0.003] compared with Canadians (−0.07/year; 95% CI = −0.11 to −0.03; P = 0.02), and Haitians (−0.10/year; 95% CI = −0.12 to −0.07; P = 0.001). Africans were also less likely to develop AIDS. Conclusion:Despite having similar demographic, socioeconomic, and nutritional status to Haitians, Africans infected with non-B clade HIV had slower rates of disease progression compared with both Haitians and Canadians, with both groups being infected by the clade B virus. Our findings suggest that viral subtype may be an important predictor of HIV natural history in a developed medical setting.
A Perspective on Mesenchymal Stromal Cell Transplantation in the Treatment of Sepsis

ABSTRACT Although a variety of disease-modifying agents have been studied as potential sepsis treatments, no beneficial effects on the course of sepsis, in terms of survival, have been observed until now. Because of their plasticity, mesenchymal stromal cells (MSCs) have been implicated as an effective novel therapy modality for various diseases and are widely used for cellular therapies and tissue engineering. The existing knowledge supports the idea that MSCs might be beneficial in sepsis treatment. Our objective was to selectively address the evidence, based on multistep processes, supporting the potential of MSC-based therapies in clinical sepsis trials. In this study, we performed a stepwise approach to defend the evaluation of MSC treatments for sepsis from the bench to the bedside. Altogether, the reviewed data postulate that the signals produced by inflamed tissues might determine the functional effects of MSCs. These effects include bacterial clearance, suppression of inflammation, antiapoptosis, or stimulation of regenerative responses. We conclude that the clinical application of MSCs is a feasible and well-tolerated approach and therefore may have benefits for patients with sepsis.
How Dangerous Is Obesity? Issues in Measurement and Interpretation

THE PREVALENCE of obesity is rising in nearly all regions of the world (Finucane et al. 2011). In the United States, the adult prevalence of obesity increased from 15 percent in 1976–1980 to 31 percent in 1999–2000 and to 38 percent in 2013–2014 (Flegal et al. 1998; Ogden et al. 2015; Flegal et al. 2012). Although it is well known that obesity raises risks for a variety of diseases, including cardiovascular disease, diabetes, and cancer (Asia Pacific Cohort Studies Collaboration 2004; Bogers et al. 2007; Wilson et al. 2008; Wolin, Carson, and Colditz 2010; Narayan and Boyle 2007), much uncertainty remains regarding the effects of excess weight on an individual’s risk of death. For example, two large studies estimated that relative to the normal weight category, overweight and moderate obesity were associated with statistically significant increases in the risks of dying (Global BMI Mortality Collaboration 2016;Whitlock et al. 2009). A recentmeta-analysis, however, estimated that these same categories were associatedwith reduced likelihood of death, an association that was significant for overweight but not for moderate obesity (Flegal et al. 2013). Recognizing the potential effect of rising obesity on mortality levels in the United States, the 2015 Technical Advisory Panel to the Social Security Administration recommended modeling the impact of changing levels of obesity in its projections (Technical Panel on Assumptions and Methods 2015). However, uncertainty is compounded in estimates and projections of the impact of obesity on the health of populations because these estimates are highly sensitive to small differences in relative risks (Flegal et al. 2005). A recent review found that published estimates of the proportion of deaths attributable to obesity in the United States ranged from 3 to 15 percent (Flegal, Panagiotou, and Graubard 2015). The first value would imply a relatively minor role for obesity, while the second figure would suggest that obesity is among the leading causes of death in the United States. A study of the impact of overweight and obesity on international differences in life expectancy found that high levels of obesity in the US accounted for 55 percent of its life expectancy shortfall using one set of risk factors but only 30 percent using another set (Preston and Stokes 2011).
Wrist-worn accelerometers in assessment of energy expenditure during intensive training

We assessed the ability of the Polar activity recorder (AR) to measure energy expenditure (EE) during military training. Twenty-four voluntary male conscripts participated in the study and wore an AR on the non-dominant wrist 24 h a day for 7 d. The AR analyzed and stored the frequency of hand movements (f_hand) into memory at 1 min intervals. The relationship between f_hand and EE was studied over a 7 d period of military training using the doubly labeled water (DLW) technique. In addition, the relationship between f_hand and EE was analyzed during walking and running on a treadmill with an indirect calorimeter (IC), and f_hand was measured during a supervised 45 min field march test where the conscripts carried combat gear. EE was expressed as physical activity level (PAL), total energy expenditure (TEE), and activity-induced energy expenditure adjusted for body mass (AEE/BM). Over the 7 d period, f_hand alone explained 46% of inter-individual variation in PALDLW. After inclusion of body height and mass in the model used to predict PALDLW from f_hand, a very high positive correlation and a low standard error of estimate (SEE) were observed between the AR and DLW techniques: for TEE r = 0.86 (p < 0.001), the SEE was 6.3%, and for AEE/BM r = 0.84 (p < 0.001), the SEE was 12.8%. In the treadmill exercise, f_hand correlated highly with PALIC (r = 0.97 ± 0.02). In the 45 min field march test, the AR measured similar f_hand as on the treadmill at the same speed. In conclusion, the wrist-worn AR can be regarded as a reliable and valid method for assessing EE during intensive training.
Application-driven dimensioning of a Coarse-Grain Reconfigurable Array

In this paper, we have scaled-up a Coarse-Grain Reconfigurable Array (CGRA) in specific widths to evaluate matrix-vector multiplication and radix-4 64-point Fast Fourier Transform (FFT) algorithms. The evaluation of different CGRAs is based on complexity in application mapping, performance and area utilization. Reducing the product development time and achieving higher reliability has always been the need of industry and system integrators. The low-level designers and application developers need higher performance with minimum resources. Based on our evaluation, we propose a choice of array sizes for fulfilling the needs of both system integrators and low-level designers.
Brucellosis in mammals of Costa Rica: An epidemiological survey

Brucellosis has been an endemic disease of cattle and humans in Costa Rica since the beginning of XX century. However, brucellosis in sheep, goats, pigs, water buffaloes, horses and cetaceans, has not been reported in the country. We have performed a brucellosis survey in these host mammal species, from 1999–2016. In addition, we have documented the number of human brucellosis reported cases, from 2003–2016. The brucellosis seroprevalence in goat and sheep herds was 0.98% and 0.7% respectively, with no Brucella isolation. Antibodies against Brucella were not detected in feral or domestic pigs. Likewise, brucellosis seroprevalence in horse and water buffalo farms was estimated in 6.5% and 21.7%, respectively, with no Brucella isolation. Six cetacean species showed positive reactions against Brucella antigens, and B. ceti was isolated in 70% (n = 29) of striped dolphins (Stenella coeruleoalba). A steady increase in the diagnosis of human brucellosis cases was observed. Taking into account the prevalence of brucellosis in the various host mammals of Costa Rica, different measures are recommended.
Norwegian Norms and Factor-Structure of Phonemic and Semantic Word List Generation

Word list generation (WLG) tasks are used world wide as measures of executive function, although the tests are sensitive also to deficits in other cognitive functions. Norms derived from English-speaking samples are often used in Norway, even though the consequences of language differences are not yet been assessed. The reliability of WLG testing in Norway is increased by the norms presented in the first part of the study. The validity of WLG tests as measures of executive function is addressed in the second part, by performing a factor-analysis of neuropsychological performance in a mixed psychiatric sample. Education contributed most to performance. There were no sex-differences in overall performance. Factor analysis indicated that phonemic WLG is a more specific measure of executive function than semantic WLG. Semantic WLG correlated higher with basal processing speed, thus being more sensitive to aging. In conclusion the clinical neuropsychologist is advised to control for reduction in basal processing speed before interpreting WLG scores as specific deficits in executive function. The Norwegian norms correspond well with most comparable studies in other languages, thus failing to show any language specific effects.
THE TREATMENT WITH TRANILAST, A MAST CELL BLOCKER, FOR IDIOPATHIC OLIGOZOOSPERMIA

Although many drug treatments have been reported to theoretically improve semen parameters in male infertility, a standard method has not been established. The authors examined whether tranilast, a mast cell blocker, improves fertility and/or semen parameters in severe oligozoospermia. Seventeen patients with a sperm density of less than 10 2 10 6 sperm/mL and their fertile partners were enrolled in this study. Patients were prescribed tranilast 300 mg/day for at least 12 weeks. Semen and blood samples were collected before and after the prescription of tranilast for 12 weeks. Semen parameters, serum gonadotropins, luteinizing hormone, follicle-stimulating hormone, serum testosterone, and testicular size were evaluated. One patient complained of mild drowsiness during treatment. The sperm count was significantly increased after administration of tranilast in 7 patients (41.1%), although sperm motility was not altered. Semen volume and normal morphology were also unaltered. Three pregnancies were achieved. Endocrine profile and testicular size were unchanged. Tranilast, a mast cell blocker, is clinically useful for the treatment of severe idiopathic oligozoospermic men.
A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins

Two small fragments of a novel human gammaherpesvirus genome known as Kaposi's sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (HHV-8) have been shown to be present in virtually all AIDS and non-AIDS KS lesions, as well as in body cavity-based lymphomas (BCBL) and in multicentric Castleman's disease. We have extended those studies by identifying and sequencing a third fragment of HHV-8 DNA encoding a viral thymidylate synthetase (TS) gene. Use of this viral TS fragment as a probe led to the identification and mapping of a cluster of overlapping phage lambda clones from a BCBL tumor DNA genomic library that spanned 48 kb on the left-hand side of the HHV-8 genome between the equivalents of open reading frame 6 (ORF6) and ORF31 of herpesvirus saimiri (HVS). DNA sequencing of a 17-kb segment encompassing a gammaherpesvirus divergent locus (DL-B) between ORF11 and ORF17 revealed the presence of nine viral ORFs with predicted gene products related to cellular proteins. These include the complete TS gene and a dihydrofolate reductase (DHFR) gene, four novel cytokine genes (encoding viral interleukin-6, viral MIP-1A, viral MIP-1B, and BCK) that have not previously been found to be encoded by a virus, and a bcl-2 homolog. This region in HHV-8 also contains the T1.1 abundant lytic cycle nuclear RNA gene and encompasses two genes (or exons) encoding proteins with C4HC3 zinc finger domains of the PHD/leukemia-associated protein subtype. The latter are related to the spliced immediate-early IE1 protein of the gamma-2 class herpesvirus bovine herpesvirus type 4 and a similar motif found in HVS ORF12. Although genes for TS and DHFR enzymes are also encoded by HVS (ORF70 and ORF2), both occur at different genomic loci than in HHV-8, and the HHV-8 DHFR protein is much farther diverged from human DHFR than is the HVS version, implying that they were probably acquired as host cell cDNAs by independent evolutionary events. Transcripts from the IE1-A, IE1-B, DHFR, and MIP-1B genes were all detected by Northern blot hybridization analysis in a BCBL cell line at 12 h after induction with butyrate but were not present before induction, indicating that these are all primarily lytic cycle genes. We conclude that the DL-B locus of gammaherpesviruses displays considerably more variability that previously appreciated and that expression of many of these genes is likely to have important implications for HHV-8 biology and therapy.
Harnessing knowledge workers' participation for IT planning effectiveness: The informational and motivational mediating effects of users' microplanning behaviour

In most organizations, knowledge is produced on a continuous basis such that formal planning methods fail to capture it on time for utilization into effective IT solutions. Microplanning, as user-led informal planning behaviour, allows users as knowledge workers to continuously use their knowledge and skills to identify opportunities for using IT or replanning its existing use. This is the informational effect of microplanning. Microplanning is also an empowering process which enhances users' own motivation. This empowerment effect is referred to as the motivational effect. User microplanning behaviour therefore constitutes the main construct of the model of microplanning effectiveness described in this study. It yields effectiveness through two paths, informational and motivational. After operational definitions for the variables were derived, the two main hypotheses of the study were empirically tested on a sample of 263 knowledge workers. Results of the study fully support the informational and motivational effects of microplanning.
A New Look at Naram-Sin and the "Great Rebellion"

L'auteur etudie les relations entre un texte paleobabylonien (de provenance inconnue), relatant la Grande Rebellion contre Naram-Sin et le compte rendu qui en est donne dans les copies paleobabylonniennes des inscriptions historiques de Naram-Sin (empire d'Akkad) et, d'une maniere plus generale, de la nature des relations entre le genre litteraire et le genre historique dans les textes cuneiformes mesopotamiens
Three cdg Operons Control Cellular Turnover of Cyclic Di-GMP in Acetobacter xylinum: Genetic Organization and Occurrence of Conserved Domains in Isoenzymes

ABSTRACT Cyclic di-GMP (c-di-GMP) is the specific nucleotide regulator of β-1,4-glucan (cellulose) synthase in Acetobacter xylinum. The enzymes controlling turnover of c-di-GMP are diguanylate cyclase (DGC), which catalyzes its formation, and phosphodiesterase A (PDEA), which catalyzes its degradation. Following biochemical purification of DGC and PDEA, genes encoding isoforms of these enzymes have been isolated and found to be located on three distinct yet highly homologous operons for cyclic diguanylate, cdg1, cdg2, andcdg3. Within each cdg operon, apdeA gene lies upstream of a dgc gene.cdg1 contains two additional flanking genes,cdg1a and cdg1d. cdg1a encodes a putative transcriptional activator, similar to AadR of Rhodopseudomonas palustris and FixK proteins of rhizobia. The deduced DGC and PDEA proteins have an identical motif structure of two lengthy domains in their C-terminal regions. These domains are also present in numerous bacterial proteins of undefined function. The N termini of the DGC and PDEA deduced proteins contain putative oxygen-sensing domains, based on similarity to domains on bacterial NifL and FixL proteins, respectively. Genetic disruption analyses demonstrated a physiological hierarchy among the cdg operons, such that cdg1contributes 80% of cellular DGC and PDEA activities andcdg2 and cdg3 contribute 15 and 5%, respectively. Disruption of dgc genes markedly reduced in vivo cellulose production, demonstrating that c-di-GMP controls this process.
Abnormal accumulation of intestinal fluid following ingestion of an unabsorbable carbohydrate in patients with irritable bowel syndrome: an MRI study

Postprandial discomfort following intake of poorly absorbable, but fermentable carbohydrates is a common complaint in patients with irritable bowel syndrome (IBS). We used lactulose as a model substance for this group of symptom triggering carbohydrates, aiming to visualize the intestinal response in IBS patients compared to healthy controls.
[Evaluation of the immunological response to hepatitis B vaccine in health care professionals].

Clinical trials have shown the safety and efficacy of Hepatitis B (HB) vaccination, but it is well known that host and immunization factors can affect the response to HB vaccine. In order to assess the importance of some of these factors we evaluated the immune response of 86 health care workers who received three doses of H-B-Vax intramuscularly (deltoid), at days 0, 30 and 180. Serum samples were taken after each dose and anti-HBs antibodies were determined by quantitative radioimmunoassay. The results showed that males had a diminished immune response to the first dose of HB vaccine (31.7% x 53.3%, p < 0.05) and had geometric mean titers (GMT) of anti-HBs lower than females at the end of the vaccination program (2109.4 x 2453.8, p > 0.05). Smokers had a lower rate of seroconversion after the first dose (29.7% x 53.1%, p < 0.05) and reached lower GMT (2015.2 x 2453.8, p > 0.05) than non-smokers. There were no statistically significant differences between individuals younger or older than 35 years old, in either immunological response of level of anti-HBs.
The critical role of caregivers in achieving patient-centered care.

Achieving high-quality, cost-effective medical care remains an elusive goal of the US health care system, but there is widespread agreement that patientcentered care will be a key ingredient.1 Yet for frail elders and patients with advanced illness, many of whom have multiple chronic diseases, patient-centered care is impossible without caregiver involvement. Although advocacy groups such as the National Alliance for Caregivers have long endorsed attention to family members and prominent research organizations such as the newly created Patient-Centered Outcomes Research Institute mention families in their research agendas, the critical role of caregivers deserves considerably more attention from clinicians.
It is time to test low level laser therapy in Great Britain

Low level laser therapy (LLLT) has been used in Eastern Europe and Asia for the treatment of a wide range of conditions for many years. Its continued acceptance in these populations reflects the efficacy with which it is regarded both by clinicians and their patients. Although there have been a substantial number of reports on its clinical benefit and some practitioners have used the technique in North America and Australasia it has yet to be subjected to detailed assessment through randomised clinical trials. The purpose of this review is to stimulate interest in the technique and to encourage rigorous research into its potential value.
Negative Regulation of Prolactin Receptor Stability and Signaling Mediated by SCFβ-TrCP E3 Ubiquitin Ligase

ABSTRACT Ubiquitin-dependent degradation of hormone receptors is emerging as a key mechanism that regulates the magnitude and duration of hormonal effects on cells and tissues. The pituitary hormone prolactin (PRL) is involved in regulating cell differentiation, proliferation, and survival. PRL engages its receptor (PRLR) to initiate various signaling cascades, including the phosphorylation and activation of Stat5. We found that PRL promotes interaction between PRLR and the F-box protein β-TrCP2, which functions as a substrate recognition subunit of the SCFβ-TrCP E3 ubiquitin ligase. This interaction requires PRLR phosphorylation and the integrity of serine 349 within a conserved motif, which is similar to conserved motifs present in other substrates of SCFβ-TrCP. The PRLRS349A mutant is resistant to ubiquitination and is more stable than its wild-type counterpart. Phosphorylated PRLR undergoes ubiquitination by SCFβ-TrCP in vitro. Knockdown of β-TrCP expression inhibits the ubiquitination and degradation of PRLR and promotes PRL-dependent phosphorylation of Stat5 as well as Stat5-dependent transcription in cells. Furthermore, the activation of Stat5 and the stimulation of cell growth by PRL are augmented in cells expressing the PRLRS349A mutant. These data indicate that PRLR is a novel SCFβ-TrCP substrate and implicate β-TrCP as an important negative regulator of PRL signaling and cellular responses to this hormone.